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  • bioavailability  (130)
  • Nitrogen fixation  (116)
  • Springer  (246)
  • Blackwell Publishing Ltd
  • 1980-1984  (246)
  • 1925-1929
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  • Springer  (246)
  • Blackwell Publishing Ltd
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  • 101
    ISSN: 1432-1041
    Keywords: ranitidine ; duodenal ulceration ; pharmacokinetics ; non-responders ; therapeutic response ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of orally administered ranitidine were studied in 17 male patients with chronic duodenal ulceration. The patients were divided into 2 groups, 10 responders and 7 nonresponders, on the basis of their endoscopic response to ranitidine treatment. The 10 responders were studied both after a single 150 mg dose (SD) and after multiple dosing (MD) with ranitidine 150 mg twice daily for 4 weeks. The area under the curve (AUC) and maximum concentration (Cmax) were significantly higher (p〈0.01 andp〈0.05, respectively) after MD than after SD, but the half-life (t1/2) and minimum concentration (Cmin) 12 h postdosing did not differ. The non-responders were studied after MD only and their pharmacokinetic characteristics were compared with those of responders. No differences between the 2 groups were found. However, 2 non-responders had particularly low plasma ranitidine levels and high acid output. Such patients may need larger doses of ranitidine for adequate suppression of gastric acid. Five patients (4 responders and 1 non-responder) received ranitidine 20 mg i.v. The drug followed a two-compartment model, with mean values for t1/2β, volume of distribution steady-state and total plasma clearance of 80 min, 701 and 680 ml/min, respectively. The oral bioavailability of ranitidine in these 5 patients showed wide variation (27–76%; mean 51%).
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  • 102
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    European journal of clinical pharmacology 24 (1983), S. 761-767 
    ISSN: 1432-1041
    Keywords: theophylline ; bioavailability ; sustained release tablet ; pharmacokinetics ; Theograd-250
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of theophylline after oral administration of a new sustained release tablet Theograd®-250 mg was studied in 7 healthy volunteers, under fasting and non-fasting conditions. Whilst fasting the bioavailability was moderate at 64±22% (mean±SD), whereas in the non-fasting state the relatively high bioavailability of 90±13% was found. The drug appeared to be significantly more slowly absorbed when a tablet was taken after a meal, than when it was ingested on an empty stomach. In the former case, the peak level was reached after 6.9±1.0 h, whereas in the fasting state the maximum serum concentration occurred 4.0±1.7 h after administration of the drug. Despite the slow absorption, the peak non-fasting level of 4.4±1.4 mg·l−1 was significantly higher than the 3.1±1.0 mg·l−1 observed in the fasting state. The profiles of the serum concentration-time curves showed that the concentration remained above 75% of Cmax for 8.7±1.3 h in the fasting and 9.0±1.1 h in the non-fasting state. It was concluded that to define the optimal dosage regime for sustained release oral dosage forms of theophylline, the influence of food on absorption from these preparations should be taken into account. Based on the present results, Theograd®-250 mg tablets have predictable absorption and a high (90%) bioavailability if taken after a meal.
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  • 103
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    European journal of clinical pharmacology 25 (1983), S. 69-72 
    ISSN: 1432-1041
    Keywords: levodopa ; intestinal absorption ; small intestine ; bioavailability ; benserazide ; presystemic clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In four healthy subjects the intestinal absorption of levodopa (l-dopa) was investigated by measuring the plasma concentration of the amino acid following the administration of l-dopa at three different sites in the small intestine. In order to minimize presystemic clearance of l-dopa, the subjects were pretreated with the peripheral decarboxylase inhibitor benserazide 3×50 mg every 8 h on the previous day and 1×50 mg 2 h prior to administration of the l-dopa. L-dopa 100 mg dissolved in 0.05 N HCl and 50 mg benserazide dissolved in 0.05 N HCl were coadministered. Under these conditions no difference in tmax, cmax or AUC of l-dopa was observed between administration of the drug into the proximal or the distal part of duodenum, or into the upper part of jejunum. The results indicate that in healthy subjects, during inhibition of peripheral decarboxylase, the rate and extent of l-dopa absorption does not differ at any site in the upper small intestine.
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  • 104
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    European journal of clinical pharmacology 22 (1982), S. 265-272 
    ISSN: 1432-1041
    Keywords: pharmacokinetics ; variation of absorption ratios ; bioavailability ; dissection of variation due to absorption and intermediate processes ; oral drug application
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Differences in the plasma concentrations of drugs after oral administration are caused by two main factors: variation in absorption ratios and in the distribution processes in the body. A new method for the dissection of both types of factors is discussed. The method uses a reference regression of the AUC-values to the corresponding values after intravenous infusion of graded doses. The reference regression is estimated from an appropriate trial. Deviation of the determined AUC-values from the regression curve afford an estimate of the residual variance due to varying distribution volumes or similar random biological effects. For the estimation of absorption ratios after oral administration the drug is given orally to another sample of subjects and their AUC-values are calculated. The deviation of these AUC values due to the above mentioned random effects are simulated using the residual variance of the reference regression, and are subtracted from the observed AUC-values. Then, the differences in the corresponding absorbed doses are transformed by inverting the reference regression. From these doses the empirical distribution function and statistical parameters (e.g. quantiles) are determined. The method has the advantage that no restrictive assumptions are required, such as first order processes, dose linearity, homogeneity of variance or normal distribution of absorption ratios. Its applicability to substances with qualitative differences in their pharmacokinetics is demonstrated by appropriate examples.
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  • 105
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    European journal of clinical pharmacology 22 (1982), S. 463-467 
    ISSN: 1432-1041
    Keywords: orthostatic hypotension ; etilefrine ; dihydroergotamine ; bioavailability ; combination therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Etilefrine undergoes considerable first-pass metabolism through conjugation in the gut wall. In six volunteers bioavailability was reduced to 35% for a fast release tablet and to 17% for a sustained release preparation. The addition fo dihydroergotamine (DHE) to the sustained release preparation surprisingly increased bioavailability to 61%. The plasma levels of the main metabolite formed during the passage through the gut wall indicated an increase in the rate of enteric absorption and therefore also in bioavailability by DHE. This might be due to the influence of DHE upon the vascular resistance of the vessels in the gut wall or a change in gastro-intestinal motility with a prolongation of drug contact time within the absorbing gut segment.
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  • 106
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    European journal of clinical pharmacology 26 (1984), S. 269-270 
    ISSN: 1432-1041
    Keywords: cyclophosphamide ; cytostatic drug ; cancer therapy ; female breast cancer ; bioavailability ; rapid release formulations ; gastric juice resistant formulation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Cyclophosphamide (CP) is an alkylating cytostatic compound, which is activated to its cytotoxic form in the liver [1]. Since the therapeutic range of CP in the treatment of human tumours, is small like other cytostatics, a constant high bioavailability is essential for its oral administration. Although CP has become one of the most widely used cytostatics [2], there do not appear to have been any bioavailability investigations providing the necessary information. The development of a very sensitive gas chromatographic analytical method has now permited investigation of the pharmacokinetics of oral CP in conventional clinical doses [3, 4, 5, 6].
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  • 107
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    European journal of clinical pharmacology 27 (1984), S. 85-89 
    ISSN: 1432-1041
    Keywords: digitoxin ; radioimmunoassay ; pharmacokinetics ; bioavailability ; digitoxin metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and bioavailability of digitoxin were examined in six normal human subjects using an assay that separates digitoxin from its metabolites. After intravenous administration, the mean systemic clearance was 2.44 ml/min; the volume of distribution was 0.47 l/kg; and the elimination half-life was 6.5 days. After oral administration, the elimination half-life was 5.8 days. The bioavailability was 81.5% using the specific assay. Using a non-specific, direct serum digitoxin radioimmunoassay the bioavailability was 98.0%. Assay of aqueous fractions from extracted serum samples indicated higher levels of water-soluble metabolites following oral compared to intravenous digitoxin administration. These findings suggest that previously reported values for digitoxin bioavailability using non-specific methods may be falsely elevated due to the presence of digitoxin metabolites in serum.
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  • 108
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    European journal of clinical pharmacology 27 (1984), S. 85-89 
    ISSN: 1432-1041
    Keywords: digitoxin ; radioimmunoassay ; pharmacokinetics ; bioavailability ; digitoxin metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and bioavailability of digitoxin were examined in six normal human subjects using an assay that separates digitoxin from its metabolites. After intravenous administration, the mean systemic clearance was 2.44 ml/min; the volume of distribution was 0.47 l/kg; and the elimination half-life was 6.5 days. After oral administration, the elimination half-life was 5.8 days. The bioavailability was 81.5% using the specific assay. Using a non-specific, direct serum digitoxin radioimmunoassay the bioavailability was 98.0%. Assay of aqueous fractions from extracted serum samples indicated higher levels of water-soluble metabolites following oral compared to intravenous digitoxin administration. These findings suggest that previously reported values for digitoxin bioavailability using non-specific methods may be falsely elevated due to the presence of digitoxin metabolites in serum.
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  • 109
    ISSN: 1432-072X
    Keywords: Nitrogen fixation ; Regulation ; Guanosine 5′-diphosphate 3′-diphosphate (ppGpp)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Addition of ammonium to N2 fixing cultures of Azotobacter vinelandii, Klebsiella pneumoniae and Clostridium pasteurianum rapidly reduced the intracellular levels of guanosine 5′-diphosphate 3′-diphosphate (ppGpp) by 70–90%. This change might reflect a regulatory role of ppGpp in nitrogen metabolism.
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  • 110
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    Archives of microbiology 136 (1983), S. 20-25 
    ISSN: 1432-072X
    Keywords: Hydrogen production ; Nitrogen fixation ; Hydrogen recycling ; Hydrogenase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Mutants of Rhodopseudomonas capsulata lacking uptake hydrogenase activity have been isolated among those unable to grow photoautotrophically. Studies with these mutants showed increases in nitrogenase mediated H2 production from all substrates tested. In addition, photosynthetic synthetic growth on N2 with malate as carbon source was not affeced by the block in H2 uptake even under low light. Under these growth conditions hydrogen was observed to accumulate in mutant but not in wild-type cultures. This finding suggested that H2 was evolved by nitrogenase during N2 fixation by this photosynthetic bacterium and was efficiently recycled in the wild type.
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  • 111
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    Archives of microbiology 135 (1983), S. 287-292 
    ISSN: 1432-072X
    Keywords: Cyanobacteria ; Respiration ; Nitrogen fixation ; Heterocysts ; K m for O2 ; Anabaena variabilis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Simultaneous measurements of acetylene reduction by Anabaena variabilis and the concentration of dissolved oxygen in the suspension were made using a specially designed vessel which allowed measurements under steady-state conditions. The rate of acetylene reduction in the dark increased with increasing oxygen concentrations until a maximum value was reached at 300 μM O2 (corresponding to 30% O2 in the gas phase at 35°C). This presumably results from a requirement for energy provided by respiration. Measurements of the dependence of respiration rate on dissolved oxygen concentration were made under comparable conditions using an open system to allow conditions close to steady-state to be obtained. The respiration rate of diazotrophically grown Anabaena variabilis had a dependence on oxygen concentration corresponding to the sum of two activities. These had K m values of 1.0 μM and 69 μM and values of V max of similar magnitude. Only the high affinity activity was observed in nitrate-grown cyanobacteria lacking heterocysts, and this presumably represent activity in the vegetative cells. The oxygen concentration dependence of the low affinity activity resembled that for the stimulation of acetylene reduction. We interpret this as the result of oxygen uptake by the heterocysts. The results are consistent with the idea that in intact filaments of cyanobacteria O2 enters heterocysts much more slowly than it enters the vegetative cells.
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  • 112
    ISSN: 1432-072X
    Keywords: Ammonium export ; Ammonium assimilation ; Glutamine synthetase ; Nitrogen fixation ; Rhizobium sp. 32H1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The relationship between ammonium assimilation and ammonium export has been studied in free-living, N2-fixing Rhizobium sp. 32H1. After 55 to 67 h of microaerobic growth under a gas phase of 0.2% O2 – 1.0% CO2 – 98.8% Ar high levels of nitrogenase were observed concomitant with a slightly adenylylated glutamine synthetase (GSI) and some glutamine synthetase (GSII) activity. However, after growth of 89 h, or longer, GSI became adenylylated and the level of GSII had decreased. When the gas phase was shifted to 0.2% O2 – 1.0% CO2 – 98.8% N2, a lag was observed before ammonium export could be detected in the 55 to 67 h cultures. No lag in ammonium export was observed in the cultures previously grown for 89 h. The onset of ammonium export in the 55 to 67 h cultures was found to correlate with the adenylylation state of GSI. There appeared to be no correlation between the level of GSII and the export of ammonium. Neither an increase in the adenylylation level of GSI nor ammonium export was observed when the 55 to 67 h cultures were maintained under the Ar gas mixture.
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  • 113
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    Archives of microbiology 127 (1980), S. 163-165 
    ISSN: 1432-072X
    Keywords: Nitrogen fixation ; Arthrobacter ; Corynebacterium ; Anabaena azollae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Coryneform bacteria were found associated with the nitrogen fixing blue-green alga, Anabaena azollae in the leaf cavity of Azolla caroliniana. Plate counts indicated ca. 7,400±1,900 bacterial cells per mature leaf cavity or approximately 1 bacterial cell for every algal cell. No other type of bacterium was found in these cavities.
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  • 114
    ISSN: 1432-072X
    Keywords: Fluorescent antibody staining ; Nitrogen fixation ; Symbiosis ; Anabaena azollae ; Azolla caroliniana
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Fluorescent antibody staining indicated differences in surface antigenicity in Anabaena azollae cells fresh from the leaf cavities of the fern, Azolla caroliniana, and algae which were isolated and subcultured from this fern. Such results suggest that either changes in antigenicity occur in this phycobiont during culturing or that isolation selects for an antigenically different mutant strain capable of in vitro growth.
