应用脉冲电场凝胶电泳分析X射线诱发人骨肉瘤细？…

目的 研究电离辐射诱发人骨肉瘤肿瘤细胞ＤＮＡ双链断裂与辐射损伤修复效应,观察辐射损伤、损伤修复效应敏感性之间的关系。方法 选用强制均匀电场电泳,分别测定经不同的剂量Ｘ射线照射和相同剂量照射后培养不同时间,人骨肉瘤Ｒｈｏ０和１４３．Ｂ肿瘤细胞株ＤＮＡ双链断裂。结果 （１）Ｘ射线诱发人骨肉瘤瘤细胞的ＤＮＡ双链辐射剂量呈线性正比关系;（２）培养后的人骨肉瘤肿瘤细胞对射诱发的ＤＮＡ双链断裂具有一定修复能力     

Efficacy,Safety and Tolerability of Fesoterodine in Asian Patients with Overactive Bladder

Objectives: To assess the efficacy, safety, and tolerability of fesoterodine 4 and 8 mg once daily (QD) compared with placebo in Asian subjects with overactive bladder (OAB) after 12 weeks of treatment. Methods: This phase II, dose‐finding study consisted of a 2‐week placebo run‐in period followed by a 12‐week, randomized, double‐blind, placebo‐controlled, treatment period. Eligible subjects were aged ≥20 years with ≥8 micturitions per 24 h and ≥1 urgency urinary incontinence (UUI) episodes per 24 h reported in a 3‐day diary. The subjects were randomized to receive placebo, fesoterodine 4 mg, or fesoterodine 8 mg QD for 12 weeks. Results: Of 1232 subjects who entered the placebo run‐in period, 951 received double‐blind treatment. The mean number of UUI episodes per 24 h at baseline was 2.2 among the three treatment groups. The two fesoterodine groups showed statistically significant decreases from baseline in the mean number of UUI episodes per 24 h at week 12 (primary endpoint) compared with placebo. Most all‐causality adverse events (e.g. dry mouth and constipation) were mild or moderate. The percentage of subjects with severe adverse events was low and similar among the treatment groups (placebo, 1.3%; fesoterodine 4 mg, 1.9%; fesoterodine 8 mg, 1.0%). Conclusion: Fesoterodine 4 and 8 mg QD were significantly better than placebo in improving OAB symptoms. Overall, the two fesoterodine dosing regimens were well tolerated. These results suggest that fesoterodine 4 and 8 mg QD are effective and well‐tolerated treatments for OAB in Asian subjects.     

Gefitinib-induced autologous antitumor immunity

Aim:   We previously reported that thromboxane (TX) B2, p-selectin, and the cytokine that is regulated on activation, normal T expressed and secreted (RANTES) were elevated in patients with non-small cell lung cancer (NSCLC) treated with gefitinib. It is reported that macrophages are activated by platelets. We hypothesized that macrophages were activated in patients medicated with gefitinib, and we measured their plasma macrophage inflammatory protein (MIP)-1 beta.
Methods:   Patients with NSCLC not curable by surgery were entered in the study and received gefitinib at a dose of 250 mg/day over a period of two weeks. Blood samples were drawn before and after administration and MIP-1 beta was measured by enzyme-linked immunosorbent assay.
Results:   A total of 28 patients, 42–82-years of age (median, 67); 16 men and 12 women, were the subjects of the study: 21 had adenocarcinomas and seven squamous cancers. Partial response to gefitinib occurred in 11 patients, 12 had stable disease and five had progressive disease. The mean serum level of MIP-1 beta in the 28 evaluable patients increased significantly after gefitinib medication for 1 and 2 weeks from a baseline of 101 ± 19 pg/mL to 139 ± 25 pg/mL at one week ( P  < 0.05) and 131 ± 29 pg/mL at 2 weeks ( P  < 0.05).
Conclusion:   Immunological markers related to activated platelets including MIP-1 beta as well as thromboxane A2 p-selectin and RANTES, are elevated in patients undergoing therapy with gefitinib. We speculate that gefitinib has a potential autologous immunological anti-tumor activity.     

