ISSN:0892-6638    

DOI:10.1096/fasebj.6.3.1497701

出版商:Wiley    

年代:1992

数据来源: WILEY

ISSN:0892-6638    

DOI:10.1096/j.1530-6860.1992.tb93348.x

出版商:Wiley    

年代:1992

数据来源: WILEY

ISSN:0892-6638    

DOI:10.1096/fasebj.6.3.1740230

出版商:Wiley    

年代:1992

数据来源: WILEY

ISSN:0892-6638    

DOI:10.1096/fasebj.6.3.1740231

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

Gastric ulcer is a multifaceted, pluricausal illness. Knowledge of the pathophysiology of gastric ulcer disease remains incomplete. Current pharmacological management of gastric ulceration is directed primarily at the reduction or neutralization of gastric acid secretion despite evidence that patients with this disease often exhibit normal gastric secretory activity. Attempts have been made to prevent or reduce gastric mucosal injury by cytoprotective agents without diminishing gastric acidity. We review several alternate explanations for the cause of gastric ulcers by examining various experimental models of gastric mucosal damage, including ethanol‐, stress‐, and nonsteroidal antiinflammatory drug‐induced gastric lesions. We also discuss possible new strategies for the treatment of ulcer disease, particularly novel pharmacological targets arising from research conducted with these models. Growing realization that factors other than gastric secretion contribute significantly to the development of gastric ulcer disease prompts the conclusion that these same factors represent viable treatment alternatives.—Glavin, G. B.; Szabo, S. Experimental gastric mucosal injury: laboratory models reveal mechanisms of pathogenesis and new therapeutic strategies.FASEB J.6: 825‐831; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.3.1740232

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

The adrenergic receptors are members of the superfamily of G protein‐coupled receptors. There are three major types of adrenergic receptors: α1, α2, and β. Each of these three major types can be divided into three subtypes. Within the α1‐adrenergic receptors, α1Aand the subtypes have been defined pharmacologically on the basis of reversible antagonists, such as WB4101 and phentolamine, and the irreversible antagonist chloroethylclonidine. In at least some tissues the mechanism of action of the α1Asubtype is related to activation of a calcium channel, whereas the α1Breceptor exerts its effect through the second messenger inositol trisphosphate. Both of these receptor subtypes as well as a third, the α1C, have been identified by molecular cloning. Three pharmacological subtypes of the α2‐adrenergic receptor have also been identified. Prototypic tissues and cell lines in continuous culture have been developed for each of these subtypes, which facilitated their study. The definition of the α2subtypes has been based on radioligand binding data and more limited functional data. All three subtypes have been shown to inhibit the activation of adenylate cyclase and thus reduce the levels of cAMP. Three α2‐adrenergic receptor subtypes have been identified by molecular cloning in both the human and rat species. There is reasonable agreement between the pharmacological identified subtypes and those identified by molecular cloning.—Bylund, D. B. Subtypes of α1‐ and α2‐radrenergic receptors.FASEB J.6: 832‐839; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.3.1346768

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

Many mechanisms may account for immune‐mediated pathology after viral infections. Although several means have been hypothesized to play a role in disease, a widely accepted mechanism for viral‐induced autoimmunity is molecular mimicry. It is thought that damage could result from an immune response to similar regions shared between virus and the host. Using computer‐aided analysis, many sequence homologies have been identified between virus and host antigens. Using peptides corresponding to these regions, immunologic cross‐reactivity has been found. In some cases, monoclonal antibodies to peptides of these regions have been shown to directly induce or augment disease in animal models. Using this approach to identify similar regions, it is possible to associate a known autoantigen with an infectious agent in autoimmune diseases in which there is no known etiologic agent. Conversely, it would also be possible to associate a known viral constituent with an unknown host antigen. Furthermore, identification of disease‐inducing regions of autoantigens or viral proteins may lead to immunotherapeutic approaches to establish tolerance or anergy to such disease‐inducing regions.—Barnett, L. A. Fujinami, R. S. Molecular mimicry: a mechanism for autoimmune injury.FASEB J.6: 840‐844; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.3.1740233