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  • 115
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    Archives of microbiology 129 (1981), S. 238-239 
    ISSN: 1432-072X
    Keywords: Rhizobium ; Disaccharide ; Bacteroid ; Transport ; Nitrogen fixation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Slow growing strains of rhizobia appear to lack both uptake systems and catabolic enzymes for disaccharides. In the fast-growing strains of rhizobia there are uptake mechanisms and catabolic enzymes for disaccharide metabolism. In Rhizobium leguminosarum WU 163 and WU235 and R. trifolii WU290, sucrose and maltose uptake appears to be constitutive whereas in R. meliloti WU60 and in cowpea Rhizobium NGR234 uptake of these disaccharides is inducible. There is evidence that there are at least two distinct disaccharide uptake systems in fast-growing rhizobia, one transporting sucrose, maltose and trehalose and the other, lactose. Disaccharide uptake is via an active process since uptake is inhibited by azide, dinitrophenol and carbonyl cyanide m-chlorophenylhydrazone but not by arsenate. Bacteroids of R. leguminosarum WU235 and R. lupini WU8 are unable to accumulate disaccharides.
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  • 116
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    Archives of microbiology 130 (1981), S. 38-43 
    ISSN: 1432-072X
    Keywords: Nitrogen fixation ; Gene expression ; Regulation ; Messenger RNA ; Transcription ; Klebsiella pneumoniae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Nitrogenase messenger RNA synthesis in Klebsiella pneumoniae was determined by labelling cells with (3H)uracil and isolating total RnA, which was then hybridized to filterbound recombinant plasmid pSA30 DNA carrying the nitrogenase structural genes nifH, D, and K. Derepression of nitrogenase mRNA starts 1.5 h before the onset of nitrogenase activity (as measured by acetylene reduction). Exposure of nif-derepressed cultures to either NH 4 + , air, or high temperatures (39° C) results in a rapid decrease of the synthesis rates both of nitrogenase mRNA and nitrogenase polypeptides. Nitrogenase mRNA is remarkably stable. After blocking transcription with rifampicin, hybridizable and actively translatable nitrogenase mRNA survives with an average half-life of 18 min. Half-lives are considerably shorter when rifampicin-inhibited cultures are simultaneously shifted to conditions which are non-permissive for nitrogenase synthesis, pointing to some posttranscriptional influence on nitrogenase mRNA stability. In all experiments performed there was no evidence for uncoupling of nitrogenase mRNA synthesis from nitrogenase mRNA translation, indicating that nitrogenase synthesis is regulated solely by transcriptional control.
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  • 117
    ISSN: 1432-072X
    Keywords: Rhizobium trifolii ; Symbiosis ; Nodulation ; Nitrogen fixation ; Symbiotic genes ; Reiterated sequences ; Plasmid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A Rhizobium trifolii symbiotic plasmid specific gene library was constructed and the physical organisation of regions homologous to nifHDK, nifA and nod genes was determined. These symbiotic gene regions were localised to u 25 kb region on the sym-plasmid, pPN1. In addition four copies of a reiterated sequence were identified on this plasmid, with one copy adjacent to nifH. No rearrangement of these reiterated sequences was observed between R. trifolii bacterial and bacteroid DNA. Analysis of a deletion derivative of pPN1 showed that these sequences were spread over a 110 kb region to the left of nifA.
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  • 118
    ISSN: 1432-072X
    Keywords: Ammonia assimilation ; Lichen symbioses ; Nitrogen fixation ; 15N kinetics ; Peltigera canina
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract On following N2-incorporation and subsequent metabolism in the lichen Peltigera canina using 15N as tracer, it was found, over a 30 min period, that greatest initial labelling was into NH 4 + followed by glutamate and the amide-N of glutamine. Labelling of the amino-N of glutamine, aspartate and alanine increased slowly. Pulse-chase experiments using 15N confirmed this pattern. On inhibiting the GS-GOGAT pathway using l-methionine-dl-sulphoximine and azaserine, 15N enrichment of glutamate, alanine and aspartate continued although labelling of glutamine was undetectable. From this and enzymic data, NH 4 + assimilation in the P. canina thallus appears to proceed via GS-GOGAT in the cyanobacterium and via GDH in the fungus; aminotransferases were present in both partners. The cyanobacterium assimilated 44% of the 15N2 fixed; the remainder was liberated almost exclusively as NH 4 + and then assimilated by fungal GDH.
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  • 119
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    Archives of microbiology 135 (1983), S. 103-109 
    ISSN: 1432-072X
    Keywords: RNA polymerase ; Transcription ; Nitrogen fixation ; Symbiosis ; Rhizobium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract DNA-dependend RNA polymerase (EC 2.7.7.6) from Rhizobium japonicum was purified. The subunit structure was found to be ββ′α2σ, with the following apparent molecular weights determined by electrophoresis: M r (β and β') 150,000 each, M r (σ) 96,000, M r (α) 40,000, M r (holoenzyme) 490,000, M r (core enzyme) 380,000. The recovery of σ was 28%. RNA polymerase from aerobically grown R. japonicum cells and from nitrogen-fixing cells have the same electrophoretic properties suggesting that no chemical modification of the enzyme occurs when cells undergo this metabolic differentiation. The enzyme is Mg2+-dependent, rifampicin-sensitive, and has optimal activity at alkaline pH (8–10) and at 35–40° C. It binds strongly to bacteriophage T7 promoters, weakly to antibiotic resistance genes, and not at all to cloned R. japonicum nif DNA. Preliminary in vitro transcription experiments, including nif DNA as template, revealed that additional factors may be required for selective transcription from promoters.
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  • 120
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    Archives of microbiology 136 (1983), S. 219-221 
    ISSN: 1432-072X
    Keywords: Xanthobacter ; Nitrogen fixation ; Oxygen sensitivity ; Nitrogen metabolism ; Glutamine synthetase ; Glutamate synthase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract N2-fixation was investigated in the chemoautotrophic hydrogen bacterium Xanthobacter H4-14. N2-fixing batch cultures of this organism could only be grown at pO2 values of around 0.02 bar, and in continuous culture dissolved oxygen tensions above 16 μM were found to inhibit N2-fixation. Xanthobacter H4-14 utilized a variety of amino acids, nitrate and ammonia as nitrogen sources. Cell-free extracts from steady-state continuous cultures of ammonia grown, nitrate grown and N2-fixing Xanthobacter were assayed for the presence of ammonia assimilation enzymes. No alanine dehydrogenase or glutamate dehydrogenase activity was detected. Ammonia was assimilated exclusively via the glutamine synthetase/glutamate synthase pathway, irrespective of the extracellular concentration of ammonia.
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  • 121
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    Archives of microbiology 124 (1980), S. 161-167 
    ISSN: 1432-072X
    Keywords: Nitrogen fixation ; Photosynthesis ; Green alga ; Chl a and b ; DCMU ; Light and O2 dependency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A unicellular alga which can grow in the light without a combined nitrogen source was isolated from a hot spring. The cells were almost spherical, usually 5–10 μm in diameter. Absorption spectra of the watersoluble pigments and of the acetone-extracted ones revealed the existence of chlorophyll a and b and the absence of phycobilins. Thin sections examined by electron microscopy revealed an eukaryotic organization with features typical of the coccoid green algae (the Chlorococcales). Cells divided by internal cytokinesis and subsequent liberation of daughter cells from the parental wall, in a way similar to Chlorella. The alga reduced acetylene to ethylene and incorporated 15N2 into cell protoplasm when incubated in a low oxygen atmosphere. Nitrogenase activity was light-dependent, microaerophilic and thermophilic. Although the association of symbiotic nitrogen fixing prokaryotes with the cells may still be possible, any such organisms have not so far been detected.
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  • 122
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    Archives of microbiology 127 (1980), S. 115-118 
    ISSN: 1432-072X
    Keywords: Proteus mirabilis ; Serratia marcescens ; Erwinia herbicola ; Nitrogen fixation ; nif genes ; his genes ; Plasmids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Plasmid pRD1, an R plasmid of the P incompatibility group which carries his and nif genes from Klebsiella pneumoniae in addition to drug resistance markers derived from RP4, was transferred to His- mutants of Serratia marcescens, Erwinia herbicola and Proteus mirabilis. His+ transconjugants were obtained at low but different frequencies according to recipient genus. Transconjugants all acquired the drug resistance, and were Nif+ in S. marcescens and E. herbicola, having acetylene-reducing activities of the same order of magnitude as the parent K. pneumoniae and fixing 15N2. No evidence for nif expression in P. mirabilis transconjugants was obtained though the nif genes were present.
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  • 123
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    Archives of microbiology 132 (1982), S. 219-224 
    ISSN: 1432-072X
    Keywords: Rhizobium ; Nitrogen fixation ; Nodules ; Soybean
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Several mutants defective in nodulation were isolated from Rhizobium japonicum strains 3I1b110 and 61A 76. Mutants of class I do not form nodules after incubation with soybean [Glycine max (L.) Merrill] for 17 days, but will do so by 28 days. When host plants other than G. max are infected with several of these strains, there is no detectable difference in the time of nodulation or size of nodules as compared to the wild type. Two mutants of class I (i. e., SM1 and SM2) have been shown previously to be altered in the lipopolysaccharide portion of their cell wall. Mutants of class II are not slow to nodulate but form fewer nodules than the wild type on all the host plants tested. Mutants of class III are unable to form nodules. Some bacteriophage-resistant mutants, altered in cell surface structure, fall into this class. Two mutants of class III do not bind to soybean roots.
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  • 124
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    Archives of microbiology 133 (1982), S. 172-177 
    ISSN: 1432-072X
    Keywords: Beggiatoa ; Nitrogen fixation ; Acetylene reduction ; Nitrate assimilation ; Microaerobic ; Isolation of marine strains
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Four newly isolated marine strains of Beggiatoa and five freshwater strains were tested for nitrogen fixation in slush agar medium. All strains reduced acetylene when grown microaerobically in media containing a reduced sulfur source and lacking added combined nitrogen. The addition of 2 mmol N, as nitrate or ammonium salts, completely inhibited this reduction. Although not optimized for temperature or cell density, acetylene reduction rates ranged from 3.2 to 12 nmol·mg prot-1 min-1. Two freshwater strains did not grow well or reduce acetylene in medium lacking combined nitrogen if sulfide was replaced by thiosulfate. Two other strains grew well in liquid media lacking both combined nitrogen and reduced sulfur compounds but only under lowered concentrations of air. All freshwater strains grew well in medium containing nitrate as the combined nitrogen source. Since they did not reduce acetylene under these conditions, we infer that they can assimilate nitrate.
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  • 125
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    Archives of microbiology 133 (1982), S. 312-317 
    ISSN: 1432-072X
    Keywords: Rhizobium japonicum ; Rhizobium leguminosarum ; Formate metabolism ; Formate dehydrogenase ; Nitrogen fixation ; Nitrogenase ; Bacteroids ; Symbiosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Formate metabolism supported nitrogen-fixation activity in free-living cultures of Rhizobium japonicum. However, formate0dependent nitrogense activity was observed only in the presence of carbon sources such as glutamate, ribose or aspartate which by themselves were unable to support nitrogenase activity. Formate-dependent nitrogenase activity was not detected in the presence of carbon sources such as malate, gluconate or glycerol which by themselves supported nitrogenase activity. A mutant strain of R. japonicum was isolated that was unable to utilise formate and was shown to lack formate dehydrogenase activity. This mutant strain exhibited no formate-dependent nitrogenase activity. Both the wild-type and mutant strains nodulated soybean plants effectively and there were no significant differences in the plant dry weight or total nitrogen content of the respective plants. Furthermore pea bacteroids lacked formate dehydrogenase activity and exogenously added formate had no stimulatory effect on the endogenous oxygen uptake rate. The role of formate metabolism in symbiotic nitrogen fixation is discussed.
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  • 126
    ISSN: 1432-072X
    Keywords: Nitrogen fixation ; Nitrogenase regulation ; Glutamine synthetase ; Methionine suofoximine ; Rhodospirillaceae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Methionine sulfoximine (MSX), an irreversible inhibitor of glutamine synthetase of Rhodopseudomonas palustris restored nitrogenase activity to cells in which nitrogenase had been completely inhibited by ammonia switch-off. After addition of MSX, there was a lag period before nitrogenase activity was fully restored. During this lag, glutamine synthetase activity progressively decreased, and near the time of its complete inhibition, nitrogenase activity resumed. Nitrogenase switch-off by ammonia thus required active glutamine synthetase. Glutamine itself caused nitrogenase inhibition whose reversal by MSX depended on the relative ratio of MSX to glutamine. Unlike ammonia, glutamine inhibited nitrogenase under conditions where glutamine synthetase activity was absent. This indicates that glutamine is the effector molecule in nitrogenase switch-off, for instance by interacting with the enzymatic system for Fe protein inactivation. The effects of glutamine and MSX were also dependent on the culture age. Possible explanation for this and for the competitive effects are a common binding site within the regulatory apparatus for nitrogenase, or, in part, within a common transport system. Some observations with MSX were extended to Rhodopseudomonas capsulata and agreed with those in R. palustris.
