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Biomedical subjects

Y Takeda

Publications and source records attributed to Y Takeda.

At least 577 records · Page 32Linked to original sources
PubMed1995

[A case of thrombocytopenia due to heparin therapy for a progressing ischemic stroke].

A 44-year-old man was admitted, complaining of weakness of his left limbs. On admission, he was oriented and cooperative. He showed positive Barré sign only on the left leg. Deep tendon reflexes were unremarkable; pathological reflexes were negative. There was no cerebellar ataxia or sensory deficit. Immediately after admission, monoplegia of the left leg progressed. He was started on heparin infusion therapy. His paralysis had been resolved by the 5th day. MRI of the brain demonstrated an infarction involving the body of the corpus callosum, the right cingulate gyrus, and the right paracentral lobule. Neuropsychologic examination demonstrated a disturbance of interhemispheric transfer of position. On the 10th day he developed Klebsiella ozaenae bacteremia. On the 11th day, platelet count was 9.2 x 10(4)/microliter. Antithrombin III, thrombin antithrombin III complex, D-dimer, and FDP levels were unremarkable, which is quite atypical for DIC associated with bacterial infection. Platelet factor 4 and beta-thromboglobulin levels were remarkably high, suggesting activated platelet aggregation. We made a diagnosis of heparin-induced thrombocytopenia and discontinued heparin infusion. Three days later, platelet count began to increase and creatinine levels returned normal. All patients receiving heparin should be monitored for platelet count.

Adult↗
PubMed1995

[Studies on the bone metabolisms in either after natural menopause or surgical menopause: implications of IGF-IGFBP system for postmenopausal osteoporosis].

It is well established that accelerated bone loss occurs in association with estrogen deprivation as seen following the natural menopause and in premenopausal women undergoing surgical oophorectomy (i.e., surgical menopause). We have measured serum levels of bone biochemical markers after both natural menopause and surgical menopause. Circulating levels of insulin-like growth factor-I (IGF-I), which is considered to be the local regulator of osteoblast activity and one of its binding protein, insulin-like growth factor binding protein-4 (IGFBP-4) which binds to IGF-I and suppress its biological activity, were also measured. Bone mineral density measured by dual energy X-ray absorptiometry was decreased more rapidly after surgical menopause. A concomitantly higher rate of bone turnover as assessed by bone biochemical markers was observed after surgical menopause, and thus the levels of procollagen type I C-peptide, pyridinoline and deoxypyridinoline were increased. The serum levels of IGF-I were significantly reduced after natural menopause compared with that after surgical menopause. The levels of IGF-I were correlated with bone mineral density after natural menopause (r = 0.62, p < 0.001), but no significant correlation was observed between these two variables after surgical menopause. The binding activity of IGFBP-4 was significantly greater after surgical menopause than after natural menopause. A stronger inverse correlation existed between the binding activity of IGFBP-4 and bone mineral density after surgical menopause (r = -0.90, p < 0.001) compared to that after natural menopause (r = -0.29, p < 0.05). The simplest explanation is that whereas the loss of bone depends upon the decreased level of IGF-I after natural menopause, after surgical menopause it depends upon the increased level of IGFBP-4.

Bone Density↗
PubMed1995

Effect of FK 506 on the expression of endothelin receptor mRNA in the vasculature.

Tacrolimus (FK 506) is a new, more powerful immunosuppressant and is more effective in the prevention and treatment of allograft rejection in humans than cyclosporine (CysA). The present study was conducted to determine whether FK 506 increases ET(A) receptor mRNA in blood vessels in rats. FK 506 5 mg/kg/day for 4 weeks increased blood pressure and expression of ET(A) receptor mRNA in mesenteric arteries of Wistar-Kyoto rats. However, 0.5 mg/kg/day of FK 506 did not increase blood pressure or ET(A) mRNA levels in the vasculature. The dose of 0.1 microM CysA used in clinical practice induced expression of ET(A) receptor mRNA in cultured rat vascular smooth-muscle cells (VSMCs). A clinical dose (0.01 microM) of FK 506 did not increase expression of ET(A) receptor mRNA in VSMCs. However, 0.1 microM FK 506 increased the levels of ET(A) receptor mRNA in VSMCs. These results indicate that the upregulating effect of FK 506 on the ET(A) receptor in the vasculature may contribute to the genesis of FK 506-induced hypertension. The lower incidence of complications seen with FK 506 may be due in part to its use at a lower clinical dose compared to that of CysA.

