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

The expression of three EBV open reading frames (ORF's), BBRF3, BILF1 and BMRF2 in Epstein-Barr virus (EBV)-transformed B lymphocytes from ataxia-telangiectasia (A-T) homozygotes, was studied. A-T is a human recessive genetic disorder which predisposes homozygotes and heterozygotes to cancer. Computer analysis (Robson-Garnier) was used to study the secondary structure of EBV ORF's. Three ORF's (BBRF3, BILF1 and BMRF2) found by the Kyte and Doolittle computer method to have multiple hydrophobic domains in the putative polypeptides were selected, and the polypeptides were selected, and the respective cloned EBV DNA fragments were used as probes to detect mRNA in the normal and L-6 A-T lines that was not present in the L-15 A-T line. The probe for BILF1 detected two mRNA species (3.7 and 2.0 kb) in the normal lymphoblastoid and A-T L-6 lines, while only the 3.7 kb mRNA was expressed in the A-T L-15 lymphoblasts. The probe for BMRF2 detected two mRNA species (3.7 and 2.1 kb) in the EBV-transformed normal lymphoblasts and in one A-T line (L6). The BMRF2 mRNAs were not detected in the other A-T line (L-15). This study indicated that regulation of the three EBV genes in two EBV-transformed A-T lymphoblastoid lines, differs from that in the EBV-transformed normal lymphoblastoid line. In the A-T line L-6, the three EBV genes were expressed as in EBV-transformed lymphoblastoid cells originating from a normal donor (L-21) and in the P3HR1 Burkitt's lymphoma cell line. The A-T line L-15 differed from L-6 and the other cell lines in that it expressed only one (3.7 kb) RNA species from BILF1 ORF, while ORFs BBRF3 and BMRF2 were not expressed. Since A-T L-15 line contains EBV DNA genomes, and EBV VCA is not present in these cells prior to or after TPA treatment, it is suggested that EBV gene expression is regulated by these A-T lymphoblastoid cells in a manner different from that which operates in other EBV transformed cell lines.
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PMID:Differential expression of Epstein-Barr virus (EBV) genes BBRF3, BILF1, and BMRF2 in EBV-transformed lymphoblastoid lines from ataxia-telangiectasia patients. 284 95

We have provided experimental evidence in favour of the hypothesis that carcinogenesis is triggered by at least two chromosomal events, which must occur in a single diploid somatic cell in a specific time sequence: (i) specific recessive mutational or epigenetic chromosomal change(s) resulting in a heterozygous (m/+), latently premalignant state (initiation); this must be followed by (ii) a chromosomal rearrangement involving the affected locus, and leading to homozygosity (m/m) or hemizygosity (m/o), and subsequent expression of the recessive malignant character (promotion). The complete carcinogen, MNNG, induced mutations (6-thioguanine-resistance), chromosomal rearrangements and SCEs in V79 Chinese hamster cells. TPA, a potent tumour promoter, induced only SCEs and specific chromosomal effects. Antipain, a protease inhibitor and a known inhibitor of both carcinogenesis and tumour promotion, inhibited only the MMNG-induced chromosomal rearrangements (but not mutagenesis and SCEs) and the TPA-induced chromosomal events. These results suggest that (1) both TPA-induced and MNNG-induced chromosomal rearrangements are caused by the activation or induction of mitotic recombination and hence appear to be preventable; (2) chromosomal rearrangement is a rate-limiting step in carcinogenesis; and (3) if mutagenesis is involved in carcinogenesis, it is probably not sufficient. The existence of the human cancer-prone syndromes, Bloom's, Fanconi's anaemia and ataxia telangiectasia, which involve spontaneous chromosomal rearrangements analogous to those induced by carcinogens in normal cells, strongly supports our hypothesis that carcinogenesis involves two chromosomal events. We discuss the implications of this work to carcinogenicity testing and cancer prevention strategies.
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PMID:Chromosomal events in carcinogenic initiation and promotion: implications for carcinogenicity testing and cancer prevention strategies. 700 84

