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T Murakami

Publications and source records attributed to T Murakami.

At least 397 records · Page 22Linked to original sources
PubMed1999

Evaluation of regional liver function by gadolinium-EOB-DTPA-enhanced MR imaging.

We evaluated the role of magnetic resonance (MR) imaging with gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA), in estimating regional liver function in a rat ischemia-reperfusion model. Ischemic liver damage was induced in the right lobe by vascular clamping for 0 (sham), 30 (I-30), 60 (I-60), and 90 min (I-90 group). The ischemic lobes in the I-60 and I-90 groups was clearly visualized as a high intensity area in the T1 images at late phase of Gd-EOB-DTPA enhancement, Moreover, the T1/2 of signal intensity in ischemic lobes significantly correlated with the duration of vascular clamping. We also observed significant correlation between T1/2 and ATP concentration in the liver tissue (r = -0.719, P = 0.04). Our results indicate that MR imaging with Gd-EOB-DTPA is useful for evaluation of regional liver function in rats.

Animals↗
PubMed1999

Differential effects of adenosine receptor subtypes on release and reuptake of hippocampal serotonin.

To clarify the effects of adenosine receptor subtypes (A1, A2 and A3) on hippocampal serotonin (5-HT) release and 5-HT reuptake activity, hippocampal extracellular 5-HT levels were determined in vivo by microdialysis in freely moving rats. Selective 5-HT reuptake inhibitor (SSRI) fluoxetine and DU24565 increased extracellular 5-HT levels. Adenosine and A1 receptor agonist, 2-chloro-N6-cyclopentyl-adenosine (CCPA), decreased extracellular 5-HT levels, whereas non-selective antagonist, caffeine, and A1 antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT) increased them. When 5-HT reuptake activity was inhibited by DU24565 and fluoxetine, the effects of CPT and CCPA on 5-HT level were enhanced. A2A receptor agonist, CGS21680, A2 receptor agonist, PD125944, A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX), and A3 receptor agonist, N6-2-(4-aminophenyl)ethyladenosine (APNEA) did not affect 5-HT levels; however, when A1 receptor was blocked by CPT, 5-HT levels were increased by adenosine, CGS21680 and PD125944, and decreased by DMPX and APNEA. Under conditions of A1 receptor blockade, pretreatment with DU24565 or fluoxetine, enhanced the stimulatory effects of CGS21680 and PD125944 as well as inhibitory effects of DMPX on 5-HT level, whereas the inhibitory effect of APNEA was abolished. These results indicate that the stimulatory effects of A2 receptor and inhibitory effects of A3 receptor on hippocampal extracellular 5-HT levels are masked or abolished by the inhibitory effects of A1 receptor. In addition, hippocampal serotonergic transmission might be modulated by hippocampal presynaptic adenosine receptor subtypes, and hippocampal 5-HT reuptake activity might be modulated by hippocampal A3 receptor.

Adenosine↗
PubMed1999

Evaluation of an implantable motor-driven left ventricular assist device.

A console based implantable motor-driven left ventricular assist device (LVAD) was developed and tested. Ten sheep weighing 42-73 kg (mean, 54.4 kg) were used as the experimental animals. Four animals survived 5-12 h (mean, 9.5 h). The mean pump flow was 1.63 L/min, ranging from 0.8 to 2.5 L/min. The cause of termination was respiratory failure in 3 animals, bleeding in 2, ventricular fibrillation in 2, vent tube obstruction in 1, thrombus formation in 1, and mechanical failure of the driving console in 1. Following the in vivo studies, the computer regulated controller was tested in a mock circulatory system. The LVAD provided 5.34 L/min of maximum output against a mean afterload of 80 mm Hg with a filling pressure of 15 mm Hg when the pump rate was 80 bpm in the fixed rate mode. With an increase in the pump afterload from 80 to 140 mm Hg, the total system efficiency varied from 7.81 to 8.34% when the pump preload was 15 mm Hg. An ultracompact, completely implantable electromechanical VAD has been under development. This device should fit in a 60 kg adult. As the next step, we are preparing to implant this ultracompact implantable VAD with an electronic controller in an animal model with better results being expected.