Animals↗
PubMed1995

Inhibition by dexamethasone of human neutrophil apoptosis in vitro.

We investigated in this study the effect of a synthetic glucocorticoid hormone, dexamethasone (Dex), on apoptosis of human peripheral blood neutrophils. Dex inhibited spontaneous and tumor necrosis factor-alpha (TNF-alpha)-induced neutrophil apoptosis in a concentration- and time-dependent manner. This effect of Dex on neutrophil apoptosis was completely reversed by a glucocorticoid receptor antagonist, RU38486, and by cycloheximide. The decrease in sensitivity to TNF-alpha-induced apoptosis cannot be ascribed to a down-modulation of TNF receptors on these cells. These observations suggest that a glucocorticoid hormone participates in the regulation of neutrophil apoptosis and that inhibition of human neutrophil apoptosis by Dex is mediated through glucocorticoid-receptor-induced de novo synthesis of macromolecules. Possible mechanisms and implications of this phenomenon are discussed.

Apoptosis↗
PubMed1995

[Inspection of carbon monoxide in imported tilapia].

Carbon monoxide in imported tilapia was determined with a gas chromatograph equipped with a molecular sieve 13x column (2.3 m), a methanizer and a FID for the inspection of imported food. The concentration of carbon monoxide in the sample, which was vacuum packed and suspected to be treated with carbon monoxide, was 16 x 10 micrograms/kg in fish meat, and 37 x 10(3) microliters/l in the bubble in the package. On the other hand, carbon monoxide in the reference, which was vacuum packed but was not treated with carbon monoxide, was 10 micrograms/kg in fish meat and 76 microliters/l in the bubble in the package. Carbon monoxide was less than 4 micrograms/kg in two vacuum packed fish meat of tilapia sold in a market in Tokyo. From these results, the suspected sample was concluded to be treated with carbon monoxide for color fixating of protoheme in fish meat.

Carbon Monoxide↗
PubMed1994

Vascular aldosterone. Biosynthesis and a link to angiotensin II-induced hypertrophy of vascular smooth muscle cells.

Mineralocorticoids have been suggested to act on blood vessels, leading to increased vasoreactivity and peripheral resistance. However, the site of their production has so far been believed to be only the adrenal cortex. Here, we show direct evidence that vascular cells per se are aldosteronogenic, possessing their own system that responds to the steroid. Using polymerase chain reaction after reverse transcription, the CYP11B2 mRNA encoding the key enzyme for the biosynthesis of aldosterone was detected in both endothelial cells and smooth muscle cells cultivated from human pulmonary artery. The aldosterone receptor (type 1 mineralocorticoid receptor) gene was also found to be expressed in smooth muscle cells and, to a lesser extent, in endothelial cells. CYP11B2 gene expression in smooth muscle cells was stimulated by angiotensin II, the effector peptide of the renin-angiotensin system. Furthermore, the angiotensin II-induced increase in [3H]leucine incorporation in smooth muscle cells was significantly enhanced by aldosterone but inhibited by ZK 91587, a type 1 mineralocorticoid receptor antagonist. This may indicate that vascular aldosterone participates in the angiotensin II-induced hypertrophy of vascular smooth muscle cells. The present study therefore provides the starting point for a novel understanding of the molecular basis of vascular remodeling and hypertension.

Aldosterone↗
PubMed1994

Establishment of a human small-cell lung-cancer subline resistant to okadaic acid.

Okadaic acid (OA), a specific protein phosphatase inhibitor, has various biological functions. To elucidate the mechanism of OA resistance, we have established a small-cell lung-cancer subline (H69/OA100) resistant to the growth-inhibitory effect of OA; this was done by using the parental cell line (H69) and increasing the concentration of OA. H69/OA100 was about 8 times more resistant to OA than H69. Intracellular retention of the fluorescent OA derivative in H69/OA100 was the same as that in H69. The catalytic activity of protein phosphatase from H69/OA100 was significantly reduced compared with that from H69. The protein phosphatase from H69/OA100 was 3.6 times more resistant to OA than that from H69. We examined the effect of OA on the activity of the immunoprecipitated protein phosphatase type I (PPI) and type 2A (PP2A) from the 2 cell lines. The PPI and PP2A from H69/OA100 showed more resistance to OA than those from H69. We next examined the effect of OA on the cell cycle of H69 and H69/OA100. In H69, G2/M block was observed at an OA concentration of 30 ng/ml whereas in H69/OA100, no G2/M block was observed at concentrations up to 100 ng/ml OA. We finally evaluated the amount of p34cdc2 kinase expression and the phosphorylation status of p34cdc2. There was no difference in p34cdc2 expression between H69 and H69/OA100 at several concentrations of OA. However, dephosphorylation of p34cdc2 was observed at 30 ng/ml OA in H69, but not in H69/OA100 up to 100 ng/ml OA. These data suggest that the resistance to OA and the resistance of the cell-cycle block to OA in H69/OA100 might be due to alteration of protein phosphatase activity.