Defective response to thrombopoietin and impaired expression of c-mpl mRNA of bone marrow cells in congenital amegakaryocytic thrombocytopenia

Congenital amegakaryocytic thrombocytopenia (CAMT) is an uncommon disorder in newborns and infants, characterized by isolated thrombocytopenia and megakaryocytopenia in the first year without physical anomalies. The defect of thrombopoiesis is not well understood. Recently, thrombopoietin (TPO), the ligand for the c-mpl receptor, was cloned. Accumulating evidence from in vitro and in vivo studies indicate that TPO plays a key role in the regulation of megakaryocytopoiesis. In this study we examined the effect of TPO on megakaryocyte colony formation from a patient with CAMT using a plasma-containing methylcellulose clonal culture. The in vitro results demonstrated a defective response to TPO in megakaryocyte colony formation from bone marrow mononuclear cells (MNC) of the patient, although interleukin-3 (IL-3) but not stem cell factor (SCF) induced only a small number of megakaryocyte colonies. These findings indicated that thrombocytopenia in CAMT could not be corrected by administration of TPO in vitro. Additionally, clonal cultures containing SCF, IL-3, IL-6 and erythropoietin showed decreased numbers of erythroid and myelocytic progenitors in the bone marrow of the patient. The serum TPO level measured by enzyme-linked immunosorbent assay was significantly higher than that in healthy controls. By PCR, marrow MNC from healthy children and from a patient with essential thrombocytosis expressed c-mpl mRNA, whereas no c-mpl mRNA was detected in marrow MNC from the patient with CAMT. There was no difference in the CD34 expression and c-kit mRNA between the CAMT patient and healthy children. The results of this study suggest that the pathophysiology in CAMT may be a defective response to TPO in haemopoietic cells through impaired expression of c-mpl mRNA.     

Biochemical and Morphological Investigation on the Ataxic Mutant Shambling Mouse

ABSTRACT Ataxic Shambling mouse was investigated biochemically as well as morphologically to find any specific changes which would be compatible with their ataxic behaviors. Biochemical studies revealed that calcium uptake by the brain synaptosomes of ataxic mouse was decreased to about 30% at 30 mM potassium medium of the control and that the neuron specific enolase activity was lowered a half the value of control synaptosomes, while morphological investigations by Baker's staining for phospholipids disclosed little evidences of phospholipidosis in the nervous tissues and in other organs of the ataxic Shambling mouse. NAD dehydrogenase as well as myosin ATPase staining on the hindlimb muscles of the ataxic Shambling mouse showed a local atrophy and a certain derangement of muscle fibers.
These results were discussed in relation to our previous finding of lowered phosphatidylserine synthesis by the brain microsomes which participated at the neuronal transport and transmission in the synaptosomes. Consequently, the ataxic behaviors of Shambling mouse would be ascribed to defective metabolism of phspholipids and decreased brain specific enolase in the synaptosomal fractions which may possibly result in reduced calcium uptake by the synaptosomes regulating neural transmission processes.     

EFFECT OF SOTALOL AGAINST REPERFUSION-INDUCED ARRHYTHMIAS IN SPRAGUE-DAWLEY AND WISTAR RATS

Summary— The effect of (±)-sotalol (aβ-blocker with class III antiarrhythmic activity) against reperfusion-induced arrhythmias was studied in artificially ventilated, open-chest, Sprague-Dawley and Wistar rats. Coronary artery occlusion was produced for 5 min and reperfusion allowed for 10 min. A somewhat different arrhythmic profile was observed between saline-treated rats of the 2 strains studied, with more Sprague-Dawley rats experiencing an irreversible ventricular fibrillation (VF) upon reperfusion, compared to Wistar rats, in whom a combination of reversible ventricular tachycardia (VT) and VF was more frequently observed. No difference in action potential characteristics and ventricular effective refractory period determined in vitro , nor in myocardial noradrenaline content, was found between the 2 strains of rats. (±)-Sotalol (5 and 10mg/kg, IV) showed marked β-blocking activity and reduced the mean duration of VT-VF in both strains studied. It also produced similar increases in action potential duration and refractory period in vitro in these 2 strains. In a different series of experiments, the antiarrhythmic action of the racemic form was compared to that of (+)-sotalol using Wistar rats. (+)-Sotalol had much less β-blocking activity, and was found to be similarly effective against reperfusion-induced VT-VF. It is concluded that the antiarrhythmic effect of sotalol against reperfusion-induced arrhythmias may not be related to β-adrenergic blockade but probably to class III type activity. Despite differences in the profile of reperfusion-induced arrhythmias between Sprague-Dawley and Wistar rats, both strains were sensitive to the antiarrhythmic action of (±)-sotalol.     

