Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the recent studies conducted in patients with various types of primary immunodeficiency diseases, an increased frequency of HLA-A1 or HLA-A2 antigens was reported. In order to determine the frequency of the histocompatibility antigens in ataxia telangiectasia (A-T), HLA typing was carried out in 30 patients with A-T along with their 23 parents and 4 siblings. The results were compared with 138 healthy controls. That study showed no significant difference for the frequencies of 19 HLA antigens of the A and B loci between the controls and A-T patients or their parents-siblings.
 ...
PMID:Histocompatibility (HLA) factors in ataxia telangiectasia. 65 94

There is an increased prevalence (P less than 0.001) of IgA deficiency in children with juvenile-onset insulin-dependent diabetes mellitus (9/366) but not in adults with insulin-dependent diabetes (0/421). The juvenile diabetics with IgA deficiency have other immune-associated diseases, such as thyroiditis and chronic active hepatitis, and have a history of infections. Four of the nine IgA-deficient diabetics we studied have autoantibodies to endocrine organs. Seven of eight have the HLA-B8, a proportion significantly (P less than 0.05) greater than control populations. Based on the clinical findings of IgA deficiency and multiple autoantibodies in patients with ataxia-telangiectasia and chronic mucocutaneous candidiasis, diseases associated with thymus deficiency, we suspect that thymus deficiency and autoimmunity may play a role in the pathogenesis of some types of juvenile-onset diabetes mellitus. In addition, an excess morbidity of the IgA-deficient juvenile diabetic population may explain the lack of IgA deficiency in older insulin-dependent diabetic individuals.
 ...
PMID:Immunopathology of juvenile-onset diabetes mellitus. I. IgA deficiency and juvenile diabetes. 72 Jul 69

Antenatal diagnosis is now available for most severe inherited immune deficiencies. Several techniques are used: the development of methods for sampling fetal tissue as soon as the tenth week of gestation has made possible the antenatal diagnosis of immune deficiencies associated with detectable enzyme defects, and, in combination with recent molecular biology techniques, can be expected to allow early identification of severe combined immune deficiencies due to the absence of T lymphocyte precursors, agammaglobulinemia, and some instances of X-linked chronic granulomatous disease. A great number of immune deficiencies can be identified by direct studies of fetal lymphocytes or polymorphonuclear leukocytes in fetal blood sampled by fetoscopy at the twentieth week of gestation. Fetal blood studies combined with skin biopsy examination allows the diagnosis of immune defects associated with partial albinism such as Chediak-Higashi disease. No reliable antenatal diagnostic method is as yet available for two severe diseases: Wiskott-Aldrich syndrome, that can be expected to become detectable in utero using molecular biology techniques, and ataxia-telangiectasia. Antenatal diagnosis of a severe immune deficiency does not necessarily indicate termination of the pregnancy as in some cases, such as severe combined immune deficiencies, HLA-identical bone marrow transplantation at birth or in utero is permanently successful in over 90% of cases.
 ...
PMID:[Prenatal diagnosis of severe and hereditary immune deficiencies]. 266 29

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.
 ...
PMID:Defective specific antiinfluenza virus antibody production in vitro by lymphocytes from patients with ataxia-telangiectasia. 387 88

Nine HLA-typed multiplex nuclear families segregating ataxia-telangiectasia (A-T), an autosomal recessive disorder, were studied. Linkage analysis performed by lod scores and by a previously published sib pair method revealed no evidence for linkage between A-T and HLA. An alternative method of linkage detection, previously applied to xeroderma pigmentosum (XP) and HLA, was reexamined and found to contain an error. As a consequence, neither of these "DNA repair disorders" appears to be linked to HLA.
 ...
PMID:Ataxia-telangiectasia and xeroderma pigmentosum: no evidence of linkage to HLA. 746 73

It is most unlikely that there is a single 'pre-eclampsia (PE) gene'. We are probably looking for a cluster of polymorphisms which, possibly in conjunction with environmental factors, predispose to the development of the condition. Accurate phenotyping is vital for any genetic studies of PE, and since the disease is only clinically-detectable in the second half of pregnancy, is particularly difficult. It is increasingly likely that there is a fetal genetic contribution which can only be examined after birth. Candidate genes examined on the basis of displayed or hypothetical pathophysiological effects, but for which no evidence of association or linkage has been found have included HLA-DRbeta, HLA-G, and tumour necrosis factor alpha (chromosome 6), angiotensin-converting enzyme (chromosome 17) and CuZn superoxide dismutase (chromosome 21). Chromosomal exclusion mapping and a pedigree study suggest a role for genes on chromosomes 1, 3, 4, 9 or 18. Two genes concerned with clotting, those for factor 5 and methylenetetrahydrofolate reductase, lie on chromosome 1. Both have polymorphisms present in significantly higher frequency in women with PE, as well as showing functional abnormality. They probably predispose to the development of the condition, without being necessary for it. The angiotensinogen (Aogen) gene also lies on chromosome 1. The renin-angiotensin system may be activated during the early stages of PE and subsequently suppressed. In some populations, a relatively common polymorphism is present in raised frequency in women with PE, but it is also raised in non-pregnant hypertensive subjects. However, it is in partial linkage disequilibrium with another polymorphism which shows significantly distorted transmission from mother to fetus in PE pregnancies. Furthermore, its expression is significantly raised in the decidual spiral arteries; abnormal placentation is a feature of PE. We have also shown that a relatively common polymorphism in the angiotensin AT1 receptor gene (chromosome 3) is associated with raised density of the receptor. Thus far, studies of candidate genes have been on a small scale and have very much reflected the pathophysiological research interests of the investigators. The multifaceted nature of PE and the difficulties of accurate phenotyping require the accumulation of a large, very carefully phenotyped, database. It is hoped that funding will become available this year in the UK to allow the collection of such a database. The introduction of chip technology should allow genome scanning of the resource.
 ...
PMID:What is the place of genetics in the pathogenesis of pre-eclampsia? 1056 60

