摘要:

Inflammation is caused by release of chemicals from tissues and migrating cells. Most strongly implicated are the prostaglandins (PGs), leukotrienes (LTs), histamine, bradykinin, and, more recently, platelet‐activating factor (PAF) and interleukin‐1. Evidence for their involvement comes from studies with competitive antagonists for their receptors and inhibitors of their synthesis. H1histamine antagonists are effective for hay fever and some skin allergies such as urticaria, which indicates the importance of histamine in these conditions. Symptoms of rheumatoid arthritis are alleviated by the aspirinlike anti‐inflammatory drugs, which inhibit the cyclo‐oxygenase enzyme and reduce synthesis of prostanoids. Corticosteroids prevent the formation of both PGs and LTs by causing the release of lipocortin, which by inhibition of phospholipase A2reduces arachidonic acid release. They suppress the inflammation of rheumatoid arthritis and asthma. Currently, high doses of nonsedating H1antihistamines and PAF antagonists are being tested for the treatment of allergic asthma.—Vane, J.; Botting, R. Inflammation and the mechanism of action of anti‐inflammatory drugs.FASEB J.1: 89‐96; 1987.

ISSN:0892-6638    

DOI:10.1096/fasebj.1.2.3111928

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

The aim of this symposium on molecular biology in physiology was to introduce molecular biology to physiologists who had relatively little exposure to the new developments in this field, so that they can become conversant on this topic and contribute to the advancement of physiology by incorporating molecular biological approaches as a part of their research arsenal. After the discussion of the basic concepts, terminology, and methodology used in molecular biology, it was shown how these basic principles have been applied to the study of the genes encoding two membrane proteins that have important transport functions (band 3 and ATPase). The second half of the symposium consisted of papers on the state‐of‐the‐art developments in the application of molecular biology to the studies of the atrial natriuretic factor and renin genes, adenylate cyclase‐coupled adrenergic receptors, acetylcholine receptors and sodium channel, and long‐term and short‐term memories. The ultimate goal is that these examples will provide an impetus for the opening of new frontiers of research in physiology by taking advantage of the tools developed from recent advances in molecular biology.— Chien, S.; Gargus, J. J. Molecular biology in physiology.FASEB J.1: 97‐102; 1987.

ISSN:0892-6638    

DOI:10.1096/fasebj.1.2.2886391

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

Antigen‐specific, major histocompatability complex‐restricted recognition by classical T cells is mediated by a T cell receptor (TCR) consisting of a disulfide‐linked αβ heterodimer. During the search for the genes encoding the α and β proteins, a third immunoglobulinlike gene, termed γ, was uncovered. Like theTCRα and β genes, theTCRγ gene consists of variable and constant segments that rearrange during T cell development in the thymus. Although the physiological role ofTCRγ remains an enigma, much has been learned with the recent identification of the protein products of this gene family in both mice and humans. The γ chain is associated with a partner chain, termed δ. The γδ heterodimer is associated with an invariant T3 complex, very similar to that associated with the αβ heterodimer, and appears predominantly, if not exclusively, on cells with a CD4−, CD8−phenotype both in the thymus and in the periphery. TCR γδ is the first T3‐associated receptor to appear during thymocyte development and defines a separate T cell lineage distinct from αβ‐bearing cells. Although TCR αβ‐bearing cells and TCR γδ‐bearing cells follow parallel developmental pathways, the diversity of expressed γδ receptors is extremely limited relative to that of αβ receptors.— Pardoll, D. M.; Kruisbeek, A. M.; Fowlkes, B. J.; Coligan, J. E.; Schwartz, R. H. The unfolding story of T cell receptor γ.FASEB J.1: 103‐109; 1987.

