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Biomedical subjects

M Hirata

Publications and source records attributed to M Hirata.

At least 55 records · Page 3Linked to original sources
PubMed2001

Reversible hepatofugal portal flow after liver transplantation using a small-for-size graft from a living donor.

We describe a case of reversible hepatofugal portal flow 1 week after transplantation of a small-for-size liver graft from a living donor. A transient increase in intrahepatic portal vascular resistance was the suspected cause. The portal venous flow normalized after residual collateral channels had been interrupted surgically. The patient was discharged on the 90th postoperative day. Liver transplant clinicians should be aware that hepatofugal flow can occur with small-for-size liver grafts, despite sufficient portal venous flow immediately after transplantation.

Female↗
PubMed2001

Ceramic endoprosthesis for aggressive giant cell tumors near the knee: eight cases followed for more than 10 years.

Eight patients with locally aggressive giant cell tumor were treated with marginal resection and implantation of a ceramic endoprosthesis with a non-hinged knee joint. The patients have been followed-up for between 10 to 16 years. Newly formed bone appeared at the junction between implant and cortex and in 2 cases subsidence of the implant was seen. All the patients had good function of the knee and no revision was needed.

Adult↗
PubMed2001

A vitamin D analog ameliorates glomerular injury on rat glomerulonephritis.

OCT (22-oxa-calcitriol), a vitamin D analog, has been reported to show strong inhibitory effects on mesangial cell proliferation in vitro. In the present study, we report a study of the effect of OCT on anti-thy-1 glomerulonephritis. Both OCT and 1,25(OH)(2)D(3) significantly inhibited mesangial cell proliferation, the degree of glomerulosclerosis, and albuminuria at day 8 compared to the disease control group. The OCT-treated group showed normal calcium levels but the 1,25(OH)(2)D(3)-treated group showed higher levels. The disease control group showed a marked increase of type I and type IV collagens, and alpha-smooth muscle actin (alpha-SMA) compared to the normal group. The treatment of OCT or 1,25(OH)(2)D(3) significantly reduced the expression of these proteins. The mRNA of the glomeruli of anti-thy-1 model expressed significantly higher levels of type I and type IV collagens, and alpha-SMA at day 8 compared to normal rats. Treatment with OCT or 1,25(OH)(2)D(3) inhibited the mRNA expressions of type I and type IV collagens, as well as that of alpha-SMA. These data demonstrate that OCT inhibits mesangial cell proliferation and extracellular matrix expansion with a low calcemic activity. Disease control rats showed significantly increased levels of transforming growth factor-beta1 protein in the glomeruli, but treatment with OCT or 1,25(OH)(2)D(3) markedly reduced this expression. The levels of mRNA in glomeruli were also consistent with these protein levels. Therefore, the suppressive effect of OCT may be mediated by inhibition of transforming growth factor-beta1. The present results suggest that OCT has potential for use in therapeutic strategy for the treatment of glomerulonephritis without inducing hypercalcemia.

Actins↗
PubMed2001

Method for measuring mutagen formation potential (MFP) on chlorination as a new water quality index.

A novel water quality index, the mutagen formation potential (MFP) is proposed for use in evaluation of the quality of drinking water which may contain pollutants capable of forming mutagens when chlorinated under the conditions used in water purification processes. A method for measuring MFP was established as follows. The water sample to be tested is diluted until the TOC reaches 3-4 mg l-1, the pH is adjusted to 7.0 +/- 0.2, sodium hypochlorite is added to obtain conditions where Cl/TOC = 3-4 mg Cl (mg C)-1, and the water sample is left standing for 24 +/- 2 h at room temperature. Thereafter, 21 of the chlorinated water sample at pH 2.0 +/- 0.1 is passed through a Sep-Pak Plus CSP-800 cartridge to adsorb any mutagens formed, and DMSO is applied to the cartridge to desorb the mutagens. Then, a 2 ml sample of the eluate is collected after the DMSO had begun to flow out of the cartridge and evaluated by the Ames Salmonella mutagenicity assay (preincubation method).

