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  • Chemistry  (6,722)
  • Analytical Chemistry and Spectroscopy  (803)
  • Engineering
  • hypertension
  • 1980-1984  (7,030)
  • 1925-1929
  • 1983  (7,030)
Collection
Keywords
Publisher
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  • 1980-1984  (7,030)
  • 1925-1929
Year
  • 1
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    Phase transition and crystal structure of the 37 degrees C form of cholesterol (1983)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1983-05-06
    Description: Crystalline cholesterol undergoes a phase transition a few degrees below human body temperature. The high-temperature form has an unusually complex structure with 16 independent molecules. In the transition two molecules change side chain conformation, four reorient about their long axes, and ten remain unchanged. The transition mechanism implies relatively nonspecific intermolecular interactions, qualitatively consistent with the behavior of cholesterol in biomembranes. The transition preserves a remarkably closely obeyed pseudosymmetry present in the structure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hsu, L Y -- Nordman, C E -- GM15259/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1983 May 6;220(4597):604-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6836303" target="_blank"〉PubMed〈/a〉
    Keywords: Body Temperature ; Chemical Phenomena ; Chemistry ; *Cholesterol ; Crystallization ; Humans ; Magnetic Resonance Spectroscopy ; Molecular Conformation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation (1983)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1983-05-06
    Description: Arachidonic acid plays a central role in a biological control system where such oxygenated derivatives as prostaglandins, thromboxanes, and leukotrienes are mediators. The leukotrienes are formed by transformation of arachidonic acid into an unstable epoxide intermediate, leukotriene A4, which can be converted enzymatically by hydration to leukotriene B4, and by addition of glutathione to leukotriene C4. This last compound is metabolized to leukotrienes D4 and E4 by successive elimination of a gamma-glutamyl residue and glycine. Slow-reacting substance of anaphylaxis consists of leukotrienes C4, D4, and E4. The cysteinyl-containing leukotrienes are potent bronchoconstrictors, increase vascular permeability in postcapillary venules, and stimulate mucus secretion. Leukotriene B4 causes adhesion and chemotactic movement of leukocytes and stimulates aggregation, enzyme release, and generation of superoxide in neutrophils. Leukotrienes C4, D4, and E4, which are released from the lung tissue of asthmatic subjects exposed to specific allergens, seem to play a pathophysiological role in immediate hypersensitivity reactions. These leukotrienes, as well as leukotriene B4, have pro-inflammatory effects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Samuelsson, B -- New York, N.Y. -- Science. 1983 May 6;220(4597):568-75.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6301011" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arachidonic Acids/metabolism/pharmacology/physiology ; Bronchi/drug effects ; Cats ; Chemical Phenomena ; Chemistry ; Cricetinae ; Guinea Pigs ; Haplorhini ; Humans ; Hypersensitivity, Immediate/*physiopathology ; Inflammation/*physiopathology ; Leukocytes/drug effects/metabolism ; Leukotriene B4/pharmacology/*physiology ; Mice ; Microcirculation/drug effects ; Rabbits ; Rats ; SRS-A/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    Bromine residue at hydrophilic region influences biological activity of aplysiatoxin, a tumor promoter (1983)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1983-12-16
    Description: Aplysiatoxin and debromoaplysiatoxin, which are isolated from the seaweed, Lyngbya gracilis, differ in their chemical structure only by the presence or absence of a bromine residue in the hydrophilic region. The function and the structure-activity relation of the hydrophilic region are not known. Aplysiatoxin increased malignant transformation, stimulated DNA synthesis, and inhibited the binding of phorbol-12,13-dibutyrate and epidermal growth factor to cell receptors. Debromoaplysiatoxin inhibited the binding of these two substances as strongly as aplysiatoxin but did not increase malignant transformation or stimulate DNA synthesis. These results indicate that a slight change in the chemical structure of the hydrophilic region of aplysiatoxin affects its abilities to increase cell transformation and stimulate DNA synthesis and that the abilities of the tumor promoters to inhibit the binding of phorbol-12,13-dibutyrate and epidermal growth factor are dissociable from their abilities to increase cell transformation and stimulate DNA synthesis under some circumstances.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shimomura, K -- Mullinix, M G -- Kakunaga, T -- Fujiki, H -- Sugimura, T -- New York, N.Y. -- Science. 1983 Dec 16;222(4629):1242-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6316505" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Caenorhabditis elegans Proteins ; Carcinogens/*pharmacology ; Carrier Proteins ; Cell Line ; Cell Transformation, Neoplastic/*drug effects ; Chemical Phenomena ; Chemistry ; DNA/biosynthesis ; Epidermal Growth Factor/metabolism ; Lactones/analysis/*pharmacology ; *Lyngbya Toxins ; Mice ; Phorbol 12,13-Dibutyrate ; Phorbol Esters/metabolism ; *Protein Kinase C ; Receptor, Epidermal Growth Factor ; Receptors, Cell Surface/metabolism ; *Receptors, Drug ; Structure-Activity Relationship
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    DNA-binding proteins (1983)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1983-09-09
    Description: The structures of three proteins that regulate gene expression have been determined recently and suggest how these proteins may bind to their specific recognition sites on the DNA. One protein (Cro) is a repressor of gene expression, the second (CAP) usually stimulates gene expression, and the third (lambda repressor) can act as either a repressor or an activator. The three proteins contain a substructure consisting of two consecutive alpha helices that is virtually identical in each case. Structural and amino acid sequence comparisons suggest that this bihelical fold occurs in a number of proteins that regulate gene expression, and is an intrinsic part of the DNA-protein recognition event. The modes of repression and activation by Cro and lambda repressor are understood reasonably well, but the mode of action of CAP is still unclear.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takeda, Y -- Ohlendorf, D H -- Anderson, W F -- Matthews, B W -- GM20066/GM/NIGMS NIH HHS/ -- GM28138/GM/NIGMS NIH HHS/ -- GM30894/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1983 Sep 9;221(4615):1020-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6308768" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Chemical Phenomena ; Chemistry ; *DNA Helicases ; DNA-Binding Proteins ; Escherichia coli/genetics ; Gene Expression Regulation ; Models, Chemical ; Protein Conformation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
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    Antiviral agents (1983)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1983-06-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Krenitsky, T A -- Beauchamp, L -- New York, N.Y. -- Science. 1983 Jun 10;220(4602):1106.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6857236" target="_blank"〉PubMed〈/a〉
    Keywords: Acyclovir/metabolism ; *Antiviral Agents/metabolism ; Chemical Phenomena ; Chemistry ; Humans ; Vidarabine/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    Metastable species of hemoglobin: room temperature transients and cryogenically trapped intermediates (1983)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1983-05-06
    Description: Resonance Raman spectra of photolyzed carbonmonoxyhemoglobin obtained with 10-nanosecond pulses are compared with the spectra of photolyzed carbonmonoxyhemoglobin stabilized at 80 K. In comparing the deoxy with the photodissociated species, the changes in the Raman spectra are the same for these two experimental regimes. These results show that at ambient and cryogenic temperatures the heme pocket in liganded hemoglobin is significantly different from that of deoxyhemoglobin. It is concluded that measurements of the properties of intermediate species from photodissociated hemoglobin stabilized at low temperatures can be used to probe the short-lived metastable forms of hemoglobin present after photodissociation under biologically relevant solution conditions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ondrias, M R -- Friedman, J M -- Rousseau, D L -- New York, N.Y. -- Science. 1983 May 6;220(4597):615-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6836305" target="_blank"〉PubMed〈/a〉
    Keywords: Carboxyhemoglobin ; Chemical Phenomena ; Chemistry ; Freezing ; *Hemoglobins ; Humans ; Ligands ; Spectrum Analysis, Raman ; Temperature
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    Irreversible ligands with high selectivity toward delta and mu opiate receptors (1983)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1983-04-15
    Description: Alkylating agents that display strong selectivity for opiate receptor types delta or mu were prepared by appropriate modification of the structures of the strong analgesics fentanyl, etonitazene, and endoethenotetrahydrooripavine. The availability of these substances should facilitate studies of the structural basis of receptor specificity and of the physiologic roles of these receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rice, K C -- Jacobson, A E -- Burke, T R Jr -- Bajwa, B S -- Streaty, R A -- Klee, W A -- New York, N.Y. -- Science. 1983 Apr 15;220(4594):314-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6132444" target="_blank"〉PubMed〈/a〉
    Keywords: Alkylation ; Animals ; Benzimidazoles/analogs & derivatives/metabolism ; Brain/physiology ; Cells, Cultured ; Chemical Phenomena ; Chemistry ; Enkephalin, Methionine/analogs & derivatives/metabolism ; Fentanyl/analogs & derivatives/metabolism ; *Isothiocyanates ; Ligands ; Rats ; Receptors, Opioid/*metabolism/physiology ; Thebaine/analogs & derivatives/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Electronic Resource
    Electronic Resource
    Cadralazine (ISF 2469): Dose-related antihypertensive activity after single oral administration to patients (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 157-161 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; cadralazine ; single dose ; dose response curve ; hypotensive action ; prolonged effect ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cadralazine (ISF 2469) was administered to 24 hypertensive patients in single oral doses of 7.5, 10, 15, 20 and 30 mg, according to a single-blind, placebo-controlled, within-patient change-over design. The study was done in 2 stages: in the first a range including the upper and lower doses was studied (7.5, 15, 30 mg and placebo), and in the second the range of doses was restricted (10, 15, 20 mg and placebo). The drug produced a significant decrease in blood pressure in the supine and standing positions. The decrease became clinically important starting from the 15 mg dose. Its action was still significant 12 h after administration. A significant increase in heart rate was also observed. All the effects were correlated with the dose. Side effects occurred mainly after the 30 mg dose. Thus, cadralazine, in a single oral dose in man, showed good antihypertensive activity starting from the 15 mg dose, and its effect was dose-related, slow in onset and long-lasting.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613810
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  • 9
    Electronic Resource
    Electronic Resource
    Increased oral clearance of metoprolol in pregnancy (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 217-220 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; pregnancy ; hypertension ; kinetics ; pre-eclampsia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of oral metoprolol was studied in 5 women during the last trimester of pregnancy and 3 to 5 months after delivery. After a single oral dose of 100 mg the individual peak plasma concentration in the pregnant state was only 20–40% of that after pregnancy. The plasma half-lives of metoprolol were about the same during (average 1.3 h) and after pregnancy (average 1.7 h). By contrast, the area under the plasma concentration versus time curve was much smallerduring (mean 262 nmol/l×h) thanafter (mean 1298 nmol/l×h) pregnancy, resulting in an average apparent oral clearance (Clo) of metoprolol that was 4.4times higher during (362 ml×kg−1 body-weight×min−1) than after pregnancy. The increased Clo in pregnancy is assumed to be due to enhanced hepatic metabolism of the drug. The possible clinical consequence of the difference in the disposition of metoprolol is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613820
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  • 10
    Electronic Resource
    Electronic Resource
    Changes in renal function induced by endralazine, a new antihypertensive drug (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 307-314 
    Details
    ISSN: 1432-1041
