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)

It is the purpose of this review to analyse prevalence and pathogenesis of tumours occurring in the diverse conditions of primary and secondary immunodeficiencies. In general, most states of immunodeficiences are connected with a highly increased tumour risk. However, there is circumstantial evidence that immunodeficiency-related malignancies do not primarily result from an impaired immunosurveillance. With special regard to ataxia-telangiectasia it has been found that congenital chromosomal instability deregulates the maturation of immunocompetent lymphoid cells by interfering with their natural DNA rearrangements and eventually leads to false recombinatory events with oncogenetic consequences in a parallel way. Malignancies in primary common variable or in secondary (e.g. AIDS) immunodeficiency may result from an impaired immunity to oncogenic viruses or from chronic immune damage due to secondary autoimmune disorders.
 ...
PMID:[Tumors in immunodeficiency syndromes]. 172 56

Ataxia-telangiectasia (AT) is a heterogeneous autosomal recessive disorder marked by cerebellar ataxia, oculocutaneous telangiectases, hypersensitivity to ionizing radiation, immunodeficiency, and cancer susceptibility. AT is also a spontaneous chromosomal breakage syndrome, notable for tissue-specific cytogenetic changes and telomeric fusions. Molecular characterization of rearrangements specific to T-lymphocytes suggests that a DNA repair/processing defect is potentially responsible for the diverse array of chromosomal abnormalities observed in a variety of AT cell types.
 ...
PMID:The cytogenetics of ataxia telangiectasia. 175 58

The association between cancer and immunodeficiency is well established. In common variable immunodeficiency (CVI), a primary immunodeficiency disease characterized by low serum immunoglobulins and poor antibody production, we previously reported a total of 13 cancers in 11 individuals arising in continuously observed group of patients. Of the 13, 7 were NHL and 1 was a myeloma which progressed to lymphoma. We report here the histologic, immunologic, cytogenetic, and clinical features of these 8 NHL along with 3 new lymphomas which have appeared in this group (now 117 patients). From our studies, the lymphomas which have arisen in CVI share certain features with the lymphomas which appear in the childhood immunodeficient syndromes. Wiskott Aldrich Syndrome, Ataxia Telangiectasia, or severe combined immunodeficiency: they are similar in overall frequency (13%), are often B-cell in origin, and extranodal in location. However, unlike the lymphomas of the immunodeficient child, lymphomas in CVI may be more differentiated and secrete immunoglobulin. For CVI patients with stage I or II disease, as for non-Hodgkin lymphomas in general, the prognosis is good. In our group, NHL in CVI have appeared most often in females of the 5th to 7th decade and not in childhood. Cytogenetic studies in lymphomas show that cytogenic abnormalities, including chromosomal translocation, can be found in this group, but more studies will be needed to assess the frequency of these events.
 ...
PMID:Non-Hodgkin lymphoma in common variable immunodeficiency. 182 73

We report on a microcephalic, growth-retarded newborn girl without major anomalies who has chromosome instability in lymphocytes and fibroblasts. Frequent involvement of bands 7p13, 7q34, 14q11, and 14q32 suggested the diagnosis of ataxia telangiectasia (AT) or a related disorder. Supportive evidence was radioresistant DNA synthesis in fibroblasts and radiation hypersensitivity of short-term lymphocyte cultures. Follow-up for nearly 4 years showed largely normal development, and no signs of telangiectasia, ataxia, or immunodeficiency. Serum AFP levels turned from elevated at age 5 months to normal at age 2 years. We propose that our patient belongs to the expanding category of "AT-related" genetic disorders, probably to the Nijmegen breakage syndrome.
 ...
PMID:Chromosome instability and X-ray hypersensitivity in a microcephalic and growth-retarded child. 188 49

The TCR/CD3 complex plays a central role in antigen recognition and activation of mature T cells, and, therefore, abnormalities in the expression of the complex should induce unresponsiveness of T cells to antigen stimulus. Using flow cytometry, we detected and enumerated variant cells with loss or alteration of the surface TCR/CD3 expression among human mature CD4+ T cells. The presence of variant CD4+ T cells was demonstrated by isolating and cloning them from peripheral blood, and their abnormalities can be accounted for by alterations in TCR expression such as defects of protein expression and partial protein deletion. The variant frequency in peripheral blood increased with aging in normal donors and was highly elevated in patients with ataxia telangiectasia, an autosomal recessive inherited disease with defective DNA repair and variable T cell immunodeficiency. These findings suggest that such alterations in TCR expression are induced by somatic mutagenesis of TCR genes and can be important factors related to age-dependent and genetic disease-associated T cell dysfunction.
 ...
PMID:Spontaneous loss and alteration of antigen receptor expression in mature CD4+ T cells. 197 77

Ataxia-telangiectasia is a syndrome with many facets, involving a progressive cerebellar ataxia, immunodeficiency, cancer susceptibility, radiosensitivity, defects in DNA repair/processing, chromosomal breakage and rearrangements, elevated serum alphafetoprotein, and premature aging. Ataxia-telangiectasia is an autosomal recessive disorder, rare in outbred populations; carriers of the ataxia-telangiectasia gene may be as common as 1 in 60 and have subclinical radiosensitivity and cancer susceptibility. One estimate suggests that 8.8% of patients with breast cancer could be carriers of ataxia-telangiectasia. These carriers may be responsible for underestimating normal tolerance doses for radiation therapy by 15% to 20%; thus by preselecting and excluding carriers of ataxia-telangiectasia from cohorts of patients with cancer, conventional radiation doses might be increased so as to improve greatly the efficacy of radiotherapy. The genes for the 3 most common ataxia-telangiectasia complementation groups, which include 97% of tested families, have recently been localized to the long arm of chromosome 11.
 ...
PMID:Ataxia-telangiectasia: an interdisciplinary approach to pathogenesis. 200 80

