Tsuyoshi Higuchi

Hypercholesterolemia accelerates bone loss in postmenopausal women

Objectives To clarify the effect of lipid profiles on postmenopausal bone loss using a longitudinal method and to determine whether cytokines are involved in bone loss. Methods The subjects were Japanese residents participating in the Iwaki Health Promotion Projects. Women with one or more of the following factors were excluded: a history of surgical menopause, current or past users of bisphosphonates or current user of other drugs known to influence bone and lipid metabolism, and current medication for diabetes or hypertension. Consequently, 99 postmenopausal women (61.2 ± 7.7 years old) and 85 premenopausal women (41.2 ± 8.6 years old) were selected for this study. The osteo-sono-assessment index (OSI) of the left calcaneal bone was obtained twice at 1-year intervals and the annual percentage change in OSI was calculated. Serum total cholesterol, high and low density lipoprotein cholesterol, triglycerides, homocysteine and cytokines such as adipocytokines, interleukins and tumor necrosis factor-α were measured. Postmenopausal women were grouped into three groups according to their basal cholesterol level, and the relationship between basal cholesterol level and annual change in OSI was studied. Results The annual percentage change in OSI in postmenopausal women with a serum total cholesterol level ≥240 mg/dl was significantly higher compared to those with a normal total cholesterol level, suggesting that hypercholesterolemia accelerates postmenopausal bone loss. No significant differences were seen in any of the cytokines that presumably cause bone resorption. Conclusion These results showed that hypercholesterolemia has an inverse effect on bone loss independent of cytokines presumed to mediate bone loss.

Hyaluronate depolymerization activity induced by progesterone in cultured fibroblasts derived from human uterine cervix

High‐molecular‐weight [14C]hyaluronate was incubated with cultured fibroblasts from human uterine cervix and skin, and then the depolymerization of the hyaluronate was investigated. [14C]Hyaluronate in the medium of skin fibroblasts was depolymerized into a constant molecular weight (M r about 40,000), whereas that of cervix fibroblasts was not depolymerized, irrespective of incubation period. However, when progesterone was added to the medium of cervix fibroblasts, hyaluronate was depolymerized to the same extent as that in skin fibroblasts. The reducing terminal sugar of the depolymerized hyaluronate was N‐acetylglucosamine. These results suggest that a hyaluronate‐depolymerizing enzyme, endo‐β‐N‐acetylglucosaminidase, was induced by progesterone in cultured fibroblasts derived from human uterine cervix.

A method for determination of galactosyltransferase I activity synthesizing the proteoglycan linkage region

An assay method was devised for measuring the activity of galactosyltransferase I (UDP-D-galactose:D-xylose galactosyltransferase), which is one of the enzymes synthesizing the linkage region between the core protein and glycosaminoglycan chains of proteoglycan. For this method, the reaction mixture contained a fluorescent substrate, 4-methylumbelliferyl-beta-D-xyloside as an acceptor, UDP-galactose as a donor and D-galactal as a competitive inhibitor of endogenous beta-galactosidase in the enzyme solution. The reaction mixture was incubated at 37 degrees C with enzyme solution prepared from an extract of cultured cells, and galactosyl-xylosyl-4-methylumbelliferone was produced as a reaction product. Measurement of galactosyltransferase I activity was performed by separation and quantitative analysis of this reaction product using high-performance liquid chromatography. Utilizing this method, easier and more sensitive detection of galactosyltransferase I activity in a cell-free system became possible. Application of the method revealed that cultured human skin fibroblasts contained galactosyltransferase I activity.

Secondary acute nonlymphocytic leukemia following successful chemotherapy combining cisplatin, doxorubicin, and cyclophosphamide for stage IV epithelial ovarian cancer

Abstract Although chemotherapy is indispensable for the treatment of ovarian cancer, secondary acute leukemia has become increasingly important as one of the most unfavorable late effects according to widespread long-term chemotherapy. We report a patient suffering from acute nonlymphocytic leukemia (ANLL) 3 years after treatment for stage IV ovarian cancer began.

4-Methylumbelliferone inhibits hyaluronate synthesis in human uterine cervical fibroblasts

Aim:  Hyaluronate plays an important role in the regulation of cervical function during parturition. In our previous study we showed that 4‐methylumbelliferone (MU) suppresses hyaluronate synthesis by cultured human skin fibroblasts. The present study investigated the effects of MU on fibroblasts obtained from the human uterine cervix and assessed the possibility of controlling cervical ripening with MU.

Blood pressure during pregnancy is a useful predictive maker for hypertension and dyslipidemia later in life, a population-based, cross-sectional study

OBJECTIVE Pregnancy is an opportunity for women to become aware of their risk of cardiovascular disease (CVD), because physiologic responses to dynamic hemodynamic changes can be observed during pregnancy. Accordingly, we hypothesized that blood pressure levels during pregnancy may be associated with the risk of CVD later in life. STUDY DESIGN We used data from the Iwaki Health Promotion Project and designed a population-based, cross-sectional study. In this study, Maternity Health Record Books were collected from women over 40 years of age in order to obtain reliable data regarding past pregnancies. Of a total of 642 women, 432 were selected according to the study criteria. MAIN OUTCOME MEASURES The associations between blood pressure levels during pregnancy and major CVD risk factors (hypertension and dyslipidemia) were analyzed retrospectively. RESULTS A 10 mmHg increase in the mean diastolic blood pressure level between gestational weeks 12 and 42 conferred a 1.70- and 1.55-fold increase in the risk of hypertension and dyslipidemia, respectively, in later life. CONCLUSIONS Blood pressure levels during pregnancy may be associated with CVD risk and could therefore be a useful predictive marker.

4-Methylumbelliferone inhibits hyaluronate synthesis in cultured fibroblasts from the human uterine cervix

Background: Hyaluronate plays an important role in the regulation of cervical function during parturition. In a previous study, we reported that 4-methylumbelliferone (MU) suppresses hyaluronate synthesis by cultured human skin fibroblasts. In the present study, the effect of MU on hyaluronate synthesis was investigated in cultured fibroblasts from the human uterine cervix. Methods: The cells were incubated with [3H]glucosamine in the presence of various concentrations of MU, and the effect of MU on hyaluronate synthesis was investigated. Then, the cells were preincubated in media that contained various concentrations of MU. After 72 h, the medium was removed and the cells were incubated with fresh medium containing [3H]glucosamine for 48 h. The amount of [3H]hyaluronate synthesized was measured. Results: MU added to the medium of cultured cells reduced the synthesis of hyaluronate in a dose-dependent manner. After MU was removed from the medium, hyaluronate synthesis recommenced and the amount of [3H]hyaluronate synthesized was similar to the control level. Conclusion: The MU-induced suppression of hyaluronate synthesis may contribute to the control of cervical ripening during human pregnancy.