    Keywords: endralazine ; hypertension ; blood pressure ; heart rate ; renal clearance ; plasma renin activity ; plasma aldosterone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of endralazine, a new antihypertensive hydrazinopyridazine derivative, on heart rate, mean blood pressure (mBP), glomerular filtration rate (GFR), effective renal plasma flow (CPAH), urine volume (V), the clearance of Na, K, urea (Ur) and uric acid (UA), plasma renin activity (PRA) and plasma aldosterone (PA) were studied in hypertensive patients after a single oral dose of 10–15 mg, and after 8–17 days of treatment with daily doses of 15–90 mg. In the acute experiments, heart rate increased by 27%, mBP decreased on average by 17% and GFR by 33% and CPAH fell by only 5%. Urine volume and electrolyte clearance were also depressed. There was a significant increase in PRA and PA. The fall in GFR correlated directly with mBP, CPAH and the product (mBP×CPAH). The logarithms of the Na clearance and V were correlated with GFR and mBP. The logarithms of the fractional excretion of Na and water also correlated with mBP, suggesting that tubular reabsorption of sodium and water may be affected by change in mBP. The fractional potassium excretion correlated directly with CPAH and ln PA. In contrast, on sustained daily treatment, mBP was less depressed (9%), but GFR increased strikingly by 27% and CPAH by 46%. The body weight increased by 4.5% as a consequence of salt and water retention. GFR was correlated with CPAH, the product (mBP×CPAH) and the increase in body weight. Thus, the improvement in GFR and effective renal plasma flow observed under these conditions may be due, in part, to volume expansion. However, a direct renal vasodilating effect of the drug appears to be the more important determinant.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00610046
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  • 11
    Electronic Resource
    Electronic Resource
    Effect of indapamide on the baroreceptor reflex in essential hypertension (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 579-583 
    Details
    ISSN: 1432-1041
    Keywords: indapamide ; hypertension ; baroreflex ; vascular reactivity ; heart rate ; blood pressure change
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of chronic treatment with indapamide on blood pressure (BP), baroreceptor sensitivity (BRS) and vascular reactivity (VR) were investigated in 10 patients with essential hypertension. After 3 months of therapy with indapamide 2.5 mg/d the mean arterial pressure (MAP) had decreased from 135±6 to 112±2 mmHg (p〈0.001); the heart rate (HR) had not changed, VR had decreased from 6.1±1.2 to 4.8±1.8 (pg·min·kg)−1 (p〈0.05), and BRS had increased from 8.3±3.7 to 12.2±5.3 ms/mmHg (p〈0.005), with a leftshift of the relationship between BP and heart period. An inverse correlation was found between the pre-treatment systolic blood pressure and the change in baroreceptor sensitivity after indapamide (r=0.59; p〈0.05). In conclusion, chronic treatment with indapamide enhances BRS and resets the reflex. The resetting may account for the lack of tachycardia at rest observed after treatment with indapamide. The mechanism by which indapamide interferes with the baroreceptor reflex requires further investigations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542204
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  • 12
    Electronic Resource
    Electronic Resource
    Plasma nifedipin levels and fall in blood pressure in a 53 year old woman (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 143-144 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; nifedipine ; plasma concentration ; blood pressure response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544032
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  • 13
    Electronic Resource
    Electronic Resource
    Sequential changes in plasma renin activity and plasma catecholamines in mildly hypertensive patients during acute, furosemide-induced body-fluid loss (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 299-302 
    Details
    ISSN: 1432-1041
    Keywords: furosemide ; hypertension ; plasma renin activity ; plasma adrenaline ; plasma noradrenaline ; body fluid loss ; diuretic response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To evaluate the role of adrenergic mechanisms in the acute response of renin to furosemide, plasma renin activity (PRA) and plasma catecholamine concentrations were measured for 3 h after i.v. administration of furosemide 1 mg/kg to 8 patients with mild essential hypertension. Furosemide induced a prompt and long-lasting increase in renin, with PRA more than doubled at all times. The increase in PRA within the first 30 min paralleled the peak increases in urinary water and sodium flow rates, and significant decreases in plasma volume and central venous pressure. There was no change in plasma catecholamine concentrations. Plasma noradrenaline was increased significantly at 60 min and adrenaline at 90 min, once furosemide had induced a marked loss of body-fluid and ∼65% decrease in central venous pressure. Both catecholamines remained elevated until the end of the study, whereas urinary water and sodium flow rates had returned to their pre-treatment values by 150 min. Mean blood pressure was essentially unchanged throughout the study, whereas heart rate increased significantly after 90 min. The findings suggest that in mildly hypertensive patients adrenergic mechanisms are not involved in the initial renin response to furosemide, but they come into play later, probably as a result of reflex sympathetic activation triggered by marked volume depletion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01037937
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  • 14
    Electronic Resource
    Electronic Resource
    Ketanserin in essential hypertension: Effects during rest and exercise (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 307-312 
    Details
    ISSN: 1432-1041
    Keywords: ketanserin ; hypertension ; blood pressure ; plasma noradrenaline ; exercise ; orthostatic reflexes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ketanserin is a new, specific serotonin receptor blocking agent, which causes vasodilatation, presumably by an action on the vascular wall. The antihypertensive response to ketanserin 40 mg twice daily as monotherapy was assessed in 8 patients with essential hypertension. The investigation was an 8 week, double-blind, cross over study, which also included measurements during isometric (handgrip) and dynamic exercise (bicycle ergometry), as well as determination of plasma catecholamines and ketanserin. Ketanserin caused a reduction of supine and standing systolic and diastolic blood pressure (BP) during rest and a slight bradycardia. Although there was attenuation of the pressor response to handgrip, treatment with ketanserin did not really affect the changes in BP or heart rate during exercise, i.e. the base-line differences remained the same. There was no significant correlation between the effect on BP and the plasma level of ketanserin. The changes in BP produced by ketanserin showed little correlation with the initial levels of plasma catecholamines or with alterations in those levels. Although the results did not indicate direct interference by ketanserin with sympathetic tone, the lack of reflexogenic tachycardia, as well as the lack of increase in plasma noradrenaline during hand grip, indicates at least some modulation of autonomic function. It is concluded that ketanserin lowers BP in essential hypertension without interference with cardiovascular reflexes during standing or exercise, and that the compound may offer an alternative approach in the treatment of hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01037939
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  • 15
    Electronic Resource
    Electronic Resource
    Felodipine — A new vasodilator, in addition to β-receptor blockade in hypertension (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 571-575 
    Details
    ISSN: 1432-1041
    Keywords: beta-blocker ; felodipine ; calcium antagonist ; hypertension ; vasodilator ; side effects ; plasma levels ; metoprolol ; propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind, cross-over trial, 10 men with primary hypertension, not adequately controlled with a β-blocker alone, were also given felodipine or placebo for periods of one week. Placebo was administered single-blind for 2 weeks and 1 week, respectively, before randomization and between treatments. The dose of felodipine ranged from 6.25 mg to 25 mg. The addition of felodipine resulted in a pronounced (20%), statistically significant reduction in blood pressure (BP) and a small but significant increase in heart rate (HR). The effects were seen within 1–2 h and were maximal after 3–4 h. During steady state treatment the duration of BP reduction was at least 12 h. No orthostatic reaction was seen. There was a significant correlation between the plasma concentration of felodipine and change in BP. The most frequently reported side-effects were headache and ankle oedema, the latter probably being due to pronounced pre-capillary vasodilatation. There was no weight increase and thus no indication of general water retention. No clinically significant change in laboratory variables and no influence on the P-Q time were seen. Thus, felodipine in combination with a β-blocker seems to be a useful addition to the treatment of hypertensive patients whose BP is not adequately controlled with a β-blocker alone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542340
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  • 16
    Electronic Resource
    Electronic Resource
    Cardiovascular response to exercise and regional haemodynamics during treatment with prizidilol hydrochloride (SK&F 92 657) in moderately severe essential hypertension (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 577-580 
    Details
    ISSN: 1432-1041
    Keywords: prizidilol ; hypertension ; exercise test ; beta-blockade ; vasodilatation ; haemodynamic effects ; vascular tone ; muscle blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fourteen men with moderately severe essential hypertension were treated with prizidilol hydrochloride 400–700 mg once daily (mean±S.D. 612±56 mg/day). The study was open and ambulatory, with an initial placebo period followed by dose titration of prizidilol. Prior to treatment and during optimal control of blood pressure cardiovascular adaptation was examined in a submaximal exercise test. Plethysomographic assessment of vascular flow, resistance and tone in the calf musculature during supine rest and during maximal vasodilatation was also performed. A highly significant reduction in systolic (from 164±4.5 to 141±2.7 mmHg; p〈0.001) and diastolic blood pressure (from 105±1.6 to 87±1.3 mmHg; p〈0.001) at supine rest was noted during therapy with prizidilol. There was no significant change in heart rate. Systolic pressure in the standing position was reduced (from 159±4.2 to 139±2.9 mmHg; p〈0.001) and so was the diastolic pressure (from 111±2.5 to 95±1.9 mmHg; p〈0.001). The heart rate in the standing position was significantly increased compared to supine rest in the placebo period and during optimal treatment with prizidilol. The β-adrenoceptor blocking properties of prizidilol were apparent as a reduction in the exercise-induced heart rate response at even the lowest work load. During prizidilol therapy an increase in resting calf muscle blood flow was found from 3.1±1.5 ml/min·100 ml to 4.3±2.1 ml/min·100 ml (p〈0.025). Vascular resistance and vascular tone were significantly reduced. No change regarding blood flow or resistance during maximal vasodilatation was noted. It is considered that prizidilol has a clear antihypertensive effect combining β-receptor blocking and vasodilator properties.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542341
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  • 17
    Electronic Resource
    Electronic Resource
    Absence of an effect of mianserin on the actions of clonidine or methyldopa in hypertensive patients (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 15-19 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; mianserin ; clonidine ; methyldopa ; depression ; α2 receptors ; interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The concurrent administration of tricyclic antidepressants has been shown in man to result in a clinically significant impairment of the antihypertensive effect of clonidine. This interaction is thought to be related to competition for central α2 receptors where clonidine acts as an agonist and the tricyclics act as antagonists. Although it seems to cause less cardiovascular effects than tricyclic antidepressants, the tetracyclic antidepressant, mianserin also has been reported to be an α receptor antagonist and may, therefore, also interfere with the antihypertensive activity of centrally-acting drugs. This study investigates the effects of acute and chronic mianserin administration in patients with essential hypertension established on long term treatment with either clonidine or methyldopa. The first dose of mianserin was not associated with an increase in blood pressure and during a further two weeks of mianserin therapy there were no significant alterations in blood pressure, supine or erect. Similarly, mianserin did not alter heart rate either after acute or after chronic administration. Mianserin itself had a sedative effect but there was no interference with the sedation attributable to clonidine or methyldopa. Mianserin caused no reduction in salivary flow and did not influence the reduced saliva production caused by clonidine. Both clonidine and methyldopa are associated with a reduction in sympathetic outflow but there was no evidence in this study of any further change in plasma noradrenaline or 24 h urinary catecholamine excretion. This study demonstrates that if mianserin is given acutely or chronically, it does not interfere with the effects of the centrally acting antihypertensive drugs, clonidine and methyldopa. Mianserin may therefore be a suitable antidepressant for patients receiving these antihypertensive agents if drug treatment for depression is indicated.
