Quantitative risk assessment of the introduction of rabies into Japan through the importation of dogs and cats worldwide.

Japan has been free from rabies since 1958. A strict import regimen has been adopted since 2004 consisting of identification of an animal with microchip, two-time rabies vaccination, neutralizing antibody titration test and a waiting period of 180 days. The present study aims to quantitatively assess the risk of rabies introduction into Japan through the international importation of dogs and cats and hence provide evidence-based recommendations to strengthen the current rabies prevention system. A stochastic scenario tree model was developed and simulations were run using @RISK. The probability of infection in a single dog or cat imported into Japan is estimated to be 2·16 × 10-9 [90% prediction interval (PI) 6·65 × 10-11-6·48 × 10-9]. The number of years until the introduction of a rabies case is estimated to be 49 444 (90% PI 19 170-94 641) years. The current import regimen is effective in maintaining the very low risk of rabies introduction into Japan and responding to future changes including increases in import level and rabies prevalence in the world. However, non-compliance or smuggling activities could substantially increase the risk of rabies introduction. Therefore, policy amendment which could promote compliance is highly recommended. Scenario analysis demonstrated that the waiting period could be reduced to 90 days and the requirement for vaccination could be reduced to a single vaccination, but serological testing should not be stopped.

Sales of veterinary antimicrobial agents for therapeutic use in food-producing animal species in Japan between 2005 and 2010.

The use of veterinary antimicrobial agents in animals can result in the emergence and selection of resistant bacteria in food-producing animals. This study elucidated the use of veterinary antimicrobial agents in Japan in terms of milligrams of active ingredient sold per kilogram of biomass between 2005 and 2010. Data on sales of antimicrobial agents and on the biomass of the target animal species were compiled from statistics published bythe Japanese Ministry of Agriculture, Forestry and Fisheries. The quantities of antimicrobials used varied between animal species: the highest usage was observed in pigs (392 to 423 mg/ kg), followed by beef cattle (45 to 67 mg/kg), broiler chickens (44 to 63 mg/kg) and dairy cattle (33 to 49 mg/kg). For the animal species combined, usage of third- and fourth-generation cefalosporins, fluoroquinolones and macrolides ranged from 0.10 to 0.14 mg/kg biomass, 1.1 to 1.3 mg/kg biomass and 7.8 to 10.6 mg/kg biomass, respectively.

[Tricuspid annuloplasty, pulmonary valve replacement, ventricular septal defect (VSD) patch closure, and right-sided maze procedure 23-years after corrective repair of tetralogy of Fallot].

Postoperative pulmonary valve regurgitation, stenosis of the right ventricular outflow tract, conduit failure, ventricular septal patch leak, secondary tricuspid valve regurgitation, and various arrhythmias are the major complications that develop after surgical repair of tetralogy of Fallot in adults. A 27-year-old male with pulmonary regurgitation, tricuspid regurgitation, residual ventricular septal defect (VSD), low left ventricular function, and chronic atrial fibrillation underwent tricuspid annuloplasty, pulmonary valve replacement with a stentless aortic valve, VSD patch closure, and right-sided maze procedure, and the postoperative course was uneventful. The cardiothoracic ratio decreased, sinus rhythm was restored, and the patient's complaints were relieved. Reoperation at the optimal time after corrective repair of tetralogy of Fallot in adults may improve the outcome.

Three major dietary patterns are all independently related to the risk of obesity among 3760 Japanese women aged 18-20 years.

