p53 mutations in early neoplastic lesions of the urinary bladder in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine

Rat experimental models using Ar-butyl-Af-(4-hydroxybutyl) nitrosamine(BBN) as an initiating agent have been widely used to studycarcinogenic processes in the urinary bladder. In this study,early neoplastic lesions from 10 male F344 rats treated with0.05% BBN for 16 weeks were analyzed for changes in the H-rasor p53 genes by polymerase chain reaction (PCR)-single strandconformation polymorphism (SSCP) analysis and subsequent DNAsequencing. Lesions were pooled for each of the 10 rats andsix showed point mutations in the p53 gene and one in the H-rasgene. These results would indicate that BBNinduced rat urinarybladder carcinomas are similar to human urinary bladder carcinomaswith respect to alterations in the p53 and H-ras genes and thatp53 gene alterations are relatively early events in rat urinarybladder carcinogenesis induced by BBN treatment     

Epidemiologic Survey of Children with End-Stage Renal Disease

We performed an epidemiologic study on the basis of a questionnaire survey of 162 children with end-stage renal disease (ESRD). Sixty-nine (43%) of our 162 children, including 25 detected at mass screening of urine, were found by chance hematuria and/or proteinuria. The three major causes of ESRD in our children were chronic glomerulonephritis (CGN) in 56, congenital anomalies of the urinary tract in 30, and nephrotic syndrome (NS) in 27. The renal pathology in 39 children with CGN or NS was focal glomerular sclerosis in 15, diffuse mesangial GN in 7, IgA GN in 5, membranoproliferative GN in 3, membranous GN in 3, and unclassified in 6. Forms of dialysis initiated were hemodialysis in 91 children, continuous ambulatory peritoneal dialysis (PD) in 66, and intermittent PD in 5. Renal transplantation was performed on 38 children, and the graft and the patient survival rates were 76% and 89%, respectively. The survival rate of our 162 children for a mean follow-up of 8.1 years was 77%. In conclusion, an integrated program of maintenance dialysis and transplantation provides a favorable life for children with ESRD.     

Histopathological Analysis of Invasive Bladder Carcinomas Induced by 3,2'-Dimethyl-4-aminobiphenyl in Hamsters

Histopathological characteristics of urinary bladder tumors induced in Syrian golden hamsters by 3,2'-dimethyl-4-aminobiphenyl (DMAB) were analyzed. DMAB was subcutaneously injected in corn oil at a concentration of 100 mg/kg once a week for 20 weeks and ethinyl estradiol (EE) was administered in the diet at a dose of 0.75 ppm throughout the experiment. A small group of animals was killed at week 20 and all survivors were killed at week 50. Urinary bladder carcinomas were induced in 14 of 18 hamsters (78%; 0.89/animal) in the DMAB+EE group and 11 of 17 (65%; 0.88/animal) in the DMAB alone group in males, and in 11 of 14 (79%; 0.79/animal) in the DMAB+EE group and 4 of 5 (80%; 0.80/animal) in the DMAB alone group in females examined between weeks 20 and 50. All were non-papillary invasive transitional cell carcinomas partly demonstrating glandular and/or squamous differentiation, and most carcinomas developed in the bladder neck. Degree of invasion was clearly correlated with degree of morphological atypism in the transitional cell carcinomas, hut not with squamous or glandular differentiation. No sex difference or modifying effect of EE on DMAB urinary bladder carcinogenesis was evident. No bladder carcinomas were observed in non-DMAB-treated animals.     

