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1.
Dig Dis Sci ; 42(7): 1394-9, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9246035

ABSTRACT

Helicobacter pylori (Hp) has strong urease activity and produces a large amount of ammonia in the stomach. In animal studies, ammonia was shown to accelerate cell kinetics of gastric mucosa, and long-term exposure of the stomach to ammonia leads to mucosal atrophy. To understand this process, we examined the effects of ammonia on the growth and cell cycle progression of human gastric cancer cell lines (HGC-27, MKN1, MKN45) using flow-cytometric analysis. In each cell line, ammonia inhibited the cell growth in a dose-dependent manner and caused significant accumulation of S-phase cells at a cytostatic dose. DNA synthesis of HGC-27 cells treated with ammonia was also suppressed to about 50% of that of the untreated cells. Similar effects were observed on addition of ammonium chloride at the same concentration, while adjusting the pH of the media with NaOH alone to that with the cytostatic dose of ammonia did not affect the cell cycle progression. These observations indicate that ammonia induces S-phase arrest in gastric cells independently of pH.


Subject(s)
Ammonia/pharmacology , Stomach Neoplasms/pathology , Tumor Cells, Cultured/drug effects , Adenocarcinoma/pathology , Carcinoma, Adenosquamous/pathology , Cell Cycle/drug effects , Cell Division/drug effects , DNA, Neoplasm/biosynthesis , DNA, Neoplasm/drug effects , Dose-Response Relationship, Drug , Flow Cytometry , Humans , Hydrogen-Ion Concentration , S Phase
2.
Arerugi ; 44(12): 1361-8, 1995 Dec.
Article in Japanese | MEDLINE | ID: mdl-8871290

ABSTRACT

Frequency of and factors associated with sensitization by Japanese cedar pollen (JCP) and Japanese cedar pollinosis (JCPS) were analyzed by a cross-sectional method. Four hundred and five primary school children in a rural town were examined by a questionnaire filled out by their parents and a serum test in May, 1994. Children with positive JCP specific IgE antibody (CAP-RAST score > = 1) comprised 39%, and those with a score of 2 or more, 35%. Prevalence of JCPS defined as positive IgE antibody and "definite symptoms" (any nasal and/or conjunctival symptom continuing for three weeks or more in March and/or April) was 8%, and that of JCPS defined as positive IgE antibody and "definite or possible symptoms" (no condition for duration) was 22%. Children with a high total IgE antibody level (> = 250 U/ml) comprised 26%. The JCP specific IgE antibody level revealed a strong positive correlation with the total IgE antibody level. Past and family history of allergic disease in general was associated with a total IgE antibody level stronger than the JCP specific IgE antibody level, and the history was also associated with allergic-like symptoms except for JCPS stronger than the symptoms of JCPS. Passive smoking by family and use of kerosene stove were negatively associated with the highest level of JCP specific IgE antibody and was not associated with other levels. One explanation may be that allergic disposition influences smoking habits, but the unique condition of nasal mucosa for allergic reaction should be considered.


Subject(s)
Antibody Formation , Immunoglobulin E/biosynthesis , Pollen/immunology , Rhinitis, Allergic, Seasonal/immunology , Antibodies/blood , Child , Cross-Sectional Studies , Heating , Humans , Immunoglobulin E/blood , Rhinitis, Allergic, Seasonal/etiology , Tobacco Smoke Pollution
3.
Mech Ageing Dev ; 84(1): 39-54, 1995 Sep 29.
Article in English | MEDLINE | ID: mdl-8719776

ABSTRACT

We investigated age-related changes in the production of TNF at the cellular level using immunocompetent peritoneal and spleen cells from C3H/He mice of various ages. The density of cultured peritoneal macrophages and spleen cells required for TNF production was at least 5 x 10(5) cells/dish. The optimal concentration of OK-432 for 24-h culture of peritoneal macrophages (1 x 10(6) cells) and spleen cells (1 x 10(7) cells) was 0.5 and 0.1 KE/ml, respectively. Among peritoneal cells, adherent macrophages were the major TNF-producing cells, whilst nonadherent T or B cells alone did not produce TNF after stimulation with OK-432. In the case of spleen cells, T or B cells were involved in the production of TNF when cultured with a few adherent cells in the presence of OK-432. However, T or B cells alone failed to produce TNF. Production of TNF by peritoneal macrophages from both male and female mice increased significantly with aging. In contrast, although TNF production by spleen cells tended to increase with aging, no significant change was noted. The total number of peritoneal and spleen cells, respectively increased up to about 18 months after birth with B cells being principally responsible for this age-related increase. We previously reported that systemic production of TNF increases with aging. The present study of TNF production at the cellular level in mice indicated (1) that TNF production per macrophage increased with aging, and (2) that the number of T and B cells involved in the production of TNF in the presence of macrophages also increased at least up to middle age.


