Effects of Nonanal,trans-2-Nonenal and 4-Hydroxy-2,3-trans-nonenal on Cyclooxygenase and 12-Lipoxygenase Metabolism of Arachidonic Acid in Rabbit Platelets

The effects of nonanal, trans-2-nonenal and 4-hydroxy-2,3-trans-nonenal on the formation of thromboxane B₂ (TXB₂), 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) from exogenous arachidonic acid in washed rabbit platelets were examined. Nonanal and trans-2-nonenal at concentrations ranging from 0.25 to 2 μm inhibited TXB₂, HHT and 12-HETE formation, reducing the amounts of these three arachidonic acid metabolites by 50% at nonanal and trans-2-nonenal concentrations of approximately 0.25 μm. The inhibition of TXB₂, HHT and 12-HETE formation induced by 4-hydroxy-2,3-trans-nonenal (50% inhibition by 4-hydroxy-2,3-trans-nonenal at a concentration of approximately 100 μm) was 400 times weaker than that induced by nonanal and trans-2-nonenal. These results suggest that nonanal and trans-2-nonenal can be modulators of platelet arachidonic acid metabolism by affecting the activity of cyclooxygenase and 12-lipoxygenase.     

Effects of glycyrrhizin on immune-mediated cytotoxicity

Intravenous administration of glycyrrhizin is known to decrease elevated plasma transaminase levels in patients with chronic viral hepatitis, in which immune-mediated cytotoxicity by cytotoxic T lymphocytes and tumour necrosis factor (TNF)-α is considered to play an important pathogenic role. However, the immunological interpretation of the transaminase-lowering action of glycyrrhizin is not known. Studies were performed to elucidate this action immunologically by assessing the effects of glycyrrhizin on immune-mediated cytotoxicity using an antigen-specific murine CD4⁺ T hybridoma line, which exhibits cytotoxicity against antigen-presenting cells after stimulation with specific antigen, and a murine TNF-α-sensitive fibroblast line. Glycyrrhizin inhibited the cytotoxic activity of the T cells against antigen-presenting cells and also suppressed TNF-α-induced cytotoxicity in the TNF-α-sensitive cell line in vitro. These results suggest that the decrease of elevated transaminase levels by glycyrrhizin in patients with chronic viral hepatitis is mediated in part by inhibition of immune-mediated cytotoxicity against hepatocytes.     

抗CEA抗体C2-45重链恒定区的置换与活性鉴定

目的:将抗癌胚抗原(CEA)单克隆抗体(mAb)C245(IgG4)转变成IgG1,增强其在抗肿瘤免疫中的作用。方法:采用PCR从C245(IgG4)基因中克隆VH和Vk基因,并插入到含有人IgG1恒定区(CH)基因的杆状病毒表达载体pAckCH3中。用构建的重组基因感染Sf9昆虫细胞,将获得的高滴度重组病毒用于最终表达重组蛋白。应用免疫亲和层析法,纯化培养上清中表达的重组蛋白C245(IgG1),并鉴定其与CEA结合的能力和CH的生物学功能CDC及ADCC。结果:经CH置换形成的重组蛋白C245(IgG1),既保留了对于表达CEA的肿瘤细胞的结合,又比原抗体C245(IgG4)的补体依赖的细胞毒作用(CDC)和抗体依赖的淋巴细胞的细胞毒作用(ADCC)强得多。结论:成功地应用基因工程的方法制备了置换CH的抗CEA的人抗体C245(IgG1),使其在肿瘤的免疫治疗中具有更广泛的应用价值。     

A female infant successfully treated by ganciclovir for congenital cytomegalovirus infection

An 11 month old female infant, diagnosed as having congenital cytomegalovirus (CMV) infection and suffering from pneumonia and intractable diarrhea, was treated with 9-(1,3-dihydroxy-2-propoxymethyl) guanine (DHPG), intravenously for 8 weeks. Watery diarrhea ceased and pneumonia associated with massive endotracheal aspirates was reduced. No leukopenia, thrombocytopenia or other side effects were observed during the therapy. The clinical findings suggest that DHPG might be an effective and safe agent for the treatment of both intestinal and lower respiratory CMV infection in young infants.     