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  • 127
    ISSN: 1432-072X
    Keywords: Azotobacter vinelandii ; Continuous culture ; Oxygen control ; Nitrogen fixation ; Respiratory protection
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    Topics: Biology
    Notes: Abstract Azotobacter vinelandii strain OP was grown in continuous culture at various dissolved oxygen concentrations of air (100% air saturation of the medium=225 ±14 μM O2). Sucrose was added as carbon source and either dinitrogen or ammonia as nitrogen sources. Irrespective of the nitrogen source steady state cultures showed the following general responses with dissolved oxygen concentrations increasing from about 1% to 30% air saturation: (i) cell protein levels, (ii) the amount of cell protein formed per sucrose consumed as well as (iii) nitrogenase activity decreased by at least a factor of two while (iv) cellular respiration increased. At higher oxygen concentrations the parameters changed only slightly, if at all. Increasing the sucrose concentration in the inflowing medium (s R) from 3 g/l to 15 g/l increased the total level of cellular respiration with nitrogen-fixing cultures but was more pronounced with ammonium-assimilating cultures. With nitrogen-fixing cultures cell protein levels increased five-fold while the ratio of protein formed per sucrose consumed as well as cellular nitrogenase activity remained unaffected. With ammonium-assimilating cultures the cell protein level was only doubled and the level of cell protein formed per sucrose consumed was decreased at the higher s R. Increasing the dilution rate at a constant oxygen concentration of 45% air saturation resulted in an almost parallel increase of both cellular respiratory and nitrogenase activity at low and moderate dilution rates. At high dilution rates nitrogenase activity increased steeply over the respiratory activity. Nitrogen-fixing cultures adapted to various oxygen concentrations were subjected to oxygen stress by increasing the oxygen concentration for 7 min. In all cases, this resulted in a complete inhibition (‘switch-off’) of nitrogenase activity. Upon restoration of the original oxygen concentration nitrogenase activity returned to a decreased level. The discussion arrives at the conclusion that some of the results are incompatible with the concept of respiratory protection of nitrogenase.
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  • 128
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    Archives of microbiology 136 (1983), S. 81-83 
    ISSN: 1432-072X
    Keywords: Ammonia production ; Anabaena ; Cyanobacteria ; Nitrate reductase ; Nitrogen fixation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In the filamentous heterocystous cyanobacterium Anabaena sp. strain ATCC 33047 dinitrogen fixation and nitrate reduction are mutually exclusive processes. Nitrate promotes nitrate reductase synthesis and represses nitrogenase formation. Inhibition of ammonium assimilation by l-methionine-d,l-sulfoximine (MSX) alleviates the repressive effect of nitrate on nitrogenase synthesis, thus indicating that the nitrate effect is indirect through metabolites generated from the ammonium derived from nitrate reduction. In MSX-treated cells both nitrate reduction and dinitrogen fixation take place simultaneously, although at different sites of the filament, without any apparent competition for the required reducing power. The MSX-treated Anabaena cells generate ammonium from both nitrate and dinitrogen, simultaneously.
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  • 129
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    Archives of microbiology 138 (1984), S. 212-216 
    ISSN: 1432-072X
    Keywords: Denitrification ; Nitrate respiration ; Nitrous oxide reduction ; Nitrogen fixation ; Azospirillum
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    Topics: Biology
    Notes: Abstract Nitrous oxide reduction can consistently be demonstrated with high activities in cells of Azospirillum brasilense Sp 7 which are grown anaerobically in the presence of low amounts of nitrite. Azospirillum can even grow anaerobically with nitrous oxide in the absence of any other respiratory electron acceptor. Nitrous oxide reduction by Azospirillum is inhibited by acetylene, amytal and weakly by carbon monoxide. Azospirillum converts nitrous oxide to molecular nitrogen without the formation of ammonia. The cells must, therefore, be supplied with ammonia from nitrogen fixation during anaerobic growth with nitrous oxide. When no other nitrogen compound besides nitrous oxide is available in the medium, the bacteria synthesize nitrogenase from protein reserves in about 2 h. Nitrogenase synthesis is blocked by chloramphenicol under these conditions. In contrast, the addition of nitrate or nitrite to the medium represses the synthesis of nitrogenase. Nitrous oxide reduction by Azospirillum and other microorganisms is possibly of ecological significance, because the reaction performed by the bacteria may remove nitrous oxide from soils.
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  • 130
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    Archives of microbiology 130 (1981), S. 96-100 
    ISSN: 1432-072X
    Keywords: Nitrogen fixation ; Nitrate respiration ; Denitrification ; Assimilatory nitrate reduction ; Dissimilatory nitrate reduction ; Acetylene reduction ; Azospirillum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Azospirillum spp. participate in all steps of the nitrogen cycle except nitrification. They can fix molecular nitrogen and perform assimilatory nitrate reduction and nitrate respiration. Culture conditions have been defined under which nitrate is used both as terminal respiratory electron acceptor and as nitrogen source for growth. Nitrate and, possibly to a very limited extent, nitrite, but not sulfate, iron or fumarate support anaerobic respiration. Under anaerobic conditions, nitrate can also supply energy for nitrogen fixation but without supporting growth. Nitrate-dependent nitrogenase activity lasts only for 3–4 h until the enzymes of assimilatory nitrate reduction are synthesized. Nitrite accumulates during this period and inhibits nitrogenase activity at concentrations of about 1 mM.
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  • 131
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    Archives of microbiology 140 (1984), S. 215-217 
    ISSN: 1432-072X
    Keywords: Glutathione reductase ; Cyanobacteria ; Nostoc muscorum ; O2 protection ; Glutathione ; Nitrogen fixation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Glutathione reductase activity was detected and characterized in heterocysts and vegetative cells of the cyanobacterium Nostoc muscorum. The activity of the enzyme varied between 50 and 150 nmol reduced glutathione· min-1·mg protein-1, and the apparent Km for NADPH was 0.125 and 0.200 mM for heterocysts and vegetative cells, respectively. The enzyme was found to be sensitive to Zn+2 ions, however, preincubation with oxidized glutathione rendered its resistance to Zn+2 inhibition. Nostoc muscorum filaments were found to contain 0.6–0.7mM glutathione, and it is suggested that glutathione reductase can regenerate reduced glutathione in both cell types. The combined activity of glutathione reductase and isocitrate dehydrogenase in heterocysts was as high as 18 nmol reduced glutathione·min-1·mg protein-1. A relatively high superoxide dismutase activity was found in the two cell types; 34.2 and 64.3 enzyme units·min-1·mg protein-1 in heterocysts and vegetative cells, respectively. We suggest that glutathione reductase plays a role in the protection mechanism which removes oxygen radicals in the N2-fixing cyanobacterium Nostoc muscorum.
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  • 132
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    Archives of microbiology 132 (1982), S. 333-337 
    ISSN: 1432-072X
    Keywords: Anabaena variabilis Kütz ; 14C-prelabeled blue-green algae ; Interaction respiration/photosynthesis ; CO2 exchange ; Nitrogen fixation
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    Topics: Biology
    Notes: Abstract Prelabeled Anabaena variabilis Kütz. evolves 14CO2 in the light with KCN and DCMU (2,4-dichlorophenyl-1,1-dimethylurea) present, comparable to the dark control without inhibitors added. Double-reciprocal plots of CO2 release vs. light intensity with either KCN or KCN+DCMU present result in two straight lines intersecting at the ordinate. Apparently, reducing equivalents originating from carbohydrate catabolism are channeled into the photosynthetic electron-transport chain, competing for electrons from photosystem II. Under these conditions, the CO2 release is accompanied by a light-dependent oxygen uptake, presumably due to oxygen-reducing photosystem-I activity while ribulose-bisphosphate carboxylase is inhibited by KCN. Comparing nine blue-green algae it was shown that only nitrogen-fixing species release substantial amounts of CO2 in the light with KCN or KCN+DCMU present. This release is particularly obvious with Anabaena variabilis Kütz. under nitrogen-fixing conditions, but small when the alga is grown with combined nitrogen. We conclude that nitrogen-fixing species share a common link between respiratory and photosynthetic electron transport. The physiological role may be electron supply of nitrogenase by photosystem I.
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  • 133
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    Archives of microbiology 133 (1982), S. 6-10 
    ISSN: 1432-072X
    Keywords: Rhodospirillaceae ; Rhodopseudomonas globiformis ; Nitrogen metabolism ; Nitrogen fixation ; Glutamine synthetase
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    Notes: Abstract Rhodopseudomonas globiformis strain 7950 grew with a variety of amino acids, urea, or N2 as sole nitrogen sources. Cultures grown on N2 reduced acetylene to ethylene; this activity was absent from cells grown on nonlimiting NH 4 + . Glutamate dehydrogenase could not be detected in extracts of cells of strain 7950, although low levels of an alanine dehydrogenase were present. Growth ofR. globiformis on NH 4 + was severely inhibited by the glutamate analogue and glutamine synthetase inhibitor, methionine sulfoximine. High levels of glutamine synthetase (as measured in the γ-glutamyl transferase assay) were observed in cell extracts of strain 7950 regardless of the nitrogen source, although N2 and amino acid grown cells contained somewhat higher glutamine synthetase contents than cells grown on excess NH 4 + . Levels of glutamate synthase inR. globiformis were consistent with that reported from other phototrophic bacteria. Both glutamate synthase and alanine dehydrogenase were linked to NADH as coenzyme. We conclude thatR. globiformis is capable of fixing N2, and assimilates NH 4 + primarily via the glutamine synthetase/glutamate synthase pathway.
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  • 134
    ISSN: 1432-072X
    Keywords: Cyanobacteria ; Ultrastructure ; Nitrogen fixation ; Water stress ; Taxonomy ; DNA ; Plasmids
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    Notes: Abstract Two strains of desiccation-tolerant coccoid cyanobacteria, Chroococcus S24, a marine form, and Chroococcus N41, a cryptoendolith isolated from a hot-desert rock, have been characterized. The mol % DNA base compositions of the strains are 47.1 and 48.9% respectively. Plasmid DNA was not detected in either strain. The pigment contents and nutritional characteristics of the strains are identical. Both lack phycoerythrinoid pigments and, in culture, behave as slow-growing halotolerant marine forms with elevated requirements for Na+, Cl−, Mg2+ and Ca2+. Sucrose was the only carbon source of those tested that supported photoheterotrophic growth. Each strain synthesizes nitrogenase under anaerobic conditions but not in air. Morphologically the two strains are indistinguishable. They are considered to be independent isolates of the same cyanobacterial species. Chroococcus N41 was studied in detail with the electron microscope. When brought to equilibrium at matric water potentials of-168 MPa and lower (to-673 MPa=c0.12a w) the protoplast shrinks, but the cells maintain the same size and diameter as those at-2,156 kPa (MN medium; control); the sheath expands and remains attached to the cell wall outer membrane by fibrils. The cell wall, cell membrane, thylakoid membranes, cyanophycin granules and carboxysomes appeared intact in desiccated cells.
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  • 135
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    Theoretical chemistry accounts 60 (1982), S. 579-587 
    ISSN: 1432-2234
    Keywords: Nitrogen fixation ; Nitrogen complexes ; Carbon monoxide complexes ; Electronic effects
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    Topics: Chemistry and Pharmacology
    Notes: Abstract MNDO method is used to study the interaction of nitrogen and carbon monoxide molecules with a proton, hydrogen atom, hydride ion, hydrogen molecule ion and hydrogen molecule. Predicted geometries and heats of reaction of different complexes are presented. The wave functions are analyzed in terms of ground state charge distributions and overlap populations. Electronic effects accompanying complexation are also discussed.
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  • 136
    ISSN: 1432-2048
    Keywords: Nitrogen fixation ; Nodule development ; Senescence (nodules) ; Vigna
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    Topics: Biology
    Notes: Abstract Cowpea (Vigna unguiculata (L.) Walp cv. Vita 3) seedlings inoculated with Rhizobium strain CB756 were cultured with their root systems maintained in air or in Ar: O2 (80:20, v/v) during early nodule development (up to 24 d after sowing). Compared with those in air, seedlings in Ar:O2 showed progressive N deficiency with inhibited shoot growth, reduced ribulose-1,5-bisphosphate carboxylase and total protein levels and loss of chlorophyll in the leaves. Nodule initiation, differentiation of infected and uninfected nodule tissues and the ultrastructure of bacteriod-containing cells were similar in the air and Ar: O2 treatments up to 16 d after sowing. Thereafter the Ar: O2 treatment caused cessation of growth and development of nodules, reduced protein levels in bacteroids and nodule plant cells, and progressive degeneration of nodule ultrastructure leading to premature senescence of these organs. Provision of NO 3 - (0.1–0.2 mM) to Ar: O2-grown seedlings overcame the abovementioned consequences of N2 deficiency on nodule and plant growth, but merely delayed the degenerative effects of Ar: O2 treatment on nodule structure and senescence. Treatment of Ar: O2-grown seedlings with NO 3 - greatly increased the protein level of nodules but the increase was largely restricted to the plant cell fraction as opposed to the bacteroids. By contrast, NO 3 - treatment of air-grown seedlings increased protein of bacteroid and host nodule fractions to the same relative extents when compared with air-grown plants not supplemented with NO 3 - . These findings, taken together with studies of the distribution of N in nodules of symbiotically effective plants grown from 15N-labeled seed, indicate that direct incorporation of fixation products by bacteroids may be a critical feature in the establishment and continued growth of an effective symbiosis in the cowpea seedling.
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  • 137
    ISSN: 1432-2048
    Keywords: Glutamine synthetase ; Leghaemoglobin ; Nitrogenase ; Nitrogen fixation ; Phaseolus ; Rhizobium
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    Notes: Abstract The activities of glutamine synthetase (GS), nitrogenase and leghaemoglobin were measured during nodule development in Phaseolus vulgaris infected with wild-type or two non-fixing (Fix-) mutants of Rhizobium phaseoli. The large increase in GS activity which was observed during nodulation with the wild-type rhizobial strain occurred concomitantly with the detection and increase in activity of nitrogenase and the amount of leghaemoglobin. Moreover, this increase in GS was found to be due entirely to the appearance of a novel form of the enzyme (GSn1) in the nodule. The activity of the form (GSn2) similar to the root enzyme (GSr) remained constant throughout the experiment. In nodules produced by infection with the two mutant strains of Rhizobium phaseoli (JL15 and JL19) only trace amounts of GSn1 and leghaemoglobin were detected.