Subject(s)
Aging/metabolism , Peritoneal Cavity/cytology , Spleen/metabolism , Tumor Necrosis Factor-alpha/biosynthesis , Animals , B-Lymphocytes/metabolism , Cell Count , Female , Macrophages, Peritoneal/metabolism , Male , Mice , Mice, Inbred C3H , Picibanil/pharmacology , Spleen/cytology , T-Lymphocytes/metabolism
4.
Eur J Gastroenterol Hepatol ; 7 Suppl 1: S79-81, 1995 Aug.
Article in English | MEDLINE | ID: mdl-8574744

ABSTRACT

AIM: Ammonia is a cytotoxic factor of Helicobacter pylori that is involved in gastric mucosal injury. This study was designed to show whether ammonia has an effect on the cell-cycle progression in human gastric cells in vitro. MATERIALS AND METHODS: We studied the effects of ammonia and ammonium chloride on cell growth and cell-cycle progression of the human gastric cancer cell line HGC-27. We cultured HGC-27 cells and counted viable cells by trypan blue dye exclusion 24 h after the addition of various concentrations of ammonia or ammonium chloride. DNA contents of nuclei were analysed by flow-cytometry. RESULTS: Ammonia and ammonium chloride inhibited the proliferation of HGC-27 cells dose-dependently. Flow-cytometric analysis showed S-phase accumulation of HGC-27 cells treated with ammonia and ammonium chloride at cytostatic doses. CONCLUSIONS: These results suggest that ammonia and ammonium chloride inhibit the growth of gastric cells in S phase. This mechanism may make a significant contribution to the pathogenesis of Helicobacter pylori-associated gastric mucosal atrophy.


Subject(s)
Ammonia/adverse effects , Ammonium Chloride/adverse effects , Helicobacter pylori , Stomach Neoplasms/etiology , Atrophy/chemically induced , Cell Division/drug effects , DNA, Bacterial/drug effects , Disease Progression , Dose-Response Relationship, Drug , Flow Cytometry , Gastric Mucosa/drug effects , Gastric Mucosa/pathology , Humans , S Phase , Stomach Neoplasms/chemically induced , Stomach Neoplasms/microbiology , Tumor Cells, Cultured
5.
Nihon Eiseigaku Zasshi ; 50(2): 622-30, 1995 Jun.
Article in Japanese | MEDLINE | ID: mdl-7630030

ABSTRACT

Risk factors for Japanese cedar pollinosis including past or family history of allergic diseases, smoking and passive smoking, dwelling conditions, and life events were analyzed by a case control method. Patients with Japanese cedar pollinosis (22 males and 67 females) were matched with a corresponding number of patients without potential symptoms of pollinosis according to sex and age (+/- 5 years). The mean age was 39 years in both groups. The odds ratio (OR) was calculated by McNemar's method and the conditional logistic regression model. The design and methodology in this study were somewhat inadequate so that the validity of the results is limited. The most important problem was no-matching according to exposure to pollen. Significantly high OR for past history of allergic disease (8.80, 95% confidence interval (CI); 3.49-22.2), atopic sermatitis (9.00, 95% CI; 1.14-71.0), and a sibling history of allergic disease (3.25, 95% CI; 1.06-9.97) were consistent with former genetical studies. ORs were lower than unity for current smokers (0.36, 95% CI; 0.11-1.13) and those smoking 10 cigarettes/day or more (0.20, 95% CI; 0.04-0.91) relative to nonsmokers. The OR for passive smoking from 7-15 years of age as a result of the father's smoking habit (0.38, 95% CI; 0.17-0.86) was also significantly low. Smoking was suggested to increase the level of total and antigen-specific IgE in serum by former studies, so that sensitization and symptoms should be studied separately. The high OR of residents in a business or light industrial area (5.00, 95% CI; 1.45-17.3) suggested an association with air pollution.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Rhinitis, Allergic, Seasonal/etiology , Adolescent , Adult , Aged , Air Pollutants, Occupational/adverse effects , Case-Control Studies , Child , Female , Humans , Male , Middle Aged , Odds Ratio , Risk Factors , Smoking/adverse effects , Trees
6.
Nihon Koshu Eisei Zasshi ; 42(5): 313-21, 1995 May.
Article in Japanese | MEDLINE | ID: mdl-7647348