Animals↗
PubMed1999

Role of P-glycoprotein in distribution of rhodamine 123 into aqueous humor in rabbits.

PURPOSE: Examination of the contribution of functional P-glycoprotein (P-gp), an ATP-dependent efflux pump, in blood-aqueous barrier in rabbits. METHODS: Rhodamine-123 (Rho-123), a P-gp substrate, was administered intravenously via the marginal ear vein of rabbits. Rhodamine B (Rho-B), an analogue of Rho-123, was also injected with the same dose, as a reference compound. Quinidine at different concentrations was applied topically to the corneal surface by eye drops prior to the intravenous administration of a Rho compound. The aqueous distribution (a ratio of concentration in aqueous humor to that in plasma) of these Rho compounds was analyzed in relation to the aqueous concentration of quinidine. Transport study across Caco-2 cell monolayers was carried out to examine the involvement of P-gp in Rho-B transport. RESULTS: It was proved that Rho-B is not a P-gp substrate by a transport study across Caco-2 cell monolayers, in contrast to Rho-123 (a P-gp substrate). The aqueous distribution of Rho-123 given intravenously was significantly lower than that of Rho-B. Topical quinidine (a P-gp inhibitor) markedly increased the aqueous distribution of Rho-123, depending on the aqueous concentrations of quinidine, though it did not affect the aqueous distribution of Rho-B. CONCLUSIONS: The contribution of functional P-gp in blood-aqueous barrier was clearly demonstrated by analyzing the aqueous distribution of Rho-123 in the presence or absence of quinidine. These experiments only allow us to address one part of the blood-aqueous barrier, the capillary endothelium, and, to do so by using different substrates for P-gp, a sort of chemical analogy with the presumed blood-aqueous barrier across capillary endothelia. The alteration of P-gp function by pharmacotherapy or in pathological state should be considered in the ophthalmic medical treatment.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Immunosuppressive effects of the heat shock protein 90-binding antibiotic geldanamycin.

Ansamycin antibiotic, geldanamycin has a unique pharmacological effect to bind to heat shock protein 90 (hsp90) and deplete hsp90 substrates. We investigated the immunopharmacological effects of geldanamycin. Geldanamycin depleted cellular Raf-1 of rat splenic cells without affecting the steady state levels of hsp90 and downstream mitogen activated protein (MAP) kinases, ERK1 and ERK2. In parallel, it inhibited mitogen-induced nuclear factor-kappa B (NF-kappa B) activation in these cells. Geldanamycin also had a potent suppressive effect on recall antigen-induced T cell proliferation, with an IC50 value of 1 nM. In vivo, geldanamycin suppressed the progression of adjuvant-induced arthritis dose-dependently. These results suggest that geldanamycin exerts an immunosuppressive effect partly through destabilizing Raf-1, and raise a new strategy for the prevention of inflammatory diseases.

Animals↗
PubMed1999

Involvement of dopamine D1-like receptors in mediating increases in protein secretion from rabbit lacrimal gland.

To identify and localize the dopamine receptor subtypes in rabbit lacrimal gland which mediate protein secretion, the effects were determined of different dopamine receptor subtype agonists, antagonists, and a beta adrenergic antagonist on this process. Protein secretion into the medium was quantified with the Bradford assay. Dopamine increased protein secretion between 10(-7) and 10(-4)M, and it could be maintained for a subsequent 80 min. The relatively selective D1-like receptor agonist, SKF-38393 (10(-4)M) had a similar effect which was suppressed by the D1-like receptor antagonist, SCH-23390. However, neither the D2-like receptor agonist, quinpirole (10(-4)M), nor the selective D2-like receptor antagonist, sulpiride (10(-4)M) altered either the basal level or the stimulated response to dopamine. The dopamine (10(-4)M)-elicited increases in protein secretion were completely suppressed in the presence of either 10(-4)M propranolol or 10(-4)M bretylium. Protein secretion in rabbit lacrimal gland is mediated by dopaminergic nerves through stimulation of the presynaptic D1-like receptor.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1999

Dietary prevention of azoxymethane-induced colon carcinogenesis with rice-germ in F344 rats.

