ISSN:0892-6638    

DOI:10.1096/fasebj.4.11.2199282

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Kidney disease, characterized by proteinuria and glomerular lesions, is a common complication of spontaneous diabetes mellitus in many animal species. It occurs in animals with hypoinsulinemia, hyperinsulinemia, or impaired glucose tolerance. The renal functional and structural abnormalities in spontaneously diabetic animals resemble human diabetic nephropathy in many respects. Mesangial expansion and glomerular basement membrane thickening, two structural hallmarks of diabetic glomerulopathy in humans, are the most frequently encountered lesions in animals. In addition, a nodular form of mesangial expansion that resembles but is not identical with human nodular glomerulosclerosis or the Kimmelstiel‐Wilson lesion has been observed in some animal models. Other abnormalities, such as exudative hyaline lesions and arteriolar hyalinosis, have also been noted occasionally in other models. Although diabetic animals may develop kidney disease that resembles human diabetic nephropathy, no single animal model develops renal changes identical to those seen in humans. Nonetheless, animal models with spontaneous diabetic kidney disease may be useful for investigating the mechanisms of development of diabetic nephropathy and the effects of various treatment modalities on the progression of renal disease.—Velasquez, M. T.; Kimmel, P. L.; Michaelis, O. E., IV Animal models of spontaneous diabetic kidney disease.FASEB J.4: 2850‐2859; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.11.2199283

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Interleukin 1 (IL 1), IL 6, and tumor necrosis factor (TNF) are typical examples of multifunctional cytokines involved in the regulation of the immune response, hematopoiesis, and inflammation. Their functions are widely overlapping but each shows its own characteristic properties. IL 6 was originally identified as a B cell differentiation factor, and thus one of the major functions of IL 6 is antibody induction. Transgenic mice have provided much needed information on the pathophysiological role of cytokines. With IL 6 transgenic mice, deregulation of the IL 6 expression was suggested to be involved in the generation of plasmacytoma/myeloma and mesangium proliferative glomerulonephritis. Thecis‐regulatory elements andtransactingnuclear factor (or factors) for the IL 6 expression (NF‐IL 6) have been identified. NF‐IL 6 was shown to be a member of a C/EBP family, and the possible involvement of NF‐IL 6 not only in the IL 6 regulation but also in the induction of various acute phase proteins was also observed. The findings suggest the presence of a positive regulatory loop in acute‐phase reaction. IL 1 receptor belongs to an Ig superfamily, but the IL 6 receptor is a member of a newly identified cytokine receptor family. The IL 6 receptor system was shown to be composed of a ligand binding chain and a signal‐transducing molecule. IL 6 was found to trigger the association of these two polypeptide chains. This unique mechanism may be applied to other cytokine receptor systems.— Akira, S.; Hirano, T.; Taga, T.; Kishimoto, T. Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF).FASEB J.4: 2860‐2867; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.11.2199284

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Cell‐cell and cell‐substratum interactions are mediated through several different families of receptors. In addition to targeting cell adhesion to specific extracellular matrix proteins and ligands on adjacent cells, these receptors influence many diverse processes including cellular growth, differentiation, junction formation, and polarity. Several families of adhesion receptors have been identified. These include:1) the integrins, heterodimeric molecules that function both as cell‐substratum and cell‐cell adhesion receptors;2) the adhesion molecules of the immunoglobulin superfamily, which are involved in cell‐cell adhesion and especially important during embryogenesis, wound healing, and the inflammatory response;3) the Cadherins, developmentally regulated, calcium‐dependent homophilic cell‐cell adhesion proteins;4) the LEC‐CAMs, cell adhesion molecules with lectin‐like domains that mediate white blood cell/endothelial cell adhesion; and5) homing receptors that target lymphocytes to specific lymphoid tissue. In this review we summarize recent data describing the structure and function of some of these cell adhesion molecules (with special emphasis on the integrin family) and discuss the possible role of these molecules in development, inflammation, wound healing, coagulation, and tumor metastasis.— Albelda, S. M., Buck, C. A. Integrins and other cell adhesion molecules.FASEB J.4: 2868‐2880; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.11.2199285