ABSTRACT

A randomized controlled trial was conducted to evaluate the efficacy of smoking cessation instruction given to general smokers at an annual physical examination. Four hundred and twenty-six male and 42 female clients were randomly assigned to an intervention group (I), and 413 males and 76 females were assigned to a control (C) group. The I group was given an approximately 2-minute smoking cessation instruction by physicians, answered a quiz concerning tobacco, chose their own behavioral goals and were handed a leaflet on how to quit smoking. Subjects in both groups responded to a self-administered questionnaire and a 6-month and 12-month follow-up was performed by post card or telephone. The I group received an encouragement card one month after instruction and abstainers of the I group were awarded a telephone card at the 6-month follow-up. The results were as follows: 1) The male I group exhibited 7.3% (6 months), 10.1% (12 months) abstinence rates and the male C group 4.4% (6 months), 5.3% (12 months), respectively. The difference in 12-month abstinence rates was statistically significant. 2) The female I group exhibited abstinence rates of 16.7% (6 months), 23.8% (12 months) and the female C group 14.5% (6 months), 17.1% (12 months), respectively. 3) A multivariate analysis of smoking cessation showed that lower nicotine dependency, strong determination for smoking cessation, and being female were significant factors for abstinence at the 6-month follow-up. At 12 months, the smoking cessation instruction also became a significant factor. These data suggest that a simple smoking cessation instruction at an annual physical examination was effective for general smokers.


Subject(s)
Patient Education as Topic , Physical Examination , Smoking Cessation , Smoking Prevention , Adult , Female , Humans , Male , Middle Aged , Multivariate Analysis
7.
Nihon Shokakibyo Gakkai Zasshi ; 91(6): 1075-85, 1994 Jun.
Article in Japanese | MEDLINE | ID: mdl-8028200

ABSTRACT

To evaluate the psycho-social factors of peptic ulcer, we carried out a comparative study. Seventy-six men and 19 women with peptic ulcers diagnosed at seven hospitals in Kyoto, Osaka and Hyogo Prefectures in Japan were surveyed during November 1990 about their daily hassles, depressive state, social support and life style using a self-administered questionnaire. The results were compared to those for two control groups. One control group was diagnosed with normal, atrophic gastritis, or superficial gastritis by the gastro-duodenal endoscopic examinations in the same hospitals. The other control group consisted of participants in a health-screening examination at one of the above hospitals. There were no significant differences between patients and controls in daily hassles, depressive state, and social support. However, being unmarried, smoking and eating irregular meals significantly increased the relative risk of peptic ulcer in men and family history of peptic ulcer significantly increased the risk in women.


Subject(s)
Peptic Ulcer/psychology , Social Support , Stress, Psychological , Adolescent , Adult , Aged , Female , Humans , Life Style , Male , Middle Aged , Risk , Surveys and Questionnaires
8.
Nihon Koshu Eisei Zasshi ; 41(5): 452-60, 1994 May.
Article in Japanese | MEDLINE | ID: mdl-8049513

