ISSN:0892-6638    

DOI:10.1096/fasebj.4.2.2298340

出版商:Wiley    

年代:1990

数据来源: WILEY

ISSN:0892-6638    

DOI:10.1096/fasebj.4.2.2404815

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Research efforts investigating the pathophysiology of adipose tissue have often focused separately on either the metabolic or cardiovascular components of an expanding fat mass. However, the growth and development of the fat cells and their vasculature are closely interrelated, a fact that has been established through more than a century of diverse studies of adipose tissue. Recently, the prevalence of obesity in the United States has stimulated investigations into the cardiovascular and metabolic correlates occurring with excessive lipid deposition and subsequent adipose tissue expansion. These investigations have resulted in conclusive evidence that, from a cardiovascular perspective, obesity results in an elevated blood volume and cardiac output, accompanied by an expansion of adipose water space, whereas from a metabolic aspect, the disease is characterized by adipocyte enlargement and associated alterations in metabolic pathways and hormonal responsiveness. Because these separate areas of research have independently shown interdepot differences in perfusion requirements and metabolic adaptations during the transition from the lean to obese state, adipocyte expansion may be partially dependent on the pattern of vascularity. This hypothesis is discussed by examining the integral relationship between the cardiovascular system and adipocyte metabolism, hopefully providing new insight into control of the pathophysiological processes of an expanding adipose organ.— Crandall, D. L.; DiGirolamo, M. Hemodynamic and metabolic correlates in adipose tissue: pathophysiologic considerations.FASEB J.4: 141‐147; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.2.2404816

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Laminin is a large (900 kDa) mosaic protein composed of many distinct domains with different structures and functions. Globular and rodlike domains are arranged in an extended four‐armed, cruciform shape that is well suited for mediating between distant sites on cells and other components of the extracellular matrix. The α‐helical coiled‐coil domain of the long arm is involved in the specific assembly of the three chains (A, B1, B2, and possible variants) of laminin and is the only domain composed of multiple chains. It is terminated by a large globular domain composed of five homologous subdomains formed by the COOH‐terminal part of the A chain. Sites for receptor‐mediated cell attachment and promotion of neurite outgrowth reside in the terminal region of the long arm. A second cell attachment site, a cell signaling site with mitogenic action, binding sites for the closely associated glycoprotein nidogen/entactin, and regions involved in calcium‐dependent aggregation are localized in the short arms. These domains, which to a large extent are composed of Cys‐rich repeats with limited homology to EGF, are the most highly conserved regions in laminins of different origin. At present, most structural and functional data have been collected for a laminin expressed by a mouse tumor, which can be readily isolated in native form and dissected into functional fragments by limited proteolysis. Increasing information on laminins from different species and tissues demonstrates considerable variations of structure. Isoforms of laminin assembled from different chains are focally and transiently expressed and may serve distinct functions at early stages of development even before being laid down as major components of basement membranes.— Beck, K.; Hunter, I.; Engel, J. Structure and function on laminin: anatomy of a multidomain glycoprotein.FASEB J.4: 148‐160; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.2.2404817

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Hep G2, a liver cell line derived from a human hepatoblastoma that is free of known hepatotropic viral agents, has been found to express a wide variety of liver‐specific metabolic functions. Among these functions are those related to cholesterol and triglyceride metabolism. Confluent Hep G2 monolayers express normal low‐density lipoprotein (LDL) receptors and continue to internalize and metabolize chylomicrons, very low‐density lipoproteins (VLDL), LDL, and high‐density lipoproteins. In lipoprotein‐free medium, apolipoproteins A‐I, A‐II, B, C, and E accumulate in the medium together with cholesterol, cholesteryl ester, triglyceride, and all the primary bile acids. The regulation of their synthesis and secretion is not fully known and their interrelationships have not been established. Because Hep G2 cells express these and other components of cholesterol and triglyceride metabolism, they are a microcosm for studying the central role of the liver.—Javitt, N. B. Hep G2 cells as a resource for metabolic studies: lipoprotein, cholesterol, and bile acids.FASEB J.4: 161‐168; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.2.2153592

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Retroviruses of the type C morphology have been implicated in a wide variety of diseases in animals and humans. The human T cell leukemia viruses types I (HTLV‐I) and II (HTLV‐II), the prototypic human‐type C retroviruses, have been identified as the causative agents of some forms of human leukemia and neurological disorders. The genetic structure and regulation of the HTLVs are more complex than their avian and murine leukemia virus counterparts. In addition to thegag, pol, andenvgenes that encode the characteristic virion proteins of all replication competent retroviruses, the genomes of HTLV encode the nonstructural proteins, Tax and Rex, which are required for regulating viral gene expression. To understand what appears to be a complex mechanism of disease induction by HTLV, elucidating the regulation and function of the viral gene products and the interaction of these products with each other, as well as with cellular factors, will be critical. This review focuses primarily on regulation of HTLV gene expression in the infected human T lymphocyte, but also discusses analogous gene regulation by the human immunodeficiency virus (HIV). It concentrates specifically on the role these gene products play in virus replication and, ultimately, pathogenesis.—Green, P. L.; Chen, I. S. Y. Regulation of human T cell leukemia virus expression.FASEB J.4: 169‐175; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.2.2404818