The modifying effect of dietary administration of defatted rice-germ and gamma-aminobutyric acid (GABA)-enriched defatted rice-germ on azoxymethane (AOM)-induced colon carcinogenesis was investigated in two experiments with male F344 rats. In the first experiment (the pilot study), the effects of the defatted rice-germ, the GABA-enriched defatted rice-germ and rice-germ on AOM-induced (15 mg/kg body wt once a week for 3 weeks) formation of aberrant crypt foci (ACF) were examined. The latter two preparations (2.5% in the diet) significantly inhibited ACF formation (P < 0.005). In the second experiment, a long-term study of the effects of rice-germ was done. One group was treated with AOM alone, four groups received the carcinogen and were fed the diets containing 2.5% rice-germ or 2.5% GABA-enriched defatted rice-germ for 5 (initiation phase) or 30 weeks (post-initiation phase), two groups were treated with rice-germ or GABA-enriched defatted rice-germ alone and one group was kept on the basal diet. At the termination of the study, dietary exposure to rice-germ during the initiation phase significantly reduced the incidence of colonic adenocarcinoma (71 versus 29%, P < 0.01). GABA-enriched defatted rice-germ or rice-germ during the post-initiation phase also decreased the frequency of colonic adenocarcinoma (71 versus 20%, GABA-enriched defatted rice-germ feeding, P < 0.01; 27%, rice-germ feeding, P < 0.01). These data suggest that constituents of rice-germ are possible dietary preventatives for human colon cancers.

Animals↗
PubMed1999

Oestrogen receptor alpha and beta mRNA expression in human endometrium throughout the menstrual cycle.

We examined the localization of oestrogen receptor (ER) beta mRNA in the human endometrium throughout the menstrual cycle using non-radioactive in-situ hybridization with Brigati-tailed oligonucleotides. The findings were compared with those of ERalpha in order to examine the possible biological significance of ERbeta in the human endometrium. Both ERalpha and ERbeta mRNA expression were detected in all major human uterine cell types, including glandular epithelial cells, stromal cells and smooth muscle cells of the uterine wall, at every menstrual cycle stage. However, ERalpha mRNA expression was more prominent than that of ERbeta in all cell types throughout the menstrual cycle. In proliferative phase endometrium, ERalpha mRNA was expressed in both glandular epithelial and stromal cells, while ERbeta mRNA was expressed predominantly in glandular epithelial cells. Although the same pattern was observed in the secretory phase, both the ERalpha and ERbeta mRNA expression was relatively weaker. These results suggest that oestrogenic effects occur predominantly through ERalpha, but that ERbeta may also play a role in the modulation of oestrogenic action, especially on glandular epithelial cells in the human endometrium throughout the menstrual cycle.

Endometrium↗
PubMed1999

Postoperative tetany in Graves disease: important role of vitamin D metabolites.