ABSTRACT

A survey was conducted to examine the prevalence of depressive symptomatology among residents of a rural community using the Center for Epidemiologic Studies Depression (CES-D) Scale. Subjects were 220 men and 319 women aged between 30 and 69 who participated in annual community health examinations. The relation of depressive symptomatology to the results of physical examination, self-rated health status, subjective symptoms and lifestyles were also examined. The results are as follows. 1) Of the subjects, 13.2% of the men and 16.3% of the women had depressive symptomatology (CES-D score > or = 16), with 4.5% of the men and 9.4% of the women having moderate or severe depressive symptomatology (CES-D score > or = 20). Prevalence was higher for younger men and for women in their forties, but these differences were not statistically significant. 2) There was a weak correlation between depressive symptomatology and the results of physical examination. Self-rated health status was more significantly correlated with depressive symptomatology. Self-rated health status and depressive symptomatology each correlated independently with the number of symptoms experienced by the subjects over the past year. The subjective symptoms that were correlated with depressive symptomatology were different from those correlated to self-rated health status. Men and women also had differences in links between depressive symptomatology, self-rated health status and symptoms experienced. 3) Lifestyles of those who had depressive symptomatology were worse than those who did not. But only duration of sleep and food intake had statistically significant relation to depressive symptomatology. Only weak correlations between lifestyles and self-rated health status were observed.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Depression/epidemiology , Health Status , Life Style , Rural Health , Adult , Aged , Female , Humans , Japan/epidemiology , Male , Middle Aged , Prevalence
9.
Nihon Koshu Eisei Zasshi ; 41(2): 140-6, 1994 Feb.
Article in Japanese | MEDLINE | ID: mdl-8161830

ABSTRACT

This study examined the direct association between medical costs and cigarette smoking and modification of interest in visiting medical facilities. The study sample consisted of 966 males 30 years of age or older in a rural town in Kyoto Prefecture, who were members of the National Health Insurance. The subjects were respondents to a previous questionnaire about smoking in February, 1989. There were 544 current smokers, 226 ex-smokers and 141 nonsmokers. Fifty-five subjects did not answer the question about smoking habits. Outpatient medical costs paid by National Health Insurance for the fiscal year 1989 were analyzed. Average medical costs of ex-smokers were the highest of all groups-current, ex-, and non-smokers (30-49, 50-69, and 70+ years of age). Those of current smokers and of the combined current or ex-smokers group were higher than those of non-smokers (30-49 and 50-69 years of age). None of these differences were significant by nonparametric test. The effect of smoking on medical costs was evaluated by odds ratio of the largest class of costs (50,000+ yen for 30-49 years of age, 200,000+ yen for 50-69 years of age, and 500,000+ yen for 70+ years of age) for various types of smokers compared with non-smokers by logistic regression. The odds ratios of current, ex-, and current or ex-smokers 30-49 and 50-69 years of age were between 2 to 3, but not significant. The odds ratio of subjects 70 years of age or older was smaller than unity and not significant.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
National Health Programs/economics , Smoking/adverse effects , Adult , Aged , Aged, 80 and over , Health Expenditures , Humans , Japan , Male , Middle Aged , Rural Population , Surveys and Questionnaires
10.
Nihon Eiseigaku Zasshi ; 48(6): 1048-57, 1994 Feb.
Article in Japanese | MEDLINE | ID: mdl-8126927

ABSTRACT

Reproducibility of results from a self-administered questionnaire on dietary habits (the frequency of taking various foods and eating habits), smoking and drinking was examined to study the reliability of the questionnaire, stability of lifestyle, and the validity of the questionnaire in assessing lifestyle as a risk factor in chronic diseases. The study sample included 120 males and 173 females in a rural town in Kyoto Prefecture, who participated in a series of three health examinations in 1988, 1989, and 1992. A survey using the same questionnaire was performed before each health examination. Reproducibility was assessed by correlation (Spearman's rank correlation coefficient or kappa coefficient), exact agreement of category answered, and comparison of mean frequency. An attempt was made to separate reliability and stability from reproducibility using the data from the questionnaire obtained in the three years. Good reproducibility for one-year and four-year intervals was found for foods taken habitually or often (boiled rice, cooked rice gruel with tea, milk, coffee, fruits and bread), and habits (eating breakfast, some eating habits, smoking and drinking). The same was also found for cigarette or alcohol consumption among current consumers except that cigarette consumption over a four-year interval was more likely to change. The reliability of the questionnaire and stability of these items were considered satisfactory, suggesting that the questionnaire was a valid method of assessing long-term lifestyle. Poor reproducibility of results regarding consumption of green-yellow and other vegetables indicated both poor reliability and a change in consumption over four years, and suggested poor validity. However, disagreement in more than one category of vegetables was not large and misclassification in assessing them as risk factors and changes in frequency of consumption may not be large either. Although correlation coefficients for the items of dairy food and eating snacks were fair, disagreement in more than one category was relatively large which may have caused misclassification. The mean frequency of consumption of pickles and fishpaste, ham or sausage significantly decreased over the four year interval. This may reflect the influence of health education on reducing salt intake.