OBJECTIVE: To examine associations between dietary patterns and obesity. DESIGN: Cross-sectional study. SUBJECTS: A total of 3760 Japanese female dietetic course students aged 18-20 years from 53 institutions in Japan. MEASUREMENTS: Diet was assessed over a 1-month period with a validated self-administered diet history questionnaire with 148 food items, from which 30 food groups were created and entered into a factor analysis. Body mass index (BMI) was calculated from self-reported body height and weight. RESULTS: Mean BMI (+/-s.d.) was 20.9+/-2.8 kg m(-2). Four dietary patterns were identified. After adjustment for several confounding factors and total energy intake, the 'Healthy' pattern, characterized by high intakes of vegetables, mushrooms, seaweeds, potatoes, fish and shellfish, soy products, processed fish, fruit and salted vegetables, was significantly associated with a lower risk of BMI> or =25 (odds ratio of the highest quintile vs lowest, 0.57; 95% confidence interval: 0.37-0.87; P for trend <0.05). In contrast, the 'Japanese traditional' pattern, characterized by high intakes of rice, miso soup and soy products, and the 'Western' pattern, characterized by high intakes of meats, fats and oils, seasonings, processed meats and eggs, were both significantly associated with an increased risk of BMI> or =25 (OR: 1.77; 95% CI: 1.17-2.67; P for trend <0.01 and OR: 1.56; 95% CI: 1.01-2.40; P for trend=0.04, respectively). CONCLUSION: Three major dietary patterns, Healthy, Japanese traditional and Western, were all independently and significantly related to the risk of obesity even among a relatively lean young Japanese female population.

Sodium orthovanadate suppresses DNA damage-induced caspase activation and apoptosis by inactivating p53.

We previously reported that p42/SETbeta is a substrate for caspase-7 in irradiated MOLT-4 cells, and that treating the cells with sodium orthovanadate (vanadate) inhibits p42/SETbeta's caspase-mediated cleavage. Here, we initially found that the inhibitory effect of vanadate was due to the suppression of caspase activation but not of caspase activity. Further investigations revealed that vanadate suppressed upstream of apoptotic events, such as the loss of mitochondrial membrane potential, the conformational change of Bax, and p53 transactivation, although the accumulation, total phosphorylation, and phosphorylation of six individual sites of p53 were not affected. Importantly, vanadate suppressed p53-dependent apoptosis, but not p53-independent apoptosis. Finally, gel-shift and chromatin immunoprecipitation assays conclusively demonstrated that vanadate inhibits the DNA-binding activity of p53. Vanadate is conventionally used as an inhibitor of protein tyrosine phosphatases (PTPs); however, we recommend that the influence of vanadate not only on PTPs but also on p53 be considered before using it.

Thymic hyperplasia in patients with Graves' disease. Identification of thyrotropin receptors in human thymus.

Thymic size and density were studied in 23 untreated patients with Graves' disease and 38 control subjects using computed tomography. Both thymic size and density were higher in untreated patients with Graves' disease than in control subjects in the age-matched group. After treatment with antithyroid drugs, both thymic size and density were significantly reduced, with a concomitant decrease in thyrotropin receptor antibodies. PCR of human thymic cDNA using primers for human thyrotropin receptor amplified a fragment in a size expected for the receptor, and its nucleotide sequence was identical to human thyrotropin receptor cDNA in the thyroid. Northern blot analysis of human thymic poly(A)+ RNA demonstrated the presence of the full length form of thyrotropin receptor mRNA. Western blot analysis of human thymic membrane using anti-thyrotropin receptor peptide antibodies demonstrated a band of 100 kD that was also observed in the thyroid membrane. Immunohistochemistry of thymic tissue using mouse antihuman thyrotropin receptor monoclonal antibodies demonstrated the immunostaining of epithelial cells. These results indicate that thymic hyperplasia is apparently associated with Graves' disease and suggest that thymic thyrotropin receptor may act as an autoantigen that may be involved in the pathophysiology of development of Graves' disease.

Association between dietary fiber, water and magnesium intake and functional constipation among young Japanese women.

OBJECTIVE: Most research on constipation has focused on dietary fiber intake. Here, we examined the intake of water and magnesium, nutrients possibly associated with constipation, as well as that of dietary fiber in relation to constipation. DESIGN: Cross-sectional study. SUBJECTS: A total of 3835 female Japanese dietetic students aged 18-20 years from 53 institutions in Japan. METHODS: Dietary intake was estimated with a validated, self-administered diet history questionnaire. Functional constipation was defined using the Rome I criteria. RESULTS: The prevalence of functional constipation was 26.2%. Neither dietary fiber intake (mean=6.4 g/4186 kJ) nor intakes of total water and water from fluids were associated with constipation. Conversely, low intake of water from foods was associated with an increasing prevalence of constipation. In comparison with women in the first (lowest) quintile, the multivariate adjusted odds ratio (OR) (95% confidence interval (CI)) for women in the second, third, fourth, and fifth quintiles were 0.72 (0.57, 0.90), 0.78 (0.62, 0.98), 0.71 (0.56, 0.89), and 0.77 (0.61, 0.97), respectively (P for trend=0.04). Additionally, low magnesium intake was associated with increasing prevalence of constipation. Compared with women in the first quintile, the multivariate adjusted OR (95% CI) for women in the second, third, fourth and fifth quintiles were 0.70 (0.56, 0.88), 0.75 (0.60, 0.95), 0.73 (0.58, 0.92) and 0.79 (0.63, 0.996), respectively (P for trend=0.09). CONCLUSIONS: Low intakes of water from foods and magnesium are independently associated with an increasing prevalence of functional constipation among a population whose dietary fiber intake is relatively low.

