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
In the second article in this series we describe some of the newer options in respiratory support and pharmacological intervention which, although largely experimental at present, may prove to be of benefit in the future. 相似文献
Three reports describing the morbidity resulting from intubation-induced arytenoid cartilage dislocation are presented. Significant factors contributing to such an injury are: retrognathia, dental malocclusion, a large tongue base and intubation inexperience. We advise that in all patients who undergo a difficult intubation the possibility of arytenoid dislocation should be considered. A ventilating bronchoscope should be readily available upon extubation, to deal with any acute airway problem that may arise. Treatment modalities are discussed and the advantages of a combined anaesthetic and ENT approach highlighted. 相似文献
Methods: Gene therapy was tested for inducing functional angiogenesis in the superficial rat epigastric island flap to allow earlier
pedicle division. Autologous rat fibroblasts were grown, harvested, cultured and retrovirally transfected to produce platelet-derived
growth factor AA (PDGF-AA), an angiogenetically active protein. Stable gene expression was monitored by PDGF-AA enzyme-linked
immunosorbent assay (ELISA). One hundred and eighty animals were divided into three groups (I–III) and a bilateral flap created
in each animal. In all experiments, the right-sided flap was subjected to experimental treatment and the left-sided flap served
as control (1 ml saline 0.9%). During flap elevation, group I received 5×106 GMFB (genetically modified fibroblasts) plus 1 ml Dul-becco's modified Eagle's medium. Group II was treated with 5×106 NMFB (non-modified fibroblasts) plus 1 ml medium and group III received 1 ml medium only. The flaps were sutured back and
the vascular pedicle was bilaterally ligated and divided in each of ten animals during the following 6 days. After 7 days,
the flaps were harvested, the amount of necrosis measured and histologically examined. Results: The GMFB produced up to 560 times more PDGF-AA than the NMFB, measured by ELISA. The GMFB-treated flaps tolerated surgical
division of the vascular pedicle significantly earlier than groups II and III. Histologically, fibroblasts persisted in all
flaps of groups I and II, without major inflammatory reaction. In all GMFB-treated flaps, massive angiogenesis could be demonstrated.
Conclusion: By means of retroviral gene transfer, autologous rat fibroblasts can be genetically modified for stable expression of the
PDGF-A gene to produce high amounts of PDGF-AA, which is angiogenetically active. After injection into the panniculus carnosus,
these cells induce functional angiogenesis to permit earlier division of the vascular pedicle in this flap model.
Received: 5 January 1998 / Accepted: 17 June 1998 相似文献
Monoclonal antibodies are able to provide information on the surface topography of biopolymers. Antibodies capable of inhibiting the activities of cutinase and parathion hydrolase have been identified in order to probe the sites of pesticide inhibition. Kinetic studies were employed to determine whether organophosphate pesticide binding was directly prevented by antibody binding. Prior binding of chlorfenvinphos and methyl paraoxon to cutinase inhibited subsequent binding by the monoclonal anti‐cutinase antibodies. The role of antibodies in probing enzyme structure is discussed. 相似文献
Background: Increased carboxyhemoglobin concentrations in patients receiving inhalation anesthetics (desflurane, enflurane, and isoflurane) have been reported. Recent in vitro studies suggest that dry carbon dioxide absorbents may allow the production of carbon monoxide.
Methods: The authors used high fresh oxygen flow (5 or 10 l/min) through a conventional circle breathing system of an anesthesia machine for 24 or 48 h to produce absorbent drying. Initial studies used 10 l/min oxygen flow with the reservoir bag removed or with the reservoir bag left in place during absorbent drying (this increases resistance to gas flow through the canister). A third investigation evaluated a lower flow rate (5 l/min) for absorbent drying. Water content of the absorbent and temperature were measured. Pigs received a 1.0 (human) minimum alveolar concentration desflurane anesthetic (7.5%) for 240 min using a 1 l/min oxygen flow rate with dried absorbent. Carbon monoxide concentrations in the circuit and carboxyhemoglobin concentrations in the pigs were measured.
Results: Pigs anesthetized with desflurane using Baralyme exposed to 48 h of 10 l/min oxygen flow (reservoir bag removed) had extremely high carboxyhemoglobin concentrations (more than 80%). Circuit carbon monoxide concentrations during desflurane anesthesia using absorbents exposed to 10 l/min oxygen flow (reservoir bag, 24 h) reached peak values of 8,800 to 13,600 ppm, depending on the absorbent used. Carboxyhemoglobin concentrations reached peak values of 73% (Baralyme) and 53% (soda lime). The water content of Baralyme decreased from 12.1 +/- 0.3% (mean +/- SEM) to as low as 1.9 +/- 0.4% at the bottom of the lower canister (oxygen flow direction during drying was from bottom to top). Absorbent temperatures in the bottom canister increased to temperatures as high as 50 [degree sign] Celsius. With the reservoir bag in place during drying (10 l/min oxygen flow), water removal from Baralyme was insufficient to produce carbon monoxide (lowest water content = 5.5%). Use of 5 l/min oxygen flow (reservoir bag removed) for 24 h did not reduce water content sufficiently to produce carbon dioxide with desflurane. 相似文献
The increasing interest in 5-fluorouracil (5-FU) modulation and the development of new antifolates has focused attention in recent studies on the expression of the target enzyme thymidylate synthase (TS) as a determinant of drug sensitivity and resistance. Resistance to TS-directed drugs has been shown to occur in vitro and in vivo with increased expression of the enzyme (determined by enzymatic assays as well as protein and gene expression assays). Several studies have evaluated the role of TS as a prognostic indicator of clinical response to chemotherapy containing TS-directed drugs. We have used a polyclonal antibody to recombinant human TS to establish a silver-enhanced immunogold staining method to localize TS in human tumours. Human tumour cell lines with acquired resistance to TS inhibitors owing to increased levels of TS were used to confirm the specificity of immunostaining. Stained sections were evaluated by image analysis. Immunostaining in tumour sections was greatly reduced (>80%) by preabsorption of the antiserum with recombinant TS. The method was used to determine the extent of TS immunostaining in 134 primary human colorectal tumours. The results were then compared with the clinical outcome and response to chemotherapy for the treatment of subsequent metastatic disease. A wide range (approximately 100-fold) of TS immunostaining was observed in these primary tumour sections. Normal mucosal tissue levels were 5-10 times lower than those observed in the adjacent tumour tissue. The values for TS immunostaining did not correlate with clinical endpoints, such as time from diagnosis to relapse, response to chemotherapy for disseminated disease, nor with Dukes'' staging. This lack of correlation may be because this group of patients was selected on the basis of their need for palliative chemotherapy and did not include patients who were cured of their disease. Also, primary tumour TS expression may not give a good indication of the TS expression in metastatic lesions. The prognostic significance of TS protein expression in primary and metastatic lesions requires further evaluation. 相似文献