Subject(s)
Alcohol Drinking , Feeding Behavior , Smoking , Adult , Aged , Female , Humans , Male , Middle Aged , Reproducibility of Results , Surveys and Questionnaires
11.
Microbiol Immunol ; 38(3): 217-23, 1994.
Article in English | MEDLINE | ID: mdl-7915815

ABSTRACT

Inbred C57BL/6 (B6) mice which had received an inoculation of allogeneic spleen cells showed remarkable antitumor activity against syngeneic tumor challenge with B16 melanoma cells 3 days after the allogeneic cell inoculation. This antitumor activity was not specific to the inoculated alloantigen, since the challenging B16 cells are syngeneic to B6 mice and since it was induced by BALB/c spleen cells as well as C3H/He spleen cells. The antitumor activity was sensitive to an in vivo treatment with anti-asialo GM1 (AGM1) antiserum or anti-Thy.1 monoclonal antibody (mAb) just before the tumor challenge and was resistant to an in vivo treatment with anti-CD8 (Ly.2) mAb. These results suggest that AGM1+Thy.1+CD8- activated natural killer (NK) cells were generated by alloantigen inoculation and took an important part in the antitumor effect of the alloantigen inoculation.


Subject(s)
Isoantigens/immunology , Killer Cells, Natural/immunology , Melanoma, Experimental/immunology , Spleen/immunology , Animals , Antibodies, Monoclonal , Antigens, Ly/immunology , Antigens, Surface/immunology , Cytotoxicity, Immunologic , G(M1) Ganglioside/immunology , Injections, Intraperitoneal , Membrane Glycoproteins/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Mice, Inbred C57BL , Spleen/cytology , T-Lymphocytes, Regulatory/immunology , Thy-1 Antigens , Tumor Cells, Cultured
12.
Nihon Koshu Eisei Zasshi ; 40(12): 1091-100, 1993 Dec.
Article in Japanese | MEDLINE | ID: mdl-8111081

ABSTRACT

To assess the combined influence of blood pressure and body mass index (BMI) on death from all-cause and circulatory diseases, a retrospective cohort study was performed in a community of Kyoto from 1978 to 1991. Between 1978 and 1982, 1,629 people (650 men and 979 women) aged 40-69 years, representing 76.6% of this age group in the community, were screened for entry into this study. A total of 134 deaths were observed and death by circulatory diseases was 36.6% of the all-cause deaths. The survival rate, calculated by the Kaplan-Meier method, was higher among normotensives [systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) < 90] compared to borderline hypertensives (SBP = 140-159 and/or DBP = 90-94) and hypertensives (SBP > = 160 or DBP > = 95, or using antihypertensive medication) for subjects aged 50-69 years both males and females. The hazard ratio of all-cause and circulatory disease mortality for sex, age, blood pressure and BMI as covariables was estimated from the Cox proportional hazard model. The hazard ratio (95% confidence interval) was greater for circulatory disease mortality [2.76 (1.37-5.75) for borderline hypertensive and 2.53 (1.21-5.26) for hypertensive] than for all-cause mortality [1.86 (1.22-2.84) for borderline hypertensive and 2.03 (1.32-3.10) for hypertensive]. These results indicate that hypertension increases risk of circulatory disease mortality and decreases survival rate. While the effect of obesity was not as strong for circulatory disease mortality as blood pressure, an increase in hazard ratio with increasing BMI was suggested in this study.


Subject(s)
Blood Pressure/physiology , Body Mass Index , Longevity/physiology , Adult , Age Factors , Aged , Cardiovascular Diseases/mortality , Female , Humans , Japan , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Factors , Sex Factors , Survival Rate
13.
Nihon Koshu Eisei Zasshi ; 40(12): 1111-9, 1993 Dec.
Article in Japanese | MEDLINE | ID: mdl-8111083

