EXPRESSION OF CYCLIN-DEPENDENT KINASE INHIBITOR p21WAF1/CIP1 IN NON-NEOPLASTIC MUCOSA AND NEOPLASIA OF THE STOMACH: RELATIONSHIP WITH p53 STATUS AND PROLIFERATIVE ACTIVITY

The expression of the p53-inducible cyclin-dependent kinase inhibitor p21^WAF1/CIP1 in non-neoplastic mucosa, adenoma, and adenocarcinoma of the stomach was examined immunohistochemically and its relationship with p53 expression and proliferative activity was analysed. In normal gastric mucosa as well as in intestinal metaplasia the epithelial cells at the surface which showed no proliferative activity expressed p21whereas the cells in the deep area of the glands expressing Ki-67 did not. In the neoplastic lesions, the expression of p21^WAF1/CIP1 was detected in 78 per cent (112/144) of the adenomas and 76 per cent (262/343) of the adenocarcinomas. The incidence of p21^WAF1/CIP1 expression did not differ among histological types of gastric carcinoma. The strong expression of p21^WAF1/CIP1 was more frequently observed in carcinomas invading into submucosa or in cases of stages 2, 3, and 4 than in carcinomas limited to the mucosa or in stage 1 cases. The incidence of strongly positive cases was higher in carcinomas with lymph node metastasis than in those without metastasis. There was no apparent correlation between the expression of p21^WAF1/CIP1 and the abnormal accumulation of p53 or with proliferative activity measured by Ki-67 expression. These findings overall suggest that p21^WAF1/CIP1 might be associated with the senescence of non-neoplastic gastric epithelial cells; that a p53-independent pathway might be substantially involved in the induction of p21^WAF1/CIP1 in gastric neoplasia; and that the proliferative activity of gastric cancer might not be solely dependent on control of the cell cycle by p21^WAF1/CIP1.     

嘌呤类生物碱Theacrine对SIRT3调节的脂肪酸代谢相关基因影响

目的 探讨嘌呤类生物碱1,3,7,9-四甲基尿酸（Theacrine）对Sirtuin3（SIRT3）调节的脂肪酸代谢相关基因的影响。方法 对3T3-L1前脂 肪细胞进行诱导分化,并在诱导的第5天对细胞培养液中加入不同浓度的Theacrine孵育,采用实时荧光PCR（RT-PCR）方法测定细胞内SIRT3及脂肪酸代谢相关基因的表达。 并对正常小鼠灌胃给予低、中、高剂量的Theacrine（10,20,40 mg·kg-1）及Caffeine（20 mg·kg-1）1h后,采用RT-PCR测定小鼠肝脏组织、棕色脂肪组织中SIRT3及脂 肪酸代谢相关基因LCAD、ATP5c、UCP1、HTGL、FABP4等基因的表达,同时采用Western Blotting检测肝脏中SIRT3的蛋白表达。 结果 与正常对照组比较,Theacrine可以上 调3T3-L1前脂肪细胞在分化过程中SIRT3、LCAD、FABP4、LPL的表达。低剂量的Theacrine可显著上调小鼠肝脏中SIRT3基因,高剂量则表现为抑制作用,与其蛋白表达结果一 致。同时,低、高剂量的Theacrine分别显著提升及抑制小鼠肝脏中LCAD、FABP4、HTGL、ATP5c等基因表达。此外,低剂量的Theacrine对小鼠棕色脂肪中SIRT3、LCAD等基因 表达的影响不大,但显著上调了UCP1的基因表达。结论 一定剂量的Theacrine能调节相关基因影响脂肪酸代谢,该作用可能与其上调SIRT3的表达相关。     

A study of cognitive development and behavior problems in mentally retarded children

