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Biomedical subjects

M Ueki

Publications and source records attributed to M Ueki.

At least 37 records · Page 2Linked to original sources
PubMed2001

Beneficial effects of pravastatin in peri- and postmenopausal hyperlipidemic women: a 5-year study on serum lipid and sex hormone levels.

OBJECTIVES: The aims of the present study are to assess the 5 year effects of pravastatin on serum lipids and lipoproteins in women around the menopause and to assess the effects of pravastatin on serum gonadotropins and sex steroid levels over a long-term period. METHODS: We evaluated the long-term efficacy of pravastatin on serum lipid levels (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride) in 121 patients (47 premenopausal and 74 postmenopausal women) suffering from primary hypercholesterolemia. The effects of this lipid-lowering drug on serum gonadotropins and sex steroids (estradiol, estrone, and testosterone) are also reported. RESULTS: Pravastatin produced a remarkable reduction in the serum total cholesterol level of 19.2+/-9.3% (P<0.0001) and 18.9+/-11.8% (P<0.0001), and in LDLl-cholesterol of 25.1+/-18.7% (P<0.0001) and 24+/-18.0% (P<0.0001) after 24 and 60 months' treatment, respectively. In hypertriglyceridemia, pravastatin also produced a remarkable reduction in triglyceride of 29.3+/-27.3% (P<0.0001) and 39.9+/-20.4% (P<0.0001) after 24 and 60 months of treatment, respectively. We found that serum gonadotropins and sex steroid levels changed naturally as a function of age from pre-therapy levels in the premenopausal patients after 60 months of treatment. CONCLUSIONS: Pravastatin was well tolerated over 5 years and was a very effective lipid-lowering agent for both hypercholesterolemia and hypertriglyceridemia with no effect on the biosynthesis of sex steroids. These findings suggest that pravastatin can be used in the treatment of hypercholesterolemia with/without high triglyceride levels in women around the menopause.

Anticholesteremic Agents↗
PubMed2001

Tetranuclear titanium 7,7'-modified binaphtholate cluster as a novel chiral Lewis acid catalyst.

Chiral tetranuclear Ti cluster, a cubic structure constituted of four Ti atoms and OHs, and six (R)-binaphthols (BINOL) bridged two Ti atoms as ligands, is shown to be a novel chiral Lewis acid catalyst for the [2+3] cycloaddition reaction with nitrones. The chiral Ti clusters with 7,7'-substituted (R)-BINOL ligands was synthesized to give enhanced enantiomeric excesses up to 78% ee.

Journal Article↗
PubMed2001

Vascular smooth muscle cell growth-promoting factor/F-spondin inhibits angiogenesis via the blockade of integrin alphavbeta3 on vascular endothelial cells.

Vascular smooth muscle cell growth-promoting factor (VSGP) was originally isolated from bovine ovarian follicular fluid as a stimulator of vascular smooth muscle cell proliferation. Homology searches indicate that bovine and human VSGPs are orthologs of rat F-spondin. Here, we examined whether recombinant human VSGP/F-spondin affected the biological activities of endothelial cells. VSGP/F-spondin did not affect the proliferation of human umbilical vein endothelial cells (HUVECs); however, it did inhibit VEGF- or bFGF-stimulated HUVEC migration. To clarify the mechanism of this inhibitory effect, we examined the adhesion of HUVECs to extracellular matrix proteins. VSGP/F-spondin specifically inhibited the spreading of HUVECs on vitronectin via the functional blockade of integrin alphavbeta3. As a result, VSGP/F-spondin inhibited the tyrosine phosphorylation of focal adhesion kinase (FAK) when HUVECs were plated on vitronectin. Moreover, VSGP/F-spondin inhibited the activation of Akt when HUVECs on vitronectin were stimulated with VEGF. VSGP/F-spondin inhibited tube formation by HUVECs in vitro and neovascularization in the rat cornea in vivo. These results indicate that VSGP/F-spondin inhibits angiogenesis at least in part by the blockade of endothelial integrin alphavbeta3.