Angiotensin-II (AII), which stimulates steroidogenesis in bovine adrenocortical (BAC) cells through the phosphoinositides pathway, activates p42-p44 mitogen-activated protein kinases (MAPKs) after 5 min of treatment (EC50 = 0.1 nM). This activation is 1) completely inhibited by the AII receptor AT1 subtype antagonist Dup 753 (10 microM), but unaffected by the AT2 antagonist PD 123177; 2) not reproduced by the AT2 agonist CGP 42112A; 3) insensitive to pretreatment with pertussis toxin; and 4) abolished by a 48-h preexposure of the cells to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA; 1 microM), which down-regulates protein kinase-C activity. Fibroblast growth factor-2, a potent mitogen for BAC cells, which acts through its tyrosine kinase receptor, also activates MAPK (EC50 = 0.3 in a TPA-insensitive manner, while exhibiting no detectable effect on BAC cell steroidogenesis. In contrast, ACTH, which stimulates steroidogenesis via cAMP and inhibits BAC cell proliferation, does not stimulate MAPK. Indeed, ACTH completely blocks (IC50 = 0.01 nM) the stimulation of MAPK by AII, fibroblast growth factor-2, or TPA. Therefore, bovine adrenocortical cells provide an example of positive and negative hormonal regulation of MAPK activity through a cross-talk between the inositide-, cAMP-, and growth factor-activated tyrosine kinase pathways.
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PMID:Hormonal regulation of mitogen-activated protein kinase activity in bovine adrenocortical cells: cross-talk between phosphoinositides, adenosine 3',5'-monophosphate, and tyrosine kinase receptor pathways. 786 5

The goal of our current research was to investigate the antioxidative effects of methanolic extracts from different parts of adlay seed and their antiproliferative activity in malignant human cells. The methanolic extracts from different parts of adlay seeds were from the hull (AHM), testa (ATM), bran (ABM), and polished adlay (PAM). AHM exhibited greater capacity to scavenge superoxide anion radicals in the PMS-NADH system than ATM, ABM, or PAM. The scavenging capacities of AHM and ATM on hydrogen peroxides were about 20% at a dose of 250 microg/mL. Using the method of deoxyribose degradation to assess damage caused by hydroxyl radicals, AHM was found to inhibit damage in deoxyribose at a higher concentration. However, ATM, ABM, and PAM exhibited prooxidative activity at the same concentration. The inhibitory effect on enzymatic oxidation of xanthine to uric acid was found to follow the order AHM > ATM =. ABM. However, PAM was inactive. All test samples were positive for inhibition of TPA-induced free radical formation on neutrophil-like leukocytes and were found to follow the order AHM > ATM > ABM > PAM. When human histolytic lymphoma U937 monocytic cells were exposed to tert-butyl hydroperoxide, AHM protected the cells against the cytotoxicity caused by tert-butyl hydroperoxide. In addition, AHM exhibited antiproliferative activity against human histolytic lymphoma U937 monocytic cells in a dose-dependent manner. The antiproliferative properties of AHM appear to be attributable to its induction of apoptotic cell death as determined by flow cytometry. These results show that AHM displays multiple antioxidant effects and induces apoptosis of malignant human cells.
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PMID:Antagonism of free-radical-induced damage of adlay seed and its antiproliferative effect in human histolytic lymphoma U937 monocytic cells. 1131 97

The marmoset adrenal is interesting as it is developmentally similar to humans and other primates, but in adulthood 17,20-lyase activity is very low. One possible explanation is an altered regulation of P450c17 expression by AT1-R. We investigated the expression and zonal distribution of the AT1-R in marmoset adrenal glands and adrenocortical cells in culture since it is known that AT1-R is a regulator of P450c17 expression and activity. AT1-R was expressed strongly in the ZG and to diminishing degrees through the remainder of the cortex. There was negative expression in a putative ZI. Dispersed adrenocortical cells retained AT1-R protein as detected by ICC. Cells cultured for several days and treated in serum-free media for 48 h maintained AT1-R expression, as measured by western. However, at that 48 h time point, treatment with Forsk, AII, TPA, or the combination of A+F or T+F did not appear to effect AT1-R expression. We conclude that marmoset adrenals express AT1-R similarly to humans and other higher mammals, adrenocortical cells retain AT1-R expression in culture, and consistent with other adrenal cell culture models, AT1-R expression is not lost in response to agonists long term.
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PMID:Expression of AT1-R in marmoset whole adrenal glands and adrenocortical cells in culture. 1566 21

