Long-term wheel-running can prevent deterioration of bone properties in diabetes mellitus model rats.

OBJECTIVES: The purpose of this study was to examine the effects of long-term wheel-running on tibia bone properties in T2DM Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: Ten five-week-old male OLETF rats were used as experimental animals and 5 Long-Evans Tokushima Otsuka (LETO) rats as controls. Half of OLETF rats performed daily voluntary wheel-running for 17 months (OLETF-EXE), while neither the remainder of OLETF nor LETO rats had exercise. At the end of experiment, in addition to serum biochemical and bone formation/resorption marker analyses, bone mass, trabecular bone microarchitecture and cortical bone geometry were analyzed in left tibia, and bone mechanical strength of right tibia was measured. RESULTS: Tibia bone mass, trabecular bone microarchitecture, cortical bone geometry and bone mechanical strength deteriorated in diabetic OLETF rats. However, such deterioration was obviously attenuated in OLETF-EXE rats, which maintained normal levels of blood glucose, HbA1c and blood urea nitrogen. CONCLUSIONS: Daily wheel-running could prevent the deterioration of bone properties in OLETF rats. This would be induced mainly by suppressing the development of T2DM. Regular physical exercise may be a potent strategy for preventing not only the development of diabetes but also the deterioration of bone properties in patients with chronic T2DM.

Coping strategies and risk of cardiovascular disease incidence and mortality: the Japan Public Health Center-based prospective Study.

AIMS: Coping strategies may be significantly associated with health outcomes. This is the first study to investigate the association between baseline coping strategies and cardiovascular disease (CVD) incidence and mortality in a general population cohort. METHODS AND RESULTS: The Japan Public Health Center-based prospective Study asked questions on coping in its third follow-up survey (2000-04). Analyses on CVD incidence and mortality included 57 017 subjects aged 50-79 without a history of CVD and who provided complete answers on approach- and avoidance-oriented coping behaviours and strategies. Cox regression models, adjusted for confounders, were used to determine hazard ratios (HRs) according to coping style. Mean follow-up time was 7.9 years for incidence and 8.0 years for mortality.The premorbid use of an approach-oriented coping strategy was inversely associated with incidence of stroke (HR = 0.85; 95% CI, 0.73-1.00) and CVD mortality (HR = 0.74; 95% CI, 0.55-0.99). Stroke subtype analyses revealed an inverse association between the approach-oriented coping strategy and incidence of ischaemic stroke (HR = 0.79; 95% CI, 0.64-0.98) and a positive association between the combined coping strategy and incidence of intra-parenchymal haemorrhage (HR = 2.03; 95% CI, 1.01-4.10). Utilizing an avoidance coping strategy was associated with increased mortality from ischaemic heart disease (IHD) only in hypertensive individuals (HR = 3.46; 95% CI, 1.07-11.18). The coping behaviours fantasizing and positive reappraisal were associated with increased risk of CVD incidence (HR = 1.24; 95% CI, 1.03-1.50) and reduced risk of IHD mortality (HR = 0.63; 95% CI, 0.40-0.99), respectively. CONCLUSION: An approach-oriented coping strategy, i.e. proactively dealing with sources of stress, may be associated with significantly reduced stroke incidence and CVD mortality in a Japanese population-based cohort.

Associations between hazard indices of di-n-butylphthalate and di-2-ethylhexylphthalate exposure and serum reproductive hormone levels among occupationally exposed and unexposed Chinese men.

The knowledge on the dose-response relationships between cumulative phthalate exposure and reproductive hormones in human are lacking. To assess the characteristics of the associations between hazard index (HI) of cumulative di-n-butylphthalate (DBP) and di-2-ethylhexylphthalate (DEHP) exposures and serum concentrations of free testosterone (fT), estradiol, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), we used restricted cubic spline function to characterize the dose-response curves between the HI values and reproductive hormones for 74 male workers occupationally exposed to high levels of DBP and DEHP, and 63 male construction workers as comparison group matched for age and smoking status. The median of HI value was 5.30 for exposed workers, 53.0-fold that of unexposed workers (0.10). 89.2% of exposed workers and 1.6% of unexposed workers have HI over 1.00. We observed a borderline significantly negative association between HI and fT in exposed workers (r=-0.195, p=0.096), but not in unexposed workers. The exposed workers showed inverted long-tailed J-shaped fT and FSH curves, and small changes in the LH curve, whereas unexposed workers had inverted and flattened-S-shaped fT and mirror-S-shaped LH and FSH curves. Both T production and hypothalamo-pituitary-testis (HPT) axis function were damaged in workers with high HI of phthalate exposures. HPT feedback function was activated in workers with both high and low HI, and plays an important role in preventing fT level from further decreasing with a rise in HI.