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Cellular responses to many hormones and neurotransmitters wane rapidly despite continuous exposure of cells to these stimuli. This phenomenon, termed desensitization, has been particularly well studied for the stimulation of cAMP levels by plasma membrane β‐adrenergic receptors (βAR). The molecular mechanisms underlying rapid βAR desensitization do not appear to require internalization of the receptors, but rather an alteration in the functioning of βAR themselves that uncouples the receptors from the stimulatory G protein Gs. This uncoupling phenomenon involves phosphorylation of βAR by at least two kinases, PKA and the βAR kinase (βARK), which are activated under different desensitizing conditions. Receptor phosphorylation by the two kinases leads to desensitization of the receptor response via distinct biochemical mechanisms, and additional cytosolic factors appear to be involved in the case of βARK. Numerous experimental approaches have been used recently to elucidate the molecular details of this ubiquitous biological process.— Hausdorff, W. P.; Caron, M. G.; Lefkowitz, R. J. Turning off the signal: desensitization of β‐adrenergic receptor function.FASEB J.4: 2881‐2889; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.11.2165947

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Energy expenditure for thermogenesis in brown adipose tissue (BAT) serves either to maintain body temperature in the cold or to waste food energy. It has roles in thermal balance and energy balance, and when defective, is usually associated with obesity. BAT can grow or atrophy; it is usually atrophied in obese animals. Control of BAT thermogenesis and growth is by the sympathetic nervous system, with integration of signals in the hypothalamus. Sensory nerves may also be involved. Understanding the control of growth and differentiation of BAT is important for discovering how to reactivate it in obesity. Studies on control of gene expression in BAT are concentrating on thermogenically important components such as the uncoupling protein (which allows BAT mitochondria to operate in a thermogenic uncoupled mode), lipoprotein lipase (which allows BAT to compete with white adipose tissue for dietary lipid), and thyroxine 5'‐deiodinase (which allows endogenous triiodothyronine generation, part of the control of differentiation and growth of BAT). Differentiation of BAT cell precursors in culture has recently been achieved. BAT is present in adult humans and some anti‐obesity drugs are targeted to stimulation of BAT thermogenesis. However, extrapolation to humans of results of studies of BAT requires the development of novel approaches to the noninvasive assessment of amount and function of human BAT.— Himms‐Hagen, J. Brown adipose tissue thermogenesis: interdisciplinary studies.FASEB J.4: 2890‐2898; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.11.2199286

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Secondary18O isotope effects have been developed as a tool for determining transition state structures in enzymatic and nonenzymatic phosphoryl transfer reactions.18O substitution in the nonbridge oxygens of a phosphoryl group makes the reaction go faster when the bond order is higher to these oxygens in the transition state than in the reactant, whereas the reaction goes slower if the bond order is less. The isotope effects are measured by the remote label method, using an isotope ratio mass spectrometer for analysis. The bond order top‐nitrophenolate ion when it is the leaving group is indicated by the secondary15N isotope effect in the nitro group, with a value of 1.0028 representing nearly complete bond cleavage. It appears that the transition states for phosphoryl transfer have no more than one negative charge on the nonbridge oxygens, so that reactions of monoesters are dissociative, reactions of triesters are associative, and reactions of diesters are SN2 with half bond order to entering and leaving groups.— Cleland, W. W. Secondary18O isotope effects as a tool for studying reactions of phosphate homo‐, di‐, and triesters.FASEB J.4: 2899‐2905; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.11.2199287