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  • 138
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    Journal of pharmacokinetics and pharmacodynamics 10 (1982), S. 157-172 
    ISSN: 1573-8744
    Keywords: sulfisoxazole ; pharmacokinetics—unbound drug ; pharmacokinetics—total drug ; bioavailability ; healthy volunteers ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Plasma concentrations of total and unbound sulfisoxazole were followed after single intravenous and oral doses of 1 g sulfisoxazole and during a 500-mg, four-time-a-day dosing regimen in six healthy males, using a specific high pressure liquid Chromatographic assay method. Saturable plasma protein binding was observed at total concentrations above 80–100 mg/liter. The clearance of sulfisoxazole was 18.7±3.9ml/min for total drug and 232±64ml/min for unbound drug. Renal elimination, on the average, accounted for 49% of the clearance of sulfisoxazole. The apparent volume of distribution for total drug was 10.9±2.0 liters and 136±36 liters for unbound drug, indicating that sulfisoxazole is primarily distributed extracellularly. Accumulation of N4-acetyl-sulfisoxazole during multiple dosing did not affect the disposition of sulfisoxazole. Adjusting for variable renal clearances between oral and intravenous administration and using the unbound plasma concentrations, the bioavailability for an oral dose of sulfisoxazole was found to be 0.95±0.04.
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  • 139
    ISSN: 1573-8744
    Keywords: phenytoin ; bioavailability ; Michaelis-Menten parameters
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The bioavailability of phenytoin from rapid release capsule and oral solution formulations relative to that of a slow release capsule formulation was assessed in five patients who had participated in a three-way crossover study performed at steady state. The subjects then underwent dosage adjustment utilizing the slow release formulation, and estimates of their Michaelis-Menten parameters thus obtained were utilized in calculating the relative bioavailabilities. In addition, expected changes in steady-state plasma phenytoin concentrations were calculated assuming initial levels of 15 mg/liter, with increases and decreases in bioavailability of 10%. The consequences of such alterations in the extent of phenytoin absorption or average content of the dosage form may be clinically significant, particularly where the initial phenytoin level is equal to or greater than the patient's operative Km.
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  • 140
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    Journal of pharmacokinetics and pharmacodynamics 10 (1982), S. 465-494 
    ISSN: 1573-8744
    Keywords: disopyramide ; pharmacokinetics ; bioavailability ; metabolite ; half-life ; protein binding ; disease states ; drug-drug interaction
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Current information on the pharmacokinetics of disopyramide is reviewed with emphasis on the implications for antiarrhythmic therapy. The absolute bioavailability, the disposition half-life, the plasma clearance, and the renal clearance for normal subjects and patients are discussed. Drug-drug interactions are discussed, and a new flexible intravenous dosing schedule is proposed.
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  • 141
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    Journal of pharmacokinetics and pharmacodynamics 10 (1982), S. 335-348 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; bioavailability ; growth ; literature growth ; logistic function
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The literature growth in pharmacokinetics and bioavailability between the years 1964 and 1980 is analyzed. During much of this period, the literature doubled approximately every 1.6 years. However, during the period 1978–1980, little or no growth was observed. During the period 1950–1967, the total chemical literature increased exponentially with a half-life of 8.28 years; between 1968 and 1980, the half-life was 12.4 years. Thus, the pharmacokinetic literature increased at a much more rapid pace than did the total chemical literature in general. The subject of growth is considered in a general context, particularly as influenced by psychological, sociological, political, and economic factors. It is concluded that while mathematical functions may adequately describe past literature trends, they have little if any utility in predicting future trends in specific research areas such as pharmacokinetics.
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  • 142
    ISSN: 1573-8744
    Keywords: chloramphenicol-3-monosuccinate ; chloramphenicol-1-monosuccinate ; chloramphenicol ; bioavailability ; pharmacokinetics ; intravenous administration ; adult patients
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of chloramphenicol (CAP) and total chloramphenicol succinate (CAPS) were studied in eight hospitalized adult patients with normal renal and hepatic function receiving intravenous chloramphenicol sodium succinate therapy. The steady-state peak concentrations of CAP (8.4–26.0 μg/ml) occurred at an average of 18.0 min (range 5.4–40.2) after cessation of the chloramphenicol sodium succinate infusion. Unhydrolyzed CAPS prodrug, representing 26.0±7.0% of the dose, was recovered unchanged in the urine indicating that the bioavailability of CAP from a dose of intravenous chloramphenicol succinate is not complete. A pharmacokinetic model was developed for simultaneous fitting of CAP and CAPS plasma concentration data. Pharmacokinetic parameters determined by simultaneous fitting were: V, 0.81±0.18 liters/kg; t1/2, 3.20 ±1.02 hr; CLB, 3.21±1.27 ml/min/kg for chloramphenicol; and V, 0.38±0.13 liters/kg; t1/2, 0.57±0.12hr; CLB, 7.72±1.87 ml/min/kg for total chloramphenicol succinate.
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  • 143
    ISSN: 1573-8744
    Keywords: hydrochlorothiazide ; triamterene ; hydroxytriamterene sulfate ; pharmacokinetics ; bioavailability ; renal clearance ; interaction
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Hydrochlorothiazide, triamterene, and hydroxytriamterene sulfate were monitored in the plasma and urine of 24 healthy young men taking single doses of a liquid preparation containing both hydrochlorothiazide and triameterene, liquid preparations containing either of these drugs alone, and a combination tablet recently formulated with a dose ratio of hydrochlorothiazide: triamterene (1∶1,5) found to give optimal potassium-sparing effect. In contradiction to a recent publication, no interaction between the drugs affecting the bioavailability or renal clearance of either could be demonstrated. The previous report of drug-drug interaction probably arose from formulationrelated problems with bioavailability from the two capsule and two tablet products which had been studied. A well-formulated hydrochlorothiazide-triamterene combination tablet promotes plasma concentrations and urinary excretion of hydrochlorothiazide, triamterene, and hydroxytriamterene sulfate which are virtually identical to those seen after either a combination liquid dosage form or simple liquid forms containing only one of the two drugs.
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  • 144
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    Journal of pharmacokinetics and pharmacodynamics 10 (1982), S. 231-245 
    ISSN: 1573-8744
    Keywords: nitrazepam ; i.v. ; oral ; rectal administration ; protein binding ; pharmacokinetics ; bioavailability
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and bioavailability of nitrazepam following intravenous, oral (tablet), and rectal (solution) administration were studied in seven healthy, young male volunteers. Nitrazepam plasma concentrations were determined by electron-capture GLC; pharmacokinetic evaluations were made by compartmental analysis (NONLIN) and compared with the results obtained by a less stringent modelling of the data. The plasma concentration-time profile was similar for all three routes of administration. Mean kinetic parameters as obtained by compartmental analysis of i.v. nitrazepam were: distribution half-life 17 min; volume of distribution after equilibrium 2.14 liters/kg; total plasma clearance 61.6 ml/min; elimination half-life 29.0 h. The mean protein unbound fraction of nitrazepam in plasma was 12.3% and the clearance of the unbound fraction was 506 ml/min. Absorption of oral nitrazepam started after the elapse of a lag time (mean value 12 min) and occurred as an apparent first-order process in all but one subject, with a mean absorption half-life of 16 min. Distribution and elimination half-lives were comparable with those following i.v. administration. Following rectal administration of the nitrazepam solution, rapid first-order absorption occurred with a mean lag time of 4 min and a mean absorption half-life of 9 min. Peak times (median 18 min) were significantly shorter than following oral administration (median 38 min), but there was little difference in peak concentrations. The distribution half-life was similar to i.v. and oral administration, but the elimination half-lives were longer with a mean value of 33.1 h. Following i.v. administration a good agreement was found between the results obtained by compartmental analysis using NONLIN and those obtained by a less stringent modelling of the data. Following oral and rectal administration, a good agreement between the two procedures was found for the elimination half-life; estimation of bioavailability, however, was higher by compartmental analysis. The mean bioavailability data showed that absorption is complete when nitrazepam is given orally and almost 20% lower when it is given rectally, but considerable interindividual differences were observed.
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  • 145
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    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 561-576 
    ISSN: 1573-8744
    Keywords: methylprednisolone ; bioavailability ; pharmacokinetics ; oral and parenteral administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract This study was conducted to evaluate the influence of route of administration upon the bioavailability and pharmacokinetics of methylprednisolone sodium succinate. Fourteen healthy adult male volunteers received 40 mg doses of methylprednisolone as the following treatments after an overnight fast in a 4-way crossover design: (a) as a 1 ml i.v. bolus;(b) as a 1 ml i.m. injection;(c) administered as an oral solution;and (d) as 5×8 mg oral tablets. Both the ester and free methylprednisolone were determined in plasma and urine. Study results indicate that the ester is rapidly and extensively converted to free methylprednisolone after all routes. The extent of methylprednisolone absorption was equivalent after i.v. and i.m. administration. Both orally administered treatments resulted in a lower extent of absorption attributed to a first-pass effect. Although a slightly lower extent of absorption was demonstrated following the oral administration of the methylprednisolone sodium succinate solution relative to the methylprednisolone oral tablets, this average difference of 9% would probably be of minimal therapeutic importance.
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  • 146
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    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 289-313 
    ISSN: 1573-8744
    Keywords: protein binding ; pharmacokinetics ; bioavailability ; disopyramide ; heart failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and bioavailability of total (bound plus unbound) and unbound disopyramide were compared following the simultaneous administration of an oral dose of disopyramide and an intravenous dose of14C-disopyramide in five normal volunteers and in 11 patients with congestive heart failure. The binding of disopyramide varied between 60 and 92% in patients and between 81 and 88% in normal subjects at postequilibrium drug concentrations of 10−7M. The binding of disopyramide to serum protein was concentration-dependent in all study subjects at serum concentrations achieved following drug administration. The association constant for the first binding site in serum from normal subjects and patients averaged 8.7X105 M−1 and 4.4X10 5 M−1, respectively (p 〈 0.05). The unbound clearance of disopyramide averaged 277ml/min and 209 ml/min in normal subjects and in patients (p 〈 0.05). When normalized for body weight, the unbound clearance between patients and normal subjects was not significantly different. The elimination half-life of unbound concentrations in normal subjects and in patients averaged 4.9 and 6.1 h, respectively (p 〈 0.05). The clearance and elimination half-life of total disopyramide was the same in both groups. Although the bioavailability of disopyramide averaged 0.85 in both groups, it was more variable in patients owing to the variability in the fraction of the dose absorbed. The unbound renal clearance and volume of distribution at steady state of disopyramide was related to cardiac index. The ratio of elimination half-lives of total and unbound disopyramide was related to the extent of serum protein binding.
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  • 147
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    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 463-481 
    ISSN: 1573-8744
    Keywords: bioavailability ; absorption ; deconvolution ; computer program for deconvolution ; algorithm for deconvolution ; drug input evaluation ; input response in linear pharmacokinetic systems ; pentobarbital absorption ; cimetidine absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The procedure of deconvolution to evaluate the rate and the extent of input from absorption data and data from intravenous administration is the most fundamental and least assumptive method of accurately evaluating drug absorption in linear pharmacokinetics. It is shown for linear systems that if the absorption response and the response from an intravenous infusion or bolus administration are both well approximated by a polyexponential function, then the rate of absorption can be expressed as a sum of exponentials. An algorithm and computer program are presented whereby the absorption function is uniquely defined from the model-independent parameters of the polyexponential expressions fitted to the absorption data and data from intravenous administration. Fitting a sum of exponentials to data has become a routine procedure in pharmacokinetics. The method presented therefore makes the previously complex task of deconvolution a simple procedure. The deconvolution approach is discussed in relation to conventional methods of evaluating drug absorption and appears to have some distinct advantages over these methods. The method is tested using simulated data and demonstrated using pentobarbital and cimetidine data from human subjects.
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  • 148
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    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 243-255 
    ISSN: 1573-8744
    Keywords: quinidine ; bioavailability ; absorption ; solutions ; rapidiy releasing tablets ; humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The gastrointestinal absorption of quinidine from three commercially available tablet products has been compared to that from a quinidine sulfate solution previously found to have 70% of the systematic availability of an intravenous dose. Quinidine gluconate solution was included in the study to compare the absorption characteristics of the two quinidine salts. The tablets were given in a counterbalanced sequence preceded by one quinidine solution and followed by the other in a crossover design. The three tablets proved to be equivalent to one another with respect to extent and rate of absorption. The absorption properties of the two solutions were indistinguishable. The tablets were equivalent to the solutions in extent but not in rate of absorption.
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  • 149
    ISSN: 1573-8744
    Keywords: theophylline ; absorption ; bioavailability ; enteric release ; tablets ; plasma concentrations ; dissolution data
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    Topics: Chemistry and Pharmacology
    Notes: Abstract In a single-dose bioavailability study, Wales, Robinson, Columbia, and Choledyl (Warner/Chilcott) enteric-coated tablets all allowed a bioavailability of theophylline (99%±25%, 102%±23%,103%±18%, and 98%±15%;mean±SD, n=12) statistically indistinguishable from that of the standard uncoated tablet (Searle 200 mg aminophylline). Only the Wales and Choledyl tablets (7.6, 4.2 hr) could be shown (p〈0.05) to generate a peak plasma theophylline concentration later than the standard (1.4 hr). All tablet brands demonstrated a significant lag time before appearance of theophylline in the plasma, and both Wales and Choledyl tablets also had a (t peak -t tag )statistically different from that of the standard. Despite misleading indications from the mean plasma profile (plasma concentrations at each sampling time averaged over all subjects), plasma data from the individual participants and in vitrodissolution data show that, while release of theophylline from the Wales tablet might be inordinately slow, this is not a sustained-release preparation. Of the enteric-coated tablets only the Columbia product allowed significant levels in the first sample after dosage. Five of the 18 Columbia doses gave rise to 40–99%of the peak concentration in the 1- hr sample. In vitro,it takes 39±14 min for 40% of the theophylline content of Columbia tablets to dissolve in simulated intestinal fluid. Surprisingly rapid delivery of an entericcoated tablet to the duodenum would appear to be required to allow a significant percentage of theophylline to be dissolved and absorbed before 1 hr. None of 12 Columbia tablets tested in vitro,however, allowed dissolution of more than 0.2% of their theophylline content during 1 hr immersion in simulated gastric fluid. Since once in intestinal fluid Columbia tablets appear to dissolve more rapidly than the other enteric products, it is not clear whether the five Columbia tablets in question had imperfections or whether, in fact, this tablet brand more closely than the others represents the ideal of immediate release once in the duodenum. Plasma samples should be taken as early as 15 min after dosage when evaluating the bioavailability of enteric release products.