Dietary fiber intake, dietary glycemic index and load, and body mass index: a cross-sectional study of 3931 Japanese women aged 18-20 years.

OBJECTIVE: Few observational studies have investigated dietary fiber intake and dietary glycemic index (GI) and glycemic load (GL) simultaneously in relation to obesity, particularly in non-Western populations. We examined the associations between dietary fiber intake and dietary GI and GL, and body mass index (BMI) in young Japanese women. DESIGN: Cross-sectional study. SUBJECTS: A total of 3931 female Japanese dietetic students aged 18-20 years from 53 institutions in Japan. METHODS: Dietary fiber intake and dietary GI and GL (GI for glucose=100) were assessed by a validated, self-administered, diet history questionnaire. BMI was calculated from self-reported body weight and height. RESULTS: Mean values of BMI, dietary fiber intake, dietary GI and dietary GL were 21.0 kg/m(2), 6.5 g/4186 kJ, 65.1 and 82.1/4186 kJ, respectively. White rice (GI=77) was the major contributor to dietary GI and GL (45.8%). After controlling for potential dietary and nondietary confounding factors, dietary fiber intake was negatively correlated with BMI (adjusted mean=21.1 kg/m(2) in the lowest and 20.7 kg/m(2) in the highest quintiles; P for trend=0.0007). Conversely, dietary GI and GL were independently positively correlated with BMI (20.8 and 21.2 kg/m(2); P for trend=0.03, and 20.5 and 21.5 kg/m(2); P for trend=0.0005, respectively). CONCLUSIONS: Dietary fiber intake showed an independent negative association with BMI, and dietary GI and GL showed an independent positive association with BMI among relatively lean young Japanese women.

Preservation of ovarian function by ovarian shielding when undergoing total body irradiation for hematopoietic stem cell transplantation: a report of two successful cases.

The purpose of this study was to evaluate the possibility of preserving ovarian function by ovarian shielding to reduce the irradiation dose in total body irradiation (TBI). The subjects in the study were females aged less than 40 years, who were undergoing allogeneic hematopoietic stem cell transplantation using a TBI-based regimen and who desired to have children after transplantation. For ovarian shielding, abdominal computed tomography (CT) and skin marking were performed in both the supine and prone positions, prior to the TBI. A pair of columnar blocks was placed just above the patient's body. Thus far three patients have been treated. The serum estradiol level decreased to an undetectable level (<8.5 pg/ml) after transplantation and the follicle-stimulating hormone (FSH) level increased above 90 mIU/ml in all patients and they became amenorrheic. However, regular menstruation recovered in patients no. 1 and 2 about 800 and 370 days after transplantation, respectively, with a decrease in the serum FSH level. Menstruation did not recover in patient no. 3, and serum estradiol was transiently detected above 20 pg/ml. The preservation of ovarian function was made possible by ovarian shielding. However, a longer follow-up is needed to know if normal pregnancy and delivery can occur.

DNA-dependent protein kinase activity correlates with Ku70 expression and radiation sensitivity in esophageal cancer cell lines.

We investigated the relationship between DNA-dependent protein kinase (DNA-PK) activity and radiation sensitivity using 14 esophageal cancer cell lines, TE 1-14. DNA-PK activities differed significantly among the cell lines. The highest DNA-PK activity observed in TE-8 was more than two times higher than the lowest DNA-PK activity observed in TE-5. Significant correlation was observed between DNA-PK activity and D0 (r = 0.766; P = 0.0008). Western blots analysis revealed a significant correlation between DNA-PK activity and Ku70 expression, suggesting that the regulation in DNA-PK activity was associated with Ku70 expression. The data suggest that the measurement of DNA-PK activity and/or Ku70 expression may provide a useful way to predict radiation sensitivity.