Abstract Cognitive development in seventy-one mentally retarded children (19 autistic, 52 non-autistic; aged 7–19 years) from a school for handicapped children was studied, using Ohta's scale for evaluating cognitive development level based on language comprehension (Ohta's stage), and other developmental scales. Behavior problems were also examined. The present study reports on the utility of Ohta's stage in non-autistic children, and the relationship between cognitive development level and behavior problems in mentally retarded children. In non-autistic children, there were temporal correlations between Ohta's stage and other development scales (a standard developmental test, speech development, symbolic play development, imitation development), suggesting that in non-autistic children as well, Ohta's stage may serve well as a scale for cognitive development, and reflect symbolic representational functioning. In non-autistic children, most behavior problems in feeding, elimination and sleeping, hyperkinesis, hypokinesis, stereotyped behaviors, self-injurious behavior and licking were closely associated with cognitive development level, and were more often noted in children of lower cognitive development level rather than only in the severely mentally retarded children. Some behavior problems may often occur in the sensorimotor period and hardly occur in the symbolic representational period.     

Impact of thrombocytosis and C-reactive protein elevation on the prognosis for patients with renal cell carcinoma

AIM: C-reactive protein (CRP) elevation is reportedly a prognostic factor in patients with renal cell carcinoma (RCC). Thrombocytosis has recently been reported also to be a prognostic factor in RCC and, like CRP, to be related to inflammatory cytokines such as interleukin-6. The aim of this study was to evaluate the importance of both thrombocytosis and CRP elevation in tumor recurrence and prognosis for patients with RCC. METHODS: The clinical records of 178 patients who underwent radical nephrectomy were reviewed. Thrombocytosis was defined as a platelet count >or=350,000/mm(3), and CRP elevation was defined as a CRP level >or=1.0 mg/dL. Disease-free survival and cause-specific survival rates were calculated. Independent predictors for recurrence and prognosis were determined. RESULTS: Patients with thrombocytosis and patients with elevated CRP levels had significantly higher pathological T stage, clinical stage, tumor size, histological grade, and percentage of microvascular invasion than did patients without THC and patients with CRP levels <1.0 mg/dL, respectively. There was a significant correlation between platelet counts and CRP levels. Multivariate analysis showed that distant metastasis, tumor size, grade 3 components, and CRP elevation were independent predictors for prognosis but thrombocytosis was not. In N0M0 RCC patients, tumor size, microvascular invasion, and CRP elevation were independent predictors for recurrence. CRP elevation and tumor size were independent predictors for prognosis. CONCLUSIONS: Platelet count and CRP level are strongly correlated in patients with RCC, but only CRP elevation is an independent predictor for recurrence and prognosis.     

CYTOKINE LEVELS IN CYSTIC RENAL MASSES ASSOCIATED WITH RENAL CELL CARCINOMA

Purpose

We compared cytokine levels in fluid from renal cysts with and without renal cell carcinoma.

Materials and Methods

Fluid was aspirated from 18 renal cysts without (benign) and 21 with renal cell carcinoma (malignant). Serum from patients with renal cell carcinoma and healthy controls was collected and cytokines were measured by enzyme-linked immunosorbent assay.

Results

Interleukin-6 (IL-6) and basic fibroblast growth factor concentrations were higher in malignant than benign cysts or serum (p <0.006). Epidermal growth factor levels were significantly higher in malignant cysts and serum than in benign cysts (p <0.01). IL-6 levels in malignant cysts positively correlated with the erythrocyte sedimentation rate (R = 0.80) and C-reactive protein (R = 0.86), and they were higher in grade 3 than in grade 2 tumors. Basic fibroblast growth factor levels were significantly higher in malignant cysts associated with hypervascular than hypovascular tumors (p = 0.029).

Conclusions

Cytokine levels in aspirated fluid may help to identify malignant renal cysts and indicate the characteristics of coexisting tumors.     

Two Cases of Bronchial Asthma After Treatment with Amiodarone

Amiodarone is a highly effective antiarrhythmic agent for the prevention of life-threatening arrhythmias. Two cases are described of patients who developed bronchial asthma after treatment with amiodarone. The bronchial asthma resolved after the dose of amiodarone was decreased in both patients. To our knowledge, an association between amiodarone and severe bronchial asthma has previously been reported only once in the medical literature. Physicians should note that amiodarone may cause bronchospasm in susceptible patients.     

