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191.
Development of male contraceptive vaccine - a perspective   总被引:1,自引:0,他引:1  
This paper reviews the recent advances that have occurred inthe area of development of a male contraceptive vaccine. Thevaccine candidates considered for review are hormone/hormonereceptor-based proteins including luteinizing hormone-releasinghormone (LHRH)/LH, follicle stimulating hormone (FSH), as wellas LH and FSH receptor proteins. The review also highlight theadvances in our basic understanding of gonadotrophin actionwhich have led to development of these vaccines. Focus is mainlyon studies in the non-human primate which may be directly relevantto projected studies in the human. The data indicate that thevaccines are well tolerated by the primate (including the humanbased on limited data) and do not give rise to any known toxicsymptoms or immediate health hazards. The response to the immunogenhas been uniform and it may be possible to increase antibodytitres as well as prolong the immune response by adding acceptableimmune stimulators to the adjuvant cocktail and developing betterimmunization schedules or immunogen delivery systems. Contraceptivevaccines for the male are a feasible proposition and attentionshould now be focussed on evaluating carefully the bioefficacyof antibodies raised to recombinant ovine FSHß orFSH receptor protein fragments in both human and non-human primates.The advantage of the FSH/FSH receptor over the LHRH/LH-basedvaccine lies in the fact that the former does not require anexogenous testosterone supplement to maintain accessory glandfunction, libido etc. The LHRH/LH-based vaccine results in azoospermia,while the FSH vaccine causes the production of low numbers ofpoor quality spermatozoa which are incapable of impregnatingcycling females.  相似文献   
192.
Reid  DM; Jones  CE; Vostal  JG; Shulman  NR 《Blood》1990,75(11):2194-2203
We have found that Western blots (WBs) of whole platelets exposed to normal autologous or homologous sera commonly have bands at 90 to 95 (95) Kd, and less often at 100 to 110, 80 to 85, 60 to 75, and 50 to 60 Kd when developed with antiglobulins. The percentages of normal sera producing a 95-Kd band with anti-immunoglobulin G (IgG), -IgA, and -IgM are 85, 50, and 30, respectively. Antiglobulin reagents alone also produce background bands on WBs that we have shown correspond to levels of platelet-associated Igs (PAIgs) or their derivatives. Titers of 95 Kd-reactive IgG in normal sera range from 10 to 1,280 (85% less than or equal to 50), and the reaction appears to be partially F(ab')2- mediated. The 95-Kd protein is internal and differs in many respects from surface glycoproteins IIIa, IV, and V of similar apparent molecular weight. In thrombocytopenic patients there was no correlation between severity of thrombocytopenia or PAIgG of platelet eluates and corresponding serum titers of 95 Kd-reactive IgG. Some WB reactions previously reported as evidence of autoimmunity may represent normal variations in reactions of Igs with internal platelet proteins. These reactions may be immunospecific or analogous to nonspecific, partially F(ab')2-dependent binding of Igs by certain bacterial proteins.  相似文献   
193.
Markovic  OS; Shulman  NR 《Blood》1977,50(5):905-914
Optimal conditions necessary for the cytochemical demonstration of megakaryocyte (Mk) and platelet acid phosphatase (AP) were determined. Methanol, a constituent of fixatives commonly used in AP cytochemistry, was found to inhibit MkAP, and the degree of inhibition varied with Mk maturity. Immature Mk contained predominantly methanol-resistant AP, and mature Mk, predominantly methanol-sensitive AP. Platelets contained methanol-sensitive AP similar to mature Mk, suggesting that this enzyme provides an index of platelet formation by Mk. Soluble platelet AP showed three bands on polyacrylamide gel electrophoresis, visualized by the same reactions applied cytochemically. Two bands, accounting for 98% of the platelet AP activity, were slow moving and methanol sensitive; and one fast moving band accounting for 2% of activity was methanol resistant. Measurement of Mk and platelet AP isoenzymes may prove to have applications in evaluating Mk function.  相似文献   
194.
Bone marrow transplant patients are at increased risk for infections with polysaccharide encapsulated organisms and respond poorly to polysaccharide vaccines. We evaluated the effect of donor immunization with Haemophilus influenzae type b (HIB) polysaccharide-conjugate vaccine on recipient antibody responses following allogeneic bone marrow transplantation. Thirty-two allogeneic transplant patients and their donors were immunized before transplantation with HIB-conjugate, tetanus toxoid and 23-valent pneumococcal vaccines. Following transplantation, patients received HIB-conjugate and tetanus toxoid vaccines at 3, 6, 12, and 24 months and 23-valent pneumococcal vaccine at 12 and 24 months. Thirty-three patients with unimmunized donors were immunized following transplantation in an identical manner. Patients whose donors were immunized had significantly higher total anti-HIB antibody concentrations at 3 months (P = .0001), 6 months (P = .0001), 12 months (P = .0001), and 24 months (P = .002) after transplant compared with patients whose donors were unimmunized. Higher antitetanus toxoid antibody concentrations were also noted in patients with immunized donors, whereas donor immunization with pneumococcal vaccine had no effect on antibody concentrations following transplantation. Donor immunization with HIB-conjugate vaccine resulted in higher antibody concentrations in patients as early as 3 months after allogeneic transplantation and may be an effective strategy to prevent HIB infections.  相似文献   
195.
