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  • 1
    Electronic Resource
    Electronic Resource
    Nonreceptor mediated nuclear accumulation of insulin in H35 rat hepatoma cells (1992)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 153 (1992), S. 607-613 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: We previously demonstrated that insulin accumulated in the nucleus in several cell types and partially characterized the uptake mechanisms and pathways in H35 rat hepatoma cells. Nuclear accumulation of insulin was energy independent, time, temperature, and insulin concentration dependent, but apparently nonsaturable. This study investigated further the initial endocytotic pathways that contribute to the nuclear accumulation of insulin using trypsin treatment of the cells to prevent insulin binding to its plasma membrane receptor. Total cell-associated, intracellular, and nuclear insulin were compared in control and trypsin-treated H35 hepatoma cells. Trypsin treatment markedly decreased total cell-associated and intracellular insulin as well as the nuclear accumulation of insulin when cells were incubated with 2.8 ng/ml insulin. When the cells were incubated with 100 ng/ml insulin, trypsin treatment totally inhibited insulin binding to the plasma membrane for at least 90 min. However, intracellular accumulation of insulin was reduced by only 50% at 60 min, and trypsin treatment failed to inhibit the nuclear accumulation of insulin. Chemical extraction and Sephadex G-50 chromatography revealed nuclear associated insulin in trypsin-treated cells was identical to that in control cells incubated with either 2.8 or 100 ng/ml insulin. These results suggest that a nonreceptor mediated uptake pathway, i.e., fluid-phase endocytosis, contributed significantly to the nuclear accumulation of insulin at high insulin concentrations, but at lower insulin concentrations the receptor-mediated pathway predominated. No matter which initial endocytotic route was used to internalize insulin, the insulin apparently associated with the same nuclear matrix proteins. This association of insulin with the nuclear matrix may be involved in regulation of nuclear events such as cell growth and differentiation or gene transcription. © 1992 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1041530323
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  • 2
    Electronic Resource
    Electronic Resource
    Behavioral sensitivity of rats to extremely-low-frequency magnetic fields (1994)
    New York, NY [u.a.] : Wiley-Blackwell
    Bioelectromagnetics 15 (1994), S. 411-426 
    Details
    ISSN: 0197-8462
    Keywords: operant conditioning ; Pavlovian conditioning ; magnetic field ; detection ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Work in our laboratory has revealed autonomic and/or behavioral sensitivity of mice, rats, and a domestic fowl to extremely-low-frequency (ELF) or nominally static magnetic (B) fields at flux densities between 250 and 1700 μT (rms). To extend our work, an automated exposure and data-acquisition system was used with the technique of conditional suppression to assess behavioral sensitivity to time-varying B fields. Each of five rats was exposed aperiodically to a B field during 3 min warning periods that terminated in a brief electric shock. The difference between rates of lever pressing during B-field warning periods and rates during immediately antecedent, 3 min control periods was analyzed at frequencies of 7, 16, 30, 60, and 65.1 Hz. To produce equivalent induced voltages in the rat at each frequency, graded flux densities were established that ranged from 1900 μT at 7 Hz to 200 μT at 65.1 Hz. Analysis of differences in lever-pressing rates revealed that in a given session of testing the rats would increasingly suppress responding when exposed to a B field, but this trend was independent of frequency. This experiment provides evidence of behavioral sensitivity by a mammal to an ELF magnetic field. © 1994 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bem.2250150505
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  • 3
    Electronic Resource
    Electronic Resource
    Exposure to 60 Hz magnetic fields in the electric utility work environment (1994)
    New York, NY [u.a.] : Wiley-Blackwell
    Bioelectromagnetics 15 (1994), S. 21-32 
    Details
    ISSN: 0197-8462
    Keywords: ELF ; EMF ; exposure assessment ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Research that has attempted to examine the relationship between work exposures to magnetic fields and health effects has suffered from limited exposure information. Power-frequency electric and magnetic (EM) field exposures vary substantially between industries, occupations, and individuals. In this study magnetic field data were collected for a variety of occupational categories within an electric utility. The sampling procedures emphasized craft occupations that were presumed to have higher exposures to magnetic fields. The objectives were to provide better exposure information for an ongoing cancer mortality study, examine the relationship between different summary measures of magnetic field exposure, and make available descriptive information useful for exposure reduction and worker education. Principal components analysis (PCA) and Varimax rotation were used to explore the relationships between the different summary measures among all utility workers and among the subset of electrical craft occupations. Discriminant analysis was used to assess summary measures of exposure that differentiated occupational groups. Measurements for 770 days generated a total of 42378 hours of magnetic field data. Eleven summary indices of exposure were calculated for specific occupational groups. These include arithmetic mean, geometric mean, median, 95th and 99th percentiles, and fraction of measurements exceeding .5, 1, 5, 10, and 100 μT. Electrical craft occupations had higher work exposures than non-craft occupations. Electricians and substation operators had the highest exposures among craft occupations.We identified subsets of summary measures that were intercorrelated. The first PCA axis included the geometric mean, median, and the fractions exceeding 0.5 and 1.0 μT. This set of measures also were best at discriminating occupational groups. The relevance of these findings may become more important if consistent associations are found between particular occupations and disease and particular occupations and magnetic field summary measures. Further research is needed to evaluate these exposure assessment findings. © 1994 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bem.2250150107
