ISSN:0892-6638    

DOI:10.1096/fasebj.5.9.1860612

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

An attitude survey has revealed vividly contrasting institutional atmosphere and working conditions at U.S. medical schools. Environments at about one‐fourth of the schools were judged to be highly positive with regard to subjective atmosphere, career development, and faculty‐administration relations. Environments at another one‐fourth of all schools were judged to be highly negative in all of these areas. Recognizing the existence of these differences is necessary before administrative remedies for many of the problems at the latter group of schools can be implemented.—Lanks, K. W.; Li, P.‐W. Contrasting work environments of medical school faculty.FASEB J.5: 2233–2235; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.9.1860613

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

The uncoupling protein (UCP) is a proton/anion transporter found in the inner mitochondrial membrane of brown adipocyte. Although UCP has not been detected in mitochondria from any other tissue, it shares structural and catalytic properties with several other mitochondrial carrier proteins. Although UCP was discovered only recently it is one of the most extensively studied mitochondrial carrier proteins. Many tools useful in research on UCP have been developed such as antibodies and cDNAs corresponding to UCP of several animal species. More recently, the mouse, rat, and human genes encoding for UCP have been isolated and sequenced. The availability of these various tools has led to several significant observations. UCP gene expression is strongly controlled at the level of transcription by signals that are activated after the stimulation of brown adipocytes by norepinephrine. The comparison of UCP gene with the genes encoding the adenine nucleotide translocator revealed the existence of structural and evolutionary homologies. Moreover, in humans the UCP gene and one form of adenine nucleotide translocator gene are located on the same chromosome. Recently, the expression of functional UCP in various heterologous systems was achieved (Xenopusoocytes, CHO cells, yeasts). These data will facilitate studies of the structure/function relationship in UCP (identification of residues involved in H+transport, Cl−transport, nucleotide binding, mitochondrial targeting …). Another aspect of the present research on UCP is the understanding of mechanisms that control the UCP gene and the differentiated commitment of adipose precursor cells to thermogenic brown adipocytes. The multifaceted aspects of research on UCP make this protein interesting in areas of research as different as studies of ion translocating mechanisms, cellular specificity of gene transcription, control of gene expression by neuromediators, adipocyte differentiation, and the pharmacological treatment of obesity.—Ricquier, D.; Casteilla, L.; Bouillaud, F. Molecular studies of the uncoupling protein.FASEB J.5: 2237–2242; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.9.1860614

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

The nuclear hormone receptor superfamily is characterized by an impressive functional diversity of its members despite a remarkable overall structural unity. A variety of ligands bind specifically to them and these receptors control gene networks that have profound effects on growth, development, and homeostasis. The ligand‐receptor complexes recognize transcriptional enhancer DNA sequences, the hormone response elements, resulting in induction or repression of gene activity. The similarity between all these hormone response enhancer elements, as well as between the receptors themselves, indicates a conserved general strategy for the hormonal control of transcription by steroids. The activated receptors bind to responsive promoters and most likely mediate the assembly of stage‐ and tissue‐specific transcription factor complexes that stimulate or inhibit gene expression.—Wahli, W.; Martinez, E. Superfamily of steroid nuclear receptors: positive and negative regulators of gene expression.FASEB J.5: 2243–2249; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.9.1860615

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

Vaccination against tumor, either as a prophylactic procedure or as a mode of treatment, has been a distant goal of immunologists for many years. Ideally, the less specific therapies such as chemotherapy would be replaced by an anti‐tumor immune response in the host that would be present on a continuing basis. However, progress has been hampered by a lack of understanding of the role of viruses in human tumor development and the molecular nature of tumor‐associated antigens. Recent developments using the techniques of molecular biology and monoclonal antibody reagents are beginning to remedy this deficiency so that vaccination has become a real possibility for certain human cancers. The natural fluctuations in growth rates of some human tumors, and the observation that tumors can occasionally remain dormant for years, has led to the idea that the host has an intrinsic ability to control tumor growth, and that this ability is a property of the immune system. Attempts to enhance this putative control are being made by treating the host with defined biological modifiers that stimulate cells involved in immunity in vivo, and by seeking and expanding such cells in vitro before reinfusing them into the host. These attempts to harness the immune system to attack tumor cells that have evaded the host's defenses might be considered optimistic, but they will at least tell us a great deal about tumor cell behavior and the ability of the host to influence it.—Stevenson, F. K. Tumor vaccines.FASEB J.5: 2250–2257; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.9.1860616