Animals↗
PubMed2001

Vascular endothelial growth factor C gene expression is closely related to invasion phenotype in gynecological tumor cells.

OBJECTIVE: The correlation between the gene expression of various angiogenic factors and in vitro invasive activity in 16 human gynecological cancer cell lines was investigated. METHODS: Semiquantitative reverse transcription polymerase chain reaction analysis was performed to investigate the mRNA expression levels of vascular endothelial growth factors (VEGF-A, -B, -C, and -D), basic fibroblast growth factor (bFGF), and matrix metalloproteinase (MMP)-2 with beta-actin coamplified as an internal standard. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into reconstituted basement membrane were evaluated by haptotactic migration and invasion assay. RESULTS: Expression of VEGF-A mRNA was detected in all 16 cell lines, whereas the relative expression levels of other VEGF family members and bFGF, differed markedly among the cell lines. There was a statistical correlation between VEGF-C gene expression and the number of cells that migrated and invaded (P < 0.01). However, expression of mRNAs of other angiogenic factors did not correlate with motility and invasive activity of the cells. Moreover, there was a close correlation between VEGF-C and MMP-2 gene expression levels (P < 0.05). CONCLUSION: Tumor cells that produce VEGF-C may have a higher invasive and metastatic potential because of their capacity to pass through tissue barriers.

DNA, Neoplasm↗
PubMed2001

Effects of ulinastatin (urinary trypsin inhibitor) on ATP, intracellular pH, and intracellular sodium transients during ischemia and reperfusion in the rat kidney in vivo.

PURPOSE: To investigate the effects of ulinastatin on renal ischemia-reperfusion injury, we monitored the dynamic changes in ATP, intracellular pH (pHi), and intracellular sodium (Nai) in rats in vivo. METHODS: Renal ischemia was induced by clamping the abdominal aorta for 30 min followed by reperfusion for 60 min. Ulinastatin, 50,000 U.kg(-1) (UTI group), or normal saline (NS group) was infused for 30 min before ischemia. (31)P- and double quantum (23)Na-NMR were used to monitor ATP, pHi, and Nai. RESULTS: During ischemia, ATP was rapidly depleted and Nai increased to the same extent in both groups. After 60 min reperfusion, Nai in the NS group was almost restored to the preischemic baseline level (117.2 +/- 7.4% of the baseline value), but the recovery of ATP was incomplete (60.9 +/- 7.7%). The recovery of Nai in the UTI group began earlier than in the NS group with better recovery of ATP. The pHi values showed severe acidosis in the NS group compared with the UTI group during ischemia and reperfusion. As for ultrastructural findings, after 60 min reperfusion, the mitochondria were less swollen and less disorganized with respect to the membrane and the cristae in the UTI group. CONCLUSION: The transcellular sodium gradient is restored before the ATP level is normalized during postischemic reperfusion. Ulinastatin might protect mitochondrial conformation during ischemia, and facilitate functional recovery of the ionic pump after reperfusion.

Journal Article↗
PubMed2001

Synthesis and chain length-anti-HIV activity relationship of fully N- and O-sulfated homooligomers of tyrosine.

Fully N- and O-sulfated homooligomers from octamer to nonadecamer of tyrosine were obtained as their sodium salts, aO3S-[Tyr(SO3Na)]n-ONa (n = 8-19), from reaction mixtures of tyrosine with sulfur trioxide trimethylamine and pyridine comlexes, respectively, in pyridine. Their anti-HIV activity increased along with the increase of the chain length up to the dodecamer, maintained the same level to the length of the heptadecamer and then decreased. The maximal activity level was the same as or higher than that of dextran and curdlan sulfates.

Anti-HIV Agents↗
PubMed2001

Synthesis and anti-HIV activity of nonatyrosine N- and O1-9-decasulfate.

