Akio Sato

University of Yamanashi, Kōhu, Yamanashi, Japan

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Publications (28)59.77 Total impact

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    ABSTRACT: Although dietary restriction (DR) is common in modern society, research about hepatic metabolism and the hepatotoxicity induced by DR has been conducted less intensively than that induced by fasting. In the present study, we fed male Wistar rats at five levels of food intake for one day, including conventional feeding (60 kcal), three of DR (45, 30, and 15 kcal), and fasting (0 kcal), and observed the metabolic changes of hepatic cytochrome P450 2E1(CYP2E1) and the hepatotoxicity of chloroform (CHCl(3)) and carbon tetrachloride (CCl(4)). The CYP2E1 content was significantly increased in 15 kcal-food and fasting groups. The hepatic glutathione (GSH) content, which protects the liver from hepatotoxic agents, was depleted in 15 kcal-food and fasting groups. After the challenge by CHCl(3) and CCl(4), the activities of aspartate aminotransferase and alanine aminotransferase, marker enzymes for liver damage, were elevated remarkably at all food groups. Moreover, their activities increased significantly in DR groups, in comparison to the corresponding 60 kcal-food group. After the challenge, the hepatic GSH content was also depleted significantly in 15 kcal-food and fasting groups. CHCl(3) was cleared by hepatic metabolism about 8-10 times faster than that of CCl(4). Similarly, the areas under the blood concentration-time curve of CCl(4) was as much as twice that of the corresponding CHCl(3). In conclusion, when food was restricted to less than half of conventional amount, hepatic metabolism was affected and the hepatotoxicity induced by CCl(4) or CHCl(3) was augmented by, at least in part, CYP2E1 induction and GSH depletion.
    The Tohoku Journal of Experimental Medicine 09/2007; 212(4):379-87. · 1.37 Impact Factor
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    ABSTRACT: Breast cancer has become the most common cancer among women worldwide. Although the consumptions of milk and dairy products were considered to be a risk factor for breast cancer in some epidemiological studies, the results were inconsistent. In the present study, female Sprague-Dawley rats received a single oral dose of 5mg 7,12-dimethylbenz(a)anthracene (DMBA). One week later, the animals were divided into four groups: whole milk (WM), artificial whole milk (A-WM), non-fat milk (NFM) or artificial non-fat milk (A-NFM) mixed with commercial powder chow. Rats were palpated weekly to monitor tumor development. At week 20 after DMBA administration, rats were decapitated and the volume and weight of mammary tumor were recorded. Tumor incidence, the cumulative number of tumors and the sums of tumor volume were higher in the WM and NFM groups than in the A-WM and A-NFM groups both at palpation and at autopsy. Combining our previous studies, we found the consumption of milk promoted the development of DMBA-induced mammary tumors in rats independent of the fat level.
    Cancer Detection and Prevention 02/2007; 31(4):339-43. · 2.52 Impact Factor
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    ABSTRACT: Cows' milk contains considerable quantities of estrogens, mainly in the form of estrone sulfate (ES). To determine whether the commercial milk has any biologically significant hormonal effects, 2 series of uterotrophic tests were performed, 1 with young ovariectomized rats and the other with sexually immature rats. Thirty-six rats were used for each test. They were divided into 3 groups of 12 animals each, and were kept for 7 days on powdered chow with 1 of 3 drinking solutions: low-fat milk (LFM), artificial milk (AM, negative control), or AM containing ES at 100 ng/ml (positive control). At autopsy, both the wet and blotted uterine weights were measured. The cell heights of uterine epithelia in ovariectomized rats were also determined. The significance of differences among groups was tested by Dunnett's multiple comparisons test. In each test, the weights of the uteri in the LFM group were significantly greater than those of the respective weights in the AM group (p < 0.01). Furthermore, in ovariectomized rats, the uterine epithelial-cell height in the LFM group was significantly greater than that observed in the AM group (p < 0.01). The uterotrophic effect of 100 ng/ml ES solution was greater than that of LFM in immature rats (p < 0.01), whereas the effect of the solution was almost comparable to that of LFM in young ovariectomized rats (p > 0.05). In conclusion, commercially available milk has uterotrophic effects in both young ovariectomized rats and sexually immature rats.