Chlorine Compounds↗
PubMed2001

Involvement of the phosphoinositide 3-kinase/protein kinase B signaling pathway in insulin/IGF-I-induced chondrogenesis of the mouse embryonal carcinoma-derived cell line ATDC5.

The embryonal carcinoma-derived cell line, ATDC5, differentiates into chondrocytes in response to insulin/insulin-like growth factor-I (IGF-I) stimulation. In the present study, we examined whether insulin/IGF-I stimulation caused activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) pathway in ATDC5 cells. We also determined whether the insulin-stimulated differentiation of ATDC5 cells into chondrocytes could be mimicked by activation of the PKB pathway alone. ATDC5 cells produced phosphatidylinositol 3,4,5-trisphosphate and the pleckstrin homology domain of PKB was recruited to the plasma membrane in response to insulin stimulation. This was probably a result of activation of PI3K because the PI3K inhibitors, wortmannin and LY294002, inhibited both responses, although the effective concentrations were as high as 10 microM. Insulin stimulation caused the chondrogenic differentiation of ATDC5 cells as assessed by chondrogenic nodule staining with alcian blue. The addition of wortmannin or LY294002, PI3K inhibitors, suppressed the staining, and the suppression was reversible, indicating the effect of the inhibitors is not toxic. Finally, we exogenously expressed a constitutively-activated from of PKB (myristoylated PKB, myr-PKB) in ATDC5 cells, and found the chondrogenic differentiation of ATDC5 cells to form nodules occurred in the absence of insulin stimulation. The kinase-negative mutant of myr-PKB did not caused differentiation, indicating that kinase activity is required. These results support the hypothesis that the PI3K/PKB signaling pathway is involved in the chondrogenic differentiation of ATDC5 cells in response to insulin/IGF-I stimulation. This is the first report that demonstrates the involvement of phosphoinositide signaling in the induction of chondrogenesis from undifferentiated cells.

Androstadienes↗
PubMed2001

Revised structures for senegalensin and euchrenone b(10).

Two prenylated isoflavones (1 and 2) with a hydroxyisopropyldihydrofuran moiety have been isolated from the wood of Erythrina suberosa var. glabrescence. The structure of compound 1 was in agreement with that of the previously reported senegalensin, isolated from the stem bark of Erythrina senegalensis. The structure of senegalensin was revised from structure 2 to structure 1 by spectroscopic means. Compound 2, the regioisomer of 1, was confirmed as euchrenone b(10) by comparison with the spectral data of the reported euchrenone b(10), isolated from the roots of Euchresta horsfieldii. The structure of 2 was established by 2D NMR spectroscopic analysis and by the X-ray crystallographic analysis of its p-bromobenzoyl derivative (2b).

Chromatography, Gel↗
PubMed2001

Long-term production of erythropoietin after electroporation-mediated transfer of plasmid DNA into the muscles of normal and uremic rats.

The anemia associated with chronic renal failure is one of the best target diseases for erythropoietin (Epo) gene transfer. We previously reported a short-term (1 month) study of continuous rat Epo delivery by muscle-targeted gene transfer of plasmid DNA expressing rat Epo (pCAGGS-Epo) using in vivo electroporation in normal rats. Here, we performed a long-term pharmacokinetic study of continuous Epo delivery by this method in normal rats and uremic five-sixths nephrectomized rats. In normal rats, Epo gene expression and sufficient erythropoiesis occurred with Epo gene transfer in a dose-dependent manner, and persisted for at least 11 weeks. Repeated administration of the plasmid DNA effectively produced erythropoiesis. Similar erythropoiesis was observed in the uremic rats, and persisted for more than 15 weeks. Both normal and uremic rats showed a significant decrease in platelet count. Moreover, the uremic rats showed Epo-induced hypertension, which is the major side-effect of recombinant human Epo. These results demonstrate that muscle-targeted pCAGGS-Epo transfer by in vivo electroporation is a useful procedure for the long-term continuous delivery of Epo in both normal and uremic rats.