OBJECTIVE: To test the authors' hypothesis of the causal mechanism(s) of postoperative tetany in patients with Graves disease. SUMMARY BACKGROUND DATA: Previous studies by the authors suggested that postoperative tetany in patients with Graves disease occurs during the period of bone restoration and resulted from continuation of a calcium flux into bone concomitant with transient hypoparathyroidism induced by surgery. PATIENTS AND METHODS: A prospective study was carried out to investigate sequential changes in serum levels of intact parathyroid hormone (iPTH), calcium and other electrolytes, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)2D), and bone metabolic markers in 109 consecutive patients with Graves disease who underwent subtotal thyroidectomy. RESULTS: Preoperative serum iPTH levels negatively correlated with ionized calcium levels and positively correlated with 1,25(OH)2D or 1,25(OH)2D/25OHD. After the operation, there was a significant decline in levels of ionized calcium, magnesium, and iPTH. Serum iPTH was not detected in 15 patients after surgery. Four of these 15 patients, and 1 patient whose iPTH level was below normal, developed tetany. Preoperative serum ionized calcium levels were significantly lower, and iPTH levels were higher, in the 5 patients with tetany than in the 11 patients who did not develop tetany despite undetectable iPTH levels. The tetany group had significantly lower serum 25OHD levels and higher 1,25(OH)2D levels, and had increased 1,25(OH)2D/25OHD as an index of the renal 25OHD-1-hydroxylase activity than those in the nontetany group. These results suggest that patients with a high serum level of iPTH as a result of low serum calcium levels (secondary hyperparathyroidism) are susceptible to tetany under conditions of hypoparathyroid function after surgery. CONCLUSIONS: Postoperative tetany occurs in patients with secondary hyperparathyroidism caused by a relative deficiency in calcium and vitamin D because of their increased demand for bone restoration after preoperative medical therapy concomitant with transient hypoparathyroidism after surgery. Calcium and vitamin D supplements may be recommended before and/or after surgery for patients in whom postoperative tetany is expected to develop.

Adolescent↗
PubMed1999

Clinical late phase II trials of MultiHance (Gd-BOPTA) for the magnetic resonance imaging of liver tumors in Japan.

OBJECTIVE: The purpose of the study was to evaluate the safety and efficacy of Gd-BOPTA for liver imaging and to determine the most appropriate clinical dose to administer. METHODS: Gd-BOPTA was administered at a dose of 0.05 (group A), 0.1 (group B), or 0.2 (group C) mmol/kg to 201 patients suspected of having malignant liver tumors who had been referred for magnetic resonance imaging. Dynamic phase images (T1-weighted gradient echo sequences obtained during breath-hold), images obtained within 10 min of Gd-BOPTA injection (spin echo images) and delayed images obtained at 40-120 min after Gd-BOPTA injection (T1-weighted spin echo and gradient echo sequences during breathhold) were acquired. All post-contrast images were compared with pre-contrast images (T1- and T2-weighted sequences) obtained immediately prior to Gd-BOPTA administration. Safety was assessed in terms of the incidence of adverse events. RESULTS: The contrast efficacy for the dynamic study was classified as ( ) in 39.7% (27/68), 55.4% (36/65), and 47.0% (31/66) for groups A, B, and C, respectively. The contrast efficacy within 10 min of the injection was classified as ( ) in 7.6% (5/66), 16.9% (11/65), and 12.5% (8/64) for groups A, B, and C, respectively. The contrast efficacy at 40-120 min post-injection was classified as ( ) in 4.4% (3/68), 21.5% (14/65), and 20.0% (13/65) for groups A, B, and C, respectively with significant differences noted between groups A and B and groups A and C. As regards safety, the overall incidence of adverse reactions was 3.5% (7/199). CONCLUSION: Gd-BOPTA is a safe and efficacious contrast agent for use in both dynamic phase imaging and delayed (40-120 min) static imaging. A dose of 0.1 mmol/kg Gd-BOPTA appears to be the ideal dose for use in liver imaging in Japan.

Adult↗
PubMed1999

Epstein-Barr virus-associated gastric carcinoma and atrophic gastritis.

Although Epstein-Barr virus (EBV) has been reported to be present in some 7% of gastric carcinomas, the nature of the background gastric mucosa of carcinoma has not been elucidated. The authors evaluated the degree of gastritis in the background gastric mucosa of EBV-associated gastric carcinoma. EBV was detected using in situ hybridization for EBV-encoded small ribonucleic acid 1 (EBER-1) in carcinoma cells. The authors compared gastritis in surgically resected stomachs with 8 EBER-1-positive and 16 EBER-1-negative gastric carcinomas of a similar histologic type using histologic variables of the Updated Sydney System. All eight lesions of EBER-1-positive gastric carcinomas had intestinal metaplasia in the background. Mild to moderate glandular atrophy was common in both groups. Many of the tested lesions, 87.5% of EBER-1-positive and 62.5% of EBER-1-negative lesions, were located near the mucosal atrophic border. The background gastric mucosa for EBV-associated gastric carcinomas is rich in atrophic changes. EBV-associated gastric carcinomas are located near the mucosal atrophic border.

