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

The clinical and pathological features are described in a child with ataxia-telangiectasia, complicated by fatal disseminated herpes simplex virus infection. Herpes simplex virus was isolated from the patient's blood, and the histopathological findings in the skin, liver and adrenals were consistent with herpes simplex virus infection. The patient had a combined immune deficiency state, as a part of the ataxia-telangiectasia syndrome. She had imparied cellular immune response to herpes simplex virus and developed no antibodies against the virus. To our knowledge, this is the first fatal case of disseminated herpes simplex virus infection in ataxiatelangiectasia.
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PMID:Disseminated Herpes simplex virus infection in ataxia-telangiectasia. 69 12

We used a shuttle vector based on the Epstein-Barr virus origin of plasmid replication (oriP) to determine the types of mutations induced by depurination in human cells. Plasmid DNA was incubated at pH 2 at 40 degrees C for various times to induce up to 20 apurinic (AP) sites per 9.7-kb plasmid and electroporated into lymphoblastoid cells derived from either a normal individual or an ataxia telangiectasia patient. After replication of the vector in the human cells, plasmid DNA was isolated and analyzed for mutations induced in the plasmid-encoded herpes simplex virus type 1-thymidine kinase gene. Both the frequencies and types of mutations induced by depurination were essentially identical for normal and ataxia telangiectasia cells. The mutant frequency at 20 AP sites/plasmid was 10-fold to 13-fold greater than that observed for untreated DNA. Deletion and frameshift events accounted for 46-55% of the mutants induced by depurination. The induced deletions were relatively small (median size, 100-150 bp) and characterized by short (1-5 bp) regions of sequence homology at the endpoints. These mutations and the frameshifts, a majority of which occurred in runs of identical nucleotides, are consistent with a model involving AP-site-induced template dislocation during DNA synthesis. A broad spectrum of base-substitution mutations, which accounted for 19-36% of the induced mutants, was observed. The apparent preference for insertion opposite AP sites in human cells was G (43-55%) greater than A approximately C (18-21%) greater than T (9-14%). Our results in human cells contrast markedly with those published previously for the mutational specificity of AP sites in Escherichia coli, in which a large majority of the mutants resulted from insertion of an A opposite the abasic site.
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PMID:Mutagenesis by apurinic sites in normal and ataxia telangiectasia human lymphoblastoid cells. 150 43

Immunochemical study of blood sera from mice immunized with rabbit immunoglobulins (AT1) to herpes simplex virus type I (HSV-I) detected antiidiotypic antibodies AT2 in five of them (antiID). The affinity-purified antiID were shown to induce in syngeneic mice production of antibody (AT3) interacting with HSV-I antigen. In vitro, antiID (AT3) were shown to neutralize the virus activity. Analysis of the results suggests that the antiID imitate the antigenic properties of HSV-I and can induce specific immune response.
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PMID:[Anti-idiotypic antibodies to the herpes simplex type-1 virus neutralize the virus' infectious activity]. 166 20

Herpes simplex virus type 1 (HSV-1) subgenomic sequences from 0.743 to 0.782 map units have been molecularly cloned as plasmid AT1 and shown to inhibit stable DNA-mediated gene transformation of Ltk- cells with the HSV-1 thymidine kinase (tk) gene. Here it is shown that AT1 also inhibits transient gene expression. Expression from the chloramphenicol acetyltransferase (CAT) gene under the control of either the HSV-1 tk gene or the Rous sarcoma virus (RSV) promoter was inhibited when cotransfected into Ltk- and CV-1 cells with equimolar amounts of AT1. AT1 was subcloned as three overlapping plasmids called AT1a, alpha 27 and AT1b. The alpha 27 plasmid encodes the HSV-1 immediate early gene, alpha 27; AT1a possesses sequences that specify an open reading frame in HSV-1 strain KOS used in these studies, although the significance of this open reading frame is unknown; AT1b possesses the sequences for UL55 and UL56, also genes for which no function has been reported. No single subclone or pair of subclones demonstrated significant inhibition of transient gene expression. Cotransfection of all three subclones did result in inhibition of RSV-CAT gene expression, suggesting that information from each subclone is necessary. One of the three subclones, alpha 27, contains the HSV-1 immediate early gene, alpha 27, so the possibility that other immediate early genes could substitute for alpha 27 was tested. Inhibition of RSV-CAT gene expression was also achieved by cotransfection of AT1a and AT1b with either an alpha 0- or alpha 4-containing plasmid, suggesting that the role of the alpha 27-containing plasmid can be replaced by other alpha genes with trans-regulating capability. Finally, AT1a and AT1b linker insertion mutants have been constructed and used to study the role these plasmids play in mediating inhibition. These results suggest that AT1 contains HSV-1 functions in addition to that of alpha 27 that interfere with gene expression.
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PMID:Inhibition of transient gene expression with plasmids encoding herpes simplex virus type 1 UL55 and alpha genes. 184 42

Radiosensitive fibroblasts from patients with ataxia telangiectasia (AT) were studied for their proficiency in two putative eukaryotic SOS-like responses, namely the enhanced reactivation (ER) and enhanced mutagenesis of damaged viruses infecting pre-irradiated versus mock-treated cells. A previous report indicated that, unlike normal human cells, a line of AT fibroblasts (AT5BIVA) could not be induced to express ER of damaged parvovirus H-1, a single-stranded DNA virus, by UV- or X-irradiation. In the present study, AT5BIVA fibroblasts were also distinguished from normal cells by the inability of the former to achieve enhanced mutagenesis of damaged H-1 virus upon cell UV-irradiation. In contrast, dose-response and time-course experiments revealed normal levels of ER of Herpes simplex virus 1, a double-stranded DNA virus, in X- or UV-irradiated AT5BIVA cells. Taken together, these data point to a possible deficiency of AT cells in a conditioned mutagenic process that contributes to a greater extent to the recovery of damaged single-stranded than double-stranded DNA. Such a defect may concern the replication of damaged DNA or the generation of signals promoting the latter process and may be related to the lack of radiation-induced delay that is typical of AT cell DNA synthesis.
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PMID:Impaired recovery and mutagenic SOS-like responses in ataxia telangiectasia cells. 255 Jul 22