Animals↗
PubMed2001

Noninvasive diagnosis of the degree of hepatic fibrosis using ultrasonography in patients with chronic liver disease due to hepatitis C virus.

BACKGROUND: Chronic liver disease is characterized by progressive hepatic fibrosis and changes in hepatic haemodynamics. This study has addressed the possibility of a noninvasive diagnosis of the degree of hepatic fibrosis by evaluating the velocity of blood in the hepatic vasculature. Materials and methods The maximum velocity of blood at the portal vein and hepatic artery was measured in 80 patients with chronic liver diseases (19 with liver cirrhosis; 61 with chronic hepatitis) and in 20 normal volunteers by Doppler ultrasonography. The arterio-portal ratio (A/P ratio) was calculated by dividing the maximum velocity of blood (Vmax) in the hepatic artery with the Vmax in the portal vein. Multivariate analysis was used to disclose the independent predictors of the degree of hepatic fibrosis. RESULTS: The levels of A/P ratio were significantly higher in patients with liver cirrhosis (LC) compared to those with chronic hepatitis (CH) and normal controls. Probit analysis revealed that the value of A/P ratio at which CH becomes LC was A/P >or= 3.5. The levels of A/P ratio were also significantly higher in patients with severe fibrosis compared with mild (P < 0.0001) and moderate (P < 0.0001) fibrosis. Multivariate analysis disclosed right A/P ratio (P = 0.0001), left A/P ratio (P = 0.013), and platelet counts (P = 0.0172), as the only independent predictors of the degree of hepatic fibrosis. CONCLUSIONS: A/P ratio may be used for the noninvasive diagnosis of the degree of hepatic fibrosis in patients with chronic liver diseases.

Adult↗
PubMed2001

Contribution of conformational stability of hen lysozyme to induction of type 2 T-helper immune responses.

It is important to identify characteristics that confer on proteins the potential to induce allergenic sensitization and allergenic disease. Protein allergens carry T-cell epitopes that are capable of inducing a type 2 T helper (Th2) cell response. There is limited information regarding factors that govern the allergenicity of proteins. We previously reported that a decrease in the conformational stability of hen-egg lysozyme (HEL) enhanced its capacity to activate HEL-specific T cells owing to the increased susceptibility to intracellular antigen processing. To determine whether the conformational stability of HEL makes for a critical contribution to allergenic sensitization in vivo, we immunized BALB/c mice with HEL derivatives of different conformational stability, but which retained a similar three-dimensional structure. The magnitude of in vivo T-cell responses, evaluated by ex vivo proliferative responses of lymph node T cells from mice primed with various HEL derivatives, was inversely correlated with conformational stability, as was interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) production by splenic T cells in response to HEL. Immunization of the least stable derivative led to a potent IL-4 response and to immunoglobulin E (IgE) antibody production. We propose that the intrinsic allergenicity of proteins can be determined by the degree of conformational stability.

Animals↗
PubMed2001

Schistosoma japonicum egg granuloma formation in the interleukin-4 or interferon-gamma deficient host.