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

The molecular signals controlling liver regeneration are becoming rapidly defined. Control of growth in regenerating liver has advanced from elusive serum factors and nutrient effects to identification of entirely new growth factors with apparent liver specificity as well as establishment of meaningful gene expression patterns for growth factors already known. Based on studies with hepatocyte cultures and gene expression in regenerating liver, the substances EGF, TGFα, HBGF‐1 (aFGF), and two new substances (HPTA/HGF and Hepatopoietin B) have been defined as complete mitogens for hepatocytes and implicated in control of liver growth. The amino acid sequence of HPTA/HGF recently became clear and revealed interesting structural homologies in a molecule that might become the largest known growth factor. The plasticity of growth responses seen in liver may be controlled by these factors as well as by comitogenic substances such as norepinephrine which, although nonmitogenic per se, can initiate growth in hepatocytes exposed to the above mitogenic growth factors or mitogenic inhibitors such as TGFβ. The role of the latter in cessation of DNA synthesis in liver regeneration will be discussed, presenting the positive and negative evidence that constitutes the TGFβ paradox of liver regeneration.—Michalopoulos, G. K. Liver regeneration: molecular mechanisms of growth control.FASEB J.4: 176‐187; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.2.2404819

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

A new strategy for the delivery of cytotoxic agents to solid tumors is described in which monoclonal antibodies are used as carriers for enzymes to tumor cell surfaces. The enzymes are chosen for their abilities to convert relatively noncytotoxic drug precursors (prodrugs) into active anticancer drugs. The drugs thus formed can then penetrate into nearby tumor cells, resulting in cell death. A number of prodrugs have been developed that can be transformed into active anticancer drugs by enzymes of both mammalian and non‐mammalian origin. The enzymes have been shown to localize into tumors when linked to monoclonal antibodies that bind to tumor‐associated antigens. In vivo studies indicate that MAb‐enzyme/prodrug combinations can result in antitumor activities significantly greater than those of the prodrugs or drugs given alone. This is most likely due to the generation of large amounts of active drug at the tumor site.— Senter, P. D. The activation of prodrugs by antibody‐enzyme conjugates: a new approach to cancer therapy.FASEB J.4: 188‐193; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.2.2404820

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Previous studies of the substrate specificity of the purified insulin receptor tyrosine kinase using synthetic random polymers have demonstrated that the receptor kinase phosphorylates poly (Glu, Tyr) 4:1 but not poly (Glu, Tyr) 1:1. In the present study, insulin treatment of Chinese hamster ovary cells overexpressing the human insulin receptor was found to stimulate the ability of their membrane extracts to phosphorylate poly (Glu, Tyr) 1:1. It was concluded that this activity was due to the receptor itself because:1) it was precipitated with a monoclonal antibody to the receptor;2) the addition of various membrane extracts to purified insulin receptor preparations stimulated the ability of these preparations to phosphorylate poly (Glu, Tyr) 1:1; and3) certain purified proteins, including bovine serum albumin and casein, were also capable of stimulating the purified receptor to phosphorylate poly (Glu, Tyr) 1:1. The effect of albumin was dose‐dependent; 0.5 and 10 mg/ml bovine serum albumin stimulated the phosphorylation of poly (Glu, Tyr) 1:1 by 2‐ and 230‐fold, respectively. In contrast, albumin had no effect on the phosphorylation of poly (Glu, Tyr) 4:1. These results indicate that the activity of the insulin receptor kinase on certain substrates can be modulated by the presence of other proteins.—Yonezawa, K.; Roth, R. A. Various proteins modulate the kinase activity of the insulin receptor.FASEB J.4: 194‐200; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.2.2153593

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Collagenase digests of adipose tissue of the 3 to 4‐month‐old rat contain groups of 20‐100 tightly arranged cells (islets) that copurify with the free‐floating fat cells. When cultured along with mature adipocytes the islets give rise to cells, initially fibroblast‐like, which rapidly proliferate, acquire lipid droplets, and differentiate into small adipocytes within 4‐6 days without the addition to the medium of the agents usually required to produce differentiation in stromal‐vascular preadipocytes. Differentiation of these cells is independent of confluence and begins as early as day 2 of culture. The proportion of islet‐derived cells that differentiate is directly correlated with the number of mature adipocytes simultaneously present in the culture (r= .709;P<0.001). Culture medium exposed to mature adipocytes demonstrated differentiation‐promoting activity, suggesting a paracrine effect of these cells. Islets may in vivo constitute a source for newly formed adipocytes in the adult rat. The differentiation of these potential adipocytes may be regulated, at least in part, by the mature fat cells via a paracrine effect.—Carraro, R.; Lu, Z.; Li, Z.‐H.; Johnson, J. E., Jr.; Gregerman, R. I.FASEB J.4: 201‐207; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.2.2298341

出版商:Wiley    

年代:1990

数据来源: WILEY