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Macrophage responses to recombinant IFN‐γ decline during aging, as measured by two criteria of macrophage activation, O2−and TNF‐α secretion. The production of O2−by macrophages in response to opsonized‐zymosan and recombinant rat IFN‐γ is 75% lower in 23‐month‐old rats than in 3‐month‐old rats. Furthermore, the secretion of TNF‐α in response to IFN‐γ and LPS is almost absent in macrophages from aged rats. Production of both O2−and TNF‐α by resident peritoneal macrophages from specific pathogen‐free aged rats in response to priming and triggering stimuli was partially or fully restored by implantation of syngeneic pituitary grafts from young rats. These data demonstrate that macrophages from aged rats are defective in their response to a priming signal induced by IFN‐γ, and they suggest that impaired macrophage responses during aging may be reversible.— Davila, D. R.; Edwards, C. K., III; Arkins, S.; Simon, J.; Kelley, K. W. Interferon‐γ‐induced priming for secretion of superoxide anion and tumor necrosis factor‐α declines in macrophages from aged rats.FASEB J.4: 2906‐2911; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.11.2165948

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

An investigation was conducted to assess the effects of various β‐galactoside specific lectins on the growth of vascular cells in vitro. The plant lectins from peanut (Arachis hypogaea), mushroom (Agaricus bisporus), and coral tree (Erythrina corallodendron) were used in these studies with the ultimate purpose of comparing those findings with data derived with the lectin isolated from rat lung. Peanut lectin was added to confluent and subconfluent cultures of smooth muscle cells (SMC), pulmonary arterial (PEC), and aortic endothelial cells (BAEC) at concentrations of 2, 3.5, and 7.0 μg/ml. There was a dose‐dependent increase in cell proliferation for both confluent and subconfluent SMC, with maximal stimulation noted between 3.5 and 7 μg/ml of peanut lectin. A dose‐dependent stimulation of PEC proliferation was also found with maximal stimulation between 3.5 and 7.0 μg/ml. Peanut lectin did not stimulate BAEC to multiply. The stimulation of PEC and SMC by peanut lectin could be prevented by the addition of 50 mM lactose. Peanut and mushroom lectin stimulated the proliferation of sparse cultures of SMC in a dose‐dependent fashion in both standard (10% fetal bovine serum, or FBS) or low (0.5% FBS) serum to about the same degree. Coral tree lectin did not have a significant stimulation of proliferation under either serum conditions. The incorporation of [3H]thymidine into the DNA of PEC was increased 30 and 150% by peanut lectin and lung galaptin, respectively, under standard serum conditions. However, under low serum conditions, both lectins increased incorporation by about the same extent (93 and 78% for peanut lectin and galaptin, respectively). Both lectins produced a 30% increase in DNA synthesis by SMC under standard serum conditions, and about a 200% increase under low serum conditions. These studies indicate that β‐galactoside specific lectins such as lung galaptin have mitogenic activity toward vascular cells.— Sanford, G. L.; Harris‐Hooker, S. Stimulation of vascular cell proliferation by β‐galactoside specific lectins.FASEB J.4: 2912‐2918; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.11.2379767

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Guinea pigs fed a diet low in zinc develop clinical signs of apparent neurological origin. The signs include abnormal posture and locomotion as well as hypersensitivity to touch. In this study, electrophysiological and biochemical measurements were made on sciatic nerves from zinc‐deficient and repleted animals as well as on controls fed either ad libitum or restricted to maintain weight comparable to those consuming the deficient diet. Both in vivo and in vitro measurements showed decreased motor nerve conduction velocity (NCV) in nerves of deficient animals. A longitudinal study showed excellent correlation of NCV and severity of clinical signs. Nerves from zinc‐deficient guinea pigs had decreased Na,K‐ATPase activity, but the number of sodium channels, as determined by saxitoxin binding, was not affected. It was concluded that the clinical signs of neuropathy in zinc deficiency are associated with impaired NCV and decreased Na,K‐ATPase activity of peripheral nerves. The zinc‐deficient guinea pig provides a useful model to study the biochemical defect in a peripheral neuropathy.— O'Dell, B. L.; Conley‐Harrison, J.; Besch‐Williford, C.; Browning, J. D.; O'Brien, D. Zinc status and peripheral nerve function in guinea pigs.FASEB J.4: 2919‐2922; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.11.2165949

出版商:Wiley    

年代:1990

数据来源: WILEY