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Biomedical subjects

R Miike

Publications and source records attributed to R Miike.

At least 37 records · Page 2Linked to original sources
PubMed1997

A population-based case-control study of the CYP2D6 and GSTT1 polymorphisms and malignant brain tumors.

Previous studies of associations of metabolic polymorphisms with the occurrence of malignant brain tumors have suggested that there is a significantly increased risk of development of adult gliomas in individuals who carry a poor metabolizer CYP2D6 variant allele and the GSTT1 null genotype. To investigate this further, a population-based case control study of adult glioma in the San Francisco Bay area was conducted. Patients (n = 188) diagnosed with brain tumors and controls (n = 166) were enrolled using random digit dialing and were frequency matched for age, ethnicity and gender. Genotyping for the polymorphisms was performed using standard PCR-based techniques. The analysis of the data was restricted to Caucasians because the prevalence of these traits is known to vary by ethnicity. No overall association of either the GSTT1 null genotype or CYP2D6 homozygous variant PM genotype was observed with the occurrence of brain tumors. However, when stratified by histopathologic subtype, there was a significantly increased risk for oligodendroglioma associated with the GSTT1 null genotype, with an OR of 3.2 (95% CI 1.1-9.2). These data suggest that the GSTT1 polymorphism may play a role in the development of a subset of malignant brain tumors in adults, and indicate the need for further studies.

Adult↗
PubMed1996

Stimulatory influence of soy protein isolate on breast secretion in pre- and postmenopausal women.

Soy foods have been reported to have protective effects against premenopausal breast cancer in Asian women. No studies have been reported on potential physiological effects of dietary soy consumption on breast gland function. We evaluated the influence of the long-term ingestion of a commercial soy protein isolate on breast secretory activity. We hypothesized that the features of nipple aspirate fluid (NAF) of non-Asian women would be altered so as to resemble those previously found in Asian women. At monthly intervals for 1 year, 24 normal pre- and postmenopausal white women, ages 30 to 58, underwent nipple aspiration of breast fluid and gave blood and 24-h urine samples for biochemical studies. No soy was administered in months 1-3 and 10-12. Between months 4-9 the women ingested daily 38 g of soy protein isolate containing 38 mg of genistein. NAF volume, gross cystic disease fluid protein (GCDFP-15) concentration, and NAF cytology were used as biomarkers of possible effects of soy protein isolate on the breast. In addition, plasma concentrations of estradiol, progesterone, sex hormone binding globulin, prolactin, cholesterol, high density lipoprotein-cholesterol, and triglycerides were measured. Compliance was assessed by measurements of genistein and daidzein and their metabolites in 24-h urine samples. Excellent compliance with the study protocol was obtained. Compared with NAF volumes obtained in months 1-3, a 2-6-fold increase in NAF volume ensued during months 4-9 in all premenopausal women. A minimal increase or no response was found in postmenopausal women. No changes were found in plasma prolactin, sex hormone binding globulin, cholesterol, high density lipoprotein cholesterol, and triglyceride concentrations. Compared with concentrations found in months 1-3 (no soy), plasma estradiol concentrations were elevated erratically throughout a "composite" menstrual cycle during the months of soy consumption. No significant changes were seen in plasma progesterone concentrations. No significant changes were found in plasma estrogen levels in postmenopausal women. A moderate decrease occurred in the mean concentration of GCDFP-15 in NAF in premenopausal women during the months of soy ingestion. Of potential concern was the cytological detection of epithelial hyperplasia in 7 of 24 women (29.2%) during the months they were consuming soy protein isolate. The findings did not support our a priori hypothesis. Instead, this pilot study indicates that prolonged consumption of soy protein isolate has a stimulatory effect on the premenopausal female breast, characterized by increased secretion of breast fluid, the appearance of hyperplastic epithelial cells, and elevated levels of plasma estradiol. These findings are suggestive of an estrogenic stimulus from the isoflavones genistein and daidzein contained in soy protein isolate.