A long-term follow-up study of severe variant of central serous chorioretinopathy

PURPOSE: To facilitate understanding of the long-term course and visual outcome of a severe variant of central serous chorioretinopathy. DESIGN: Consecutive observational case series. PATIENTS AND METHODS: The authors reviewed 25 patients with multifocal posterior pigment epitheliopathy and bullous retinal detachment, who had a mean follow-up time of 10.6 years (range, 6-22 years), with reference to the demographic feature, fundus changes, recurrence, and final anatomic and visual outcome. Two patients underwent optical coherence tomography. RESULTS: The patients were 21 men and 4 women, with a mean age at disease onset of 43.1 years (range, 30-63 years). Twenty-one patients were otherwise healthy, and four developed ocular disease during systemic corticosteroid therapy for metabolic or autoimmune diseases including systemic lupus erythematosus. The disease was bilateral in 21 patients (84%). Nine patients (36%) presented initially with classic central serous chorioretinopathy, followed by its severe variant 7 months to 9 years later. Active disease was characterized by multifocal exudative lesions in the posterior pole and bullous retinal detachment with shifting subretinal fluid in the inferior periphery. Optical coherence tomography of exudative lesions disclosed cloudy and fibrinous subretinal fluid. The exudative lesions were self-limited or responded to photocoagulation. During the follow-up period, 13 patients (52%) showed 1 to 5 recurrent disease, but the disease eventually became quiescent with multifocal atrophic scars in the posterior pole with or without atrophic tracts in the inferior periphery. Final best-corrected visual acuity was 2020 or better in 24 of 46 affected eyes (52%) of 25 patients and 2040 or better in 37 eyes (80.4%). CONCLUSIONS: A severe variant of central serous chorioretinopathy characterized by multifocal posterior exudations and bullous inferior retinal detachment with shifting subretinal fluid may affect otherwise healthy, middle-aged males or individuals receiving systemic corticosteroid therapy for metabolic or autoimmune diseases. Exudative chorioretinal lesions are self-limited or respond to photocoagulation. Recurrence is common, but the disease eventually becomes quiescent with favorable visual acuity unless the macula is damaged.     

Beneficial effect of T-1095, a selective inhibitor of renal Na+-glucose cotransporters,on metabolic index and insulin secretion in spontaneously diabetic GK rats

1. To investigate the pharmacological effects of T-1095, this novel derivative of phlorizin was administered to GK rats for 8 weeks. T-1095 treatment significantly lowered plasma glucose and glycosylated haemoglobin (HbA1c) levels, but did not significantly affect bodyweight. 2. T-1095 treatment did not affect 3.3 mmol/L glucose-induced insulin secretion in the isolated perfused pancreas of GK rats. 3. The peak insulin release in T-1095-treated GK rats was significantly higher during the first phase than in untreated GK rats (3-4 min after beginning 16.7 mmol/L glucose perfusion). The total amount of insulin secreted during the first phase in T-1095-treated GK rats was significantly higher than in untreated GK rats (35.3 +/- 1.4 vs. 27.3 +/- 2.5 ng in T-1095-treated compared with untreated rats, respectively). 4. During the second phase, insulin release in T-1095-treated GK rats was somewhat higher than in untreated GK rats (7-30 min after beginning 16.7 mmol/L glucose perfusion). The total amount of insulin secreted during the second phase in T-1095-treated GK rats was significantly higher than in untreated GK rats (88.2 +/- 6.1 vs. 68.1 +/- 5.7 ng, respectively). 5. The total amount of insulin secreted during perfusion in T-1095-treated GK rats was significantly higher than in untreated GK rats (123.5 +/- 7.3 vs. 95.4 +/- 7.7 ng, respectively). 6. These data show that the metabolic indices, plasma glucose and HbA1c levels and insulin secretion are significantly improved by T-1095 treatment in GK rats, which are spontaneously diabetic rats, suggesting its usefulness as a novel oral therapeutic antidiabetic agent.     