To develop a potent and effective anti-HIV compound with a definite polyanionic structure, synthesis of oligotyrosine sulfates by oligomerization with simultaneous sulfation of tyrosine was tried. One component was successfully isolated from the mixture containing many products as its sodium salt (Y-ART-4) and was identified as the salt of nonatyrosine N- and O1-9-decasulfate, NaO3S-[Tyr(SO3Na)]9-ONa. Anti-HIV activity of Y-ART-4, determined from the protection it provided against HIV-induced cytopathic effects, was almost the same with that of dextran sulfate and curdlan sulfate.

Anti-HIV Agents↗
PubMed2001

Apoptosis in the normal human amnion at term, independent of Bcl-2 regulation and onset of labour.

This study was designed to detect apoptosis in the human amnion and to elucidate the signalling pathway involved in its regulation. Samples of human amnion were obtained from 34 women (weeks 11-42 of gestation) and studied using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) method with light microscopy (LM) and transmission electron microscopy (TEM). Apoptotic regulators in the samples were studied by immunohistochemistry and caspase activity assay. The TUNEL method with LM demonstrated that the percentage of TUNEL-positive cells in the amniotic epithelium was the highest in weeks 40-41 of gestation (P < 0.05) independent of the onset of labour, and the cells were often detached from the epithelium into the amniotic cavity at term. The TUNEL method with TEM clearly showed the characteristic features of apoptosis such as the nuclear condensed chromatin with abundant free 3'-OH DNA ends, cell shrinkage and a decrease in the number of desmosomes, except for the presence of apoptotic bodies. Fas and Fas ligand (FasL) were constantly expressed on apical membranes of amniotic epithelial cells from weeks 16-27 through to 40-41 of gestation, while no Bcl-2 expression was observed throughout the gestational periods. Activities of caspase-3 and caspase-8, but not of caspase-9, were higher in weeks 40-41 than those from weeks 16-27 of gestation (P < 0.01). We conclude that apoptosis in term amniotic epithelium is independent of Bcl-2 regulation and onset of labour, and may play an important role in the fragility and rupture of human fetal membranes at term.

Amnion↗
PubMed2001

Isolation, and biological properties of a new cell cycle inhibitor, curvularol, isolated from Curvularia sp. RK97-F166.

A new cell growth inhibitor, curvularol, was isolated from the fermentation broth of Curvularia sp. RK97-F166. Curvularol showed no antibacterial activity, and very weak antifungal activity. However, curvularol inhibited the cell cycle progression of normal rat kidney (NRK) cells in G1 phase at 150 ng/ml. Curvularol induced the morphological reversion of srcts-transformed NRK cells at 100 ng/ml, and inhibited protein synthesis same as cycloheximide.

Animals↗
PubMed2001

A facile and effective screening method for p21WAF1 promoter activators from microbial metabolites.

We have developed a novel p21WAF1 promoter activator screening system based on rapid and facile luciferase activity assay of a model cell system (H1299/tsp53-luc cells), a stable luciferase expression cell line established by transfecting H1299/tsp53 cells with a reporter gene construct pWWP-Luc-BSD. This plasmid was constructed by subcloning the 2.4 kb p21WAF1 promoter and a 2.6 kb of luciferase cDNA fragment activated by the p21WAF1 promoter into a pMAM2-BSD expression vector containing the blasticidin S deaminase gene (BSD). A BSD-resistant clone H1299/tsp53-luc#4, showing the highest response to p53 activation (by temperature shift from 37 degrees C to 32 degrees C) by luciferase production, was used for screening microbial culture broths. Among approximately 1200 screened samples, trichostatin A related compounds and a new compound, lucilactaene, were isolated. This provides an effective and facile screening system for p21WAF1 promoter activators which should be of considerable value in the rapid identification of new anticancer agents.

Antibiotics, Antineoplastic↗
PubMed2001

Estrogen replacement therapy in postmenopausal women: a study of the efficacy of estriol and changes in plasma gonadotropin levels.

