Distribution of glutathione and glutathione-related enzyme systems in mitochondria and cytosol of cultured cerebellar astrocytes and granule cells

The cellular and regional distribution of glutathione (GSH) and GSH-related enzyme systems involved in cellular defense against reactive oxygen species and electrophilic xenobiotics in the nervous system has been extensively studied. However, little is known about the subcellular distribution of GSH systems in brain tissue and cultured neural cells. The present study investigates the distribution of mitochondrial and cytosolic GSH and GSH-related enzymes in cultured cerebellar astrocytes and granule cells, and compares them with levels in the adult rat cerebellum. Cytosolic GSH levels and cytosolic activities of glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) in astrocytes were 57, 153, 245, and 92% higher than those found in granule cells, respectively. In contrast, granule cells contained significantly higher mitochondrial GSH levels than astrocytes. Granule cells also demonstrated comparable mitochondria/cytosolic concentrations of GSH and GR, GPX and GST activities to those observed in the cerebellar tissue, whereas ratios in astrocytes were markedly lower. Although in vitro treatments with 100 μM ethacrynic acid depleted both cytosolic and mitochondrial GSH in cultured astrocytes and granule cells in a time-dependent fashion, cellular GSH in granule cells was more resistant to the GSH-depleting agent than astrocytes. These results suggest that although GSH and GSH-related enzymes are abundant in cytosolic compartments of astrocytes, mitochondrial pools are relatively small. Since brain mitochondria are sites of significant hydrogen peroxide generation, the mitochondrial localization of GSH and its associated enzymes in neural cells provide important defenses against toxic oxygen species in the nervous system. Differences in subcellular distribution of GSH systems in individual neural cell types may provide a basis for selective cellular and/or subcellular expression of neurotoxicity.     

贫血患者血清红细胞生成素浓度的测定及临床意义

用小鼠胎肝细胞体外血浆凝块培养红系集落(Erythroid colong formig unit inculturc,E-CFUc)方法,以红细胞生成素(Erythropoietin,EPO)850323为标准试剂,测定正常人、贫血病人血清EPO浓度。实验用妊娠13～15d小鼠胎肝细胞。血清均经透析处理,培养液中加量最大不超过10％。EPO(850323)在培养液中浓度为2.5～100mU/ml。血清EPO(mU/ml)测定结果:28例正常人为48.O±17.7,12例再生障碍性贫血病人为946～>10000,1例巨幼细胞性贫血病人为500,1例缺铁性贫血病人为400和18例慢性肾功能衰竭病人则为94.2±87.6。结果表明:贫血病因对血清EPO浓度有影响。     

Expression of c-erbB-2 protein in keratinocytes of oral mucosal lichen planus and subsequent squamous cell carcinoma

Oral mucosal lichen planus (OMLP) is a well recognized mucosal disease with unknown etiology. Considerable controversy exists as to whether OMLP is intrinsically premalignant, or if the disorder facilitates the development of oral mucosal squamous cell carcinoma (OMSCC) by external factors. The aim of the present study was to investigate the expression of c-erbB-2 protein in the keratinocytes of initial biopsies of oral mucosal disorders diagnosed as OMLP with no evidence of epithelial dysplasia. and to compare the results with the expression of c-erbB-2 protein in subsequent biopsies obtained from the same patients. These results were compared with the findings from control groups (patients with dysplasia with no evidence of OMLP, patients with OMSCC with no evidence of OMLP and normal oral mucosa). The expression of the c-erbB-2 protein was evaluated by immunohistochemical staining of the gene product with the avidin-biotin-complex method using paraffin-embedded tissue sections. Five of the initial biopsies from patients with OMLP expressed the c-erhB-2 protein and one did not. None of the OMLP cases that subsequently showed evidence of dysplasia expressed the c-erhB-2 protein, and of the three OMSCC specimens from the patients with OMLP. two were negative and one expressed c-erbB-2 protein. The specimens from the control groups all expressed the c-erhB-2 protein. The results indicated the probability of the absence of c-erbB-2 staining being an indication of a potential for neoplastic transformation in OMLP with dysplastic changes.     

Granular cell tumours of the lower respiratory tract

Granular cell tumours rarely involve the lower respiratory tract. We report eight cases surgically resected at our institution. There were four females and four males, aged between 18 to 56 years (mean 40). One tumour associated with a peripheral lung adenocarcinoma was asymptomatic. The other lesions presented with obstructive pneumonitis (3 cases), haemoptysis (2), dyspnea (1) or cough (1). These tumours were tracheal (1) or bronchial (6) and one case was located in the lung parenchyma. Four cases were multicentric with associated lesions located in a bronchus (2), the oesophagus (1) or a mediastinal lymph node (1). All tumours, with the largest diameter ranging from 0.5–4.5 cm, were histologically invasive. The tumours were positive for S-100 protein, neuron specific enolase, KP1 (CD68) and vimentin. No tumour expressed desmin, keratin or p53 oncoprotein. Our study demonstrates that, in spite of marked anatomical and clinical polymorphism, the rare granular cell tumours of the lower respiratory tract have a constant histological appearance. Our observations confirm that large tumours (> 8–10 mm) usually extend beyond the tracheo-bronchial cartilages and, therefore, only surgical treatment may avoid recurrence.     