The roles of interleukin (IL)-4 and interferon (IFN)-gamma in Schistosoma japonicum egg granuloma formation were investigated in cercariae-infected (infection model) or after implantation of laid parasite eggs (egg implantation model) in cytokine deficient mice. Two weeks after hepatic egg-implantation, a markedly decreased mononuclear cell infiltration and lack of multinuclear cell formation were characteristic features in IL-4 deficient mice. By 4 weeks (late stage), the cellular reactions around the eggs were negligible in the deficient mice. Compared to the controls, there was a drastic reduction in the production of the Th2 cytokines, IL-4, IL-5 and IL-13. MCP-1 levels were also significantly lowered. In mice experimentally infected with cercariae, granuloma cellularity in both the wild-type and IL-4 deficient mice at 45 days and 10 weeks postinfection was analogous to the egg implantation model at 2 and 4 weeks. Overall, the effects of IFN-gamma deficiency on granuloma induction differed markedly from the IL-4 results. Two weeks after egg implantation, IFN-gamma deficient mice showed suppressed neutrophil response and hepatic necrosis with confluent mononuclear cell infiltration along the outer layer of granulomas. By 4 weeks, there was a decrease in cell infiltration, fibrosis and MCP-1 production while IL-10 production increased. While these early characteristic features for IFN-gamma deficiency were common to both the egg implantation (at 2 and 4 weeks) and cercariae infection model (at 45 days), there was a surprising difference, i.e. marked fibrosis was found in the late stages (at 10 weeks postinfection) of cercariae-infected mice, but not in parasite egg implanted mice. Furthermore, while IL-13 levels were unchanged, both MCP-1 and IL-4 production were significantly lower at 10 weeks in comparison with wild-type. The present study clearly demonstrates the importance of both Th1 and Th2 cytokine responses in S. japonicum egg-induced granuloma formation.

Animals↗
PubMed2001

Effect of nitric oxide synthase inhibition on Schistosoma japonicum egg-induced granuloma formation in the mouse liver.

Nitric oxide (NO) plays diverse roles in a variety of pathological processes. We investigated the role of NO in Schistosoma japonicum egg-induced granuloma formation in a mouse hepatic model. Immunohistological analysis revealed that there is the most intense and extensive inducible nitric oxide (iNOS) expression 2 weeks after egg implantation, and thereafter it decreased considerably with time. Treatment with nitric oxide synthase inhibitors, NIL (L-N6- (iminoethyl)-lysine) or N(omega)-nitro-L-arginine methyl ester (L-NAME), resulted in two different types of unusual granulomas at 2 weeks. One type showed suppressed fibrosis, while another showed foreign body-type multinuclear cell formation which frequently appeared particularly when 50 microg/ml NIL was given. At 3 weeks following treatment, fibrotic granulomas with scanty peripheral cellularity was obvious. However, there were no apparent changes after this period (at 4 weeks). Cytokine analysis in NIL-treated mice showed a significant increase of IL-4 and IL-13 production at 2 weeks. These findings indicated that nitric oxide contributes to granuloma development during the early stages, probably through the regulation of Th2 cytokine production.

Animals↗
PubMed2001

Visualization of oxygen-concentration-dependent production of nitric oxide in rat hippocampal slices during aglycemia.

Our novel fluorescent indicator, DAF-FM, permits the bioimaging of nitric oxide (NO) in living cells with high resolution in space and time, with stable intensity above pH 5.8. A membrane-permeable derivative, DAF-FM DA, was applied to imaging of NO generated in rat hippocampal slices by exposure to an aglycemic medium. NO production was observed mainly in the CA1 area, and was dependent on the concentration of O(2). During exposure to an anoxic-aglycemic medium, NO was hardly produced, while marked elevation of intracellular Ca(2+) was observed. Production of NO increased sharply as soon as the perfusate was changed to the normal medium. These results suggest that NO synthase is activated after reperfusion rather than during ischemia.

Animals↗
PubMed2001

Two-generation reproductive toxicity study of tributyltin chloride in male rats.

A 2-generation reproductive toxicity study of tributyltin chloride (TBTCl) was conducted in male rats using dietary concentrations of 5, 25, and 125 ppm TBTCl to evaluate its effect on sexual development and the reproductive system. F1 males were killed on postnatal day 119 and F2 males were killed on postnatal day 91. TBTCl affected the male reproductive system of rats. The weights of the testis and epididymis were decreased and homogenization-resistant spermatid and sperm count were reduced mainly in the 125 ppm TBTCl group. Histopathologic changes were also observed in the testis of this group and included vacuolization of the seminiferous epithelium, spermatid retention, and delayed spermiation. However, the changes were minimal in nature. The weight of the ventral prostate was decreased to 84% of the control value in the 125 ppm group in the F1 generation and decreased to 84 and 69% of the control value in the 25 ppm and 125 ppm TBTCl groups, respectively, in the F2 generation. The serum 17beta-estradiol concentration was also decreased to 55% of the control value in the 125 ppm group in the F1 generation and decreased to 78 and 57% of the control value in the 25 ppm and 125 ppm TBTCl groups, respectively, in the F2 generation. However, the serum concentrations of luteinizing hormone (LH) and testosterone were not decreased in these groups. These changes corresponded with those caused by aromatase inhibition and therefore TBTCl might be a weak aromatase inhibitor in male rats.

