Takashi Yanagawa

Postnatal exposure to chlorinated dioxins and related chemicals on thyroid hormone status in Japanese breast-fed infants

Effects of postnatal exposure to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and coplanar polychlorinated biphenyls (Co-PCBs) on thyroid hormone status were studied in the peripheral blood of 36 breast-fed Japanese infants. Estimated total intakes of these chemicals in toxic equivalent quantity (TEQ) converted into 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) from the breast milk significantly and negatively correlated with the levels of triiodothyronine (T3) and thyroxine (T4) in the blood of breast-fed babies. Therefore, exposure to background levels of the highly toxic organochlorine chemicals through the breast milk may cause some effects on thyroid hormone status in Japanese infants.

Postnatal exposure to chlorinated dioxins and related chemicals on lymphocyte subsets in Japanese breast-fed infants

Effects of postnatal exposure to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and coplanar polychlorinated biphenyls (Co-PCBs) on lymphocyte subpopulations were investigated in the peripheral blood of 36 breast-fed Japanese babies. As a result, estimated total intakes of these chemicals in toxic equivalent quantity (TEQ) converted into 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) equivalents from the breast milk positively and negatively correlated with the respective percentages of CD4+ and CD8+ lymphocytes in the blood of breast-fed babies. Consequently, the ratios of CD4+ to CD8+ T cells showed significant increasing tendency with the estimated total TEQ intakes. Therefore, our study suggests that exposure to background levels of the highly toxic organochlorine compounds through the breast milk influences the human neonatal immune system.

Nuclear Y-Box Binding Protein-1, a Predictive Marker of Prognosis, Is Correlated with Expression of HER2/ErbB2 and HER3/ErbB3 in Non-small Cell Lung Cancer

Introduction: Nuclear expression of Y-box binding protein-1 (YB-1) is closely associated not only with global drug resistance and expression of several growth factor receptors in various human malignancies but also with overall patient survival. Methods: The effect of YB-1 knockdown on expression of epidermal growth factor receptor (EGFR) family proteins was examined by Western blot using human lung cancer cell lines. Immunohistochemistry was used to evaluate the expression of nuclear YB-1 and EGFR family proteins in patients with non-small cell lung cancer (NSCLC) (n = 104). Results: In the five NSCLC cell lines, expressions of EGFR, human epidermal growth factor receptor 2 (HER2), HER3, and hepatocyte growth factor receptor (c-Met) in PC-9 cells; of HER2 and c-Met in EBC-1 cells; and of HER3 in QG56 cells were down-regulated by YB-1 knockdown. By immunohistochemical analysis, we observed that HER3 expression was significantly negatively correlated with nuclear YB-1 expression in squamous cell carcinoma (p = 0.038). HER2 expression was positively correlated with nuclear YB-1 expression in adenocarcinoma (p = 0.052). Nuclear expression of YB-1 correlated with overall survival of all patients (p = 0.028) and of patients with adenocarcinoma (p = 0.007). Furthermore, there was a significant difference in therapeutic efficacies of gefitinib between patients with nuclear YB-1 expression and those with non-nuclear YB-1 expression in patients with NSCLC (p = 0.004, n = 26) but not between those with high and those with low expression of EGFR, HER2, HER3, and c-Met. Conclusion: Nuclear YB-1 expression might be essential for the malignant phenotype in lung cancer patients and might be an important biomarker for the development of therapeutic strategy against NSCLC.

The mg-procedure in ranked set sampling

Abstract The MG-procedure in ranked set sampling is studied in this paper. It is shown that the MG-procedure with any selective probability matrix provides a more efficient estimator than the sample mean based on simple random sampling. The optimum selective probability matrix in the procedure is obtained and the estimator based on it is shown to be more efficient than that studied by Yanagawa and Shirahata [5]. The median-mean estimator, which is more efficient and could be easier to apply than that proposed by McIntyre [2] and Takahashi and Wakinoto [3], is proposed when the underlying distribution function belongs to a certain subfamily of symmetric distribution functions which includes the normal, logistic and double exponential distributions among others.

Projection-method Mantel-Haenszel estimator for K 2×J tables

Abstract A projection method is introduced to generalize the Mantel-Haenszel estimator for estimating the common odds ratios in K 2 × J (J > 2) tables. The method provides estimators in an explicit form and needs no iterative computation. It is shown that the generalized Mantel-Haenszel estimator proposed by Greenland, and Yanagawa and Fujii is obtained by this method as a special case. Furthermore, selecting appropriate weight, it is shown that the method leads to an estimator that is asymptotically equivalent to the generalized Mantel-Haenszel estimator proposed by Liang. A dually consistent estimator of the variance of the estimator is proposed. The characteristics of these estimators have been evaluated by Monte Carlo means.

Prevalence of HTLV-I-associated myelopathy among HTLV-I carriers in Saga, Japan.

Surveying the disease by sending questionnaires to all physicians of the Saga Medical Association, we tabulated 19 definite cases of HTLV-I-associated myelopathy (7 males and 12 females) as of January 31, 1988. The population at risk of HTLV-I carriers was estimated by applying sex- and age-specific anti-HTLV-I antibody-positive rates among blood donors at the Saga Red Cross Blood Center in the fiscal year of 1986 to the population of Saga Prefecture in 1982. The crude prevalence rates among HTLV-I carriers from 20 to 69 years of age per 100,000 were 65.7 for males and 86.9 for females, respectively. The summary prevalence rates with 95% confidence intervals were 46.5 (14.3-97.3) for males and 74.9 (35.3-129.2) for females. There was no remarkable difference in the age-specific prevalence rates in either sex. The crude and summary rates among females were higher than those among males, but the difference was not statistically significant.

On mantel-haenszel type estimators in simple nested case-control studies

We are concerned with nested case-control studies in this article. For proportional hazards model, a class of over-all estimators of hazard ratios is presented when simple samples are drawn from risk sets. These estimators have the form of the Mantel-Haenszel estimator of odds ratio, and are consistent not only for large strata, but also for sparse data. Consistent estimators of the variances of the proposed hazard ratio estimators are also developed. An example is given to illustrate the proposed estimators.

Incorporating historical controls using a random-effects model with a normal prior

Employing a variance stabilization transformation, a random-effects model with a normal prior is proposed for incorporating historical controls in the estimation of dose-response relationships. The advantages and disadvantages of maximum likelihood and empirical Bayes estimators are discussed. A two-stage method is introduced for the prudent use of historical controls.

A method for estimating incidence rates of onchocerciasis from skin-snip biopsies with consideration of false negatives

The aim of this study is to estimate incidence rates of onchocerciasis from skin-snip biopsies, based on incomplete data obtained in field surveys, with consideration of false negatives. The method of maximum likelihood is employed and the effect of false negatives on the incidence rates is discussed.

No-Observed-Adverse-Effect Levels in Severity Data

Abstract Toxicity data are often categorized by severity of response and dose level with the assumption that there is a tolerated dose below which there is no toxicity. For data from a controlled experiment, the largest observed dose at or below the tolerated dose is called the no-observed-adverse-effect level (NOAEL). The problem of identifying the NOAEL can be viewed statistically as estimating the maximal observed dose for which there is no increased severity or frequency of toxic response. We previously proposed a method based on the Akaike information criterion (AIC) for the case with only two response levels (presence or absence of a toxic endpoint). We show here that repeated applications of that method to suitably defined subsets of data provide the maximum penalized likelihood estimate of the NOAEL when there are multiple severity levels, under a slight modification of the continuation-ratio logit model. Three sets of data on controlled exposure of rodents are used to illustrate the method.