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)

The human immune system has evolved multiple cellular and humoral defense mechanisms against the lymphotropic virus, EBV. NK cells, suppressor T-cells, cytotoxic K-cells, memory T-cells, and humoral immune responses usually subdue the virus into latency. Individuals with immune deficiency are at great risk of developing immunoregulatory disturbances and lymphoproliferative diseases when confronted by EBV. The infection of B-cells by EBV provokes a marked activation of immunoregulatory T-cells and requires restoration of immune homeostasis during convalescence. This is accomplished with difficulty in an individual with significant immune defects. The X-linked lymphoproliferative syndrome is an exemplary model for studying EBV in immune deficient individuals. Boys with XLP can develop acquired agammaglobulinemia, aplastic anemia, chronic or fatal IM, and a variety of B-cell malignant lymphomas following infection by the virus. We have identified multiple immune defects in the patients and progressive immunoregulatory disturbances following infection by the virus. Other patients with immune deficiency syndromes, i.e., ataxia telangiectasia or the renal transplant recipient, are also at increased risk for developing EBV-induced lymphoproliferative diseases. Moreover, certain families are at increased risk for EBV-associated malignancies, especially those with a triad of manifestations (i.e., autoimmunity, immunodeficiency, and lymphoma). Chromosomal breakage as seen in patients with ataxia telangiectasia may predispose to leukemogenesis. Immunoregulatory defects are also probably predisposing factors to lymphomagenesis. Both inherited and acquired defects can render persons vulnerable to leukemia and lymphoma.
 ...
PMID:Immunodeficiency as a factor in lymphomagenesis. 633 Jun 65

2 mutant mouse cells M10 and Q31 were examined for chromosomal aberrations induced by ultraviolet radiation (UV) and 4-nitroquinoline-1-oxide (4NQO), as compared with mouse lymphoma L5178Y cells. Q31 cells are UV- and 4NQO-sensitive cells isolated from L5178Y cells. M10 cells are similar but are sensitive to ionizing radiation and 4NQO. After treatment with UV or 4NQO, chromatid-type aberrations in these cell strains were induced more frequently in the first mitotic cells, at late fixation times. After UV exposure (2.4 J/m2), the maximal frequencies of chromatid-type breaks in Q31 cells were about 5 times higher than in L5178Y cells. In M10 cells such breaks were only as frequent as in L5178Y cells. After 4NQO treatment (50 ng/ml) the frequencies of chromatid-type breaks in M10 and Q31 cells were significantly higher than in L5178Y cells. From these results and those of previous studies (Takahashi et al., 1982), M10 cells may be considered hypersensitive to gamma-rays and 4NQO, but not to UV, and thus react similarly to L5178Y cells. The hypersensitivity of M10 cells to 4NQO may result from a defect in the ionizing-radiation repair mechanism as has been suggested to occur in ataxia telangiectasia (AT) cells. Q31 cells are hypersensitive to UV and 4NQO, but not to gamma-rays. Q31 cells may be considered to be deficient in a UV-like repair pathway. In conclusion, characteristics of murine M10 and Q31 cells are compared with those of human AT and xeroderma pigmentosum (XP) cells.
 ...
PMID:Chromosomal hypersensitivity in mutant M10 and Q31 mouse cells exposed to ultraviolet radiation (UV) and 4-nitroquinoline-1-oxide (4NQO). 640 61

Five patients with primary immunodeficiency and cancer are presented. Two children with ataxia-telangiectasia developed acute lymphoblastic leukemia and malignant lymphoma of B-like origin with chromosome damage and unusual prevalence of antibodies to E.B.V. early antigen. A bone sarcoma occurred in a patient with common variable hypogammaglobulinemia. At least two infants who died with severe combined immunodeficiency had at autopsy congenital myelomonocytic leukemia and malignant lymphoma. These cases indicate the high risk for development of cancer in patients with primary abnormalities of the immune system and suggest the heterogeneity and complexity of pathogenic mechanisms.
 ...
PMID:[Primary immunologic deficiencies and cancer. 5 anatomo-clinical case reports]. 657 32

