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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have selected 11 patients with primary immunodeficiency disorders predominantly affecting T lymphocyte function (four with ataxia-telangiectasia (AT), four with common variable immunodeficiency (CVI) and one each with Wiskott-Aldrich syndrome, hyper-IgE syndrome and combined immunodeficiency) with defective gamma interferon (IFN-gamma) production in vitro. Induction with phytohaemagglutinin showed low interleukin 2 (IL-2) production concomitant with reduced IFN-gamma titres. However the addition of 10 U/ml of rIL-2 to cultures stimulated with staphylococcal enterotoxin B or galactose oxidase failed to restore IFN-gamma production in defective cases. IFN-gamma was titrated by both bioassay and immunoradiometric assay, ruling out the possible release of inactive or altered IFN-gamma molecules. Normal levels of IFN-gamma were found in patients of patients with AT, as well as in two AT and two CVI cases, demonstrating heterogeneity of defects within these syndromes. Soluble inhibitors or cellular suppression of IFN-gamma were not observed in mixing experiments. The possibility that defective interaction between accessory cells and T lymphocytes might account for the poor response to the inducing agents was ruled out as no IFN-gamma was produced using a calcium ionophore--which bypasses this step--in seven patients with absolute IFN-gamma deficiency.
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PMID:Evidence that defective gamma interferon production in patients with primary immunodeficiencies is due to intrinsic incompetence of lymphocytes. 313 28

Patients with a primary immunodeficiency syndrome have an increased risk of developing a malignancy. Lymphoreticular malignancies are the most common malignancies in these patients. Patients with ataxia telangiectasia (AT) also appear to be at a high risk for the development of nonlymphoid tumors--in particular, carcinomas of the gastrointestinal tract and central nervous system tumors. We describe a child with an immunodeficiency and slight neurological manifestations. During childhood she developed three consecutive primary malignancies.
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PMID:Three consecutive primary malignancies in one patient during childhood. 315 74

An increased incidence of malignancies occurs in ataxia telangiectasia. These are most frequently hematopoietic in children and epithelial in adults. Both cellular immunodeficiency and chromosome damage have been implicated in their etiology. There has been only one report of a salivary malignancy, a parotid mucoepidermoid carcinoma. We describe a second salivary malignancy, a metastasizing acinic cell carcinoma of the parotid gland, that developed in a 33-yr-old woman with ataxia telangiectasia. The marked chromosomal abnormalities that were present may have been involved in the pathogenesis of her tumor.
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PMID:Ataxia telangiectasia and acinic cell carcinoma of the parotid gland. 317 93

The peripheral blood leukocytes of 6 children with clinical data suggestive of primary cellular immunodeficiencies were studied in an attempt to define the cellular basis of these disorders. The phenotype and function of T and B cells were investigated. According to the clinical and laboratory features, the patients were classified as one case of severe combined immunodeficiency (SCID), two of ataxia-telangiectasia (AT), one of Wiskott-Aldrich syndrome (WAS), one of DiGeorge syndrome (DSG), and one of cellular immunodeficiency (CID). The laboratory investigations together with the clinical manifestations permitted a diagnosis of primary immunodeficiency diseases.
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PMID:Primary immunodeficiency diseases: a presentation of 6 cases. 326 46

Two sisters with a complex clinical pattern, including microcephaly, microgenia, defects of skin pigmentation, anal stenosis/atresia, and combined immunodeficiency together with spontaneous chromosomal instability and cellular hypersensitivity to X-rays and bleomycin are described. Complementation studies on heterokaryons proved that the underlying genetic defect is non-allelic with that of patients with ataxia telangiectasia (complementation groups AB-E) and the Nijmegen breakage syndrome, but identical with the case described by Conley et al. (1986).
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PMID:A new chromosomal instability disorder confirmed by complementation studies. 327 55

Ataxia-telangiectasia is an autosomal recessive disorder characterized by early ataxia, oculocutaneous telangiectasias, sinopulmonary infections, selective immunodeficiency, and a high risk of malignancy. The appearance of the telangiectasias often allows the diagnosis to be made in a child with ataxia.
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PMID:Ataxia-telangiectasia. 330 35