Serum IgD levels were determined in 66 patients with well-defined primary immunodeficiency diseases. The two major groups of patients consisted of those with ataxia-telangiectasia (38 patients) and those with selective IgA deficiency (11 patients). The ataxia-telangiectasia patients tended to have higher serum IgD levels while no significant difference was found in the serum IgD levels of the selective IgA deficiency patients when compared with the controls. No correlation was found between the IgD levels and the presence of frequent infections in both patient groups or the associated disorders present in the selective IgA deficiency patients. The percentage of low serum IgD phenotype in the normal subjects was similar to that described in the literature.
 ...
PMID:Serum IgD concentrations in immunodeficiency diseases. 209 53

In ataxia-telangiectasia, B-cell and T-cell deficiencies are thought to be due to a defect of rearrangements of immunoglobulin and T-cell receptor genes. T cells recognize antigens through two types of CD3-associated receptors: alpha/beta chains on mature cells and gamma/delta chains mostly on immature cells. We studied 10 patients with ataxia-telangiectasia and found that most had a relative increase of circulating T cells bearing gamma/delta receptors rather than alpha/beta receptors, as compared with normal subjects (P less than 0.001). Patients with other immune deficits, including eight with common variable immunodeficiency, one with Wiskott-Aldrich syndrome, two with hyperimmunoglobulinemia E syndrome, and one with severe combined immunodeficiency, had normal ratios of gamma/delta-bearing to alpha/beta-bearing cells. A marked predominance of gamma/delta-bearing T cells was found in a patient with a primary T-cell defect. The relative increase in gamma/delta-bearing T cells in the patients with ataxia-telangiectasia was largely accounted for by cells that reacted with the monoclonal antibody BB3, an apparently distinct subset of T cells that selectively express the C gamma 1 gene product of the T-cell receptor. Although they had normal ratios of gamma/delta-bearing to alpha/beta-bearing T cells, the patients with common variable immunodeficiency had a significant increase (P = 0.01) in the number of T cells expressing C gamma 2 that reacted with the monoclonal antibody delta-TCS-1. We conclude that the increased ratio of gamma/delta-bearing to alpha/beta-bearing T cells in ataxia-telangiectasia may reflect both a recombinational defect that interferes with T-cell and B-cell gene rearrangements and an inability to repair damage to the DNA.
 ...
PMID:Relative increase of T cells expressing the gamma/delta rather than the alpha/beta receptor in ataxia-telangiectasia. 221

Ataxia telangiectasia (AT) is a primary immunodeficiency syndrome characterized by cerebellar ataxia, extrapyramidal signs, oculocutaneous telangiectasia, recurrent respiratory infections and development of malignancies. AT is a complex autosomal recessive disorder involving several systems other than lymphoid cells or the central nervous system. Such a diversity of abnormalities includes hypersensitivity of fibroblasts and lymphocytes to ionizing radiation (anomaly of DNA repair), non-random chromosomal rearrangements in lymphocytes, elevated serum level of alpha-fetoprotein, premature aging and endocrine disorders. A DNA processing or repair protein is the suspected common denominator in this pathology. Whatever the putative common underlying mechanism, AT patients have profound alterations of the humoral and cellular immune system whose mechanisms should be discussed in terms similar to those for other immunodeficiency diseases. The usual immunological abnormalities in this disease include decreased levels of CD 3 and CD 4 positive T lymphocytes, impaired delayed hypersensitivity, hypoplasia of thymus, decreased blast transformation in vitro in response to mitogen or antigenic stimulation, and decreased levels of serum IgA, IgE, and IgG 2 subclass. In this paper, the results of our recent studies on the defects of B cells in patients with AT were presented. (1) We found that the geometric means of IgA production in the supernatants of the lymphoblastoid cell lines established by EB virus, from all patients with AT, were significantly lower than those from healthy controls (P less than 0.01). (2) IgG subclasses of the patients' sera were also measured by ELISA, and IgG 4 was defective in four cases among six patients with AT.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Ataxia telangiectasia and characterization of its immunological disorders]. 215 3

A gene locus for ataxia-telangiectasia (A-T) is in chromosome region 11q22 to 11q23 and predisposes to cancer. Ataxia-telangiectasia patients appear to have two separate clinical patterns of malignancy. One pattern involves solid tumors, which have not been stressed and which include malignancies in the oral cavity, breast, stomach, pancreas, ovary, and bladder. Detection of a solid tumor in an A-T patient should serve as a warning. It heralds a markedly elevated risk of another malignancy in that patient. The second pattern of neoplasia in A-T is well recognized and consists of lymphocytic leukemia and non-Hodgkin's lymphoma. These malignancies may relate to immunodeficiency in A-T and to chromosome breakage and rearrangement, which are a feature of A-T. These two patterns of malignancy may be truly separate and reflect different mechanisms of malignancy in A-T, or they may not really be separate but instead reflect a single mechanism of malignancy. The situation in A-T is reminiscent of that in the acquired immunodeficiency syndrome (AIDS), in which Kaposi's sarcoma occurs with mild immunodeficiency and pneumocystis carinii pneumonia occurs with more profound immunodeficiency owing to the human immunodeficiency virus. Next to pulmonary disease, cancer is the leading cause of death in A-T.
 ...
PMID:Cancer in ataxia-telangiectasia patients. 218 34


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>