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291.
In ovarian neoplasms, BRAF, but not KRAS, mutations are restricted to low-grade serous tumours 总被引:7,自引:0,他引:7
Sieben NL Macropoulos P Roemen GM Kolkman-Uljee SM Jan Fleuren G Houmadi R Diss T Warren B Al Adnani M De Goeij AP Krausz T Flanagan AM 《The Journal of pathology》2004,202(3):336-340
Genes of the RAF family, which mediate cellular responses to growth signals, encode kinases that are regulated by RAS and participate in the RAS/RAF/MEK/ERK/MAP-kinase pathway. Activating mutations in BRAF have recently been identified in melanomas, colorectal cancers, and thyroid and ovarian tumours. In the present study, an extensive characterization of BRAF and KRAS mutations has been performed in 264 epithelial and non-epithelial ovarian neoplasms. The epithelial tumours ranged from adenomas and borderline neoplasms to invasive carcinomas including serous, mucinous, clear cell, and endometrioid lesions. It is shown that BRAF mutations in ovarian tumours occur exclusively in low-grade serous neoplasms (33 of 91, 36%); these included serous borderline tumours (typical and micropapillary variants), an invasive micropapillary carcinoma and a psammocarcinoma. KRAS mutations were identified in 26 of 91 (29.5%) low-grade serous tumours, 7 of 49 (12%) high-grade serous carcinomas, 2 of 6 mucinous adenomas, 22 of 28 mucinous borderline tumours, and 10 of 18 mucinous carcinomas. Of note, two serous borderline tumours were found to harbour both BRAF and KRAS mutations. The finding that at least 60% of serous borderline tumours harbour mutations in two members of the ERK-MAP-kinase pathway (BRAF 36%, KRAS 30%) compared with 12% of high-grade serous carcinomas (BRAF 0%, KRAS 12%) indicates that the majority of serous borderline tumours do not progress to serous carcinomas. Furthermore, no BRAF mutations were detected in the other 173 ovarian tumours in this study. 相似文献
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John P. Hatch Patricia J. Moore Steve Borcherding Margaret Cyr-Provost Nashaat N. Boutros Ermias Seleshi 《Journal of behavioral medicine》1992,15(1):89-112
Thirty-four subjects meeting diagnostic criteria for episodic tension-type headache and 42 who rarely experienced headaches participated in two laboratory sessions in which cephalic electromyographic (EMG) activity, electrodermal activity, heart rate, and finger temperature were recorded. Subjects performed relaxation, choice reaction time, psychomotor tracking, voluntary muscle contraction, and cold pressor tasks. Headache subjects showed significantly greater EMG activity than controls during baseline and stressful task performance. During relaxation, both groups reduced EMG activity from baseline levels, and there was no significant difference in EMG level between the groups during relaxation. Headache subjects reported higher levels of subjective anxiety, depression, anger, and stress than controls. Headache subjects also reported higher levels of pain than controls, and headache subjects reported greater pain during stressful task performance relative to baseline and recovery periods.This research was supported by NIH Grant R01-NS-25114. 相似文献
294.
Allcock RJ Windsor L Gut IG Kucharzak R Sobre L Lechner D Garnier JG Baltic S Christiansen FT Price P 《Human mutation》2004,24(6):517-525
The region spanning the tumor necrosis factor (TNF) cluster in the human major histocompatibility complex (MHC) has been implicated in susceptibility to numerous immunopathological diseases, including type 1 diabetes mellitus and rheumatoid arthritis. However, strong linkage disequilibrium across the MHC has hampered the identification of the precise genes involved. In addition, the observation of "blocks" of DNA in the MHC within which recombination is very rare, limits the resolution that may be obtained by genotyping individual SNPs. Hence a greater understanding of the haplotypes of the block spanning the TNF cluster is necessary. To this end, we genotyped 32 human leukocyte antigen (HLA)-homozygous workshop cell lines and 300 healthy control samples for 19 coding and promoter region SNPs spanning 45 kb in the central MHC near the TNF genes. The workshop cell lines defined 11 SNP haplotypes that account for approximately 80% of the haplotypes observed in the 300 control individuals. Using the control individuals, we defined a further six haplotypes that account for an additional 10% of donors. We show that the 17 haplotypes of the "TNF block" can be identified using 15 SNPs. 相似文献
295.
Patricia Mariani-Kurkdjian Hélène Cavé Jacques Elion Chantal Loirat and Edouard Bingen 《Clinical microbiology and infection》1997,3(1):117-119
Objective: To reassess the occurrence of verocytotoxin-producing Escherichia coli (VTEC) in French hemolytic uremic syndrome (HUS) patients.
