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Biomedical subjects

M Kuratsune

Publications and source records attributed to M Kuratsune.

At least 19 recordsLinked to original sources
PubMed2006

PDGF receptor tyrosine kinase inhibitor suppresses mesangial cell proliferation involving STAT3 activation.

Proliferation of mesangial cells is a hallmark of glomerular disease, and understanding the regulatory mechanisms is critically important. The purpose of this study was to examine the relationship between mesangial cell proliferation and phosphorylated signal transducer and activator of transcription (STAT) 3 and to determine whether the PDGF receptor tyrosine kinase inhibitor STI 571 inhibited mesangial cell proliferation via modulation of STAT3. In this study, we investigated for the first time, the glomerular expression of phosphorylated STAT3 in paraffin sections from animals with experimental mesangial proliferative glomeronephritis. Phosphorylated STAT3 colocalized with many proliferating mesangial cells. We also demonstrated that treatment with STI 571 reduced mesangial cell proliferation and phosphorylated STAT3 signalling both in vitro and in vivo. In vivo, STI 571 treatment reduced the number of glomerular mesangial cells positive for both phosphorylated STAT3 and proliferating cell nuclear antigen. In summary, phosphorylated STAT3 is strongly expressed during mesangial cell proliferation and STI 571 induced suppression of mesangial cell proliferation involves inhibition of phosphorylated STAT3 signalling.

Animals↗
PubMed1999

Interleukin-6 localization and the prognosis of IgA nephropathy.

Various cytokines and growth factors may be involved in IgA nephropathy. To clarify whether interleukin-6 was a prognostic factor for this disease, we investigated interleukin-6 positivity of renal biopsy specimens and its relationship with the prognosis. The subjects were 90 patients with IgA nephropathy (42 males and 48 females with a median age of 32.7 +/- 13.8 years). Renal biopsy specimens were stained for interleukin-6 using an enzyme-antibody method. Fifty-two of 90 patients showed glomerular positivity for interleukin-6. Among the patients positive for interleukin-6, 24-hour urinary protein excretion and serum creatinine levels were significantly higher at the time of biopsy than in the patients without interleukin-6 positivity, while creatinine clearance was significantly lower. In the interleukin-6-positive patients without steroid therapy, serum creatinine increased significantly after 1 year (Deltas-Cr; 1.04 +/- 0.45 mg/dl) and creatinine clearance decreased significantly (DeltaCcr; -11.7 +/- 3.2 ml/min) compared to the interleukin-6-negative patients without steroid therapy. Steroid therapy improved 24-hour urinary protein excretion, serum creatinine, and creatinine clearance in the interleukin-6-positive patients, while these parameters worsened without steroid therapy. On the other hand, the IL-6-negative patients showed no differences of clinical parameters irrespective of the presence or absence of steroid therapy. In conclusion, glomerular interleukin-6 positivity may be a prognostic factor and an indicator of the need for steroid therapy in IgA nephropathy.

Adolescent↗
PubMed1991

An improved method for the detection of differential survival between normal and xeroderma pigmentosum lymphoblastoid cell lines in culture with 4-nitroquinoline-1-oxide.

The effects of the UV-mimetic chemical 4-nitroquinoline-1-oxide (4-NQO) upon cell lines heterozygous or homozygous for the recessive mutant xeroderma pigmentosum (XP) were investigated. Human lymphoblastoid cell lines, which were established from 4 XP homozygote patients (XPL15, XPL17, XPL19 and XPL20). 2 XP heterozygote individuals (XPPL17 and XPML17) and 58 normal individuals, were cultured in the presence of 4-NQO at doses of 0, 2, 4 and 8 x 10(-6) M. Then the total cell number was counted and the viability of the cells was measured by the dye exclusion method using trypan blue and a newly devised fluorometric method with fluorescein diacetate. Results showed that 4-NQO affected, in increasing order of impairment, the cell lines: normal less than XP heterozygote less than XP homozygote.

4-Nitroquinoline-1-oxide↗
PubMed1988

A case-control study of gastric cancer and diet in northern Kyushu, Japan.

