Apoptosis and expression of apoptotic regulators in the human testis following short- and long-term anti-androgen treatment

Apoptosis and its augmentation by androgen withdrawal is an important event in the testis. In other tissues apoptosis is regulated by genes belonging to the bcl-2 family. However, little is known about these pathways in the human testes. Human testes were obtained from patients with prostate cancer, undergoing orchidectomy for permanent androgen ablative treatment. The patients were either untreated or had previously received short- or long-term anti-androgen therapy by cyproterone acetate or GnRH agonist (goserelin). In comparison with untreated patients, testicular testosterone concentrations were reduced by 83% in patients treated with cyproterone acetate and by 99% in patients treated with goserelin. Apoptotic cells were identified in tissue sections by in-situ end labelling of fragmented DNA. The expression of Bcl-2, Bcl-xl, Bax, p53 and poly(ADP) ribose polymerase (PARP) was demonstrated in tissue extracts by Western blotting. Apoptotic germ cells were present in the spermatogenic epithelium of untreated patients and patients who received short-term anti-androgen treatment. There were few or no apoptotic cells in the seminiferous tubules following long-term anti-androgen treatment. Following short- term treatment, the concentrations of the apoptosis-related proteins examined did not change. However, in the long-term treated testes, Bcl- xl and PARP expression declined, Bax and p53 protein concentrations were unchanged, and Bcl-2 was up-regulated. In conclusion, apoptosis occurs in spermatogenic cells of the human testis and may contribute to the regulation of germ cell populations. The apoptosis-related gene products which have been described in other tissues are present in the human testis and are modulated by androgenic stimuli.      

支气管内活瓣治疗晚期肺气肿的随机研究

背景和目的:支气管内活瓣可以使气体从肺叶中排出而不允许其进入,从而导致肺叶容积减少,改善晚期肺气肿患者的过度肺充气症状,提高肺功能和运动耐量.方法:比较支气管内活瓣和标准疗法治疗非均质性肺气肿的安全性和有效性.疗效判定选择FEV1和6 min步行试验占预计值%的变化进行对比.     

Overexpressed nitric oxide synthase in portal-hypertensive stomach of rat: A key to increased susceptibility to damage?

BACKGROUND & AIMS: Portal hypertension predisposes gastric mucosa to increased injury. The aim of this study was to determine whether overexpression of constitutive nitric oxide synthase (cNOS) is responsible for increased susceptibility of portal-hypertensive (PHT) gastric mucosa to damage. METHODS: In gastric specimens from PHT and sham-operated rats, cNOS messenger RNA expression was determined by Northern blotting and cNOS protein expression by Western blotting, immunohistochemistry, and enzyme activity assay. Extent of ethanol- induced gastric mucosal necrosis, mucosal blood flow, and gastric NOS activity in PHT and sham-operated rats was determined after administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) or saline. RESULTS: cNOS messenger RNA level, cNOS enzyme activity, and fluorescence signals for cNOS were increased significantly in PHT rats compared with controls. Inhibition of overexpressed cNOS by L-NAME (5 mg/kg) significantly reduced ethanol-induced mucosal necrosis and normalized blood flow in PHT gastric mucosa, whereas this dose of L- NAME significantly increased mucosal necrosis in sham-operated rats. CONCLUSIONS: Portal hypertension activates the cNOS gene with overexpression of cNOS protein in endothelia of gastric mucosal vessels. Excessive NO production by overexpressed cNOS may play an important role in the increased susceptibility of PHT gastric mucosa to damage. (Gastroenterology 1997 Jun;112(6):1920-30)     

The two-year follow-up of a randomized comparison of in-patient multidisciplinary team care and routine out-patient care for active rheumatoid arthritis

The long-term effects of a period of 11 days of in-patient multidisciplinary team care were compared with routine out-patient care in 80 patients with active rheumatoid arthritis (RA). Endpoint measures included swollen and tender joint counts, the patient's assessment of pain, the patient's and the physician's assessments of disease activity, the ESR and the Health Assessment Questionnaire (HAQ). Two years after hospitalization, all 39 patients randomized to the in- patient group and 39 out of 41 patients randomized to the out-patient group were evaluable. At 2 yr, in the in-patient group the improvement according to mean changes from baseline was greater than that in the out-patient group for all endpoint measures except for the HAQ score, the differences not reaching statistical significance. Averaged over the time points 2, 52 and 104 weeks, the improvement was significantly greater in the in-patient group than in the out-patient group, except for the ESR and HAQ score. In conclusion, a short period of in-patient multidisciplinary team care has a beneficial effect on disease activity over a period of 2 yr and should be considered as a useful treatment modality in patients with active RA.      

Platelet antithrombin defect in malignancy: platelet protein alterations

Sixty-eight patients with malignant disease were divided into two groups based on the results of the platelet antithrombin test (PAT). The normal group had a PAT clotting time ranging from 21.4 to 29.8 seconds, which was equivalent to 25% to 65% inactivation of the 2 U of thrombin added to the test system. The other group showed abnormal PAT clotting time, less than 21.4 seconds or less than 25% thrombin inactivation. The polypeptide composition of platelets from the two patient groups was analyzed by sodium dodecyl sulfate (SDS)- electrophoresis on 7.5% polyacrylamide gels. A polypeptide of 180,000 apparent mol wt was decreased or absent in both Coomassie blue- and Alcian blue-stained gels of the platelets from patients whose PAT was abnormal; this polypeptide comigrated with purified platelet thrombospondin. Tritium labeling of platelet surface glycoproteins by the periodate-borohydride method followed by two-dimensional electrophoresis was performed on platelets of seven patients with abnormal PAT. When they were compared with ten patients with normal PAT, a glycoprotein of 140,000 apparent mol wt with a pl of 4.5 to 5.2 was decreased in platelets of all seven patients with abnormal PAT. Nitrocellulose replicas of one-dimensional gels of platelets from 13 of 14 patients with abnormal PAT showed decreased reaction with an anti- human platelet glycocalicin antiserum. Platelets of these same patients also showed a decreased or absent platelet agglutination induced by ristocetin. Patients with normal PAT had a mean agglutination slope of 1.25 +/- 0.6 (n = 26) as compared with 0.37 +/- 0.34 (n = 26) for the abnormal PAT group (P less than .001). Results indicate that platelets from a subpopulation of tumor patients characterized by decreased platelet antithrombin activity have alterations in two platelet glycoproteins, identified as GPIb and thrombospondin.