Adult↗
PubMed1995

Facial wrinkling in men and women, by smoking status.

OBJECTIVES: This study examined the association of smoking status and pack-years of smoking with facial wrinkling in men and women. METHODS: We conducted a cross-sectional study of 299 never smokers, 551 former smokers and 286 current smokers, aged 30 through 69 years, drawn from a health maintenance organization. Smoking status, pack-years of smoking, and potential confounding variables were assessed by questionnaire. Facial wrinkle category, a dichotomous variable, and facial wrinkle score, a computed continuous variable, were assessed by blinded standardized visual assessment. Wrinkling was so uncommon among 30- through 39-year-old subjects that analyses were restricted to subjects aged 40 and over (227 never smokers, 456 former smokers, and 228 current smokers). RESULTS: With age, average sun exposure, and body mass index controlled, the estimated relative risk of moderate/severe wrinkling for current smokers compared to never smokers was 2.3 (95% confidence interval [CI] = 1.2, 4.2) among men and 3.1 (95% CI = 1.6, 5.9) among women. Pack-years was positively associated with facial wrinkle score in women aged 40 through 69 years and in men aged 40 through 59 years. In both groups, the increased risk of wrinkling was equivalent to about 1.4 years of aging. CONCLUSIONS: Our results support earlier findings that risk of facial wrinkling is greater in cigarette smokers than in never smokers.

Adult↗
PubMed1994

A semiquantitative dietary history questionnaire for Chinese Americans.

An 84-item, semiquantitative dietary history questionnaire was developed for epidemiologic studies of diet and diseases in Chinese Americans. The questionnaire is a 30-minute, face-to-face administered instrument designed especially for assessing mixed dishes; it consists of a food list and requires information on frequency of consumption and portion estimation. A nutrient database was compiled from many sources, but mostly from US Department of Agriculture publications. The relative validity of this food frequency questionnaire was tested among 74 Chinese women between the ages of 30 and 60 years living in the San Francisco Bay area against a 1-day recall deemed a typical day's diet. Correlation coefficients of nutrients from both methods ranged from 0.2 for total fat to 0.7 for calcium and were all statistically significant at less than the 0.001 level. Agreement between these two methods was assessed by the percentage of misclassification of quartile distributions. Around 10% were grossly misclassified and 50% were correct estimates of intake in the same highest quartile, while 73% were correctly placed in the two highest quartiles. This food frequency questionnaire can reasonably estimate the usual dietary intakes among Chinese Americans for epidemiologic studies, but further validation would be needed.

Adult↗
PubMed1993

Breast cancer risk associated with abnormal cytology in nipple aspirates of breast fluid and prior history of breast biopsy.

The authors previously reported an increased risk of breast cancer in women from the San Francisco Bay Area first enrolled between 1973 and 1980 with proliferative cytologic findings (hyperplasia, moderate hyperplasia, and atypia) compared with women with normal cytologic findings in breast fluids obtained by nipple aspiration and with women from whom breast fluid could not be obtained. To look for factors which might modify the risks associated with cytology, the authors examined several standard breast cancer risk factors: parity, age at first pregnancy, age at menarche, family history of breast cancer, and prior history of breast biopsy. Among women aged 30 years or over, only prior biopsy modified the effect of proliferative cytologic findings on the risk of breast cancer (p < 0.10). For those women with no prior biopsy, breast cancer incidence was 5% (47 of 985) among women with normal cytology and 5% (13 of 277) among women with proliferative findings, whereas among those women with normal cytology and 18% (11 of 62) among women with proliferative cytology. Age-adjusted as well as multivariate-adjusted relative risks indicated that the increased risk of breast cancer associated with proliferative cytologic findings was largely confined to women who had a prior history of breast biopsy.

Adult↗
PubMed1992

Breast cancer incidence in women with abnormal cytology in nipple aspirates of breast fluid.