Method: From March 1991 to January 1995, direct detection of verotoxin genes (VT) by the polymerase chain reaction (PCR) was performed on stool samples from 169 patients suffering from HUS.
Results: Fifty-one were PCR positive (30.1%); one was positive for the VT1 gene and the others for the VT2 gene. VTEC was isolated from only 32 of the 51 PCR-positive samples. E. coli O157:H7 was isolated from five patients. E. coli O111 was isolated from seven patients during an outbreak of HUS. Among the other VT2 E. coli strains, only four were serotypable. Of the 51 PCR-positive stools, 19 were culture negative for VTEC.
Conclusions: This study provides evidence that in France E. coli O157 and other VTEC serotypes are involved in HUS. 相似文献
Method: From March 1991 to January 1995, direct detection of verotoxin genes (VT) by the polymerase chain reaction (PCR) was performed on stool samples from 169 patients suffering from HUS.
Results: Fifty-one were PCR positive (30.1%); one was positive for the VT1 gene and the others for the VT2 gene. VTEC was isolated from only 32 of the 51 PCR-positive samples. E. coli O157:H7 was isolated from five patients. E. coli O111 was isolated from seven patients during an outbreak of HUS. Among the other VT2 E. coli strains, only four were serotypable. Of the 51 PCR-positive stools, 19 were culture negative for VTEC.
Conclusions: This study provides evidence that in France E. coli O157 and other VTEC serotypes are involved in HUS. 相似文献
296.
Mapping of translocation breakpoints on the short arm of chromosome 19 in acute leukemias by in situ hybridization 总被引:1,自引:0,他引:1
Non-random translocation involving the short arm of chromosome 19 are frequently observed in acute leukemias. Recent studies have shown that the 19p13 genes E2A and LYLl, both of which encode helix-loop-helix proteins, lie at two different translocation breakpoints in acute lymphoblastic leukemias (ALL). The E2A gene is involved by the t(1;19)(q23;p13) in acute pre-B-cell leukemias and the LYL1 gene is structurally altered by a t(7;19)(q34;p13) in T-cell ALL. To assess the role of these genes in other leukemia-associated translocations we mapped their locations with respect to the t(11;19)(q23;p13) and t(4;19)(q21;p13) translocation breakpoints carried by T-ALL cell lines SUP-T13 and SUP-T8a, respectively. In situ hybridization studies indicated that the E2A and LYL1 genes are physically distinct from the t(4;19) and t(11;19) breakpoints. Using these and other 19p13 translocation breakpoints as landmarks, we established a partial physical map of 19p: 19pter-E2A-INSR-LYL1-[t(4;19)]-19cen. These data should help guide molecular studies to further characterize 19p13 breakpoints and mapping of genes in this chromosomal region. 相似文献
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300.
Patricia Lowrimore David Mulvihill Andrew Epstein Michael McCormack Yuh-Hwa Wang 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2004,(1):15-18
Tardive dyskinesia (TD) is a drug-induced syndrome of involuntary movements often associated with neuroleptic treatment of psychiatric conditions. Huntington's disease (HD) and other neurological conditions are caused by CAG nucleotide repeat expansions in specific genes. We, therefore, explore the hypothesis that TD may be related to CAG repeat expansion by using the repeat expansion detection (RED) method as a measure of CAG content without knowledge of the location of the responsible gene. The number of CAG repeats ([CAG](n)) from persons with schizophrenia or schizoaffective disorders with (n = 10) and without (n = 9) TD are determined. A comparison of [CAG](n) in persons with (56.90 +/- 23.45 repeats) and without (57.00 +/- 19.35 repeats) TD was not statistically different. The total [CAG](n) was determined by combining [CAG](n) for both groups. The median of 45 repeats was used to divide the total into two groups (SG1 and SG2 with smaller and larger [CAG](n) fragments, respectively) and a means analysis of the two subgroups based on [CAG](n) demonstrated that SG1 (n = 10 samples at 45 repeats per sample, mean [CAG](n) = 45.00 +/- 0.00) was significantly smaller than SG2 (n = 9, ranging from 48 to 120 repeats, mean = 70.22 +/- 24.83; P < 0.005). Thus, this lends support to the idea of CAG repeat expansions in the study population. Results are encouraging that a larger population and a more structured subject selection process may yield more meaningful information about the relationship between CAG repeat expansion and TD. 相似文献