The analysis of thymidine phosphorylase examined by ELISA in bladder cancer

PURPOSE: Some reports suggest that the high level expression of thymidine phosphorylase (TP), which is known as one of angiogenic factors, is related to high malignancy and also poor prognosis in the field of gastrointestinal cancer. So the authors investigated the expression of TP in bladder cancer. MATERIALS AND METHODS: The expression of TP in cancer tissues and normal tissues, which were obtained during transurethral resection of the tumor of 66 patients with initial primary bladder cancer, was examined by enzyme-linked immunosorbent assay (ELISA). And relationship of the TP expression and clinicopathologic factors was investigated. RESULTS: The level of TP expression was significantly high in cancer tissues compared with normal tissues (P < 0.0001). About the level of TP expression of cancer tissues, there was a significant difference between G1 and G3 in grade (P = 0.0099), Ta and T2 or greater (P = 0.0059), Ta, T1 and T2 or greater (P = 0.0157) in T stage, papillary and non-papillary in surface form (P = 0.0056), pedunculated and sessile in tumor shape (P = 0.0458), and 1 cm or under and 3 cm or greater in size (P = 0.0267). The level was higher in latter, respectively. About the level of TP expression of normal tissues, the level was significantly higher in the cases with sessile tumor than the cases with pedunculated tumor (P = 0.0078). CONCLUSION: There is correlation between the level of TP expression of cancer tissues and their grade of malignancy, so we can expect that the level of TP expression of cancer tissues will be a prognostic factor. And what does it mean in the fact that the level of TP expression of normal tissues in patients with sessile tumor is higher? It should be clear after accumulation of the cases and collecting the episodes in the follow-up period.     

A crucial role of Nrf2 in in vivo defense against oxidative damage by an environmental pollutant, pentachlorophenol.

Our goal was to elucidate roles of Nrf2 in in vivo defense against pentachlorophenol (PCP), an environmental pollutant and hepatocarcinogen in mice. We examined oxidative stress and cell proliferation, along with other hepatotoxicological parameters, in the livers of nrf2-deficient (wild:+/+, heterozygous:+/-, homozygous:-/-) animals fed PCP in their diet at doses of 0, 150, 300, 600, or 1200 ppm for 4 weeks. For measurement of methoxyresorufin-O-demethylase (CYP 1A2), NAD(P):quinone oxidoreductase 1 (NQO1), and UDP-glucuronosyltransferase (UDP-GT), an additional study was performed with all but the 150-ppm dose. Significant elevation of 8-hydroxydeoxyguanosine (8-OH-dG) levels in the liver DNA was observed only in -/- mice treated with PCP at 1200 ppm. Levels of thiobarbituric-acid-reactive substances (TBARS) were also raised significantly compared to those of the relevant +/+ mice. Bromodeoxyuridine labeling indices (BrdU-LIs) of hepatocytes in -/- mice were significantly higher at all doses than those in the relevant +/+ mice. Relative liver weights were unchanged in mice lacking Nrf2, whereas liver weight in +/+ and +/- mice was increased. Significant elevations of serum ALP activity, but not ALT and AST activity, occurred at 600 ppm and above in -/- mice compared to the relevant +/+ mice. Histopathologically, centrilobular hepatocyte necrosis was severe in the -/- mice that received 600 ppm. Although CYP 1A2 activity was elevated in all treated mice, increases in NQO1 levels and UDP-GT activities did not occur only in -/- mice. These data suggest that Nrf2 plays a key role in prevention of PCP-induced oxidative stress and cell proliferation.     