ISSN:0892-6638    

DOI:10.1096/fasebj.1.2.2956146

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

Proteases having a neutral pH optimum and an absolute requirement for calcium ion are found in virtually all mammalian cells. Association of calcium‐dependent proteases and a specific inhibitor protein with biological membranes seems to be an important regulatory feature of this proteolytic system, and it is likely that membranes are preferred sites for calcium‐dependent protease action. Several recent hypotheses for the physiological function of calcium‐dependent proteolysis are consistent with a membrane‐associated protease action. Calcium‐dependent proteases may participate in cell membrane fusion: the proteolysis of membrane proteins, which is required for the efficient fusion of erythrocytes, may be catalyzed by these enzymes. There is also evidence for the involvement of calcium‐dependent proteolysis in postsynaptic membrane remodeling in the hippocampus after long‐term potentiation. Although the relationship of the proteolysis to synaptic function is not known, it could have important physiological or pathophysiological consequences. Finally, it has recently been suggested that calcium‐dependent proteolysis may be a physiologically significant mechanism for activating membrane‐associated protein kinase C after exposure of some cell types to phorbol esters or other mitogens. Further pursuit of these hypotheses may reveal a novel role for intracellular calcium‐regulated proteolysis in membrane‐associated cell functions.— Mellgren, R. L. Calcium‐dependent proteases: an enzyme system active at cellular membranes?FASEB J.1: 110‐115; 1987.

ISSN:0892-6638    

DOI:10.1096/fasebj.1.2.2886390

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

The effect of the protein kinase C enzyme inhibitor H‐7 on the noncardiogenic lung edema induced by phorbol myristate acetate (PMA) in mice was examined. Lung edema was assessed by measurement of125I‐labeled albumin leak into the lung. The results showed that pretreatment of mice with H‐7 nearly prevents the albumin leak induced by PMA, whereas post‐PMA treatment with H‐7 had less of an effect on the albumin leak, although it was still significant.— Struhar, D.; Harbeck, R. J. Inhibition of induced acute lung edema by a novel protein kinase C inhibitor.FASEB J.1: 116‐118; 1987.

ISSN:0892-6638    

DOI:10.1096/fasebj.1.2.3609609

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

Cholinergic agents decrease myocardial contractility in part by inhibiting adenylate cyclase (EC 4.6.1.1) activity. We have found that after a prolonged preincubation period (>6 h), washout of cholinergic agents from embryonic chick hearts or cultured heart cells results in a persistent increase in their basal and catecholamine‐stimulated cAMP content. Membranes prepared from pretreated cells have elevated basal, forskolin‐, and catecholamine‐stimulated adenylate cyclase activities. This myocardial adaptation to cholinergic agents is analogous to changes in nerve cells and other cell types after prolonged exposures to narcotics or other inhibitors of adenylate cyclase, respectively. A rapid (<5 min) adaptation response to cholinergic agents can also be demonstrated in heart cells by quickly blocking agonist action with atropine. Atropine alone has no effect, but after a brief preincubation period with agonists (methacholine or oxotremorine), the addition of atropine transiently enhances catecholamine‐stimulated cAMP accumulation by 2.5‐fold. These responses are absent in heart cells pretreated with pertussis toxin. The data indicate that the response is not mediated by the phosphoinositide pathway, which has been demonstrated to be insensitive to pertussis toxin in chick heart. Enhanced cAMP accumulation after termination of muscarinic agonist action may provide an explanation for the observation that acetylcholine sometimes produces biphasic contractile responses.— Linden, J. Enhanced cAMP accumulation after termination of cholinergic action in the heart.FASEB J.1: 119‐124; 1987.

ISSN:0892-6638    

DOI:10.1096/fasebj.1.2.2440752

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

Several tumor cells secrete significantly increased amounts of the plasminogen activator urokinase, a trypsinlike serine protease, whose biological function in tumor biology is unclear. In this study we report that cells of the human epidermal tumor cell line CCL 20.2 express about 80,000 high‐affinity urokinase receptors per cell that bind active as well as diisopropylfluorophosphate‐treated high‐molecular‐weight (HMW) urokinase. Low‐molecular‐weight (LMW) urokinase is not bound to the receptor. Occupation of these receptors by active HMW urokinase stimulates cell proliferation independently in the presence of plasminogen in the culture medium. LMW urokinase has again no effect on cell proliferation. Calculated on a molar basis, this effect is about 28% of that of epidermal growth factor. Active HMW urokinase might therefore provide an autocrine receptor‐mediated growth‐promoting mechanism for tumor cells similar to those described for other growth factors.— Kirchheimer, J. C.; Wojta, J.; Christ, G.; Binder, B. R. Proliferation of a human epidermal tumor cell line stimulated by urokinase.FASEB J.1: 125‐128; 1987.

