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131.
Silvestri JM Chen ML Weese-Mayer DE McQuitty JM Carveth HJ Nielson DW Borowitz D Cerny F 《American journal of medical genetics》2002,114(1):46-50
In the present study, we sought to identify genetic variation in the metabotropic glutamate receptor 3 (GRM3) gene, which has been mapped to chromosome 7q21.1-q21.2 [Scherer et al., 1996] and might contribute to genetic predisposition to schizophrenia and/or bipolar affective disorder. Using single-strand conformation analysis (SSCA), we screened the complete coding sequence as well as adjacent splice sites of the GRM3 gene in a sample of 46 bipolar affective and 46 schizophrenic patients. We detected three sequence variants: a rare C/T substitution at nucleotide position +885 (T209T), a C/T substitution at nucleotide position +2130 (Y624Y), and a more common C/T substitution at nucleotide position +1131 (A291A). The occurrence of the +1131C/T variant was investigated in a sample of bipolar affective patients (n=283), schizophrenic patients (n=265), and ethnically matched controls (n=227). We observed a significant overrepresentation of the +1131T allele in schizophrenic patients when compared to controls (P=0.0022). This finding was followed up in an independent sample of schizophrenic patients (n=288) and controls (n=162) and 128 schizophrenic trios but could not be confirmed. It is therefore unlikely that this variant plays a major role in predisposing to schizophrenia and/or bipolar affective disorder at least in the German population. 相似文献
132.
Lehmann A Katayama S Harrison C Dhut S Kitamura K McDonald N Toda T 《Genes to cells : devoted to molecular & cellular mechanisms》2004,9(5):367-382
Skp1 is a central component of the E3 ubiquitin ligase SCF (Skp1-Cullin-1-F-box). It forms an adapter bridge between Cullin-1 and the substrate-determining component, the F-box protein. In order to establish the role of Skp1, a temperature sensitive (ts) screen was carried out using mutagenic PCR (polymerase chain reaction) and 9 independent ts mutants were isolated. Mapping the mutated residues on the 3-D structure of human Skp1 suggested that the mutants would be compromised in binding to F-box proteins but not Cullin-1 (Pcu1). In order to assess the binding properties of ts Skp1, 12 F-box proteins and Pcu1 were epitope-tagged, and co-immunoprecipitation performed. This systematic analysis showed that ts Skp1 retains binding to Pcu1. However, binding to three specific F-box proteins, essential Pof1, Pof3 involved in maintaining genome integrity, and nonessential Pof10, was reduced. skp1ts cells exhibit a G2 cell cycle delay, which is attributable to activation of the DNA damage checkpoint. Intriguingly, contrary to pof3 mutants, in which this checkpoint is required for survival, checkpoint abrogation in skp1(ts) suppresses a G2 delay and furthermore almost rescues the ts phenotype. The activation mechanism of the DNA damage checkpoint therefore differs between pof3Delta and skp1(ts), implicating a novel role for Skp1 in the checkpoint-signalling cascade. 相似文献
133.
Comparison of electron microscopy, enzyme-linked immunosorbent assay, solid-phase radioimmunoassay, and indirect immunofluorescence for detection of human rotavirus antigen in faeces. 下载免费PDF全文
C J Birch N I Lehmann A J Hawker J A Marshall I D Gust 《Journal of clinical pathology》1979,32(7):700-705
Four techniques were compared for their practicability, speed, and sensitivity for the detection of human rotavirus. Radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) were found to be the most sensitive means of identifying rotavirus, and, once processed, up to 40 specimens could be examined daily. Electron microscopy, although less sensitive than these techniques, had the advantage of being able to detect other viral agents present in faecal extracts. Indirect immunofluorescence failed to detect rotavirus as often as the other three methods. In laboratories where routine examination of faecal specimens from patients with gastroenteritis is required, ELISA and RIA are useful alternatives to electron microscopy. 相似文献
134.
Jennifer S Myers Lisa M Bellini Jon B Morris Debra Graham Joel Katz John R Potts Charles Weiner Kevin G Volpp 《Academic medicine》2006,81(12):1052-1058
PURPOSE: To assess internal medicine and general surgery residents' attitudes about the effects of the Accreditation Council for Graduate Medical Education duty hours regulations on medical errors, quality of patient care, and residency experiences. METHOD: In 2005, the authors surveyed 200 residents who trained both before and after duty hours reform at six residency programs (three internal medicine, three general surgery) at five academic medical centers in the United States. Residents' attitudes about the effects of the duty hours regulations on the quality of patient care, residency education, and quality of life were measured using a survey instrument containing 19 Likert scale questions on a scale of 1 to 5. Survey responses were compared using the Student's t-test. RESULTS: The response rate was 80% (159 residents). Residents reported that whereas fatigue-related errors decreased slightly, errors related to reduced continuity of care significantly increased. Additionally, duty hours regulations somewhat decreased opportunities for formal education, bedside learning, and procedures, but there was no consensus that graduates would be less well trained after duty hours reform. Residents, particularly surgical trainees, reported improvements in quality of life and reduced burnout. CONCLUSIONS: Residents in medicine and surgery had similar opinions about the effects of duty hours reform, including improved quality of life. However, resident opinions suggest that reduced fatigue-related errors have been offset by errors related to decreased continuity of care and that the quality of the educational experience may have declined. Quantifying the degree to which regulating duty hours affected errors related to discontinuity of care should be a focus of future research. 相似文献
135.