A case-control study of gastric cancer was done in a rural area of northern Kyushu, Japan, in relation to dietary habits especially focusing on the relationship with the consumption of broiled fish. The study was based upon 139 cases of newly diagnosed gastric cancer at a single institution, 2,574 hospital controls and 278 controls sampled randomly from the residents of the study area (with sex and year of birth matched). No association was observed between the consumption of broiled fish and gastric cancer risk whether three types of broiled fish (raw fish, dried fish and salted fish) were analyzed separately or as a single category. However, consistently in the comparisons with both sets of controls, the risk of gastric cancer was inversely related with the consumption of fruits and positively associated with cigarette smoking. A decreased risk of gastric cancer was also noted among those with high consumption of green tea (10 or more cups per day).

Adult↗
PubMed1987

Cigarette smoking, alcohol and cancer mortality: a cohort study of male Japanese physicians.

Mortalities from selected sites of cancer among 5,130 male Japanese physicians followed up for 19 years were examined in relation to smoking and drinking habits surveyed in 1965. With smoking habit classified into three categories (never/past, 1-19 and greater than or equal to 20 cigarettes/day) and drinking habit into four (never/past, occasional, less than 2 and greater than or equal to 2 go of sake/day), the effects of the two factors and their combined effect were analyzed by using the Cox proportional hazard model. Interaction of smoking and drinking was found to be negligible for the sites of cancer studied (upper aerodigestive tract, esophagus, stomach, large bowel, liver and lung), and independent relationships of smoking and drinking with upper aerodigestive cancer were confirmed. Smoking, besides being strongly associated with lung cancer, was also weakly, but significantly, related to stomach cancer. Liver cancer showed no association with smoking whereas this cancer was significantly related to alcohol consumption. The present findings provide further evidence for the association between cigarette smoking and stomach cancer but do not support the relationship recently suggested between smoking and liver cancer.

Alcohol Drinking↗
PubMed1987

A cohort study on mortality of "yusho" patients: a preliminary report.

In 1968, a mass food poisoning (yusho) occurred in western Japan involving more than 1,850 people, the majority of whom were residents of Fukuoka and Nagasaki prefectures. The poisoning is now understood to have been caused by ingestion of a commercial brand of rice oil contaminated with polychlorinated derivatives of biphenyls, dibenzofurans, quaterphenyls, and some other related compounds. The number of deaths seen among 1,761 victims (887 males and 874 females) from the date of official registration as yusho up to the end of 1983 was compared with the expected number of deaths which was calculated on the basis of the national age, sex, and cause-specific death rates. Neither significantly increased nor significantly decreased mortality was seen among overall causes of death in males and females. A significant excess mortality was seen for malignant neoplasms at all sites in males but not in females. Neither significantly increased nor decreased mortality was seen for cancer of the esophagus, stomach, rectum and colon, pancreas, breast, and uterus. For cancer of the liver, however, a considerably increased mortality was seen in both males and females but the excess was statistically significant only in males. It was also notable that such increased mortality due to liver cancer was seen mainly among the patients living in Fukuoka prefecture but not at all among those in Nagasaki prefecture which approximate the yusho patients in Fukuoka prefecture in number. Deaths from chronic liver diseases and liver cirrhosis were also found to be increased in both sexes but the increase was not statistically significant.

Cohort Studies↗
PubMed1987

Effect of cigarette smoking and dietary factors on the amount of N-nitrosothiazolidine 4-carboxylic acid and N-nitroso-2-methyl-thiazolidine 4-carboxylic acid in human urine.