Natural Products: Effects of Sho-saiko-to Extract on Fibrosis and Regeneration of the Liver in Rats

Sho-saiko-to, one of the most widely used Chinese herbal preparations, has long been used for the treatment of chronic liver diseases. We have investigated its effect in retarding the process of liver fibrosis and accelerating liver regeneration, especially its effect on Ito cells that are thought to be deeply involved with liver fibrosis. Sho-saiko-to extract and its active constituents were orally administered to rats with dimethy lnitrosamine-induced liver-injury. After treatment with sho-saiko-to extract hepatic function improved, histopathological results confirmed repair of liver tissue, and retinoid levels increased. On the other hand, when active constituents of sho-saiko-to extract were administered alone, liver retinoid levels remained low, implying that interaction among active constituents of the extract was suppressing Ito cell activation. When sho-saiko-to extract was administered to 70% hepatectomized normal and liver-injured rats, liver weight, the number of S-phase-cells and retinoid levels increased with time. However, these changes were different for normal and liver-injured rats, suggesting that the site of action of sho-saiko-to extract in regenerating liver is different for normal and liver-injured rats. These results show that sho-saiko-to extract was useful for suppressing the activation of Ito cells.     

Paradoxically Shortened QT Interval after a Prolonged Pause

We analyzed Holter ECG recordings in 15 patients with episodes of prolonged RR intervals > 2.5 seconds. In 13 patients, the QT interval showed a linear prolongation when RR interval was < 1.5 seconds and became relatively flat at longer RR intervals. In the remaining two patients, the QT and RR intervals were correlated within physiological range of RR intervals. However, at longer RR intervals, the QT interval was unexpectedly shortened and constant. The paradoxically shortened QT interval observed in the present 2 cases may indicate an abnormal adaptation of repolarization time to an abrupt increase in the preceding RR intervals.     

Significance of the progression of respiratory symptoms for predicting community‐acquired pneumonia in general practice

Background and objective: Early diagnosis improves outcomes in patients with community‐acquired pneumonia (CAP). However, prediction of CAP based on symptoms and signs is difficult. The present study investigated the evaluation of progression of symptoms as a factor for predicting the occurrence of CAP in general practice. Methods: Consecutive patients (n = 406) suspected of having CAP on routine clinical examination were studied retrospectively. Selection of patients with suspected CAP was based on progression of symptoms after 5 days, as well as published criteria. Diagnostic yields for the recommended criteria and our proposed criteria were then compared. Scoring systems for the prediction of CAP were designed, based on the results of multiple regression analysis. The diagnostic performance of these systems, including or excluding symptom progression, was compared using the areas under receiver operating characteristic curves. Results: The sensitivity and specificity of the recommended criteria and our proposed criteria were 0.75 and 0.44, and 0.93 and 0.38, respectively. Sputum production, dyspnoea, fever > 38°C, heart rate > 100 beats/min, decreased breath sounds, coarse crackles and progression of symptoms significantly increased the likelihood of CAP. Areas under receiver operating characteristic curves analysis showed that the diagnostic prediction of CAP was significantly improved when the scoring system included progression of symptoms. Conclusions: Progression of symptoms was a significant factor for predicting CAP and selecting patients who required CXR. Inclusion of progression of symptoms among the other recommended criteria, namely, dyspnoea, fever > 38°C, heart rate > 100 beats/min and abnormal chest findings, improved prediction of the incidence of CAP in general practice.     

Urinary schistosomiasis in a Japanese man

A 29-year-old Japanese man with a history of travel to Africa visited the Department of Urology, Nara Medical University complaining of intermittent asymptomatic gross hematuria over a period of 30 months. As he was suspected of being infested with schistosomal parasites based on his past history of swimming in Malawi Lake during his stay in Egypt two years previously, we examined his urine microscopically for the presence of Schistosoma haematobium eggs and diagnosed him as having urinary schistosomiasis. Endoscopic examination revealed multiple small erythematous torose lesions on the right posterior wall of the urinary bladder. Since he was treated by oral administration of praziquantel every 6 h for 2 days (total daily dose of 2400 mg), a specific anthelmintic drug for schistosomiasis, the disease has been successfully kept under control without significant lesions in the bladder mucosa after the immediate disappearance of the eggs in his urine.