Proceedings of the Association of American Physicians最新文献

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Inherited variability of tumor necrosis factor production and susceptibility to infectious disease. 肿瘤坏死因子产生的遗传变异性和对传染病的易感性。
Proceedings of the Association of American Physicians Pub Date : 1999-07-01 DOI: 10.1046/j.1525-1381.1999.99237.x
J C Knight, D Kwiatkowski
{"title":"Inherited variability of tumor necrosis factor production and susceptibility to infectious disease.","authors":"J C Knight,&nbsp;D Kwiatkowski","doi":"10.1046/j.1525-1381.1999.99237.x","DOIUrl":"https://doi.org/10.1046/j.1525-1381.1999.99237.x","url":null,"abstract":"<p><p>Tumor necrosis factor (TNF) is a critical mediator of host defense against infection but may cause severe pathology when produced in excess. Individuals vary in the amount of TNF produced when their peripheral blood mononuclear cells are stimulated in vitro, and family studies indicate that much of this variability is genetically determined. Since the TNF response to infection is partly regulated at the transcriptional level, TNF promoter polymorphisms have been the subject of intense interest as potential determinants of disease susceptibility. A single nucleotide polymorphism at nucleotide -308 relative to the transcriptional start site has been associated with susceptibility to severe malaria, leishmaniasis, scarring trachoma, and lepromatous leprosy. Some experimental data indicate that this polymorphism acts to upregulate TNF transcription, but this remains controversial. Detailed analysis of multiple genetic markers at this locus and more sophisticated investigations of TNF transcriptional regulation, in different cell types and with a wide range of stimuli, are required to understand the molecular basis of these disease associations.</p>","PeriodicalId":20612,"journal":{"name":"Proceedings of the Association of American Physicians","volume":"111 4","pages":"290-8"},"PeriodicalIF":0.0,"publicationDate":"1999-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21284156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 134
Sidney C. Werner 1909-1994 西德尼·c·沃纳1909-1994
Braverman
{"title":"Sidney C. Werner 1909-1994","authors":"Braverman","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":20612,"journal":{"name":"Proceedings of the Association of American Physicians","volume":"111 4","pages":"369-70"},"PeriodicalIF":0.0,"publicationDate":"1999-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21284756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inosine monophosphate dehydrogenase: A molecular switch integrating pleiotropic GTP-dependent beta-cell functions. 肌苷单磷酸脱氢酶:整合多效gtp依赖的β细胞功能的分子开关。
Proceedings of the Association of American Physicians Pub Date : 1999-07-01 DOI: 10.1046/j.1525-1381.1999.99245.x
S A Metz, A Kowluru
{"title":"Inosine monophosphate dehydrogenase: A molecular switch integrating pleiotropic GTP-dependent beta-cell functions.","authors":"S A Metz,&nbsp;A Kowluru","doi":"10.1046/j.1525-1381.1999.99245.x","DOIUrl":"https://doi.org/10.1046/j.1525-1381.1999.99245.x","url":null,"abstract":"<p><p>Studies of pancreatic islet function in the pathogenesis of type 2 diabetes mellitus have tended to focus on the short-term control of insulin secretion. However, the long-term control of beta-cell mass is also relevant to diabetes, since this parameter is reduced substantially even in non-insulin-dependent diabetes in humans. In animal models of type 2 diabetes, the normal balance between beta-cell proliferation and programmed cell death is perturbed. We take the perspective in this overview that inosine monophosphate dehydrogenase (IMPDH; EC 1.1.1. 205) may represent a previously neglected molecular integrator or sensor that exerts both functional (secretory) and anatomical (proliferative) effects within beta-cells. These properties reflect the fact that IMPDH is a rate-limiting enzyme in the new synthesis of the purine guanosine triphosphate (GTP), which modulates both exocytotic insulin secretion and DNA synthesis, as well as a number of other critical cellular functions within the beta-cell. Alterations in the expression or activity of IMPDH may be central to beta-cell replication, cell cycle progression, differentiation, and maintenance of adequate islet mass, effects that are probably mediated both by GTP directly, and indirectly via low molecular mass GTPases. If GTP becomes depleted, a hierarchy of beta-cell functions becomes progressively paralyzed, until eventually the effete cell is removed via apoptosis.</p>","PeriodicalId":20612,"journal":{"name":"Proceedings of the Association of American Physicians","volume":"111 4","pages":"335-46"},"PeriodicalIF":0.0,"publicationDate":"1999-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21284760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 16
Sidney C. Werner. 1909-1994. 西德尼·c·沃纳,1909-1994。
Proceedings of the Association of American Physicians Pub Date : 1999-07-01 DOI: 10.1046/J.1525-1381.1999.99002.X
L. Braverman
{"title":"Sidney C. Werner. 1909-1994.","authors":"L. Braverman","doi":"10.1046/J.1525-1381.1999.99002.X","DOIUrl":"https://doi.org/10.1046/J.1525-1381.1999.99002.X","url":null,"abstract":"","PeriodicalId":20612,"journal":{"name":"Proceedings of the Association of American Physicians","volume":"51 1","pages":"369-70"},"PeriodicalIF":0.0,"publicationDate":"1999-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85753396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Thalassemia and malaria: new insights into an old problem. 地中海贫血和疟疾:对老问题的新认识。
Proceedings of the Association of American Physicians Pub Date : 1999-07-01 DOI: 10.1046/j.1525-1381.1999.99235.x
J B Clegg, D J Weatherall