The effects of cigarette smoking and dietary factors on urinary excretion of N-nitrosothiazolidine 4-carboxylic acid (NTCA; N-nitrosothioproline) and N-nitroso-2-methylthiazolidine 4-carboxylic acid (NMTCA; N-nitroso-2-methylthioproline) were studied in a male volunteer and in healthy Japanese subjects from the general population and Seventh-Day Adventists (SDA). Twenty-four-hour urine samples from the male volunteer were collected on 20 smoking days and 20 nonsmoking days during ingestion of a fixed diet, and the amounts of urinary N-nitrosamino acids were analysed by gas chromatography-thermal energy analysis. Cigarette smoking caused about two-fold (significant) increases in the amounts of NTCA and NMTCA in the volunteer. In the male subjects from the general population, not controlled for diet, the amounts of NTCA and NMTCA in 24-h urines of smokers were also significantly higher than those of the nonsmokers. The urinary excretions of NTCA and NMTCA in SDA were lower than those of nonsmokers in the general population. It was concluded that cigarette smoking is one of the important factors in determining the amounts of NTCA and NMTCA in human urine. Dietary factors also apparently influence the urinary levels of these N-nitrosamino acids. In addition, an apparent sex difference in the urinary excretion of NTCA and NMTCA (about two-fold higher in females) was observed in the general population but not in SDA. The N-nitrosoproline (NPRO) level was significantly higher in SDA than in nonsmokers in the general population.

Adult↗
PubMed1986

Alcohol and mortality: a cohort study of male Japanese physicians.

The relationship between drinking habit surveyed in 1965 and cause-specific mortality over 19 years was investigated in 5135 male Japanese physicians taking into account smoking habit and separating ex-drinker from non-drinker. As compared with non-drinkers, daily drinkers with high consumption had a significantly increased mortality from all causes. Drinking was significantly related to the so-called alcohol-related causes of death; upper aerodigestive cancer, liver cancer and liver cirrhosis. Mortality from acute myocardial infarction was inversely related to drinking, whereas other coronary heart disease showed a somewhat higher mortality among men consuming a large amount of alcohol than among non-drinkers. There was a weak, but significant, association between stroke and drinking, and the relation did not differ between haemorrhagic stroke and other stroke. No obvious relationship with drinking was observed for cancers of the stomach, large bowel, pancreas and lung.

Alcohol Drinking↗
PubMed1986

Epidemiologic studies on possible health effects of intake of pyrolyzates of foods, with reference to mortality among Japanese Seventh-Day Adventists.

To elucidate the effect of intake of mutagenic and/or carcinogenic pyrolysis products of proteins and amino acids on carcinogenesis in man, we have undertaken two epidemiologic cohort studies: one concerning the possible association of broiled fish consumption with cancer and the other concerning the cancer mortality among Japanese Seventh-Day Adventists. The main findings of these studies are described.

Animals↗
PubMed1986

Dietary fiber in the Japanese diet as investigated in connection with colon cancer risk.

The low risk of colon cancer among the Japanese suggests a high intake of dietary fiber. Composite diets for 1959, 1970, and 1979 were prepared using food consumption data from the National Nutrition Survey in Japan and analyzed for non-starch polysaccharides (NSP) at the Dunn Clinical Nutrition Centre in Cambridge. The results showed that average intake of NSP by Japanese in the above years did not exceed 13 g per day, which is as low as the corresponding intake by the Scandinavians and the British, whose risk of colon cancer is known to be high.

Colonic Neoplasms↗
PubMed1986

Cancer mortality among patients undergoing cholecystectomy for benign biliary diseases.

Potential risks of gastrointestinal cancers after cholecystectomy were examined among 1238 patients who had had their gallbladders extirpated for benign biliary diseases from 1951 to 1970. The observed deaths between 1953 and 1984 were compared with the expected values which were calculated from death rates in Japan. No appreciable excess mortality was found for stomach cancer, colorectal cancer or pancreas cancer in relation to cholecystectomy. Observed and expected deaths during the whole observation period were 29 vs. 31.58 for stomach cancer, 8 vs. 6.50 for colorectal cancer overall, 5 vs. 3.19 for colon cancer and 3 vs. 3.51 for pancreas cancer. The corresponding figures in the 10 years or more after cholecystectomy were 14 vs. 19.06 for stomach cancer, 5 vs. 4.66 for colorectal cancer and 3 vs. 2.38 for colon cancer. A notably increased mortality from liver cancer was observed, but it was considered to be related not to cholecystectomy itself but to blood transfusion.