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  • 150
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    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 347-362 
    ISSN: 1573-8744
    Keywords: griseofulvin ; bioavailability ; HPLC assay ; plasma levels ; human study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The relative bioavailability of ten marketed dosage forms of griseofulvin was evaluated in two separate crossover studies. Each study utilized 12 healthy subjects, with eight of the subjects being common to both studies. Plasma griseofulvin concentrations were determined 1, 2, 3, 4, 6, 8, 10, 25, 34, 49, and 73 hr after dosing, using a high-pressure liquid chromatographic method. The “high-dose” study compared four microsize dosage forms administered as 500-mg doses and two ultramicrosize formulations given as 250-mg doses. The “low-dose” study employed four 250-mg microsize products and two 125-mg ultramicrosize products. The individual plasma level-time profiles for the majority of doses suggested prolonged absorption of microsize griseofulvin. The ultramicrosize dosage forms exhibited peak concentrations which were not significantly different (p〉0.05) from those of the microsize products administered as twice the dose. In the high-dose study, the two 250-mg ultramicrosize dosage forms exhibited areas under the plasma level-time curve (AUC) which were significantly (p〈0.05) less than the AUCs for all but one of the 500-mg microsize products. In the low-dose study the AUCs for the ultramicrosize products were significantly lower than the AUCs for all of the microsize dosage forms. Significant differences were also noted among the AUCs for the microsize products, although the maximum difference was less than 20% in both studies. A comparison of the AUCs observed in the high- and low-dose studies revealed that the AUCs for two of the 500-mg microsize dosage forms were only approximately 75% the AUC predicted from the 250-mg dose for the eight subjects common to both studies. All other formulations exhibited a dose proportionality for AUC.
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  • 151
    ISSN: 1573-8744
    Keywords: theophylline ; absorption ; bioavailability ; sustained release ; tablets ; plasma concentrations ; mean plasma concentrations ; steady-state projections
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Absorption of theophylline from three commercial products labeled as sustained release was compared to the absorption from a standard uncoated tablet (Searle 200-mg aminophylline tablet) in a single-dose study. Aminodur tablets (Cooper) and Slophyllin Gyrocap capsules (Dooner) had bioavailability (100.2%±19.8% and 98.5%±13.8%) statistically indistinguishable from that of the standard but showed significantly slower absorption (peak times of 10,4±2.8 and 4.36±1.35 hr) and lower peak plasma concentrations (13.9±4.5 and 22.6±3.5gmg/ml/g dose) than the standard (t peak ,1.52±0.45 hr; Cpeak,28.l±6.2μg/ml/g dose). The time of the plasma concentration peak (2.47±1.38 hr) after a dose of Tedral S.A. (Warner/Chilcott) was not statistically different from that after the standard, but both the peak concentration (16.0±3.9 gmg/ml/g dose) and bioavailability (76.0±18.4%) were. Multiple-dose projections from single-dose data indicate that of the three test products only Aminodur maintains reasonably constant interdose plasma levels during 12 hourly dosing. With an 8 hourly dosing schedule Gyrocaps also might be satisfactory. Reasonable predictions of the plasma concentrations arising from Aminodur doses have been made using a single-compartment body model and assuming input from an outer followed by an inner layer of the tablet. Typically a single dose of a preparation designed for constant release of drug over 12 hr should not produce a plasma concentration plateau in subjects with an average 6.1-hr drug half-life. The apparent plateau in the mean plasma profile (i.e., concentrations at each sampling time averaged over all subjects) for Aminodur doses is evaluated. The interpretation commonly being implied in the publication of mean profiles from bioavailability studies is misleading, particularly when applied to sustained-release preparations.
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  • 152
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    Journal of pharmacokinetics and pharmacodynamics 9 (1981), S. 41-58 
    ISSN: 1573-8744
    Keywords: transepidermal ; pharmacokinetics ; bioavailability ; drug surveillance ; compliance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Continuous transepidermal drug collection (CTDC) has been proposed for use in assessing ethanol intake and in monitoring compliance with therapeutic regimens. Exploration of a theoretical basis for use of CTDC in these circumstances and for its use in assessing other aspects of drug disposition kinetics was undertaken. Effects of single and multicompartmental drug disposition models, single dose and multiple dose regimens, with regular and irregular doses and dosing intervals, and zero-order, first-order, and Michaelis-Menten excretion patterns were explored. First-order transepidermal drug transfer was assumed with and without back transfer from the collection device. These analyses suggest that the utility of CTDC is severely restricted when back transfer from the collection device is substantial. With back transfer minimized, CTDC may be a useful tool for assessing amount of drug exposure, compliance with therapeutic regimens, and relative bioavailability, but offers little advantage over discrete sampling of other body fluids in the study of other aspects of drug disposition kinetics.
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  • 153
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    Journal of pharmacokinetics and pharmacodynamics 9 (1981), S. 389-417 
    ISSN: 1573-8744
    Keywords: Prednisone ; prednisolone ; dose-dependent ; pharmacokinetics ; biotransformation ; protein binding ; bioavailability ; transcortin binding ; interconversion ; renal clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Six healthy male volunteers were given 5, 20, and 50 mg of oral prednisone and 5, 20, and 40 mg doses of intravenous prednisolone. Plasma and urine concentrations of prednisone and prednisolone were determined by HPLC, and the binding of prednisolone to plasma proteins was measured by radioisotopic and equilibrium dialysis techniques. The pharmacokinetics of both oral prednisone and intravenous prednisolone were dose-dependent. The mean oral dose plasma clearances of prednisone ranged from 572 ml/min/ 1.73 m 2 for the 5mg dose to 2271 ml/min/1.73 m 2 for the 50 mg dose. Changes in prednisone half-life were insignificant, but increases in the half-life of its metabolite were dose-dependent. The systemic plasma clearance of i.v. prednisolone was dose-dependent and increased from 111 to 194 ml/min/1.73 m 2 over the 5 to 40 mg i.v. dosage range. The steady-state volume of distribution also increased, but little change in mean transit time and half-life was found. The binding of prednisolone to plasma proteins was markedly concentration-dependent, and a two compartment, nonlinear equation was used to characterize the effective binding of prednisolone to transcortin and albumin. The apparent pharmacokinetic parameters of protein-free and transcortin-free prednisolone were relatively constant with dose. The interconversion of prednisone and prednisolone varied with time and dose, although prednisolone concentrations dominated by 4-to 10-fold over prednisone. In urine, 2–5% of either administered drug was excreted as prednisone and 11–24% as prednisolone. The apparent renal clearances of both steroids were also nonlinear and unrelated to protein binding. These studies indicate that the pharmacokinetics of prednisone and prednisolone are dose-dependent and that protein binding does not fully explain their apparent nonlinear distribution and disposition.
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  • 154
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    Journal of pharmacokinetics and pharmacodynamics 9 (1981), S. 535-551 
    ISSN: 1573-8744
    Keywords: sisomicin ; pharmacokinetics ; bioavailability ; two-compartment open model
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Detailed analyses of the pharmacokinetics of sisomicin administered at doses of 25, 50, and 100 mg intravenously and intramuscularly to healthy volunteers established that the drug is handled by a two-compartment open model system with a disposition (elimination) half-life of 2.6 hr. The kinetic estimates over this dose range are linear and independent of dose and were verified by a 60-min infusion experiment in which dose and the maximum serum concentration achieved (5 μg/ml) were predicted correctly. Sisomicin was rapidly distributed to the tissue compartment, and equilibrium between the central and the tissue compartment was established by 30 min after dosing. Renal clearance (55 ml/min) of sisomicin was about 30% less than total body clearance (78 ml/min). Total urinary excretion of sisomicin during a 24-hr period following drug administration was about 70% of the dose. The disposition kinetics of sisomicin following intramuscular administration are similar to those obtained following rapid intravenous administration. Intramuscular bioavailability of sisomicin for the doses of 25, 50, and 100 mg was greater than 95%. Based on these results, various initial loading infusion doses and maintenance infusion rates were calculated to provide specific desired peak and steady-state serum sisomicin concentrations rapidly. The purpose was not to expose patients to potentially toxic high peak concentrations of drug while maintaining these concentrations during the current therapeutic dosing intervals of 8 to 12 hr.
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  • 155
    ISSN: 1573-8744
    Keywords: diazepam ; controlled release ; bioavailability ; single dose ; steady-state
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    Topics: Chemistry and Pharmacology
    Notes: Abstract A controlled release formulation of diazepam was compared to equal daily doses of the trade tablet under single day and steadystate conditions. Virtually no differences were found in the mean steadystate concentrations of diazepam or its metabolite, N-desmethyldiazepam, when the subjects received the 5 mg trade tablet three times daily or the 15 mg controlled release formulation once daily. Similarly, there was no difference in mean diazepam or N-desmethyldiazepam plasma concentrations when single doses of the controlled release formulation were given to fed or fasted volunteers. These data indicate that the controlled release formulation produces plasma concentrations of diazepam and N-desmethyldiazepam comparable to those achieved with the same daily dose of the trade product given three times daily, suggesting that these regimens can be used interchangeably.
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  • 156
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    Journal of pharmacokinetics and pharmacodynamics 9 (1981), S. 725-738 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; chlorpheniramine ; first-pass effect ; bioavailability ; gut metabolism
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The oral absolute bioavailabilities of chloropheniramine (CPM) in four rabbits (New Zealand White, male, mean wt. 3.71 kg), averaged 0.06±0.03, 0.11±0.08, and 0.09±0.01 following a 3, 10.5, and 21 mg/kg dose, respectively. The individual bioavailability data and the AUCof one of the demethylated metabolites, desdimethyl CPM (DDCPM) obtained following different doses suggested the existence of saturable presystemic elimination. Two rabbits received an additional 10.5 mg/kg dose of CPM through portal vein infusion. Based on the oral, intraportal vein and i.v. studies, the mean extraction ratios of gut and the liver calculated for these two rabbits averaged 0.58 and 0.76, respectively. The latter value agreed well with the estimated hepatic extraction ratio from the in vitro liver homogenate study (0.89) or from the i.v. studies (0.83). The extensive prehepatic first-pass effect observed in the present study was consistent with similar findings in humans and dogs.
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  • 157
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    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 205-214 
    ISSN: 1573-8744
    Keywords: bioavailability ; clearance ; V area ; V ss
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The limitations of using estimates of extent of bioavailability (F) based on the assumption that either clearance (CL) or Varea remain, constant are discussed in relation to the situation where CL changes between doses. When estimates of F assume CL to remain constant, the entent of the error is the same for all drugs where the percentage change in CL is the same. Assuming Varea to remain constant, the error in F will vary between drugs for similar percentage changes in CL and is related to the extent to which the kinetics of the disposition process deviate from a one compartment body model. A noncompartmental method is described where, provided the reference dose is given intravenously, F can be estimated based on the assumption that Vss remains constant between doses. This method is more accurate than those based on the assumption that either CL or Varea remain, constant when CL changes between doses, but is subject to error when the terminal loglinear slope of Cp vs. time better reflects the process of absorption rather than elimination.
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  • 158
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    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 315-331 
    ISSN: 1573-8744
    Keywords: theophylline ; antacids ; interaction ; bioavailability ; steady state
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract We examined the influence of a large-volume, therapeutic antacid regimen, administered for three full days, on the steady-state bioavailability of a conventional-release and sustained-release theophylline product, Aminophyllin and Theodur, respectively. Nine stable asthmatics voluntarily completed a four-phase investigation requiring a total stay of 12 days in the Clinical Research Unit. The treatments consisted of administration of the formulations mentioned with and without antacids to each patient in a randomized sequence. Four patients participated in an additional phase where antacids were administered q2h around the clock for three days. After coadministration of theophylline plus antacids for two days, theophylline therapy was discontinued while numerous blood samples were obtained over 22 hr and analyzed for theophylline content via radioimmunoassay. Antacids had no predictable, consistent influence on theophylline absorption rate as determined by the absorption rate constant, the time to maximal theophylline concentration, or the lag time for theophylline absorption. Antacids had no detectable influence on theophylline elimination half-life and had no consistent, statistically significant effect on the extent of theophylline bioavailability, according to measurements of maximal concentration, AUCmeasured over the appropriate steady-state dosing interval, or elimination-rate adjusted AUC.The substantial intraindividual changes for all parameters of theophylline bioavailability that occurred for control and treatment phases likely represent spontaneous, random between-day variability in theophylline disposition independent of antacid administration, as evidenced by the comparability of the percent coefficient of variation for parameters of biovailability across all phases. Our data demonstrate that therapeutic antacid administration has no effect on steady-state theophylline bioavailability and does not alter the intrinsic variability in theophylline absorption. Based on the results of our data, it is unlikely that a clinically significant (〉20%) decrease in theophylline absorption would occur in any patient treated intensively with antacids concurrently.
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  • 159
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    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 83-91 
    ISSN: 1573-8744
    Keywords: bioavailability ; bioequivalence ; hypothesis tests ; sample size determination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The clinical problem of testing for equivalence in comparative bioavailability trials is restated in terms of the proper statistical hypotheses. A simple t-test procedure for these hypotheses has been devloped that is more powerful than the methods based on usual (shortest) and symmetric confidence intervals. In this note, this new procedure is explained and an example is given, including the method for sample size determination.
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  • 160
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    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 529-545 
    ISSN: 1573-8744
    Keywords: bioavailability ; nitrofurantoin ; capacity-limited elimination
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The influence of route of administration on the absolute bioavailability and GI tract absorption of nitrofurantoin was investigated in rabbits. The disposition of nitrofurantoin was described by a one-compartment model with simultaneous first-order and Michaelis-Menten type elimination kinetics, and bioavailability was estimated by nonlinear assessment. The plasma levels following oral administration were significantly lower than those after intravenous administration, and absolute Fvalues for oral administration were approximately 0.3. However, Fvalues following intraduodenal administration and portal vein infusion were nearly unity, and it was concluded that the reduction of bioavailability following oral administration could not be attributed to metabolism by intestinal microflora or to the hepatic first-pass effect. Thus, reduction of Fvalues following oral administration is probably due to gastric degradation of the drug. The effects of factors influencing bioavailability, such as water volume taken with the drug, change of gastric emptying rate and effect of particle size, were also investigated. Increase of volume of water administered tended to improve the bioavailability, and a particle size dependency was also observed.