{"title":"Thalassemia and malaria: new insights into an old problem.","authors":"J B Clegg,&nbsp;D J Weatherall","doi":"10.1046/j.1525-1381.1999.99235.x","DOIUrl":"https://doi.org/10.1046/j.1525-1381.1999.99235.x","url":null,"abstract":"<p><p>The hemoglobinopathies are probably the world's most common genetic diseases: The World Health Organization has estimated that at least 5% of the population are carriers for one or other of the most serious forms, the alpha- and beta-thalassemias and the structural variant hemoglobins S, C, and E, which are found at polymorphic frequencies in many countries. All these hemoglobinopathies are believed to provide protection against malaria, and it is thought that, in malarial regions of the world, natural selection has been responsible for elevating and maintaining their gene frequencies, an idea first proposed 50 years ago by J.B.S. Haldane. Epidemiological studies undertaken in the 1950s on hemoglobin S in Africa provided support for the \"malaria hypothesis,\" but until recently it has proved extremely difficult to verify it for the thalassemias. The application of molecular methods has, however, provided new opportunities to address this old question. Population and molecular genetic analysis of thalassemia variants, and microepidemiological studies of the relationship between alpha-thalassemia and malaria in the southwest Pacific, have provided unequivocal evidence for protection. Surprisingly, some of this protection appears to derive from enhanced susceptibility in very young thalassemic children to both Plasmodium falciparum and, especially, P. vivax, and this early exposure appears to provide the basis for better protection in later life.</p>","PeriodicalId":20612,"journal":{"name":"Proceedings of the Association of American Physicians","volume":"111 4","pages":"278-82"},"PeriodicalIF":0.0,"publicationDate":"1999-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21284153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 100
Understanding the genetic basis of susceptibility to mycobacterial infection. 了解霉菌感染易感性的遗传基础。
Proceedings of the Association of American Physicians Pub Date : 1999-07-01 DOI: 10.1046/j.1525-1381.1999.99242.x
M Levin, M Newport
{"title":"Understanding the genetic basis of susceptibility to mycobacterial infection.","authors":"M Levin, M Newport","doi":"10.1046/j.1525-1381.1999.99242.x","DOIUrl":"10.1046/j.1525-1381.1999.99242.x","url":null,"abstract":"<p><p>Genetic factors have long been suspected of determining susceptibility and resistance to mycobacterial infection. The recent identification of families with a unique susceptibility to mycobacterial infection, and the identification of mutations in the genes for either the interferon-gamma (IFN-gamma) receptor or the interleukin (IL)-12 receptor as the cause of the defect, has provided an important clue to the pathways critical for resistance to mycobacterial infection in humans. Although the genetically determined absence of key cytokines or their receptors results in susceptibility to lethal mycobacterial infections in early childhood, it is likely that more subtle mutations that result in only partial dysfunction of macrophage upregulation pathways may play a role in susceptibility to tuberculosis (TB) and leprosy in the general population.</p>","PeriodicalId":20612,"journal":{"name":"Proceedings of the Association of American Physicians","volume":"111 4","pages":"308-12"},"PeriodicalIF":0.0,"publicationDate":"1999-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21284157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 36
In memoriam. Abner McGhee Harvey. 1911-1998. 为纪念。艾伯纳·麦吉·哈维,1911-1998。
V A McKusick
{"title":"In memoriam. Abner McGhee Harvey. 1911-1998.","authors":"V A McKusick","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":20612,"journal":{"name":"Proceedings of the Association of American Physicians","volume":"111 4","pages":"365-8"},"PeriodicalIF":0.0,"publicationDate":"1999-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21361146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sidney C. Werner. 1909-1994. 西德尼·c·沃纳,1909-1994。
L E Braverman
{"title":"Sidney C. Werner. 1909-1994.","authors":"L E Braverman","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":20612,"journal":{"name":"Proceedings of the Association of American Physicians","volume":"111 4","pages":"369-70"},"PeriodicalIF":0.0,"publicationDate":"1999-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21361153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Thematic Review Series VI: Skin Gene Therapy Introduction. 专题综述系列六:皮肤基因疗法简介。
Proceedings of the Association of American Physicians Pub Date : 1999-05-09 DOI: 10.1046/j.1525-1381.1999.99200.x
S I Katz
{"title":"Thematic Review Series VI: Skin Gene Therapy Introduction.","authors":"S I Katz","doi":"10.1046/j.1525-1381.1999.99200.x","DOIUrl":"https://doi.org/10.1046/j.1525-1381.1999.99200.x","url":null,"abstract":"","PeriodicalId":20612,"journal":{"name":"Proceedings of the Association of American Physicians","volume":"111 3","pages":"183"},"PeriodicalIF":0.0,"publicationDate":"1999-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21222926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Systemic replacement therapy from genetically modified epidermal keratinocytes. 转基因表皮角质形成细胞的系统性替代疗法。
Proceedings of the Association of American Physicians Pub Date : 1999-05-01 DOI: 10.1046/j.1525-1381.1999.99226.x
L B Taichman
{"title":"Systemic replacement therapy from genetically modified epidermal keratinocytes.","authors":"L B Taichman","doi":"10.1046/j.1525-1381.1999.99226.x","DOIUrl":"https://doi.org/10.1046/j.1525-1381.1999.99226.x","url":null,"abstract":"<p><p>Epidermal keratinocytes are a potential vehicle for gene transfer and systemic delivery. We review data showing that epidermis-secreted protein does indeed reach the circulation, and we discuss factors that bear upon the issue of how much protein epidermal keratinocytes can deliver to the circulation.</p>","PeriodicalId":20612,"journal":{"name":"Proceedings of the Association of American Physicians","volume":"111 3","pages":"206-10"},"PeriodicalIF":0.0,"publicationDate":"1999-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21222930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 21
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