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Biomedical subjects

I Kato

Publications and source records attributed to I Kato.

At least 739 records · Page 41Linked to original sources
PubMedDate not supplied

A selective amplifier gene for tamoxifen-inducible expansion of hematopoietic cells.

BACKGROUND: We have developed a novel system for expansion of gene-modified hematopoietic stem/progenitor cells to overcome the low efficiency of current gene transfer methodology. This system involves 'selective amplifier genes', that encode fusion proteins between the granulocyte colony-stimulating factor receptor (GCR) and the hormone-binding domain of estrogen receptor (ER). Hematopoietic progenitors expressing the chimeras showed estrogen-responsive growth in a controllable manner. However, endogenous estrogen may activate the fusion proteins in vivo, depending on the hormonal status of the subjects. METHODS: We replaced ER with a mutant receptor (TmR) which specifically binds to 4-hydroxytamoxifen (Tm), to overcome limitations with wild-type ER. Interleukin-3 (IL-3)-dependent Ba/F3 cells and hematopoietic progenitor cells transduced with the resultant fusion proteins (GCRTmR and delta GCRTmR) were examined for ligand-inducible growth. RESULTS: GCRTmR- and delta GCRTmR-expressing Ba/F3 showed IL-3-independent growth in response to Tm, while the cells were unresponsive to estrogen at concentrations up to 10(-7)-10(-6) M. Furthermore, murine bone marrow cells transduced with GCRTmR and delta GCRTmR formed colonies in methyl-cellulose medium in response to Tm, while virtually no colonies appeared with 10(-7) M estrogen or without cytokines. CONCLUSIONS: These results suggest that influences of the endogenous estrogen can be almost eliminated by using the GCRTmR/Tm or delta GCRTmR/Tm system to expand gene-modified hematopoietic stem/progenitor cells.

Animals↗
PubMedDate not supplied

Regulation of the human immune response to HBsAg: effects of antibodies and antigen conformation in the stimulation of helper T cells by HBsAg.

The role of accessory cells (antigen-presenting cells) in binding HBsAg in the response of human T cells to this antigen was studied. Antibodies to HBsAg of IgG class increased significantly the amount of HBsAg that was captured and internalized by accessory cells in vitro. On the other hand, antibodies to HBsAg of IgM class or the F(ab')2 and Fab fragments of antibodies to HBsAg of IgG class did not modify the amount of HBsAg associated to these cells. HBsAg that was subjected to various denaturing treatments (acid, organic solvents, urea and heat) was compared for its capacity to react with antibody to HBsAg and stimulate the response of helper T lymphocytes. Results presented here indicate that HBsAg denatured by treatment with formic acid was captured by accessory cells and presented to the T cells much more efficiently than the native HBsAg. These results suggest that the response of helper T lymphocytes to some antigens such as HBsAg can be affected greatly by the presence of antibodies or the antigens' conformation.

Antigen-Presenting Cells↗
PubMedDate not supplied

Hyperuricemia in an infant with Taussig-Bing anomaly and interruption of the aortic arch.

Hyperuricemia is commonly recognized in adolescents and adults with cyanotic congenital heart disease. We report a case of a male infant with hyperuricemia, Taussig-Bing anomaly, and interruption of the aortic arch. The patient underwent correction of interrupted aortic arch and pulmonary arterial banding at the age of 7 days. Hyperuricemia appeared when he was 2 months old (max 17.7 mg/dl) and persisted until he underwent a Jatene operation at the age of 10 months. The hyperuricemia improved gradually after the disappearance of hypoxia and polycythemia. The laboratory findings suggest that hyperuricemia can result from uric acid overproduction due to secondary polycythemia, impairment of uric acid excretion by the kidney, or the acceleration of anaerobic metabolism. Allopurinol and benzbromarone together were partially effective treatments for hyperuricemia in this patient with cyanotic congenital heart disease.

Abnormalities, Multiple↗
PubMedDate not supplied

Testicular degeneration induced in rat offspring by maternal treatment with sobuzoxane.

Pregnant rats were orally administered sobuzoxane (an antitumor drug) during various days of gestation and the testicular development of their offspring was examined histopathologically on day 21 after birth. When 15.6 to 250 mg/kg of sobuzoxane was given every day from day 7 to 17 of gestation, seminiferous tubules devoid of spermatogonia and/or spermatocytes were found in a dose related manner. The critical period for testicular degeneration was identified to be day 13 and 14 of gestation by single administration experiments and single treatment with 15.6 to 250 mg/kg of sobuzoxane on day 14 of gestation gave a dose-dependent incidence of the tests abnormality. These results suggest that the testis abnormality in offspring from dams treated with sobuzoxane is due to inhibition of the proliferation of primordial germ cells during testis organogenesis.

