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BC Odum JS O''Keefe W Lara GT Rodeheaver RF Edlich 《Canadian Metallurgical Quarterly》1998,16(6):875-879
OBJECTIVE: To investigate the lymphocyte subpopulations (T4, T8 and macrophages) and major histocompatibility (MHC) II antigens in patients with superficial bladder cancer before and after intravesical instillations of recombinant interferon-gamma (IFN-gamma). PATIENTS AND METHODS: Four intravesical weekly instillations of either 1.3 mg (20 patients, group A) or 0.7 mg (11 patients, group B) IFN-gamma were administered in 31 evaluable patients (28 men and three women, mean age 68.5 years). The CD4+, CD8+, CD68+ and HLA-DR antigens were detected immunohistochemically in tumours and a marker tumour before and after intravesical instillations. RESULTS: The median number of T4 lymphocytes increased from 15 per high-power field (HPF) to 27.5 in group A (P = 0.0029) and to 45 in group B (P = 0.0117). Macrophages increased from 6 cells/HPF to 15 cells/HPF in group A (P = 0.0029) and from 2 to 8.75 cells/HPF in group B (P = 0.0117). The T8 lymphocyte subpopulation decreased from 4 to 3 cells/HPF (P = 0.0231) in group A and from 5 to 2 cells/HPF (P = 0.0759) in group B. The median percentage of HLA-DR antigens increased from 1.5% to 18% in general, (P < 0.001), from 2.5% to 15% in group A (P = 0.0064) and from 0% to 20% in group B (P = 0.0077). The induction of HLA-DR antigens was statistically significant in those receiving the lower dose (from 0% before instillation to 20% afterward, P = 0.0277), while it was not with the higher dose (from 0% to 5%, P = 0.068). Irrespective of the dose of IFN used. T4 lymphocytes and macrophages increased significantly after treatment in patients in whom the tumour HLA-DR antigens were either up-regulated or remained stable. The median net increase in T4 cells was 17.5 and 30 cells/HPF for groups A and B, respectively (P = 0.0429). CONCLUSION: T4 lymphocytes, macrophages and HLA-DR antigens increased after intravesical IFN-gamma in patients with superficial bladder cancer, but T8 lymphocytes decreased. Irrespective of the drug dose used, patients with either upregulated or stable HLA-DR antigens after treatment showed the same pattern of changes in the lymphocyte subpopulations. The two doses generally had the same effect on the immunological variables assessed but the lower dose was more effective in inducing HLA-DR antigens and in increasing the number of T4 lymphocytes in the tumours. 相似文献
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Mullenbach GT; Chiu CY; Gyenes A; Blaney J; Rosenberg S; Marlowe CK; Brown S; Stratton-Thomas J; Montelione GT; George-Nascimento C; Stauber G 《Protein engineering, design & selection : PEDS》1998,11(6):473-480
Six mutants of human epidermal growth factor (EGF), which carry singlepoint substitutions within a surface patch proposed to juxtapose the boundreceptor, were prepared and characterized for receptor affinity andmitogenicity. Receptor affinities relative to EGF are G12Q > H16D >Y13W > Q43A approximately = H16A approximately = EGF >> L15A.Notably, the reduced receptor affinity of mutant L15A indicates that Leu15probably contributes substantially to receptor binding whereas unalteredreceptor affinities observed for analogs H16A and Q43A indicate thatneither His16 nor Gln43 contributes significantly to this interaction. Onthe other hand, the observed enhanced receptor affinities of analogs G12Q,Y13W and H16D highlight surface loci where additional productivereceptor-binding contacts can be introduced. Interestingly, at acidic pHanalog H16A reveals substantially greater receptor affinity than that ofEGF, a property which may offer enhanced therapeutic utility in acidicenvironments in vivo. 相似文献
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J Permert J Larsson GT Westermark MK Herrington L Christmanson PM Pour P Westermark TE Adrian 《Canadian Metallurgical Quarterly》1994,330(5):313-318
Population-based psychiatric admission rates vary across geographic areas, but reasons for this variation are unknown. Insofar as Community Mental Health Centers (CMHCs) provide outpatient services that may deter the need for hospitalization, the presence and structural characteristics of CMHCs may have an impact on a population's psychiatric admission rates. This study uses small area analysis to examine how general hospital psychiatric admission rates are associated with CMHC characteristics. Based on a survey of all CMHCs in Iowa and corresponding small area variation data, it was found that population admission rates were higher in areas closer to the CMHC and lower in outlying catchment areas, adjusting for age, sex, and urban/rural differences in populations. There was little evidence that differences in staffing and service variables influenced admission rates, although greater CMHC staff coverage by social workers and psychiatric residents was associated with lower admission rates. The results suggest that CMHCs do not lower an area's hospitalization rate, and in fact, the presence of CMHCs may promote a "supplier-induced demand" phenomenon of higher admissions. 相似文献
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R Robinson GT McCarthy O Bandmann M Dobbie R Surtees NW Wood 《Canadian Metallurgical Quarterly》1999,66(1):86-89
Traditional Chinese drugs (TCDs) have played a key role for Chinese people in the treatment of diseases since ancient times. The use of TCDs has generated a great amount of information in the past thousand years about the relationship between natural products and the human body. However, up to now, our understanding on the mode of action of the TCD is still limited. Considering that the basic mechanism of all drug function involves the interaction between the drug and biological receptors at the molecular level, we propose to connect TCDs with modern medicine theory through molecular structures. We propose to explain functions of TCDs by using the knowledge developed in modern molecular biology, pharmacology, computer chemistry, and biochemistry. We are working on a computer-aided Chinese drug study that is discussed in this paper. A short introduction on the progress of our research is also given. 相似文献