ABSTRACT

Participants in a community secondary prevention action sponsored by the local government were compared with non-participants with respect to utilization of medical facilities for medical examinations. The study sample consisted of 1,013 males and 1,042 females aged 40 years or over, in a rural town in Kyoto prefecture, who were members of the National Health Insurance. Data from National Health Insurance records, such as date of consultation and type of medical examinations, were analyzed. The secondary prevention action sponsored by the town consisted of a multiphasic health check for circulatory or other chronic diseases, and screenings for tuberculosis and cancers of the stomach, lung, breast and cervix. Medical examinations included urine test, blood cell count, electrocardiography, laboratory tests for serum transaminases, serum glucose, and fecal occult blood, X-ray or endoscopy of the stomach, chest X-ray, mammography, and cervical cytology. Results of the study showed that those who attended the town sponsored secondary prevention action were more likely to utilize local medical facilities, and those who did not participate were likely to visit facilities outside the town. Medical facilities, both local and outside the town, had a larger proportion of examinations corresponding to health examinations or stomach cancer screening than the town office, however, the town office had a larger proportion of lung or cervical cancer screening. The health examination and stomach cancer screening in the town office, and in the medical facilities appeared to be redundant while lung and cervical cancer screening were complemented tests at medical facilities. When these examinations are targeted as modifying factors in the natural history of diseases, consideration should be given to both the records of secondary prevention actions as well as medical records of other medical facilities that may be utilized.


Subject(s)
Health Facilities/statistics & numerical data , Physical Examination/statistics & numerical data , Preventive Health Services/statistics & numerical data , Adult , Aged , Female , Humans , Japan , Male , Middle Aged , National Health Programs , Neoplasms/diagnosis , Rural Population/statistics & numerical data
14.
Nihon Eiseigaku Zasshi ; 48(4): 830-7, 1993 Oct.
Article in Japanese | MEDLINE | ID: mdl-8254989

ABSTRACT

We report a comparative study of the Standardized Mortality Ratio (SMR) for circulatory system diseases and diet in a rural town and a fishing town in Kyoto Prefecture. SMR was assessed during the 5-year period from 1983 through 1987, and compared with the standard age- and sex-adjusted demographic and mortality statistics compiled by the National Census Bureau of Japan in 1985. A food frequency questionnaire in which the respondents evaluated their food consumption during the previous 1-year period was used to assess diet. The questionnaire was administered during February 1989 in the rural town and during February 1990 in the fishing town. In comparison with the standard statistics, SMR was higher in the rural town and lower in the fishing town. The inhabitants of the fishing town more frequently consumed low-fat and low-sodium foods, such as fish, potatoes, tofu, and green, yellow and other vegetables, and less frequently consumed high-fat and high-sodium foods, such as meat, fried food, pickles, than did the inhabitants of the rural town. The residents of the fishing town also consumed a greater variety of foods in one week. The two towns differ in geography and economic structure, and their inhabitants have different life-styles and eating habits. The lower SMR for circulatory system diseases in the fishing town may be related to the greater consumption of fish and vegetables with lower meat and salt intake, as well as the balanced of diet.


Subject(s)
Cardiovascular Diseases/mortality , Diet , Fisheries , Rural Population , Adult , Aged , Agriculture , Female , Humans , Japan , Male , Middle Aged , Sex Factors , Surveys and Questionnaires
15.
Nihon Eiseigaku Zasshi ; 48(4): 852-8, 1993 Oct.
Article in Japanese | MEDLINE | ID: mdl-8254992

ABSTRACT

We investigated age-related changes in the capacity for tumor necrosis factor (TNF) production in young and aged inbred C3H/He mice by injecting them with OK-432, a biological response modifier (BRM). An intravenous injection of 0.4mg of OK-432 was found to induce TNF production and two consecutive injections of 2KE of OK-432 induced much higher TNF production. Both the single and two consecutive injections of OK-432 induced significantly higher TNF production in aged mice than in young ones. Furthermore, the TNF-productive response to the two consecutive injections of OK-432 seemed to increase with aging. Male mice tended to show a marginally higher TNF-productive response than females. The mechanism by which aged mice have a higher capacity for TNF production is not clear. The following possibilities are conceivable. 1) Macrophages which are major TNF producer cells may be activated in aged mice. 2) Specific T cells which are cross-reactive to antigenic determinants in OK-432 may be increased in number in aging mice and activate macrophages effectively to produce TNF when stimulated by OK-432. In general, immunological functions tend to decline with aging. Our present results, however, suggest that by using an appropriate BRM we may be able to induce higher TNF production in the aged. This might lead to effective prevention and therapy for tumors, which increase in incidence with age.