Gastric Mucosa↗
PubMed1999

Transforming growth factor-beta isoforms and receptors in endometriotic cysts of the human ovary.

PROBLEM: The present study examined the presence and cellular distribution of transforming growth factor-beta1, 2, and 3 isoforms and their type I and II receptors in endometriotic cysts of the ovary, relative to their presence in normal endometrial tissue. METHOD OF STUDY: Thirteen control samples of normal endometrium in the proliferative phase and 11 ovarian endometriotic cysts were examined by immunohistochemistry for transforming growth factor-beta1, 2, and 3 isoforms and their type I and II receptors. RESULTS: Immunoreactivity for all ligands and receptors was detected in both normal endometrium and endometriotic cysts. Isoform-specific differences in immunostaining were not detected. Expression of all ligands and receptors was significantly increased in epithelial cells of endometriotic cysts compared with those of normal endometrium. On the other hand, stromal cells in normal endometrium and endometriotic cysts were only faintly immunostained. Inflammatory cells infiltrating among endometriotic stromal cells contained the highest immunostaining intensity for all ligands and receptors. We identified nearly all inflammatory cells as macrophages using a specific antibody. CONCLUSIONS: These findings suggest that macrophages in endometriotic tissue are a major source of transforming growth factor-beta, which may be an important regulator of cell proliferation in endometriotic cysts through paracrine and autocrine actions.

Activin Receptors, Type I↗
PubMed1999

A phosphonate-induced gene which promotes Penicillium-mediated bioconversion of cis-propenylphosphonic acid to fosfomycin.

Penicillium decumbens is able to epoxidize cis-propenylphosphonic acid (cPA) to produce the antibiotic fosfomycin [FOM; also referred to as phosphonomycin and (-)-cis-1,2-epoxypropylphosphonic acid], a bioconversion of considerable commercial significance. We sought to improve the efficiency of the process by overexpression of the genes involved. A conventional approach of isolating the presumed epoxidase and its corresponding gene was not possible since cPA epoxidation could not be achieved with protein extracts. As an alternative approach, proteins induced by cPA were detected by two-dimensional gel electrophoresis. The observation that a 31-kDa protein (EpoA) was both cPA induced and overaccumulated in a strain which more efficiently converted cPA suggested that it might take part in the bioconversion. EpoA was purified, its amino acid sequence was partially determined, and the corresponding gene was isolated from cosmid and cDNA libraries with oligonucleotide probes. The DNA sequence for this gene (epoA) contained two introns and an open reading frame encoding a peptide of 277 amino acids having some similarity to oxygenases. When the gene was subcloned into P. decumbens, a fourfold increase in epoxidation activity was achieved. epoA-disruption mutants which were obtained by homologous recombination could not convert cPA to FOM. To investigate the regulation of the epoA promoter, the bialaphos resistance gene (bar, encoding phosphinothricin acetyltransferase) was used to replace the epoA-coding region. In P. decumbens, expression of the bar reporter gene was induced by cPA, FOM, and phosphorous acid but not by phosphoric acid.

Amino Acid Sequence↗
PubMed1999

Determinant in human immunodeficiency virus type 1 for efficient replication under cytokine-induced CD4(+) T-helper 1 (Th1)- and Th2-type conditions.