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  • 4
    Electronic Resource
    Electronic Resource
    Lithium as a normal metabolite: Some implications for cyclotron resonance of ions in magnetic fields (1988)
    New York, NY [u.a.] : Wiley-Blackwell
    Bioelectromagnetics 9 (1988), S. 387-391 
    Details
    ISSN: 0197-8462
    Keywords: H fields ; trace elements ; nutrition ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Cyclotron resonance of ions has been proposed as a mechanism by which weak, extremely-low-frequency (ELF) electromagnetic fields can act on biological systems. Critics of a mechanism predicated on resonance of lithium have argued that this element is virtually absent from the internal milieu of mammals and otherwise plays no role in the normal physiological functioning of the organism. Sophisticated techniques of trace-element analysis have recently revealed that lithium is a normal constituent of tissues of assayed mammals, including those of rats and human beings. There is evidence, too, that lithium is an important, biologically-active element. Cyclotron resonance may or may not be a mechanism by which ELF- and static-magnetic fields at low strengths combine to affect the organism, but rejection of this mechanism on the grounds that lithium is absent or is physiologically inadequate is unwarranted. Lithium is normally present and is metabolically active in many tissues, especially those of the of the neuroendocrine system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bem.2250090409
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  • 5
    Electronic Resource
    Electronic Resource
    Metabolic relations in the termite - protozoa symbiosis: Temperature effects (1942)
    Philadelphia : Wiley-Blackwell
    Journal of Cellular and Comparative Physiology 19 (1942), S. 211-219 
    Details
    ISSN: 0095-9898
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1030190209
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  • 6
    Electronic Resource
    Electronic Resource
    Functions of the IGFs in early mammalian development (1993)
    New York, NY [u.a.] : Wiley-Blackwell
    Molecular Reproduction and Development 35 (1993), S. 421-426 
    Details
    ISSN: 1040-452X
    Keywords: Preimplantation embryo ; Protein database ; Growth factors ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: The identification of growth factors and/or receptors produced by mammalian embryos or present in the maternal reproductive tract is of basic interest, as well as having practical application. Early studies established that receptors binding insulin and the insulin-like growth factors (IGFs) are expressed by preimplantation mouse embryos. These studies have been confirmed at the molecular level using RT-PCR techniques. In addition, high resolution electron microscopy has shown that insulin is internalized by the cells of the blastocyst stage mouse embryo, and that immunologically intact insulin is detectable in the cells of the trophectoderm and inner cell mass. Similar studies with gold labelled IGF-I have shown that this ligand is also bound and internalized by mouse blastocysts. However, although all blastocysts express receptors that bind IGF-I on the basolateral cell surface of the trophectoderm, only 30% exhibit apically located receptors. In order to elucidate the functions of IGFs in early mouse development, we are in the process of constructing protein databases for embryos at the eight-cell and blastocyst stage. By the use of the database, it should prove possible to elucidate targets of growth factor action. © 1993 Wiley-Liss, Inc.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/mrd.1080350417
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  • 7
    Electronic Resource
    Electronic Resource
    Proline oxidase in cultured mammalian cells (1977)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 91 (1977), S. 369-376 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: We sought a cultured cell line with Proline Oxidase activity to study the regulation and physiologic role of the enzyme in mammalian tissues. Among the cell lines tested, only LLC-RK1 cells, derived from rabbit kidney, had significant Proline Oxidase activity; the Km for proline of the enzyme from these cells was similar to that for the liver enzyme. LLC cells, Proline Oxidase positive, were able to convert proline to CO2. In contrast, CHL cells, Proline Oxidase negative, did not have this capability. The presence of Proline Oxidase in LLC cells and the absence of the enzyme in fibroblasts suggest that Proline Oxidase may serve as a marker enzyme for distinguishing parenchymal kidney cells from fibroblasts in culture. Cells transformed by SV40 virus and cells transformed by methylcholanthrene had activities higher than the parent cell line, but this effect of transformation could not be generalized to all transformed cells. Finally, L-hydroxy proline at 100-fold greater concentration than substrate L-proline failed to decrease proline oxidation. This finding suggests distinct degradative enzymes for these two amino acids.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1040910306
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  • 8
    Electronic Resource
    Electronic Resource