The appearances of the lungs on radiographs and computed tomographic (CT) scans were correlated with degree of uptake on gallium scans and results of pulmonary function tests (PFTs) in 27 patients with sarcoidosis. CT scans were evaluated both qualitatively and quantitatively. Patients were divided into five categories on the basis of the pattern of abnormality at CT: 1 = normal (n = 4); 2 = segmental air-space disease (n = 4); 3 = spherical (alveolar) masslike opacities (n = 4); 4 = multiple, discrete, small nodules (n = 6); and 5 = distortion of parenchymal structures (fibrotic end-stage sarcoidosis) (n = 9). The percentage of the volume judged to be abnormal (CT grade) was correlated with PFT results for each CT and radiographic category. CT grades were also correlated with gallium scanning results and percentage of lymphocytes recovered from bronchoalveolar lavage (BAL). Patients in CT categories 1 and 2 had normal lung function, those in category 3 had mild functional impairment, and those in categories 4 and 5 showed moderate to severe dysfunction. The overall CT grade correlated well with PFT results expressed as a percentage of the predicted value. In five patients, CT scans showed extensive parenchymal disease not seen on radiographs. CT grades did not correlate with the results of gallium scanning or BAL lymphocytes. The authors conclude that patterns of parenchymal sarcoidosis seen at CT correlate with the PFT results and can be used to indicate respiratory impairment.  相似文献   
196.
197.
OBJECTIVES: To describe the clinical characteristics and outcomes of tuberculosis (TB) in elderly people.
DESIGN: Observational analysis of a prospective cohort of adults with TB (1995–2004). A case–control study to determine attributable mortality to TB in very old people was done.
RESULTS: Of 319 patients with TB, 109 (34.2%) were aged 65 and older. The older group was more likely to have comorbidities (1.4% vs 0.4%; P <.001), extrapulmonary and disseminated TB (50.4% vs 26.1%; P <.001), toxicity (22% vs 9.8%; P =.006), and 30-day mortality (18.3% vs 1.6%; P <.001). When patients aged 65 to 79 were compared with those aged 80 and older, only differences in TB-related mortality were detected (9.8% vs 44.4%; P =.01). In the attributable mortality analysis, 30-day and 6-month mortality were higher in very old patients with TB than in controls without TB (41.7% vs 11.1%, P =.005; 45.8% and 19.4%, P =.01, respectively). No differences in mortality were shown when excluding patients with postmortem TB diagnosis or those who died within the first 72 hours of diagnosis.
CONCLUSION: Older people with TB had a higher frequency of atypical features, more adverse drug reactions, and greater TB-related mortality than younger people. Data suggest that very old patients with TB have higher mortality, but if diagnosed early and adequately treated, very old patients with TB do not have greater mortality than those without.  相似文献   
198.
BACKGROUND & AIMS: Patients with chronic hepatitis C and persistently normal alanine aminotransferase (ALT) levels have been routinely excluded from large randomized treatment trials; consequently, the efficacy and safety of antiviral therapy in this population are unknown. METHODS: Patients with at least 3 normal ALT values over an 18-month period were randomized (3:3:1) to treatment with peginterferon alfa-2a 180 mug/wk plus ribavirin 800 mg/day for 24 weeks (212 patients), the same combination for 48 weeks (210 patients), or no treatment (69 patients) in a multinational study. All patients were monitored for 72 weeks. The primary measure of efficacy was sustained virologic response (SVR), defined as undetectable serum hepatitis C virus (HCV) RNA by qualitative polymerase chain reaction at the end of 24 weeks of untreated follow-up. RESULTS: No patient cleared HCV RNA in the untreated control group. SVR rates of 30% and 52% were obtained in the 24- and 48-week treatment groups, respectively. In patients infected with HCV genotype 1, SVR rates of 13% and 40% were obtained with 24 and 48 weeks of treatment, respectively (P < .0001). In patients infected with genotypes 2 or 3, SVR rates were 72% and 78% with 24 and 48 weeks of treatment, respectively (P = .452). Treatment-related flares in ALT activity were not observed. CONCLUSIONS: The efficacy and safety of peginterferon alfa-2a and ribavirin combination therapy in patients with chronic hepatitis C and persistently normal ALT levels are similar to that in patients with elevated ALT levels. The indication for treatment of hepatitis C can be evaluated independently from baseline ALT activity.  相似文献   
199.
Inflatable artificial urinary sphincters provide excellent voluntary continence. Eighty-four consecutive patients underwent implantation of artificial urinary sphincters for intractable urinary incontinence; 33 patients had 58 episodes of sphincter malfunction, and eight patients had eight complications involving a functional prosthetic sphincter. Retrospective analysis was performed to determine the value of plain radiography of the pelvis in patients with sphincter malfunction or complication. The cause of malfunction in the majority of patients was a system leak and subsequent loss of hydraulic fluid (31 occurrences; 53%). Plain radiography permitted correct identification of all instances of fluid leakage in patients with opacified prostheses. Plain radiographs were of no value in examining patients with nonopacified prostheses or the complications of cuff erosion or wound infection. Due to the low cost and noninvasive nature of plain radiography of the pelvis, we conclude that it should be used as the initial diagnostic modality in patients with previously opacified but currently dysfunctional artificial urinary sphincters.  相似文献   
200.
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