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  • 161
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    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 437-450 
    ISSN: 1573-8744
    Keywords: first-pass ; bioavailability ; Michaelis-Menten ; volume of distribution ; absorption rate constant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Two approaches used for bioavailability determination of drugs with Michaelis-Menten elimination kinetics were examined by computer simulation. The first method involved treating the drug as though its clearance remained constant during elimination, and the conventional method of taking the ratio of areas under the curve resulting from the oral and intravenous doses was used to calculate bioavailability. The second approach involved using the Michaelis parameters, Vmax and Km,to determine concentration dependent clearance values, but based these calculations on peripheral drug concentrations rather than on concentrations entering or in the liver. We have developed a simulation method that was used to test the accuracy of the above two methods. In the simulations described, Vmax, Km,and hepatic blood flow were chosen to represent a drug with an extraction ratio of 0.9 under linear conditions, but with Michaelis-Menten kinetics occurring at the doses given. Absorption was assumed to be first-order, and metabolism was assumed to occur only in the liver. These simulations showed that the most accurate determination of bioavailability requires knowledge of the direct contribution of oral absorption to the concentration of drug entering the liver. Unexpectedly, the results also showed that if a drug has a large volume of distribution or a large absorption rate constant, or both, use of the much simpler conventional method of bioavailability determination may be appropriate even in cases where the degree of saturation is substantial.
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  • 162
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    Journal of pharmacokinetics and pharmacodynamics 9 (1981), S. 1-14 
    ISSN: 1573-8744
    Keywords: prednisone ; prednisolone ; dexamethasone ; pharmacokinetics ; tobacco ; smoking ; bioavailability ; corticosteroids ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of oral prednisone and oral dexamethasone were examined in 18 healthy male adults. Eight subjects also received intravenous prednisolone and intravenous dexamethasone. Half of each group were cigarette smokers as confirmed by plasma thiocyanate concentrations. Plasma and urine concentrations of prednisone and prednisolone were assayed by high performance liquid chromatography, while plasma dexamethasone was measured by radioimmunoassay. There were no statistically significant differences between smokers and nonsmokers in the systemic availability of prednisolone (75 versus 84%), oral dose clearance of prednisone (29 versus 27 ml/min/kg), systemic prednisolone clearance (2.8 versus 2.9 ml/min/kg), or in the interconversion rates, volumes of distribution, or urinary recoveries of prednisone and prednisolone. Similarly, the pharmacokinetics of dexamethasone were unaffected by smoking. A limited correlation (r=0.55) was found between the high oral dose clearances of prednisone and the lower values of dexamethasone (6.73 and 5.71 ml/min/kg in smokers and nonsmokers). A two- to threefold variability occurred in oral dose clearances of each steroid with partial intrasubject covariance. Unlike the anticonvulsants, which markedly induce corticosteroid metabolism, smoking has no effect on their pharmacokinetics and should not complicate therapy with these drugs.
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  • 163
    ISSN: 1573-5036
    Keywords: Groundnut fertilization ; Nigeria ; Nitrogen fixation ; Nodulation ; Nutrient uptake ; Tropical soils
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract It was observed in a long-term fertility study that P application results in better nodulation and seed yield. The N yield per plant increased significantly with P, K, and B application, but the promoting effect of K and B on N content per plant was not reflected in the final yield. Data on mean nutrient uptake indicate that about 63% of N, 68% of P, 23% of K, 4% of Ca and 24% of Mg were present in the kernels, the remainder being in the haulm and shells. Soil will be exhausted fast if the nutrient rich groundnut residues are completely exported from the field and not compensated by adequate fertilizer application. Judicious use of fertilizers on groundnut has been shown to yield more than 100 kg of biologically fixed N per hectare.
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  • 164
    ISSN: 1573-5036
    Keywords: Clover ; Fertilizer ; Lotus ; Nitrogen fertilizer ; Nitrogen fixation ; Nitrogen source ; Nodulation ; Trifolium repens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Studies under growth cabinet conditions investigated the effect of source and concentration of nitrogen and timing of nitrogen application on the growth and nitrogen fixation byLotus pedunculatus cv. Maku andTrifolium repens cv. S184. KNO3, NaNO3 and NH4NO3 were added at transplanting at the following rates: 3.33, 7.78 and 13.33 mg N/plant. KNO3 was added at 3.33 and 7.78 mg N/plant at 0, 6, 12, 18, 24 or 30 days after transplanting. Lotus shoot weight increased with all increasing nitrogen sources but clover only responded to KNO3 and NaNO3. The root weight of both species increased with increasing KNO3 and NH4NO3. The percentage increase in lotus and clover shoot growth was greater than that of root growth when KNO3 was added within a week of transplanting. Increases in growth by both species resulted from added nitrogen except with lotus when NaNO3 was applied where increased nitrogen fixation also contributed to increased growth. Weight and number of effective nodules on both species were increased with 3.33 mg N per plant as KNO3 but nitrogen fixation was not affected. Addition of 13.33 mg N as NaNO3 reduced weight and number of effective nodules in both species and also nitrogen fixation by lotus. KNO3 increased growth and nodulation of both species when applied within one week after transplanting. Nodulated lotus plants responded to KNO3 by increasing growth but not nodulation. KNO3 appeared to affect infection and development of nodules on lotus and may affect the growth of existing nodules on clover.
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  • 165
    ISSN: 1573-5036
    Keywords: Moisture stress ; Nitrogen fixation ; Tropical forage legume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary The effect of soil moisture stress on growth, nodulation and nitrogenase activity of two tropical forage legumes,Macroptilium atropurpureum cv. Siratro andDesmodium intortum cv. Greenleaf was studied in a pot experiment. After ten weeks growth, the highest moisture stress (20 per cent water holding capacity) significantly reduced only the top weight of both plants. Moisture stress progressively retarded top growth in the two legumes. Similar trends were also observed in defoliated plants. Moisture stress had little or no effect on the nodulation or nitrogenase activity of the plants.
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  • 166
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    Plant and soil 59 (1981), S. 201-206 
    ISSN: 1573-5036
    Keywords: Acetylene reduction ; Coffee plantation ; Inga jinicuil ; Nitrogen fixation ; Nodule biomass ; Woody legume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Nodule biomass and yearly C2H2 reduction rates are reported forInga jinicuil, a leguminous tree used for shade in Mexican coffee plantations. Annual fixation by this species approximates 35 kg ha−1; which, when compared to nitrogen additions from fertilizers, represents an important nitrogen input to the coffee ecosystem.
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  • 167
    ISSN: 1573-5036
    Keywords: Azotobacter vinelandii ; Gnotobiotic cultures ; Nitrogen fixation ; Oryza sativa Rhodopseudomonas capsulata
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary An all glass tight growth chamber, entirely sterilizable, has been constructed to carry out axenic and gnotobiotic cultures of rice plants (Oryza sativa L.). When grown in liquid medium and in the absence of combined nitrogen but in the presence of the diazotrophsAzotobacter vinelandii andRhodopseudomonas capsulata, rice plants exhibited a complete biological cycle from germination up to ear stage, during a period of time similar to the one encountered in french paddy soil of Camargue. In one experiment, mannitol was given to rice culture medium together withAzotobacter vinelandii andRhodopseudomonas capsulata. In another experiment, mannitol was not given together with Rhodopseudomonas, and still positive nitrogen gain was obtained, although it was less than culture with mannitol. When15N labeled cells of Rhodopseudomonas were added in rice culture medium,15N was partly transferred to rice plant. Among the nitrogen substances excreted from the bacteria in the rhizosphere medium, large organic molecules were shown to be the most abundant in our experimental conditions. Moreover, the concentration of free ammonia or aminoacids present in the rice rhizosphere were always compatible with a bacterial nitrogenase activity.
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  • 168
    ISSN: 1573-5036
    Keywords: Bacteroids ; Cowpea ; Nitrogen fixation ; Peanut ; Rhizobium ; Siratro
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Acetylene reduction activity and nitrogen accumulation in the plant top per unit nodule mass were compared among peanut, cowpea and siratro plants nodulated by six different strains of Rhizobium. Peanut was found to have several fold higher values than cowpea and siratro for both parameters for all strains of Rhizobium which nodulated it effectively, but the bacteroid content of the peanut nodules was similar to those of cowpea and siratro.
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  • 169
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    Plant and soil 62 (1981), S. 331-336 
    ISSN: 1573-5036
    Keywords: Legumes ; Nitrogen fixation ; 15N
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary The combination of using15N for determining the amount of nitrogen fixed by a legume crop in field experiments and the labelling of only one treatment at a time in each treatment combination is shown to be conceptually and experimentally valid for determining the effect of cultural practices on the amount of nitrogen fixed by a legume crop.
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    Plant and soil 63 (1981), S. 283-289 
    ISSN: 1573-5036
    Keywords: Afzelia quanzensis ; Brachystegia spiciformis ; Ectomycorrhiza ; Miombo woodland ; Nitrogen fixation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Ectomycorrhizae were found in root samples of the treesAfzelia quanzensis Welw. andBrachystegia spiciformis Benth. (Caesalpiniaceae), collected in the coastal miombo type woodland 50 km west of Dar-es-Salaam, Tanzania. Root nodules with a structure resembling that of nitrogen-fixing root nodules of other leguminous plants were observed in theA. quanzensis material. The climate of the locality is rather dry, and strongly seasonal. In the tropics, ectomycorrhizae have previously been found only in humid or rain forest climate zones.
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  • 171
    ISSN: 1573-5036
    Keywords: Drought stress ; Nitrogen fixation ; Nodulation ; Prosopis spp ; Semi-arid ; Tree legumes ; Water potential
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary The literature does not contain a field report of nodulation for the xerophytic tree legumes of the genus Prosopis despite their widespread occurrence in semi-arid regions of the world. A phraetophytically simulated greenhouse experiment was conducted with mesquite in a 3m deep soil column to determine if nodules would form in deper depths where moisture is more abundant. The upper 0.5m in the soil column was allowed to dry to 2200 kPa but the 3.2 m depth was maintained at soil moistures more positive than 70 kPa by water additions to the bottom of the soil column. Over 100 nodules and an acetylene reduction rate of 1.9 mg/h were observed at the 3.2m depth. Nodulation or acetylene reduction were not observed closer than 2.7m from the surface. Air temperatures during these assays exceeded 45°C. Leaf xylem water potentials were in the 2800–3500 kPa range.
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  • 172
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    Plant and soil 65 (1982), S. 383-396 
    ISSN: 1573-5036
    Keywords: Frankia ; Microbial ecology ; Nitrogen fixation ; Purshia ; Revegetation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Nitrogen fixing trees and shrubs may be useful in revegetation efforts. Speculation that insufficient endophyte populations in surface soils may limit non-leguminous symbiotic nitrogen fixation in marginal land was explored.Purshia tridentata andP. glandulosa seedlings were grown in greenhouse trials using ten soils from nativePurshia sites. Treatments include a control, an inoculated treatment, and six mmole nitrogen amendment. When inoculated with aP.tridentata crushed nodule inoculum, two of five non-nodulating soils and three sparsely nodulating soils produced well nodulated plants. Inoculation also increased nodule mass, total nitrogen, nitrogen content and shoot dry mass in plants from some of the soils. Of the three soils failing to produce nodulated plants when inoculated, one produced plants that responded well to nitrogen additions but failed to nodulate under low nitrogen conditions; another produced severely stunted plants indicating nutritional limitations on the host; and the third produced plants that were not nitrogen deficient. An application of nitrogen completely suppressed nodulation in all but one soil. The twoPurshia species were similar in nodulation, nitrogen fixation and growth, although important exceptions exist that indicate species may differ in adaptability to certain soil conditions.
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  • 173
    ISSN: 1573-5036
    Keywords: Acridine orange ; Cochliobolus sativus ; Common root rot ; Nitrogen fixation ; Nuclear staining ; Roots ; Senescence ; Wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Natural senescence of the root cortex was assessed by nuclear staining, for cultivars and chromosome substitution lines of spring wheat known to differ in (1) susceptibility to common root rot, (2) total rhizosphere populations and (3) ability to support growth of a free-living nitrogen-fixing bacterium. Together, three root rot susceptible wheat lines showed significantly more cortical senescence than did three resistant lines; the susceptible lines also support larger rhizosphere populations. The wheat line that supports growth of a nitrogen-fixing bacterium showed significantly less cortical death than did any other line. Substitution of chromosome pairs 5B or 5D between the parent cultivars Rescue and Cadet substantially altered the amount of root cortex death, which is thus genetically determined. It is suggested thatCochliobolus sativus and other weak parasites benefit from early natural senescence of the root cortex, and that the degree of susceptibility or resistance of wheat lines to common root rot is at least partly determined by differences in cortical senescence.
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  • 174
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    Plant and soil 68 (1982), S. 55-67 
    ISSN: 1573-5036
    Keywords: Klebsiella ; Nitrogen fixation ; Oryza sativa ; Phyllosphere ; Rice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary The beneficial effect of spraying some highly active phyllosphere N2-fixing microorganisms on high and low yielding cultivars of rice plants as compared with that of urea applied at different doses are described. The dry weight, N-content, 1000 grain weight, and yield were remarkably increased in all cases with the application of phyllosphere microorganisms. The performance of two isolates KUP4 and KUPBR2 with IR-8 and IR-26 rice, was better than that of 52 kg urea-N per hectare. IR-579 rice leaves in association with some phyllosphere bacteria reduced acetylene at the rate of 664–816 nmoles/g leaf/h. In IR-26 rice the effect of application of bacterial suspension at three phases of plant growth corresponded very well with that of urea application in three split doses under identical conditions. Recommended fertilizer rates produced the same yield as the half dose plus bacterial spray in the cultivars Pankaj and Rupsail. Fertilizer application in Pankaj and Rupsail rice reduced nitrogenase activity and the beneficial effects of phyllosphere N2-fixation was reduced by 40–55%.
