Kroc Foundation series最新文献

{"title":"Defective specific antiinfluenza virus antibody production in vitro by lymphocytes from patients with ataxia-telangiectasia.","authors":"R Yarchoan,&nbsp;C C Kurman,&nbsp;D L Nelson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The ability of lymphocytes from 11 patients with ataxia-telangiectasia to produce specific antiinfluenza virus antibody in vitro was evaluated. Lymphocytes from these patients produced markedly less antibody than lymphocytes from normal controls when stimulated with type A influenza viruses. Additional studies were undertaken to evaluate the function of the B cells, T cells, and adherent cells of these patients in specific antibody production. B cells from the AT patients produced one-third to one-half as much antiinfluenza virus antibody as did B cells from normals when stimulated with the polyclonal activator Epstein-Barr virus or, in the two cases studied, when stimulated with influenza virus in the presence of normal HLA-identical T-cells, suggesting that a partial B-cell defect contributed to the deficient antibody response in these patients. Helper T-cell function of T-cells from two patients was evaluated in coculture with their HLA-identical sibling's B cells; these studies revealed that the patients' T-cells could provide less help than normals' T-cells but that this help was not entirely deficient. Furthermore, T-cells from AT patients could provide allostimulated helper T-cell function in coculture with allogeneic normal B cells. Taken together, these results suggest that partial defects of B- and T-cell function both contribute to the decreased antiinfluenza virus antibody production by patients with AT.</p>","PeriodicalId":77744,"journal":{"name":"Kroc Foundation series","volume":"19 ","pages":"315-29"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14992987","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}

{"title":"Altered DNA synthesis in irradiated and unirradiated ataxia-telangiectasia cells.","authors":"R B Painter","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>DNA synthesis in cells from ataxia-telangiectasia (AT) patients differs from that in normal cells in two principal ways. In unirradiated cultures, AT cells have a lower inherent rate of DNA synthesis (and, therefore, a longer S phase) than normal cells and, in cultures exposed to ionizing radiation, DNA synthesis is not inhibited as it is in normal cells; this radioresistant DNA synthesis is due to completely resistant DNA chain elongation and partially resistant DNA replicon initiation. It is probable that the defects in DNA synthesis in irradiated and unirradiated cells are related and are at least partially involved in the pathogenesis of this syndrome.</p>","PeriodicalId":77744,"journal":{"name":"Kroc Foundation series","volume":"19 ","pages":"89-100"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14980664","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}

{"title":"Complementation analysis of ataxia-telangiectasia.","authors":"N G Jaspers,&nbsp;R B Painter,&nbsp;M C Paterson,&nbsp;C Kidson,&nbsp;T Inoue","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In a number of laboratories genetic analysis of ataxia-telangiectasia (AT) has been performed by studying the expression of the AT phenotype in fused somatic cells or mixtures of cell-free extracts from different patients. Complementation of the defective response to ionizing radiation was observed frequently, considering four different parameters for radiosensitivity in AT. The combined results from studies on cultured fibroblasts or lymphoblastoid cells from 17 unrelated families revealed the presence of at least four and possibly nine complementation groups. These findings suggest that there is an extensive genetic heterogeneity in AT. More extensive studies are needed for an integration of these data and to provide a set of genetically characterized cell strains for future research of the AT genetic defect.</p>","PeriodicalId":77744,"journal":{"name":"Kroc Foundation series","volume":"19 ","pages":"147-62"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14979749","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}

{"title":"Selective vulnerability in the nervous system.","authors":"R M Herndon","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77744,"journal":{"name":"Kroc Foundation series","volume":"19 ","pages":"257-67"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13563104","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}

{"title":"Genetic linkage studies in ataxia-telangiectasia: Gm markers.","authors":"R A Gatti,&nbsp;M Boehnke,&nbsp;M Crist,&nbsp;R S Sparkes","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Gm marker studies were performed on seven families with ataxia-telangiectasia in order to determine genetic linkage. For statistical analysis, the disorder was assumed to be monogenic. Using LOD scores computed by the program LIPED, tight linkage was excluded at a recombination fraction of less than or equal to 2 cM. This distance (equivalent to approximately two million nucleotides) includes most or all of the 14q32 chromosomal region.</p>","PeriodicalId":77744,"journal":{"name":"Kroc Foundation series","volume":"19 ","pages":"163-72"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"15047813","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}

