ISSN:0892-6638    

DOI:10.1096/fasebj.8.6.8168686

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

The chasm that C. P. Snow noted between the two cultures of science and the humanities may be part of an explanation for the success of the animal rights movement. Many philosophers, who represent the culture of the humanities, take an animal liberation position in the ethical debate about the use of animals in research. One who does not is Peter Carruthers. He presents a valuable critique of two important animal liberation ethicists, Tom Regan and Peter Singer, analyzing their thinking on the origins of ethical ideas and the source of ethical motivation. He identifies problems in their theories leading to conclusions that defy common sense about the value of human life. As an alternative, Carruthers introduces John Rawls' theory of contractualism. This theory provides a framework within which medical researchers and the public at large can defend the humane use of animals in research. His work promises to help bridge the gap between scientists and representatives of the humanities.—Parker, J. Help from philosophy: responding to the animal rights challenge.FASEB J.8: 375‐377; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.6.8168687

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

An image of the tissue distribution of specific mRNAs, proteins, enzymes, or antigens is conveniently obtained by “printing” the cut surface of a tissue section onto a suitable substrate film and developing the film with appropriate reagents. It is also possible to localize metabolites by tissue printing. Most plant tissues leave a physical print/impression with detailed anatomical information. Epidermal surfaces of growing organs can be printed without damaging the organ. We provide this review to encourage further use and further development of these convenient and helpful procedures.—Varner, J. E., Ye, Z. Tissue printing.FASEB J.8: 378‐384; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.6.8168688

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

Thromboembolic disorders are commonly associated with cardiovascular, infectious, and neoplastic disease. A major link in the pathophysiology of thrombosis is the excessive triggering of the coagulation pathways by the initiating cofactor molecule termed tissue factor, an integral membrane glycoprotein. The tissue factor extracellular ligand binding domain is predicted to fold in an architecture similar to the cytokine receptor homology module. Functional sites in tissue factor have been defined by a combination of antibody, chemical cross‐linking, and mutational analyses providing a model for cofactor function that involves discrete interactions with both enzyme and substrate. The understanding of the structural basis of tissue factor function promises to facilitate rational design of inhibitor molecules for defined functional sites, eventually leading to effective in vivo therapeutics.—Ruf, W., Edgington, T. S. Structural biology of tissue factor, the initiator of thrombogenesis in vivo.FASEB J.8: 385‐390; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.6.8168689

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

Lymphocyte activation requires the transmission of signals from molecules at the plasma membrane to nuclear signals that regulate gene expression. In recent years, several immunosuppressive compounds have been used as probes to identify important and potentially novel molecules involved in lymphocyte signal transduction processes. The immunosuppressants cyclosporin A (CsA), FK506, and rapamycin have been studied in particular detail. Two distinct classes of immunosuppressant binding proteins have been identified, and collectively termed immunophilins. The cyclophilin family of immunophilins binds CsA, whereas the FK506‐binding protein (FKBP) family binds FK506 and rapamycin. This review will discuss both the endogenous functions of immunophilins as well as their roles in mediating immunosuppression.—Fruman, D. A., Burakoff, S. J., Bierer, B. E. Immunophilins in protein folding and immunosuppression.FASEB J.8: 391‐400; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.6.7513288

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

Tumor metastasis is a major cause of death for cancer patients. This review proposes that the final steps in the development of a distant metastasis may be the most productive targets for clinical development. It cannot be guaranteed that, in “metastasis‐free” patients, tumor cells have not invaded out of the primary lesion, intravasated and extravasated from the circulatory system, and are sitting at distant sites as occult micrometastases. The remaining processes involved in outgrowth at metastatic sites, colonization and angiogenesis, are reviewed. Colonization is thought to be accomplished by clonally dominant cell populations through progressive independence from exogenous growth factors, production of growth factors, and stimulatory proliferative responses to traditionally inhibitory cytokines. Therapeutic efforts aimed at interrupting the switch in tumor cell responsiveness to cytokines, rather than to any one specific cytokine, may be most successful at inhibiting metastatic colonization. Angiogenesis has been demonstrated to be directly or indirectly induced by a plethora of cytokines. Partial suppression of neovascularization can be achieved in tissue culture and animal models using various natural and pharmaceutical angiostatic agents. However, as with clonal dominance, such agents must be able to suppress the redundant effects of angiogenesis‐promoting factors. This review discusses the current literature on colonization and angiogenesis, emphasizing its underlying mechanisms and potential therapeutic applications.—Weinstat‐Saslow, D., Steeg, P. S. Angiogenesis and colonization in the tumor metastatic process: basic and applied advances.FASEB J.8: 401‐407; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.6.7513289

