EXPERIMENTAL MESANGIOPROLIFERATIVE GLOMERULONEPHRITIS IN RATS INDUCED BY INTRAVENOUS ADMINISTRATION OF ANTI-THYMOCYTE SERUM

Focal glomerulonephritis was induced in rats, by a single intravenous injection of anti-Thy-1.1 antibody (ATS). One hour after the administration, the glomeruli of affected rats developed necrotic changes of the mesangial cells while after two hours, mesangiolytic changes appeared. From six days onwards, focal segmental mesangial proliferation which persisted until 30 days, occurred. This is thought to be the first report of experimental nephritis induced by pure anti-mesangial antibody.     

Serum gamma-glutamyl transpeptidase levels and hypertension in non-drinkers: a possible role of fatty liver in the pathogenesis of obesity related hypertension

The relationships between increases in body mass index (BMI) and increases in hypertension were compared between non-drinkers with elevated serum gamma-glutamyl transpeptidase (gamma-GTP) levels (> or = 50 U/l) and those with normal levels, who comprised 10,952 men and 22,107 women aged 40-59 years recruited from an occupational health clinic. Hypertension was found in 16.1% and 13.5% of the men and women, and elevated serum g-GTP was found in 10.8% and 2.8% of the men and women, respectively. The prevalences of hypertension and elevated serum gamma-GTP levels were both increased with increased BMI. Hypertension was, however, shown to be 1.5 times more prevalent in the persons with elevated serum gamma-GTP levels than in those with normal levels in both sexes, even after adjusting for BMI by a multiple logistic analysis. It can be concluded that elevations of serum gamma-GTP, which are probably a reflection of fatty liver in the non-drinkers, are closely related to the development of hypertension associated with increased obesity.     

足底板对类风湿性关节炎患者足底压的影响

目的 :测定类风湿性关节炎病人足底压 ,评价足底板的生物力学效应。方法 :12名女性类风湿性关节炎病人和 8名健康女性进行年龄和体重匹配。用 F- Scan系统进行动态足底压测量 ,Kistler床反力平台用以校正测量精确性。测量足底峰压和垂直分力 ,评价足底板的生物力学表现。结果 :类风湿性关节炎病人中足底压明显高于健康人。使用足底板后 ,足底总的峰压明显降低 ,前足、后足峰压减低 ,中足峰压增高。而垂直分力改变不大。结论 :足底板能显著降低足底压力 ,使足底压力重分布 ,减轻类风湿足痛。特殊设计的足底板对类风湿足痛的治疗能起重要的作用     

PTEN loss in intraductal carcinoma of the prostate has low incidence in Japanese patients

Clinical and genomic features of prostate cancer (PCa) vary considerably between Asian and Western populations. PTEN loss is the most frequent abnormality in intraductal carcinoma of the prostate (IDC-P) in Western populations. However, its prevalence and significance in Asian populations have not yet been well studied. In the present study, we evaluated PTEN expression in IDC-P in a Japanese population and its association with ERG expression. This study included 45 and 59 patients with PCa with and without IDC-P, respectively, who underwent radical prostatectomy. PTEN loss was observed in 10 patients with PCa with IDC-P (22%) and nine patients with PCa without IDC-P (17%). ERG expression was relatively frequent in patients with PCa with PTEN loss, although a significant difference was not observed. The co-occurrence of PTEN loss and ERG expression was observed in four patients with PCa with IDC-P and one without IDC-P. PTEN loss and ERG expression did not affect progression-free survival, regardless of the presence of IDC-P. The frequency of PTEN loss in IDC-P is lower in Asian patients than in Western patients. Our results indicate that mechanisms underlying IDC-P in Asian populations are different from those of Western populations.     

Clinicopathological features of hereditary breast cancer

The possible role of germline mutations ofBRCA1 andBRCA2 as causative agents of familial breast cancer was assessed. Their possible involvement in the carcinogenesis of hereditary breast cancer was investigated using 63 clinically suspect families. Twenty-one lineages (33.3%) had mutations in one of the twoBRCA genes. This relatively low incidence suggested that germline mutations in unknown genes are involved in the carcinogenesis of hereditary breast cancer in the Japanese population. However, the clinicopathological features characteristic of hereditary breast cancer, such as early disease onset, a high incidence of bilateral breast cancer, and a high incidence of multiple primary carcinomas in other organs were confirmed in the present study.     

Pharmacokinetic and Pharmacological Profiles of Free and Liposomal Recombinant Human Erythropoietin After Intravenous and Subcutaneous Administrations in Rats

Purpose. Recombinant human erythropoietin (Epo) is used frequently through intravenous (i.v.) and subcutaneous (s.c.) administration for the clinical treatment of the last stage of renal anemia. We encapsulated Epo in liposomes to develop an alternative administration route. The purpose of our study was to evaluate the pharmacokinetics and the pharmacological effects of liposomal Epo in comparison with the Epo after i.v. and s.c. administration to rats. Methods. Epo was encapsulated in liposomes composed of dipalmitoylphosphatidylcholine (DPPC) and soybean-derived sterol mixture (SS) prepared by the reversed-phase evaporation vesicle method. After filtration through a 0.1 m polycarbonate membrane, liposomes were gel filtered (Epo/liposomes). Results. Epo/liposomes showed higher pharmacological activity than Epo/liposomes before gel filtration after i.v. administration to rats. Non-encapsulated Epo lost its activity, whereas encapsulated Epo in liposomes retained it. The pharmacological effects of Epo/liposomes were greater than those of Epo after i.v. administration. Epo/liposomes afforded 3–9 times higher AUC, lower clearance and lower steady-state volume of distribution than Epo after both i.v. and s.c. administrations. Epo/liposomes had an improved pharmacokinetic profile compared with Epo. S.c. administration of Epo/liposomes at 7 h may penetrate primarily (40% of dose) through the blood as a liposome and partly (7% of dose) in lymph. Conclusions. Epo/liposomes may reduce the frequency of injections required for a certain reticulocyte effect in comparison to Epo. The lower clearance of Epo/liposomes may increase the plasma concentrations of Epo, which increases the efficacy.