Importance of intra-individual variation in tumour volume of hepatic colorectal metastases.

AIMS: The efficacy of surgical resection for multiple colorectal hepatic metastases (MCHM) has been controversial. We examined the survival of patients who received surgery for MCHM and examined the factors associated with survival. METHODS: A retrospective analysis was performed of 50 consecutive patients who received hepatic resections for MCHM, defined as four or more metastatic lesions of colorectal cancer. RESULTS: Overall survival after hepatic resection for MCHM was 48% at 3years and 43% at 5years (median survival, 22.3months). Multivariate analyses revealed that a coefficient of variation (CV) in volume of hepatic metastases in each individual patient above 1.8 (P=0.01, HR=4.08, 95% CI=1.33-12.5) was the only poor prognostic factor after resection of MCHM. CONCLUSIONS: A CV in volume of hepatic metastases in each individual patient above 1.8 predicts poor survival after hepatectomy of MCHM. Thus, the CV in volume of hepatic metastases in each individual patient might be useful in planning the therapeutic strategy for patients with MCHM.

Fish intake and serum levels of organochlorines among Japanese women.

This study evaluates background serum levels of selected organochlorine compounds among Japanese women of reproductive age and investigates whether lifestyle factors, especially dietary factors, may be associated with these levels. A cross-sectional study was performed on 80 Japanese women, aged 26-43 years, who complained of infertility and were confirmed not to have endometriosis. The serum levels of total toxic equivalency (TEQ), 18 polychlorinated dibenzo-p-dioxins (PCDDs)/polychlorinated dibenzofurans (PCDFs), 4 coplanar polychlorinated biphenyls (cPCBs), 36 ortho-substituted polychlorinated biphenyls (PCBs), and 13 chlorinated pesticides or their metabolites were measured and data were collected on the women's age, residence, occupation, body mass index (BMI), smoking and alcohol habit and 6 dietary intakes (fish, meats, rice, vegetables, fruits and dairy products). The serum median level of total TEQ was 25.1 pg TEQ/g lipid, that of PCDDs/PCDFs/cPCBs was 11.5 pmol/g lipid, that of PCBs was 0.46 nmol/g lipid, and that of total pesticides was 1.32 nmol/g lipid. The serum levels of total TEQ, PCDDs/PCDFs/cPCBs, PCBs and pesticides were positively associated with age (P for trend=0.003, 0.01, 0.005 and 0.01, respectively) and frequent fish consumption (P for trend=0.002, 0.003, 0.0003 and 0.006, respectively). Other lifestyle factors were not associated with serum organochlorine levels. The present study suggests that Japanese women who consume fish frequently in their reproductive period tend to accumulate organochlorines in their bodies.

Association between endometriosis and genetic polymorphisms of the estradiol-synthesizing enzyme genes HSD17B1 and CYP19.

BACKGROUND: Endometriosis, an estrogen-dependent disease, is believed to be influenced by multiple genetic and environmental factors. Here, we evaluated whether the risk and severity of endometriosis are associated with polymorphisms in estradiol-synthesizing enzyme genes: the Ser312Gly polymorphism in 17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1) and the Arg264Cys polymorphism in cytochrome P450, subfamily XIX (CYP19). METHODS: All participants underwent diagnostic laparoscopy, and the stage of endometriosis was determined according to the Revised American Fertility Society classification. Of the 138 women enrolled, 59 had no endometriosis, 21 had stage I, 10 had stage II, 23 had stage III and 25 had stage IV. SNPs were discriminated by allele-specific oligonucleotide hybridization. RESULTS: Individuals having at least one A-allele (A/G or A/A genotype) of HSD17B1 showed a significantly increased risk of endometriosis (A/G genotype: adjusted OR, 3.06; 95%CI 1.21-7.74; A/A genotype: adjusted OR, 3.02; 95%CI 1.08-8.43). There was a significant trend associating A/G + A/A genotypes with severity of endometriosis (P for trend < 0.01). No statistically significant association was found for the CYP19 polymorphism. CONCLUSIONS: Evidence for association between the Ser312Gly polymorphism in HSD17B1 and endometriosis was found in a Japanese population. The A-allele of HSD17B1 appears to confer higher risk for endometriosis.

Analytical method of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in human hair by column-switching liquid chromatography-mass spectrometry.