Research review: DNA polymerases as molecular markers of the regenerating capacity of hepatocytes

Hepatocyte regeneration has been widely investigated, with the mitotic index and the incorporation of [³H]thymidine being used as regeneration markers. We focused on the induction of DNA replication enzymes, particularly DNA polymerases (pol) α, δ, and ε. Using rat models, we have shown that the activity of pol α in crude liver extract well represents the regenerating capacity of hepatocytes. Using pol α as an indicator, we analyzed liver regeneration in rat models under various conditions: obstructive jaundice, external or internal biliary drainage, and the obstruction of portal vein branches. It has been revealed that the ligation of the common bile duct alone induces a certain amount of hepatocyte proliferation. It was striking that external biliary drainage suppressed regeneration capacity in cholestatic rat liver after partial hepatectomy. The strong regeneration in nonligated lobes induced by portal branch ligation was similar to the liver regeneration seen after partial hepatectomy with respect to the induction of DNA polymerases. Taken together, the aspects of DNA replication, particularly the induction of DNA polymerases, may contribute to shedding new light on the regeneration of human liver. This work was supported in part by a Grant-in-Aid for General Scientific Research and for Cancer Research from the Ministry of Education, Science and Culture, Japan, and by grants from the Uehara Memorial Foundation     

Ultrastructural and immunohistochemical study of Ewing's sarcoma and related tumors: Morphological neural markers suggesting neural histogenesis in 32 small round-cell sarcomas

The purpose of this study was to validate the hypothesis of neural histogenesis of Ewing's sarcoma of bone and related tumors by light microscopic, electron microscopic, and immunohistochemical analysis. We studied 32 round-cell sarcomas (19 cases of Ewing's sarcoma of bone, 3 extraskeletal Ewing's sarcomas, 5 peripheral primitive neuroectodermal tumors (PNET) and 5 cases of unclassified small round-cell type of neurogenic sarcoma (NS). Immunoreactivity for MIC2 was observed in all cases of Ewing's sarcoma and PNET, and in 1 cases of NS. Positive immunoreactivity for neural markers (NSE, synaptophysin, S-100) was found frequently in some tumors. Ultrastructurally, some specific features of neural differentiation, such as a fragmented basal lamina and neurosecretory granule-like particles, were found even in typical cases of Ewing's sarcoma of bone, which presented without a rosette arrangement and were almost negative for neural immuno-markers, but positive for MIC2. These ultrastructural neural features were observed less frequently in Ewing's sarcoma of bone than in PNET and NS. However, no significant correlation was demonstrated between the immunoreactivity for neural markers and the ultrastructural and histological neural features. These results support the hypothesis of a neural origin of Ewing's sarcoma and related neoplasms, and suggest that some overlapping entity could persist in PNET and Ewing's sarcoma and that this entity could be seen in histological and immunohistochemical studies of both tumors.     

胃癌病人天然杀伤细胞活性监测

报道微量细胞毒试验——LDH 释放法用于对胃癌病人临床免疫的监测.测定100例正常人和50例胃癌病人外周血 NK 细胞毒.结果:正常人值为36.10±5.68,胃癌组中,10例早期胃癌为28.76±4.70,25例进展期胃癌为14.51±5.80,15例晚期胃癌为11.86±4.43,与正常人值比较,P 值分别>0.05,<0.01和<0.01.NK 细胞毒活性随胃癌病变的进展和肿瘤体积的增大而逐渐降低,手术切除肿瘤后可有不同程度回升,甚至恢复到正常水平。长期化疗能损伤 NK 活性.     

Effect of cortisone on cells at the bone-marrow interface

Summary A study of the association between the rate of proliferation of marrow fibroblast-like stromal cells (in vitro) and the rate of endosteal bone mineralization (EsMR) (in vivo) was undertaken in an osteopenic rat model. We report than 200 g male rats treated with cortisone acetate (5 mg/day for 7 days) exhibit decreases in marrow fibroblast colony-forming units (FCFU) and tetracycline-based measurements of EsMR at the level of the femoral midshaft. In cortisone-treated rats recovering for 1–3 weeks, the FCFU census and EsMR normalized during the first posttreatment week, remained at control levels after 2–3 weeks, and exhibited a relapse in the third week which signified only partial recovery. These changes were unrelated to patterns of body weight gain. The data indicate that the FCFU census can serve to index endosteal osteoblast vigor.     

Cisplatin-associated anaemia in patients with solid tumours

We have reviewed the incidence of cisplatin-induced anaemia in patients affected with solid tumours treated with at least three courses of first-line cisplatincontaining regimens. In our experience, a low percentage (5%) of patients required transfusions of red blood cells. We think it is of the utmost importance to adopt uniform criteria in monitoring and treatment of patients at risk of developing cisplatin anaemia and to identify subsets of patients to eventually treat with erythropoietin.     

补肾中药对雄激素致不孕大鼠卵巢核仁组成区蛋白的影响

观察补肾中药对雄激素致不孕大鼠卵巢核仁组成区蛋白的影响。用ＳＤ雌性大鼠幼仔，出生９ｄ龄注射丙酸睾丸酮，制成雄激素致不孕大鼠（ＡＳＲ）模型。８０ｄ龄灌服补肾中药水溶液两周。１００ｄ龄心脏灌注处死。以核仁组成区蛋白嗜银染色（ＡｇＮＯＲ）和增殖细胞核杭原（ＰｃＮＡ）为指标，观察卵巢颗粒细胞、间质腺细胞的形态学变化。结果：补肾中药能够使ＡＳＲ卵巢颗粒细胞增殖、卵泡发育。治疗组的ＡｇＮＯＲ和ＰｃＮＡ计数明显高于模型组，而与对照组之间无显著差异。结论：补肾中药的这种作用可能是通过调节了下丘脑－垂体－卵巢性腺功能的结果，从而促使卵巢颗粒细胞发育、卵泡成熟。