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41.
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Vinay Puri Andrew McQuillin Khalid Choudhury Susmita Datta Jonathan Pimm Srinivasa Thirumalai Robert Krasucki Jacob Lawrence Digby Quested Nicholas Bass Helen Moorey Jenny Morgan Bhaskar Punukollu Gomathinayagam Kandasami David Curtis Hugh Gurling 《Neuropsychopharmacology》2007,61(7):873-879
BACKGROUND: Linkage studies by us and others have confirmed that chromosome 1q23.3 is a susceptibility locus for schizophrenia. Based on this information, several research groups have published evidence that markers within both the RGS4 and CAPON genes, which are 700 kb apart, independently showed allelic association with schizophrenia. Tests of allelic association with both of these genes in our case control sample were negative. Therefore, we carried out further fine mapping between the RGS4 and CAPON genes. METHODS: Twenty-nine SNP and microsatellite markers in the 1q23.3 region were genotyped in the United Kingdom based sample of 450 cases and 450 supernormal control subjects. RESULTS: We detected positive allelic association after the eighth marker was genotyped and found that three microsatellite markers (p = .011, p = .014, p = .049) and two SNPs (p = .004, p = .043) localized in the 700 kb region between the RGS4 and CAPON genes, within the UHMK1 gene, were associated with schizophrenia. Tests of significance for marker rs10494370 remained significant following Bonferroni correction (alpha = .006) for multiple tests. Tests of haplotypic association were also significant for UHMK1 (p = .009) using empirical permutation tests, which make it unnecessary to further correct for both multiple alleles and multiple markers. CONCLUSIONS: These results provide preliminary evidence that the UHMK1 gene increases susceptibility to schizophrenia. Further confirmation in adequately powered samples is needed. UHMK1 is a serine threonine kinase nuclear protein and is highly expressed in regions of the brain implicated in schizophrenia. 相似文献
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M. A. Curtis 《Journal of periodontal research》1997,32(1):133-139
The production of extracellular proteolytic enzymes is a widely used strategy by human parasites including bacteria, protozoa and helminths in order to ensure survival in the colonized host. The potential benefits to the organism arise through modifications to the external environment of the cell and include the release of essential nutrients, the disablement/deregulation of the host defences and the exposure of previously shielded substrata as new sites for colonization. Damage to the host may arise through direct proteolysis of structural proteins, deregulation of the inflammatory response or the compromising of the local host defences below the threshold necessary for effective defence. In order to examine these interactions and how they may be regulated in the periodontal diseases, we are examining the properties of proteases of the oral anaerobe Porphyromonas gingivalis with specificity for arginyl peptide bonds (ArgI, ArgIA and ArgIB): a family of enzymes which has been shown to exert effects on a variety of host proteins with roles in the control of inflammation and tissue homeostasis. Analysis of the gene for ArgI (protease polyprotein for ArgI - prpRl) together with structural and immunochemical studies of these 3 interrelated forms indicates that they may be regarded as critical determinants in multiple aspects of the life cycle of the organism via both proteolysis and binding processes. Together with the highly conserved nature of the gene, the data suggest that the PrpRI of P. gingivalis is an essential colonization determinant which may play an important role in the periodontal disease process. 相似文献
46.
D R Poyner N J Birdsall C Curtis P Eveleigh E C Hulme E K Pedder M Wheatley 《Molecular pharmacology》1989,36(3):420-429
The muscarinic receptor from the cerebral cortex, heart, and lacrimal gland can be solubilized in the zwitterionic detergent 3-(3-cholamidopropyl)dimethylammonio-2-hydroxy-1-propane sulfonate (CHAPSO) with retention of high affinity [3H]N-methyls-copolamine binding. However, in this detergent there are significant differences in the binding properties of the receptors, compared with those observed in membranes and digitonin solution. Some agents retain a degree of selectivity. In the heart and cortex, agonists can bind with high affinity to a receptor-GTP-binding protein complex. A second, lower affinity, agonist binding state is also present, which resembles a class of sites seen in membranes but not in digitonin solution. The high affinity agonist binding state has been resolved from the lower affinity state on sucrose density gradient centrifugation. Hydrodynamic analysis suggests that the high affinity state is approximately 110,000 Da larger than the lower affinity state. The binding properties of the receptor in CHAPSO can be altered to those seen in digitonin by exchanging detergents after CHAPSO solubilization. 相似文献
47.
