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991.
Melvin G McInnis Danielle M Dick Virginia L Willour Dimitrios Avramopoulos Dean F MacKinnon Sylvia G Simpson James B Potash Howard J Edenberg Elizabeth S Bowman Francis J McMahon Carrie Smiley Jennifer L Chellis Yuqing Huo Tyra Diggs Eric T Meyer Marvin Miller Amy T Matteini N Leela Rau J Raymond DePaulo Elliot S Gershon Judith A Badner John P Rice Alison M Goate Sevilla D Detera-Wadleigh John I Nurnberger Theodore Reich Peter P Zandi Tatiana M Foroud 《Neuropsychopharmacology》2003,54(11):1265-1273
BACKGROUND: In 1989 the National Institute of Mental Health began a collaborative effort to identify genes for bipolar disorder. The first 97 pedigrees showed evidence of linkage to chromosomes 1, 6, 7, 10, 16, and 22 (Nurnberger et al 1997). An additional 56 bipolar families have been genotyped, and the combined sample of 153 pedigrees studied. METHODS: Three hierarchical affection status models were analyzed with 513 simple sequence repeat markers; 298 were common across all pedigrees. The primary analysis was a nonparametric genome-wide scan. We performed conditional analyses based on epistasis or heterogeneity for five regions. RESULTS: One region, on 16p13, was significant at the genome-wide p <.05 level. Four additional chromosomal regions (20p12, 11p15, 6q24, and 10p12) showed nominally significant linkage findings (p =.01). Conditional analysis assuming epistasis identified a significant increase in linkage at four regions. Families linked to 6q24 showed a significant increase in nonparametric logarithms of the odds (NPL) scores at 5q11 and 7q21. Epistasis also was observed between 20p12 and 13q21, and 16p13 and 9q21. CONCLUSIONS:The findings are presented in rank order of nominal significance. Several of these regions have been previously implicated in independent studies of either bipolar disorder or schizophrenia. The strongest finding is at 16p13 at D16S748 with an NPL of 3.3, there is evidence of epistasis between this locus and 9q21. Application of conditional analyses is potentially useful in larger sample collections to identify susceptibility genes of modest influence that may not be identified in a genome-wide scan aimed to identify single gene effects. 相似文献
992.
993.
994.
Harriet E. Gershon Edmund C. Lattime Osias Stutman 《Mechanisms of ageing and development》1980,13(3):253-264
In order to further our understanding of the reasons for the increased susceptibility of aged animals to autoimmunity, neoplasms and infectious diseases, experiments were performed to determine the ability of an aged environment to induce and support tolerance to major histocompatibility complex (MHC) determinants as well as to support the development of a specific immune response to modified self-determinants. The degree and mechanisms of tolerance to host and donor histocompatibility antigens were studied in bone marrow chimeras of the type (C57B1/6 × CBA)F1 → (C57B1/6 × DBA/2)F1 (BCF1 and BDF1, respectively). BCF1 bone marrow donors were 6 weeks old and BDF1 hosts were 18 months old at the time of chimerization. Four to ten months later, chimeras were found to be fully tolerant to all three parental haplotypes and competent to respond to fourth-party strains as assessed in both mixed lymphocyte reactions and cell-mediated lympholysis. Tolerance to parental haplotypes could not be attributed to active suppression of reactivity.The aged host environment proved incapable of supporting the development of anti-modified self-reactivity as attested by the fact that neither the senescent BDF1 mice nor the BCF1 → BDF1 chimeras established in aged hosts could respond to trinitrophenol-modified autologous parental cells. In contrast, young BDF1 mice and BCF1 → BDF1 chimeras established in young adult hosts were competent to respond to trinitrophenol-modified autologous and parental cells in an MHC restricted fashion. The significance of these results to the susceptibility of aged animals to intracellular parasitic infections and neoplasia is discussed. 相似文献
995.
There were no significant differences noted between bipolar manic-depressive patients and normal controls for plasma phenylalanine or tyrosine following an L-phenylalanine loading test given to determine if some affective illness may be related to the heterozygous phenotypic expression of phenylketonuria (reduced liver phenylalanine hydroxylase). The test was able to distinguish known PKU heterozygotes from the other subjects. It is possible that other heterozygous states may be implicated in the development of some psychiatric disorders. 相似文献
996.
L Spitz 《Journal of the Royal Society of Medicine》1982,75(7):525-529
Twenty severely mentally retarded children with significant gastrooesophageal reflux were submitted to surgical treatment. In all patients vomiting was present to a distressing degree in 5 children, 3 of whom required extensive surgery to overcome the obstruction. All had failed to respond to conservative measures. Although the postoperative complication rate was high (50%), the final result in the majority of patients was highly satisfactory. 相似文献
997.
DOM was administered to five subjects, each of whom received 6 mg of the drug daily for 3 consecutive days. Tolerance was observed. This finding is correlated with prior studies of behavioral biochemical and electrophysiologic aspects of DOM tolerance in cats. 相似文献
998.
Plasma antipyrine half-lives and metabolic clearances were measured after a single oral dose of antipyrine in 10 control subjects, 12 patients with gallstones, and 9 patients having undergone cholecystectomy for cholesterol cholelithiasis, to determine whether impairment of hepatic antipyrine metabolism occurs in patients with cholesterol cholelithiasis. The plasma antipyrine half-life and metabolic clearances in the control subjects were 11.7±1.0 hours and 42.5±3.3 ml/min, respectively; in patients with gallstones, 12.3±1.3 hours and 36.0±3.2 ml/min, respectively; and in patients having undergone cholecystectomy, 13.2±1.8 hours and 33.8±4.2 ml/min, respectively. Values for antipyrine half-life and metabolic clearance were not statistically different in these three groups. This study suggests the presence of normal hepatic antipyrine metabolism in patients with cholesterol cholelithiasis. 相似文献
999.
1000.
A case of cyst of seminal vesicle associated with ipsilateral renal agenesis in a twenty-three-year-old man presenting primarily with rectal symptoms is reported. The usual symptoms had been urinary bladder irritation and pain on ejaculation. The embryologic development of this rare entity is discussed. 相似文献