Administration, Oral↗
PubMedDate not supplied

Lung cancer: a prospective study of smoking, occupation, and nutrient intake.

A cohort study of lung cancer was conducted among 7,961 Japanese-American men who were interviewed and examined during 1965-1968. Information was collected about their smoking history, occupation, and nutrient intake. After 22 y, 227 incident cases of lung cancer were identified. Cigarette smoking significantly increased lung cancer risk. The relative risk (RR) was 3.1 for past smokers and 11.4 for current smokers, compared with never smokers. We separated lung cancer cases according to histological type, and it was found that current smokers had a RRs of 16.0 for squamous/small-cell carcinoma and 6.8 for adenocarcinoma of the lung. Unskilled manual workers had a significantly higher risk (RR = 1.5; 95% confidence interval, 1.1-2.2) for lung cancer than workers who were engaged in nonmanual occupations. There was no association between lung cancer and the 24-h intake of total calories, protein, fat, dietary cholesterol, carbohydrates, and alcohol, but this may have resulted from the limitations of a 24-h dietary questionnaire.

Aged↗
PubMedDate not supplied

Intra- and inter-individual variability in measurements of biomarkers for oxidative damage in vivo: Nutrition and Breast Health Study.

Oxidative stress has been implicated in the pathogenesis of various chronic diseases, such as cancer, cardiovascular disease and inflammatory conditions, as well as in ageing. Although a number of markers are now available, little is known about the reliability of single measurements of such markers in healthy individuals. The study examined the distribution of variance for three oxidative stress markers, 8-oxo-2'-deoxyguanosine (8-oxodG), 5-hydroxymethyl-2'-deoxyuridine (5-OHmdU) and total 8-isoprostane-F2alpha, which were measured every 3-6 months over 1 year in blood and breast nipple aspirate fluid (NAF) for 103 premenopausal women. For both plasma and NAF, the between-subject variances of 8-isoprostane-F2alpha were consistently greater than the within-subject variances. Consequently, their reliability coefficients were close to the level of those for cholesterol. On the other hand, the within-subject variances were much greater than the between-subjects variances for blood 5-OHmdU, resulting in low reliability coefficients, i.e. <0.3. Overall, the reliability coefficients for blood 8-oxodG were between those of 8-isoprostane-F2alpha and 5-OHmdU, but closer to those of 8-isoprostane-F2alpha. The results suggest that the reliability of oxidative stress markers may vary considerably depending on the type of marker. Caution should be exercised in selecting markers as well as in determining the number of study subjects or the number of samples per subject in a study. There also may be ample room to optimize laboratory techniques to quantify markers of oxidative DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗
PubMedDate not supplied

Risk factors for HPV DNA detection in middle-aged women.

BACKGROUND AND OBJECTIVES: Strong epidemiologic evidence indicates that human papillomavirus (HPV) is the main etiologic factor of cervical cancer. A few cohort studies suggest that most HPV infections are transient in young women and that persistent HPV infections are more common in older women. Little is known about the determinants of persistent HPV infections. The present study was aimed at increasing our knowledge about these determinants. GOALS: To identify risk factors for genital HPV DNA detection among cytologically normal middle-aged women. STUDY DESIGN: Eight hundred ten women who participated as control subjects in three case-control studies on cervical cancer in Spain, Colombia, and Brazil were included in this study. After an interview, women underwent a gynecologic examination with collection of exfoliated cells for a Papanicolaou smear and HPV DNA detection. Human papilloma virus DNA was detected by polymerase chain reaction (PCR)-based hybridization techniques. RESULTS: The HPV positivity rate was 10.5% in the whole population, but was higher in the areas with high incidence of cervical cancer (17% in Brazil and 13% in Colombia) than in Spain (4.9%), which is a low-risk area for cervical cancer. Age was related to the prevalence of HPV DNA in Brazil, but not in Spain and Colombia. In univariate analyses in all three countries, the prevalence of HPV DNA was positively associated with the number of lifetime sexual partners and inversely associated with the levels of family income and with age at first sexual intercourse. There was four times increase in the odds ratio (OR) of HPV infection in women who had six or more lifetime sexual partners compared with those with one or less. The use of any kind of contraceptive tended to decrease the OR for HPV detection. Their ORs ranged from 0.44 (barrier methods) to 0.48 (oral contraceptives). In Spain and Colombia, antibodies against Chlamydia trachomatis were positively associated with the prevalence of HPV DNA. In a final multivariate model, the positive associations with lifetime number of sexual partners, socioeconomic status, and C. trachomatis persisted. CONCLUSIONS: These results support the sexual transmission of HPV and suggest that socioeconomic status and antibodies to C. trachomatis are independent predictors of HPV detection in middle-aged cytologically normal women.