Base Sequence↗
PubMed1994

DNA-dependent protein kinase (Ku protein-p350 complex) assembles on double-stranded DNA.

The Ku protein is an autoantigen that consists of 70- and 80-kDa polypeptides. It associates with double-stranded DNA at free ends. In the present study, we examined the ability of anti-Ku antibodies to immunoprecipitate various structures from extracts of HeLa cells prepared at different salt concentrations. Under physiological conditions, these antibodies identified a complex containing the Ku protein and the 350-kDa component (p350) of DNA-dependent protein kinase (DNA-PK), which appeared to be closely associated on the DNA strand. In reconstitution experiments with cell extracts and biochemically purified components, the Ku protein-p350 complex formed only in the presence of double-stranded DNA. The reconstituted complex was catalytically active. Together with previous studies, these results indicate that the Ku protein interacts with DNA to create a binding site for p350 as the DNA-PK holoenzyme assembles.

Antigens, Nuclear↗
PubMed1994

Reversal of multidrug resistance by tyrosine-kinase inhibitors in a non-P-glycoprotein-mediated multidrug-resistant cell line.

We have already established a human leukemia sub-line resistant to the growth-inhibitory effect of TPA (12-O-tetradecanoylphorbol 13-acetate) (K562/TPA) derived from K562. K562/TPA was found to be a non-P-glycoprotein-mediated multidrug-resistant cell line, in which intracellular drug accumulation was not reduced. In K562/TPA, adriamycin (ADM) was distributed mainly in the cytoplasm and was scarcely observed in the nucleus. We determined the relative levels of multidrug-resistance-associated protein (MRP), which was recently identified as the novel transporter. The relative levels of MRP in K562/TPA were the same as in K562. Although the catalytic activity of K562/TPA topoisomerase II was about half that of the parental cells, resistance to other drugs could not be explained by topoisomerase-II activity. To elucidate the mechanism of drug resistance in K562/TPA, we tried to find chemicals that would reverse the drug resistance. Tyrosine-kinase inhibitors enhanced the cytotoxicity of anti-neoplastic drugs against K562/TPA. Therefore we examined the modification of nuclear ADM accumulation in K562/TPA by one of these tyrosine-kinase inhibitors, genistein. Although the amount of ADM was decreased in the nuclei of K562/TPA cells, it was significantly increased after incubation in the presence of genistein. The formation of DNA single-strand breaks by ADM, etoposide, and ACNU was significantly lower in K562/TPA than in K562, but was significantly increased in the presence of genistein. These results suggest that genistein could overcome drug resistance by enhancing the accumulation of drug into the nuclear fraction of K562/TPA.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

The significance of enteroaggregative Escherichia coli in the etiology of hospitalized diarrhoea in Calcutta, India and the demonstration of a new honey-combed pattern of aggregative adherence.

Previous studies have identified enteroadherent Escherichia coli that exhibit localized adherence, diffuse adherence and atypical diffuse adherence as diarrhoeagenic agents associated with infantile diarrhoea in Calcutta, India. In this study, a DNA probe specific for enteroaggregative adherence was used to determine the etiological significance of enteroaggregative E. coli in the causation of diarrhoea. From a total of 330 strains of E. coli recovered from 159 cases of acute secretory diarrhoea and 174 cases of invasive diarrhoea, 20 strains hybridized with the probe, whereas of the 25 E. coli strains recovered from 25 healthy controls only 1 strain hybridized with the probe. Of the 21 probe positive strains, 19 adhered to HeLa cells in the typical stacked-brick pattern while 2 strains recovered from 2 cases of secretory diarrhoea adhered to the glass surface in a hitherto undescribed formation which we have termed, based on the appearance, as the honey-comb pattern. The enteroaggregative E. coli strains identified in this study did not produce any conventional enterotoxins and were significantly associated with patients with secretory diarrhoea (10.7%) than with invasive diarrhoea (1.7%). The results of this study indicate that enteroaggregative E. coli play a causal role in acute secretory diarrhoea in this part of the world which lends credence to the involvement of a potent toxin in the pathogenesis of EAggEC mediated infections.