ISSN:0892-6638    

DOI:10.1096/fasebj.1.2.3038646

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

Elevation of rat abdominal skin flaps, followed by ligation and division of the left inferior neurovascular pedicle, resulted in only a 40% survival of the area normally perfused by the ligated artery and vein. Superoxide dismutase (SOD) (EC 1.15.1.1) administered i.v. (20,000 U/kg) 30 min before flap elevation increased survival to 52%. SOD derivatized with polyethylene glycol, which increases circulating half‐life, was more effective, increasing survival to 80%. This protective effect resulted from the catalytic activity of the derivatized enzyme because inactivation by treatment with H2O2eliminated its effect on skin flap survival. An equimolar mixture of Desferal and MnCl2, which catalyzes the dismutation of O2−in vitro, improved survival to 72%. Desferal‐Fe3+, which lacks in vitro SOD activity, or Mn2+alone did not affect the survival of skin flaps, but Desferal alone was nearly as effective as the Desferal‐Mn2+mixture. This effect of Desferal may result from acquisition of and subsequent removal of iron in vivo. These results support the view that the superoxide radical or a product derived from it plays a role in limiting the survival of island skin flaps.— Huang, L.; Privalle, C. T.; Serafin, D.; Klitzman, B. Increased survival of skin flaps by scavengers of superoxide radical.FASEB J.1: 129‐132; 1987.

ISSN:0892-6638    

DOI:10.1096/fasebj.1.2.3038647

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

The Z band in skeletal muscle has two distinct structural states —a relaxed (small square or ss) form and a maximally activated (basket weave or bw) form. We have examined by electron microscopy and optical diffraction Z lattice forms and dimensions and A band spacings in relaxed, tetanized, stretched, and stretched‐and‐tetanized rat soleus muscle. We have tested the independent contributions of passive load, active tension, and sarcomere length to Z band state. As the A band spacing decreased with increasing load and increasing sarcomere length in the untetanized muscles, the Z lattice remained in the ss form and the Z spacing changed only slightly. Computer‐enhanced images from digitized electron micrographs showed that the ss Z lattice resisted deformation regardless of load or method of stretching. In contrast, when the muscle was tetanized at sarcomere lengths of up to 2.7 μm, the Z lattice assumed the bw form and the Z spacing was increased by 20%. Regardless of lattice form, Z spacing did not vary significantly with sarcomere length. Images from freeze‐substituted preparations showed both lattice forms comparable to those in images from glutaraldehyde‐fixed muscles. Thus, Z band state appears to be a function of the presence (or absence) of active tension. Our previous three‐dimensional model is compatible with these observations and with the substructures revealed by computer‐enhanced images of both lattice forms.—Goldstein, M. A.; Michael, L. H.; Schroeter, J. P.; Sass, R. L. Z band dynamics as a function of sarcomere length and the contractile state of muscle.FASEB J.1: 133‐142; 1987.

ISSN:0892-6638    

DOI:10.1096/fasebj.1.2.3609610

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

Dopamine β‐hydroxylase (DβH) (EC 1.14.17.1) from adrenal medulla is a glycoprotein with approximately 5% carbohydrate by weight. The oligosaccharide chains of this enzyme were enzymatically removed with various glycosidic enzymes (endoglycosidases D, F, and H; glycopeptidase F; α‐mannosidase; neuraminidase; and β‐galactosidase). The time course of deglycosylation was monitored by polyacrylamide gel electrophoresis, and evidence for sugar removal was shown by a modification of the Western blot technique utilizing125I‐labeled concanavalin A and by amino acid analysis. Protein was detected in the gel by using specific antibodies and125I‐labeled protein A. Steady‐state kinetic data of deglycosylated DβH show minor differences between the native and the deglycosylated protein. TheKmvalues for tyramine were 2.17 and 1.66 mmwhereas theKmvalues for oxygen were 0.18 and 0.14 mmfor the native and the deglycosylated protein, respectively. TheVmaxvalues (pH 5.0) for the two forms of the enzyme were comparable, with the deglycosylated DβH being 15% lower. These data indicate that the oligosaccharide moieties present on DβH do not play a role in catalysis.— Hamos, J.; Desai, P. R.; Villafranca, J. J. Characterization and kinetic studies of deglycosylated dopamine β‐hydroxylase.FASEB J.1: 143‐148; 1987.

ISSN:0892-6638    

DOI:10.1096/fasebj.1.2.3609611

出版商:Wiley    

年代:1987

数据来源: WILEY