Subject(s)
Aging/metabolism , Immunologic Factors/pharmacology , Picibanil/pharmacology , Tumor Necrosis Factor-alpha/biosynthesis , Animals , Cells, Cultured , Female , Male , Mice , Mice, Inbred C3H , Picibanil/administration & dosage , Stimulation, Chemical
16.
Oncogene ; 8(4): 1063-7, 1993 Apr.
Article in English | MEDLINE | ID: mdl-8455933

ABSTRACT

Cytosine methylation of CpG sites in the promoter region of eucaryotic genes is involved in the inactivation of expression of certain genes. Given that methylation can lead to reduced transcription, it is possible that expression of tumor-suppressor genes is also inactivated by hypermethylation, thereby contributing to the etiology of cancer. Recently we found five sporadic retinoblastoma tumors (16% of all unilateral cases) with hypermethylation of the 5' end of the retinoblastoma gene without detecting any structural abnormalities. However, it is unclear whether the promoter of the retinoblastoma gene is actually inactivated by its hypermethylation. Here we show that specific hypermethylation in the promoter region of the retinoblastoma gene reduces its expression to only 8% of the unmethylated control. Furthermore, we have found that two transcription factors important for the promoter activity, an activating transcription factor (ATF)-like factor and the retinoblastoma binding factor 1, do not bind when their recognition sequences are CpG methylated. These results in vitro strongly support the hypothesis that CpG methylation of the human tumor-suppressor gene can result in the inactivation of the gene and thus lead to oncogenesis.


Subject(s)
Genes, Retinoblastoma , Retinoblastoma Protein/genetics , 5-Methylcytosine , Base Sequence , Cell Line , Consensus Sequence , Cytosine/analogs & derivatives , Cytosine/metabolism , Gene Expression , Humans , In Vitro Techniques , Methylation , Molecular Sequence Data , Promoter Regions, Genetic , RNA, Messenger/genetics , Transcription Factors/metabolism
17.
Cancer Res ; 53(6): 1328-31, 1993 Mar 15.
Article in English | MEDLINE | ID: mdl-8443813

ABSTRACT

Genistein, an isoflavone, is a specific inhibitor of tyrosine kinase and topoisomerase II. However, its effect on cell growth is unknown. Therefore, we examined the effects of genistein on cell growth and cell cycle progression and compared its effects with other flavonoids. Genistein inhibited in a dose-dependent manner the growth of HGC-27 cells derived from human gastric cancer. Flow-cytometric analysis showed that genistein almost completely arrested the cell cycle progression at G2-M. This effect was reversible when genistein was removed from the culture medium. In contrast, other flavonoids such as flavone, luteolin, and the structurally similar daidzein arrested the cell cycle at G1. Consistent with the flow-cytometric analysis, microscopic observation showed that genistein did not increase the mitotic index, which supposes that genistein may arrest the cell cycle at G2 or early M. These results suggest that the G2-M arrest by genistein is a unique effect among flavonoids.


Subject(s)
G2 Phase/drug effects , Growth Inhibitors/pharmacology , Isoflavones/pharmacology , Mitosis/drug effects , Genistein , Humans , Mitotic Index/drug effects , Stomach Neoplasms/pathology , Tumor Cells, Cultured/drug effects
18.
Nihon Shokakibyo Gakkai Zasshi ; 89(8): 1484-90, 1992 Aug.
Article in Japanese | MEDLINE | ID: mdl-1404976

ABSTRACT

Treatment of isolated parietal cells from guinea pig gastric mucosa with ethanol caused a rapid increase in [Ca2+]i and concomitant decrease in the capacity for carbachol-stimulated acid secretion in a dose dependent manner. Carbachol rapidly increased the [Ca2+]i from trimethoxybenzoic acid 8-(diethylamino)-octyl ester sensitive intracellular pool. In contrast, the increase with ethanol was through La3+ sensitive Ca2+ channel from external source, which suppressed the Ca2+ response subsequently stimulated with carbachol. Pretreatment of the cells with EGTA or La3+ completely prevented the elevation of [Ca2+]i with ethanol and preserved the Ca2+ response to carbachol. These findings indicate that ethanol-induced elevation of [Ca2+]i may desensitize the stimulation of carbachol. Furthermore, treatment of the parietal cells with ethanol increased the activity of protein kinase C in both cytosolic and membrane fractions of the cells. Activation of protein kinase C with phorbol diester suppressed the capacity for acid secretion. These results suggest that ethanol may inhibit the carbachol-stimulated acid secretion through the desensitization of Ca2+ response and the activation of protein kinase C.