A column-switching liquid chromatography-mass spectrometry was developed for quantification of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in human hair. Hair sample was digested in 1N NaOH at 100 degrees C, and PhIP was extracted using a Blue-Chitin column. The recovery rate was 73%, the limit of quantification was 50 pg/g hair, and intra-day and inter-day variations were 6.3 and 11.7%, respectively. PhIP was found in 42 of the 46 hair samples from 23 healthy volunteers: 110-3878 pg/g hair. The intrapersonal correlation between the first and second analyses was r = 0.85 (95% confidence interval, 0.65-0.94). A positive correlation was observed between PhIP levels and melanin content in hair. This study indicates the ability of this method to detect levels of PhIP in hair.

Dynamic response of the pulmonary circulation in continuous flow artificial heart systems.

Pulmonary circulation dynamics is important when considering bi-ventricular assist devices (BiVAD) or total artificial heart (TAH) systems and in investigating the mechanism of atrial collapse in order to design better control algorithms. In this study, we investigated pulmonary circulation dynamics in a continuous flow artificial heart system by performing acute tests on a mature goat. By varying the right pump speed, we were able to observe the dynamic response of the left atrial pressure (LAP) and simulate conditions that result in atrial suction. The results showed a time constant characteristic of a compliance lag in LAP response to changes in right pump output in the TAH configuration. These results may prove useful in the design of a new mock circulatory system that incorporates the dynamics of the pulmonary circulation, and in the improvement of existing control algorithms that prevent atrial wall collapse.

Leukocyte 8-hydroxydeoxyguanosine and aromatic DNA adduct in coke-oven workers with polycyclic aromatic hydrocarbon exposure.

OBJECTIVE: To investigate the potential for exposure to polycyclic aromatic hydrocarbons (PAHs) to induce oxidative DNA damage, we conducted a cross-sectional study in coke-oven workers employed at an iron-steel factory. METHODS: The study population contained 119 coke-oven workers from different work areas of the oven and 38 controls. Personal information on age, employment duration, smoking habit and alcohol consumption was obtained at an interview. Leukocyte 8-hydroxydeoxyguanosine (8-OHdG) was measured by high performance liquid chromatography with electrochemical detection. Leukocyte aromatic DNA adducts as effective dose, and urinary 1-hydroxypyren as internal dose, were also measured, and used to analyze the relationship of 8-OHdG with other biomarkers for PAH exposure, tobacco smoke and alcohol consumption. RESULTS: The leukocyte 8-OHdG revealed a wide inter-individual variation. The highest 8-OHdG level was detected in bottom-workers of the coke-oven. There were significant differences among the four different work areas ( P=0.02). We could not find significant correlation between 8-OHdG levels and urinary 1-hydroxypyrene, but a weakly positive correlation was found between 8-OHdG and leukocyte aromatic DNA adducts among all subjects (r=0.19 P=0.03). We could not observe any effect of smoking and alcohol drinking on 8-OHdG production. CONCLUSION: We could not find clear evidence that PAH exposure induces oxidative DNA damage.

Chip ligating human genomic DNA serves as storage material and template for polymerase chain reaction.

A chip was developed to store DNA for medical research. The optional restriction site fixed on the chip can randomly ligate with whole human genomic DNA treated by the corresponding restriction enzyme. PCR can then use the chip as template DNA. Moreover, a chip fixing two restriction sites (e.g. EcoRI and HindIII) showed the amplification by PCR for any location of genomic DNA. Repetitive PCRs have confirmed that a DNA chip can be stored by at -4 degrees C for 2 years.

[Metastatic lung tumor: report of two cases].

We herein report 2 cases of metastatic lung tumor. The first case was a 59-year-old female, who had undergone a left radical mastectomy for the treatment of breast cancer 18 years before. She was found to have a pulmonary nodule in the left lower lobe on the routine chest radiograph. She underwent a video-assisted thoracic surgery (VATS) partial resection of the left lower lobe. Tumor was diagnosed as a lung metastasis of the breast cancer microscopically. The second case was a 77-year-old man, who had undergone a right nephrectomy for the treatment of renal cell carcinoma. He was found to have 2 nodules in the right lung (1 in the middle lobe and the other in the lower lobe) on the follow-up computed tomography (CT) scan of the chest. He underwent VATS partial resections of the right middle and lower lobes. While the tumor in the lower lobe was diagnosed as a lung metastasis of the renal cell carcinoma, the tumor in the middle lobe turned out a primary lung cancer.