Cytogenetic studies were performed on three patients with chronic T cell leukemia and on one patient with T cell lymphoma. One of the patients had leukemic cells derived from a suppressor T cell clone, another expressed OKT3, 4, and 8, and cells of the other two were derived from a helper T cell clone. All patients had an abnormal karyotype in peripheral blood or bone marrow cultured with or without mitogen. Modal chromosome numbers were 42 and 44/45 in one patient each and 47 in the 2 others. The structural and numerical abnormalities involved almost all chromosomes, except no. 19 and the X chromosome. All patients had a rearrangement of the long arm of no. 14, with a break at band 14q11;3 patients also had a break at 14q32. An inversion of 14q occurred in two patients; a tandem translocation involving both no. 14 chromosomes and a translocation between no. 14 and no. 17 each occurred in one patient. The break in 14q at band q11 in our cases resembles the chromosome change reported in ataxia telangiectasia. This provides added support for the proposal that a 14q rearrangement involving band q11-12, with or without an accompanying break in 14q32, may confer a proliferative advantage on lymphocytes, especially on those of T cell origin.
 ...
PMID:Cytogenetic studies on patients with chronic T cell leukemia/lymphoma. 660 68

The mouse lymphoma L5178Y cell line and its radiosensitive variants M10 and LX830 were examined for DNA synthesis after X-irradiation. The dose-response curves show that the rates of DNA synthesis immediately after exposure are reduced in a dose-dependent fashion and that the extents of reduction in these 3 cell lines are similar to one another. But a difference was observed in the recovery of DNA synthesis with time of incubation. The recovered levels in M10 and LX830 cells were much higher than those in L5178Y cells at high doses of X-rays. These results are discussed in relation to radioresistant DNA synthesis in ataxia telangiectasia cells.
 ...
PMID:Inhibition and recovery of DNA synthesis after X-irradiation in radiosensitive mouse-cell mutants. 684 78

Replicon behavior in radiosensitive Ataxia telangiectasia (A-T) fibroblasts and mouse lymphoma L5178Y (LS) cells was studied by DNA fiber autoradiography. LS cells, irradiated at 13 Gy, showed a similar reduction in rate of DNA chain growth and initiation of replicons as did resistant (LR) cells. A progressive increase in the intensity of [3H]TdR labeling of many replicons was observed after irradiation in the LS cells, but not in LR cells. This indicated a reduced or absent endogenous dTTP supply after irradiation in the LS cells, implicating a defect in nucleoside precursor production. Irradiated normal human and A-T cells did not show this effect. After 2 Gy, the frequency of initiation of replicons into synthesis was temporarily reduced in the normal human but not in the A-T cells. After 20 Gy, the rate of DNA chain growth was preferentially reduced in the normal human cells, but an increase was observed in the A-T cells. This increased rate could be explained in terms of a normal supply of complexes involved in chain elongation being distributed over a reduced number of initiated replicon clusters in the A-T cells.
 ...
PMID:Differences in replicon behavior between X-irradiation-sensitive L5178Y mouse lymphoma cells and A-T fibroblasts using DNA fiber autoradiography. 685 82

We recently showed (Scott and Zampetti-Bosseler 1980) that X-ray sensitive mouse lymphoma cells sustain more chromosome damage, mitotic delay and spindle defects than X-ray resistant cells. We proposed that (a) chromosome aberrations contribute much more to lethality than spindle defects, and (b) that DNA lesions are less effectively repaired in the sensitive cells and give rise to more G2 mitotic delay and chromosome aberrations. Our present results on human fibroblasts with reported differential sensitivity to ionizing radiation (i.e. normal donors and patients with ataxia telangiectasia and retinoblastoma) support the first hypothesis since we observed a positive correlation between chromosome aberration frequencies and cell killing and no induced spindle defects. Our second hypothesis is however not substantiated since X-ray sensitive fibroblasts from the ataxia patient suffered less mitotic delay than cells from normal donors. A common lesion for mitotic delay and chromosome aberrations can still be assumed by adopting the hypothesis of Painter and Young (1981) that the defect in ataxia cells is not in repair but in a failure of DNA damage to initiate mitotic delay. In contrast to other reports, we found the retinoblastoma cells to be of normal radiation sensitivity (cell killing and aberration).
 ...
PMID:Cell death, chromosome damage and mitotic delay in normal human, ataxia telangiectasia and retinoblastoma fibroblasts after x-irradiation. 697 65