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

Acetylcholine signals through two types of unrelated membrane receptors referred to as nicotinic (nAChR) and muscarinic (mAChR) acetylcholine receptors. Nicotinic acetylcholine receptors were the first neurotransmitter receptors to be purified, cloned, and sequenced, and much is known about these proteins. In contrast, until 5 years ago relatively little was known about the muscarinic receptors. Since then there has been an explosion of information concerning the structure, signaling, and regulation of what is now known to be a family of muscarinic receptors. This review discusses the five identified members of the mAChR family and their coupling to the multiple G proteins that allow mAChRs to modulate many different types of signal transduction pathways. The five members of this family that have been identified so far have striking homology in their hydrophobic membrane domains but possess distinct cytoplasmic domains between the fifth and sixth membrane‐spanning regions. These cytoplasmic domains appear to contain important determinants for receptor/G protein interaction and are likely to contain phosphorylation sites that regulate these interactions. mAChR agonists have been shown to induce phosphorylation of mAChR in intact cells, and the evidence that suggests that receptor phosphorylation may play a role in the regulation of receptor function is discussed.—Hosey, M. M. Diversity of structure, signaling, and regulation within the family of muscarinic cholinergic receptors.FASEB J.6: 845‐852; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.3.1740234

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

Breast cancer is the leading cause of cancer death in women in the industrialized world, and the rates of breast cancer incidence are rising. Although risk is high in industrialized societies, it is low in nonindustrialized areas. The search for the causes of breast cancer has not yet yielded a convincing explanation for the geographic and temporal patterns in the occurrence of breast cancer. Generation of electric power is a hallmark of industrialization, and two products of electric power, light‐at‐night (LAN) and electromagnetic fields (EMF), may affect breast cancer risk. Exposure to either LAN or EMF can decrease production of melatonin by the pineal gland. Melatonin, in turn, has been shown to suppress mammary tumorigenesis in experimental animals. Moreover, recent epidemiological findings indicate an increased risk of breast cancer in workers occupationally exposed to EMF. On the basis of these considerations, it is proposed that the use of electrical power accounts, in part, for the higher risks of breast cancer in industrialized societies.—Stevens, R. G.; Davis, S.; Thomas, D. B.; Anderson, L. E.; Wilson, B. W. Electric power, pineal function, and the risk of breast cancer.FASEB J.6: 853‐860; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.3.1740235

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

Proteoglycans are produced by most eukaryotic cells and are versatile components of pericellular and extracellular matrices. They belong to many different protein families. Their functions vary from the physical effects of the proteoglycan aggrecan, which binds with link protein to hyaluronan to form multi‐molecular aggregates in cartilage; to the intercalated membrane protein CD44 that has a proteoglycan form and is a receptor and a cell‐binding site for hyaluronan; to heparan sulfate proteoglycans of the syndecan and other families that provide matrix binding sites and cell‐surface receptors for growth factors such as fibroblast growth factor (FGF). One feature that recurs in proteoglycan biology is that their structure is open to extensive modulation during cellular expression. Examples of protein changes are known, but a major source of structural variation is in the glycosaminoglycan chains. The number of chains and their length can vary, as well as their pattern of sulfation. This may result in the switching of different chain types with different properties, e.g., chondroitin sulfate and heparan sulfate, and it may also result in the selective expression of sulfated chain sequences that have specific functions. The control of glycosaminoglycan structure is not well understood, but it does appear to be used to change the properties of proteoglycans to suit different biological needs. Proteoglycan forms of proteins are thus important modifiers of the organization of the pericellular and extracellular matrices and modulators of the processes that occur there.—Hardingham, T. E., Fosang, A. J. Protoglycans: many forms and many functions.FASEB J.6: 861‐870; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.3.1740236

出版商:Wiley    

年代:1992

数据来源: WILEY