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

Chromosome studies of human tumors have provided important clues to the location of relevant genes and the mechanisms by which their growth regulatory functions have been altered. In the last decade, molecular dissection of chromosome translocations in hematopoietic tumors and chromosomal deletions in solid tumors have been particularly helpful in demonstrating the involvement of a few previously known oncogenes and a wide variety of previously unknown “cancer genes,” which often differ from one type of tumor to another, and normally may either stimulate or inhibit cell growth. These studies have also helped to clarify the importance of multiple genetic lesions in the development of most tumors, and the recently acquired information is already being used in clinical diagnosis and management. In addition, new specific treatments will ultimately result from these findings, but the work to date also clearly indicates that no single, simple answer to human cancer will be forthcoming.—Nowell, P. C. Cytogenetic approaches to human cancer genes.FASEB J.8: 408‐413; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.6.8168690

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

Glucokinase is one of the four hexokinases present in mammalian tissues. It is expressed in two cell types that have to respond to changes in the blood glucose concentration, the liver parenchymal cell and the β‐cells of pancreatic islets. The former are responsible for the metabolism and storage of an important part of the ingested glucose, whereas the latter secrete insulin in response to an increase in the blood glucose level. One major characteristic of glucokinase is that it has a relatively low affinity for glucose and displays positive cooperativity for this substrate, despite the fact that it is a monometic enzyme. Furthermore, unlike other hexokinases, it is not inhibited by micromolar (physiological) concentrations of glucose 6‐phosphate but by a regulatory protein that transduces the effect of fructose 6‐phosphate and of fructose 1‐phosphate. The purpose of this review is to describe these aspects of the regulation of glucokinase.— Van Schaftingen, E., Detheux, M., Veiga da Cunha, M. Short‐term control of glucokinase activity; role of a regulatory protein.FASEB J.8: 414‐419; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.6.8168691

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

In epithelia, adhesive interactions participate in specific histogenetic events and also instate a morphological polarization that is linked to the vectorial functioning of the epithelium. Cell polarity is a recurring event in differentiation, first observed in the preimplantation embryo and then during organogenesis, whereas in oncogenesis a breakdown of polarity may occur. We review here recent work on adhesive interactions in the liver parenchyma. We focus on the effect of cell‐biomatrix interactions on hepatocyte function and polarization, on the integration of adhesive cell‐cell and cell‐matrix interactions, and on the correlation between structural differentiation and adhesion during hepatic development, regeneration, and oncogenesis. Although highlighting morphological differences between the liver and other epithelia, we stress that adhesion‐mediated effects such as substratum regulation of differentiation, feedback control of matrix synthesis, and integration of intercellular and cell‐matrix interactions, shown to transpire in the liver, most probably occur in other parenchymal tissues too.—Stamatoglou, S. C., Hughes, R. C. Cell adhesion molecules in liver function and pattern formation.FASEB J.8: 420‐427; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.6.8168692

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

The functional significance of the isoform diversity of the calmodulin‐dependent plasma membrane Ca2+‐ATPase (PMGA) is largely unknown. To determine whether the mRNA synthesis of different isoforms of the enzyme is regulated in a differentiation‐specific manner, we investigated the expression of isoform‐specific mRNAs in muscle and neuronal cells during differentiation by reverse transcription PCR. In the rat, the ubiquitous PMCA splicing variants 1b and 4b formed the typical PMCA isoform pattern of L6 myoblasts, the heart‐derived cell line H9c2(2‐1), two different fibroblast cell lines (FR and NRK‐49F), smooth muscle, and endothelial cells. In addition to these two enzymes, novel expression of the splicing variants 1c, 1d, and 4a was induced during myogenic Differentiation of L6 and H9c2(2‐1) cells. A similar isoform subtype switch could be detected during differentiation of the neuronal PC‐12 cells induced by nerve growth factor (NGF). The isoform‐specific mRNAs 1c, 1d, and 4a were not expressed in cells other than myocytes and neurons, and therefore may be specific for excitable cells. The mRNA for isoform 1d was heart‐ and skeletal muscle‐specific. To determine whether expression of a differentiation‐specific PMCA mRNA pattern is under control of a myogenic determination factor, myogenin was constitutively expressed in rat fibroblasts. These cells converted to multinucleated myotubes, which displayed the PMCA isoform‐specific mRNAs 1c, 1d, and 4a, typical of differentiated muscle cells. We conclude that:1) the distribution of the various PMCA isoform‐specific mRNAs and their splicing variants is cell type‐ and development‐specific;2) expression of the myogenic determination factor myogenin is sufficient to direct alternative splicing generating muscle‐specific PMCA mRNA species; and3) PMCA isoforms and/or splicing variants may play a role in determining functions of terminally differentiated muscle and neuronal cells and possibly during the differentiation process itself.—Hammes, A., Oberdorf, S., Strehler, E. E., Stauffer, T., Carafoli, E., Vetter, H., Neyses, L. Differentiation‐specific isoform mRNA expression of the calmodulin‐dependent plasma membrane [Ca2+‐ATPase.FASEB J.8: 428‐435; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.6.8168693

出版商:Wiley    

年代:1994

数据来源: WILEY