Urinary bisphenol A and plasma hormone concentrations in male workers exposed to bisphenol A diglycidyl ether and mixed organic solvents.

AIMS: To evaluate effects of exposure to bisphenol A diglycidyl ether (BADGE) on urinary excretion of bisphenol A, and plasma gonadotrophic hormones and testosterone in male epoxy resin sprayers. METHODS: Cross sectional study of 42 workers whose job was to spray epoxy resin hardening agents including BADGE and mixed organic solvents, and 42 matched control workers without BADGE use in the same machine plants. RESULTS: Concentrations of urinary bisphenol A were higher in the epoxy resin sprayers (median 1.06 micro mol/mol creatinine) compared with the controls (median 0.52 micro mol/mol creatinine). Urinary metabolite concentrations of organic solvents used were all higher in the epoxy resin workers compared with the controls. Endocrinological examination showed different concentrations of follicle stimulating hormone (FSH) between the epoxy sprayers (median 5.3 mIU/ml) and the controls (median 7.6 mIU/ml). FSH showed a mild correlation with urinary bisphenol A, but not with the metabolites of organic solvents. Luteinising hormone and free testosterone concentrations did not differ between the two groups. CONCLUSION: BADGE may generate bisphenol A endogenously. Results suggest that bisphenol A may disrupt secretion of gonadotrophic hormones in men. The clinical significance of endocrine disrupting effects by bisphenol A should be further investigated in male workers exposed to bisphenol A.

Residuals of beta-hexachlorocyclohexane, dichlorodiphenyltrichloroethane, and hexachlorobenzene in serum, and relations with consumption of dietary components in rural residents in Japan.

To estimate levels of organochlorine residuals in the Japanese population and the contribution of dietary factors to these levels, we determined serum levels of beta-hexachlorocyclohexane (beta-HCH), hexachlorobenzene (HCB), p,p'-dichlorodiphenyldichloroethane (p,p'-DDD), 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE) and p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) in 41 volunteers (14 men and 27 women) in a rural area of Northern Japan. These organochlorine levels were measured using gas-chromatography mass-spectrometry. By a self-administered dietary history questionnaire, the usual dietary intake was estimated. Their median levels (range) were as follows: beta-HCH, 0.50 (0.05-1.50); HCB, 0.20 (0.02-0.70); and total DDT (p,p'-DDE + p,p'-DDT), 5.0 (0.9-31.0) ng/ml serum. Levels of p,p'-DDD were detected in only seven subjects (0.05-0.6 ng/ml serum). The beta-HCH levels were increased with rice and milk intakes, but the least squares means were not simply increased according to the quartile of the intakes. Concerning HCB, fish intake showed a borderline significant correlation (0.20, P = 0.052). In terms of total DDT, intakes of meat, fish, vegetable and milk showed a positive relationship, although none of them provided statistically significant results. No other statistically significant relation between any organochlorines and any food intakes examined was observed in this study. The present study suggests that organochlorine compounds are transported into the human body via foods in the Japanese population. Their effects on health should thus be investigated and monitored.

Urinary 1-hydroxypyrene in coke oven workers relative to exposure, alcohol consumption, and metabolic enzymes.

OBJECTIVES: To investigate the influence of personal lifestyle--such as smoking and alcohol consumption-on urinary 1-hydroxypyrene (1-OHP) concentrations in coke oven workers exposed to polycyclic aromatic hydrocarbons (PAHs) and to evaluate the association of 1-OHP concentrations with the genetic polymorphism of several metabolic enzymes including cytochrome P-450 (CYP) 1A1 and glutathione S-tranferases (GSTs). METHODS: The study population contained 162 coke oven workers and 58 controls employed at the largest iron and steel factory in China. Personal data were collected at the interview. 1-OHP in urine was measured with high performance liquid chromatography with fluorescence detection. Genetic polymorphisms were identified by the polymerase chain reaction (PCR) method. RESULTS: A positive association between excretion of urinary 1-OHP and the levels of exposure to PAHs was confirmed. Those people who consumed >or=50 g/day ethanol had significantly higher 1-OHP excretion than did other coke oven workers (p<0.01). No significant difference in urinary 1-OHP was found between smokers and non-smokers, in both controls and exposed subjects. The variant homozygotes at exon 7 of the CYP1A1 gene had significantly higher urinary 1-OHP concentrations than other CYP1A1 genotypes among the exposed workers (p=0.03). There was less association between the concentrations of 1-OHP and the GSTM1, GSTP1, or GSTT1 polymorphism. CONCLUSIONS: The present study confirmed that urinary 1-OHP is a good biomarker for exposure to PAHs. Alcohol consumption affected urinary 1-OHP excretion. The variant genotypes of the CYP1A1 gene may result in the enhancement of PAH metabolites. It is helpful to understand the role of individual susceptibility on metabolism of carcinogens. These findings suggest that the modulating effect of individual lifestyle factors or genetic nature should be considered in future studies on occupational exposure to PAHs and in evaluating the health risk from harmful chemicals.

hOGG1 exon7 polymorphism and gastric cancer in case-control studies of Japanese Brazilians and non-Japanese Brazilians.