{"title":"Sequence of cellular events in cerebellar ontogeny relevant to expression of neuronal abnormalities in ataxia-telangiectasia.","authors":"H V Vinters,&nbsp;R A Gatti,&nbsp;P Rakic","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>An attempt was made to relate expression of neuronal abnormalities in ataxia-telangiectasia (AT) to the sequence of normal cellular events in the developing human cerebellum. Previous light and electron microscopic analyses indicate that the cerebellar cortex in humans develops during a protracted period that spans 8 fetal and 12 postnatal months. However, the Purkinje cells that comprise the most obvious lesion in the AT disorder are all generated before the end of the fourth fetal month. Correlative Golgi studies in human and [3H]thymidine labeling of DNA in dividing cerebellar cells in rhesus monkey demonstrate that after the last mitotic division Purkinje cells migrate to the cortical plate where they form a well-defined stratum below the embryonic molecular layer. Only thereafter do they begin to differentiate and develop their large dendritic tree. The dendrites grow in coordination and simultaneously with the genesis of parallel fibers in the molecular layer. The parallel fibers--the horizontal portion of granule cell axons--form between the fourth fetal and twelfth postnatal month in a well-defined inside-outside order, the earliest generated fibers being situated near the Purkinje cell layer and the last fibers generated lying closer to the pial surface. The four cases of AT examined in this study showed the usual neuropathological changes, which include a variable degree of Purkinje and granule cell loss. However, we emphasize here an abnormality of dendritic arborization and the presence of displaced Purkinje cells, which are situated in the middle and superficial strata of the molecular layer. Based on the sequence of histogenetic events, we argue that neither abnormal arborization nor aberrant position could be attained after parallel fibers of the deeper strata have been laid down and after Purkinje cells have formed their dendritic tree. Therefore, we suggest that the AT disorder in these cases must affect Purkinje cell differentiation or the interaction of these cells with parallel fibers during the first half of gestation, which is considerably earlier than any other recognized expression of the disorder. The subsequent degeneration of Purkinje cells is apparently not related to the aberrant position of the somas, since many Purkinje cells situated in normal position also die and there is no evidence that displaced cells degenerate at a slower or more rapid rate. The early expression of AT in the central nervous system provides new insight into possible pathogenesis and opens new avenues for research.</p>","PeriodicalId":77744,"journal":{"name":"Kroc Foundation series","volume":"19 ","pages":"233-55"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14980661","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}

{"title":"On the nature of a \"DNA-processing\" defect in ataxia-telangiectasia.","authors":"P Hanawalt,&nbsp;R Painter","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77744,"journal":{"name":"Kroc Foundation series","volume":"19 ","pages":"67-71"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14980662","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}

{"title":"Defective allosuppression in patients with ataxia-telangiectasia.","authors":"G Tosato,&nbsp;R M Blaese","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We describe a novel in vitro assay system that detects the generation of suppressor T cells after exposure of human lymphocytes to class I alloantigens. We have used this system to study immune functions in a group of seven patients with ataxia-telangiectasia (AT). Normal T lymphocytes exposed to cells differing at the A and B locus histocompatibility locus antigens (HLA) become activated for suppression of Epstein-Barr virus (EBV)-induced immunoglobulin (Ig) production. In contrast to the normal, T cells from patients with AT demonstrate no inhibitory effect after allostimulation. These data indicate that patients with AT have a profound defect involving responses to class I antigens of the major histocompatibility complex (MHC).</p>","PeriodicalId":77744,"journal":{"name":"Kroc Foundation series","volume":"19 ","pages":"331-8"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14132592","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}

{"title":"Therapeutic considerations for use of immunomodulators in the treatment of ataxia-telangiectasia.","authors":"N Stebbing","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The nature of the soluble mediators of immune regulation, the lymphokines, is now being determined and this allows consideration of new approaches to treatment of disorders involving immune dysfunction, such as ataxia-telangiectasia. The immunomodulatory effects of interleukin-2, interferons, and known chemotherapeutic agents such as cyclophosphamide are considered in relation to the immune disorders of ataxia-telangiectasia. The possible etiology of the disease and its treatment are considered in relation to the immunopathologic effects that are observed.</p>","PeriodicalId":77744,"journal":{"name":"Kroc Foundation series","volume":"19 ","pages":"339-52"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"15051461","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}

{"title":"Ataxia-telangiectasia: genetics, neuropathology, and immunology of a degenerative disease of childhood. Proceedings of a conference. Solvang, California, January 16-20, 1984.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77744,"journal":{"name":"Kroc Foundation series","volume":"19 ","pages":"1-407"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14979744","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}