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 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The occurrence of malignant proliferative diseases in patients with primary immune deficiencies is far more frequent than in normal individuals. These malignant proliferations may supervent in all types of immune deficiencies but are more frequent in the Wiskott-Aldrich syndrom, ataxia telangiectasia and variable immunodeficiencies. The incidence of malignant lymphomas is striking since they account for two thirds of the malignancies. This fact does not support the hypothesis of a faulty immunological surveillance and would be in accordance with the hypothesis of a direct role of antigenic stimulations occurring on an immune system devoid of regulatory mechanisms.
Bull Cancer 1978
PMID:[Primary immunodeficiencies and malignant proliferations (author's transl)]. 66 78

We observed two sisters with ataxia telangiectasia, one of whom developed an atypical subacute lymphocytic leukemia characterized by atypical lymphocytes and absence of palpable lymphadenopathy or hepatosplenomegaly. The lack of organomegaly in this patient may have been due to the underlying ataxia telangiectasia, which was associated with lymphoid hypoplasia. Cytogenetic studies showed a marker chromosome 14 [t(14q11:14q34)] in both patients. The sister with leukemia had other complex chromosomal aberrations in addition to the marker chromosome 14 that were stable for more than 14 mo before the patient's death from complicating infection. The development of atypical T cell leukemia has not been previously described in ataxia telangiectasia. This case further illustrates the interesting interrelationships amoung immunosuppressed states, development of lymphoid malignancy, and an emerging pattern of a propensity to chromosome 14 abnormalities in various lymphoid malignancies.
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PMID:Atypical lymphoid leukemia in ataxia telangiectasia. 69 87

Excision repair of damage due to ultraviolet radiation, N-acetoxy-2-acetyl-aminofluorene and a combination of both agents was studied in normal human fibroblasts and various cells from cancer prone patients (ataxia telangiectasia, Fanconi's anemia, Cockayne syndrome and Bloom's syndrome). Three methods giving similar results were used: unscheduled DNA synthesis by radioautography, photolysis of bromodeoxyuridine incorporated into parental DNA during repari, and loss of sites sensitive to an ultraviolet endonuclease. All cell lines were proficient in repair of ultraviolet and acetoxy acetylaminofluorene damage and at saturation doses of both agents repair was additive. We interpret these data as indicating that the rate limiting step in excision repair of ultraviolet and acetoxy acetylaminofluorene is different and that there are different enzyme(s) working on incision of both types of damages.
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PMID:Excision repair in ataxia telangiectasia, Fanconi's anemia, Cockayne syndrome, and Bloom's syndrome after treatment with ultraviolet radiation and N-acetoxy-2-acetylaminofluorene. 73 87

An assay has been developed to measure the ability of human lymphocytes to repair damage to DNA. In this assay, purified human lymphocytes are exposed to graded doses of radiation and then stimulated with phytohemagglutinin to undergo DNA replication. The rate of incorporation of thymidine in irradiated lymphocytes during the second and subsequent rounds of DNA replication is taken to be indicative of the ability of the cells to repair damage to DNA. In lymphocytes from normal individuals, X-irradiation with doses of 100 to 800 rads was found to inhibit phytohemagglutinin-stimulated thymidine incorporation proportionally to the dose of radiation without curtailing the induction of DNA polymerase. The response to phytohemagglutinin of lymphocytes from a patient with xeroderma pigmentosum after exposure to graded doses of X-irradiation was found to be similar to that of the normal controls, whereas the response after ultraviolet irradiation was markedly impaired. In contrast, lymphocytes from patients with ataxia telangiectasia were hypersensitive to X-irradiation. The data on these clinical syndromes support the idea that this assay measures DNA repair and indicates the feasibility of using this method for screening individuals for genetic deficits in DNA repair.
Cancer Res 1977 Oct
PMID:Screening for deficits in DNA repair by the response of irradiated human lymphocytes to phytohemagglutinin. 90 9

Cellular and humoral immunity, and lymphoid organ pathology, have been investigated in 10 institutionalized patients with tuberous sclerosis and 10 institutionalized matched controls without the disease. Type and incidence of infections and tumours were reviewed for each group, as was current medication. Elevated serum IgM levels were found in the patients with tuberous sclerosis, but no immunological deficiency of either cellular of humoral immunity was found, nor was there a difference in infection between the groups. Only patients with tuberous sclerosis had evidence of neoplasia. No morphological or histological abnormalities of lymph nodes, spleen or thymus were present. Explanations for the difference between tuberous sclerosis and ataxia telangiectasia are discussed, together with the effect of immuno-surveillance on the development of malignancy.
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PMID:Immunological status in tuberous sclerosis. 95 13