Impaired ambulatory venous function in lymphedema assessed by near-infrared spectroscopy.

AIM: The aim of this study was to investigate venous function in patients with leg lymphedema during exercise using near-infrared spectroscopy (NIRS), compared with that of patients with chronic venous insufficiency (CVI). METHODS: Forty-three legs of 33 patients (5 males, 28 females; mean age: 53 years) with leg lymphedema without varicose veins or deep vein thrombosis underwent a treadmill walking test with simultaneous NIRS. For comparison, 136 legs of 91 patients (35 males, 56 females; mean age: 56 years) with varicose veins as a CVI group and 45 legs of 38 healthy volunteers (23 males, 15 females; mean age: 50 years) were also evaluated in the same method. Deoxygenated hemoglobin (HHb) was continuously measured during exercise, and the ambulatory venous retention index (AVRI) of each leg was obtained from the serial changes in HHb. RESULTS: The mean AVRI of the lymphedema group was significantly higher than that of healthy legs and significantly lower than of legs with moderate or severe CVI. Furthermore, it was similar to that in the mild CVI group. CONCLUSIONS: Venous function is impaired in exercising legs with lymphedema, and corresponds to that in legs with mild venous insufficiency. The treatment of lymphedema should take CVI into consideration.

Dissolved organic matter from agricultural fields in the irrigation period.

The aim of this study was to quantify and characterize the dissolved organic carbon (DOC) of paddy fields and crop fields in Tottori, Japan. Dissolved organic carbon (DOC) and ultraviolet (UV) absorbance was measured for the filtrated water of each samples. DOC concentration and SUVA (specific UV absorbance) of biodegradation analysis samples were determined around 50 days after the incubation. In the Fukui paddy fields, DOC concentration varied seasonally from 1.1 to 10.1 mg.Cl(-1), showing higher concentration in heavy runoff of non-agriculture period in April. However, DOC concentration variation did not always correspond to rainfall. The Obadake paddy fields also showed a similar pattern with Fukui paddy fields. The daily DOC discharge per area in Fukui (up), Fukui (down), Obadake (south), Obadake (north) paddy fields influent from paddy fields were 0.02, 0.0161, 0.0135 and 0.0027 kg.a(-1).day(-1), respectively. These differences resulted from differences in agricultural types and customs of farmers according to paddy fields and fields. Also, SUVA (an indirect means to evaluate humic substances (hydrophobic fraction)) of the studied influent waters from paddy fields were generally lower than the influent waters from crop fields. The non-biodegradable DOC accounted for 50.2-98%, 46.8-85.5% of the total DOC in the paddy fields and crop fields.

A study of SS size distribution during runoff and fractionation of phosphates depending on soil size in agricultural watershed.

Characterization of the differences and algal-available fractions of P in soils, suspended solids, and bottom sediments have been the main topics of research during the past decade. However, the size distribution and properties of particulate matter in runoff have not been much studied in Japan. Here we study particle size distribution during runoff and the chemical characteristics of P in each soil size fraction and relate them to land use. The temporal variation of particulate sizes during rain events is different in each watershed. Most particles have the size in the range of 10-100 microm. Also, the percentage of BAP in TP as well as percentage of PCOD in SS also varies temporally and spatially during runoff. To investigate how soil particles characteristics depend on land use, soil samples from two watersheds are examined. For particle size distribution and specific gravity, no significant difference among watersheds is found. However, C, N, and P content are indirectly proportional to the particle size, which means smaller particle size results in larger. H2O-extracted P, NH4Cl-extracted P, NAI-P, Apatite-P, Organic-P, and TP contents in each soil particle sample vary depending on particle size, land use, and watershed.

A current life table and causes of death for insured dogs in Japan.

