ISSN:0892-6638    

DOI:10.1096/fasebj.6.7.1563589

出版商:Wiley    

年代:1992

数据来源: WILEY

ISSN:0892-6638    

DOI:10.1096/fasebj.6.7.1563590

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

The liver is a major target for both short‐ and long‐term actions of ethanol. The mechanisms that mediate the response of cells and tissues to chronic intake of ethanol are unknown, but it is likely that both adaptive and deleterious responses are triggered by short‐term interactions of the cell with ethanol. Cellular signaling processes are candidates to mediate the connection between short‐ and long‐term actions of ethanol. Receptor‐coupled signal transduction systems in the plasma membrane of many different cell types are affected by ethanol. In the liver, the signaling processes associated with phospholipases C and D are particularly responsive to ethanol. In this review, we investigate the direct and indirect short‐term effects of ethanol on the signal transduction systems in liver and discuss the possible implications for the responses of the liver to chronic ethanol exposure.—Hoek, J. B.; Thomas, A. P.; Rooney, T. A.: Higashi, K.; Rubin, E. Ethanol and signal transduction in the liver.FASEB J.6: 2386‐2396; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.7.1563591

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

Hyaluronan (hyaluronic acid) is a high‐molecular‐mass polysaccharide found in the extracellular matrix, especially of soft connective tissues. It is synthesized in the plasma membrane of fibroblasts and other cells by addition of sugars to the reducing end of the polymer, whereas the nonreducing end protrudes into the pericellular space. The polysaccharide is eatabolized locally or carried by lymph to lymph nodes or the general circulation, from where it is cleared by the endothelial cells of the liver sinusoids. The overall turnover rate is surprisingly rapid for a connective tissue matrix component (t½0.5 to a few days). Hyaluronan has been assigned various physiological functions in the intercellular matrix, e.g., in water and plasma protein homeostasis. Hyaluronan production increases in proliferating cells and the polymer may play a role in mitosis. Extensive hyaluronidase‐sensitive coats have been identified around mesenchymal cells. They are either anchored firmly in the plasma membrane or bound via hyaluronan‐specific binding proteins (receptors). Such receptors have now been identified on many different cells, e.g., the lymphocyte homing receptor CD 44. Interaction between a hyaluronan receptor and extracellular polysaccharide has been connected with locomotion and cell migration. Hyaluronan seems to play an important role during development and differentiation and has other cell regulatory activities. Hyaluronan has also been recognized in clinical medicine. A concentrated solution of hyaluronan (10 mg/ml) has, through its tissue protective and rheological properties, become a device in ophthalmic surgery. Analysis of serum hyaluronan is promising in the diagnosis of liver disease and various inflammatory conditions, e.g., rheumatoid arthritis. Interstitial edema caused by accumulation of hyaluronan may cause dysfunction in various organs.—Laurent, T. C.; Fraser, J. R. E. Hyaluronan.FASEB J.6: 2397‐2404; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.7.1563592

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

Estimates of the quantitative contribution of adipose tissue to whole‐body glucose metabolism, previously reported as 1–3%, have been revised to be on the order of 10–30%, These revised estimates come, in part, from a recognition that adipose tissue uses glucose to produce lactate and pyruvate, in addition to CO2and triglycerides. Lactate production by adipose tissue is modulated in vitro by changes in glucose, insulin, and epinephrine concentrations. In vivo, lactate production is regulated acutely by the animal's nutritional state (fed or fasted) and chronically by the degree of obesity. A strong positive correlation exists between rat fat cell size and relative conversion of glucose to lactate (r= 0.89,P<0.001). Diabetes is also associated with markedly increased lactate production in adipocytes. Fat cells from obese or diabetic rats (or humans) can metabolize to lactate as much as 50‐70% of the glucose taken up. From these recent studies, a picture is emerging in which the adipose organ may provide lactate for hepatic gluconeogenesis during fasting, and also lactate for hepatic glycogen synthesis after food ingestion. Modulation of adipocyte lactate production and contribution of adipose tissue lactate to the body's fuel economy in physiological and pathological states are the focus of this review.—DiGirolamo, M.; Newby, F. D.; Lovejoy, J. Lactate production in adipose tissue: a regulated function with extra‐adipose implications.FASEB J.6: 2405‐2412; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.7.1563593

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

The dopamine hypothesis of schizophrenia has been the dominant theoretical construction guiding research and treatment of the schizophrenic disorders over the past generation. This hypothesis, in its simplest guise, posits the presence of a functional alteration in central dopaminergic systems in the brains of schizophrenic patients. Recent findings have resulted in a greater understanding of the complexity of the central dopaminergic systems and have led to revisions of the hypothesis of a simple functional hyperactivity of central dopaminergic systems. These recent data suggest that there may be regionally restricted changes in the function of the mesotclencephalic dopamine system, and that these changes may be in opposite directions. Such changes may be associated with dysfunctions of interactions between distinct dopaminergic terminal field regions, and may be subserved by functional derangements in other transmitter systems or reflect regionally restricted changes in expression or function of distinct dopamine receptors or catecholamine synthetic enzymes, A recent FASEB symposium reviewed new advances in molecular biology, biochemistry, pharmacology, anatomy, and systems neuroscience as they relate to schizophrenia, and discussed the implications of these data for guiding future research and treatment strategies.—Goldstein, M.; Deutch, A. Y. Dopaminergic mechanisms in the pathogenesis of schizophrenia.FASEB J.6: 2413‐2421; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.7.1348713