Survey of susceptibility of methicillin-resistant Staphylococcus aureus to antimicrobial agents in Hokusetsu General Hospital

We examined the annual isolation rate, susceptibility to antimicrobial agents and coagulase types of methicillin-resistant Staphylococcus aureus (MRSA) isolated from inpatients in Hokusetsu General Hospital to ascertain the situation of MRSA isolates between 1992 and 2001. The isolation rate of MRSA in S. aureus increased annually from 1992, reaching 65.3% in 2001. The isolation rates of MRSA in the inpatients were 3.2 times greater than those in the outpatients. In the clinical specimens the isolation rate of MRSA from sputum was the highest, i.e., 32.9%. In respect of the coagulase types, type II accounted for 85.7% of the all types. MIC90 values of arbekacin, sulfmethoxazole-trimethoprin, vancomycin, teicopranin and minocycline were 4.0, 2.0, 2.0, 2.0, and 8.0 micrograms/ml, respectively.     

Characterization of functional nicotinic acetylcholine receptors involved in catecholamine release from the isolated rat adrenal gland

We tried to characterize nicotinic acetylcholine receptors involved in the release of catecholamines from the rat adrenal gland. The isolated adrenal gland was retrogradely perfused via the adrenal vein with Krebs-Ringer solution at a flow rate of 0.5 ml/min. Endogenous catecholamines, adrenaline and noradrenaline, released into the perfusate were electrochemically measured using high-performance liquid chromatography. (-)-Nicotine (3 x 10(-6)-3 x 10(-5) M) evoked the release of catecholamines (adrenaline > noradrenaline) in a concentration-dependent manner. The (-)-nicotine (10(-5) M)-induced release of catecholamines was effectively attenuated by mecamylamine (10(-7) and 10(-6) M) (a relatively selective antagonist of alpha3beta4 nicotinic receptors), but not influenced by alpha-bungarotoxin (3 x 10(-7) M) (an antagonist of alpha7 nicotinic receptors) and dihydro-beta-erythroidine (10(-5) M) (a relatively selective antagonist of alpha4beta2 nicotinic receptors). (+/-)-Epibatidine (3 x 10(-7) and 10(-6) M) (a non-selective nicotinic receptor agonist), (-)-cytisine (10(-5) and 10(-4) M) (an agonist of beta4 nicotinic receptors) and (+/-)-2-(3-pyridinyl)-1-azabicyclo(2.2.2)octane (RJR-2429) (10(-5) M) (a putative agonist of alpha3beta4 nicotinic receptors) effectively evoked the release of catecholamines (adrenaline > noradrenaline), while (E)-N-methyl-4-(3-pyridinyl)-3-butene-1-amine (RJR-2403) (up to 10(-4) M) (a selective agonist of alpha4beta2 nicotinic receptors) had no effect. The efficacies of these agonists are as follows: (+/-) epibatidine > RJR-2429>(-)-cytisine>(-)-nicotine > RJR-2403. These results suggest that alpha3beta4 nicotinic receptors are involved in the release of catecholamines from the rat adrenal gland.     

Preserved IFN-alpha production of circulating Valpha24 NKT cells in primary lung cancer patients

Human Valpha24 NKT cells bearing an invariant Valpha24JalphaQ antigen receptor, the counterpart of murine Valpha14 NKT cells, are activated by a specific ligand, alpha-GalCer, in a CD1d-dependent manner. Here, we demonstrate decreased numbers of circulating Valpha24 NKT cells in patients with primary lung cancer compared to healthy volunteers. However, Valpha24 NKT cells and DCs from lung cancer patients were functionally normal, even in the presence of tumor. Furthermore, levels of Valpha24 NKT cells in surgically resected lung tissue appeared to be equivalent to those of Valpha14 NKT cells in the mouse lung. Levels of Valpha24 NKT cells in the tumor tissue itself were increased about 2.5 times. Administration of alpha-GalCer-pulsed DCs expanded Valpha14 NKT cells in the lung more than 10 times, and the increased levels were sustained for 1 week. This may explain the previous finding that alpha-GalCer-pulsed DCs exerted strong antitumor activity in mouse lung tumor metastatic models. The potential use of alpha-GalCer-pulsed DCs for immunotherapy aimed at activating endogenous Valpha24 NKT cells in the lung of cancer patients is discussed.