Adult↗
PubMedDate not supplied

A case-control study of gallstones: a major risk factor for biliary tract cancer.

Because of the strong association between gallstones and biliary tract cancer, we conducted a case-control study of gallstones at Niigata Cancer Center Hospital. Eighty-six cases with gallstones (33 males and 53 females) and 116 hospital controls (56 males and 60 females) were surveyed by means of a self-administered questionnaire. Gallstones were categorized into cholesterol stones (25 cases) and pigment stones (30 cases) based on the appearance of the stones. In multivariate analyses based on an unconditional logistic regression model, the risk of total gallstones was positively associated with a taste for salty food (relative risk (RR) = 2.31, 95% confidence interval (CI): 1.10-4.84), an intake of lettuce and cabbage (RR = 2.98, 95% CI: 1.47-6.06) and a family history of biliary diseases (RR = 5.63, 95% CI: 1.76-17.95), and inversely associated with an intake of salted and dried fish (RR = 0.16, 95% CI: 0.04-0.64). When analyzed by type of stones, cholesterol stones were associated with a taste for oily food (RR = 3.87, 95% CI: 1.36-11.03) and pigment stones were positively associated with professional or administrative occupation (RR = 4.74, 95% CI: 1.35-16.68) and inversely associated with a taste for less greasy food (RR = 0.28, 95% CI: 0.10-0.83). Some of these results are consistent with the results of our previous study on biliary tract cancer.

Adult↗
PubMedDate not supplied

Correspondence in cancer history between husbands and wives.

To study the effect of the environments shared by spouses on the development of cancer and some chronic diseases, we analyzed the correspondence of disease history in 21,592 fathers and mothers using the baseline data of a population-based cohort study. The observed number of cases (O) whose parents had the same disease history was statistically significantly greater than the expected (E); the O/E ratio was 1.53 (95% confidence interval (CI): 1.43-1.63) for all malignant neoplasms, 5.22 (95% CI: 2.81-9.70) for esophageal cancer, 1.63 (95% CI: 1.37-1.93) for stomach cancer, 3.01 (95% CI: 1.89-4.79) for colorectal cancer, 3.90 (95% CI: 2.75-5.53) for liver cancer, 3.14 (95% CI: 1.95-5.08) for lung cancer, 6.73 (95% CI: 2.53-17.87) for bladder cancer, 1.66 (95% CI: 1.54-1.78) for apoplexy and 1.67 (95% CI: 1.51-1.86) for heart disease. The results of the present study suggest that the environmental factors shared by family members for a long time may contribute to familial aggregation of cancer and some chronic diseases.

Adult↗
PubMedDate not supplied

Computer analysis of fixation-suppression of caloric nystagmus.

Effects of the ocular fixation upon caloric nystagmus were quantitatively analyzed and compared between normal subjects and patients by using a PDP 11/40 computer. The slow-phase velocity was the best parameter to separate normal from abnormal visual fixation. An analysis of caloric nystagmus with failure of fixation-suppression (FFS) made it possible to classify patterns of FFS into three types. The combination of FFS with impairment of the optokinetic responses provides a useful diagnostic tool with respect to lesions located between the brain stem and the cerebellum.

Adult↗
PubMedDate not supplied

Transient cerebral ischemic attacks in a Japanese community, Hisayama, Japan.

During a 20-year follow-up of 1,621 men and women aged 40 and over in Hisayama, Japan, 18 were found to have suffered transient cerebral ischemic attacks (TIAs) determined by clinical symptoms based on criteria proposed by the US Joint Committee for Stroke Facilities. The average annual incidence rate for the first TIA was 0.56 per 1,000 residents. Age and high blood pressure were strong determinants of TIAs for men. Nine of the 18 cases with TIAs (50%) subsequently developed cerebral infarction, an incidence significantly higher than that in the 1,603 subjects without TIAs (10.9%). Lacunar infarcts were most commonly found on pathologic examination of patients with TIAs who had had a subsequent stroke.

Age Factors↗