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    URL: http://dx.doi.org/10.1007/BF00613921
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    Nifedipine in the treatment of difficult hypertensives (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 1-5 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; nifedipine ; calcium antagonists ; beta-blockers ; vasodilators ; diuretics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nifedipine has been assessed as a possible alternative to other third line drugs in the management of patients with difficult to control hypertension. A group of 20 patients whose blood pressure was unsatisfactory on a 3 drug regimen had their third drug stopped and after a 2 week period nifedipine was added to their beta-blocker plus diuretic therapy. Eleven became normotensive on 30 mg nifedipine daily and a further 6 on 60 mg daily; giving on overall success rate of 85%. This result was achieved with a reduction in side effects and an absence of any haemodynamic or metabolic complications.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613919
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  • 19
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    Endralazine, a new peripheral vasodilator. Evaluation of safety and efficacy over a 3 year period (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 301-305 
    Details
    ISSN: 1432-1041
    Keywords: endralazine ; hypertension ; pindolol ; peripheral vasodilator ; acetylator phenotypes ; antinuclear antibodies ; SLE-syndrome ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nineteen out-patients with moderate to severe essential hypertension were treated daily for 3 years, with an average dose of 13 mg endralazine, a new peripheral vasodilator, in free combination with pindolol 3×5 mg. The blood pressure showed a statistically significant reduction from 172/110 mmHg to 154/92 mmHg after treatment for 3 weeks. Tachyphylaxis was not observed during the 3 year period. Oedema was the most frequent side-effect, but it disappeared spontaneously. No difference in efficacy and tolerance between slow and fast acetylators was found. Only 2 patients developed a weak positive antinuclear antibody titre, which disappeared spontaneously from one during continued treatment. No clinical evidence of a systemic lupus erythematosus-like syndrome was noted. It is concluded that the differences between endralazine and hydralazine in dosage and metabolism may explain the lower immunogenic activity of endralazine.
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    URL: http://dx.doi.org/10.1007/BF00610045
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  • 20
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    Chronic propranolol administration during pregnancy (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 481-490 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; pharmacokinetics ; pregnancy ; hypertension ; naphthoxylactic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of propranolol (P) and its major metabolites, propranolol glucuronide (PGLUC), 4-hydroxypropranolol (4OHP), 4-hydroxypropranolol glucuronide (4OHPGLUC) and naphthoxylactic acid (NLA), (Walle et al. 1972) were determined, whenever possible, in the first, second and third trimesters of pregnancy in thirteen patients and also when these patients were at least three months post-partum. No correlations were found between the mean arterial blood pressure (post-therapy) or the fall in blood pressure as a result of the P therapy (p〉 〉0.05) and P dose, peak P plasma concentrations, peak 4-hydroxypropranolol (4OHP) plasma concentrations or peak (P plus 4OHP) plasma concentrations. However, a positive nonlinear relationship was found between the daily P dose (independent variable) and peak P plasma concentrations over the daily dose range 30–160 mg/day. The elimination half-lives of NLA for patients in the third trimester of pregnancy were significantly shorter (p=0.072, df=13) than those when the patients were at least three months post-partum. Also, the areas under the plasma level-time curves of NLA were significantly less (p〈0.05, df=13) for patients in the third trimester of pregnancy than when these patients were at least three months post-partum. The results of this study indicate that the pharmacokinetics of P, PGLUC, 4OHP and 4OHPGLUC are not significantly altered by pregnancy. However, the kinetics of NLA do appear to be altered. The formation of NLA by N-dealkylation of P and further oxidation, appears to be competitively inhibited by unidentified substances, perhaps endogenous steroids, especially in the third trimester when compared to at least three months post-partum.
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    URL: http://dx.doi.org/10.1007/BF00542115
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  • 21
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    Pinacidil, a new vasodilator: Pharmacokinetics and pharmacodynamics of a new retarded release tablet in essential hypertension (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 557-561 
    Details
    ISSN: 1432-1041
    Keywords: pinacidil ; hypertension ; side effects ; pharmacokinetics ; fluid retention ; retarded release tablet
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open study increasing doses of a retarded tablet formulation of pinacidil were given twice daily for four weeks to 9 patients with untreated essential hypertension (WHO I–II). In all patients a decrease in diastolic blood pressure to below 100 mmHg, or a fall exceeding 15 mmHg, was obtained 2 h after tablet intake (p〈0.02), but in only two patients was the effect maintained after 10 hours (n.s.). At a mean serum concentration of 100 ng/ml 2 h after pinacidil 30 mg, the mean blood pressure had decreased by 14 and 12.7 mmHg in the supine and erect positions, respectively (p〈0.05). In contrast, mean blood pressure 10 h after the same dose was unchanged, when the mean serum concentration was 47.5 ng/ml. No change in heart rate was observed. Pharmacokinetic and pharmacodynamic investigations showed a tendency towards a more gradual and longer lasting antihypertensive effect and serum concentration-time curve after the retarded tablet than the previous tablet. Pinacidil 40 mg in the retarded tablet reduced mean blood pressure and increased heart rate for at least 8 h. There was a linear correlation between the serum concentration and the changes in mean blood pressure, and between the changes in mean blood pressure and in heart rate. There was no indication of tachyphylaxis. A serum level of 50 ng/ml of pinacidil appeared to be the minimal effective concentration. The side effect consisted of fluid retention, and the body weight increased by 1.0 kg (p〈0.05); four patients complained of oedema. Therapy was discontinued in one patient after a fainting episode following an increase in the dose. Thus, pinacidil was able to lower blood pressure during monotherapy for 4 weeks provided that an adequate serum concentration was achieved. The present retarded tablet formulation is not suitable for b. d. dosing. The tendency towards fluid-retention suggests that pinacidil should be used in combination with a diuretic.
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    URL: http://dx.doi.org/10.1007/BF00542128
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  • 22
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    The effect of captopril and propranolol on the responses to posture and isometric exercise in patients with essential hypertension (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 721-728 
    Details
    ISSN: 1432-1041
    Keywords: captopril ; propranolol ; sympathetic nervous system ; noradrenaline ; aldosterone ; renin ; angiotensin converting enzyme ; hypertension ; isometric exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of captopril and propranolol on blood pressure, heart rate and plasma noradrenaline, renin and aldosterone, and on the responses to changes in posture and to isometric exercise were measured in patients with essential hypertension. During placebo administration blood pressure, heart rate and plasma noradrenaline rose on standing and during isometric exercise. The rise in diastolic blood pressure during isometric exercise correlated significantly with the rise in plasma noradrenaline. During captopril treatment blood pressure was significantly lower than during placebo administration when the patients were lying, standing or sitting, but the reduction during isometric exercise was not significant. Plasma renin increased, but heart rate, plasma noradrenaline and plasma aldosterone remained unchanged. The acute changes in blood pressure, heart rate and plasma noradrenaline produced by standing and isometric exercise during captopril treatment were similar to those during placebo administration. During propranolol treatment diastolic blood pressure was significantly lower than during placebo administration when the patients were lying, standing or sitting and during isometric exercise. Heart rate also fell. Plasma noradrenaline during standing, sitting and isometric exercise was significantly greater than during placebo administration. The changes in plasma noradrenaline measured during propranolol treatment with the patients supine were negatively correlated with noradrenaline values obtained during placebo administration: plasma noradrenaline fell in patients with higher, and increased in those with lower, initial concentrations. The expected acute increase in heart rate on standing and during isometric exercise was blunted by propranolol, but the changes in blood pressure and plasma noradrenaline were unaffected. We conclude that in essential hypertension noradrenaline is involved in the pressor response to isometric exercise. Angiotensin converting enzyme inhibition by captopril did not interfere with the responses of the sympathetic nervous system to postural changes and isometric exercise. During propranolol treatment there was no evidence that reduced sympathetic activity was involved in the hypotensive response.
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    URL: http://dx.doi.org/10.1007/BF00542509
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  • 23
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    Acute antihypertensive effect and pharmacokinetics of a tablet preparation of nifedipine (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 145-150 
    Details
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; pharmacokinetics ; tablet formulation ; dose-response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A tablet formulation of nifedipine was given to 8 hospitalized hypertensive men, W.H.O. stage I or II, mean age 45 years. After an initial placebo test, nifedipine 20, 40 or 60 mg was given in random order at 72-h intervals, in a single administration crossover study. The placebo and the active drug were given at 8 a.m. Blood pressure and heart rate were measured twice by the same observer, every 20 min from 7 to 8 a.m., and then hourly until 8 p.m., first in recumbency and again after 1 min of standing upright. Plasma nifedipine was assayed in samples taken hourly from 8 a.m. to noon, every 2 h from noon to 8 p.m., and 24 and 48 h after drug administration. All 3 doses significantly lowered blood pressure; the fall during recumbency was significantly larger (−18%) and lasted longer (12 h) after 60 mg than after 20 mg (−11% and 7 h). All 3 doses caused a similar increase in heart rate (+29 to +38%), which reached its maximum after 2 h and lasted for 5 h. The maximum plasma concentration and the area under the plasma concentration — time curve were dose-dependent despite large inter-subject variation. Absorption, bioavailability and elimination were linear between the 20 and 60 mg doses. Plasma nifedipine levels were strongly correlated with the concomitant decrease in mean arterial blood pressure (r=0.61,p〈0.001). Four patients experienced mild side effects (headaches, flushes, drowsiness or weakness). This tablet form of nifedipine has a potent antihypertensive action which lasts longer than that of the capsule presentation.
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    URL: http://dx.doi.org/10.1007/BF00613808
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  • 24
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    Pharmacokinetics of oral hydralazine in chronic heart failure (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 467-473 
    Details
    ISSN: 1432-1041
    Keywords: hydralazine ; heart failure ; pharmacokinetics ; bioavailability ; metabolism ; hypertension ; dapsone ; acetylator phenotype
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of various disease states, other than hypertension, on the pharmacokinetic behaviour of hydralazine is not completely known. In the present study the pharmacokinetics of oral hydralazine has been evaluated in 7 patients with severe, chronic heart failure, using 8 compensated hypertensives as controls. The pharmacokinetics was evaluated by measuring the plasma concentrations of hydralazine (“apparent” and “real” hydralazine) and hydralazine pyruvate hydrazone, and by assessing acetylator phenotype after a small dose of dapsone. The AUC (area under the plasma concentration curve) following a single, oral 50 mg dose was significantly larger in patients with chronic heart failure NYHA Class III–IV than in patients with essential hypertension without cardiac decompensation. A decreased rate of hepatic elimination of hydralazine is suggested as a major contributory factor to this finding.
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    URL: http://dx.doi.org/10.1007/BF00542113
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  • 25
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    Pharmacokinetic aspects of guanfacine withdrawal syndrome in a hypertensive patient with chronic renal failure (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 463-466 
    Details
    ISSN: 1432-1041
    Keywords: guanfacine ; hypertension ; phenobarbital ; withdrawal syndrome ; enzyme induction ; pharmacokinetics ; renal insufficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The unusual observation of a withdrawal syndrome due to guanfacine in a hypertensive patient with chronic renal failure led to a study of the kinetics of the drug in this patient. The principal pharmacokinetic parameters of guanfacine were greatly altered, with extended biotransformation and a decrease in the half-life compared to the values observed in other cases of severe renal insufficiency. Associated treatment with phenobarbital had had a considerable effect, as shown by the results of a further kinetic study 2 months after withdrawal of the phenobarbital. The findings then were in good agreement with reference values which strongly suggests a consequence of the enzyme inducing effect of phenobarbital. Advice about the dosage regimen in such cases is given.