    International Journal of Cancer 05/2006; 118(9):2363-5. · 6.20 Impact Factor
  • Journal of Health Science - J HEALTH SCI. 01/2006; 52(4):419-424.
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    ABSTRACT: To study the effect of endocrine disruptor chemicals in cow milk on female reproductive system. A two-generation reproduction was conducted according to U. S. FDA standard. Milk was fed in special bottle to Wistar rats of both sexes through two successive generations (F0 and F1) in the milk group while artificial milk was fed to rats in the control group. Twenty-four rats of each sex were mated in each group. Measurements were made according to this guideline. Reproductive parameters in the milk group such as fertility index, gestation index, weights of uterus and ovary, days of vaginal opening, estrous cycles, histological morphological changes were comparable to those in the control group. However, the means of body weight had some differences. The body weight gains increased significantly in the milk-treated group in F1 and F2 generation compared with those in the control group. The concentration of insulin-like growth factor-1 (IGF-1) in blood in the milk group was comparable to that in the control group, but the standard deviation changed greatly in the milk-treated rats. Endocrine disruptor chemicals in milk have no severe effects on the female reproductive system.
    Biomedical and Environmental Sciences 11/2005; 18(5):307-13. · 1.15 Impact Factor
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    ABSTRACT: : Voglibose is an alpha-glucosidase inhibitor used to decrease postprandial hyperglycemia in diabetic patients. Although clinical concern has not yet been raised, hepatic dysfunction has been reported in a few patients taking this drug. : In the present study, we studied the effects of voglibose on the hepatotoxicity of carbon tetrachloride (CCl(4)) and acetaminophen (APAP) in rats, since both of these agents exert their effects through isoforms of cytochrome P450. Male Sprague-Dawley rats were given a daily ration (20g) of powdered chow diet containing 0, 2.5, 5.0 or 10.0mg/100g of voglibose. Three weeks later, the rats were challenged with either 0.50g/kg CCl(4) orally or 0.75g/kg APAP intraperitoneally for biochemical examinations or killed for an in vivo metabolism study. : Voglibose at these three experimental doses potentiated CCl(4) and APAP hepatotoxicity, as evidenced by significantly increased levels of both plasma asparate transaminase (AST) and alanine transaminae (ALT). The glutathione (GSH) content was decreased while malondialdehyde (MDA) increased in the liver after CCl(4) or APAP administration. Hepatic cytochrome P450 2E1 (CYP2E1) concentration was increased at doses of 5.0 and 10.0mg/100g of voglibose and its activity increased in the three voglibose dosage groups, while hepatic cytochrome P450 3A (CYP3A) and cytochrome P450 1A2 (CYP1A2) were only slightly changed at any dose. : Our study demonstrated that voglibose can potentiate CCl(4) and APAP hepatotoxicity in rats by inducing hepatic CYP2E1.