The clinical and radiographic features of twenty-two cases of ataxia-telangiectasia are reviewed. Severity of pulmonary manifestations tended to correlate closely with severity of immunodeficiency. Observations are made upon the problem of intercurrent malignancy in ataxia-telangiectasia. The radiographic studies of patients seen at the National Institutes of Health with A-T were reviewed retrospectively and correlated with degrees of immunodeficiency determined clinically. Three fairly distinct groups with high, intermediate and low incidence of sinopulmonary disease were found. Comment is made on the problem of increased malignancy in A-T and possible clues in the detection by the radiologist.
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PMID:Ataxia-telangiectasia. 95 65

Ataxia-telangiectasia is a rare genetic disorder associated with immune deficiency, chromosome instability, and a predisposition to lymphoid malignancy. We have detected chromosomally anomalous clones of lymphocytes in eight patients with this disorder. Chromosome banding disclosed that the clones are consistently marked by structural rearrangement of the long arm (q) of chromosome 14. A translocation involving 14q was found in clones obtained from seven of the eight patients whereas a ring 14 chromosome was found in a clone obtained from the other. These findings as well as data obtained by others for patients with ataxia-telangiectasia suggest that structural rearrangement of 14q is the initial chromosomal change in lymphocyte clones of patients with this disorder. Chromosomes of lymphocytes from one of the patients were studied before and after the onset of chronic lymphocytic leukemia. Before leukemia was diagnosed, the patient had a lymphocyte clone with a 14q translocation. This clone appears to have given rise to the leukemic cells. We hypothesize that structural rearrangement of 14q is directly related to abnormal growth of lymphocytes and that it may be a step toward the development of lymphoid malignancies. Increasing evidence, provided by others, for the nonrandom involvement of 14q in African-type Burkitt's lymphoma and other lymphoid neoplasms further strengthens this hypothesis.
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PMID:Somatic rearrangement of chromosome 14 in human lymphocytes. 105 13

Although an isolated clinical case report was published in 1926 and another in 1941, ataxia-telangiectasia (A-T) was not established as a distinct entity until 1957, when it was first delineated clinicopathologically. Susceptibility to sinopulmonary infection was identified as the main cause of death and as the third major component of the syndrome; its heredofamilial nature was documented, and it was designated "ataxia-telangiectasia." In a later review of 101 published cases, lymphoreticular malignancy emerged as the second most frequent cause of death. Although the thymus was found to be absent in the first reported autopsy in 1957 and the serum IgA deficiency was first recorded in 1961, A-T was not established as an immunodeficiency disease until 1963. Thymic abnormality and dysgammaglobulinemia explain the 2 main causes of death, sinopulmonary and neoplastic, but the immunodeficiency is probably not the central defect. It does not appear to explain either of the 2 main clinical diagnostic keys, the ataxia and the telangiectasia, or any of the other seemingly unrealted multisystemic facets of this complex disorder. Some of our most provocative long-term clinical observations and recent pathologic findings in our series of 9 autopsies are discussed.
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PMID:Ataxia-telangiectasia: some historic, clinical and pathologic observations. 109 82

Although neoplasms are unusually frequent in patients with ataxia-telangiectasia, the occurrence of primary tumors of the ovary in such patients is exceedingly rare. This report describes a 17-year-old phenotypic female with ataxia-telangiectasia, who was found to harbor an ovarian gonadoblastoma and a contralateral dysgerminoma. The latter tumor has occurred in only one other patient with ataxia-telangiectasia, while an association with gonadoblastoma has never been documented previously. Additional unusual features rarely encountered in patients with gonadoblastoma included origin of the tumor within a histologically proven ovary, and a 46,XX karyotype. The possibility that the dysgerminoma also arose from a gonadoblastoma is discussed.
Cancer 1975 Nov
PMID:Ataxia-telangiectasia with ovarian gonadoblastoma and contralateral dysgerminoma. 119 68

Ataxia-telangiectasia (A-T) is an autosomal recessive syndrome associated with a greatly increased incidence of malignant neoplasms in homozygous affected individuals. Heterozygotes for the gene for A-T are thought to comprise about 1% of the general population and, therefore, it is important to know whether this gene also predisposes the heterozygous carrier to cancers. Heterozygous carriers of this gene are common among the close relatives of patients with A-T, although individual carriers cannot be identified by any clinical criterion or laboratory test. For this reason, we compared the incidence of death from malignant neoplasms in 2 families of patients with A-T to that expected in a random sample of the general population. There were 59 deaths from malignant neoplasms in relatives dying before age 75, compared to 42.6 expected (p less than 0.02). For A-T heterozygotes younger than age 45, the risk of dying from a malignant neoplasm was estimated to be greater than 5 times the risk for the general population. A-T heterozygotes may comprise more than 5% of all persons dying from a cancer before age 45. The incidence of ovarian, gastric, and biliary system carcinomas and of leukemia and lymphoma was increased in these A-T families. Other neoplasms that may be associated with this gene in heterozygotes include pancreatic, basal cell, colonic, breast, and cervical carcinomas.
Cancer Res 1976 Jan
PMID:Malignant neoplasms in the families of patients with ataxia-telangiectasia. 124


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