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    URL: http://dx.doi.org/10.1007/BF00542112
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  • 26
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    Nifedipine in the treatment of hypertension (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 713-715 
    Details
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; calcium antagonist ; plasma renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nifedipine, a calcium antagonist with a predominant vasodilator action, was evaluated for the treatment of hypertension. A 20 mg-tablet, with a slower absorption and a more sustained blood-level than provided by the 10 mg-capsule was administered to 20 patients. The duration of the trial was 20 weeks. All patients achieved a significant reduction in both systolic (p〈0.05) and diastolic (p〈0.001) blood-pressure (B.P.), but 10 patients were withdrawn before completion of the trial period. Two patients, although achieving a fall in B.P. which was significant, did not reach to target level (〈160/90) on maximal dosage, one patient suffered a stroke due to a cerebral infarct, and seven patients were withdrawn because of side-effects due mainly to vasodilatation. The remaining 10 patients obtained a satisfactory response. In nine patients, who had achieved a satisfactory result, there was no change in plasma renin activity (P.R.A.) during chronic nifedipine administration.
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  • 27
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    Long term treatment with tienilic acid or thiazides: Comparison of antihypertensive and metabolic effects (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 835-837 
    Details
    ISSN: 1432-1041
    Keywords: tienilic acid ; hydrochlorothiazide ; amiloride ; blood pressure control ; biochemical effects ; serum uric acid ; serum potassium ; prolonged treatment ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A comparison has been made of arterial pressure and major metabolic parameters during long term treatment with tienilic acid and a hydrochlorothiazide-amiloride combination, using a randomized single-blind study without cross-over. A significant fall in systolic and diastolic blood pressure and no change in most biochemical parameters was observed with both drugs. Serum uric acid concentration was decreased during tienilic acid and was slightly increased whilst subjects took the hydrochlorothiazide-amiloride combination; serum potassium was slightly decreased on tienilic acid. No sign of hepatotoxicity was detected.
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    URL: http://dx.doi.org/10.1007/BF00542531
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  • 28
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    Relationship between pharmacokinetic and pharmacodynamic behaviour of bufuralol and its metabolite Ro 3-7410 in hypertensive patients (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 479-484 
    Details
    ISSN: 1432-1041
    Keywords: bufuralol ; hypotensive therapy ; pharmacokinetics ; hypertension ; 1-hydroxybufuralol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The relationship between the plasma concentrations of bufuralol and its major hydroxymetabolite (Ro 3-7410) and β-blocking activity was studied in 10 patients with uncomplicated essential hypertension. Blood samples and haemodynamic data were obtained during rest and after a single-level exercise test on a bicycle cycloergometer, prior to and up to 32 h after administration of a single oral dose of bufuralol 30 mg. Bufuralol was rapidly absorbed, following a first-order process with a lag time. The calculated maximal plasma concentration ranged from 44.6 to 200.3 ng/ml. The half-life of bufuralol was 2.75±1.15 h (mean±SD). Up to 50% of the parent drug was transformed into Ro 3-7410, which showed less interpatient variability in concentration and a fairly constant half-life, which was three times longer than that of the parent drug. In general, the heart rate (HR) was slightly decreased, although 2/10 patients showed an initial increase. The resting HR returned to its pre-treatment level within 6 h, the exercise HR took up to 32 h to return to the pre-treatment level. The drug reduced both resting and exercise blood pressure (BP). The former was reduced from 153.0±14.2/93.5±8.5 to 134.5±14.0/77.0±6.8 mmHg (systolic/diastolic BP; mean±SD) with 6 h after treatment. Similarly, the exercise BP was reduced from 199.0±15.2/98.5±8.8 to 171.0±9.9/88.5±8.5 mmHg at the 6th h post-dosing. The BP values had not returned to their pre-treatment levels even 32 h after treatment. Thus, bufuralol and its metabolite Ro 3-7410 induced a long-lasting antihypertensive effect and inhibited the cardio-acceleratory effect of exercise, and there was a good correlation between the pharmacokinetic and pharmacodynamic behaviour of the drug.
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    URL: http://dx.doi.org/10.1007/BF00609890
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  • 29
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    Comparison of the antihypertensive effect of a double dose of metoprolol versus the addition of hydrochlorothiazide to metoprolol (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 581-583 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; metoprolol ; hydrochlorothiazide ; drug combination ; adverse reactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 27 hypertensive patients whose blood pressure could not be adequately controlled with 200 mg metoprolol Durules alone, the effect of a double dose of metoprolol Durules® (400 mg once daily) was compared with a fixed combination of 200 mg metoprolol and 25 mg hydrochlorothiazide (Selokomb®). The study followed a double-blind cross-over schedule in 2 parallel groups. The reduction in diastolic blood pressure (p〈0.01) was comparable in the two groups. A significant fall (p〈0.01) in systolic blood pressure occurred with the metoprolol/hydrochlorothiazide combination. The subsequent change from the double dose of metoprolol Durules to the combination therapy also resulted in a fall in systolic blood pressure (p〈0.05). Mean serum potassium and blood glucose levels did not change after each alteration in therapy. Most of the side-effects mentioned were mild and transient in character.
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    URL: http://dx.doi.org/10.1007/BF00542342
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    Atenolol and metoprolol: Comparison of effects on blood pressure and serum lipoproteins, and side effects (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 573-577 
    Details
    ISSN: 1432-1041
    Keywords: beta-blockers ; serum lipoproteins ; atenolol ; metoprolol ; hypertension ; VLDL ; HDL ; hypertriglyceridaemia ; hypercholesterolaemia ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Several β-blockers increase VLDL-TG and decrease HDL-cholesterol concentrations. The underlying mechanism ist not yet clear. Some studies have suggested that the effect is less pronounced during treatment with selective β-blockers. The effects of 2 such drugs, metoprolol 200 mg/day and atenolol 50 mg/day, have been compared in 50 hypertensive patients (WHO Stage I–II), mean age 47 years. Serum lipoproteins were determined in 20 patients before treatment and after treatment with either drug for 3 months. Both drugs were equally effective in reducing blood pressure. After atenolol the initial VLDL-cholesterol concentration of 1.04 mmol/l had not changed, but it rose to 1.29 mmol/l after metoprolol (p〈0.05). The HDL-cholesterol concentration 1.42 mmol/l did not fall during atenolol treatment, but during metoprolol there was a small reduction to 1.31 mmol/l (p〈0.05). Hyperlipoproteinaemia is common in hypertensive patients, 40% of the present group had hypertriglyceridaemia and 25% had hypercholesterolaemia. Thus, atenolol 50 mg was found not to affect lipoproteins, whereas metoprolol 200 mg increased the VLDL concentration in 75% of the patients.
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    Haemodynamic effects of a new vasodilator drug, felodipine, in healthy subjects (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 49-53 
    Details
    ISSN: 1432-1041
    Keywords: felodipine ; hypertension ; cardiac failure ; haemodynamic effects ; non-invasive monitoring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic effects of a new vasodilating drug, felodipine, were studied in eight, healthy, male subjects, aged 22–31 years. The drug was given as an oral solution in the dose of 0.15 mg/kg. Thirty-five minutes later further dose of 0.15 mg/kg was administered. Felodipine induced a pronounced decrease in diastolic blood pressure (maximal effect 15±4 mm Hg) and in the systemic vascular resistance. Cardiac output increased (maximum by 4.2±0.3 l/min), due to an increase both in the stroke volume and the heart rate. The maximal increase in the stroke volume (measured from echo cardiograms) and the heart rate were 33±5 ml and 23±3 beats/min, respectively. Felodipine caused a significant decrease in the pre-ejection period (23±3 ms) and an increase in the left ventricular ejection time (29±3 ms). The quotient PEP/LVET fell from 0.36±0.01 to 0.28±0.01. Significant activity of felodipine could be recorded at a plasma level of about 15 nmol/l. When the maximal haemodynamic effects were recorded the plasma level was about 40 nmol/l. After a cumulative dose of 0.30 mg/kg, there was a twofold variation in the maximal plasma level (from 31 to 61 nmol/l). The results of the present investigation are in agreement with previous haemodynamic studies in animals. It would appear that felodipine is a potent arteriolar vasodilator and it might well be of considerable value in the management of patients with hypertension or congestive cardiac failure.
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    A naturalistic study of hypertension in a rural U.K. community (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 191-197 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; beta-blocker ; diuretic ; screening ; naturalistic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A naturalistic study was set up to screen, identify and treat hypertensive patients aged 20–60 years in a rural general practice. 3,222 patients (92%) of a stable population of 3,489 were screened by 2 nurse research assistants and of these 455 patients (14%) were found to be hypertensive or borderline hypertensive. After careful assessment, 192 of these patients were found suitable for treatment and subsequently 138 entered the study. Two well recognised treatment regimes were used and no significant difference between patient response resulted. 84 patients (60.9%) completed the 2 year duration of the study discussed here. The cost of the study is not feasible in an average general practice, but day to day running of such a project, run along clearly defined treatment regimes was managed easily by 2 research assistants: this reduced, therefore, the work load on individual general practitoners.
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    Effect of the sympathetic nervous system on change in resistance of the blood—brain barrier in arterial hypertension (1983)
    Springer
    Bulletin of experimental biology and medicine 95 (1983), S. 412-414 
    Details
    ISSN: 1573-8221
    Keywords: brain ; blood-brain barrier ; hypertension ; angiotensin ; noradrenalin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00838842
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    Dependence of number of vesicles in vascular smooth muscle cells on extracellular calcium concentration (1983)
    Springer
    Bulletin of experimental biology and medicine 96 (1983), S. 1631-1633 
    Details
    ISSN: 1573-8221
    Keywords: smooth muscles ; calcium ; intracellular vesicles ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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    URL: http://dx.doi.org/10.1007/BF00835313
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    Masthead (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983) 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1002/bip.360220101
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    Theory of protein secondary structure and algorithm of its prediction (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 15-25 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A molecular theory of protein secondary structure is presented that takes account of both local interactions inside each chain region and long-range interactions between different regions, incorporating all these interactions in a single Ising-like model. Local interactions are evaluated from the stereochemical theory describing the relative stabilities of α- and β-structures for different residues in synthetic polypeptides, while long-range effects are approximated by the interaction of each chain region with the averaged hydrophobic template. Based on this theory, an algorithm of protein secondary structure prediction is proposed and examples are given of “blind” predictions made before the x-ray structural data became available.
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    Monte carlo simulations of peptide solvation (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 27-31 
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: To increase our understanding of peptide-water interactions, we are simulating the behavior of water molecules in the intermolecular channels of [Phe4Val6]antamanide dododecahydrate crystals. There is good overall agreement between the positions predicted using two alternative potential functions and those that have been observed by x-ray diffraction. Detailed differences between the predictions for the two potential functions are discussed.
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    An empirical approach to protein conformation stability and flexibility (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 49-58 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Experimental measurements of disulfide bond stability at various stages of protein folding are considered in terms of the effective concentrations of the thiol groups relative to each other; values of up to 107M are observed, so that intramolecular interactions within the interior of a protein are much more stable, and provide greater stability to the folded conformation, than those on the surface or in a flexible segment. Intramolecular interactions can have substantially lower free energies than intermolecular, for solely entropic reasons; this implies that polar interactions, such as hydrogen bonds and salt bridges, can provide net stabilization to a folded conformation, in spite of the unfolded protein having intermolecular interactions with the solvent. These considerations can account for the lower free energy and enthalpy of the folded state and are useful for considering protein flexibility.