Fibroblast cultures from six unrelated patients having a familial type of immunodeficiency combined with microcephaly, developmental delay, and chromosomal instability were studied with respect to their response to ionizing radiation. The cells from five of them resembled those from individuals with ataxia telangiectasia (AT) in that they were two to three times more radiosensitive on the basis of clonogenic cell survival. In addition, after exposure to either X-rays or bleomycin, they showed an inhibition of DNA replication that was less pronounced than that in normal cells and characteristic of AT fibroblasts. However, the patients are clinically very different from AT patients, not showing any signs of neurocutaneous symptoms. Genetic complementation studies in fused cells, with the radioresistant DNA synthesis used as a marker, showed that the patients' cells could complement representatives of all presently known AT complementation groups. Furthermore, they were shown to constitute a genetically heterogeneous group as well. It is concluded that these patients are similar to AT patients with respect to cytological parameters. The clinical differences between these patients and AT patients are a reflection of genetic heterogeneity. The data indicate that the patients suffer from a chromosome-instability syndrome that is distinct from AT.
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PMID:Patients with an inherited syndrome characterized by immunodeficiency, microcephaly, and chromosomal instability: genetic relationship to ataxia telangiectasia. 333 13

One hundred and three cases of primary immunodeficiency diseases were diagnosed among children suffering mainly from chronic and severe infections in the period 1980-1987. Predominantly antibody defects were recognized in 48 patients (46.6%), combined immunodeficiencies in 36 patients (35%), phagocytic disorders in 12 patients (11.6%), complement defects in 6 patients (5.8%), and cell-mediated disease (Di George syndrome) in 1 patient. Allergic complications were observed in 25 patients (24.2%) and malignancy-in 3 patients (2.9%). More detailed immunological studies were performed in children with X-linked agammaglobulinemia in the course of intravenous immunoglobulin therapy and in children with ataxia telangiectasia.
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PMID:Primary immunodeficiency diseases in children treated in the Children's Memorial Hospital, Poland. 341 May 9

We investigated the prevalence of phenotypically immature IgG B cells (i.e., coexpressing surface IgG and IgM) in the peripheral blood of 12 patients with hypogammaglobulinemia and in normal individuals. Patients had ataxia-telangiectasia (N = 1), hyper-IgM combined immunodeficiency (N = 1), or common variable immunodeficiency (CVI). IgG/IgM-positive B cells were evaluated by two-color immunofluorescence using fluorescein- or rhodamine-conjugated goat antiserum; to minimize artifacts due to in vivo cytophilic binding of autologous IgG, cell-bound cytophilic Ig were eluted at pH 4 and Fc receptors were blocked by heat-aggregated rabbit IgG before fluorescent staining. All patients, except two with late-onset CVI, had markedly increased proportions of double-stained IgG B cells (56 to 100% of IgG-bearing B cells) in comparison with normal individuals (11 to 33%).
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PMID:Phenotypically immature IgG-bearing B cells in patients with hypogammaglobulinemia. 348 52

Ataxia-telangiectasia (AT) is a primary genetic immunodeficiency disease predisposing to cancer. Approximately 40% of patients with AT develop malignancy, usually of the lymphoid system. Increased chromosome breakage in AT leads to rearrangements such as translocations and inversions. The preferred chromosome breakpoints in AT involve genes in the immune system: the immunoglobulin (Ig) gene loci in chromosome bands 2p12, 14q32, and 22q11 and the T cell receptor (TCR) gene loci in chromosome bands 7p13, 7q35, and 14q11. Identical chromosome breakpoints are observed in chromosome rearrangements in normal T cells, Burkitt's lymphoma, and adult T cell leukemia. Molecular analysis of these chromosome rearrangements reveals recombination between an oncogene and Ig or between Ig and TCR. In AT, chromosome rearrangements connect the immune system to lymphoid cancer.
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PMID:Chromosome changes connect immunodeficiency and cancer in ataxia-telangiectasia. 349 17


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