QT PRODACT: in vivo QT assay in anesthetized dog for detecting the potential for QT interval prolongation by human pharmaceuticals

The purpose of this study was to assess the utility of the isoflurane-anesthetized dog model for detecting the potential for QT interval prolongation by human pharmaceuticals. The effects of 10 positive compounds with torsadogenic potential, 8 negative compounds with little torsadogenic potential, and dl-sotalol as a common positive compound were evaluated in 5 facilities in accordance with the common protocol approved by QT PRODACT. Each test compound was cumulatively infused into male beagle dogs anesthetized with isoflurane. Surface lead II ECG, blood pressure, and plasma concentrations for the positive compounds were measured. Repeated administration of the vehicle examined in each facility before the start of the experiments resulted in a slight, but not significant, change in corrected QT (QTc) interval, indicating that this model only shows slight experimental variation. Although an inter-facility variability in the extent of dl-sotalol-induced QT interval prolongation was observed, dl-sotalol significantly prolonged QTc interval in all facilities. All positive compounds significantly prolonged QTc interval at plasma levels up to 10 times those in patients who developed prolonged QTc interval or TdP, whereas no negative compounds did so. These data suggest that the in vivo QT assay using the anesthetized dog is a useful model for detecting the potential for QT interval prolongation by human pharmaceuticals.     

Early onset distal muscular dystrophy with normal dysferlin expression

A 7-year-old boy, who was noted to be a slow runner at the age of 2 years, had progressive muscle weakness and atrophy, preferentially affecting distal muscles. At 3 years of age, he had scoliosis and difficulty in standing on tip-toe. Serum creatine kinase was 1074 IU/l. Muscle CT scan showed low-density areas in the lower legs and upper arms, but predominantly in the gastrocnemius and soleus muscles. Biopsy of the biceps brachii muscle showed moderate dystrophic changes with normal dysferlin expression on immunohistochemical and western blot analyses. Although muscle involvement mimicked that seen in Miyoshi myopathy (MM), the very early onset of the disease and scoliosis were quite unusual for MM. We, therefore, made the diagnosis of early onset dysferlin-positive distal muscular dystrophy, probably a new type of distal muscular dystrophy.     

Trichophyton tonsurans infection manifesting as multiple concentric annular erythemas

We report a case of dermatophytosis in a Judo wrestler caused by Trichophyton tonsurans (T. tonsurans) with clinical features that mimicked the concentric rings of tinea imbricata. Tinea imbricata is a unique dermatophytosis caused by Trichophyton concentricum (T. concentricum), observed endemically in subtropical to torrid zones and characterized by impressive concentric rings. We found three similar cases of the dermatophytosis in the literature that were reported as tinea pseudoimbricata or tinea indecisiva. All of these cases were associated with systemic or local immunosuppression, perhaps simulating the mechanism of tinea imbricata, which is known to involve the lack of delayed type hypersensitivity to T. concentricum. These cases imply that iatrogenic immunosuppression may perhaps play an important role in the development of the unique clinical features mimicking tinea imbricata. Furthermore, three of the four cases, including the presented case, were caused by T. tonsurans. It may be necessary to consider T. tonsurans infection when multiple concentric erythemas are encountered.     

Resection of the Colon Simultaneously with Pancreaticoduodenectomy for Tumors of the Pancreas and Periampullary Region: Short-term and Long-term Results

Simultaneous resection of the colon with pancreaticoduodenectomy (PD) is occasionally inevitable to accomplish curative resection in instances when a periampullary tumor involves the mesentery of the colon. However, there is little information regarding short- and long-term outcomes of this aggressive surgery. Among 95 consecutive patients who underwent PD for periampullary malignant tumors, 12 had simultaneous resection of the right colon (group 1) and 83 underwent PD alone (group 2). Intraoperative variables, postoperative morbidity and mortality, and the length of the hospital stay were comparatively analyzed. Survival was also compared between the groups in a subset of 36 pancreatic adenocarcinoma patients. Group 1 included more patients with pancreatic cancer, and portal vein resection was more frequently performed, which seemed to be associated with a significantly longer operating time (640 vs. 510 minutes) and increased total blood loss (1965 vs. 1220 ml). However, morbidity and mortality rates did not differ between the groups (50,0% and 0%, respectively, in group 1; 44.6% and 1.2%, respectively, in group 2). The median hospital stays were 67 and 48 days in groups 1 and 2, respectively. In a subset of 36 pancreatic adenocarcinoma patients, the median progression-free survivals were 6 months in both groups 1 and 2; the median overall survivals were 14 months in group 1 and 12 months in group 2. There was no statistically significant difference in survival between the groups. Simultaneous right hemicolectomy with curative intent at the time of PD could thus be performed safely and may offer a survival benefit even for individuals who have advanced pancreatic cancers with involvement of the transverse mesocolon.     