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    Conformational properties of microtubule protein: Their relation to the self-assembly process in vitro (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 87-91 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Near- and far-uv CD spectra of microtubule protein preparations have been examined to study the possible role of protein conformation in relation to the kinetics of the self-assembly of these proteins into microtubules in vitro. Although tubulin can form conformations with high helical content under apolar solution conditions, this transformation is apparently not involved in self-assembly. There is no major perturbation of tubulin near-uv CD by reagents and solution conditions favoring assembly. Thus, in these preparations, tubulin, as dimer and as oligomer with MAPs, is effectively in the conformation in which it undergoes self-assembly. This conclusion is consistent with a hybrid model of assembly of microtubule protein involving direct incorporation of oligomeric species as an alternative to the condensation polymerization of tubulin dimer as the exclusive assembly mechanism.
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    The unfolding mechanism of thermolysin (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 101-105 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The ligand-modulated kinetics of the autoproteolysis of thermolysin and the high-molecular-weight products of the reaction provide evidence for the conclusion that separation of the two structural domains is most probably the first step on the unfolding pathway of the protein under native conditions.
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    Genetic and biochemical analysis of in vivo protein folding and subunit assembly (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 125-129 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The in vivo pathway of folding and subunit assembly of a trimeric bacteriophage protein has been studied by characterizing precursors to the native protein and by analyzing temperature-sensitive mutations that kinetically block the pathway. The native trimer is formed via an intermediate composed of three partially folded chains, the protrimer. At 39°C, temperature-sensitive mutations prevent the formation of both the native trimer and the protrimer, possibly by destabilizing earlier intermediates. However, the mutations do not affect the stability of the native protein, formed at 30°C. Thus, these mutations identify amino acid residues involved in interactions that determine the folding pathway.
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    Conformational and functional properties of hemoglobin in perturbed solvent: Kinetics of O2 release (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 1677-1696 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: We studied the kinetics of O2 release by oxyhemoglobin caused by sodium dithionite, in the presence and in the absence of organic cosolvents (monohydric alcohols and formamide) at 10°C. This study was performed by using standard stopped-flow techniques coupled with microprocessor-based data acquisition. We have fitted the experimental data to a mathematical expression obtained on the basis of a two-state model that takes into account the kinetic heterogeneity between α- and β-chains and the presence of αβ-dimers in oxyhemoglobin solutions. Results indicate that the cosolvents mainly affect the allosteric parameter L, i.e., the T ⇄ R conformational equilibrium of hemoglobin, leaving the intrinsic deoxygenation rates of both R and T states almost unaltered. The L values obtained in the present work are in excellent agreement with analogous values previously estimated from oxygen equilibrium measurements.
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    Solution properties of porcine submaxillary mucin (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 1657-1675 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Porcine submaxillary mucin (PSM) is a glycoprotein composed of a protein core and frequent, short oligosaccharide side chains. We report static and dynamic light scattering experiments and intrinsic viscosities for PSM in aqueous solvent systems. In 0.1M NaCl solution, the data suggest PSM exists as large, internally branched, highly hydrated, polydisperse aggregates that slowly dissociate to give a stable species of weight-average molecular weight (Mw) 7.4 × 106. In 6M GdnHCl solution, the noncovalent bonds between PSM molecules are broken, giving a highly elongated molecule of Mw = 2.0 × 106. The irreversible nature of this dissociation suggests that the forces that stabilize the native aggregates of PSM in 0.1M NaCl are specific in nature. On reduction of PSM with mercaptoethanol, the polydispersity decreases and Mw also decreases to 9 × 105. A discrete change is observed in the solution properties of PSM in 0.1M NaCl at a concentration of 2mg/mL, manifested by a sudden decrease in the translational diffusion coefficient, an increase in viscosity number, and a decrease in slope of the osmotic compressibility. We tentatively propose that a weak and reversible secondary association process occurs at this concentration, although a purely hydrodynamic interaction cannot be ruled out.
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    Linear dichroism studies of nucleic acids. III. Reduced dichoism curves of DNA in ethanol-water and in poly(vinyl alcohol) filmsFor Part II in this series, see Matsuoka, Y. & Nordén, B. (1982) Biopolymers 21, 2433-2452. (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 1731-1746 
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The uv linear dichroism of calf thylus DNA has been studied at different degrees of orientation both in flow-oriented ethanol-water solutions and in a stretched aqueous host of poly(vinyl alcohol) (PVA). The reduced dichroism (LDR) curves in the region 250-290 nm for DNA in PVA films at 75 and 100% relative humidity (r.h.) are in fair agreement with the curves calculated for the A- and B-forms of DNA, based on the fiber structures and the π-π* transitions of the free bases. This suggests that DNA adopts its A and B conformations in PVA at 75 and 100% r.h. In ethanol, on the other hand, a deviation from the A-form spectrum shows that the conformation of DNA in the solution can differ from the fiber structure. At shorter wavelenghts, a positive contribution to LDR is explained in terms of an out-of-plane polarized n-π* transition.
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    Localized vibrational modes at a double-helix-single-strand junction (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 1759-1767 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A vibrational analysis has been performed for a double-helix-single-strand junction. A Green's function technique has been used in treating the junction as a defect on an otherwise perfect system of infinite chain homopolymers. We calculate that the hydrogen-bond stretching at the junction is amplified by a factor of two relative to the interior of the double helix, B poly(dG)-poly(dC). Breathing modes localized near the junction have also been predicted at 77 and 94 wave numbers. The calculated results are shown to be consistent with predictions from recent nmr studies.
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    Masthead (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983) 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1002/bip.360220801
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    Nmr studies of a free and protected tetrapeptide glycyl-L-prolylglycylglycine in β-turn-supporting environment (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 1853-1868 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Nmr studies of the protected and free tetrapeptide Gly-Pro-Gly-Gly were carried out in β-turn-supporting solvents, that is, in CDCl3 for Z-Gly-Pro-Gly-Gly-OMe and in Me2SO-d6 for H-Gly-Pro-Gly-Gly-OH. Comparisons with specifically α-deuterated analogs gave complete assignments of the NH and methylene regions. Analysis of chemical shifts, coupling constants, and the temperature dependence of chemical shifts show that the peptide adopts a type II β-turn conformation. This turn is stabilized for the protected tetrapeptide by two hydrogen bonds between (i) C=O (Gly1) and NH(Gly4), and (ii) urethane function NH and methyl ester C=O.
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    Computer simulation of the conformational properties of retro-inverso peptides. II. Ab initio study, spatial electron distribution, and population analysis of N-formylglycine methylamide, N-formyl N′-acetyldiaminomethane, and N-methylmalonamide (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 1901-1917 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Ab initio minimal and split-valence basis set calculations have been performed on compounds that are involved in retro-inverso modifications, i.e., gem-diaminoalkyl and malonyl structures. These calculations are compared with empirical force field calculations and the minor differences discussed. All calculations agree that the preferred helical conformation of the isolated gem-diaminoalkyl and malonyl derivatives of residues found in the retro-inverso modified peptides is 5-8 kcal/mol lower than the Ceq7 conformation preferred by the isolated peptide residues. Population analysis and contour plots of the charge distribution are used to help explain the differences between the model compounds.
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    Masthead (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983) 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1002/bip.360220901
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    Masthead (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983) 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1002/bip.360220601
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    Lysinium, argininum, glutamate, and aspartate ions in water solution (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 1449-1460 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: SCF-LCAO-MO ab initio calculations were carried out for the interaction between a charged amino acid and a water molecule. The results obtained were fitted by an analytical potential function of the atom-atom type, and the corresponding potential surfaces were examined by means of orientationally optimized isoenergy contour maps. Monte Carlo simulations were also carried out on a few selected solute-water clusters at T = 300 K, in order to obtain insight into the solvation structure.
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    Improved technique for calculating X-ray scattering intensity of biopolymers in solution: Evaluation of the form, volume, and surface of a particle (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 1507-1522 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: An improved cube method has been developed for calculating the intensity of diffuse x-ray scattering of macromolecules in solution using a certain set of their atomic coordinates. The technique is based on the ideas of B. Lee and F. M. Richards [(1971) J. Mol. Biol. 55, 374-400] and Richards [(1977) Annu. Rev. Biophys. Bioeng. 6, 151-176] on the possibility of estimating the molecular and accessible surface of a particle by “rolling” a sphere, simulating a water molecule, on its molecular surface. It is shown that this technique is more advantageous than earlier versions of the cube methods. The improved technique for calculating scattering curves was utilized for several globular proteins, and for the first time, reliable scattering curves were obtained for protein-“bound” water complexes. In the case of globular proteins and tRNA, this technique has permitted a strict evaluation of their accessible surfaces, their volumes, and, apparently for the first time, their complete molecular surfaces.
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    Masthead (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983) 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1002/bip.360220701
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    Viscometric study of the proteoglycan-hyaluronate (2:1) “dimer”: Minimum hyaluronate chain length (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 2501-2506 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 3 Ill.
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    URL: http://dx.doi.org/10.1002/bip.360221203
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    Extended retro-inverso analogs of somatostatin (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 2523-2538 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: An extended retro-inverso modification was introduced at the central six residues of the somatostatin molecule, the region of internal enzymatic degradations. The synthesis of the analog [Ala4,g-Phe6-r-D-Phe7-r-D-Trp8-r-D-Lys9-r-D-Thr10-m-R,S-Phe11]-somatostatin required a unique strategy accommodating the unusual structure. Side-chain protection based on the t-butyl group in combination with Fmoc and Nps α-amino protection was employed. The key component containing the gem-diaminoalkyl residue was generated by an iodobenzene bistrifluoroacetate-mediated reaction. The separation of diastereomers of the cyclic tetradecapeptide in highly pure form was accomplished by high-performance liguid chromatography on a semipreparative scale. The analogs exhibited very low potency in the growth hormone inhibition test in vitro. This is interpreted as the consequence of the complex structural changes created by the extended retro-inverso modification.
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    A critical evaluation of models for complex molecular dynamics: Application to NMR studies of double- and single-stranded DNA (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 2703-2726 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The nature of internal and overall motions in native (double-stranded) and denatured (single-stranded) DNA fragments 120-160 base pairs (bp) long is examined by molecular-dynamics modeling using 13C-nmr spin-relaxation data obtained over the frequency range of 37-125 MHz. The broad range of 13C frequencies is required to differentiate among various models. Relatively narrow linewidths, large nuclear Overhauser enhancements (NOEs), and short T1 values all vary significantly with frequency and indicate the presence of rapid, restricted internal motions on the nanosecond time scale. For double-stranded DNA monomer fragments (147 bp, 24 Å diam at 32°C), the overall motion is that of an axially symmetric cylinder (τx = ∼10-6 s;τZ = ∼1.8 × 10-8s), which is in good agreement with values calculated from hydrodynamic theory (τx = ∼1.8 × 10-6 s; τZ = ∼2.7 × 10-8 s). The DNA internal motion can be modeled as restricted amplitude internal diffusion of individual C—H vectors of deoxyribose methine carbons C1′, C3′, and C4′, either with conic boundary conditions (τw = ∼4 × 10-9 s, θcone = ∼21°) or as a bistable jump (τA = τB = ∼2 × 10-9 s, θ = ∼15°). We discuss the critical role in molecular-dynamics modeling played by the angle (β) that individual C—H vectors make with the long axis of the DNA helix. Heat denaturation brings about increases in both the rate and amplitude of the internal motion (described by the wobble model with τW = ∼0.2 × 10-9 s, θcone = ∼50°), and overall motion is affected by becoming essentially isotropic (τx = τZ = ∼5 × 10-8 s) for the single-stranded molecules. Since 13C-nmr data obtained at various DNA concentrations for C2′ of the deoxyribose ring is not described well by the above models, a new model incorporating an additional internal motion is proposed to take into account the rapid, extensive, and weakly coupled motion of C2′.
