検索

Administration of ferric nitrilotriacetate (Fe-NTA) in vivo causes acute renal tubular injury and finally induces renal cell carcinoma. There is accumulating evidence that these processes involve free radicals generated by Fe-NTA. To study the mechanism of renal carcinogenesis by Fe-NTA, we attempted to induce malignant transformation of primary cultured renal cells by treatment with Fe-NTA. When primary cultured renal cells (PRC) were treated continuously with Fe-NTA, all of the PRC died without transformation. On the other hand, when PRC were treated intermittently with Fe-NTA, transformed epithelial colonies were observed at 3 weeks after the first treatment. The established transformed cell line (RK523) showed drastic morphological transformation, grew in soft agar, and formed tumors when transplanted into athymic nude mice. These results indicate that the balance between cytotoxicity and mutagenecity is important for Fe-NTA induced transformation. The RK523 cell line may be a useful model for studying renal carcinogenesis in vitro.

We used a regression tree method (RTM) to determine risks of depression in children/adolescents. The survey records of 4,143 children/adolescents in a study based in Mersin, Turkey served as data in this study, and multi-step, stratified, and cluster sampling were used. Effects of 24 variables (sex, smoking, parental problems, etc.) were evaluated on depression scores. The Child Beck Depression Inventory (CBDI) was used to determine the level of depression. Subjects were into 12 different groups based on magnitudes of mean depression scores. The interactions among 7 variables determined to be risk factors are shown on a schema. The STATISTICA (ver.6.0) package program was used for all computations. Although traditional statistical methods have often been used for analysis in this field, such approaches are associated with certain disadvantages such as missing values, ignorance of interaction effects, or restriction of the shape of the distribution. To avoid such disadvantages, we therefore suggest the use of the RTM in studies involving numerical-based outcome variables and for the investigation of a large number of variables and it may be more effective than traditional statistical methods in epidemiological studies which determine risk factors.

In this study, we investigated the effects of both 25 and 50 mg daily doses of rofecoxib on the endothelial functions of patients with coronary artery disease (CAD). For this purpose, 34 patients with documented severe CAD and who were under aspirin treatment (300 mg/day) were randomized to receive 4 weeks of treatment with a placebo (n = 10, group I), rofecoxib 25 mg/day (n = 12, group II), and rofecoxib 50 mg/day (n = 12, group III). Brachial artery vasodilator responses were measured in order to evaluate endothelial function. The percentage of change in endothelial-dependent vasodilation in groups I, II, and III were similar at the baseline level and showed no significant change after treatment (6.2+/-3.9% vs. 5.9+/-3.1% and 5.8+/-3.3% vs. 5.6+/-3.8% and 6.1+/-4.5% vs. 5.8+/-4.1%, respectively; P > 0.05). Compared with the baseline, endothelium-independent vasodilatation, as assessed by nitroglycerine (NTG), remained unchanged after the treatment period (11.2+/-6.9% vs. 10.3+/-7.1% and 11.2+/-6.3% vs. 9.9+/-5.1% and 9.5+/-4.9% and 8.8+/-4.6%, respectively; P> 0.05). Treatment with both doses also showed no significant effects on high-sensitivity C-reactive protein (hs-CRP) levels and resting arterial diameters (P > 0.05). In conclusion, 4 weeks of treatment with standard and high doses of rofecoxib showed no significant effects on either endothelial-dependent or independent vasodilator response or plasma hs-CRP levels in patients with severe CAD taking concomitant aspirin.