The life expectancies and causes of death were evaluated in 299,555 dogs insured in Japan between 1 April 2010 and 31 March 2011, of which 4169 dogs died during this period. The overall life expectancy of dogs was 13.7 years. The probability of death was high in the first year of life, lowest in the second and third years, and increased exponentially after 3 years of age. The life expectancy was 13.8 years in the <5 kg body weight group, 14.2 years in the 5-10 kg body weight group, 13.6 years in the 10-20 kg body weight group, 12.5 years in the 20-40 kg body weight group and 10.6 years in the ≥40 kg body weight group. As body weight increases, life expectancy tended to decrease except in the <5 kg body weight group. The probability of death increased as dogs got older for most potential causes of death. Neoplasia resulted in the highest probability of death, especially in the large and giant breed groups. Cardiovascular system disorders were the second major cause of death and the toy group had a probability of death significantly higher than the other breed groups at age 12+.

Breed, gender and age pattern of diagnosis for veterinary care in insured dogs in Japan during fiscal year 2010.

We calculated the annual prevalence of diseases of 18 diagnostic categories in the insured dog population in Japan, using data from 299,555 dogs insured between April 2010 and March 2011. The prevalence was highest for dermatological disorders (22.6% for females and 23.3% for males), followed by otic diseases (16.4% for females and 17.2% for males) and digestive system disorders (15.7% for females and 16.4% for males). The prevalence of cardiovascular, urinary, neoplasia and endocrine disorders, increased with age; infectious diseases and injuries showed a high prevalence at young ages, and the prevalence of musculoskeletal and respiratory disorders showed a bimodal peak at young and old ages. A large variation in prevalence was observed between breeds for dermatological, otic, digestive, ophthalmological and cardiovascular disorders.

Are ovarian steroids required for ovum maturation and fertilization? Effects of cyanoketone on the in vitro perfused rabbit ovary.

An isolated perfused rabbit ovary preparation was used to determine the effects of cyanoketone, a potent inhibitor of 3 beta-hydroxysteroid dehydrogenase, on ovulation, ovum maturation and fertilizability, and steroid production. In the first experiment, cyanoketone (10(-4) M) was added to the perfusate of one ovary. The contralateral control ovary was perfused with medium alone. Thirty minutes after the onset of perfusion, hCG (50 IU) was added to the perfusate of both ovaries. The ovulatory efficiency of ovaries treated with cyanoketone plus hCG (82.3 +/- 4.6%) was similar to that of ovaries treated with hCG alone (84.8 +/- 4.4%). No difference was observed in the degree of ovum maturity or degeneration between control and cyanoketone-treated ovaries. Progesterone and estradiol production were significantly reduced by cyanoketone treatment; concentrations in the perfusate of ovaries treated with cyanoketone were 9.7% and 8.0% of the control values, respectively, 2 h after exposure to hCG. The concentration of 17-hydroxypregnenolone was not affected by cyanoketone treatment. Exposure to cyanoketone resulted in a significant (P less than 0.005) reduction in the fertilizability of ova ovulated and fertilized in vitro. In the second experiment, the percentage of ova that showed evidence of normal fertilization was significantly (P less than 0.025) increased in ovaries perfused with cyanoketone plus estradiol (64.5%) compared to that in ovaries perfused with cyanoketone alone (32.4%). In the third experiment, the addition of progesterone to the perfusate did not affect fertilizability of ovulated ova in ovaries perfused with cyanoketone plus estradiol. These results suggest that the presence of estradiol in the ovarian steroid environment may be essential for fertilizability of ova, but not for the processes of ovulation or meiotic maturation.

Pretranslational regulation of rhythmic type II iodothyronine deiodinase expression by beta-adrenergic mechanism in the rat pineal gland.