Interphase fluorescent in situ hybridization on unstimulated peripheral blood mononuclear cells (I-FISH-PBMC) is used to detect chromosomal abnormalities such as 11q-, 13q-, 17p-, and trisomy 12 in chronic lymphocytic leukemia (CLL). A total of 56 samples from 49 patients with CLL were studied using commercially available probes for chromosome regions 11q22.3 (ATM), 13q14 (13S272), 17p13 (p53) and 12 centromere (D12Z3). We compared the results obtained with I-FISH-PBMC and those with I-FISH on TPA (tetradecanoylphorbol acetate; phorbol-12-myristate-13-acetate) stimulated peripheral blood cells (I-FISH-TPA) used for conventional cytogenetics, to evaluate the usefulness of I-FISH-TPA. The proportion of abnormal nuclei obtained with the I-FISH-TPA was higher than that found with I-FISH-PBMC (P < 0.001). Consequently, 15 cases with a negative or borderline result with I-FISH-PBMC became positive with I-FISH-TPA for 11q- (n = 2), 13q- (n = 9), and trisomy 12 (n = 4). In all but one of these, chromosomal abnormalities were confirmed by either metaphase FISH or conventional G-banding. Detection of cytogenetic aberrations thus increased from 51% with I-FISH-PBMC to 78% with I-FISH-TPA. Notably, all 15 of the cases that reached the diagnostic thresholds for 11q-, 13q-, and trisomy 12 had a slight lymphocytosis. An absolute lymphocyte count <8.7 x 10(9)/L was found to be the critical threshold (P = 0.037) below which I-FISH-TPA rather than I-FISH-PBMC should be performed. Not only could I-FISH-TPA detect a higher proportion of abnormal interphase nuclei, but it could also identify abnormal CLL cases that might be overlooked with use of I-FISH-PBMC, especially those with low absolute lymphocyte counts. I-FISH-TPA is thus a reliable technique for clinical diagnostics in CLL.
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PMID:Detection of chromosomal abnormalities in chronic lymphocytic leukemia increased by interphase fluorescence in situ hybridization in tetradecanoylphorbol acetate-stimulated peripheral blood cells. 1749 59

This study aimed to determine which culture method would yield the highest culture success rate, mitotic index, banding resolution, and abnormality rate in investigation of patients with chronic lymphocytic leukemia (CLL). A range of culture techniques for conventional cytogenetic (CC) analyses was compared: 24-hour unstimulated, 72 hours incubation with additional fetal calf serum, 72 hours stimulation with interleukin 4, 72 hours stimulation with lipopolysaccharide (LPS), 72 hours stimulation with TPA (12-O-tetradecanoylphorbol 13-acetate), and 72 hours stimulation with CpG-oligonucleotide DSP30 + Interleukin-2 (IL-2). CC abnormality rates were also compared to fluorescence in situ hybridization (FISH) results using probes for CLL (LSI D13S319/13q34/CEP 12: LSI ATM/p53). Forty-five samples from 24 patients (consisting of 11 newly diagnosed and 13 previously diagnosed patients) were included. For CC, a 100.0% culture success rate was achieved (n = 45) by means of an EDTA (ethylenediaminetetraacetic acid) peripheral blood sample with an associated 62.5% CC abnormality rate (n = 24). FISH detected an abnormality rate of 75.0% (n = 24). The combined CC and FISH abnormality rate was 87.5% (n = 24). This study demonstrates that CC that uses TPA and DSP30 + IL-2 on EDTA peripheral blood is effective in the investigation of CLL and may be used as a supplement to FISH studies.
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PMID:Cytogenetic investigations of chronic lymphocytic leukemia. 2036 31

Ataxia telangiectasia (AT), an autosomal recessive disorder with a high incidence of lymphoreticular malignancies including Epstein-Barr virus (EBV)-induced lymphoproliferative disorders (LPD), was investigated to assess the susceptibility to EBV infection and oncogenesis. When the patients' lymphocytes were infected with B95-8 EBV, there was a tendency toward an enhanced growth in semisolid agar, as compared with the healthy donor counterparts. Among the preparations tested, from 14 patients, 2 cell lines showed extremely high colony forming efficiency. The lymphocytes from patients with AT did not contain a large number of EBV target cells, as determined by the maximum frequency of EBV-determined nuclear antigen (EBNA) induction prior to cellular DNA synthesis. Fourteen different lymphoblastoid cell lines derived from the 14 patients with AT were then examined for their EBV inducibility and superinfectibility. By treatment with 12-O-tetradecanoyl-phorbol-13-acetate TPA) and culturing at a lower temperature of 33-degrees-C, early antigen (EA) induction occurred approximately 6-fold and 5-fold higher, respectively, as compared with the lymphoblastoid cell lines derived from healthy controls. Viral capsid antigen (VCA) was also induced significantly by TPA or culturing at lower temperature in the lines from patients with AT, but only slightly in the control counterparts. When the lymphoblastoid cells from patients with AT were exposed to P3HR-1 EBV, EA and VCA syntheses were approximately 6- and 12-fold higher, respectively, than those in the cells derived from the healthy controls. This evidence suggested B lymphocytes of patients with AT were highly susceptible to EBV infection and possibly linked to the development of EBV-induced LPD.
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PMID:Epstein-barr-virus hypersensitivity of lymphocytes from patients with ataxia-telangiectasia. 2157 65