It was recently reported that gene therapy using hepatocyte growth factor (HGF) has the potential to preserve cardiac function after myocardial ischemia. We speculated that this HGF gene therapy could also prevent ventricular arrhythmia. To investigate this possibility, we examined the antiarrhythmic effect of HGF gene therapy in rat acute and old myocardial infarction models. Myocardial ischemia was induced by ligation of the left descending coronary artery. Hemagglutinating virus of Japan (HVJ)-coated liposome containing HGF genes were injected directly into the myocardium fourteen days before programmed pacing. Ventricular fibrillation (VF)was induced by programmed pacing. The VF duration was reduced and the VF threshold increased after HGF gene therapy ( p< 0.01). Histological analyses revealed that the number of vessels in the ischemic border zone was greatly increased after HGF gene injection. These findings revealed that HGF gene therapy has an anti-arrhythmic effect after myocardial ischemia.

The present study was performed to investigate the effects of valerian extract on the sleep-wake cycle using sleep-disturbed model rats. A significant shortening in sleep latency was observed with valerian extract at doses of 1000 and 3000 mg/kg. On the other hand, valerian extract had no significant effects on total times of wakefulness, non-rapid eye movement (non-REM) sleep, or REM sleep, even at a dose of 3000 mg/kg. Valerian extract at doses of 1000 and 3000 mg/kg showed a significant increase in the delta activity during non-REM sleep. In conclusion, valerian extract may be useful as an herbal medicine having not only sleep-inducing effects but also sleep quality-enhancement effects.

Lamivudine is widely used to treat patients with hepatitis B. However, the outcomes in patients with hepatocellular carcinoma (HCC) treated with lamivudine have not been established. This study was conducted to evaluate the outcomes of lamivudine treatment for patients with HCC using an untreated, matched control group. Thirty patients with controlled HCC orally received lamivudine. As controls, 40 patients with HCC who were not treated with lamivudine and matched for clinical features were selected. The lamivudine-treated and untreated groups were compared with respect to changes in liver function, HCC recurrence, survival, and cause of death. In the lamivudine-treated group, there was significant improvement in the Child-Pugh score at 24 months after starting treatment, while no improvement was observed in the untreated group. There was no significant difference in the cumulative incidence of HCC recurrence and survival between the groups. However, there was a significant difference in the cumulative incidence of death due to liver failure (P= 0.043). A significant improvement in liver function was achieved by lamivudine treatment, even in patients with HCC. These results suggest that lamivudine treatment for patients with HCC may prevent death due to liver failure. Further prospective randomized studies using a larger number of patients are required.

This study focused on the effects of different intervals between sessions of a hypercholesterolemia education class on post-intervention outcomes. The same comprehensive group-programme contents on hypercholesterolemia were delivered either monthly (for 6 months) or twice-monthly (for 3 months) by the same teaching professionals in a community setting. The twice-monthly programme included 46 participants (male/female = 7/39, average age: 65.8 years)and the monthly programme consisted of 48(male/female = 9/39, age: 66.4). At the beginning of the study, all subjects belonged to the 'contemplation' stage of diet and exercise habits within the Transtheoretical Model of Change. The stage-matched intervention helped many participants move to the 'action ' stage by 6 months after the last session, especially in the twice-monthly group. The change rate of exercise from the 'contemplation' stage to the 'action' stage was significantly higher in the twice-monthly group (76.1 percent) than in the monthly (54.2 percent ). In both monthly and twice-monthly formats, participants' satisfaction and understanding levels at the end of the programme were high, but were significantly higher in the twice-monthly group. Through favorable lifestyles and higher levels of satisfaction and learning, the twice-monthly format may produce more positive results in cholesterol management than the monthly format, as the shorter period of time makes the programme more intensive.

Epstein-Barr virus (EBV) is usually maintained in an asymptomatic and latent form by the host immune system, and primarily by EBV-specific cytotoxic T cells (CTLs). However, EBV has been linked to several refractory diseases such as EBV-associated hemophagocytic syndrome(EBV-AHS) and chronic active EBV infection (CAEBV). In these ectopic diseases, EBV infects T/NK cells, causing severe immunodeficiency with a very high EBV load. In recent years, the laboratory procedure to assess these types of EBV infections has been improved. In particular, real-time polymerase chain reaction (PCR) has been used to quantify the EBV load, and the MHC: peptide tetramer assay has been used to quantitate EBV-specific CTLs; these tests have been employed for the management of the illnesses associated with EBV infection. Here, we have reviewed the recent progress in the clinical application of these assays. The pathogenesis of EBV-infected T/NK cells, and the host immune response to infection, including the roles carried out by innate immunity and inflammatory cytokines, are likely to be revealed in the future.

