过氧化氢对豚鼠耳蜗功能及形态的影响

目的 在体观察过氧化氢(H2O2)对豚鼠耳蜗功能及形态的影响。方法 实验动物分为4组，分别灌流人工外淋巴液(artificial perilymph,APL)，50μMH2O2，100μMH2O2和200μMH2O2(H2O2均溶于APL中)，并用Pl和H033342双染色方法观察H2O2引起的内耳细胞损伤情况。结果 所有H2O2灌流组复合动作电位((CAP)阈移和耳蜗微音电位(CM)幅度变化与人工外淋巴液组比较差异有显著性，且各H2O2组的变化呈现出浓度依赖性；Pl和H033342双染色方法发现外毛细胞是H2O2攻击的主要靶细胞，而Hensen细胞未见任何损伤痕迹。结论 H2O2可导致耳蜗功能下降及耳蜗毛细胞损伤：Hensen细胞较毛细胞可能具有更强的抗氧化能力。     

Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma.

PURPOSE: Denileukin diftitox is a fusion protein combining diphtheria toxin and interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor. Its efficacy has been shown in CD25+ cutaneous T-cell lymphoma, but not in B-cell non-Hodgkin's lymphoma (NHL). A phase II study was performed to evaluate the efficacy and tolerability of denileukin diftitox for relapsed or refractory B-cell NHL. PATIENTS AND METHODS: Patients with relapsed or refractory B-cell NHL were eligible. Tumor CD25 expression was determined by immunohistochemistry or flow cytometry. Denileukin diftitox was administered intravenously at a dose of 18 microg/kg once daily for 5 days every 3 weeks, up to eight cycles. RESULTS: Of the 45 patients assessable for response, 32 (71%) were refractory to the last chemotherapy treatment, and all were previously treated with rituximab. Three complete responses (6.7%) and eight partial responses (17.8%) were observed, for an overall response rate of 24.5%. Nine patients (20%) had stable disease. Objective response rates were similar in CD25+ (22%) and CD25- histologies (29%), as were stable disease rates (22% and 18%, respectively). For responding patients, the median time to treatment failure was 7 months, with a median follow-up in survivors of 18 months (range, 9 to 28 months), and the projected progression-free survival at 20 months was 24% (95% CI, 0% to 60%). Most toxicities were low-grade and transient. CONCLUSION: Denileukin diftitox seems to be effective in relapsed or refractory, CD25+ and CD25- B-cell NHL and is well-tolerated at the dosage evaluated. Evaluation of denileukin diftitox in combination with other agents may be warranted.     

C-Jun NH(2)-terminal kinase mediates proliferation and tumor growth of human prostate carcinoma.

PURPOSE: C-Jun NH(2)-terminal kinase (JNK) has been implicated in numerous functions including stress responses, apoptosis,and transformation. The role in transformation is based largely on studies of isolated cell types with little indication of whether JNK plays a general role in a specific human tumor type or whether this occurs in vivo. EXPERIMENTAL DESIGN: We examined 9 human prostate carcinoma cell lines in vitro and a representative line in vivo. RESULTS: For all of the cell lines proliferation is highly correlated with serum-supported JNK activity (r(Pearson) = 0.91; P = 0.004), whereas no relationship was observed for 10 human breast cancer cell lines (r(Pearson) = -0.32). Treatment with characterized antisense oligonucleotides complementary to sequences common to either the JNK1 or JNK2 family of isoforms showed that, whereas antisense JNK1 inhibited growth by a maximum of 57%, antisense JNK2 inhibited proliferation up to 80%. Sense and scrambled control oligonucleotides had little effect (average 3.7 +/- 1.5%). Moreover, systemic treatment of mice bearing established xenografts of PC3 prostate carcinoma cells with antisense JNK1 and JNK2 led to inhibition tumor growth by 57% (P < 0.002) and 80% (P < 0.001), respectively. The difference is significant (P < 0.012). Combined antisense treatment led to a significant increase in frequency of tumor regression (P = 0.022). CONCLUSION: These results indicate that JNK is required for growth of prostate carcinoma cells in vitro and in vivo, and additionally indicate that JNK2 plays a dominant role. The JNK pathway is a novel target in the treatment of prostate carcinoma.     

KTP Laser and Neutral Red Phototherapy of Human Squamous Cell Carcinoma

Neutral red (NR) is a cationic, nontoxic vital dye employed as a histologic stain for proliferating cells; it has been used clinically for photodynamic treatment of herpes simplex virus lesions. NR is selectively taken up and concentrated by mitotic cells, an important characteristic for more effective antineoplastic agents. In the present study, UCLA-SO-P3 human squamous carcinoma cells displayed minimal toxicity when incubated with up to 50 μg/ml NR in the absence of light. However, cells incubated with greater than 0.5μg/ml NR followed by exposure to KTP laser light at 532 nm exhibited nearly 100% tumor cell death. The degree of cell toxicity was proportional to NR dose and laser light fluence. This study demonstrates that NR is an excellent cancer cell photosensitizer in vitro, and, after adding additional in vivo preclinical testing, may prove to be a useful agent in photodynamic destruction of head and neck tumors.     