Inhalation exposure to 2-ethyl-1-hexanol causes hepatomegaly and transient lipid accumulation without induction of peroxisome proliferator-activated receptor alpha in mice

2-Ethyl-1-hexanol (2EH) is a volatile organic compound known to cause sick building syndrome. However, 2EH-induced hepatotoxicity has been mainly evaluated in experiments orally administering 2EH as a metabolite of di(2-ethylhexyl) phthalate. To evaluate the hepatotoxicity risk of 2EH as an indoor air pollutant, we exposed 10-wk-old male ICR mice to 2EH by inhalation for 8 h/d, 5 d/wk for 3 months (0, 20, 60, or 150 ppm) or 6 months (0, 0.5, 10, or 100 ppm). In both experiments, relative liver weights significantly increased in the highest exposure groups. The 3-month exposure increased histopathological lipid droplets in the liver in a dose-dependent manner, hepatic triglyceride at all exposure levels, hepatic phospholipid at 150 ppm, and microsomal triglyceride transfer protein at 60 and 150 ppm; however, these changes were not observed following the 6-month of exposure. Following the 3-month exposure, alanine transaminase and peroxisomal bifunctional proteins, known markers of liver injury and peroxisome proliferation, respectively, remained unaltered. Therefore, in the present study, the inhalation concentration range of 2EH induced a toxic hypertrophic change, revealing a limited role of peroxisome proliferator-activated receptor alpha (PPARα). The liver weights may have presumably increased via a mechanism independent of PPARα activation.     

Survival Rate and Shunt Infection Incidence Following Gastrostomy in Adult Patients with an Existing Ventriculoperitoneal Shunt

Ventriculoperitoneal shunts (VPS) and gastrostomies are frequently provided in daily practice. This study investigated the incidence of VPS infection and the survival rate among adult patients who underwent gastrostomy at least 1 month after VPS placement. This single-center retrospective cohort study was conducted among patients with a VPS, who underwent a gastrostomy. This procedure was performed on a standby basis after a period of at least 1 month had elapsed since VPS placement. Subsequent VPS infection and survival rates were assessed over a period of at least 6 months. We reviewed 31 patients who had a VPS at the time of gastrostomy. Gastrostomy was performed endoscopically in 29 cases and via open surgery in 2 cases. The average interval between VPS insertion and gastrostomy was 1135.5 ± 1717.1 days. A single case of VPS infection (3.2%) was diagnosed during the study. This infection rate was not significantly different than that among 230 patients who underwent their first VPS placement (without gastrostomy) at our institution during the same time period (P = .57); there was also no significant difference in the survival rate, compared to 38 age-matched patients (with cerebrovascular disease, but without a VPS) who underwent gastrostomy (P = .73). Gastrostomy performed after an interval of at least 1 month after VPS placement was extremely safe in adult patients, and their prognosis was excellent. Additional studies are required to develop appropriate nutritional interventions for patients with a VPS.     

苦茶的化学成分

目的：对苦茶（Camellia assamica vat．kucha Chang et Wang）叶的化学成分进行研究。方法：采用水提取,聚酰胺、Sephadex LH-20、ODS柱和HPLC等手段分离纯化,通过理化常数和谱学数据鉴定化合物的结构。结果：分离鉴定了10个化合物,其中3个为嘌呤生物碱类化合物,分别为theacfine（1）,caffeine（2）,theobromine（3）;7个为茶多酚类,分别为（＋）-catechin（4）,（-）-epigallocatechin（5）,（-）-gallocatechin（6）,（-）-epigaUocatechin 3-O—gallate（7）,（-）-gallocatechin 3-O—gallate（8）,1,2,6-tri—O—galloyl-β—D—glucose（9）,gallicacid（10）。结论：化合物4-10为首次从该植物中分离得到,并首次对化合物1的核磁数据进行了全归属。