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The rationale for anti-tumour necrosis factor-alpha (anti-TNFalpha) therapy in rheumatoid arthritis (RA) is based on experiments on cultures of human rheumatoidjoint tissue, supported by experiments in animal models, all of which demonstrated that anti-TNFalpha antibody had profound effects on the disease activity. Clinical trials have substantiated this concept, and we have used the serum samples from the clinical trials, as well as biopsies to study the changes occurring during anti-TNFalpha therapy as clues to the pathogenesis of RA. The major effects of anti-TNFalpha therapy are in downregulating cytokine activity, and in reducing leucocyte trafficking to the joints.  相似文献   
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Thrombopoietin (TPO) has recently been cloned and shown to regulate megakaryocyte and platelet production by activating the cytokine receptor c-mpl. To determine whether TPO is the only ligand for c-mpl and the major regulator of megakaryocytopoiesis, TPO deficient mice were generated by gene targeting. TPO-/- mice have a >80% decrease in their platelets and megakaryocytes but have normal levels of all the other hematopoietic cell types. A gene dosage effect observed in heterozygous mice suggests that the TPO gene is constitutively expressed and that the circulating TPO level is directly regulated by the platelet mass. Bone marrow from TPO-/- mice have decreased numbers of megakaryocyte-committed progenitors as well as lower ploidy in the megakaryocytes that are present. These results demonstrate that TPO alone is the major physiological regulator of both proliferation and differentiation of hematopoietic progenitor cells into mature megakaryocytes but that TPO is not critical to the final step of platelet production.  相似文献   
64.
Since 1987 The National AIDS Council in Mexico (CONASIDA), has conducted research projects among female commercial sex workers (CSW), who are seen at the AIDS Information Centers. Through these studies, we have been able to find out how different issues influence commercial sex work in Mexico City. Since the beginning of our own studies in 1989, HIV prevalence in this particular group has remained low (0.04%-0.2%). Factors found to be associated with condom use were: educational level, not having children, more experience in sex work and younger age. Condom use was reported by 88% of the women; however, qualitative information and high STD prevalence rates suggest a much lower condom use. Mandatory HIV testing is not useful as a preventive measure among sex workers. Persuasive and structural interventions must be implemented in accordance with local and legal situations.  相似文献   
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BACKGROUND AND STUDY AIMS: Anastomotic leakage is a severe complication in gastric surgery and it is associated with a high rate of mortality. Conservative treatment sometimes is not sufficient to stem the leakages and, even when it is sufficient, it takes a long time. The present study describes the first experience in the treatment of anastomotic leakages with endoscopic clipping. PATIENTS AND METHODS: From May 1995 to December 1996, seven patients with postoperative anastomotic leakages after gastric surgery were prospectively treated in our Endoscopy Service. Metallic endoclips (MD 850, Olympus Corp., Tokyo, Japan) with prongs 12 mm long and 6 mm wide were applied, controlling the closure of the leakage by endoscopy, using radiographs to confirm the closure 24 hours later. RESULTS: Complete closure of the leakage was obtained in all seven cases. A single session of endoscopic clipping was needed for five patients while two other required, respectively, two and three sessions. The median time of leakage closure after endoscopic clipping was 2.3 days (range 1-5 days). The clips spontaneously dislodged within 1 month in five patients and within the second month in the other two patients. CONCLUSION: Endoscopic treatment of anastomotic leakages by metallic clips represents a safe and easily repeated method and, compared to conservative treatment, it seems to offer several time and cost advantages. Further studies involving a larger number of patients are needed to verify this finding.  相似文献   
68.
The objective of this study was to calculate, prepare and evaluate the Protein Efficiency Ratio (P.E.R.) and Net Protein Utilization (N.P.U.) of two infant formulas made with amaranth (Amaranthus cruentus). Both formulas were formulated to match a previously developed and tested soy-oats infant formula. No significant differences were found between the three formulas with respect to corrected Protein Efficiency Ratio (P.E.R.) and Net Protein Utilization (N.P.U.) values. Only the product made with the 1-R fraction of amaranth was found to have a significantly lower P.E.R. than casein.  相似文献   
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The impact of entrance age on reading and mathematics achievement in 1st grade was examined. Methodological problems with past research were identified, including small size of achievement differences, failure to take background variables into account, and confusion of achievement levels with degree of learning. Using a pre-post design, growth of reading and mathematics was examined in younger 1st graders, older 1st graders, and older kindergarteners. Comparisons of background information on these groups with children who were either held out prior to or retained an extra year in kindergarten, produced minimal background differences. Results revealed that younger 1st graders made as much progress over the school year as did older 1st graders and made far more progress than older kindergarteners. Overall, findings demonstrated that, in itself, entrance age was not a good predictor of learning or academic risk.  相似文献   
70.
Increased cardiovascular mortality occurs in diabetic patients with or without coronary artery disease and is attributed to the presence of diabetic cardiomyopathy. One potential mechanism is hyperglycemia that has been reported to activate protein kinase C (PKC), preferentially the beta isoform, which has been associated with the development of micro- and macrovascular pathologies in diabetes mellitus. To establish that the activation of the PKCbeta isoform can cause cardiac dysfunctions, we have established lines of transgenic mice with the specific overexpression of PKCbeta2 isoform in the myocardium. These mice overexpressed the PKCbeta2 isoform transgene by 2- to 10-fold as measured by mRNA, and proteins exhibited left ventricular hypertrophy, cardiac myocyte necrosis, multifocal fibrosis, and decreased left ventricular performance without vascular lesions. The severity of the phenotypes exhibited gene dose-dependence. Up-regulation of mRNAs for fetal type myosin heavy chain, atrial natriuretic factor, c-fos, transforming growth factor, and collagens was also observed. Moreover, treatment with a PKCbeta-specific inhibitor resulted in functional and histological improvement. These findings have firmly established that the activation of the PKCbeta2 isoform can cause specific cardiac cellular and functional changes leading to cardiomyopathy of diabetic or nondiabetic etiology.  相似文献   
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