The objective of this study was to evaluate the safety and efficacy of the humanized antibody ATM-027 in a baseline versus treatment magnetic resonance imaging-monitored study. Expansion of Vbeta5.2/5.3(+) T cells has been demonstrated in the peripheral blood, cerebrospinal fluid, and brain lesions of MS patients. In a phase I study, ATM-027 depleted these cells in peripheral blood and, in parallel, T-cell MBP reactivity and IFN-gamma expression were reduced. We studied 59 patients with relapsing-remitting MS (47 on ATM-027 and 12 on placebo) stratified for HLA-DR2 status. Monthly intravenous injections were given for 6 months. Individual dose titration was employed to obtain depletion of the target T-cell level and downregulation of antigen receptor density as monitored by flow cytometry. Five monthly magnetic resonance imaging scans were performed before treatment to establish baseline activity, six during treatment, and three during follow-up. Additional immunological assessments were performed to elucidate the mechanism of action of ATM-027. The treatment was safe and well tolerated, inducing consistent suppression of the target cell population. During run-in, active lesions were found in 78.7% (37/47) of patients treated with ATM-027. During treatment, the median number of lesions was reduced by 33% (p = 0.13) independent of DR2 status. The corresponding volume of enhancement was 221 mm(3) at baseline, with a reduction of 10% during treatment. Decreased numbers of cells expressing interferon-gamma messenger RNA, and decreased T-cell reactivity to several myelin antigens were found in ATM-027 treated patients. In conclusion, consistent suppression of Vbeta 5.2/5.3(+) T cells was achieved. However, the effect size on magnetic resonance imaging was considerably less than the targeted 60%.
 ...
PMID:Antibody-mediated suppression of Vbeta5.2/5.3(+) T cells in multiple sclerosis: results from an MRI-monitored phase II clinical trial. 1192 Oct 52

IgA deficiency is among the most common primary immune deficiency known. Its prevalence, ranging from 1/324-1/1850, depends upon the study group geographic location and its ethnicity. IgA deficiency is commonly associated with other immune defects such as IgG2, and IgG4 deficiency. In addition, ataxia telangiectasia has been associated with IgA deficiency as well. The clinical significans of IgA deficiency is presently unclear. However, increased susceptibility to atopy, autoimmunity, infections and cancer has been reported. Furthermore, majority of these diseases are bound to the mucosal surfaces; the organ where IgA is thought to have its most protective role. Recent studies focusing on the genealogy of primary IgA deficiency have found linkages to chromosome 6, 14, 18 and 22. In addition, a link to certain HLA haplotypes has been reported. Thus, further studies into the immunogenetics of IgA deficiency are needed, particularly focusing upon the question why some individuals with IgA deficiency are prone to diseases whereas others are not. In this article some of these questions are addressed, and the current literature on the topic reviewed.
 ...
PMID:[The current concept of primary IgA deficiency and its prevalence in Iceland.]. 1701 15

Mutations of the ataxia-telangiectasia-mutated (ATM) gene are responsible for the autosomal recessive disorder ataxia-telangiectasia (A-T). This study reports the first A-T prenatal diagnosis performed in Spain by direct molecular analysis. The pregnant woman had a previous child suffering from A-T due to a deletion in the ATM gene. The ATM coding region was sequenced in the A-T patient and her parents. Then, a specific polymerase chain reaction (PCR) to detect the deletion was performed for prenatal diagnosis. Additionally, polymorphic HLA loci were examined in order to exclude the possible contamination by maternal DNA. In this family of Gypsy origin, we carried out a rapid molecular diagnosis of A-T. Then, a prenatal diagnosis was carried out, identifying the deletion in the fetal DNA. Additionally, we performed a population study in unrelated Spanish Gypsies and in unrelated controls, showing that the deletion described could be a hotspot in the Spanish Gypsy population. The size of the coding region and the genomic structure, together with the absence of hotspots, make the mutation screening of the ATM gene difficult. The ability to identify ATM mutations provides a tool that can be applied in confirmatory diagnosis, genetic counselling, carrier prediction and prenatal diagnosis.
 ...
PMID:Rapid molecular prenatal diagnosis of ataxia-telangiectasia by direct mutational analysis. 1760 Aug 66

Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) are essential for responses to interferons (IFNs), most cytokines, and some growth factors. JAK/STAT signaling is not, however, sufficient for a full IFN-gamma response. Here, a convenient, robust, and quantitative flow cytometry-based kinome-wide siRNA screen has identified nine additional kinases as required for the IFN-gamma class II HLA response, seven for an antiviral response, and two for the cytopathic response to encephalomyocarditis virus (EMCV). As one example, inhibition of the IFN-gamma response by siRNA to ataxia telangiectasia-mutated (ATM) differentially affects a spectrum of IFN-gamma-stimulated mRNAs, with inhibitions being seen as early as 1 h after IFN-gamma stimulation. The implication of ATM, with its previously recognized function in chromatin decondensation, in the control of transcription early in the IFN-gamma response highlights both a role for ATM in cytokine responses and a possible correlation with the chromatin decondensation recently observed in response to IFN-gamma in mammalian cells. This work has, therefore, revealed the simplicity, power, and convenience of quantitative flow cytometry-based siRNA screens, a requirement for ATM and multiple additional kinases in the IFN-gamma response and a possible requirement for two of these kinases in the cytopathic response to EMCV.
 ...
PMID:Multiple kinases in the interferon-gamma response. 1841 54


1 2 Next >>