Macrophages and microglia are implicated in spinal cord injury, but their precise role is not clear. In the present study, activation of these cells was examined in a spinal cord injury model using 2 different antibodies against ED1 clone and ionized calcium binding adaptor molecule 1 (Iba1). Activation was observed at 1, 4, 8, and 12 weeks after contusion injury and was compared with sham operated controls. Our results indicate that activation could be observed in both the dorsal funiculus and the ventral white matter area in the spinal cord at 5 mm rostral to the epicenter of injury. For both cells, there was a gradual increase in activation from 1-4 weeks, followed by down-regulation for up to 12 weeks. As a result, we could stain macrophages by ED1 and microglia by Iba1. We concluded that macrophages may play a role in the phagocytosis of denatured dendrites after spinal cord injury, while microglia may have some cooperative functions, as they were found scattered near the macrophages.

To investigate the effect of exclusive breastfeeding on the likelihood of Japanese preschool children being overweight, population-based cross-sectional survey data from M town in Japan were used. Using the population registry of this town, all 616 preschool children were identified, and a self-administered questionnaire was sent to their parents. The exposure variable of interest was exclusive breastfeeding from birth to 6 months, and the outcome variable of interest was the children being overweight at preschool age. Statistical analyses used included logistic regression and sensitivity analyses. In the final analyses, we included 448 preschool children. Although all point estimates indicated a protective effect, logistic regression analyses showed no significant reduction in being overweight due to exclusive breastfeeding in the unadjusted model (odds ratio (OR)0.70, 95% confidence intervals:0.30-1.64), the model adjusted for birth weight (OR0.70, 95% CI:0.30-1.63), the model adjusted for child lifestyle (OR0.71, 95% CI:0.30-1.67), or the model adjusted for parental factors (OR0.46, 95% CI:0.15-1.37). In sensitivity analyses, point estimates were not significant, but a protective effect was observed. In conclusion, our results suggest that breastfeeding might have a protective effect on Japanese preschool children against being overweight, although statistical significance was not observed due to the limitation of the statistical power of the findings.

The present study was performed to clarify the effect of hypertonic saline infusion into the lung parenchyma on radiofrequency ablation (RFA) of the lungs. A total of 20 ablation zones were created in 3 pigs. The ablation zones were divided into 3 groups. Group 1 (n6) consisted of ablation zones created by applying smaller radiofrequency (RF) power without saline infusion;group 2 (n5) zones were created by applying greater RF power without saline infusion;and group 3 (n9) zones were created by applying greater RF power with saline infusion. The techniques of saline infusion included administration of hypertonic saline 1ml before RFA, followed by continuous administration at a rate of 1ml/min during the first 2min after the initiation of RFA. The ablation parameters and coagulation necrosis volumes were compared among the groups. Group 3 had a tendency toward smaller mean impedance than group 1 (p0.059) and group 2 (p0.053). Group 3 showed significantly longer RF application time than group 2 (p0.004) and significantly greater maximum RF power than group 1 (p0.001) and group 2 (p0.004). Group 3 showed significantly larger coagulation necrosis volume (mean, 1,421mm3) than group 2 (mean, 858mm3, p0.039) and had a tendency toward larger necrosis volume than group 1 (mean, 878mm3, p0.077). Although this small study had limited statistical power, hypertonic saline infusion during RFA appeared to enlarge coagulation necrosis of the lung parenchyma.