The purpose of this study was to clarify the efficacy of estriol for estrogen replacement therapy in postmenopausal women with undefined symptoms and to evaluate endocrinological changes during therapy in relation to clinical outcome. Administration of 2 mg estriol in 168 postmenopausal patients was markedly effective in 22.6% of cases, effective in 45.2%, fairly effective in 14.3%, and ineffective in 17.9% of cases. The plasma concentration of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) after administration of estriol decreased significantly (p < 0.001), by 52.2% and 32.9%, respectively for markedly effective cases, and by 39.1% and 48.0% for effective cases. In contrast, the plasma estradiol concentration remained unchanged. On the other hand, decreases in FSH and LH concentration were 13.9% and 5.9% for the fairly effective and 8.2% and 1.9% for ineffective cases, demonstrating a significantly lower decrease in plasma FSH and LH levels than in the markedly effective and effective cases (p < 0.001). For cases showing side-effects, the plasma FSH and LH levels decreased by 52.0% and 64.3%, respectively, whereas the plasma estradiol level remained unchanged. In conclusion, the efficacy of estriol was significantly correlated to the degree of decrease in plasma FSH and LH levels in patients with undefined symptoms. In addition, efficacy appeared to be correlated to the incidence of side-effects. The degree of reduction of FSH (39.1-52.2%) and LH (48.0-64.3%) from the baseline may possibly be used as a guide to the therapeutic hormone levels during HRT. The present results suggest that plasma gonadotropin levels could be a useful indicator in the management of patients undergoing estrogen replacement therapy.

Biomarkers↗
PubMed2001

Effects of unkei-to, an herbal medicine, on endocrine function and ovulation in women with high basal levels of luteinizing hormone secretion.

OBJECTIVE: To treat anovulatory women with high plasma LH levels with unkei-to. STUDY DESIGN: A total of 100 patients with polycystic ovary syndrome (n = 38) or non-polycystic ovary syndrome (n = 62) were allocated randomly into two groups. Endocrine levels (FSH, LH and estradiol), follicle growth and response to unkei-to were compared for 52 subjects in the unkei-to group and 48 subjects in the control group. RESULTS: Unkei-to induced significant decreases in plasma LH in polycystic ovary syndrome and non-polycystic ovary syndrome with high LH levels. Plasma estradiol levels increased significantly (43.5%) in eight weeks of treatment with unkei-to. Significant development of the dominant follicle was also observed in patients treated with unkei-to. When women suffering from ovulatory failure or irregular menstruation and having high plasma LH concentration were treated with unkei-to for eight weeks, a reduction in the serum LH level of at least 1 SD from baseline was noted in 45.5% of polycystic ovary syndrome patients and in 80.0% of non-polycystic ovary syndrome patients. The mean rate of reduction of serum LH was 22.2 +/- 35.7% in polycystic ovary syndrome patients and 49.7 +/- 15.3% in non-polycystic ovary syndrome patients. This reduction was significant in the non-polycystic ovary syndrome patients (P = .030). The rate of menstrual cycle improvement, including successful ovulation, was 50.0% in the polycystic ovary syndrome group and 60.0% in the non-polycystic ovary syndrome group, with no significant difference between the two groups.

Adult↗
PubMed2001

The association between postmenopausal vertebral bone mineral density and estrogen receptor gene alleles in ethnic Japanese living in western Japan.

Bone mass and its mineral content has been shown to be under genetic control. Our purpose in this study was to assess whether estrogen receptor genotypes influence changes in bone mass in post menopausal Japanese women and clarify the regional differences in Japanese women. Pvu II and Xba I restriction enzyme fragment length polymorphism of the estrogen receptor gene and its relationship with vertebral bone mineral density were examined in 300 unrelated post menopausal women, aged 42-69 years, from the Kinki region in Japan. Vertebral bone mineral density was evaluated at the lumbar spine (L2-4) by dual energy X-ray absorptiometry. We found no relationship between any single restriction site polymorphism and the Z-score of bone mineral density. However, the allelic haplotype PPXx was found to be associated with a significantly low bone mineral density (Z-score for the lumbar spine -1.118+/-1.270 vs. PPxx 0.04+/-1.150; p<0.01, vs. ppxx 0.387+/-1.226; p<0.05, respectively). We suggest that ER gene polymorphism is associated with low bone mineral density and that this partly explains the cause of post menopausal bone loss in Japanese women. The contradictory conclusions compared with previous studies in the Japanese population regarding the association of BMD with ER RFLPs demands further investigation.

