ISSN:0892-6638    

DOI:10.1096/fasebj.3.6.2703105

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Acute in vitro exposure to ethanol and other intoxicant‐anesthetics activates γ‐aminobutyric acid (GABA)‐stimulated chloride channels and inhibits voltage‐dependent calcium and sodium channels of isolated brain membranes. The question of whether these neurochemical actions are responsible for intoxication in vivo has been addressed using animal populations displaying genetic differences in sensitivity to alcohol and benzodiazepine intoxication. These genetic approaches include inbred strains, selected lines, recombinant inbred strains, and heterogeneous stocks. Genetic differences in ion channel function provide strong evidence for a role of the GABA‐stimulated chloride channel in ethanol and benzodiazepine intoxication; the role of calcium and sodium channels is less clear.— Harris, R. A.; Allan, A. M. Alcohol intoxication: ion channels and genetics.FASEB J.3: 1689‐1695; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.6.2467834

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Measurements of the contractile response to norepinephrine (NE) of a variety of arteries of three mammalian species that are commonly used in the laboratory provide evidence that tissue sensitivity and affinity of the α1‐adrenoceptor for NE covary over a range of several orders of magnitude. The quantitative relationship suggests that variation in affinity can, to a great extent, account for the variation in sensitivity found in a number of circumstances. Furthermore, it is argued that the variation in affinity appears to be continuous and thus does not provide a basis for receptor type subdivision. There is also evidence that adrenergic antagonist affinity can vary significantly in tissues. The factors that might account for this variation include differences in receptor chemical structure, in the local membrane microenvironment, and in a number of intracellular processes. A hypothesis of variable receptor affinity has been proposed. If it is correct, then variation in receptor affinity is an important functionally relevant variable that could account for selectivity of tissue responses to circulating hormones and may represent a mechanism of change in the intact organism and in disease.—Bevan, J. A.; Bevan, R. D.; Shreeve, S. M. Variable receptor affinity hypothesis.FASEB J.3: 1696‐1704; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.6.2564831

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Metal‐nucleus distances measured by paramagnetic effects on T1and interproton distances measured by the nuclear Overhauser effect have been used to determine the conformations, arrangement, locations of enzyme‐bound substrates with respect to specific amino acid residues, and to dock them into X‐ray structures of enzymes. Synthetic peptide fragments of enzymes that range from 45 to 50 residues in length in some cases retain enough secondary and tertiary structure to bind substrates with affinities and in conformations similar to those found on the complete enzymes. The entire structure of peptides of this size can be determined in solution by 2‐dimensional nuclear magnetic resonance (NMR) methods. The applications of NMR methods to enzymology are exemplified by studies of adenylate kinase, ketosteroid isomerase, staphylococcal nuclease, and DNA polymerase I.—Mildvan, A. S. NMR studies of the interactions of substrates with enzymes and their peptide fragments.FASEB J.3: 1705‐1714; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.6.2649401

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Cellular antigens encoded by tumor viruses and some antigens encoded by cellular oncogenes offer advantages as targets for immunotherapy by being inextricably associated with the neoplastic phenotype. For example, monoclonal antibodies (MAb) specific for an antigen encoded by theneuoncogene have a direct inhibitory effect on proliferation of antigen‐positive tumor cells. Many of the oncogene‐encoded cell surface molecules are growth factor receptors, as are some tumor‐associated differentiation antigens (TADAs). Therefore, it is not surprising that their level of cancer specificity is similar. There have been some promising findings from using TADAs as targets for various forms of immunotherapy, and one would expect the results to further improve by targeting to molecules that are more directly involved in cell proliferation and/or in maintaining the malignant state.— Hellström, K. E.; Hellstrom, I. Oncogene‐associated tumor antigens as targets for immunotherapy.FASEB J.3: 1715‐1722; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.6.2649402

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

RNA polymerase II is a multisubunit enzyme involved in the transcription of protein encoding genes. Recently acquired knowledge of the transcription process and of the RNA polymerase molecule as well as the isolation of subunit clones have led to a better understanding of the enzyme's functional regulation. Specific transcription initiation occurs at promoter regions located upstream of the gene and requires a minimum of five basic factors in addition to the enzyme. Furthermore, proteins that bind to specific DNA elements within the promoter also regulate transcriptional activity. Additional factors are required for the elongation and, possibly, termination of transcription. Two elongation factors, SII and TFIIF, interact directly with the RNA polymerase II molecule. Functional domains of RNA polymerase II have been determined by analysis of genomic clones for the two largest subunits of the enzyme. For example, the 240‐kDa largest subunit contains a highly phosphorylated carboxyl‐terminal heptapeptide domain repeated 26‐52 times that is absolutely required for transcription in vivo. Analysis of the polymerase molecule and its interaction with basic gene‐specific transcription factors will aid in our studies of the control of gene expression.— Saltzman, A. G.; Weinmann, R. Regulation of RNA polymerase II activity.FASEB J.3: 1723‐1733; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.6.2649403