Subject(s)
Calcium/physiology , Ethanol/pharmacology , Gastric Acid/metabolism , Parietal Cells, Gastric/drug effects , Signal Transduction/drug effects , Animals , Guinea Pigs , Male , Parietal Cells, Gastric/metabolism , Protein Kinase C/metabolism
19.
Mol Cell Biol ; 12(8): 3490-8, 1992 Aug.
Article in English | MEDLINE | ID: mdl-1321338

ABSTRACT

Transcriptional activation of human heat shock protein (HSP) genes by heat shock or other stresses is regulated by the activation of a heat shock factor (HSF). Activated HSF posttranslationally acquires DNA-binding ability. We previously reported that quercetin and some other flavonoids inhibited the induction of HSPs in HeLa and COLO 320DM cells, derived from a human colon cancer, at the level of mRNA accumulation. In this study, we examined the effects of quercetin on the induction of HSP70 promoter-regulated chloramphenicol acetyltransferase (CAT) activity and on the binding of HSF to the heat shock element (HSE) by a gel mobility shift assay with extracts of COLO 320DM cells. Quercetin inhibited heat-induced CAT activity in COS-7 and COLO 320DM cells which were transfected with plasmids bearing the CAT gene under the control of the promoter region of the human HSP70 gene. Treatment with quercetin inhibited the binding of HSF to the HSE in whole-cell extracts activated in vivo by heat shock and in cytoplasmic extracts activated in vitro by elevated temperature or by urea. The binding of HSF activated in vitro by Nonidet P-40 was not suppressed by the addition of quercetin. The formation of the HSF-HSE complex was not inhibited when quercetin was added only during the binding reaction of HSF to the HSE after in vitro heat activation. Quercetin thus interacts with HSF and inhibits the induction of HSPs after heat shock through inhibition of HSF activation.


Subject(s)
DNA-Binding Proteins/metabolism , Flavonoids/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Heat-Shock Proteins/genetics , Saccharomyces cerevisiae Proteins , Transcription Factors/metabolism , Animals , Base Sequence , Cell Line , Chloramphenicol O-Acetyltransferase/genetics , Chloramphenicol O-Acetyltransferase/metabolism , Colonic Neoplasms , DNA-Binding Proteins/genetics , Enhancer Elements, Genetic , Genistein , Heat Shock Transcription Factors , Hot Temperature , Humans , Isoflavones/pharmacology , Molecular Sequence Data , Oligodeoxyribonucleotides , Oligonucleotide Probes , Plasmids , Quercetin/pharmacology , RNA, Messenger/genetics , RNA, Messenger/isolation & purification , RNA, Messenger/metabolism , RNA, Neoplasm/genetics , RNA, Neoplasm/isolation & purification , Simian virus 40/genetics , Transcription Factors/genetics , Transfection
20.
Nihon Koshu Eisei Zasshi ; 39(7): 428-36, 1992 Jul.
Article in Japanese | MEDLINE | ID: mdl-1504337

ABSTRACT

A survey of the frequency of various kinds of foods, dietary habits, life style, and health status was performed on 2,049 men aged from 40 to 59 living in an urban area who were participants in a "human dock" medical checkup. The relationships between these factors and health status were studied in order to identify a particular life style associated with good health status. The instrument utilized in this survey was a special form of a structured questionnaire. The results are summarized below. 1. The frequency of various kinds of foods were correlated with the kind of breakfast eaten, dietary habits, physical exercise habits, daily physical activity, smoking, and occupation. The strongest correlation to frequency of various kinds of foods was found to be with the kind of breakfast eaten and dietary habits. 2. Dietary habits were also correlated to various aspects of life style: smoking, drinking, the frequency of various kinds of foods, kind of breakfast eaten, daily physical activity, sleeping hours, habits related to physical exercise, and the frequency of meals eaten away from home. Dietary habits correlated most closely with the frequency of various kinds of foods and daily physical activity. The frequency of various kinds of food and dietary habits were found to correlate with various aspects of life style, and those subjects with good overall life styles were also found to have desirable dietary life styles. The correlation of desirable dietary habits, food intake and a suitable life style with good health status was confirmed by the results of clinical blood tests used as an index of health status.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Blood Chemical Analysis , Feeding Behavior , Life Style , Humans , Male , Middle Aged
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