Stage I lymphocyte-predominant Hodgkin's disease was diagnosed in a 44-month-old girl. Although immune deficiency was suspected and IgA deficiency demonstrated, the diagnosis of an ataxia-telangiectasia (AT)-like syndrome was not confirmed until eight weeks later when results of studies on the radiosensitivity of cultured skin fibroblasts were available. The child had none of the usual physical stigmata of AT. Severe acute radiation damage followed the treatment of this child with standard doses of radiation therapy. Clinical, pathologic, and radiobiologic correlations are drawn. The diagnosis of a malignant lymphoma disorder in children under the age of five should alert clinicians to the possibility of immune deficiency and, even in the absence of classical physical signs, to AT in particular. Suggestions for the management of future similar cases are put forward.
 ...
PMID:The effects of radiation therapy for Hodgkin's disease in a child with ataxia telangiectasia: a clinical, biological and pathologic study. 709 26

We have examined the chromosomal radiosensitivities of an ionizing-radiation-and MMS-sensitive mutant (M10), and a UV- and 4NQO-sensitive mutant (Q31), isolated from mouse lymphoma L5178Y cells, with regard to killing effects. In the first mitoses after 100 R gamma-irradiations, it was found that M10 cells were highly radiosensitive in terms of chromosomal aberrations accompanying longer mitotic delay (3 h); the frequencies of both chromatid-type and chromosome-type aberrations were, respectively, about 7 and 4 times higher than that of wild-type L5178Y cells. Furthermore, chromatid exchanges, particularly triradials, isochromatid breaks with sister union, and chromatid gaps and breaks were markedly enhanced at G1 phase of M10 cells. In contrast, the chromosomal radiosensitivity of Q31 cells after 100 R irradiation was similar to that of L5178Y cells. On the other hand, spontaneous aberration frequencies (overall breaks per cell) of M10 and Q31 cells were, respectively, 5.1 and 2.2 times higher than that of wild-type L5178Y cells. The chromosomal hypersensitivity to gamma-rays in M10 cells is discussed in the light of knowledge obtained from ataxia telangiectasia cells.
 ...
PMID:Characteristics of gamma-ray-induced chromosomal aberrations in mutagen-sensitive mutants of L5178Y cells. 715 66

Within months of Roentgen's discovery of X rays, severe adverse effects were reported, but not well publicized. As a result, over the next two decades, fluoroscope operators suffered lethal skin carcinomas. Later, case reports appeared concerning leukemia in radiation workers, and infants born with severe mental retardation after their mothers had been given pelvic radiotherapy early in pregnancy. Fluoroscopy and radiotherapy for benign disorders continued to be used with abandon until authoritative reports were published on the adverse effects of ionizing radiation by the U.S. NAS-NRC and the UK MRC in 1956. Meanwhile, exposure to the atomic bombs in Japan had occurred and epidemics of delayed effects began to be recognized among the survivors: cataracts (1949), leukemia (1952) and severe mental retardation among newborn infants after intrauterine exposure (1952). No statistically significant excess of germ-cell genetic effects was detected by six clinical measurements (1956), the F1 mortality (1981), cytogenetic studies (1987) or biochemical genetic studies (1988). Somatic cell effects were revealed by long-lasting chromosomal aberrations in peripheral lymphocytes (1968), and somatic cell mutations were found at the glycophorin A locus in erythrocytes (1992). Molecular biology is a likely focus of new studies based on the function of the gene for ataxia telangiectasia (1995), a disorder in which children have severe, even lethal acute radiation reactions when given conventional doses of radiotherapy for lymphoma, to which they are prone. Also, obligate heterozygote female relatives can be studied for increased susceptibility to radiation-induced breast cancer, as suggested by clinical studies. The tumor registries in Hiroshima and Nagasaki now provide incidence data that show the extent of increases in eight common cancers and no increase in eight others (1994). The possibility of very late effects of A-bomb exposure is suggested by recent reports of increased frequencies of hyperparathyroidism, parathyroid cancers and certain causes of death other than cancer.
 ...
PMID:Delayed effects of external radiation exposure: a brief history. 748 Jun 42


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