For many years, surgery alone was the standard treatment for patients with stage I-IIIA non-small-cell lung cancer (NSCLC). However, recent studies have demonstrated that adjuvant chemotherapy provides a survival benefit. The first adjuvant chemotherapy for NSCLC was performed in the 1960s using a key drug known as cyclophosphamide. In the 1980s and early 1990s, a new anti-cancer drug, cisplatin, was developed. The first meta-analysis of this drug was conducted by the Non-small Cell Lung Cancer Collaborative Group in 1995. This analysis comparing surgery with surgery plus chemotherapy containing cisplatin produced a hazard ratio of 0.87 and suggested an absolute benefit of chemotherapy of 5% at 5 years;this difference was not statistically significant (p0.08). Several clinical trials of adjuvant chemotherapy were planned after the meta-analysis conducted in 1995, but the efficacy of adjuvant chemotherapy remained a matter of controversy. However, useful evidence was reported after 2003. The International Adjuvant Lung Cancer Collaborative Group Trial (IALT) demonstrated a 4.1% improvement in survival for patients with stage I to III NSCLC. The JBR. 10 trial demonstrated a 15% improvement in 5-year survival for the adjuvant chemotherapy arm in stage IB or II (excluding T3N0) patients. The Adjuvant Navelbine International Trialist Association (ANITA) trial reported that the overall survival at 5 years improved by 8.6% in the chemotherapy arm and that this survival rate was maintained at 7 years (8.4%) in stage II and IIIA patients. A meta-analysis based on collected and pooled individual patient data from the 5 largest randomized trials was conducted by the Lung Adjuvant Cisplatin Evaluation (LACE). This analysis demonstrated that cisplatin-based adjuvant chemotherapy improved survival in patients with stage II or III cancer. Alterna-tively, uracil-tegafur has been developed and tested in Japan. The Japan Lung Cancer Research Group (JLCRG) on Postsurgical Adjuvant Chemotherapy reported a 5-year overall survival advantage of 11% in the uracil-tegafur group patients with stage IB cancer. The efficacy of adjuvant chemotherapy with uracil-tegafur was confirmed in a meta-analysis. In conclusion, the results of phase III trials and a meta-analysis have confirmed the benefit of adjuvant chemotherapy for resected stage IB, II, and IIIA NSCLC.

This study evaluated the effects of chronic hypoxia from birth on the resistance of rat hearts to global ischemia, with special emphasis on the duration of hypoxia. Male Wistar rats were housed from birth for 4 weeks or 8 weeks either in a hypoxic environment (FiO20.12) or in ambient air (8 animals for each group). Isolated rat hearts were perfused for 40 min with oxygenated Krebs-Henseleit buffer, subjected to 20 min global no-flow ischemia at 37, and then underwent 40 min of reperfusion. A non-elastic balloon was inserted into the left ventricle and inflated until the pre-ischemic LVEDP rose to 8mmHg. Cardiac function was measured before and after ischemia. The post-ischemic percent recovery of LVDP in hypoxic hearts was worse than in normoxic hearts (4 weeks:55+/-7 vs. 96+/-3%, p0.01;8 weeks:40+/-5 vs. 92+/-4%, p0.01), and was worst in the 8-week-hypoxic hearts. Similarly, the percent recovery of dP/dt in the hypoxic hearts was lower than in the normoxic hearts (4 weeks:51+/-5 vs. 96+/-7%, p0.01;8 weeks:31+/-6 vs. 92+/-7%, p0.01), and was lowest in the 8-week-hypoxic hearts. In conclusion, cyanotic myocardium revealed an age-dependent vulnerability to ischemia-reperfusion injury in a chronic hypoxic rat model.