Joachim Böttcher M.D. Alexander Pfeil Anders Rosholm Ph.D. Max-Ludwig Schäfer Ansgar Malich M.D. Alexander Petrovitch M.D. Bettina Seidl Gabriele Lehmann M.D. Hans-Joachim Mentzel M.D. Gert Hein M.D. Gunter Wolf M.D. Werner A. Kaiser M.D. M.S. 《Journal of digital imaging》2006,19(3):279-288
Purpose Our study evaluates digital x-ray radiogrammetry (DXR) and Radiogrammetry Kit (RK) as a new diagnostic method for the measurement
of disease-related osteoporosis including quantification of joint space narrowing dependent on the severity of rheumatoid
arthritis (RA).
Materials and Methods A total of 172 unselected patients with RA underwent computerized measurements of bone mineral density (BMD) and metacarpal
index (MCI) by DXR, as well as a semiautomated measurement of joint space distances at the metacarpal–phalangeal articulation
(JSD-MCP 2–5), both were analyzed from plain radiographs of the nondominant hand.
Results Correlations between DXR-BMD and DXR-MCI vs. parameters of RK were all significant (0.34 < R < 0.61; p < 0.01). An expected negative association was observed between RK parameters and the different scoring methods (−0.27 < R < −0.59). The maximum relative decrease in BMD vs. MCI as measured by DXR between the highest and lowest RA severity group
was −27.7% vs. −27.5% (p < 0.01) for the modified Larsen Score, whereas the minimal value of relative DXR-BMD and DXR-MCI reduction could be documented
for the Sharp Erosion Score (−20.8% vs. −26.8%; p < 0.01). The relative reduction of mean JSD-MCP using RK significantly varied from −25.0% (Sharp Erosion Score) to −41.2%
(modified Larsen Score). In addition, an excellent reproducibility of DXR and RK could be verified.
Conclusion DXR in combination with RK could be a promising, widely available diagnostic tool to supplement the different scoring methods
of RA with quantitative data, allowing an earlier and improved diagnosis and more precision in determining disease progression. 相似文献
136.
OBJECTIVE: To evaluate an integrated group intervention for siblings and parents designed to increase sibling understanding of and adjustment to chronic illness and developmental disability (CI/DD). METHODS: Fifty-four well siblings (ages 8-13 years) and their parents were recruited through hospital-based and community agencies serving children with CI/DD. Measures of sibling knowledge, sibling adjustment to the disorder, sibling connectedness, and sibling global behavioral functioning were collected before and after the intervention. A subsample of 20 families completed a 3-month follow-up to assess maintenance of results. RESULTS: Sibling knowledge of the child's disorder and sibling connectedness increased, while sibling reports of negative adjustment to the disorder and parent reports of sibling global behavioral functioning decreased significantly from pre- to posttreatment for both boys and girls, regardless of the type of diagnostic condition. Improvements in sibling knowledge, connectedness, and behavioral problems maintained at 3-month follow-up. Parent satisfaction with the program was high. CONCLUSIONS: Results support the future conduct of more controlled evaluation of the integrated sibling and parent group intervention model to improve sibling knowledge of and adjustment to CI/DD. 相似文献
137.
Lehmann J Jüngel A Lehmann I Busse F Biskop M Saalbach A Emmrich F Sack U 《Journal of autoimmunity》2000,15(3):301-313
The objective of this study was to verify whether isolated rheumatoid arthritis (RA) synovial fibroblasts induce chronic arthritis in SCID mice, in analogy to whole tissue pieces. Fibroblasts were isolated from the synovial membrane of four RA patients (or controls) by out-growth and repeated-passage culture. Following flow-cytometry characterization, 2x10(6)cells were transferred into the left knee joint of SCID mice. The development of arthritis was assessed by joint swelling and histological changes. Human and murine cytokines were measured in vitro in co-cultures (or Transwelltrade mark systems) of human and murine cells. Purified RA synovial fibroblasts, but not healthy synovial or skin fibroblasts, induced hu/mu arthritis within 6 weeks. In-vitro secretion of murine and human interleukin(IL)-6, as well as murine tumour necrosis factor (TNF)-alpha, indicated cross-activation between murine macrophages and human RA fibroblasts. Soluble-factor mechanisms proved more effective than cell-contact mechanisms. Purified RA fibroblasts can, alone, induce hu/mu SCID arthritis. The cytokine profile suggests that xenogeneic interaction between human fibroblasts and murine macrophages may determine the sequence of events leading to hu/mu arthritis. 相似文献
138.