Aged↗
PubMed2001

Does the estrogen receptor gene polymorphism relate to undefined menopausal symptoms?

The present study examines the relationship between estrogen receptor (ER) gene polymorphism and undefined complaints to clarify the aging process of the genitospinal center. Pvu II and Xba I restriction fragment length polymorphism (RFLP) of the estrogen receptor (ER) gene and its relationships to undefined symptoms was examined in 507 Japanese peri- and postmenopausal women who were classified in 3 groups by serum estradiol (E2) values; group A:E2>30 pg/ml; group B:E210-30 pg/ml; group C:E2<10 pg/ml. The percentage of women grouped A was significantly higher than that of group B in genotype Pp. Furthermore, the frequency of Ppxx in group A was significantly higher than that of group B or C. On the other hand, the frequency of ppxx in group A was significantly lower than that of group B (p=0.0042) or C (p=0.049). Neither FSH nor LH differed significantly between Ppxx and ppxx. On the other hand, the plasma estradiol level differed significantly between Ppxx and ppxx (p=0.0004). Moreover, a higher incidence of mental symptoms was observed in group A than in groups B or C (p<0.01). The present results suggest that ER gene polymorphism influences aging of the genitospinal center, and may explain in part the pathophysiology and cause of undefined perimenopausal complaints.

Adipose Tissue↗
PubMed2000

Asymmetric Activation.

While nonracemic catalysts can generate nonracemic products with or without the nonlinear relationship in enantiomeric excesses between catalysts and products, racemic catalysts inherently give only a racemic mixture of chiral products. Asymmetric catalysts, either in nonracemic or racemic form, can be further evolved into highly activated catalysts with association of chiral activators. This asymmetric activation process is particularly useful in racemic catalysis through selective activation of one enantiomer of the racemic catalyst. Recently, a strategy whereby a racemic catalyst is selectively deactivated by a chiral additive has been reported to yield nonracemic products. However, reported herein is an alternative and conceptually opposite strategy in which a chiral activator selectively activates, rather than deactivates, one enantiomer of a racemic chiral catalyst. The advantage of this activation strategy over the deactivation counterpart is that the activated catalyst can produce a greater enantiomeric excess in the products-even with the use of a catalytic amount of activator relative to chiral catalyst-than that attained by the enantiomerically pure catalyst on its own. Therefore, asymmetric activation could provide a general and powerful strategy for not only the use of atropisomeric, racemic ligands but also chirally flexible and proatropisomeric ligands without enantiomeric resolution!

Journal Article↗
PubMed2000

Time course of trace of diffusion tensor [Trace(D)] and histology in brain edema.

We examined the correlation between changes in the trace of diffusion tensor [Trace(D)], regional water content and tissue ultrastructure relating to cellular (cytotoxic) and vasogenic brain edema. Cellular edema was induced by left middle cerebral artery occlusion in cats (Kuroiwa T et al., 1998). Vasogenic edema was induced in the white matter of cats by a cold lesion (Kuroiwa T et al., 1999). In cellular edema, the water content increase correlated linearly with the Trace(D) decrease in both the gray and white matter. However, both the slopes and intercepts of the correlation lines were significantly different. Hydropic astrocytic swelling was seen in both structures, and in the white matter, oligodendrocytic and myelinated axonal swelling were observed. In vasogenic edema, the increase in Trace(D) showed a significant linear correlation with the increase in tissue water content. Histologically, nerve fibers were dissociated and the extracellular space was markedly enlarged with protein-rich fluid. These result showed that the different slopes and intercepts of the water content--Trace(D) correlation lines for different subtype of brain edema, which reflect different ultrastructural localization of water, should be taken into account when evaluating brain edema using Trace(D) mapping.

Animals↗