Animals↗
PubMed2001

Inositol-1,4,5-trisphosphate-binding proteins controlling the phototransduction cascade of invertebrate visual cells.

The main phototransduction cascade in invertebrate visual cells involves the turnover of phosphatidylinositol, an important biochemical mechanism common to many signal-transduction systems. Light-activated rhodopsin stimulates guanine nucleotide exchange on the Gq class of G-protein, which activates phospholipase C to hydrolyze phosphatidylinositol 4,5-bisphosphate to inositol-1,4,5-trisphosphate and diacylglycerol. Subsequently, inositol-1,4,5-trisphosphate-binding proteins continue the signal cascade. Here, we report on the first inositol-1,4,5-trisphosphate-binding proteins demonstrated in an invertebrate visual system with our investigation of the photosensitive rhabdoms of squid. We screened the ability of proteins to interact with inositol-1,4,5-trisphosphate by affinity column chromatography with an inositol-1,4,5-trisphosphate analogue. We detected an inositol-1,4,5-trisphosphate-binding affinity in phospholipase C, receptor kinase and five other proteins in the cytosolic fraction and, surprisingly, rhodopsin in the membrane fraction. A binding assay with (3)H-labelled inositol-1,4,5-trisphosphate demonstrated the inositol-1,4,5-trisphosphate affinity of each of the purified proteins. Since rhodopsin, receptor kinase and phospholipase C are involved upstream of phosphatidylinositol turnover in the signal cascade, our result suggests that phosphatidylinositol turnover is important in feedback pathways in the signalling system.

Animals↗
PubMed2001

Japanese family with glucocorticoid-remediable aldosteronism diagnosed by long-polymerase chain reaction.

We report a Japanese family with glucocorticoid-remediable aldosteronism (GRA) in whom gene abnormality was identified by the long-polymerase chain reaction (PCR) method. The proband was a 21-year-old female incidentally found to have high blood pressure (173/107 mmHg). Laboratory tests showed hypokalemia (3.7 mmol/l), and high plasma aldosterone concentration (PAC, 234 pg/ml) with suppressed plasma renin activity (PRA, <0.1 ng/ml/h). The circadian rhythm pattern and the results of a rapid adrenocorticotrophic hormone (ACTH) test indicated ACTH-dependent changes in PAC. Imaging studies showed no adrenal mass on either side. A dexamethasone (Dexa) suppression test (1.0 mg/day orally for 7 days) showed a marked decrease of PAC 2 days after administration, and this decreased level was maintained throughout Dexa administration. High blood pressure and hypokalemia also improved during Dexa treatment. The proband's younger sister was 19 years old and had hypertension, PAC of 231 pg/ml, and PRA <0.1 ng/ml/h. The mother was 53 years old and had hypertension, PAC of 98.5 pg/ml, and PRA <0.1 ng/ml/h. The proband's elder sister was a 22-year-old normotensive with PAC of 110 pg/ml and PRA of 0.1 ng/ml. Long-PCR was performed for detection of the chimeric gene associated with GRA, using DNA samples from all four cases and two normal control subjects. Although the aldosterone synthase gene was expressed among all DNA samples, the chimeric gene was detected only in the proband, her younger sister and her mother. Our clinical data and genetic investigation confirmed the presence of GRA in this Japanese family.

Adult↗