This is a prospective study of breast cancer risk in relation to nipple aspirate fluid cytology in 2,701 volunteer white women from the San Francisco Bay Area first enrolled between 1973 and 1980. The women were not pregnant or lactating and were free of breast cancer within 6 months of entry into the study. The breast cancer status of this cohort was determined between June 1988 and April 1991. Follow-up was complete for 87% (n = 2,343) of the cohort, representing 29,961 person-years and an average of 12.7 years of follow-up. The overall breast cancer incidence was 4.4% (104 of 2,343) and rose with fluid cytology findings as follows: no fluid obtained, 2.6% (9 of 352); unsatisfactory specimen, 4.8% (15 of 315); normal cytology, 4.3% (56 of 1,291); epithelial hyperplasia, 5.5% (18 of 327); and atypical hyperplasia, 10.3% (6 of 58). Relative risks for breast cancer and their 95% confidence intervals were estimated by Cox regression, adjusting for age and year of entry. Compared with the relative risk for women who yielded no fluid, relative risks were: unsatisfactory specimen, relative risk (RR) = 1.4 (95% confidence interval (CI) 0.6-3.3); normal cytology, RR = 1.8 (95% CI 0.9-3.6); epithelial hyperplasia, RR = 2.5 (95% CI 1.1-5.5); and atypical hyperplasia, RR = 4.9 (95% CI 1.7-13.9). These findings were strongest for and were mainly confined to women aged 25-54 years. Women with atypical hyperplasia and a first-degree family history of breast cancer were six times more likely to develop breast cancer than were women with atypical hyperplasia but without a family history of breast cancer (95% CI 1.0-30.2). These findings provide strong support for our hypothesis that hyperplasia and atypical hyperplasia diagnosed in nipple aspirates of breast fluid are associated with an increased risk of breast cancer.

Adolescent↗
PubMed1991

Individual susceptibility to induced chromosome damage and its implications for detecting genotoxic exposures in human populations.

In a previous study, we observed a bimodal distribution of sensitivity to sister chromatid exchange (SCE) induction by diepoxybutane (DEB) in lymphocytes from healthy individuals. Twenty-four % of the participants had increased sensitivity to in vitro induction of SCEs and chromosomal aberrations. These same participants also had significantly higher frequencies of uninduced or baseline SCE frequencies. In the present study, we measured baseline and DEB-induced SCE frequencies in 55 healthy female volunteers. Eleven of 55 [20%] women were relatively sensitive to DEB induction of SCEs. Baseline SCE frequencies in these sensitive individuals [10.4 +/- 0.7 (SD) SCEs/cell] were significantly higher [P less than 0.001; Student's t test] than baseline SCE frequencies in the remaining 44 individuals [8.0 +/- 0.9 SCEs/cell]. Similar increases in SCEs were observed when the analysis was restricted to the upper 10% of the SCE distribution (high frequency SCE analysis). The phenotype of DEB sensitivity accounted for 58% of the variation among individual SCE scores. Given the population frequency of this sensitivity to SCE induction and the high proportion of variance in SCEs for which it accounts, failure to account for this factor could seriously distort conclusions about SCE measures associated with other environmental exposures. The most likely result of such unexplained variability (type II error) would be bias toward the null hypothesis. Also, the likelihood that individual variations contribute to false positive results is expected to be greatest in studies that compare small numbers of exposed and nonexposed individuals. To summarize, these results confirm our earlier study and show that increased baseline SCE frequencies can be indicative of increased sensitivity to certain classes of mutagenic carcinogens. Identification of DEB-sensitive persons could be used to increase the sensitivity of SCE analysis in monitoring studies to detect exposure to genotoxins.

Adult↗
PubMed1991

A proposal for examining and reporting stepwise regressions.

A common mode of regression analysis is a stepwise regression. One of the problems associated with the stepwise algorithm is that the data analyst may wrongly identify the selected variables as the important variables. We propose a simple table as an aid in examining and reporting stepwise regression analyses. The key to our proposal is recognition of 'close alternatives', that is, those variables excluded from selection by the inclusion of another variable. This presentation should encourage the analyst and reader to think in terms of sets of variables that, together, represent factors associated with the outcome.