It has been demonstrated that type II iodothyronine deiodinase is present in rat pineal gland, and the deiodinase activity markedly increases during the hours of darkness, primarily through beta-adrenergic mechanism. We have studied the relationship between pineal type II iodothyronine deiodinase messenger RNA (mRNA) and the deiodinase activity to elucidate the mechanisms involved in the nocturnal rise in pineal deiodinase activity. Northern analysis has demonstrated that type II iodothyronine deiodinase mRNA is expressed in rat pineal gland, and the mRNA markedly increases during the hours of darkness. The nocturnal increase in pineal type II iodothyronine deiodinase activity is preceded by the increase in its mRNA. Daytime isoproterenol administration resulted in a rapid increase in pineal type II iodothyronine deiodinase mRNA followed by the increase in deiodinase activity. Propranolol treatment, bilateral superior cervical ganglionectomy, or constant light exposure significantly suppressed the nocturnal rise in type II iodothyronine deiodinase mRNA as well as the deiodinase activity. Moreover, isoproterenol or (Bu)2AMP stimulated type II iodothyronine deiodinase mRNA and the deiodinase activity in cultured rat pineal glands. These results suggest that the rhythmic change in pineal type II iodothyronine deiodinase activity is regulated at least in part at the pretranslational level by a beta-adrenergic mechanism transmitted through superior cervical ganglia.

Expression and regulation of type II iodothyronine deiodinase in human thyroid gland.

We have studied the expression of type II iodothyronine deiodinase (DII) in human thyroid tumors and cultured human thyroid cells to elucidate the mechanisms involved in the regulation of DII expression in human thyroid gland. Three cases with hyperfunctioning thyroid adenoma, including a case that showed an activating mutation of G(s)alpha with a constitutive activation of cAMP production in cultured cells, and six cases with papillary thyroid carcinoma were analyzed in the present study. Free T(3) was increased, whereas free T(4) was within the normal range in all patients with hyperfunctioning thyroid adenoma. Thyroid tumor tissue and surrounding nontumor tissue were obtained at the time of surgery, and DII expression was compared between tumor tissue and nontumor tissue in each case. Northern analysis demonstrated the presence of DII messenger RNA (mRNA) approximately 7.5 kb in size in all of the tumor and nontumor tissues. DII mRNA and DII activity in hyperfunctioning thyroid adenoma were significantly increased compared with those in nontumor tissue in each case. In contrast, DII mRNA and DII activity in papillary thyroid carcinoma were decreased compared with those in nontumor tissue in each case. DII mRNA and DII activity in cultured human thyroid cells were significantly stimulated by TSH in a dose-dependent manner. The promoter activity of the human DII gene including the complete cAMP response element, transfected to cultured human thyroid cells, was stimulated by (Bu)(2)cAMP. In summary, these results suggest that DII expression in human thyroid gland is regulated at the transcriptional level through the TSH receptor-G(s)alpha-cAMP regulatory cascade, which may be related to the increase in circulating T(3) level in patients with Graves' disease and hyperfunctioning thyroid adenoma.

The effects of bradykinin on ovulation and prostaglandin production by the perfused rabbit ovary.

Involvement of the vasoactive peptide bradykinin (BK) in ovulation, oocyte maturation, and prostaglandin (PG) production was assessed using an in vitro perfused rabbit ovary preparation. In the first experiment, BK at a concentration of 0.033, 0.33, or 3.3 micrograms/ml was added to the perfusate of one ovary at hourly intervals for the first 10 h of perfusion. The contralateral control ovary was treated with medium alone parallel to the experimental ovary. Ovaries were perfused for a total of 12 h. BK induced ovulation in the absence of gonadotropin in a dose-related fashion, but did not induce maturation of ovulated ova or follicular oocytes. BK significantly stimulated PG production at all concentrations tested, but the effect was not dose related. Prostacyclin, as reflected by the concentration of 6-keto-PGF1 alpha in the perfusate, was the major PG produced. Smaller quantities of PGE2 and PGF2 alpha were present in the perfusate. After a single injection of BK (3.3 micrograms/ml), 6-keto-PGF1 alpha and PGF2 alpha production increased within 15 min and reached a maximum at 60-90 min. PGE2 did not change significantly over this time period. The addition of 1 microgram/ml indomethacin to the perfusate completely inhibited BK-stimulated PG production. However, indomethacin did not significantly affect the ovulatory efficiency of BK-treated ovaries. Neither BK nor indomethacin induced any degenerative changes in ovulated ova or follicular oocytes. The addition of a BK antagonist at 1 microgram/ml every 30 min to the perfusate resulted in an effective blockade of hCG-induced ovulation. These results suggest that BK is involved in the process of follicle rupture, but BK may induce ovulation by a mechanism(s) other than through PG stimulation.