    Hepatology Research 10/2005; 33(1):50-6. · 2.07 Impact Factor
  • Davaasambuu Ganmaa, Akio Sato
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    ABSTRACT: The continued increase in incidence of some hormone-related cancers worldwide is of great concern. Although estrogen-like substances in the environment were blamed for this increase, the possible role of endogenous estrogens from food has not been widely discussed. We are particularly concerned about cows' milk, which contains a considerable quantity of estrogens. When we name cows' milk as one of the important routes of human exposure to estrogens, the general response of Western people is that "man has been drinking cows' milk for around 2000 years without apparent harm." However, the milk that we are now consuming is quite different from that consumed 100 years ago. Unlike their pasture-fed counterparts of 100 years ago, modern dairy cows are usually pregnant and continue to lactate during the latter half of pregnancy, when the concentration of estrogens in blood, and hence in milk, increases. The correlation of incidence and mortality rates with environmental variables in worldwide countries provides useful clues to the etiology of cancer. In this study, we correlated incidence rates for breast, ovarian, and corpus uteri cancers (1993-97 from Cancer Incidence in Five Continents) with food intake (1961-97 from FAOSTAT) in 40 countries. Meat was most closely correlated with the breast cancer incidence (r=0.827), followed by milk (0.817) and cheese (0.751). Stepwise multiple-regression analysis (SMRA) identified meat as the factor contributing most greatly to the incidence of breast cancer ([R]=0.862). Milk was most closely correlated with the incidence of ovarian cancer (r=0.779), followed by animal fats (0.717) and cheese (0.697). SMRA revealed that milk plus cheese make the greatest contribution to the incidence of ovarian cancer ([R]=0.767). Milk was most closely correlated with corpus uteri cancer (r=0.814), followed by cheese (0.787). SMRA revealed that milk plus cheese make the most significant contribution to the incidence of corpus uteri cancer ([R]=0.861). In conclusion, increased consumption of animal-derived food may have adverse effects on the development of hormone-dependent cancers. Among dietary risk factors, we are most concerned with milk and dairy products, because the milk we drink today is produced from pregnant cows, in which estrogen and progesterone levels are markedly elevated.
    Medical Hypotheses 02/2005; 65(6):1028-37. · 1.18 Impact Factor
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    ABSTRACT: To examine whether the considerable quantities of increased female sex hormone levels found in modern milk as a result of modern dairy farming practices are safe for human consumption. Males and females of the P generation were maintained on a diet containing milk for 10 weeks before mating. Exposure to milk was continued up to the end of weaning of the F2b offspring. Two-generation reproduction study. Male and female Wistar Galas rats. P- and F1-generation rats were mated. Fertility, fecundity, and morphology and function of reproductive organs. Although milk had growth-promoting effects in both parents and offspring, it caused no impairments in fertility, fecundity, or reproductive organ development in either generation. However, a whole litter from a dam of the P generation was born dead, three litters in total had a pup with skeletal abnormalities, and the AGD of F2a female pups was reduced. These events occurred only in the milk-treated rats. It is unknown whether these issues had any relevance to milk or only happened by chance. Further study is required to determine whether milk from pregnant cows is completely free from adverse effects on reproductive health.
    Fertility and Sterility 11/2004; 82 Suppl 3:1106-14. · 4.17 Impact Factor
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    ABSTRACT: Commercial cow milk contains considerable amounts of estrogens. Our study assessed the effect of commercial low-fat milk on the development of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in rats. Eighty 6-week-old female Sprague-Dawley rats received a single oral dose of 5 mg DMBA. Twenty-four hours later, the animals were divided into 4 groups of 20 animals each and given 1 of 4 test solutions for 20 weeks as their drinking liquid: low-fat (1%) milk (M), artificial milk (A), estrone sulfate solution (0.1 microg/ml, E), or tap water (W). The artificial milk was formulated to supply essentially the same calories as the milk. The low-fat milk contained 378 pg/ml estrone sulfate. Tumor incidence, the cumulative number of tumors and the sum of tumor diameters were higher in the M and E groups than in the A or W groups. Overall, the development of mammary tumors was in the order: M = E > A = W. Whereas the plasma 17beta-estradiol concentration in the M group was the 2nd highest after the E group, the plasma level of insulin-like growth factor (IGF-I) was significantly higher in the M group than in the other 3 groups. In conclusion, commercially available low-fat milk promotes the development of DMBA-induced mammary tumors in rats. The degree of the promotion is almost comparable to that of 0.1 microg/ml estrone sulfate. The high estrogen content in the milk may be responsible for the promotional effects, acting in concert with other hormones such as IGF-I.