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

The hypervariable loops of an antibody molecule are supported on the relatively conservedβ‐sheeted frameworks of the heavy‐ and light‐chain variable domains (designated VH and VL domains, respectively). Residues within and flanking these loops interact with antigen and confer the specificity and affinity of antigen binding on the immunoglobulin molecule. Thus, the isolation and expression of VH and VL domain genes are of particular interest both for analysis of the determinants of antibody specificity and for generation of fragments with binding affinities for use in therapy and diagnosis. The PCR can now be used to isolate diverse repertoires of antibody VH and VL domain genes from antibody‐producing cells from different species, including humans and mice. The genes can be expressed as either secreted or surface‐bound Fv or Fab fragments, usingEscherichia coliexpression systems, and the desired antigen‐binding specificity screened for or, preferably, selected. The use ofE. colias an expression host allows the required antigen‐binding specificity to be isolated in clonal form in a matter of days. The VH and VL domain genes can also be hyper‐mutated and higher‐affinity variants isolated by screening or selection. Thus, the use of this technology should allow the isolation of novel binding specificities or specificities that are difficult to generate by hybridoma technology. It will also facilitate the isolation of human‐derived Fv/Fab fragments that may be less immunogenic in therapy. This approach therefore has almost unlimited potential in the generation of therapeutics with binding specificities to order. The fragments can be used either alone or linked to effector functions in the form of antibody‐constant domains or toxins. The new technology could prove to be a method of choice for the rapid and convenient production of designer antibodies.—Ward, E. S. Antibody engineering: the use ofEscherichia colias an expression host.FASEB J.6: 2422‐2427; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.7.1563594

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

Traditional paradigms suggest that encounter with an antigen converts naive peripheral T cells into memory cells with less stringent requirements for activation and increased capacities for lymphokine production. Recent evidence argues that this view may be oversimplified in two ways. First, an encounter with antigen in the absence of certain costimulatory factors can render a T cell anergic — that is, unable to respond to antigen under normal conditions. Second, although cells of the memory T cell population are more responsive than naive cells to some stimuli, these cells are hyporesponsive in other situations. Intrinsic resistance of memory T cells to elevation of intracellular calcium ion concentrations may contribute to their poor responsiveness to agents that activate naive cells. Thus, aspects of the costimulatory environment can determine whether a resting T cell is activated or rendered anergic and may also influence the kinds of stimuli to which a memory T cell will respond.—Jenkins, M. K.; Miller, R. A. Memory and anergy: challenges to traditional models of T lymphocyte differentiation.FASEB J.6: 2428‐2433; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.7.1563595

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

Alternating currents affect ion transport processes and ATP splitting through changes in the activation of the membrane Na,K‐ATPase. Both processes vary with the frequency, and the effective range includes the environmental 60 Hz. ATP splitting by Na,K‐ATPase suspensions decreases for the enzyme under normal conditions, with the maximum effect at 100 Hz. ATP splitting increases when the enzyme activity is lowered to less than half its optimal value by changes in temperature, ouabain concentration, etc. These observations can be explained by the effects of the ionic currents on ion binding at the enzyme activation sites. Such a mechanism could account for the effects of electromagnetic fields on cells, as the transmembrane enzyme can convey the effect of an extracellular signal into the cell via ionic fluxes, and the measured threshold field is within the range of reported biological effects.—Blank, M. Na,K‐ATPase function in alternating electric fields.FASEB J.6: 2434‐2438; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.7.1314204

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

Knowledge regarding the steps and mechanisms related to the intra‐ and interchain cross‐linking of collagen and elastin has evolved steadily during the past 30 years. Recently, effort has been directed at identifying the location and types of cross‐links that are found in collagen and elastin. There are two major groups of cross‐links: those initiated by the enzyme lysyl oxidase and those derived from nonenzymatically glycated lysine and hydroxylysine residues. The formation of enzymatic cross‐links depends on specific enzymes, amino acid sequences, and quaternary structural arrangements. The cross‐links that are derived nonenzymatically occur more adventitiously and are important to pathobiological processes. Considerable progress has been made in elucidating the pathways of synthesis for several of the enzymatically mediated cross‐links, as well as possible mechanisms regulating the specificity of cross‐linking. Although less is known about the chemistry of cross‐links arising from nonenzymatically glycated residues, recent progress has also been made in understanding possible biosynthetic pathways and control mechanisms. This review focuses on such progress and hopes to underscore the biological importance of collagen and elastin cross‐linking.—Reiser, K.; McCormick, R. J.; Rucker, R. B. Enzymatic and nonenzymatic cross‐linking of collagen and elastin.FASEB J.6: 2439‐2449; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.7.1348714

出版商:Wiley    

年代:1992

数据来源: WILEY