Specific alcoholic beverage and blood pressure in a middle-aged Japanese population: the High-risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) Study.

The purpose of this study was to clarify the effects of popular Japanese alcoholic beverages on blood pressure. We performed a cross-sectional study on 4335 Japanese male workers using baseline data from an intervention study. We defined six groups according to the type of alcoholic beverage that provided two-thirds of the subject's total alcohol consumption: beer, sake (rice wine), shochu (traditional Japanese spirits), whiskey, wine and others. The partial regression coefficients of daily alcohol intake (1 drink=11.5 g of ethanol) to systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 0.87(P<0.001, standard error (s.e.)=0.09) and 0.77(P<0.001, s.e.=0.06), respectively. A comparison among the types of alcoholic beverages mainly consumed revealed significant differences in SBP and DBP. Both SBP and DBP were highest in the shochu group. However, an analysis of covariance adjusting for total alcohol consumption resulted in the disappearance of these differences. Although after adjustment for total alcohol consumption, the shochu group exhibited a significant positive association with 'high-normal blood pressure or greater' (odds ratio 1.43, 95% confidence interval 1.06-1.95) compared with the beer group, this significant relation disappeared after adjusting for the body mass index (BMI), urinary sodium and potassium excretion. The pressor effect, per se, of popular Japanese alcoholic beverages on blood pressure may not be different among the types of alcoholic beverages after adjusting for other lifestyle factors.

Analysis of prognostic factors in newly diagnosed patients with acute promyelocytic leukemia: the APL92 study of the Japan Adult Leukemia Study Group (JALSG).

All-trans-retinoic acid (ATRA) has been incorporated in front-line therapy for newly diagnosed acute promyelocytic leukemia (APL). We conducted a multicenter study of differentiation therapy with ATRA alone or in combination with chemotherapy followed by intensive postremission chemotherapy in patients with APL (the JALSG APL92 study), and analyzed prognostic factors to increase the cure rate in our subsequent trial. From 1992 to 1997, adult patients with newly diagnosed APL received oral ATRA 45 mg/m2 daily alone until complete remission (CR) if initial leukocyte counts were < 3.0x10(9)/l, and ATRA daily plus daunorubicin (DNR) 40 mg/m2x3 days plus enocitabine (BHAC) 200 mg/m2x5 days if leukocyte counts were > or =3.0 x 10(9)/l. If peripheral blasts exceeded 1.0x10(9)/l during therapy, DNRx3 days plus BHACx5 days was added. After CR was achieved, three courses of consolidation and six courses of maintenance/intensification chemotherapy were administered. Of 376 patients enrolled, 369 were evaluable (median age 46 years, range 15-86 years; median leukocyte counts 2.0x10(9)/l), and 333 (90%) achieved CR (94% of patients treated with ATRA alone, 88% with ATRA plus later chemotherapy, 89% with ATRA plus initial chemotherapy, and 86% with ATRA plus initial and later chemotherapy). At a median follow-up of 45 months, the predicted 6-year overall and event-free survival (EFS) rates for all patients were 65% and 52%, respectively. Favorable prognostic factors for CR were younger age, no or mild purpura, high serum total protein level, low lactate dehydrogenase level, and no or mild disseminated intravascular coagulation (DIC). Favorable prognostic factors for EFS were leukocyte counts < 10.0x10(9)/l, mild DIC, and no sepsis during induction therapy. In the JALSG APL97 study, we intensified chemotherapy for patients with leukocyte counts > or =3.0x10(9)/l, and are randomly testing whether further chemotherapy is required for APL patients with negative PCR for PML/retinoic acid receptor alpha in the maintenance phase.

Hemoglobin denaturation caused by surfactants.

The properties of hemoglobin denaturation caused by two anionic surfactants (sodium dodecylsulfate and sodium lauroylmethyltaurate) were examined using spectrophotometry (multi-plate reader), circular dichroism (CD) and high-performance liquid chromatography (HPLC), and their denaturating action on hemoglobin and sorption to it were examined by various methods. Correlation and factorial analyses were applied to the experimental data and the following results were obtained: (1) High correlations were found among sorption, denaturation and alpha-helix content and the random structure of hemoglobin. (2) The alpha-helix of hemoglobin is randomized as the surfactants denature hemoglobin. (3) Factorial analysis indicates that there are two factors involved in hemoglobin denaturation, one related to the destruction of the alpha-helix and the other related to a change in the beta-structure. These two factors are related to change in the environment around the heme group. (4) Destruction of the alpha-helix seems to be one of the causes of the eye irritation produced by anionic surfactants.

Multivariate factorial analysis of data obtained in seven in vitro test systems for predicting eye irritancy.

Seven in vitro test systems used to predict eye irritancy (EYTEX, SIRC cytotoxicity, HeLa cytotoxicity, chorioallantoic membrane (CAM), liposome, red blood cell and haemoglobin denaturation test system) were applied to 12 surfactants, and the results were subjected to multivariate analysis to evaluate the relative contributions of five factors. These factors were: (1) cellular plasma membrane destruction factor, (2) haemoglobin type protein denaturation factor, (3) EYTEX-type protein denaturation factor, (4) cytotoxicity factor and (5) an unknown (unidentified) factor. The results clarified the basis on which the findings of each test system were related to the Draize results. According to the analysis, the Draize eye irritation test could be explained by the contribution of the protein denaturation factor and cellular plasma membrane destruction factor. This provides support for a previous hypothesis that the major mechanisms of eye irritation are cellular plasma membrane destruction and protein denaturation. The CAM test value showed a higher correlation coefficient (0.906) with the Draize score than did the results of any of the other test systems; this was due to the fact that these two tests showed similar patterns of dependence on the five factors as indicated by the factorial analysis. The haemoglobin denaturation test system had the next highest correlation coefficient at about 0.75. Furthermore, by using further tests to make up the deficiency of the other necessary factors, a desirable battery system could be predicted; for example, the combination of the haemoglobin-denaturation and rat red blood cell tests would provide a result similar to that of the Draize test. This study should contribute to the development of a rational basis for prediction of eye irritancy of chemicals using in vitro test systems.