Polymorphism of hOGG1 may be capable of serving as a genetic marker for individual susceptibility to various cancers because of its role in the repair of oxyradical DNA damage. We examined the distribution of the hOGG1 Ser326Cys polymorphism and its presumed correlation with gastric cancer risk in two case-control studies of different ethnic groups in São Paulo, Brazil. Potentially eligible Japanese (JB) and non-Japanese Brazilian (NJB) case subjects were defined as patients with newly diagnosed malignant neoplasms of the stomach in 13 hospitals in São Paulo. Ninety-six JBs and 236 NJBs were adopted as subjects. Two controls were matched for each JB case, and one control for each NJB case. The subjects were interviewed using a questionnaire and their blood samples were collected. A significant difference in the distribution of this polymorphism between the two ethnic groups was observed (chi(2)=58.3, P<0.01). The mutant type (Ser/Cys or Cys/Cys) was predominant (approximately 65%) in the JBs, but was only present in approximately 40% of the NJBs. Logistic regression analysis showed no significant increased risk for either the Ser/Cys or Cys/Cys type in either group. The odds ratios of the Cys allele for gastric cancer were 1.01 (95% confidence interval (CI): 0.52-1.93) in the JBs and 0.85 (95% CI: 0.57-1.26) in the NJBs. In the NJBs, a significant increased risk of smoking was shown only in the Ser/Ser type, and no increased risk was shown in the genotypes with the Cys allele. However, no statistically significant interactions were observed with smoking or other possible confounding factors. No statistically significant difference in the distribution of the polymorphism was observed between the intestinal type and diffuse type of gastric cancer in either the JBs or the NJBs. The ethnic difference in hOGG1 Ser326Cys polymorphism was much greater than the case-control difference, and this polymorphism is unlikely to be associated with gastric cancer.

[A breast cancer patient with recurrence in the thoracic wall in whom a high-dose of toremifene was effective].

The patient was a 53-year-old female who presented with a primary complaint of reddening of the left precordial skin. She had undergone mastectomy for cancer of the left breast 12 years and 4 months earlier and had received endocrine chemotherapy including TAM as a postoperative adjuvant therapy. A diagnosis of thoracic wall recurrence was made by chest CT and pathological examination of skin biopsy specimens. Toremifene (TOR) was administrated at 120 mg/day, and PR was maintained for 8 months. Even after the condition became PD, the patient has retained adequate QOL with combination therapies including radiotherapy, and is still treated on an outpatient basis 3 years after the beginning of the treatment.

[Clinical study of operated nine thymic carcinomas].

Nine cases of thymic carcinoma (5 males and 4 females) were operated in our hospital between 1990 and 1998. These cases included 4 squamous cell carcinomas, 2 small cell carcinomas, 2 undifferentiated carcinomas and one adenocarcinoma. Preoperative chemotherapy were performed in 3 cases. All cases underwent median-sternotomy followed by mediastinal irradiation, 4 had total resection of the tumor, 2 had subtotal resection and 3 had exploratory thoracotomy followed by mediastinal irradiation. Adjuvant chemotherapy were administered in 4 cases and re-operation were performed in 2 cases. We applied Masaoka's clinical staging for thymoma, nine cases consisted of 6 stage III cases, 2 stage IV b cases and one stage IV a case. Within 2 years after operation, 3 cases (two complete resection cases and one exploratory thoracotomy case) were died of the carcinoma. However, two cases of squamous cell carcinoma have been alive more than 5 years after surgery followed by chemoradiation. The remaining 4 patients are alive either with or without the carcinoma after 7 to 28 months after operation. Thymic carcinoma is not so common mediastinal tumor but is expected to increase in the future. The treatment of thymic carcinoma remains a controversial matter and the survival is poor compared with invasive thymoma, but multimodal-therapy would contribute to improvement of the results in treatment for thymic carcinoma especially in squamous cell carcinoma.