    International Journal of Cancer 08/2004; 110(4):491-6. · 6.20 Impact Factor
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    ABSTRACT: In order to investigate the effect of high carbohydrate/low fat diet on glucose tolerance and on lipid profiles, we performed a 4-week crossover study. Japanese subjects (30 patients with type 2 diabetes mellitus, 15 subjects with impaired glucose tolerance and 8 subjects with normal glucose tolerance) were allocated either 55% standard carbohydrate/30% fat (sc) or 70% high carbohydrate/15% low fat (hc) diet for four weeks, and evaluated by OGTT and various parameters. Then, the diet was crossed over to another diet, and identical parameters were re-evaluated after four weeks. Area under the glucose concentration-time curve (AUG) or triglyceride did not show significant changes between the two diets. HDL-Cholesterol and body mass index decreased significantly by hc diet. Free fatty acids and homeostasis model assessment insulin resistance index showed a tendency to be decreased by hc diet. AUG hc/sc ratio was inversely correlated with AUG or free fatty acids on standard carbohydrate diet. In conclusion, the present 4-week high carbohydrate/low fat diet may be useful to reduce body weight and insulin resistance. The 4-week high carbohydrate/low fat diet did not affect glucose tolerance as a whole. Although the 4-week high carbohydrate/low fat diet decreased HDL-Chol, it did not increase triglyceride.
    Diabetes Research and Clinical Practice 05/2004; 64(1):11-8. · 2.74 Impact Factor
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    ABSTRACT: Prostate cancer has become the most common cancer among men in the United States. Although milk consumption is considered to be a risk factor in some epidemiological studies, the results are inconsistent. A meta-analysis method was conducted to estimate the combined odds ratio (OR) between milk consumption and prostate cancer from case-control studies published between 1984 and 2003 using commercial software (comprehensive meta-analysis). The combined OR was 1.68 (95% confidence interval = 1.34-2.12) in the 11 published case-control studies. The combined OR varied little by study stratification. Additionally, we evaluated the possible risk factors in milk for prostate cancer. In conclusion, we found a positive association between milk consumption and prostate cancer. The underlying mechanisms, including fat, calcium, hormones, and other factors, should be investigated further.
    Nutrition and Cancer 02/2004; 48(1):22-7. · 2.70 Impact Factor
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    ABSTRACT: Studies to elucidate the cause of prostate cancer have met with little success to date. Epidemiological studies suggested that milk consumption is probably as one of the risk factors for prostate cancer. The studies thus focused on the fat and calcium in milk, but reached no definitive conclusion. According to the measurements of estrogen levels in milk by different studies, it was suggested that estrogen in milk was a possible risk to cause prostate cancer. One reason supporting this hypothesis is that Western diet (characterized by milk/dairy products and meat) causes a trend of increasing levels of estrogens, and Western males show a higher incidence rate of prostate cancer than Asia males. Estrogen levels in prostate fluid are also correlated very well with the prostate cancer. During several decades, estrogens, together with testosterone, was commonly used to induce the rodent model of prostate cancer. Our hypothesis also was supported by the presence of estrogen receptors in the prostate gland and the genotoxic role of estrogens on the prostate gland, as possible mechanisms. Therefore, if modern milk consumption does expose consumers to high levels of estrogen and plays an adverse role in prostate cancer, action should be taken to produce the noncontaminant milk.
    Medical Hypotheses 02/2004; 62(1):133-42. · 1.18 Impact Factor
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    ABSTRACT: The prevalence of hypertension in individuals with diabetes mellitus is higher than that in individuals without diabetes mellitus. High fiber intake decreases blood glucose and lipids levels. This study investigated the effects of cereal fiber intake on systolic and diastolic blood pressures in a rat model of type 2 diabetes mellitus. Thirty male Goto Kakizaki rats were randomly assigned to one of three groups. Each group was fed a barley diet, a white rice diet, or cornstarch diet. The rats were pair fed for 16 wk. Systolic and diastolic blood pressures were measured once every 4 wk by the photoelectric oscillometric tail-cuff method without anesthesia. The barley diet significantly decreased systolic blood pressure from week 12 and decreased the plasma levels of total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol. There were significant positive correlations between plasma lipids levels and systolic blood pressure. High fiber intake has beneficial effects on systolic blood pressure and blood lipids levels and suggests that fiber intake should be increased in individuals who have diabetes mellitus to prevent complications.