    Stimulation of the hexosemonophosphate-pentose pathway by pyrroline-5-carboxylate in cultured cells (1982)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 110 (1982), S. 255-261 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Δ1-Pyrroline-5-carboxylic acid, an intermediate in the interconversions of proline, ornithine, and glutamate, is a potent stimulator of glucose oxidation through the hexosemonophosphate-pentose pathway. The effect is observed in cultured human fibroblasts, Chinese hamster ovary cells (CHO-K1), and rabbit kidney cells (LLC-RK1). In human fibroblasts, the magnitude of the stimulation of the hexosemonophosphate-pentose pathway is dependent on the concentration of added pyrroline-5-carboxylate and the effect is observed over a wide range of glucose concentrations. The mechanism of the effect is related to the generation of oxidizing potential in the form of NADP+ by pyrroline-5-carboxylate reductase concomitant with the conversion of pyrroline-5-carboxylate to proline. In LLC-RK1 cells, a cell line unique in having proline oxidase activity, proline also stimulated hexosemonophosphate-pentose pathway activity. Although pyrroline-5-carboxylate markedly stimulated the hexosemonophosphate-pentose pathway, it had no effect on glucose metabolism in the Embden-Meyerhof pathway or the tricarboxylic acid cycle. Since the hexosemonophosphate-pentose pathway is a source of ribose-5-phosphate, the precursor of phosphoribosyl pyrophosphate, the effect of pyrroline-5-carboxylate on the hexosemonophosphate-pentose pathway may link amino acid and nucleic acid metabolism.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1041100306
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  • 9
    Electronic Resource
    Electronic Resource
    Insulin and α2-macroglobulin-methylamine undergo endocytosis by different mechanisms in rat adipocytes: I. Comparison of cell surface events (1987)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 133 (1987), S. 203-212 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: This ultrastructural study compared the endocytosis of a peptide hormone, ferritin-labeled insulin (Fm-I) or gold-labeled insulin (Au-I), and a non-hormonal ligand, gold-labeled alpha-2-macroglobulin-methylamine (Au-α2MGMA), by rat adipocytes. Quantitative analysis of the cell surface showed that coated pits occupied 0.4% of the adipocyte surface. This was one fifth to one tenth of that which has been reported on fibroblasts and hepatocytes, cell types in which receptor-mediated endocytosis has been extensively studied. In contrast, uncoated micropinocytotic invaginations were quite numerous and occupied 13.1% of the adipocyte cell surface. The frequency of microphinocytotic invaginations, 13.8 per μm2 of plasma membrane, was 7-12 times greater than has been reported on fibroblasts. Therefore, the ultrastructure of the endocytic apparatus on rat adipocytes was different from more commonly studied cell types. At 4°C, Au-α2MGMA concentrated within coated pits to a density that was 52 times greater than that on the uncoated plasma membrane. Au-α2MGMA was excluded from micropinocytotic invaginations by more than 93%; this exclusion was unrelated to the size of the Au-α2MGMA particle. In contrast, at 4°C, Fm-I did not concentrate within coated pits and occupied micropinocytotic invaginations in a random manner. At 37°C, coated pits accounted for all of the endocytosis of Au-α2MGMA, proving that these structures were functional despite their atypically low density. In contrast, greater than 99% of the endocytosis of Fm-I or Au-I occurred through micropinocytotic invaginations. These results demonstrated for the first time by a comparative, quantitative, ultrastructural method that insulin and Au-α2MGMA undergo endocytosis by dissimilar mechanisms on rat adipocytes. Dissimilarities in the endocytosis of insulin and Au-α2MGMA may be related to the different biological roles of these two molecules.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1041330202
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  • 10
    Electronic Resource
    Electronic Resource
    Insulin and α2-macroglobulin-methylamine undergo endocytosis by different mechanisms in rat adipocytes: II. Comparison of intracellular events (1987)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 133 (1987), S. 213-218 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: A previous ultrastructural study showed that gold-labeled insulin (Au-I) and the non-hormonal ligand gold-labeled alpha-2-macroglobulin-methylamine (Au-α2MGMA) underwent endocytosis by dissimilar cell surface structures on rat adipocytes. The present ultrastructural study compared the intracellular routes taken by these two ligands in adipocytes. Intracellular Au-α2MGMA was initially found within apparent coated vesicles but Au-I was not, consistent with the previous demonstration that Au-α2MGMA underwent endocytosis by coated pits whereas Au-I was internalized by uncoated micropinocytotic invaginations. Early in the endocytic pathway, the two ligands were segregated within separate small vesicles and tubulovesicles. Au-α2MGMA was concentrated in a small number of these structures whereas Au-I was sparsely distributed among a relatively large number. Subsequently, the two endocytic pathways converged as the ligands intermingled within pale multivesicular bodies and lysosome-like structures. Au-I was less efficiently transferred to lysosomes than Au-α2MGMA since a greater proportion of intracellular Au-I remained associated with small vesicles and tubulovesicles. This study indicates that early intracellular events in the endocytic pathways of insulin and α2MGMA are distinct. These findings are discussed in light of the fundamentally dissimilar biological roles of these two molecules and the possible involvement of the endocytic pathway in the insulin signaling mechanism.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1041330203
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