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    Kinetic studies of the interaction of methyl orange with poly(L-lysine) by stopped-flow with circular dichroism detection (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 2035-2044 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The interaction of methyl orange with poly(L-lysine) was studied kinetically by the stopped-flow technique with CD detection, as well as by static CD titration experiments. In the static experiments, the differences observed in the polymer-to-dye ratio dependences of the CD spectra and absorption spectra suggested at least two kinds of bound states of the methyl orange attached to the polymer. The kinetic experiments using the stopped-flow apparatus, however, revealed four distinct reaction processes. The reaction mechanism was elucidated from the concentration dependence of the time constant for each process as follows: the first process was attributed to the bimolecular binding step of methyl orange to the side chain of poly(L-lysine), the second and third process were ascribed to the intramolecular reaction of the polymer-dye complex, and the fourth process was found to be the intermolecular aggregation of the polymer-dye complex. The origin of the stacking of methyl orange on poly(L-lysine) is discussed on the basis of the characteristics of signal amplitudes obtained from the kinetic experiments for these processes.
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    Comparative study of GuHCl denaturation of globular proteins. I. Spectroscopic and chromatographic analysis of the denaturation curves of ribonuclease A, cytochrome c, and pepsinogen (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 2105-2122 
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Novel devices for the spectroscopic and chromatographic analysis of the denaturation curves of the protein are described. A multidimensional spectroscopic measuring system makes it possible to carry out simultaneous and continuous acquisition of a set of data of different spectroscopic dimensions at several wavelengths in the course of increasing or decreasing denaturational perturbation. GuHCl-gradient chromatography can provide information about the progressive change of the protein volume in the course of increasing GuHCl concentration. Thus, denaturation curves with a high data-point density can be obtained. The data-storing function by a magnetic disk memory provides enough precision for a rigorous investigation of the correlation among the curves that probe different aspects of denaturation. The GuHCl denaturation of RNase A, cytochrome c, and pepsinogen are studied to demonstrate the high performance of these devices. Three types of transitions are found in these three proteins and the multiphasic nature of the transitions is clearly detected in the last two proteins.
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    Masthead (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983) 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1002/bip.360221001
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    Quantitative relationship between the surface charge density and dynamic charge of linear polyelectrolytes in the low charge-density limit (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 2169-2172 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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    Boundaries of the universal K3 region and plateau region of the dynamic structure factor for DNA (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 2207-2217 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A sufficiently long semiflexible filamentous macromolecule is theroretically expected to exhibit three different domains of behavior of its apparent diffusion coefficient Dapp(K) as a function of scattering vector K: (1) the small wave vector limit, where Dapp(K) = D0 is the translational diffusion coefficient of the center-of-mass; (2) the universal K3 region, where Dapp(K) = (kBT/6πη)K is a universal function of K independent of any property of the molecule itself; (c) the plateau region at large K2, where Dapp(K) approaches either a plateau, or gradually sloping quasiplateau, characteristic of local (elastic) rigid-body motions of the filament. The existence of each of these different domains has now been established experimentally for at least some polymers. The boundaries of the universal K3 region and the plateau region are determined theoretically here using precise quantitative criteria for universal or plateau behavior of Dapp(K) for a Rouse-Zimm model containing N + 1 subchains with rms subchain extension b. Allowing a maximum of 13% nonuniversal behavior, the domain of the universal K3 region is given by K2R2G = K2Nb2/6 ≥ 7 and K2b2 ≤ 0.54. Allowing as much as 10% nonplateau behavior, the boundary for onset of plateau behavior is K2b2 = 18.3. Dapp(K) is at least 50% nonuniversal when K2b2/6 = 6 ln 3. Extension of these results to DNA is examined theoretically, and good agreement of the pertinent predictions with published experimental data is demonstrated.It is concluded that no truly universal K3 region exists for DNA with Mr ≤ 107 and persistence length a ≥ 450 Å, although marginally (≤17% nonuniversal) universal behavior, is exhibited in a very narrow domain 0.64 × 1010 ≤ K2 ≤ 0.84 × 1010 cm-2 for φ29 DNA (Mr = 11.5 × 106). More than 50% of Dapp(K) is governed by local (elastic) rigid-body motions when K2 = 5.23 × 1010 cm-2. The existence of a very wide region of nonuniversal apparent K3 behavior extending up to very large K2, far into the plateau region, is demonstrated in a plot of Dapp(K)/K vs K2 for the Rouse-Zimm model. This is shown to stem in part from visual artifacts of plotting Dapp(K)/K vs K2, even for rigid species.
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    Masthead (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983) 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1002/bip.360221101
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    Orientational interactions in low-concentration DNA solutions (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 2353-2366 
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The rotational relaxation tiem τ3 of DNA molecules (Mw ≃ 5 × 106) in solution has been determined by the transient electric birefringence method. The analysis of the birefringence decay makes it possible to study only the higher-molecular-weight fraction, the molecules being considered as rigid elongated particles in a short time scale. A marked concentration dependence of the relaxation time has been observed for DNA in low ionic strengths. Above a critical concentration c*, τ3 increases with the DNA concentration, c. The value of c* increases with the ionic strength. For 10-3 ionic strength (with NaCl), c* is about 10 μg/mL; then we observe the same strong concentration dependence of rotational relaxation times as recently reported for rodlike M-13 viruses [Maguire, J. F., McTague, J. P. & Rondelez, F. (1980) Phys. Rev. Lett. 45, 1891-1894]. These results may be discussed in terms of the Doi-Edwards theory for rotational relaxation time of rigid macromolecules [Doi, M. (1975) J. Phys. 36, 607-611; Doi, M. & Edwards, S. F. (1978) J. Chem. Soc. Faraday Trans. 74, 918-932] and the critical concentration above which the interactions between the molecules begin to appear allows determining the corresponding molecular length. We observe a very good agreement between the DNA lengths obtained from the c* values and by using the infinite dilution value of τ3 and Broersma's equation. Therefore, only highly diluted solutions can be used if intrinsic molecular properties based on the rotational diffusion of high-molecular-weight elongated molecules are studied.
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    Heat capacity increments: Conformational transitions in polypeptides (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 2411-2421 
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A thermodynamic treatment of the helix-coil transition of synthetic polypeptides in binary organic solvent mixtures is extended to describe isobaric heat-capacity increments associated with the phenomenon. This development resolves such increments into three components: two associated respectively with intrinsic differences between the ordered and disordered states of the macromolecule and between the coil-solvent complex and its components, and a third term derived from the temperature dependence in the fraction of coil residues bound to active solvent. Insights derived from this analysis are also applied to the discussion of some heat capacity increments associated with the denaturation of globular proteins.
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    Masthead (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983) 
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    Keywords: Chemistry ; Polymer and Materials Science
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    Laser-Raman spectra, sulfhydryl groups, and conformation of the cystine linkages of β-lactoglobulin (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 2507-2511 
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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    X-Ray diffraction studies on the structure of hydrated collagen (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 2539-2547 
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    Notes: The temperature dependence of the humidity-sensitive spacing, d, related to the lateral packing of collagen molecules was measured for fully hydrated collagen. In the vicinity of 0°C, a sudden change in d was observed, which was reversible with temperature. In the diffraction profile, below 0°C, a set of diffraction peaks identified with the hexagonal crystalline form of ice was observed. With the reduction in water content, the intensity of the set of diffraction peaks decreased and was found to be zero at a water content of 0.38 g/g collagen. These results were considered to be caused by the frozen water in collagen fibril below 0°C. According to the water content dependence of d, it was considered that up to a certain water content water absorbed would be stowed in the intermolecular space of collagen and above that water content water molecules would aggregate to make pools, i. e., extrafibrillar spaces. The unfreezable bound water was considered to be located in the intermolecular space of collagen. Size of the extrafibrillar space, determined from the intensity analysis of a smallangle x-ray scattering pattern, corroborates the speculation that the water showed in the extrafibrillar space is freezable and free. The formation of the hexagonal crystalline form of ice in the extrafibrillar space was considered to cause the sudden change in d at 0°C.
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    Die ganz normale Wissenschaft. Hrsg. von R. H. Simen. Verlag Deutscher Forschungsdienst, Bonn-Bad Godesberg 1982. 128 S., DM 16,80 (1983)
    Weinheim : Wiley-Blackwell
    Chemie in unserer Zeit 17 (1983), S. 67-67 
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    ISSN: 0009-2851
    Keywords: Chemistry ; Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1002/ciuz.19830170213
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    Der Widerspruch im eigenen Kopf. Hrsg. von H. Schöne. Verlag Deutscher Forschungsdienst, Bonn-Bad Godesberg 1982. 160 S., DM 18,80 (1983)
    Weinheim : Wiley-Blackwell
    Chemie in unserer Zeit 17 (1983), S. 67-67 
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    ISSN: 0009-2851
    Keywords: Chemistry ; Chemistry
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    Naturstoffe aus pflanzlichen Zellkulturen (1983)
    Weinheim : Wiley-Blackwell
    Chemie in unserer Zeit 17 (1983), S. 77-84 
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    Keywords: Chemistry ; Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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    Masthead (1983)
    Weinheim : Wiley-Blackwell
    Chemie in unserer Zeit 17 (1983) 
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    ISSN: 0009-2851
    Keywords: Chemistry ; Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1002/ciuz.19830170601
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    Chronik (1983)
    Weinheim : Wiley-Blackwell
    Chemie in unserer Zeit 17 (1983), S. 202-202 
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    Keywords: Chemistry ; Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
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    URL: http://dx.doi.org/10.1002/ciuz.19830170608
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    Theoriewandel in der Wissenschaftsgeschichte - Chemie im 18. Jahrhundert. Von Elisabeth Ströker. Vittorio Klostermann Verlag, Frankfurt a. M. 1982. VIII, 324 S., DM 68, - (1983)
    Weinheim : Wiley-Blackwell
    Chemie in unserer Zeit 17 (1983), S. 200-200 
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    ISSN: 0009-2851
    Keywords: Chemistry ; Chemistry
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    URL: http://dx.doi.org/10.1002/ciuz.19830170605
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    Preface (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. xi 
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    Keywords: Chemistry ; Polymer and Materials Science
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    Interactions between poly(Gly-Pro-Pro) triple helices: A model for molecular packing in collagen (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 33-36 
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Potential-energy calculations are reported on the interaction between two collagenlike triple-stranded poly(Gly-L-Pro-L-Pro) helices. Short helices can pack in a variety of orientations, but there is a unique parallel packing arrangement of the two helices for longer polypeptide chains.
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    Coupling between the helix-coil transition and nematic-isotropic transitions in polypeptide solutions (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 43-47 
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The lattice model of Flory has been extended in order to consider equilibrium between isotropic and nematic phases containing helix-coil type chains. Nearly complete exclusion of coil sequences from the lyotropic nematic phase produces an enhanced cooperativity in the helix-coil transition. In poor solvents this enhancement begins to occur at concentrations typical of some experiments.