Biliary Tract Diseases↗
PubMed1985

Genetically mediated induction of aryl hydrocarbon hydroxylase activity in mice by polychlorinated dibenzofuran isomers and 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Hepatic aryl hydrocarbon hydroxylase (AHH)-inducing potency of toxic polychlorinated aromatic hydrocarbons such as polychlorinated dibenzofurans (PCDFs), 3,4,5,3',4',5'-hexachlorobiphenyl (HCB) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was studied in four inbred strains of mice with different phenotypes of Ah locus, i.e., AHH-responsive strains: C57BL/6N and AKR/Ms Qdj, and AHH-nonresponsive strains: DBA/2Cr Slc and Qdj; DDD. Eight individual PCDF isomers or TCDD were administered IP in doses of 30 micrograms/kg; HCB was given in a dose of 120 micrograms/kg. In AHH-nonresponsive strains of mice, only TCDD significantly induced hepatic AHH activity, while in AHH-responsive strains, 2,3,7,8-tetrachlorodibenzofuran(2,3,7,8-TCDF), 1,2,3,7,8-pentachlorodibenzofuran(1,2,3,7,8-PCDF), 2,3,4,7,8-pentachlorodibenzofuran(2,3,4,7,8-PCDF), and TCDD significantly enhanced the enzyme activity, and the induced AHH activities with the three PCDF isomers were about 30-65% of those of TCDD. These results indicate that AHH responsiveness in mice segregates with the induction of AHH activity by PCDF isomers and may also segregate with the toxic potency of the isomers; i.e., toxic potencies of 2,3,7,8-TCDF, 1,2,3,7,8-PCDF, and 2,3,4,7,8-PCDF in AHH-responsive strains of mice may be much greater than those in AHH-nonresponsive strains of mice. Taking into account both the potent AHH inducibility and the high bioaccumulation of 2,3,7,8-TCDF, 1,2,3,7,8-PCDF, and 2,3,4,7,8-PCDF, these three PCDF isomers should be given greater attention with regard to environmental contamination.

Animals↗
PubMed1985

Genetically mediated induction of aryl hydrocarbon hydroxylase activity in human lymphoblastoid cells by polychlorinated dibenzofuran isomers and 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Aryl hydrocarbon hydroxylase(AHH)-inducing potency of toxic polychlorinated aromatic hydrocarbons such as polychlorinated dibenzofuran (PCDF) isomers, 3,4,5,3',4',5'-hexachlorobiphenyl (HCB) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was investigated in human lymphoblastoid cell lines with different AHH inducibility for 3-methylcholanthrene (3-MC) obtained from healthy subjects. Each of the cell lines was treated with eight individual PCDF isomers, TCDD, and HCB at doses of 1.9-15 ng/ml of culture medium, 1.9-7.5 ng/ml and 95 ng/ml, respectively. Lymphoblastoid cell lines were arbitrarily classified into three groups based on their AHH inducibilities with 3-MC (2.5 microM); low (3-MC/control = I less than 3), middle (3 less than or equal to I less than 6) and high (I greater than or equal to 6). Degrees of the enzyme inducibilities of the organochlorine compounds proportionally increased with those for 3-MC. AHH inducibilities with 2,3,4,7,8-pentachlorodibenzofuran(2,3,4,7,8-PCDF), 1,2,3,4,6,7-hexachlorodibenzofuran(1,2,3,4,6,7-HCDF) and 1,2,3,4,7,8-hexachlorodibenzofuran(1,2,3,4,7,8-HCDF) were comparable to those of TCDD at doses of 7.5 ng/ml, and about twice as high as those of 2,3,7,8-tetrachlorodibenzofuran (TCDF), at the same dose, HCB, at a dose of 95 ng/ml, did not induce enzyme activity. The experimental evidence indicated that AHH inducibility by the organochlorine compounds reflected the genetic susceptibility of the cells to the phenomenon of induction, and PCDF isomers found at relatively high concentrations in tissues of mammals exerted the highest values of AHH induction.

Aryl Hydrocarbon Hydroxylases↗
PubMed1985

Smoking and mortalities from cancer, coronary heart disease and stroke in male Japanese physicians.