    Nutrition 01/2004; 20(11-12):1003-7. · 2.86 Impact Factor
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    ABSTRACT: The present study was performed to determine the effect of long-term feeding with a high-fat/low-carbohydrate (HF/LC) diet on the onset of type-2 diabetes mellitus in normal rats. Male Wistar Imamichi rats were kept on a Control (carbohydrate 60%, fat 15%) or HF/ LC (carbohydrate 10%, fat 65%) diet for 16 mo. An intraperitoneal glucose tolerance test was performed once every 2 mo. Glucose tolerance was impaired 2 mo after the start of HF/LC diet feeding, accompanied by a decrease in the insulinogenic index. Along with time of HF/LC diet feeding, the glucose tolerance was further deteriorated with more serious impairment of insulin secretion and sensitivity. At the end of the experiment, 15 of 18 rats in the HF/LC group were diabetic, whereas only 4 of 17 rats in the Control group were diabetic. The present results demonstrate that longterm feeding with a HF/LC diet decreases the secretion and sensitivity of insulin, and induces diabetes mellitus in rats. Furthermore, long-term feeding with such a diet may produce adverse effects on the blood plasma lipid profile, with elevated levels of triglycerides, nonesterified fatty acids, total cholesterol, and reduced levels of high density protein cholesterol in the plasma.
    Endocrine 12/2003; 22(2):85-92. · 2.25 Impact Factor
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    ABSTRACT: Whether the intake of high dietary fiber may improve glycemic control in individuals with type 2 diabetes has been controversial. This study was conducted to observe the long-term effects of dietary fiber intake on glucose tolerance and lipid metabolism in rats. Thirty male type 2 diabetic model GK rats were divided randomly into 3 groups. Each group was fed either a barley (high-dietary fiber) diet, rice (low-dietary fiber) diet, or cornstarch (very-low-dietary fiber) diet. The rats were pair-fed for 9 months. The intake of the barley diet significantly improved the area under the plasma glucose concentration time curves, lowered the fasting plasma glucose and glycosylated hemoglobin levels, and decreased plasma total cholesterol (T Chol), triglycerides (TG), and free fatty acid (FFA) levels. This study demonstrated that long-term intake of barley has beneficial effects on glucose tolerance and lipid metabolism and suggests the intake of unrefined cereal foods should increase as a diet therapy for type 2 diabetes.
    Metabolism 10/2003; 52(9):1206-10. · 3.10 Impact Factor
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    ABSTRACT: To study the effects of estrogen-like products in milk on the male reproductive system. The incidence rates of testicular and prostatic cancers in 42 countries (regions), collected from the cancer incidence in five continent database (1988-1992), were correlated with the relative food consumption in these countries, which was provided by FAO database (1961-1990); two-generation reproduction test was taken by using Wistar rats according to FDA standard. Among the food items examined, milk was most closely correlated (r = 0.711) with prostatic cancer incidence, followed by meat and coffee. As for testicular cancer, cheese was most closely correlated (r = 0.804) with the incidences in ages of 20-39, followed by animal fat and milk. No significant decreases of reproductive organ weight were found after the rats had been fed a lot of milk for long time. The results suggest that further studies should be taken on the effects of estrogen-like products in milk on the male reproductive health.
    Zhonghua nan ke xue = National journal of andrology 07/2003; 9(3):186-90.
