Nonselective cation channels activated by the stimulation of muscarinic receptors in mammalian gastric smooth muscle.

Muscarinic receptors play key roles in the control of gastrointestinal smooth muscle activity. However, specific physiological functions of each subtype remain to be determined. Single cell RT-PCR experiments showed that all five subtypes of muscarinic receptors were present in circular smooth muscle cells of the guinea-pig gastric antrum. Nonselective cation channels (NSCC) activated by ACh or CCh are coupled to pertussis toxin (PTX)-sensitive Go protein through m4 subtype as well as m2 and m3 subtypes in guinea-pig stomach. CCh-activated currents (I(CCh)), especially the steady-state I-V relationship of I(CCh) showed a chracteristic U-shaped curve; reversal potential of around 0 mV and inward rectification at around +15 mV and a negative slope conductance at negative potential range. Under physiological conditions, the measured single channel conductance of NSCC was approximately 25 pS. The single channel conductance was modulated by external monovalent and divalent cations including Na+, Cs+, Li+, and Ca2+ through changing both the open probability and unitary conductance. Through the NSCC, Ca2+ can move into the cell from extracellular solution as well as Na+. Calculated fractional Ca2+ current of I(CCh) (f(Ca)) was around 1% at the 2 mM [Ca2+]o and at the 4 mM [Ca2+]o, f(Ca) was 2.3%. Quinidine blocked I(CCh) potently in a reversible manner; IC50 was 0.25 microM. There were two kinds of I(CCh) modulations through Ca(2+)-dependent pathways in guinea-pig gastric smooth muscle cells; 1) Facilitation of I(CCh) via Ca2+/CaM-dependent MLCK pathway, 2) Desensitization of I(CCh) via Ca(2+)-dependent PKC pathway. In the mouse stomach, all seven types of TRPC mRNA were detected with RT-PCR. On the basis of electrophysiological, pharmacological, and molecular biological experiments, we reported the mTRPC5 as a candidate for the NSCC activated by muscarinic stimulation in mouse stomach.     

Mycobacterium marinum infection of the hand and wrist. Results of conservative treatment in twenty-four cases

Inadequate débridement, extensive scarring, and breakdown of the wound have been commonly encountered after surgical débridement has been employed as the initial treatment of infection with Mycobacterium marinum involving the deep structures of the hand. Because of our disappointment with the results of this form of treatment, from 1982 to 1986 we treated twenty-four patients who had such an infection with rifampicin and ethambutol after a diagnostic biopsy was done. Surgical treatment was deferred until it was determined that the infection had not been controlled by the chemotherapy. The clinical outcome for these patients could be divided into three patterns: eleven patients (Group I) had a good result with no complications, three patients (Group II) had delayed healing of the wound, and ten patients (Group III) did not have a good response to conservative treatment and required one or more surgical débridements. Complications were sometimes associated with use of the drugs, and loss of visual acuity was a concern in three patients. In twenty-one (87 per cent) of the patients, at follow-up the function of the treated hand was equal to that of the other hand. Persistent pain, a discharging sinus, and previous local injection of steroids were unfavorable prognostic factors. If these factors are present, surgical débridement is advised.     

Characterization of htAKR, a novel gene product in the aldo-keto reductase family specifically expressed in human testis

In human testis, expression of a novel member of the aldo-keto reductase family was identified. Based on its testis-specific expression, we termed this protein human testis aldo-keto reductase (htAKR). In addition to four major isoforms, the existence of multiple alternatively spliced products of htAKR was detected using RT-PCR followed by nested PCR. htAKR was a homologue of mouse liver keto-reductase, AKR1E1, with close similarity in their genomic organizations. htAKR4, the longest isoform, was expressed as a non-fused native form. It exhibited a limited activity toward 9,10-phenanthrenequinone, while no activity toward the steroids or prostaglandins was demonstrated. Using the laser capture microdissection technique and RT-PCR, expression of htAKR was detected in testicular germ cells as well as in interstitial cells. The levels of htAKR mRNA in the tissues obtained from seminoma were much lower than those in normal testes. A significant decline in the htAKR expression was observed when NEC8, a cell line originated from a human testicular germ cell tumour, was exposed to phorbol 12-myristate 13-acetate or 5alpha-dihydrotestosterone. These results indicate that the expression of htAKR, down-regulated in the testicular tumour, is possibly controlled by mitogenic and hormonal signals.     