Karl A. Greene M.D. Ph.D. Curtis A. Dickman M.D. Kris A. Smith M.D. Eugene J. Kinder M.D. Joseph M. Zabramski M.D. 《Surgical neurology》1993,40(6):499-503
Reports of intracranial self-multilation by psychotic individuals are associated with severe mental disorders, criminality, or both. We describe a psychotically depressed male who drove a ballpoint pen through his right medial canthus and into his intracranial compartment. The patient developed a cavernous sinus syndrome and a traumatic dissection of the cavernous portion of the carotid artery. The pen was removed intraoperatively. Postoperatively, the patient was placed on a course of broad-spectrum antibiotics, antidepressants, and antipsychotic medications, and he has received long-term psychiatric follow-up. The literature related to these unusual cases is reviewed, and relevant surgical, medical, and psychiatric aspects of treatment are discussed. 相似文献
48.
Macroglossia and amyloidoma of the buttock: evidence of systemic involvement in dialysis amyloid 总被引:2,自引:0,他引:2
D Sethi A J Hutchison N R Cary E A Brown J R Curtis D F Woodrow P E Gower 《Nephron》1990,55(3):312-315
A 48-year-old male on cuprophane haemodialysis for 18 years, with a history of dialysis arthropathy and recurrent carpal tunnel syndrome developed macroglossia and bilateral buttock tumoral masses. The tongue and buttock masses were biopsied. Histology of both biopsies showed amyloid deposits of the beta 2-microglobulin (B2M) variety. Amyloidomas in the gluteal region and macroglossia have not been previously described in amyloid derived from B2M. These findings suggest that systemic B2M amyloidosis can have a similar tissue distribution to AL amyloidosis. This case also stresses the importance of inspection of the tongue, and palpation of the gluteal region for masses, in the assessment of patients with dialysis arthropathy. 相似文献
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J J Hansen B Nielsen P Krogsgaard-Larsen L Brehm E O Nielsen D R Curtis 《Journal of medicinal chemistry》1989,32(10):2254-2260
The enantiomers of alpha-amino-4-bromo-3-hydroxy-5-isoxazolepropionic acid (4-bromohomoibotenic acid, Br-HIBO, 1) a selective and potent agonist at one class of the central (S)-glutamic acid receptors, were prepared with an enantiomeric excess higher than 98.8% via stereoselective enzymic hydrolysis of (RS)-alpha-(acetylamino)-4-bromo-3-methoxy-5-isoxazolepropionic acid (4) using immobilized aminoacylase. The absolute configuration of the enantiomers of Br-HIBO was established by X-ray crystallographic analysis, which confirmed the expected preference of the enzyme for the S form of the substrate 4. (S)- and (RS)-Br-HIBO were potent neuroexcitants on cat spinal neurones in vivo, while (R)-Br-HIBO was a very weak excitant. Correspondingly, the S enantiomer of Br-HIBO (IC50 = 0.34 microM) was considerably more potent than the R form (IC50 = 32 microM) as an inhibitor of [3H]-(RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([ 3H]AMPA) binding to rat brain synaptic membranes in vitro. In contrast, (S)- and (R)-Br-HIBO were approximately equipotent (IC50 values of 0.22 and 0.15 microM, respectively) as inhibitors of [3H]-(S)-glutamic acid binding in the presence of CaCl2. The enantiomers of Br-HIBO showed no significant affinity for those binding sites on rat brain membranes which are labeled by [3H]kainic acid or [3H]-(R)-aspartic acid. 相似文献