Adult↗
PubMed1990

Cerumen phenotype and proliferative epithelium in breast fluids of U.S.-born vs. immigrant Asian women: a possible genetic-environmental interaction.

To determine whether a genetic-environmental interaction exists between the breast, a modified apocrine gland, its secretions, and the genetic polymorphic phenotypes of wet and dry cerumen, we examined nipple aspirate fluid (NAF) for proliferative disease in 172 U.S.-born and immigrant Chinese and Japanese women. Cytologic evidence of proliferative epithelial cells (benign hyperplasia and/or atypical hyperplasia) was found in the NAF of 36 women (20.9%). A significantly higher incidence of proliferative epithelial cells was present in the NAF of U.S.-born than in immigrant Asian women (28.6% vs. 16.5%) (p = 0.05). A higher proportion of U.S.-born Asian women with wet cerumen than women with dry cerumen had proliferative epithelial cells in NAF: 39.3% vs. 20.0% (p = 0.08). No significant difference in NAF proliferative cells was found between immigrant women with wet and dry cerumen: 15.8% vs. 17.3%; p = 0.50. A strong association of proliferative epithelial cells and cerumen phenotype was found in parous U.S.-born women (wet = 47.6% vs. dry = 16.0%; p = 0.002). No significant association with wet and dry cerumen phenotype was found in parous immigrant women (wet = 12.2% vs. dry = 20%). These findings support the hypothesis that an apocrine genetic polymorphic trait differentially influences susceptibility of the breast to proliferative disease in Asian women born in environments presumed to be of high risk for breast cancer compared to women from low risk environments.

Body Fluids↗
PubMed1990

Factors associated with obtaining nipple aspirate fluid: analysis of 1428 women and literature review.

Studies of cytologic and biochemical constituents of nipple aspirates of breast fluid have contributed to understanding the natural history of benign and malignant breast disease. We conducted multivariate analyses using 1428 women from a recent case-control study of breast disease to determine which factors were independently associated with the ability to obtain breast fluid from nonlactating women. We then compared results from these analyses to the results from five previous studies that also used the aspiration technique of Sartorius. Four factors were consistently associated across studies with increased ability to obtain breast fluid: 1) age up to 35 to 50 years; 2) earlier age at menarche; 3) non-Asian compared to Asian ethnicity; and 4) history of lactation. Exogenous estrogen use, endogenous estrogen concentrations, phase of menstrual cycle, family history of breast cancer, type of menopause, and less than full-term pregnancy consistently did not influence ability to obtain fluid. New findings from this study shed light on some apparently contradictory findings from the previous studies. In particular, this study showed that the effects of age on ability to obtain fluid appeared to be independent of the effects of menopause. Furthermore, discrepancies in previous findings on the effects of parity on ability to obtain fluid may be explained by our finding that the increased ability to obtain fluid from parous compared to nulliparous women applied only to parous women who had breastfed.

Adult↗
PubMed1989

Breast fluid cholesterol and cholesterol beta-epoxide concentrations in women with benign breast disease.

Because cholesterol 5,6-epoxides have been reported to be mutagenic, carcinogenic, and cytotoxic, we investigated the relationship of these substances in breast fluid to histopathologically defined breast disease. We measured cholesterol and its oxidation product, 5 beta,6 beta-epoxide, in breast fluids from 68 women with biopsied benign breast disease (BBD) and 135 women with no history of breast disease (controls). Each biopsy was classified according to the most severe epithelial change: (a) nonproliferative epithelia; (b) hyperplasia without atypia; or (c) hyperplasia with atypia. Similar to our previous findings in control women, breast fluid cholesterol and beta-epoxide concentrations in women with BBD were associated with factors of interest in relation to breast cancer: concentrations increased with age and were higher in white than nonwhite women and in women who were past or current smokers; concentrations were lower in women who had given birth or breastfed within 2 yr. Increased breast fluid cholesterol and beta-epoxide concentrations were significantly associated with proliferative BBD (hyperplasia with or without atypia) compared to controls. After adjustment for covariates, the odds ratio for proliferative BBD associated with detectable versus nondetectable beta-epoxide concentrations was 8.5 (95% confidence intervals, 1.1, 68.8). Our findings suggest that the histological progression from normal epithelium to hyperplasia without atypia to atypical hyperplasia is associated with progressively increasing concentrations of both cholesterol and cholesterol beta-epoxide.