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    ABSTRACT: In this study, the effects of a barley diet containing high dietary fiber on the onset and development of diabetes mellitus in spontaneously diabetic rats was investigated by comparing with a rice diet containing low dietary fiber and an alpha-corn starch diet containing very low dietary fiber. 30 male Goto-Kakizaki (GK) strain rats (8 weeks of age) were randomly assigned to 3 groups; high barley (HB) group on a barley diet (dietary fiber intake, 1.79 g/day/rat), rice (R) group on a rice diet (dietary fiber intake, 0.46 g/day/rat), and alpha-corn starch (CS) group on an alpha-corn starch diet (dietary fiber intake, 0.24 g/day/rat). The carbohydrate (70%), fat (10%), and protein (20%) contents of these 3 diets were equal, and the rats were pair-fed each diet for 3 months. Feeding for 3 months showed that fasting plasma glucose level in the HB group was significantly lower than in the R and CS groups; the glucose tolerance in the HB group was markedly improved. Moreover, the plasma cholesterol and triglyceride levels in the HB group were significantly lower than those of the R and CS groups. Our findings demonstrated that barley enabled glycemic control and improved glucose tolerance compared with rice or alpha-corn starch.
    Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene) 06/2003; 58(2):281-6.
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    ABSTRACT: We observed glucose metabolism and insulin se- cretion in healthy young men after intake of large amounts of sugar. Ten subjects, with the randomized cross-over design, ingested sucrose or maltose solution hourly from 10:00 to 13:00 (75 g in 225 ml water per time). Plasma concentrations of glucose, insulin and c-peptide were measured in fasting, at 30 min after each intake and at 2 hr after last intake. Plasma glu- cose concentration increased after the first intake and decreased to the fasting level from the second intake. Plasma insulin and c-peptide concentrations increased from the first intake and retained throughout follow- ing intakes. Plasma concentrations of glucose, insulin and c-peptide were higher in maltose group than in sucrose group and the significant differences were ob- served after the last intake. In the present study, glu- cose concentration maintained in the normal range after intake of large amounts of disaccharide and in- sulin secretion responded well to this repeated intake of disaccharide, however, maltose tended to induce insulin resistance compared with sucrose.
    Journal of Health Science - J HEALTH SCI. 01/2003; 49(3):226-228.
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    Journal of Health Science - J HEALTH SCI. 01/2003; 49(5):348-352.
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    ABSTRACT: The effect of high carbohydrate (hc) diet on glucose tolerance and on lipid profiles in patients with type 2 diabetes mellitus is contradicted. Japanese patients with mild type 2 diabetes mellitus were allocated either 55% standard carbohydrate (sc) or 80% high carbohydrate diets for 1 week, and OGTT and lipid profiles were examined. Then the diet was crossed over for another week, and OGTT and other identical parameters were re-evaluated. High carbohydrate diet improved the area under the glucose concentration-time curve (AUG) in 16/24 patients, and significantly increased and decreased 1,5-anhydroglucitol and homeostasis model assessment insulin resistance (HOMA-R) as a whole, respectively. Fasting plasma glucose (FPG) hc/sc ratio was inversely correlated with HOMA-R on a standard carbohydrate diet. High carbohydrate diet significantly decreased LDL- and HDL-cholesterol, whereas it significantly increased triglyceride. Furthermore, hc/sc ratios of the lipid parameters were inversely correlated with the respective parameters on standard carbohydrate diet. The present study indicates that high carbohydrate diet improved glucose tolerance depending on patients and the improvement in FPG was predicted by HOMA-R on a standard carbohydrate diet. The effect of high carbohydrate diet on glucose tolerance and lipid profiles should be investigated through a long-term study in the future.
    Diabetes Research and Clinical Practice 10/2002; 57(3):163-70. · 2.74 Impact Factor

Publication Stats

309 Citations
59.77 Total Impact Points


  • 2003–2007
    • University of Yamanashi
      • • Department of Obstetrics and Gynecology
      • • Faculty of Medicine
      Kōhu, Yamanashi, Japan
    • Hebei Medical University
      Chentow, Hebei, China
  • 2003–2005
    • Yangzhou University
      • • Medical College
      • • Key Laboratory of Animal Infectious Diseases of Ministry of Agriculture
      Yangzhou, Jiangsu Sheng, China