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

Phospholipids have diverse and critical roles in cellular metabolism and function. Questions about the mechanisms of regulation of phospholipid synthesis are being investigated with a variety of systems and approaches. For example, the yeastSaccharomyces cerevisiaeis an organism in which both biochemical and genetic analyses are used. Biochemical approaches have yielded considerable information on the regulatory properties of enzymes of phospholipid biosynthesis. Studies of the activity of purified phosphatidylserine synthase have suggested how that enzyme is influenced by membrane phospholipids in the cell. The enzyme that regulates mammalian phosphatidylcholine biosynthesis, CTP:phosphocholine cytidylyltransferase, is also influenced by phospholipids. In addition, the activity of this enzyme often correlates with its translocation to membranes. The location of such enzymes in the cell is of particular interest in light of the possibility that the enzymatic reactions may be efficiently coupled in vivo. Techniques to render cultured cells permeable to phosphorylated molecules indicate that the enzymes of phosphatidylcholine biosynthesis may exist in an organized compartment so that the precursors of phosphatidylcholine are efficiently channeled through the pathway. To ask how phospholipids are transported in the cell, a combined biochemical and genetic approach has been used. These studies have revealed that the phosphatidylinositol/phosphatidylcholine transfer protein, considered to mediate intracellular phospholipid transfer, is a critical component of the secretory pathway for proteins. These results have allowed formulation of a number of new questions on the regulation of phospholipid metabolism and its relationship to general membrane processes.—Kent, C.; Carman, G. M.; Spence, M. W.; Dowhan, W. Regulation of eukaryotic phospholipid metabolism.FASEB J.5: 2258–2266; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.9.1860617

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

Most small arteries are partially constricted in vivo. After excluding neurogenic, metabolic, and circulating as well as local hormonal influences, a sizeable component of tone persists which is commonly called basal tone. In the absence of such tone, cardiac output would be insufficient to maintain the circulation. This review focuses on the contribution of stretch, induced by changes in transmural pressure, and flow acting through shear forces exerted at the blood vessel wall interface, to basal tone. Evidence concerning the cellular processes that may be activated by these physical forces —the mechanotransducing systems —are discussed. The involvement of the endothelium and the role of change in membrane potential are evaluated and lead to the conclusion that pressure and flow effects do not depend exclusively on the release of endothelial factors nor the activation of voltage‐gated Ca2+channels. Stretch/pressure‐induced changes in tone show distinctive pharmacological profiles. They are dependent on extracellular calcium and yet in many instances are only weakly affected by organic Ca2+‐entry inhibitors. Flow‐dependent vascular effects, both constrictor and dilator, are both exquisitely sensitive to changes in extracellular Na+and appear to be related to its transmembrane gradient. Stretch/pressure cause activation of protein kinase C, an intracellular modulator of Ca2+‐dependent contractile processes. The existence of separate and distinctive cellular sensing and responding systems to pressure and flow raise the possibility that the smooth muscle tone of the vascular system can be influenced independently by the pressure and rate of flow of the blood.—Bevan, J. A.; Laher, I. Pressure and flow‐dependent vascular tone.FASEB J.5: 2267–2273; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.9.1860618