Thrombus of the ascending aorta: a rare cause of myocardial infarction.

We present two cases of a thrombus in the ascending aorta causing an acute myocardial infarction (AMI) and review the 10 other cases previously reported in the literature. This life-threatening condition appears to be more common in female smokers in their fifth decade. Suspicion should be raised in individuals at low risk for atherosclerotic disease with coronary angiographic findings not in keeping with the clinical presentation. The diagnosis may be obtained by transesophageal echocardiography, and we generally recommend surgical thrombectomy.     

香港与澳门中小学学校辅导发展的比较

目的 探讨香港与澳门两地中小学学校辅导的发展，就辅导工作的内容、开展情况、辅导人员在建设上的差别以及发展速度相异的原因等方面作分析。方法 本研究以香港及澳门中小学的学校辅导员／社工为调查对象，利用自编问卷方式进行调查．结果 （1）两地的辅导员都一致认为，通过学校辅导服务可以帮助中学生建立良好的社交行为及人际关系，（2）两地的中小学都在帮助学生更好地接纳他人及尊重他人这个项目上都做得较好；（3）两地的中小学校辅导的目标不再是以处理学生的偏差行为为主，转而注重学生的个人潜能发展；（4）就课堂辅导活动开展的情况来看，香港在班级辅导、全年级辅导及全校性辅导方面都做得比较好，而澳门的全校性辅导通有待加强。至于课堂以外的辅导活动，两地均以个别晤谈，团体辅导、心理卫生讲座以及工作坊等方式开展辅导活动为多。（5）在持介制度上，香港中小学都做得比较完善；（6）咨询服务方面，香港小学做得较多，而澳门则是中学做得较多；（7）新生适应服务方面，香港较澳门做得较多；（8）香港的学校比澳门学校更多地与其它机构共同合辩小区教育；（9）香港及澳门的中学辅导员主要是学校自聘／校内编制，两地的中学社工主要是由政府资助民间志愿机构派驻。香港的小学导员以学校自聘／校内编制和政府派驻为主，香港的小学社工以政府直接派驻为多；澳门的小学辅导员为政府派驻，小学社工则由政府资助民间志愿机构派驻为多。（10）对于两地学校辅导人员学历的比较，香港中学及小学专职辅导贝、专职社工的学历均较澳门为高．结论 两地在学校辅导目标上比较一致；两地均建立了发展辅导为主，预防辅导及治疗辅导并重的辅导模式；家庭问题及人际关系问题为两地中小学生的困扰问题；两地的学校辅导活动呈现一个多元化的局面，但香港较澳门丰富；澳门需要建立完善的转介机构。     

Expression of transforming growth factor-beta1 and transforming growth factor-beta receptors in hepatocellular carcinoma and dysplastic nodules.

In this study we analyzed by immunohistochemistry the expression of TGF-beta1 protein and TGF-beta receptors I and II in 4 low-grade dysplastic nodules, 2 high-grade dysplastic nodules, 6 early, 22 small, and 62 advanced hepatocellular carcinomas. The expression of TGF-beta1 protein by hepatocytes was decreased in advanced hepatocellular carcinoma compared with small or early hepatocellular carcinoma(P < .05). Frequent and intense staining of TGF-beta1 protein was noted in the sinusoidal endothelium of advanced hepatocellular carcinomas despite of its decreased staining in hepatocellular carcinoma cells. Reduced expression of TGF-beta receptors I and II compared with surrounding nontumorous tissue were noted from the early hepatocellular carcinoma stage suggesting that down-regulation of TGF-beta receptors is correlated with progression from premalignant to malignant phenotype. Reduced expression of both TGF-beta1 and TGF-beta receptor II in neoplastic hepatocytes were also significantly correlated with increased tumor size and increased proliferative activity(P < .05). These findings suggest that during hepatocarcinogenesis, the inhibitory effects of TGF-beta1 protein on hepatocellular carcinoma cells is outweighed by its effects on stromal elements, which, overall, contributes indirectly to a tumor growth stimulatory environment. Also, the growth-inhibitory effects of TGF-beta1 may have been further negated by reduced TGF-beta receptors on hepatocellular carcinoma cells.