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  • 175
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    Plant and soil 69 (1982), S. 233-238 
    ISSN: 1573-5036
    Keywords: Nitrogen fixation ; Azospirillum spp. ; Azospirillum lipoferum ; Wheat yield
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Seven isolates belonged toA. brasilense and 3 belonged toA. lipoferum. Isolates having more denitrifying capacity fixed less nitrogen in nitrogen free semi-solid malate medium. One strain ofA. lipoferum having high nitrogen fixing capacity with negative test for denitrification was tested as inoculant to supplement the nitrogen need of a wheat crop in field condition with different doses of N with and without the inoculant. While control without nitrogen yielded 1260 kg/ha the yield in inoculated treatment was 2070 kg/ha resulting in significant increase. In a treatment receiving 40 kg N/ha the grain yield was 2370 kg/ha as against yield of 3110 kg/ha in a similar treatment receiving fertiliser plus inoculant. Thus increase in yield was about 30%. Further the treatment receiving 80 kg N/ha yielded 2970 kg/ha as against yield of 4150 kg/ha in a treatment receiving inoculant alongwith the above dose of the fertiliser. Thus increase in yield due to application of inoculant was about 36%. Similarly, the uptake of N in different treatments was augmented due to inoculation of seeds with the culture.
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  • 176
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    Plant and soil 69 (1982), S. 293-297 
    ISSN: 1573-5036
    Keywords: Ecology ; Frankia ; Nitrogen fixation ; Water potential
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Growth responses of Frankia isolates to decreasing water potential were monitored in systems where potentials were controlled by KCl, NaCl and Polyethylene glycol. The highest potential tested was −2 bar (basal medium). The general pattern emerging was that isolates fromAlnus glutinosa, A. viridis andComptonia peregrina showed declining growth at potentials below −2 to −5 bar. AMyrica gale isolate showed declining growth with decreasing potential. All isolates were more sensitive to decreases in potential in a matric controlled than an osmotic controlled system. They all showed approximately 50 percent growth reduction at −5 to −8 bar, and meagre growth at −16 bar after 35 days. The Comptonia isolate was the most vigorous at low potentials. Nitrogen fixation ability was monitored for two isolates. Highest specific activities were observed between −3 and −5 bar for the Myrica isolate and between −5 and −7.5 bar for theA. glutinosa isolate.
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  • 177
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    Plant and soil 69 (1982), S. 341-352 
    ISSN: 1573-5036
    Keywords: Barley ; Nitrogen fixation ; Rhizoplane ; Rhizosphere
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Aerobic and anaerobic N2-fixing bacteria developed in the rhizosphere of barley seedlings and exhibited N2ase activity when seedlings were grown in sterilized sand-nutrient cultures containing low levels of combined nitrogen. The source of the N2-fixing bacteria appeared to be the seed. Average daily rates up to 0.9 μmoles C2H4 h−1 g−1 dry root tissue were measured, but the intensity of the activity was affected by moisture levels and concentration of combined N in the rhizosphere. Removal and washing of the roots did not remove the activity, and roots remained active even after surface-sterilization. An unidentified aerobic N2-fixing bacterium was isolated from the rhizoplane of active barley roots. Inoculation of barley seedlings with the aerobic N2-fixing bacterium enhanced N2ase activity of excised roots 10-fold, with average rates of 0.9, 1.1 and 1.3 μmoles h−1 g−1 dry root assayed under pO2 of 0.01, 0.02 and 0.04 atm respectively. The aerobic N2-fixing bacterium also exhibited N2ase activity when inoculated into the rhizosphere of oat, rice and wheat seedlings. Microscopic observations of sterilized live and stained barley roots suggest that the aerobic N2-fixing bacterium is an endophyte which infects root tissue and metamorphoses into vesicle-like structures.
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  • 178
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    Plant and soil 72 (1983), S. 321-334 
    ISSN: 1573-5036
    Keywords: Leguminous plants ; Nitrogen fixation ; Protein ; Seed ; Yield
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Mineral nitrogen did not increase grain yield and seed protein levels ofVicia faba L. andLupinus luteus L. in field trials and pot experiments. Fixed N2 was substituted by mineral nitrogen in these cases because of inhibition of N2 fixation by mineral nitrogen. Contrary to these results mineral nitrogen increased grain yields and seed protein amounts ofLupinus albus L.,Pisum sativum L., andGlycine max. (L.) Merr. The nitrogen effect was caused at an early stage by saving energy due to inhibition of N2 fixation (measurement of gas exchange by means of IRGA). In case of the N application after flowering grain, yields and seed protein levels increased because the mineral N was an additional nitrogen source for plants. At this stage the plants had ceased fixing atmospheric nitrogen. The high sink activity of growing fruits induced a lack of assimilates in nodules (determined by means of14CO2 application). The N effect was therefore the consequence of the lower assimilate pool for supplying root nodules in these plants in comparison withVicia faba L. andLupinus luteus L. Hence it follows that response to mineral nitrogen can be a criterion for discovering more effective Rhizobium-host combinations.
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  • 179
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    Plant and soil 73 (1983), S. 431-434 
    ISSN: 1573-5036
    Keywords: Nitrogen fixation ; 15N2 diffusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Description / Table of Contents: Summary The kinetic of15N2 diffusion has been measured in a system similar to that for the estimation of N2 fixation in plant microorganism associations cultivated in soil. The15N2 enrichment of the soil atmosphere reached an homogenous value one hour after injection of15N2 and is identical to that obtained by calculation, indicating that no adsorption occurs in the soil particles.
    Notes: Résumé La cinétique de diffusion du15N2 est mesurée sur un système identique à ceux pouvant être utilisés pour la mesure de fixation de l'azote chez les associations plantes-microorganismes cultivées sur sol. L'enrichissement homogène de l'atmosphère du sol est obtenu une heure environ après l'injection de15N2 et correspond à l'enrichissement calculé, ce qui indique qu'aucune adsorption n'a lieu dans les particules du sol.
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  • 180
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    Plant and soil 75 (1983), S. 131-138 
    ISSN: 1573-5036
    Keywords: Hydrogen inhibition ; Nitrogen fixation ; Peas ; Relative efficiency ; Rhizobium leguminosarum ; Root nodules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Experiments were performed to investigate the causes of low relative efficiency, RE, in legume root nodules. Nitrogen fixing activity and RE varied with time of incubation of nodules and with different temperatures and oxygen concentrations. The effects of nitrogen concentration and carbon dioxide concentration were also examined. In each case the RE was inversely related to nitrogen fixing activity; measured by acetylene reduction. Increasing the nitrogen concentration had no effect on either nitrogen fixing activity or RE. Experiments with isolated bacteroids gave higher RE values than the whole nodules from which they were isolated. All the results were consistent with hydrogen inhibition of nitrogenase within the nodule being the cause of low RE.
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  • 181
    ISSN: 1573-5036
    Keywords: Actinorhizae ; Alnus nitrida ; Frankia ; Host-specificity ; Nitrogen fixation ; Root nodules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Two different strains, An 1 and An 2, were obtained from root nodules ofAlnus nitida Endl., collected from one locality in the area of its natural habitat near Bahrin, District Swat, Pakistan. The light and electron microscopy of the isolates revealed the occurrence of septate and branched hyphae bearing sporangia and vesicles. The strains differed in their growth requirements, nitrogen-fixing ability and production of extracellular pigments, thus indicating the existence of more than oneFrankia strain in the same locality. In the absence of combined nitrogen in the medium strain An 1 formed vesicles and fixed N2 (up to 200 nmol C2H4. mg protein−1.h−1), while strain An 2 under the experimental conditions formed only few vesicles and fixed N2 at a very low rate (ca 10 nmol C2H4. mg protein−1 .h−1). The nitrogenase activity of strain An 1 was strongly affected by the O2 concentration.Frankia An 1 and An 2 were infective and effective onA. nitida andA. glutinosa but not onDatisca cannabina andElaeagnus umbellata. Both An 1 and An 2 strains were more infective and effective onA. glutinosa thanFrankia strains AvcIl and CpI1.
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    Plant and soil 77 (1984), S. 253-261 
    ISSN: 1573-5036
    Keywords: Acetylene reduction ; Beijerinckia ; Nitrogen fixation ; Paddy ; Phyllosphere ; Silicification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary An investigation was conducted to study the levels of nitrogen fixation on the leaf or sheath surfaces of four cultivars of paddy plants by using acetylene reduction technique. Varying levels of positive nitrogenase activity were observed on all the leaf surfaces. Sheath of IET 1991 cultivar showed a higher rate of fixation than the leaf surface. All the nitrogen-fixing organisms on the leaf or sheath surfaces belonged to the genus Beijerinckia. There was no correlation between the bacterial density and the level of fixation. Scanning electron microscopic data revealed that the upper surface of IET 1991 leaf was highly silicified and the microflora was either scanty or nil while the lower surface appeared quite different and harboured more micro-organisms. Similarly, the inner surface of sheath was devoid of silicification and showed the presence of micro-organisms.
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    Plant and soil 78 (1984), S. 29-43 
    ISSN: 1573-5036
    Keywords: Alnus glutinosa ; Endophyte ; Frankia ; Infectivity ; Nitrogen fixation ; Sporulation ; Variability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Frankia sp. LDAgpl, an isolate from spore positive nodules ofAlnus glutinosa, only slowly infects its host plant. Reisolates obtained from occasional nodules caused by infection with LDAgpl, are capable of infecting the alder much more rapidly. A variability analysis of LDAgpl has been performed to obtain more insight into the question whether these reisolates constitute a different genotype within LDAgpl and if the plant is exerting an influence during plant passage. High dilutions of mildly sonicatedFrankia suspensions were plated to obtain genetically homogeneous colonies. Clones thus generated showed differences in growth pattern, sporulation and C2H2-reduction on media containing propionic acid as sole C-source (P-medium). Differences in sporulation on P-medium indicate that LDAgpl was a highly heterogeneous strain. Comparisons of sporulation on several different media gave evidence that the differences in sporulation between LDAgpl clones are the result of differences in efficiency of propionic acid utilization. The differences observed between the reisolates and LDAgpl clones indicate that the reisolates constitute a different genotype, which could be selected for by the plant during the infection process. Comparison with similar changes in phenotype occuring in a spore negative type strain fromA. glutinosa is discussed.
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  • 184
    ISSN: 1573-5036
    Keywords: Actinorhizas ; Alnus nitida ; Amino acid composition ; Datisca cannabina ; Hydrogen uptake ; Inoculation ; Nitrogen fixation ; Root nodules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary The nodulation and the morphology and physiology of the nodules were studied onDatisca cannabina, a perennial herb from northern Pakistan andAlnus nitida, a nodulated tree in the same locality. Both species bear coralloid clusters of actinorhizal nodules. The main free amino acid inD. cannabina nodules was arginine while the predominant free amino acid inA. nitida nodules was citrulline. The infectivity of crushed nodules of both types of plants on their respective host was about 106 infective particles per gram of nodule fresh wt. In cross-inoculation experiments crushed nodule inoculum fromA. nitida failed to induce nodulation onD. cannabina seedlings but the crushed nodule inoculum fromD. cannabina caused low nodulation on seedlings ofA. nitida (103 infective particles. g. nodule fresh wt.). The activity of nitrogenase, hydrogenase and respiration (O2 uptake) were measured in detached nodules, nodule homogenates and the 20 μm residue and 20 μm filtrate preparations from the nodules of both species. Both species showed similar patterns of activities except that only the nodule homogenate and 20 μm residue preparations fromD. cannabina showed pronounced enhancement of the O2 uptake by succinate which was further stimulated by ADP. This has in part been explained by the presence of mitochondria in close connection with the endophyte.
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    Plant and soil 79 (1984), S. 227-234 
    ISSN: 1573-5036
    Keywords: Bacteria ; Inoculation ; Microorganisms ; Nitrogen fixation ; Phosphate solubilization ; Rice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Inoculation effect ofA. chroococcum, P. striata andA. awamorii on yield and nutrients uptake in rice was studied under green house conditions. The organisms appreciably increased the yield and uptake of nutrients with or without chemical fertilizers. Phosphorussolubilizing microorganisms and a mixture of the three showed better response than the rest of the treatments among single and mixed culture inoculations respectively. Chemical fertilizers further improved the yield and nutrients uptake. The yield response remained unaffected by replacing superphosphate with rock phosphate and microbial inoculations.
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  • 186
    ISSN: 1573-5036
    Keywords: Mesquite ; Nitrogen fixation ; 15N natural abundance ; Nodule morphology ; Rhizobium bacteria ; Woody legumes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary The relative nitrogen fixation efficiencies (RE 1-[H2 evolved÷C2H2 reduced]·100) of four mesquite (Prosopis glandulosa var.torreyana) rhizobia (Strains WR 1001, WR 1002, L5, L9) and a cowpea rhizobia (Strain 176A32) on mesquite were evaluated in a glasshouse experiment. Plant yield, shoot N accumulation, and the natural15N abundance (δ15N) of nodule tissue were determined. Strain WR 1002 failed to nodulate mesquite and strain L5 produced ineffective nodules. Among the three effective strains (WR 1001, L9, 176A32) the cowpea strain (176A32) and strain L9 had significantly higher RE than strain WR 1001. Differences in RE, however, were not accompanied by significantly higher plant yield and shoot N accumulation. The difference in15N abundance between foliar tissue and nodules (nodules minus leaves) was 0.47 δ15N for the ineffective L5 nodules, while for the effective WR 1001, L9, and 176A32 nodules, respectively, this difference was 8.35, 7.81, and 8.35 δ15N. This indicates a similar relationship between N2-fixing effectiveness and natural15N enrichment of nodules that was previously observed in soybeans (Glycine max, L. Merr.). Strains WR 1001 and L9 produced elongate, indeterminate nodules typical for mesquite. The ineffective L5 nodules had few infected cells and an abundance of cortical amyloplasts. Mesquite nodules produced by the cowpea strain were spherical and were somewhat more similar in internal morphology to determinate nodules typical of cowpea than indeterminate nodules normally associated with mesquite.