Concomitant adenosquamous carcinoma of the common bile duct and early adenocarcinoma of the gall-bladder

We report a 59 year old male with obstructive jaundice and a clinical diagnosis of carcinoma of the midportion of the common bile duct. Examination of the surgical specimen revealed a small tumour in the neck of the gall-bladder. Histologic examination revealed the tumour in the common bile duct was an adenosquamous carcinoma whereas that in the gall-bladder was an early papillary adenocarcinoma. Thus, this is a rare case of the simultaneous development of adenosquamous carcinoma and early papillary adenocarcinoma in the biliary tree.     

Laparoscopic adrenalectomy in patients with large adrenal tumors

OBJECTIVES: The maximum size of adrenal tumors that should be removed by laparoscopic adrenalectomy is controversial. We conducted a retrospective comparison of the results of laparoscopic adrenalectomy between patients with adrenal tumors > or =6 cm ('large tumors') and patients with adrenal tumors <6 cm ('small tumors'). METHODS: The participants in the study were 16 patients with large tumors and 111 patients with small tumors. The patients comprised 59 men and 68 women (mean age, 49.0 years; age range, 23-79) with varying diagnoses. Of the 16 patients with large tumors, five had Cushing's syndrome, four had pheochromocytomas, six had a non-functional tumor and one had malignant lymphoma. Adrenal tumors were confirmed by hormonal assays, biochemical tests and computed tomography. Of the 16 large tumors, five tumors were on the right and 11 were on the left. RESULTS: We found no significant differences in general demographic parameters between patients with large and small tumors. The mean duration of surgery was not significantly different between two groups. (large tumors, 210 min; small tumors,175 min). The mean volume of blood loss was 212 mL for large tumors and 30 mL for small tumors (P < 0.001, significant difference). There was no significant difference in time until walking, duration of hospitalization or number of using analgesics used. The time to first oral intake of group 1 (<6 cm) was significantly shorter than group 2 (> or =6 cm). Tumor size (> or =7.5 cm) was an independent predictor of a longer operation and greater blood loss in large tumors. CONCLUSIONS: Laparoscopic adrenalectomy for large tumors was safe and minimally invasive.     

Adverse drug reactions of intravesical bacillus Calmette–Guérin instillation and risk factors of the development of adverse drug reactions in superficial cancer and carcinoma in situ of the bladder

BACKGROUND: We examined the incidence and severity of adverse drug reactions following intravesical bacillus Calmette-Guerin (BCG) instillation for superficial bladder cancer including carcinoma in situ. We investigated the relationship between adverse drug reactions and patient background to clarify risk factors for the development of adverse drug reactions. METHODS: A total of 123 patients who underwent intravesical BCG instillation for treatment and prophylaxis between April 1997 and June 2000 were included in this study. Adverse drug reactions were divided into local and systemic categories and the severity of reactions was classified according to the presence or absence of postponement or discontinuation of instillation, with or without treatment for the reaction itself. RESULTS: Of 123 patients, 95.9% showed adverse drug effects and 50.4% needed some sort of treatment. Discontinuation of instillation due to adverse drug reactions was observed in nine patients. Regarding the necessity of treatment for adverse drug effects, the purpose of instillation and BCG dose were independent significant factors on multivariate analysis. CONCLUSION: Although there was a high rate of adverse drug reactions after intravesical BCG instillation, the rate of discontinuation of instillation was not high and serious adverse reactions were rare. The scale of the present study was small, but these results suggest that BCG instillation was well tolerated. When instillation is being performed for the purpose of treatment, and the BCG dose is 80 mg, greater attention might be needed to monitor for the development of adverse drug effects.     

Good's syndrome (hypogammaglobulinemia with thymoma) presenting intractable opportunistic infections and hyperkeratotic lichen planus

Good's syndrome (GS) is a rare acquired combined T- and B-cell immunodeficiency accompanying thymoma. This report concerns a case of a 57-year-old man with GS manifesting intractable opportunistic infections and hyperkeratotic lichen planus. He had a past history of extended thymectomy for removal of thymoma. He consulted us about scaly and exudative intractable erythematous plaque on his right forearm. The histology was compatible with phlegmon coexisting with lichen planus. Laboratory examination results indicated hypogammaglobulinemia accompanied by complete absence of B cells, which is consistent with GS. Combined treatment with immunoglobulin replacement and administration of antibiotics and antifungal drugs was effective for the phlegmon and overlying fungal infection. The patient also presented with hyperkeratotic lichen planus on both knees and the right elbow, suggesting that intractable opportunistic infection and lichen planus may be associated with GS.