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Studies of the relationship of hepatic 5'‐deiodinase activity to hepatic lipogenic capacity were conducted. Rats of the Zucker, BHE, and Sprague‐Dawley strains were used. BHE and Sprague‐Dawley rats were starved and refed a 65% glucose diet, whereas lean and obese Zucker rats were fed a stock diet; the rats were thus different in hepatic lipogenic capacity. After hepatic 5'‐deiodinase activity was determined, we found that rats genetically predisposed to increased hepatic lipogenesis had less deiodinase activity than rats without this genetic feature. The role of the interaction between the thyroid hormones and glucocorticoid in the activity of hepatic deiodinase was also studied. Adrenalectomized (ADX) or intact BHE and Sprague‐Dawley rats were injected with saline, thyroxine, or triiodothyronine and either saline or glucocorticoid. The normal Sprague‐Dawley rats made predictable adjustments to their deiodinase activity when their hormonal status was manipulated, whereas the BHE rats responded as though these manipulations were corrections rather than additions or deletions.—McIntosh, M. K.; Berdanier, C. D.; Kates, A‐L. Studies of 5'‐deiodinase activity in rats differing in hepatic lipogenic activity.FASEB J.3: 1734‐1740; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.6.2703106

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Eye lens senile cataract is a major cause of blindness, affecting the elderly in particular. The etiology of the disorder has been elusive, and attempts to delay the onset of senile cataracts have been unsuccessful. The need for more information is underscored by epidemiologists who estimate that the ability to delay cataract formation in humans by only 10 years would eliminate the need for 50% of the cataract extractions performed annually in the United States. The Emory mouse provides the best model for human senile cataracts. Feeding Emory mice a diet that was restricted in calories by approximately 21% delayed the onset of cataracts. This is the first study that demonstrates in vivo the delay of senile‐type cataracts. In these animals, aging and cataracts are associated with diverse changes in the proportion of various proteins (particularly 21, 22, 31‐34 kDa) and with transformation of proteins from a soluble to an insoluble state. In advanced cataracts, there is a loss of total protein. Within a cataract grade, there is no difference between restricted and nonrestricted animals in relative proportion of specific lens proteins or in amounts of total or soluble proteins. The transition from a clear to cataractous lens appears when the soluble‐to‐total protein ratio falls below about 0.58. The exclusive use of γ‐crystallin as an indicator of lens viability is questioned. To the extent that cataract formation is due to lens protein oxidation and/or an inability to proteolytically remove damaged protein, it would appear that caloric restriction results in enhanced protection against lens oxidative stress or in prolonged proteolytic function.—Taylor, A.; Zuliani, A. M.; Hopkins, R. E.; Dallal, G. E.; Treglia, P.; Kuck, J. F. R.; Kuck, K. Moderate caloric restriction delays cataract formation in the Emory mouse.FASEB J.3: 1741‐1746; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.6.2703107

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Tumors and activated macrophages release angiogenic factors that stimulate migration and proliferation of capillaries. We studied the development of angiogenesis before the appearance of mesotheliomas in C57B1/6 mice. Weekly i.p. injections of crocidolite asbestos fibers produced mesotheliomas after 30‐50 wk. The initial histologic response to asbestos fibers was a nodular lesion on the peritoneal lining composed of clusters of fibers, activated macrophages, and proliferating mesenchymal cells. The earliest visible evidence of angiogenesis was seen surrounding 7% of these lesions 14 days after a single injection of 200 μg of crocidolite asbestos fibers. After six weekly injections, 30% of the lesions containing asbestos fibers were surrounded by a capillary network radiating toward the center of the lesion. Other mineral fibers, including chrysotile asbestos and fiberglass, also induced angiogenesis after six weekly injections. In contrast, only 8% of the lesions containing short asbestos fibers (90.6% ≤ 2.0 μm) and 9% of the lesions containing silica particles showed evidence of angiogenesis. We conclude that tumorigenic mineral fibers induce angiogenesis in the peritoneal lining, whereas nontumorigenic mineral particles or short asbestos fibers are less effective. Ingrowth of new blood vessels around clusters of asbestos fibers may facilitate the later emergence of mesotheliomas at these sites.— Branchaud, R. M.; MacDonald, J. L.; Kane, A. B. Induction of angiogenesis by intraperitoneal injection of asbestos fibers.FASEB J.3: 1747‐1752; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.6.2467835

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Administration of different steroid hormones in vivo has distinct and specific effects on the MAO activity of the adrenal medulla. In an effort to reconstitute these effects in defined cells, we have isolated endothelial cells and chromaffin cells from the bovine adrenal medulla and tested each cell type for sensitivity to these steroids. As in the intact animal, we found that endothelial cell MAO activity was stimulated 1.5‐ to 2.5‐fold by 10 μM progesterone, hydrocortisone, and dexamethasone, inhibited by ca. 50% by 17‐α‐estradiol, but unaffected by testosterone. The type of MAO in the endothelial cells was found to be exclusively of the A type. The chromaffin cells had MAO B exclusively and were inert to treatment with dexamethasone. The mode of action of the various steroids on MAO A activity in endothelial cells seemed to be that of affecting the number of MAO molecules, as binding of [3H]pargyline, an MAO inhibitor, changed in proportion to changes in enzyme activity. Consistently, the kinetic parameters for MAO A showed changes inVmaxbut notKmunder all conditions. The specificity of steroid action on MAO A activity was also supported by the fact that steroid‐induced changes in total cell division ([14C]thy‐midine incorporation) and total protein synthesis ([14C]leucine incorporation) were seen after changes in MAO A. We conclude that the differential effects of steroids on MAO activity in the intact adrenal medulla can be reproduced in cultured adrenal medullary endothelial cells but not in chromaffin cells. Therefore we suggest that the action of these steroid hormones on the intact adrenal medulla may be restricted to the endothelial cell component of this tissue.—Youdim, M. B. H.; Banerjee, D. K.; Kelner, K.; Offutt, L.; Pollard, H. B. Steroid regulation of MAO activity in the adrenal medulla.FASEB J.3: 1753‐1759; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.6.2495232

出版商:Wiley    

年代:1989

数据来源: WILEY