Vitis coignetiae Pulliat (Yamabudo) is used as a health juice and wine based on the abundant polyphenols and anthocyanins in its fruit. However, it is not known whether the leaves of this plant confer similar benefits. This study investigated the hepatoprotective effects of aqueous extracts from Vitis coignetiae Pulliat leaves (VCPL) in an animal model of nonalcoholic steatohepatitis (NASH). Rats were fed a choline-deficient high-fat diet for four weeks to generate fatty livers. NASH was induced by oxidative stress loading. Ten weeks later, blood and liver samples were collected from anesthetized animals and assessed biochemically, histologically, and histochemically to determine the extent of oxidative stress injury and the overall effects of VCPL. Six-week VCPL extract supplementation reduced serum levels of liver enzymes, decreased CYP2E1 induction, increased plasma antioxidant activities and delayed the progression of liver fibrosis. The findings suggested that VCPL has strong radical-scavenging activity and may be beneficial in preventing NASH progression.

The present study aimed to investigate the status of physical activity and the differences in psychological factors associated with physical activity from the perspective of transtheoretical model stages between prime- and middle-aged Japanese. The study involved 375 prime-aged volunteers (175 men, 200 women) and 557 middle-aged volunteers (247 men, 310 women) living in Kuse, a town in Okayama Prefecture, Japan. We found that the prime-aged men at the preparation stage had significantly higher self-efficacy scores than at the contemplation stage (p<0.01). Middle-aged men had significantly higher self-efficacy scores at the contemplation stage than at the precontemplation stage (p<0.001). Middle-aged women, meanwhile, had significantly higher self-efficacy scores at the maintenance stage than at the action stage (p<0.01), and at the contemplation stage than at the precontemplation stage (p<0.001). The present findings provide valuable information about the differences in psychological factors affecting physical activity between prime-aged and middle-aged community-dwelling Japanese. This information may be useful to health professionals as they develop effective community-based intervention programs for target populations.

Little information is available on the mechanism of diastolic left ventricular (LV) dysfunction in patients with chronic respiratory disease complicated by hypoxia. The purpose of this study was to investigate how chronic hypoxia impairs LV diastolic function in an hypoxic animal model. Thirty-six male Wistar rats 8 weeks old were assigned to normoxia (N), chronic hypoxia (CH), and re-normoxia (RN) groups, 12 rats per group. The N group rats were kept in ambient air for 8 weeks, while the CH group was kept hypoxic for 8 weeks. After 8 weeks of hypoxia the RN group rats were kept for a further 8 weeks in ambient air. LV systolic and diastolic functions, as well as right ventricular (RV) function, were analyzed using Doppler echocardiography;we also measured the hematocrit, and weighed the LV and RV. Hematocrit, RV weight/body weight, and RV weight/LV weight were higher in the CH group than in the other 2 groups. However, most of these parameters returned to normoxia levels after re-normoxia. In the CH group, LV dimension and area were smaller than in the other 2 groups. LV systolic function was preserved in all groups;however, in the CH group, mitral flow showed a restrictive pattern, while pulmonary flow demonstrated a pulmonary hypertensive pattern with prolonged RV ejection time. In conclusion, chronic hypoxia induced pulmonary hypertension and RV hypertrophy. Although LV systolic function was preserved, diastolic function was impaired in hypoxia. Ventricular interaction may impair LV diastolic function.

The authors previously developed a mobile ecological momentary assessment (EMA) system as a real-time data collection device using a mobile phone. In this study, a real-time advice function and real-time reporting function were added to the previous system as a supportive intervention. The improved system was found to work effectively and was applied to several clinical cases, including patients with depressive disorder, dizziness, smoking habit, and bronchial asthma. The average patient compliance rate was high (89%) without the real-time advice and higher (93%) with the advice. The trends in clinical data for patients using a mobile EMA with/without the new function were analyzed for up to several months. In the case of dizziness, an improving trend in its clinical data was observed after applying the real-time advice, and in the case of depressive disorder, a stabilizing trend was observed. The mobile EMA system with the real-time advice function could be useful as a supportive intervention in behavior modification and for motivating patients in self-management of their disease.