Insulin resistance is associated with decreased clinical status in cystic fibrosis

Patients with cystic fibrosis (CF) frequently have impaired glucose tolerance and progression to diabetes (DM) with clinical features of both insulin-dependent and non-insulin-dependent diabetes. One feature of non-insulin-dependent DM is decreased insulin sensitivity, also known as insulin resistance. The goal of this study was to determine whether patients with CF exhibit insulin resistance and to determine the potential effect of insulin resistance on clinical status. We also sought to determine whether insulin resistance is associated with a specific CF genotype. We studied 18 patients with CF (8 with normal glucose tolerance, 5 with impaired glucose tolerance, 5 with DM), and 20 lean control subjects matched for age, weight, and sex. All control subjects had normal glucose tolerance. The clinical status for each CF patient was determined according to a modified National Institutes of Health scoring system. Each subject underwent a three-step hyperinsulinemic euglycemic clamp (insulin doses of 10, 40, 120 mU/m ² per minute). Results from the 120 mU/m ² per minute infusion defined maximal glucose disposal rate (defined in milligrams per kilogram body weight per minute) at steady state with peripheral insulin levels 195 ± 20 mU/ml. Subjects with CF demonstrated insulin resistance (control subjects = 13.6 ± 1.1, patients with CF = 10.2 ± 1.6 mg/kg per minute; p = 0.003). When each subgroup was compared separately with control subjects, all subgroups were statistically insulin resistant (glucose disposal rate, patients with CF and normal glucose tolerance = 10.8; those with impaired glucose tolerance = 8.4; those with DM = 10.1 mg/kg per minute), and the patients with CF with impaired glucose tolerance were the most insulin resistant. When plotted versus glucose disposal rate, a striking positive correlation between worsened clinical status and insulin resistance ( r = 0.85) is demonstrated. Furthermore, there is no correlation between insulin resistance and fasting blood glucose, subject age, or percent ideal body weight (all r values not significant). In conclusion, patients with CF exhibit insulin resistance that is associated with worsened clinical status. We believe it is the combination of insulin resistance and decreased insulin secretion that is responsible for the high incidence of CF-related diabetes. (J Pediatr 1997;130:948-56)     

The procoagulant activity of red blood cells from patients with severe preeclampsia

OBJECTIVE: Our purpose was to determine whether red blood cells from patients with severe preeclampsia may exhibit increased membrane exposure of procoagulant phospholipids (i.e., phosphatidylserine), which may initiate intravascular clotting and platelet activation. STUDY DESIGN: The study group comprised 28 women: 9 with severe preeclampsia in the third trimester of pregnancy, 10 normotensive with uncomplicated pregnancies, and 9 age-matched, nonpregnant, healthy women. The exposure of phosphatidylserine on the outer membrane phospholipid layer was analyzed with use of isolated, washed red blood cells that were added as a source of phospholipids to a “prothrombinase” coagulation complex. RESULTS: The resultant thrombin formed was measured by an amidolytic assay. Thrombin generation significantly increased on the addition of red blood cells from women with preeclampsia (741 ± 132 mU/ml/min) compared with red blood cells from normotensive pregnant (422 ± 228 mU/ml/min) and nonpregnant women (316 ± 268 mU/ml/min, p = 0.0008). CONCLUSION: This study indicates that in patients with preeclampsia the red blood cells exhibit a significant procoagulant surface that may trigger thrombin formation, thereby playing a role in the hypercoagulable state.(Am J Obstet Gynecol 1997;177:6)     

输精管结扎兔睾丸IL-1与血浆睾酮变化的研究

为了探讨输精管结扎术后睾丸IL—1的活性、来源及其与睾酮变化的关系,同步检测了结扎6、25个月家兔辜丸匀浆上清IL—1活性和血浆睾酮含量,并进行了睾丸组织IL—lmRNA的原位杂交.结果表明:(1)睾丸组织匀浆上清IL-1活性以VG6为高,与SOG6比较有显著差异(P<0.01);(2)睾丸组织IL-1mRNA的原位杂交,VG6中IL-lmRNA的杂交信号明显强于其他各组,杂交信号主要分布在曲细精管内的 Sertoli细胞和生殖细胞,也见于间质中的某些细胞中;(3)血浆睾酮含量结扎术后6个月明显降低,与对照组比有显著差异(P<0.05),IL-1活性与血浆睾酮含量呈明显的负相关关系(r=-0.595,P<0.01).故推测,结扎早期睾丸炎症所引起的巨噬细胞活化和Sertoli细胞吞噬变性精子和残余体过程增强,可能是睾丸IL-1的主要来源.输精管结扎术后IL-1活性的一过性升高可能是睾酮含量下降的原因.IL-1可能作为旁分泌调节因子抑制Leydig细胞睾酮合成.     

The health care professional's attitudes towards brain death and cadaveric organ transplantation: the influence of cadaveric donor and transplantation programs--a Malaysian survey

One of the main reasons for poor response in organ donation is the lack of positive attitudes and knowledge present in health care professionals. Definite legislation, policies and programmes dealing with brain death and cadaveric organ transplantation have shown some favourable results in terms of increasing donor rates. These programmes are mainly Western based; therefore adopting such programmes to be used locally may not be adequate or proper. To address this issue, we decided to carry out a questionnaire in two tertiary hospitals in Malaysia, one with a well establish brain death and cadaveric organ transplantation programme and one with none.