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    Strategy for trapping intermediates in the folding of ribonuclease and for using 1H-NMR to determine their structures (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 59-67 
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    Keywords: Chemistry ; Polymer and Materials Science
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    Topics: Chemistry and Pharmacology
    Notes: The major unfolded form of ribonuclease A is known to show well-populated structural intermediates transiently during folding at 0°-10°C. We describe here how the exchange reaction between D2O and peptide NH protons can be used to trap folding intermediates. The protons protected from exchange during folding can be characterized by 1H-nmr after folding is complete. The feasibility of using 1H-nmr to resolve a set of protected peptide protons is demonstrated by using a specially prepared sample of ribonuclease S in D2O in which only the peptide protons of residues 7-14 are in the 1H-form. All eight of these protected peptide protons are H-bonded. Resonance assignments made on isolated peptides containing these residues have been used to identify the protected protons. Other sets of protected protons trapped in the 1H-form can also be isolated by differential exchange, using either ribonuclease A or S. Earlier model compound studies have indicated that H-bonded folding intermediates should be unstable in water unless stabilized by additional interactions. Nevertheless, peptides derived from ribonuclease A that contain residues 3-13 do show partial helix formation in water at low temperatures. We discuss the possibility that specific interactions between side chains can stabilize short α-helixes by nucleating the helix, and that specific interactions may also define the helix boundaries at early stages in folding.
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    Multiphasic conformation transition of globular proteins under denaturating perturbation (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 93-99 
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    Keywords: Chemistry ; Polymer and Materials Science
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    Topics: Chemistry and Pharmacology
    Notes: Denaturation profiles of 17 globular proteins were studied by the spectroscopic and chromatographic methods with high-data-point density. The denaturational transitions are broadly classified into three types according to their multiphasic characteristics. In general, more or less complex internal cooperative events seem to take place in the conformation transition of globular proteins.
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    Conformational and functional properties of hemoglobin in water-organic cosolvent mixtures: Effect of ethylene glycol and glycerol on oxygen affinity (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 119-123 
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    Keywords: Chemistry ; Polymer and Materials Science
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    Topics: Chemistry and Pharmacology
    Notes: We report on the effects that the presence of ethylene glycol or glycerol has on the oxygen affinity of hemoglobin. We attribute these effects to an altered equilibrium between T and R quaternary conformations of hemoglobin and separate them into bulk-electrostatic and non-bulk-electrostatic contributions to the standard free-energy difference between the R and T states.
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    NMR analysis of structure and function of snake neurotoxins (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 139-145 
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The 270-MHz proton-nmr spectra of short neurotoxins (erabutoxins from Laticauda semifasciata and cobrotoxin from Naja naja atra) and long neurotoxins (toxin B from Naja naja and α-bungarotoxin from Bungarus multicinctus) have been analyzed. The conformation of erabutoxin b in solution is largely consistent with the x-ray crystal analysis, although the environment of His-7 in solution is definitely different from that in the crystal. The pH-dependent transition has been found for toxin B, indicating that the conformation in neutral solution is different from that in the crystal as grown from acidic solution. The deuterium-exchange rates of the amide protons for the four neurotoxins have been measured. The order of structural rigidity is the same as the order of the irreversibility of neuromuscular block by neurotoxins.
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    1H-NMR studies on poly(oxyethylene)-bound oligopeptides (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 163-169 
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    Keywords: Chemistry ; Polymer and Materials Science
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    Topics: Chemistry and Pharmacology
    Notes: Conformational studies on poly(oxyethylene)-bound homo-, oligo-, guest-host, and sequential peptides synthesized according to the liquid-phase method were carried out by means of 1H-nmr spectroscopy. The solubilizing effect of the C-terminal polymeric support allowed a thorough investigation of the secondary structure in solution.
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    Vibrational analysis of conformation in peptides, polypeptides, and proteinsThis is paper number 16 in a series of which Ref. 20 is paper 15. (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 217-225 
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    Keywords: Chemistry ; Polymer and Materials Science
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    Notes: A vibrational force field for the polypeptide chain has been developed for normal-mode analysis of such molecules. It can reproduce observed frequencies of known structures to within about 5 cm-1. We review the application of this technique to conformational problems in peptides (β-turns and their model compounds), polypeptides [the αII-helix and crystalline poly(glycine II)], and proteins (bacteriorhodopsin and glucagon).
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    1H-NMR studies on substance P hexapeptide analogs (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 247-253 
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    Keywords: Chemistry ; Polymer and Materials Science
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    Topics: Chemistry and Pharmacology
    Notes: 1H-nmr studies of [pGlu6]SP6-11, [gpGlu6,mPhe7]SP6-11, and [pGlu6,N-CH3Phe7]SP6-11 in DMSO-d6 reveal characteristic chemical shifts, 3JNH-αCH, temperature dependence, as well as deuterium exchange half-times. Marked similarities are revealed for the two first analogs, whereas the N-methylated analog is clearly different. Possible conformations are considered.
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    Conformational flexibility in a small globular hormone: X-ray analysis of avian pancreatic polypeptide at 0.98-Å resolution (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 293-304 
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    Keywords: Chemistry ; Polymer and Materials Science
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    Topics: Chemistry and Pharmacology
    Notes: The 36-amino acid avian pancreatic polypeptide has been studied by x-ray analysis at 0.98-Å resolution and refined using a restrained least-squares technique to an agreement factor of 15.6%. The polypeptide, which has a compact globular structure with a hydrophobic core, comprises a polyproline-like helix (residues 2-8) and an α-helix (residues 14-32). The molecule forms symmetrical dimers linked through zinc atoms in the crystal lattice. The high-resolution analysis defines sequence-dependent distortions in the α-helical parameters due to hydrogen bonding of water molecules and side chains. The thermal parameters indicate an increased flexibility of the main chain at the turn between the helices and in the C-terminal residues. For the first time, six-parameter anisotropic thermal ellipsoids have been refined for each atom; these define the directions of the molecular motions in the polypeptide, indicating concerted vibrations. The physiological roles of conformation, flexibility, and dynamics of this polypeptide hormone are discussed.
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    Solid-state geometry and conformation of linear, diastereoisomeric oligoprolinesAbbreviations, description of the atoms, and conventions for the conformation of the peptide chain follow the recommendations of the IUPAC-IUB Commission on Biochemical Nomenclature [(1972) Biochem. J. 126, 773-780]. Further abbreviations used are: Ac, acetyl; n-Prp, n-propionyl; Mmp, 1-(3-mercapto-2-methylpropionyl); Piv, pivaloyl; t-Boc, tert-butyloxycarbonyl; t-Aoc, tert-amyloxycarbonyl; Z, benzyloxycarbonyl; Hyp, 4-hydroxyproline; Aze, azetidine-4-carboxylic acid; Thz, thiazolidine-4-carboxylic acid; Δβ-Pro, 3,4-dehydroproline; Aib, α-aminoisobutyric acid; Pip, pipecolic acid; pGlu, pyroglutamic acid; OMe, methoxy; OBzl, benzyloxy. (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 305-317 
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    Keywords: Chemistry ; Polymer and Materials Science
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    Topics: Chemistry and Pharmacology
    Notes: We have carried out a systematic analysis of the solid-state conformational preferences of a number of linear homo-oligoprolines (to the tetramer) by ir absorption and x-ray diffraction. The peptides present different chiral sequences (tacticities), various types (urethane and amide) of N-protecting groups, and free and blocked C-termini (which imply different capabilities of forming H-bonds). The following conclusions can be drawn: (i) values for the geometry of the prolyl residue and the peptide bond in the cis and in the trans conformations are proposed; (ii) in general the conformational angles ϕ and ψ in the linear homo-oligoprolines have values appropriate for the polyproline II structure (conformation F); (iii) the pyrrolidine ring shows various types of puckering with no apparent relation to the backbone conformation; (iv) Pro-Pro peptide bonds generally take the trans conformation, the few cases of cis conformation being formed by Pro residues of different chirality; (v) the single H-bond donor  -  OH, when present, is always bonded to H-acceptors, which can be either the urethane or the amide or the peptide carbonyl but never the carbonyl group of the  -  COOH moiety.
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    Microheterogeneity of bovine myelin basic protein studied by nuclear magnetic resonance spectroscopy (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 377-380 
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    Keywords: Chemistry ; Polymer and Materials Science
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    Topics: Chemistry and Pharmacology
    Notes: Myelin basic protein isolated from bovine white matter is known to consist of a mixture of three or more “charge isomers”, which can be separated by cation-exchange chromatography. We are using 360-MHz 1H-nmr spectroscopy to establish the chemical and structural differences among them. Preliminary studies by difference spectroscopy between two of the isomers suggest (a) all aromatic residues, and probably their nearest-neighbors, are unchanged; (b) the less cationic isomer lacks one (or two) of its C-terminal Arg residues; and (c) a significant fraction of the two Met residues in the less cationic isomer is present as methionine sulfoxide.
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    Spectroscopic studies of a hydrophobic peptide in membranelike environments (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 381-385 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A hydrophobic linear peptide has been synthesized and studied over a range of environments using several complementary spectroscopic approaches, including nmr, CD, and vibrational spectroscopies. The sequence of this model peptide, carbobenzoxy-L-Pro-D-Phe-D-Ala-L-Pro-NHCH3, was designed such that a small number of “folded” conformations, stabilized by intramolecular hydrogen bonding, would be accessible to it. Additionally, the extremely hydrophobic character of the peptide favors its interactions with hydrophobic regions of a membrane. The conformational impact of the membrane environment on the peptide, and the effect of the peptide on lipid organization have been explored both in micellar media and in vesicles. To facilitate nmr analysis, the peptide has been synthesized with one of the prolines perdeuterated. Results of these studies reveal that the peptide experiences a microenvironment of moderate polarity in micellar media and causes changes in lipid structure in a vesicle that are indicative of a hydrophobic peptide-lipid interaction.
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    URL: http://dx.doi.org/10.1002/bip.360220149
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    How antigenic are antigenic peptides? (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 425-440 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Most of a protein surface is potentially antigenic, consisting of numerous overlapping domains each complementary to antibody-combining sites. These domains may include peptide sequences that are demonstrably antigenic but only when antibodies from the appropriate host individuals and species are used. Methods for locating antigenic peptide sequences are described in which hydrophilic polyamide supports are used for peptide synthesis, then solid-phase radioimmunoassay with antisera and protein A. Most antigenic domains, however, comprise amino acid side chains contributed by two or more nearby polypeptide chains. Such domains can be identified by comparing the cross-reactivities of groups of very closely related proteins towards monoclonal antibodies raised to one of them. Such studies, using myoglobins, have identified a number of residues not previously shown to be antigenic and have provided a guide for the choice of synthetic peptides which are likely to carry several immunodominant side chains. One such peptide corresponding to residues (72-89) of beef myoglobin has been shown, using CD and antibodies to the parent protein, to have interesting conformational and antigenic properties. The peptide (25-55) is also antigenic.
    Additional Material: 13 Ill.
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    URL: http://dx.doi.org/10.1002/bip.360220156
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    Some novel approaches to the design and synthesis of peptide-catecholamine conjugates (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 531-545 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A series of novel, functionalized catecholamines (congeners) has been synthesized in which, formalistically, the N-isopropyl group of isoproterenol has been extended by a linear alkyl chain of varying length, terminated by a carboxyl group. Model amide derivatives have also been prepared in order to optimize the biological activity of these derivatives and also to aid in the design of appropriate peptides for the synthesis of conjugates. As a result of these studies, a series of amino acid and monodisperse peptide carriers, containing p-aminophenylalanine as the point of attachment for the drug, was prepared, together with the corresponding conjugates. In vitro and in vivo evaluation of the congeners, model amides, and conjugates has demonstrated that the biological activity of these derivatives is extremely sensitive to structural modifications at a point far-removed from the pharmacophore, in both the congener amide and conjugate series. A number of the model amides and conjugates have proven to be highly active when tested in both in vitro and in vivo test systems. The implications of these results in terms of a novel structure-activity approach to drug design are discussed.