Adult↗
PubMed1989

Nipple aspirate fluids in adult nonlactating women--lactose content, cationic Na+, K+, Na+/K+ ratio, and coloration.

The presence of lactose in nipple secretions is considered biochemical evidence of breast secretory activity, and has been reported to occur more frequently in white compared to brownish or green colored breast fluid. We studied lactose, Na+, and K+ concentrations, the Na+/K+ ratio, and the coloration of nipple aspirate fluid (NAF) from 49 nonpregnant women. A significant relationship was found between the concentrations of lactose, Na+, and K+, and age and the coloration of NAF. Lactose was present in 22/49 (44.8%) of the NAF samples and declined with age from 100% positivity in women less than or equal to 29 years to 29% in those less than or equal to 35 years. In NAF of deep yellow, brown and green colorations, only traces of lactose were found. Na+ and K+ increased with age and with darker colorations compared to white, pale yellow, or colorless NAF. Lactose was present in NAF samples from both parous and nulliparous younger women, indicating that the breasts of many nonpregnant women respond to prolactin stimulation; hence, lactose may provide a simple marker indicating active physiologic secretory activity of the breast. As reported previously, NAF of darker coloration, containing elevated levels of cholesterol, cholesterol oxidation products, and other substances, suggests retention and impaired reabsorption of these and other products of secretion. Because of the secretion and temporary retention by the breast glands of chemical substances of exogenous and endogenous origin, including mutagens and carcinogens, lactose concentration and coloration of NAF may be useful as markers of secretion and reabsorption in future physiologically based clinical and epidemiologic studies of the pathogenesis of breast disease.

Adult↗
PubMed1988

Association of breast fluid coloration with age, ethnicity, and cigarette smoking.

Nipple aspirates of breast fluid (NAF) occur with different colorations (colorless, white, pale yellow, dark yellow, brown, green, and black). Increasing concentrations of cholesterol, cholesterol 5,6-epoxides, estrogens, and fluorescent products of lipid peroxidation have been positively associated with the dark colorations (dark yellow, brown, green, and black). Because of the absence of data on these variations in breast fluid coloration, we made an exploratory study of their possible associations with age, ethnicity, clinical breast status, and breast cancer risk factors. Dark NAF colorations increased with age among white women from 22.5% at 20-29 years to 49.2% at 50-59 years. Among Chinese and Japanese women, the overall proportion of dark breast fluids was significantly lower (highest proportion 23.5%). A positive association of dark NAF coloration was found with current cigarette smoking (odds ratio = 1.64 [1.04-2.59]). A dose response between amount smoked and dark coloration was found in women less than 50 years of age, with women who smoked more than one pack per day having an odds ratio of 2.31 (1.30-4.67). No significant association of dark NAF was found with the major breast cancer risk factors or with actual benign or malignant breast disease. The dark colorations may represent pigmented products of apocrine gland secretion, lipofuscin complexes of peroxidated lipoprotein, breakdown products of hemoglobin, and possibly, diet-related secretory products.

Adult↗
PubMed1988

Coloration of breast fluid related to concentration of cholesterol, cholesterol epoxides, estrogen, and lipid peroxides.

The coloration of nipple aspirates of breast fluid from 2,343 women were compared with breast fluid concentrations of cholesterol. cholesterol epoxides, lipid peroxides, estrogens, and immunoglobulins. Darker-colored breast fluid had significantly higher mean concentrations of cholesterol, cholesterol epoxides, lipid peroxides, and estrogens than did lighter-colored fluids, whereas no relationship of coloration with immunoglobulin levels was found.