A cohort of 5,477 male Japanese physicians was studied to examine the relationship between smoking habits and mortalities from cancer, coronary heart disease (CHD) and stroke over 12.7 years. The logistic regression analysis based on proportional hazard models was used for statistical assessment. The risks of both lung cancer and CHD were strongly associated with smoking habits in terms of the number of cigarettes smoked per day, inhalation level and age at starting to smoke. These associations were not influenced by the effect of drinking habits. However, the risk increment of lung cancer due to cigarette smoking was fairly small as compared with the data from other studies of male Caucasians. A statistically significant association was observed between upper aerodigestive cancer and cigarette smoking. But this relationship became insignificant after adjustment for drinking habits, and the risk of heavy smokers was drastically reduced. No clear association was noted between smoking and mortalities from gastric cancer and stroke.

Age Factors↗
PubMed1985

Alcohol and cancer in male Japanese physicians.

The relationship between alcohol and site-specific cancers was investigated in a follow-up study of 5,139 male Japanese physicians. Information on drinking habits was obtained by mail questionnaire in 1965, and cancer deaths over 12.7 years were analyzed with drinking habits classified into five categories; nondrinker, ex-drinker, occasional drinker, and daily drinker whose intake of alcohol was equivalent to less than 2 or 2 and more go of sake (1 go sake congruent to 27 ml alcohol). Both age and smoking habits were taken into account in the calculation of death rates based on man-years at risk. Logistic regression analysis was also performed on cummulative mortality data. Upper aerodigestive cancer was strongly associated with alcohol consumption, giving some confidence in the validity of the present study. Excluding ex-drinkers, the risk of stomach cancer and liver cancer was gradually increased from nondrinkers to daily drinkers with lower intake of alcohol, but no further increase was noted for daily drinkers with larger consumption. Logistic regression did not show any significant associations between drinking habits and these two cancers, but the number of deaths from liver cancer was still small. Not particular patterns were observed for cancers of the large bowel and lung.

Adult↗
PubMed1985

Inducing potency of aryl hydrocarbon hydroxylase activity in human lymphoblastoid cells and mice by polychlorinated dibenzofuran congeners.

Aryl hydrocarbon hydroxylase (AHH)-inducing potency of eight polychlorinated dibenzofuran (PCDF) isomers, 3,4,5,3',4',5'-hexachlorobiphenyl (HCB) and 2,3,7,8-tetrachlorodibenzo-p-dioxon (TCDD) in two inbred mouse strains (AHH responsive and nonresponsive mouse strains) and eight human lymphoblastoid cell lines (four males and four females) was investigated to evaluate their relative toxic potency. In AHH nonresponsive DBA mouse strain, only TCDD induced hepatic AHH activity at a dose of 30 micrograms/kg, while in AHH responsive C57 mouse strain, six PCDF isomers besides TCDD could enhance the enzyme activity significantly. 2,3,7,8-Tetrachlorodibenzofuran (2,3,7,8-TCDF), 1,2,3,7,8-pentachlorodibenzofuran (1,2,3,7,8-PCDF) and 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PCDF) showed the highest AHH inducing activity among the PCDF isomers tested. In contrast with the results obtained from the mouse experiments, in human lymphoblastoid cells, 2,3,4,7,8-PCDF, 1,2,3,4,6,7-hexachlorodibenzofuran (1,2,3,4,6,7-HCDF) and 1,2,3,7,8-hexachlorodibenzofuran (1,2,3,4,7,8-HCDF) elicited the highest AHH induction and were as potent AHH inducers as TCDD. These observations suggest that toxicities of 2,3,4,7,8-PCDF, 1,2,3,4,6,7-HCDF and 1,2,3,4,7,8-HCDF in human tissues may be comparable to that of TCDD. It was also observed that in both male and female human cell lines, the degree of AHH inducibilities of these compounds were roughly parallel to that of 3-methylcholanthrene, possibly indicating that genetic susceptibility among human population to the toxic compounds are also present similar to those reported among mouse strains.

Animals↗