Herpes Simplex Virus (HSV-1) was used to probe the expression of enhanced reactivation (ER) in cells from patients with ataxia telangiectasia (AT). The survival of UV-irradiated HSV-1 was increased as a result of UV- or X-preirradiation of both AT and normal cells. This result contrasts with our previous observation showing that contrary to normal cells AT cells are deficient for ER of a single-stranded DNA parvovirus. A difference between the molecular processes underlying ER of single- and double-stranded DNA viruses might explain these results.
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PMID:[Cells of patients with ataxia telangiectasia show a normal capacity of radio-induced reactivation of damaged HSV-1 virus]. 283 2

To date, the acquired immunodeficiency syndrome (AIDS) has been identified in over 50 children in the US, including those with associated hemophilia, high-risk environmental factors (Haitian background, parental intravenous drug abuse, or prostitution), and blood transfusions. The evaluation of an infant or young child in whom AIDS is suspected requires exclusion of congenital disorders of immune function. A specific test is not currently available, but inclusion criteria for childhood AIDS have been developed. The diseases accepted as indicative of underlying cellular immunodeficiency children are the same as those used in defining AIDS in adults, with the exclusion of congenital infections such as toxoplasmosis or herpes simplex virus infection in the 1st month of life or cytomegalovirus infection in the 1st 6 months of life. Specific conditions that must be excluded in children are primary immunodeficiency diseases (e.g., DiGeorge syndrome, Wiskott-Aldrich syndrome, ataxia-telangiectasia, neutrophil function abnormality) and secondary immuno-deficiency associated with immunosuppressive therapy, lymphoreticular malignancy, or starvation. Almost all young children with AIDS have hepatosplenomegaly, interstitial pneumonitis, and poor growth. The average age of 36 US child AIDS victims studied in detail was 5 months at presentation with findings suggestive of severe immunodeficiency. Mucocutaneous candidiasis was present in 75% of these 36 children, and Pneumocystis carinii and cytomegalovirus were each isolated from 30% of cases. Normal T4:T8 ratios occur in about 15% of pediatric AIDS cases. Laboratory evidence of polyclonal hypergammaglobulinemia generally supports the AIDS diagnosis. Recurrent infection and malnutrition are major problems in the clinical management of child AIDS patients.
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PMID:Acquired immune deficiency syndrome in childhood. 298 8

Recombination frequencies for two sets of genetic markers of herpes simplex virus were determined in various host cells with and without ultraviolet irradiation of the virus. UV irradiation increased the recombination frequency in all the cell types studied in direct proportion to the unrepaired lethal damage. In human skin fibroblasts derived from a patient with xeroderma pigmentosum (XP) of complementation group A, a given dose of UV stimulated recombination more than that in fibroblasts from normal individuals. On the other hand, UV stimulation of HSV recombination was slightly less than normal in fibroblasts derived from a patient with a variant form XP and from an ataxia telangiectasia patient. Caffeine, an agent known to inhibit repair of UV damage, reduced recombination in most of the cell types studied and did not suppress the UV-induced increase in recombination. These findings suggest that for virus DNA with the same number of unrepaired UV-lesions, each of the tested cell types promoted HSV-recombination to an equivalent extent.
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PMID:Genetic recombination of herpes simplex virus, the role of the host cell and UV-irradiation of the virus. 624 34

Human skin fibroblasts derived from a healthy individual and from a child with the genetic disorder ataxia telangiectasia were infected with herpes simplex virus type 1 (HSV-1). The virus infection did not affect the synthesis of procollagen but inhibited its release from the cells.
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PMID:HSV-1 infection inhibits procollagen and protein secretion from normal and ataxia telangiectasia cultured skin fibroblasts. 625 35

Peripheral blood leukocytes (PBL) isolated from five patients with ataxia telangiectasia (AT) proved more difficult to transform following addition of exogenous Epstein-Barr virus than PBL isolated from AT heterozygotes or normal adults. PBL isolated from one AT patient transformed within the range expected for normal PBL. Once established in culture, the resulting lymphoblastoid cell lines (LCLs) were immortal and, though they grew slower than normal control LCLs, provided useful material for studying cellular phenotypes associated with AT lymphoid cell lines. All the resulting LCLs established from ataxia were more sensitive to X-irradiation than were LCLs established from controls as measured by colony formation in microtiter plates. Furthermore, X-ray-induced inhibition of semiconservative DNA synthesis in ataxia LCLs was less than that seen in normal LCLs. These results are in agreement with those obtained using cultured AT fibroblasts, indicating that in vitro transformation by exogenously added Epstein-Barr virus does not alter the phenotype of the ataxia cell as measured by these two parameters. However, no deficiency in X-ray-induced excision repair of DNA was demonstrable in LCLs established from four AT patients. Nor was there a deficiency in AT LCL host cell reactivation of herpes simplex virus X-irradiated under anoxic conditions. Taken together, these data point toward a defect in ataxia lymphoblasts other than repair enzyme(s) per se, one possibly associated with chromosomal structure, function, or modification.
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PMID:Transformation and repair replication in lymphocytes from ataxia telangiectasia. 630 13


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