Breast↗
PubMed1987

Influence of pregnancy and lactation on serum and breast fluid estrogen levels: implications for breast cancer risk.

We investigated estrogen (estrone and estradiol) levels in serum and in nipple aspirates of breast fluid in relation to reproductive and menopausal characteristics in 104 normal women. In general, breast fluid and serum estrogen levels were not correlated and breast fluid estrogen levels were approximately 5 to 45 times higher than serum levels. Serum estrogen levels were lower in post-menopausal than in pre-menopausal women. In contrast, breast fluid estrogen levels were approximately the same in pre- and post-menopausal women. Breast fluid estrogen mean levels were lower in pre-menopausal parous women than in nulligravidous or nulliparous women whereas serum estrogen levels did not differ in these 3 groups. Breast fluid estrogen levels were positively correlated with months since last birth or since last breast-feeding. Estrogen levels were low in nipple aspirates of breast milk but gradually increased in breast fluid of non-lactating women over a period of several years after cessation of lactation. Serum estrogen levels did not increase with months since last breast-feeding. We were unable to evaluate the post-partum effect of pregnancy without lactation due to the small numbers of these subjects. The high concentrations of estrogen in breast fluid and the absence of a relationship to serum estrogen levels may explain why prior serum studies have failed to link variations in serum estrogens with breast cancer risk. The prolonged low levels of breast fluid estrogens following full-term birth and lactation may, in part, provide a mechanism by which parity reduces breast cancer risk.

Body Fluids↗
PubMed1987

Breast fluid cholesterol and cholesterol epoxides: relationship to breast cancer risk factors and other characteristics.

We measured levels of cholesterol and its oxidation products, 5,6 alpha- and beta-epoxides and their common hydrolysis product cholestane triol, in breast fluids of women without breast disease, compared these levels to serum cholesterol levels, and explored associations of these breast fluid measurements with known breast cancer risk factors and other characteristics. Subjects were 105 women with no history of breast disease from whom breast fluid could be obtained by nipple aspiration. The four breast fluid measurements were significantly correlated with each other (P less than 0.0001) but none was correlated with serum cholesterol. In subsequent analyses restricted to breast fluid cholesterol and cholesterol beta-epoxide, cholesterol levels (but not beta-epoxide levels) increased with age and were higher in white than nonwhite women. Both measurements were low in women who were lactating, who were parous, or who had breast-fed. The lower levels among parous women persisted for at least 2 years postpartum or postlactation. Because breast fluid levels of cholesterol beta-epoxide are reduced for some time following a birth or cessation of lactation, the alveolar-ductal systems of parous women presumably have less cumulative exposure to this potentially carcinogenic substance. This biochemical mechanism may, in part, explain the observed reduction of breast cancer risk associated with parity.

Adult↗
PubMed1987

Benign and malignant breast disease: initial study results of serum and breast fluid analyses of endogenous estrogens.

Design, methods, and study population of a long-term multidisciplinary investigation of benign and malignant breast disease were reported. This initial report focused on the relation of menstrual, reproductive, and other factors to serum and breast fluid estrogen measures [estradiol (E2), estrone (E1), percent free estrogen, and sex hormone binding globulin] among control women. After adjustment for the factors found to be related to the various estrogen measures, estrogen levels in women with benign and malignant disease were compared to those of controls. Findings were as follows: a) little evidence of any relation of most breast cancer risk factors with the various serum estrogen parameters studied; b) differences in breast fluid estrogen levels that may be relevant to the protective effect of parity on breast cancer risk; c) markedly higher levels of E2 and E1 in breast fluid than in serum and no evidence of a correlation of serum with breast fluid measures; d) no support for the hypothesis that breast cancer patients have higher serum percent free E2 than controls or women with benign breast disease; and e) higher breast fluid E2 and E1 levels in women with biopsied benign breast disease than in controls.

Adult↗