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

Selenium has a highly specific metabolism centered around its incorporation as selenocysteine into selenoproteins. An outline of this metabolism has emerged from recent molecular biological and biochemical studies of bacteria and animals. A unique tRNA, designated tRNA[Ser]Sec, is charged with L‐serine, which is then converted through at least two steps to selenocysteine. With the aid of a unique translation factor, the selenocysteinyl‐tRNA[Ser]Secrecognizes specific UGA codons in mRNA to insert selenocysteine into the primary structure of selenoproteins. Turnover of selenoproteins presumably liberates selenocysteine which is toxic in its free form. Selenocysteineβ‐lyase catabolizes free selenocysteine and makes its selenium available for reuse. Proteins contain almost all the selenium in animals. Of the known selenoproteins, the glutathione peroxidases contain the most selenium. Cellular and plasma glutathione peroxidases are products of different genes but have 44% identity of amino acid sequence. There is evidence for other proteins of this family. Selenoprotein P is an unrelated protein with multiple selenocysteines in its primary structure. It contains most of the selenium in rat plasma. Studies of the regulation of cellular glutathione peroxidase by selenium have yielded conflicting results, but there is a strong suggestion that mRNA levels of the rodent liver glutathione peroxidase decrease in selenium deficiency. This could be a mechanism for directing selenium to the synthesis of other selenoproteins. Although present knowledge allows construction of an outline of selenium metabolism, several steps have not been characterized and little is known about mechanisms of its regulation.—Burk, R. F. Molecular biology of selenium with implications for its metabolism.FASEB J.5: 2274–2279; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.9.1830557

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

Carcinogenesis can be induced experimentally by exposure to exogenous agents or it can occur spontaneously without intentional or active intervention. Carcinogenesis can be actively induced by chemicals, radiation, infectious biological agents, transgenesis, or selective breeding. In the human and occasionally when testing potential carcinogens in animals, cancer may result from passive exposure to carcinogens encountered in the ambient environment or from changes in the internal milieu of the animal. Many carcinogens alter the structure of DNA resulting in carcinogenesis, but a significant number of carcinogens do not appear to act through this mechanism. When the action of specific carcinogenic agents is considered in relation to the stages of cancer development, initiation, promotion, and progression, the mechanism of the induction of carcinogenesis by DNA‐reactive agents that alter genomic structure can be reconciled with those agents that do not act in this manner. As some cells are fortuitously initiated by uncontrolled variables such as irradiation and through changes in normal processes, the stimulation of growth and altered genetic expression by nongenotoxic agents may result indirectly in cancer development. The final stage of carcinogenesis, progression, can occur spontaneously, enhanced by formation and propagation of genetic errors due to increased cellular proliferation associated with the promotion stage. In addition, chemical and viral agents that lack the capacity for initiation and promotion may actively convert cells in the stage of promotion to the stage of progression. Therefore, the diverse mechanisms of action of carcinogenic agents in relation to their effects on specific stages in the natural history of cancer development allow for greater congruence of many of the theories of carcinogenesis. The influence of the roles of nongenotoxic carcinogenic agents and the potential role of progressor agents on the carcinogenesis process allow a more accurate identification of the potential risk that specific carcinogenic agents pose for increasing human cancer.—Pitot, H. C., and Dragan, Y. P. Facts and theories concerning the mechanisms of carcinogenesis.FASEB J.5: 2280–2286; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.9.1860619

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

Aside from its well‐known anticoagulant action, heparin has many other biologic effects. Recent data emphasize the immunomodulatory effects of low dose heparin. The agent alters the traffic of lymphocytes blocking their expression of heparanase, an enzyme that digests the extracellular matrix allowing cell penetration to target tissues. It also has a weak direct immunosuppressive action in vitro and in vivo. Oral administration of heparin may cause immunosuppression, although the effects are weaker than after subcutaneous administration.—Gorski, A.; Wasik, M.; Nowaczyk, M.; Korczak‐Kowalska, G. Immunomodulating activity of heparin.FASEB J.5: 2287–2291; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.9.1860620

出版商:Wiley    

年代:1991

数据来源: WILEY