Cytokines are potent stimuli for CD4(+)-T-cell differentiation. Among them, interleukin-12 (IL-12) and IL-4 induce naive CD4(+) T cells to become T-helper 1 (Th1) or Th2 cells, respectively. In this study we found that macrophage-tropic human immunodeficiency virus type 1 (HIV-1) strains replicated more efficiently in IL-12-induced Th1-type cultures derived from normal CD4(+) T cells than did T-cell-line-tropic (T-tropic) strains. In contrast, T-tropic strains preferentially infected IL-4-induced Th2-type cultures derived from the same donor CD4(+) T cells. Additional studies using chimeric viruses demonstrated that the V3 region of HIV-1 gp120 was the principal determinant for efficiency of replication. Cell fusion analysis showed that cells expressing envelope protein from a T-tropic strain effectively fused with IL-4-induced Th2-type culture cells. Flow cytometric analysis showed that the level of CCR5 expression was higher on IL-12-induced Th1-type culture cells, whereas CXCR4 was highly expressed on IL-4-induced Th2-type culture cells, although a low level of CXCR4 expression was observed on IL-12-induced Th1-type culture cells. These results indicate that HIV-1 isolates exhibit differences in the ability to infect CD4(+)-T-cell subsets such as Th1 or Th2 cells and that this difference may partly correlate with the expression of particular chemokine receptors on these cells. The findings suggest that immunological conditions are one of the factors responsible for inducing selection of HIV-1 strains.

Cell Fusion↗
PubMed1999

Inhibitory mechanism of the CXCR4 antagonist T22 against human immunodeficiency virus type 1 infection.

We recently reported that a cationic peptide, T22 ([Tyr(5,12), Lys(7)]-polyphemusin II), specifically inhibits human immunodeficiency virus type 1 (HIV-1) infection mediated by CXCR4 (T. Murakami et al., J. Exp. Med. 186:1389-1393, 1997). Here we demonstrate that T22 effectively inhibits replication of T-tropic HIV-1, including primary isolates, but not of non-T-tropic strains. By using a panel of chimeric viruses between T- and M-tropic HIV-1 strains, viral determinants for T22 susceptibility were mapped to the V3 loop region of gp120. T22 bound to CXCR4 and interfered with stromal-cell-derived factor-1alpha-CXCR4 interactions in a competitive manner. Blocking of anti-CXCR4 monoclonal antibodies by T22 suggested that the peptide interacts with the N terminus and two of the extracellular loops of CXCR4. Furthermore, the inhibition of cell-cell fusion in cells expressing CXCR4/CXCR2 chimeric receptors suggested that determinants for sensitivity of CXCR4 to T22 include the three extracellular loops of the coreceptor.

Amino Acid Sequence↗
PubMed1999

Decreased amplitude of left ventricular posterior wall motion with notch movement to determine the left posterior septal accessory pathway in Wolff-Parkinson-White syndrome.

OBJECTIVE: To determine preoperatively, by analysing asynchronous left ventricular wall motion, whether to approach through the right ventricle or the left ventricle when carrying out catheter ablation of the accessory pathway in Wolff-Parkinson-White syndrome, especially in patients with the pathway located on the septum. METHODS: 73 patients with manifest Wolff-Parkinson-White syndrome who underwent successful catheter ablation were studied. Location of accessory pathway was classified as right ventricular side: right anterior paraseptum, right anterior, right lateral, right posterior, anterior septum, midseptum, right posterior septum; left ventricular side: left posterior septum, left posterior, left lateral, left anterior. Asynchronous systolic wall motion was analysed by cross sectional echocardiography. RESULTS: Echocardiography showed that the amplitude of left ventricular posterior systolic wall motion was reduced when the pathway was located on the left ventricular side as opposed to the right ventricular side (mean (SD), 11.1 (1.7) v 12.9 (1.1) mm, p < 0.001), especially in patients with left posterior septal accessory pathway (9.7 (0.8) mm). There were no overlapping values between the left posterior septal accessory pathway and the right ventricular side accessory pathway. Posterior wall notch motion was observed in all patients with a left posterior septal accessory pathway (9/9), but not at all in patients with pathways located on the right ventricular side of the septum. In patients with a septal accessory pathway, an ECG algorithm provided poor information (relatively low sensitivity, specificity, and predictive value) for determining whether the subsite faced either the left (left posterior septum) or the right ventricle (anterior septum, midseptum, right posterior septum). CONCLUSIONS: Decreased amplitude of left ventricular posterior wall motion with notch movement is an important finding for accessory pathways located on the left posterior septum. These findings provided clinically useful information for determining whether to approach catheter ablation from the right or the left ventricle.

Adolescent↗