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    URL: http://dx.doi.org/10.1002/bip.360220166
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    Specific and nonspecific macromolecule-drug conjugates for the improvement of cancer chemotherapy (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 557-567 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Antineoplastic drugs such as daunomycin, adriamycin, methotrexate, 5-fluorouridine, cytosine arabinoside, and platinate were bound to antibodies directly or via a polymeric bridge. The drug antibody conjugates retained most of their drug and antibody activities when tested in vitro. Daunomycin-antibody conjugates were shown to penetrate tumor cells in the conjugated form. In animals, daunomycin-antibody conjugates were at least as effective chemotherapeutically as the corresponding free drugs and considerably less toxic. In some tumor systems, the daunomycin-antibody conjugates represented an improvement over the free drug. This improvement was restricted in some tumors to a particular injection route of the tumor and the treatment.
    Additional Material: 6 Ill.
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    URL: http://dx.doi.org/10.1002/bip.360220168
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    Synthesis and spectroscopic characterization of insulin derivatives containing one or two poly(ethylene oxide) chains at specific positions (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 569-573 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: We describe a synthetic method aimed at specifically coupling poly(ethylene oxide) (PEO) to proteins without altering their spectroscopic properties. To do so, we have first modified the alcohol end group of PEO to an acid end group (PEO-COOH). Coupling of PEO-COOH to Gly A1 methylsulfonylethyloxycarbonyl (Msc) protected insulin yielded NαB1,N∊B29-(PEO)2-insulin. Conversely, coupling of PEO-COOH to insulin whose Gly A1 and Lys B29 amino groups were protected with Msc yielded NαB1-PEO-insulin. The products were obtained in a spectroscopically pure form and characterized by uv and CD spectroscopy. Conformational and biological studies are in progress.
    Additional Material: 2 Ill.
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    URL: http://dx.doi.org/10.1002/bip.360220169
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    Poly(2-aminodeoxyadenylic acid): Circular dichroism and thermal stability of its complexes and their relevance to phage DNA in which A is replaced by 2NH2A (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 597-600 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 2 Ill.
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    URL: http://dx.doi.org/10.1002/bip.360220204
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    Crystal structure and conformation of a cyclic tetrapeptide cyclo(L-Pro-Sar)2 containing all-cis peptide units (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 633-641 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The crystal structure and conformation of the synthetic cyclic tetrapeptide, cyclo(L-Pro-Sar)2, was determined by x-ray analysis. The peptide crystallizes in the orthorhombic space group P212121 with cell parameters a = 9.277(1), b = 12.884(1), and c = 15.581(2) Å. The crystal structure was solved by the symbolic addition procedure for direct phase determination and least-squares refinement using 1796 reflections, which led to the final R value of 0.043. This structure provides the first example observed in a crystal of a cyclic tetrapeptide in which all four peptide units have been found in the cis conformation with ω angles deviating slightly by 2°-10° from the ideal value of 0°. It was also found that the two Pro Cα-CO single bonds assumed a trans′ (ψ = 159.6° and 158.4°) conformation. Adjoining average planes of the peptide groups fall at nearly right angles to each other. The pyrrolidine ring conformations of the two prolyl residues are in the envelope form, with Cγ carbon out of the least-squares planes for the remaining four atoms.
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    URL: http://dx.doi.org/10.1002/bip.360220208
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    An analysis of the sequence dependence of the structure and energy of A- and B-DNA models using molecular mechannics (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 969-1002 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Molecular-mechanics calculations have been carried out on the base-paired hexanucleoside pentaphosphates d(TATATA)2, d(ATATAT)2, d(A6)·d(T6), d(CGCGCG)2, d(GCGCGC)2, and d(C6)·d(G6) in both A- and B-DNA geometries. The calculated relative energies of these polymers are consistent with the relative stabilities of the polymers found experimentally. In particular, the results of our calculations support the observation that the homopolymer d(A)n·d(T)n is more stable in a B-DNA conformation, while the homopolymer d(G)n·d(C)n is more stable in an A-DNA conformation. The molecular interactions responsible for these differential stabilities include both inter- and intrastrand base stacking, as well as base-phosphate interactions. While definitive experiments on the heteropolymer stabilities have not yet been carried out, the results of our calculations also suggest a greater stability of the purine-3′,5′-pyrimidine sequence over the pyrimidine-3′,5′-purine sequence in both the A- and B-conformations. The reason for this greater stability lies in the importance of the inherent directionality (5′ → 3′ vs 3′ → 5′) of phosphate-base and base-base interactions. The largest conformation change observed on energy refinement is sugar repuckering, which occurs mainly on pyrimidine-attched sugars and only in the B-DNA geometry. We suggest a molecular mechanism, specifically, differential base-sugar steric interactions involving neighboring sugars, to explain why this repuckering occurs more with d(A6)·d(T6) than with other isomers.
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    URL: http://dx.doi.org/10.1002/bip.360220316
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    Salt- and sequence-dependence of the secondary structure of DNA in Solution by 31P-nmr spectroscopy (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 879-893 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: We examined three sonicated, specific-seqiemce polydeoxynucleotides in solution over a wide range of concentrations of several salts by 13P-nmr spectroscopy, and we found that the alternating copolymer poly(dAdT)·poly(dAdT) exhibits a dinucleotide repeat unit in all five salts and at all concentrations studied, as indicated by the presence of a doubled in its 31P-nmr spectra. The two components of the doublet show selective shift effects. The upfield component is assigned to dApdT in the gauche--gauche- conformation and shifts upfield in all four monovalent salts used, relative to a single-stranded oligonucleotide control. The downfield component is assigned to dTpdA in the trans-gauche- conformation and shifts downfield with increasing CsF concentration but remains essentially constant in LiCl, NaCl, and CsCl. These changes indicate a fast noncooperative transition for poly(dAdT)·poly-(dAdT) from a presumed right-handed dinucleotide-repeat B-form to another conformation with a dinucleotide-repeat structure, via a continuum of structures that may differ in the extent of the winding of the double helix. Ethanol causes the upfield component to collapse into the other component, indicating conversion to a structure with a mononucleotide repeat unit and a trans-gauche- conformation. Up to 1M Mg2+ appears to have no significant effect on the phosphodiester conformations of poly(dAdT)·poly(dAdT). By contrast, poly-(dGdC)·poly(dGdC) gives a slow cooperative transition from what is considered to be a right-handed regular B-form to a left-handed Z-form on increasing MgCl2 and NaCl concentrations, although we observed no changes in chemical shifts below the transition points. The homopolymer poly(dA)·poly(dT) exhibits no unusual shift effects or transitions upon the addition of salts when compared to the oligonucleotide control and is considered to be a regular B-form with a gauche--gauche- phosphodiester backbone conformation. These differences emphasize the distinct secondary structures of DNAs of different sequences and their selective responses to changes in solution conditions.
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    URL: http://dx.doi.org/10.1002/bip.360220310
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    1H-nmr studies on the dinucleoside monophosphates containing 2′-halogeno-2′-deoxypurinenucleosides: Effects of 2′-substitutes on conformation (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 1189-1202 
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    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Seven dinucleoside monophosphates containing 2′-halogeno-2′-deoxypurine nucleoside residue, dAfl-U, dAcl-U, dAbr-U, dAio-U, dGfl-U, and dIfl-C, were chemically synthesized and investigated by 1H-nmr spectroscopy at 300 MHz. The sugar and backbone conformations of these compounds were analyzed by the spectral pattern of furanose proton resonances; and the extents of base-base interaction were estimated from chemical shifts and their temperature-dependent changes of base-proton resonances. It is found that the population of C3′-endo conformer and the extent of base-base interaction decrease as the electronegativity of 2′-substituent decreases in dAx-U (x = fl, cl, br, and io) series. The C3′-endo (3E) population and the base-base interaction in Nfl-U (N = A,G)-type dimers as well as dIfl-C are relatively higher than the corresponding natural ribo-dimers but can be recognized as grossly similar to the conformation of regular RNA dimers.
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    URL: http://dx.doi.org/10.1002/bip.360220412
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    Masthead (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983) 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bip.360220501
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    Raman spectra and normal vibrations of dipeptides. I. Glycylglycine (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 1267-1283 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: We studied the Raman spectra of the zwitterionic glycylglycine crystal (GG) and its N-deuterated analog. A normal coordinate analysis on its α-crystalline form was performed and the effects of intra-and intermolecular couplings are discussed. A modified Urey-Bradley potential was used as a model of the intramolecular force field. Factor group splittings are described by the use of intermolecular potentials consisting of nonbonded atom-atom interactions and dipole-dipole interactions. Effects of hydrogen bonds on the vibrational frequencies of amino and carboxylate groups are also analyzed.
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    URL: http://dx.doi.org/10.1002/bip.360220503
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    Peptaibol antibiotics: Conformational preferences of synthetic emerimicin fragmentsThis is part 90 of the Linear Oligopeptides series. For part 89, see Toniolo, C., Bonora, G. M., Anzinger, H. & Mutter, M. (1982) Macromolecules (in press). (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 1335-1356 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The ir absorption and CD conformational analyses of solutions of the protected 2-9 fragment of the peptaibol antibiotics emerimicins III and IV \documentclass{article}\pagestyle{empty}\begin{document}$ \rlap{--} (Aib_3 \rlap{--} )L - Val - Gly - L - Leu\rlap{--} (Aib_2 \rlap{--} ) $\end{document} and related short sequences are consistent with the presence of a right-handed α-helix for the octapeptide, while the tri-, tetra-, and pentapeptides adopt a 310-helix, either right- or left-handed, depending on the amino acid sequences. The structural preferences of solid-state \documentclass{article}\pagestyle{empty}\begin{document}$ Z\rlap{--} (Aib_3 \rlap{--} )L - Val - OMe $\end{document} and \documentclass{article}\pagestyle{empty}\begin{document}$ Z\rlap{--} (Aib_3 \rlap{--} )L - Val - Gly - OMe $\end{document} have been determined by x-ray diffraction. In accord with the solution data, incipient 310-helices, formed by two and three β-turns, have been found for the tetra- and pentapeptides, respectively. The tetrapeptide helix has the left-handed screw sense, while that of the pentapetide is right-handed, thus confirming the conclusions of the CD analysis of the solution.
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    URL: http://dx.doi.org/10.1002/bip.360220507
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    Mobility of oligopeptides on normal-phase silica: Effect of positional isomerism (1983)
    New York : Wiley-Blackwell
    Biopolymers 22 (1983), S. 1401-1407 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Isomeric oligopeptides composed of five methionyl residues and one glycyl residue or of five γ-methyl-L-glutamyl residues and one glycyl residue all exhibit marked differences in retention on normal-phase silica. When the glycyl residue is at internal positions of hexa or heptapeptides, the peptide elutes most rapidly form the μPorasil column. Comparison of the effect of positional isomerism on retention in short oligopeptides with the effect on retention of hexamers and heptamers suggests that a change in peptide conformation may be responsible for the change in oligopeptide mobility.
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    URL: http://dx.doi.org/10.1002/bip.360220511
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