Conventionally, the carrying angle of the elbow is measured using simple two-dimensional radiography or goniometry, which has questionable reliability. This study proposes a novel method for estimating carrying angles using computed tomography that can enhance the reliability of the angle measurement. Data of CT scans from 25 elbow joints were processed to build segmented three-dimensional models. The cross-sectional centerlines of the ulna and the humerus were traced from the 3D models, and the angle between 2 vectors formed from the centerlines of the humerus and the ulna was defined as the "three-dimensional carrying angle." These angles were compared with those measured by simple radiograph. Two cases of angular deformity were underwent surgery based on this preoperative surgical planning, and the postoperative 3D carrying angles were evaluated using the proposed method. The mean value of the calculated three-dimensional carrying angle was 20.7 degrees +/-3.61, while it was 16.3 degrees +/-3.21 based on simple radiography without statistical difference. Based on the 3D carrying angle estimations, 2 surgical cases of cubitus deformities were planned by comparison with the normal contra-lateral elbow. Postoperative angle estimations confirmed that the corrected angles were nearly identical to the planned angles for both cases. The results of this study showed that the carrying angle can be accurately estimated using three-dimensional CT and that the proposed method is useful in evaluating deformities of the elbow with high reliability.

Angiogenesis is an essential event in the development of synovial inflammation in rheumatoid arthritis (RA). The aim of the current study was to investigate the expression of vasohibin-1, a novel endothelium-derived vascular endothelial growth factor (VEGF)-inducible angiogenesis inhibitor, in the RA synovium, and to test the effect of inflammatory cytokines on the expression of vasohibin-1 by RA synovial fibroblasts (RASFs). Synovial tissue samples were obtained at surgery from patients with osteoarthritis (OA) and RA, and subjected to immunohistochemistry to investigate the expression and distribution of vasohibin-1 relevant to the degree of synovial inflammation. In an in vitro analysis, RASFs were used to examine the expression of vasohibin-1 and VEGF mRNA by real-time PCR after stimulation with VEGF or inflammatory cytokines under normoxic or hypoxic conditions. The immunohistochemical results showed that vasohibin-1 was expressed in synovial lining cells, endothelial cells, and synovial fibroblasts. In synovial tissue, there was a significant correlation between the expression of vasohibin-1 and histological inflammation score (p0.002, r0.842). In vitro, stimulation with VEGF induced the expression of vasohibin-1 mRNA in RASFs under normoxic conditions, and stimulation with cytokines induced vasohibin-1 mRNA expression under a hypoxic condition. These results suggest that vasohibin-1 was expressed in RA synovial tissue and might be regulated by inflammatory cytokines.

The annual number of suicides in Japan increased sharply in 1998, and since that time it has consistently exceeded 30,000 per year. In this study, we analyze a database of personal and background characteristics of 824 cases (605 men, 219 women) who completed suicide in Okayama Prefecture in 2002 and 2003. The data were obtained with cooperation from the police. Using the methodologies in a previous European study as a model, we classified the suicide methods into 8 categories. To examine the generational and regional differences in the choice of methods, we stratified the sample into 4 age groups (<-24, 2544, 4564, and >-65) and 2 regional groups (Okayama/Kurashiki vs. other areas). Our results on gender differences in 7 of the suicide methods were mostly similar to the European data. However, our data showed a remarkably higher proportionate male-to-female mortality ratio for poisoning by other substances (ICD-10, X65-X69 codes) (1.83, 1.15-2.92). In terms of generational differences in the choice of suicide methods, the Mantel-Haenszel test of homogeneity was significant for most of the categories in our study, suggesting an impact of age on how people commit suicide. There were no remarkable regional differences in our sample. An epidemic curve for suicides via carbon monoxide poisoning using charcoal briquets revealed a trend of time clustering not observed in the other 6 means. The database constructed and used in this study contains richer information than conventional death statistics and is expected to provide helpful knowledge and insights for future epidemiological studies.