New simple method for small, dense LDL: development of a new quantification method and clinical significance

Small, dense LDL (S LDL) is regarded as a significant risk factor for coronary heart disease (CHD) and has also been reported its high appearance in type 2 diabetic patients. Although ultracentrifugation and electrophoresis based methods are currently used for the measurement of S LDL, such methods are either too laborious or expensive for clinical use. We have developed a simple method for quantification of S LDL. The new method consists of two steps; first to filter out large buoyant LDL and other apoB-containing lipoproteins by forming aggregates of these unintended lipoproteins with a heparin-manganese based reagent; and second to measure S LDL-cholesterol (S LDL-C) in the penetrate solution, the mixture of HDL and S LDL, on automated general chemistry analyzers. Comparison with the ultracentrifugation method yielded a correlation coefficient of 0.900 and an equation of y = 1.090x-1.8 (n = 146). Positive correlation was observed with total LDL-C level and also with triglyceride level (r = 0.782 and r = 0.526, respectively) while negative correlation was observed with LDL particle size (r = 0.658). As for the study with various types of hyperlipidemia sample, the highest level of S LDL-C was observed in combined hyperlipidemia patients. Patients with CHD had higher S LDL-C than control group (45.2 +/- 22.1 in the CHD vs. 36.7 +/- 16.9 in the control), however no difference was seen in total LDL-C level between the two groups (117.6 +/- 35.0 in the CHD vs. 115.7 +/- 30.1 in the control). Patients with type 2 diabetes also showed higher S LDL-C (54.0 +/- 22.7). S LDL-C/LDL-C ratios were also significantly higher in CHD patients and in type 2 diabetes patients than the control group (39.9 +/- 16.7 in the CHD, 37.6 +/- 13.0 in the type 2 diabetes and 31.0 +/- 9.9 in the control). Our findings suggest that this method can measure S LDL reliably with a simple procedure and that the analysis of S LDL-C can give a better index for the risk assessment of CHD than total LDL-C.     

Sequential evaluation of the national medical expenditures for asthma care in Japan

BACKGROUND: It has been reported that the prevalence of asthma is on the rise in various countries; but studies on its effects on national medical expenditures are scarce. METHODS: From the outcome of the "Estimates of National Medical Care Expenditures" and "Patient Survey" compiled by the Statistics and Information Department, Minister's secretariat, the Ministry of Health, Labour, and Welfare of Japan, medical expenditures on asthmatic patients in Japan were sequentially examined. RESULTS: It was found that the percentage of asthmatic patients to the general medical care expenditures has been on the steady increase. A closer examination revealed that the percentage of asthmatic outpatients receiving care increased while those receiving care as inpatients decreased. CONCLUSION: The relationships between the percentage of the number of asthmatic patients utilizing medical services and the expenditures for their care differed between inpatients and outpatients.     

Effects of static load on the weight and protein content in the leg muscles of the mouse: a simulation of prolonged standing in the workplace

To simulate the effects of prolonged standing in the workplace on the leg muscles, we subjected mice to centrifugation for 6 wk. The absolute wet weight of leg muscles and internal organs of mice were measured after exposure to 3G by centrifugation for 6 wk and at 2 wk after removal of centrifugation. The weight of the soleus muscle (antigravity muscle) significantly increased after 6-wk exposure to centrifugation, but it decreased to its control weight 2 wk after removal of centrifugation. In contrast, the wet weights of the anterior tibial muscle, liver, and kidneys of mice centrifuged for 6 wk were significantly lower than those of the control mice; they had returned to control levels 2 wk after removal of centrifugation. It was therefore suggested that prolonged standing enlarged the leg muscles but its effect did not last for a long period of time after stopping prolonged standing. Western blot analysis of proteins extracted from the soleus muscle showed that vinculin and alpha-actinin in the centrifuged mice increased slightly, but there were no differences in the heat shock protein 70 (HSP70) and desmin levels between the centrifuged mice and control mice. No difference in HSP 70 suggested that muscle damage did not exist after 6 wk centrifugation.