Bacterial Adhesion↗
PubMed1994

Plasma and leukemic cell pharmacokinetics of high-dose N4-behenoyl-1-beta-D-arabinofuranosylcytosine in acute leukemia patients.

The pharmacokinetics of N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BHAC), a lipophilic antitumor analog of 1-beta-D-arabinofuranosylcytosine (ara-C), was investigated, by assay of plasma and leukemic cells of ten acute leukemic patients receiving 60-minute intravenous (IV) infusion of 700 mg/m2 BHAC, for BHAC and 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (ara-CTP) by high-performance liquid chromatography, ara-C by radioimmunoassay, and 1-beta-D-arabinofuranosyluracil (ara-U) by gas chromatography-mass fragmentography. The plasma concentration of BHAC reached a maximum (173.4 +/- 75.3 micrograms/mL) at the end of the infusion and then declined in a biphasic pattern with an initial-phase half-life (t1/2 alpha) of 1.00 +/- .36 hours and a second-phase half-life (t1/2 beta) of 4.28 +/- 2.35 hours. That of ara-C similarly reached a maximum (102.2 +/- 39.9 mg/mL) at the end of the infusion and then declined with t1/2 alpha of 1.37 +/- 1.11 hours and t1/2 beta of 11.2 +/- 4.31 hours. Intracellular ara-CTP concentration increased in a linear-accumulation manner for the first 4 hours after the infusion, reached a maximum of .081 +/- .112 micrograms/10(7) cells at approximately 7 hours, and then declined very slowly in accordance with a one-compartment model with t1/2 of 13.56 +/- 9.62 hours.

Antineoplastic Agents↗
PubMed1994

Characterization of an etoposide-resistant human ovarian cancer cell line.

Etoposide (VP-16) is one of the most important anticancer agents available and is used in many chemotherapeutic regimens. To characterize resistance to this drug, we established a VP-16-resistant human ovarian cancer cell line, SKOV3/VP, by continuous stepwise exposure of SKOV3 cells to VP-16. The degree of resistance to VP-16 of SKOV3/VP was about 25 times that of the parent cell line (SKOV3), and SKOV3/VP showed cross-resistance to teniposide, adriamycin, CPT-11, and vincristine. The accumulation of [3H]-VP-16 observed in SKOV3/VP cells was about half that seen in SKOV3 cells, and the accumulation of Adriamycin by this resistant cell line was also lower than that of its parent. Overexpression of neither the multidrug resistance gene mdr-1, the multidrug-resistance-associated protein (mrp) gene, nor P-glycoprotein was detected using reverse transcriptase-polymerase chain reaction analysis and flow cytometry with MRK-16, a monoclonal antibody against P-glycoprotein. The topoisomerase II activity of nuclear extracts from SKOV3/VP cells was lower than that from the parental cells, as was the amount of DNA topoisomerase II, demonstrated by immunoblotting. These results suggest that the mechanism responsible for the multidrug resistance of this cell line may be attributable to changes on its DNA topoisomerase II and to its reduced accumulation of the drugs as compared with the parental line SKOV3.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Analysis of effector T cells against the murine syngeneic tumor MethA in mice orally administered antitumor polysaccharide SPR-901.

The growth of MethA tumor was significantly inhibited by oral administration of the alpha-glucan SPR-901 in BALB/c (+/+) mice but not in nude mice. Mice treated orally with SPR-901 exhibited an augmentation of antigen-specific resistance against rechallenge with the tumor cells. The tumor-neutralizing activity of regional lymph node cells from MethA-bearing mice against the tumor was augmented by oral administration of SPR-901. The tumor-neutralizing activity of lymph node cells from SPR-901-treated mice mainly appeared in Lyt2+ cells. Furthermore, lymphokine-activated killer activity of these cells was enhanced by administration of SPR-901. The antitumor effect of SPR-901 was abrogated in mice depleted of either L3T4+ or Lyt2+ cells, and in cyclosporin-A-treated mice. These results suggest that Lyt2+ cells are important effector cells in MethA-bearing mice orally administered SPR-901 and that functional exertion of both Lyt2+ and L3T4+ T cells is necessary for the antitumor effect of orally administered SPR-901 in vivo.

Adjuvants, Immunologic↗