Lewandrowski KU Bondre SP Wise DL Trantolo DJ 《Bio-medical materials and engineering》2002,12(3):259-270
The tissue response of subchondral bone to a biodegradable fixation device manufactured in the shape of a screw and made of polylactide with a hydroxyapatite buffer were implanted through the articular surface of the intercondylar portion of the distal rabbit femur. One screw was implanted per animal. The screws had a core diameter of 3.2 mm and an outer diameter of 4.5 mm. At insertion, the implants were cut flush with the articular surface. After follow-up times of 8 and 16 weeks, the specimens were examined radiographically and histomorphometrically. The intact contralateral femur served as a control for comparison. Only minimal signs of degradation of the polymer could be seen in the histologic specimens. These implant degradation sites were commonly areas of new bone formation adjacent to the screw implant. A brim of repair tissue was formed at the entrance and exit of the implant channel. The width of the repair tissue from the tissue-implant boundary towards the center of the entrance hole varied greatly between the specimens, from 80 to 750 microm. In most specimens this bridging tissue consisted of newly formed bone and undifferentiated mesenchymal tissue. Degenerative chondrocyte clustering occurred in the pre-existing cartilage within a 400 microm wide zone from the tissue-implant interface into the recipient tissues. Some new-bone formation was seen to envelop the implant in all specimens, but the fractional osteoid formation surface of the trabeculae was only significantly higher in the screw-implanted 16-week specimens, when compared to the non-operated contralateral controls. Although the bony osteotomy was invariably healed in all specimens with good implant integration, the quality and quantity of the reparative tissue of the articular cartilage near the screw hole was variable. This study showed that large polylactide implants, which are buffered with hydroxyapatite show benign tissue responses and good implant osteointegration when implanted in bone. They may be suitable for fixation of small bone fractures. However, insertion through intra-articular surfaces may require further improvement of the implant material to avoid the degenerative repair processes seen in this study. 相似文献
139.
Though much research about the public's views of scientists, genetic research and its moral, ethical, and social implications exists, little has been done to investigate how scientists view their own role(s) in public discussions and policy formation related to genetic research and technologies. We interviewed 20 academic geneticists in the United States about their perceptions of the roles they and others (e.g., professional societies, the public, ethicists, and elected officials) do and should play in the formation of science policy, the communication of science to the public, and the public discussions of moral and ethical issues raised by scientific advances. The participants in our study thought that scientists should be more actively involved in public outreach and science policy formation, but frequently they felt ill-equipped and unsupported by their peers and institutions to pursue these activities. Furthermore, many were skeptical of or did not trust elected officials--who they consider uninformed about the issues and too driven by political agendas--to formulate sound science policy. They do, however, have faith in the ability of scientific societies to influence policy effectively, and some thought that societies should play a larger role, both in science policy and as a liaison between scientists and the public. Finally, participants offered suggestions for increasing the involvement and influence of scientists in science-policy formation and public discourse. 相似文献
140.
Irina Lehmann Carmen Rder-Stolinski Karen Nieber Gundula Fischder 《Experimental and toxicologic pathology》2008,60(2-3):185-193
An in vitro cell culture system based on an air/liquid culture technique was developed which allows a direct exposure of cells to volatile chemicals without medium coverage. For the establishment of the experimental system, chlorobenzene was used as a model compound. Chlorobenzene is a volatile organic compound which is mainly used as a solvent. Beside other adverse health effects, chlorobenzene exposure has been shown to be associated with respiratory tract irritations, Th2 differentiation, and allergic sensitizations. Human peripheral blood mononuclear cells (PBMC) and lung epithelial cells (A549) were exposed to chlorobenzene via gas phase for 20 h. Additionally, PBMC were incubated with culture supernatants from exposed lung epithelial cells. High chlorobenzene concentrations (100 g/m(3)) induced IL-8 production in A549 cells, whereby lower concentrations (10 microg/m(3)-1 g/m(3)) stimulated the secretion of the monocyte chemoattractant protein-1 (MCP-1). A direct effect of chlorobenzene on the cytokine secretion of PBMC was not found. However, if PBMC were incubated with culture supernatants of exposed lung cells, an enhanced production of the Th2 cytokine IL-13 was observed. This induction was prevented in the presence of an anti-MCP-1 antibody. Our data suggest that chlorobenzene induces the production of inflammatory mediators in lung cells. The primary chlorobenzene caused release of MCP-1 in lung epithelial cells may secondarily result in a Th2 differentiation in T lymphocytes. These findings may contribute to the understanding of how chlorobenzene mediates the development of inflammatory reactions in the airways and contributes to the development of an allergic reactivity. 相似文献