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  • 187
    ISSN: 1573-5036
    Keywords: Actinorhizae ; Datisca cannabina ; Frankia ; Nitrogen fixation ; Root nodules ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary The fine structures of the microsymbiont inside the root nodules ofDatisca cannabina have been studied by light, by transmission- and by scanning-electron microscopy. The endophyte is prokaryotic and actinomycetal in nature. The hyphae are septate and branched, diameter 0.3–0.5 μm. The tips of hyphae are swollen to form electron-dense, clubshaped to filamentous vesicles, ranging in diameter: 0.4–1.4 μm. The endophyte penetrates through walls of the cortial cells. The infected zone is kidney shaped and confined to one side of the acentric stele. The orientation of infection is reversed from other actinorhizae exceptCoriaria. The hyphae are near the host cell wall and vesicles are directed towards the central vacuole. Vesicles are aseptate and no collapsing of the vesicle cell wall (void area) has been observed. Vesicle clusters structures are globular with an opening at one side of the cluster. The host cell is multinucleate or contains a lobed nucleus. Groups of mitochondria are located in between the hyphae, suggesting a strong association between the host and the endophyte for energy supply and amino acid production. The consequences of the inability to separate the mitochondria from the vesicle clusters in nodule homogenates in physiological studies have been discussed. Isolated vesicles clusters showed dehydrogenase activity, indicated by the presence of formazan crystals, after incubation with NADH and NBT. Strongest reducing activity was found within the vesicles. The possible role of filamentous vesicles in nitrogen fixation has been discussed.
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  • 188
    ISSN: 1573-5036
    Keywords: Acetylene reduction ; Actinomycete-nodulated ; Legume ; Lime ; Mine spoil ; Nitrogen fixation ; Reclamation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary An acid mine spoil in Southern Indiana was amended with lime (CaCO3) (0.0, 12.5, 25 and 39t/ha) and planted withElaegnus umbellata Thunb.,Alnus glutinosa Gaertn.,Robinia pseudoacacia L.,Robinia fertilis Ashe, ‘Arnot’,Myrica pensylvania Lois,Caragana arborescens L. andShepherdia argentea Nutt. Survival and soil data were collected periodically and plants were harvested 15 months after planting. Nodule and top dry weights were determined and acetylene reduction assays performed on the nodules. Addition of lime caused significant increases in pH, and 39 t/ha of lime were required to maintain a pH above 5.5. Survival of plant material was greatest at the highest lime addition, although response of individual species varied.Elaeagnus umbellata, R. pseudoacacia, R. fertilis ‘Arnot’, andA. glutinosa appeared more tolerant of the harsh conditions. OnlyC. arborescens showed a linear increase in top dry weight due to lime addition.Alnus glutinosa andS. argentea achieved statistically the same growth regardless of pH, andR. fertilis ‘Arnot’ andE. umbellata did not increase in top dry weight above an addition of 25 t/ha.Robinia pseudoacacia achieved maximum top dry weight at 25 t/ha, whereasM. pensylvanica growth declined with increasing pH. Nodule dry weights increased with increasing pH; however,S. argentea showed greater nodule dry weights at lower lime levels. Acetylene reduction rates increased with lime addition.Elaegnus umbellata did not respond above 25 t/ha lime, whereasA. glutinosa did not show an increase until this point.
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    Plant and soil 55 (1980), S. 163-165 
    ISSN: 1573-5036
    Keywords: Acetylene reduction ; Nitrogen fixation ; Rhizobium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary A method is described to demonstrate nitrogen fixation by free-living Rhizobium cells. After aerobic growth in a nutrient solution, the bacteria are centrifuged. Acetylene reduction by the rhizobial cells in the pellet can be measured within a few days. Hydrogen gas frequently stimulates acetylene reduction.
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    Plant and soil 74 (1983), S. 395-406 
    ISSN: 1573-5036
    Keywords: Fix− mutants ; Fix+ revertants ; Macroptilium lathyroides ; Nitrogen fixation ; Rhizobium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Eight ineffective mutant strains were isolated from N-methyl-N'-nitro-N-nitrosoguanidine mutagenized cultures of cowpea Rhizobium strain 32H1. Strains CR1, CR2, CR3, CR4, CR5 and CR6 induced more, but smaller, nodules than the wild type. With the exception of strain CR2, these mutant strains reduced less than 1% of the amount of acetylene reduced by the wild type, in both the free-living and symbiotic assays. Strain CR2 reduced acetylene in the free-living assay but not in the symbiotic assay. Strains CR7 and CR8 responded variably (5–20% of the wild type) in free-living and symbiotic acetylene reduction assays. Nodules also varied from small white to normal-sized pink nodules. The phenotypic characteristics of the mutant strains were consistant with all leguminous plants tested and were stable upon reisolation from nodules. Fully effective revertants were selected from 4 of the ineffective mutant strains by the use of the leguminous plant,Macroptilium lathyroides. Serology, patterns of resistance to anti-bacterial agents, phage-typing, and antibiotic resistance markers were used to confirm strain identification.
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    Plant and soil 64 (1982), S. 251-253 
    ISSN: 1573-5036
    Keywords: Competition of Rhizobium ; Nitrogen fixation ; Nodulation ; Vigna radiata
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Competition of five strains of Rhizobium of the cowpea group, onVigna radiata (L) Wilcjeck variety ML 5, was tested in loamy clay and loamy sand soils. Strains RM 6 and RM 5 were effective nodulators in loamy clay soil, and strains MNH, M 20 and RM 6 were effective nodulators in loamy sand soil. Strains RM 6 and MNH predominated nodule formation in loamy clay and loamy sand soils respectively.
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    Plant and soil 64 (1982), S. 263-266 
    ISSN: 1573-5036
    Keywords: Blue-green algae ; Nitrogen fertilisers ; Nitrogen fixation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary The effects of ammonium or nitrate-nitrogen on biological nitrogen fixation by an algal crust are compared. Nitrate-nitrogen up to 3.0 μmoles N g−1 sand/algal crust at 60% water holding capacity did not affect fixation, whereas an ammonium-nitrogen concentration of 0.2 μmoles N g−1 crust markedly depressed fixation. Consequences of these differential effects are considered.
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    Plant and soil 66 (1982), S. 21-28 
    ISSN: 1573-5036
    Keywords: Agro-forestry ; Acetylene reduction ; Leucaena leucocephala ; Nematode root knots ; Nitrogen fixation ; Nodule biomass ; Woody legume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary The nitrogen fixation rate in a 4-year-old stand of the woody legumeLeucaena leucocephala (Lam.) de Wit. was estimated in the field at a rather dry site in Tanzania by use of an acetylene reduction technique. The diurnal mean value during April–May was 35 nmol C2H4 mg−1 (dry weight) nodules h−1, with a variation between 22±8 and 48±12 nmol C2H4 mg−1 (dry weight) nodules h−1 in early morning and at midday, respectively. The nodule biomass was determined by auger sampling to be 51±16 kg (dry weight) ha−1. Most of the nodules were found at the 10–30 cm soil depth level. A rough calculation of the amount of nitrogen fixed annually arrived at 110±30 kg ha−1. The results give strong support for the use ofL. leucocephala for soil enrichment in less humid areas of tropical Africa.
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  • 194
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    Plant and soil 66 (1982), S. 125-127 
    ISSN: 1573-5036
    Keywords: Charcoal ; Garden pea ; Inoculation ; Nitrogen fertilisation ; Nitrogen fixation ; Nodulation ; Pisum sativum ; Wood charcoal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary In a factorial pot experiment on garden peas investigating the effect of growing medium, inoculation, nitrogen fertilisation and charcoal addition, shoot growth was significantly better in John Innes potting compost than in 50/50 peat/sand compost and when receiving nitrogen fertilisation but was depressed by the presence of wood charcoal. In the peat/sand medium, root systems were smaller but carried more and larger nodules. The number of nodules was increased by inoculation but the addition of carbon decreased root size, nodule number and nodule size.
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  • 195
    ISSN: 1573-5036
    Keywords: Aluminium toxicity ; Nitrogen fixation ; Nodulation ; Stylosanthes hamata ; Stylosanthes humilis ; Stylosanthes scabra
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Effects of three solution aluminium concentrations (0, 25, and 100μM) on nitrogen fixation by well-nodulated plants ofStylosanthes hamata, Stylosanthes humilis andStylosanthes scabra are reported. Plants were inoculated with Rhizobium CB756 and grown for 21 days in an aluminium-free nutrient solution at pH 5.3 before imposition of the aluminium treatments. Nitrogen fixation was measured both by the increase in total nitrogen content of the plants and acetylene reduction in roots of plants harvested at 10 and 20 days after imposition of the aluminium treatments. Solution aluminium concentrations as high as 100μM, had no detrimental effect on nitrogen fixation in any species.
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  • 196
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    Plant and soil 66 (1982), S. 413-416 
    ISSN: 1573-5036
    Keywords: Growth ; Nematicide ; Nitrogen fixation ; Nodulation ; Peanut ; Rhizobium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary The effect of two granular nematicidesviz. oxamyl and fenamiphos, on the nodulation and growth of Rhizobium inoculatedArachis hypogaea L. was studied in glasshouse and field trials. In the glasshouse trial at the suggested rates of application shoot fresh weight was significantly reduced by oxamyl whilst root fresh weight was similarly affected by fenamiphos. In the field trial vegetative growth and plant emergence were significantly reduced by both nematicides. Nodulation at the higher rates of application was increased by both oxamyl and fenamiphos whilst oxamyl caused a significant increase in pod number at the highest rate of application.
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  • 197
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    Plant and soil 68 (1982), S. 321-329 
    ISSN: 1573-5036
    Keywords: Alginate ; A value ; Endomycorrhiza ; Glomus mosseae ; Inoculant ; Nitrogen fixation ; Rhizobium japonicum ; Soybean
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary This field study was undertaken to determine the effect of inoculation withGlomus mosseae on N2 fixation and P uptake by soybean. The inoculation withGlomus mosseae was achieved using a new type of inoculant, alginate-entrapped (AE) endomycorrhizal fungus. N2 fixation was assessed using the A value method. In P-fertilized plots, inoculation with AEGlomus mosseae increased the harvest index based on dry weight (+20%) and N content of seeds (+17%), the A value (+31%) and %N derived from fixation (+75%). Inoculation with AEGlomus mosseae decreased the coefficient of variation for the A value and for the dry weights of the different plant parts.
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  • 198
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    Plant and soil 69 (1982), S. 265-273 
    ISSN: 1573-5036
    Keywords: Azotobacter chroococcum ; Fertilizers ; Farmyard manure ; Nitrogen ; Nitrogen fixation ; Potassium ; Phosphorus ; Yields of grain stover ; Zea mays
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Field trials were conducted during theKharif seasons of 1979 and 1980 to examine the effect of the nitrogen-fixing bacteriumAzotobacter chroococcum (isolate M4) on yields of maize and N-economy. Different levels of nitrogen and farmyard manure (FYM) were supplied to assess their interaction with Azotobacter inoculation. Seed inoculation without fertilization raised grain and stover yields significantly. FYM coupled with inoculation gave higher yields than either could singly. The financial gain due to an increase in grain yield upon applying per ha 80 kg N, 10×103 kg FYM and Azotobacter over the treatment 40N + FYM + Azotobacter was offset by the cost of the additional N; thus, the higher N-application was not economical. Azotobacter inoculation was economically most efficient at lower doses of fertilizer nitrogen which not only increased yields but resulted in a saving of fertilizer N when applied in combination with FYM.
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  • 199
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    Plant and soil 69 (1982), S. 275-280 
    ISSN: 1573-5036
    Keywords: Azotobacter chroococcum ; Fertilizers ; Farmyard manure ; Zea mays ; Maize ; Nitrogen ; Nitrogen fixation ; Phosphorus ; Potassium ; Total nitrogen uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary The economic feasibility of using cultures of nitrogen fixing microorganisms in programmes to increase crop production, as a selfgenerating source of nitrogen, has been proved beyond doubtviz. Legume-Rhizobium symbiosis and blue green algal ‘fertilizer’ for rice. The extent to which the free living, N-fixing, aerobic, heterotropicAzotobacter chroococcum could replace the application of nitrogenous fertilizer to maize was investigatedin vivo. Total nitrogen uptake (kg ha−1) by maize after inoculation with Azotobacter combined with moderate applications of nitrogen fertilizer and farmyard manure was influenced significantly and resulted in a higher nitrogen concentration in grain and stover along with a higher yield.
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  • 200
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    Plant and soil 69 (1982), S. 391-399 
    ISSN: 1573-5036
    Keywords: Associative nitrogen fixation ; Inoculation ; Nitrogen fixation ; Root exudate ; Soil bacteria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Organic components leaked fromSorghum bicolor seedlings (‘root exudates’) were examined by recovering14C labelled compounds from root solutions of seedlings inoculated withAzospirillum brasilense, Azotobacter vinelandii orKlebsiella pneumoniae nif-. Up to 3.5% of the total14C recovered from shoots, roots, and nutrient solutions was found in the root solutions. Inoculation with Azospirillum and Azotobacter increased the amounts of14C and decreased the amounts of carbohydrates in the root solutions. When sucrose was added as a carbon source for the bacteria, the increase of14C in the solutions did not occur. Quantities of14C found in the root solutions were proportional to amounts of mineral nitrogen supplied to the plants. Bacterial growth also was proportional to nitrogen levels. When sorghum plants were grown in soil and labelled with14CO2, about 15% of the total14C recovered within 48 hours exposure was found in soil leachates.
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