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Biomedical subjects

R Horiuchi

Publications and source records attributed to R Horiuchi.

At least 19 recordsLinked to original sources
PubMed2005

Changes in apparent systemic clearance of propofol during transplantation of living related donor liver.

BACKGROUND: Propofol is used during living-related donor liver transplantation because its metabolism is not greatly affected by liver failure. However, the pharmacokinetics of propofol during liver transplantation have not been fully defined. The purpose of this study was to evaluate the apparent systemic clearance of propofol during the dissection, anhepatic and reperfusion phases of living-related donor liver transplantation, and to estimate the role of the small intestine and lung as extrahepatic sites for propofol disposition. METHODS: Ten patients scheduled for living-related donor liver transplantation were enrolled in the study. Anaesthesia was induced with vecuronium 0.1 mg kg(-1) and propofol 2 mg kg(-1), and then maintained by 60% air, 0.5-1.5% isoflurane in oxygen and a constant infusion of propofol at 2 mg kg(-1) h(-1). Apparent systemic clearance during the dissection, anhepatic and reperfusion phases was calculated from the pseudo-steady-state concentration for each phase. Disposition in the small intestine was determined by measuring arteriovenous blood concentration in 10 liver transplantation donors. Pulmonary disposition was determined by measuring the arteriovenous blood concentration in 10 recipients during the anhepatic phase. The data are expressed as mean (sd). RESULTS: Apparent systemic clearances in the dissection, anhepatic and reperfusion phases were 1.89 (sd 0.48) litre min(-1), 1.08 (0.25) litre min(-1) and 1.53 (0.51) litre min(-1), respectively. The concentration of propofol in the portal vein was lower than in the radial artery. The intestinal extraction ratio calculated from the concentration in the radial artery and portal vein was 0.24 (0.12). There were no significant differences in propofol concentrations between the radial and pulmonary arteries. CONCLUSION: Apparent systemic clearance was decreased by approximately 42 (10)% during the anhepatic phase compared with the dissection phase. After reperfusion, liver allografts rapidly began to metabolize propofol. The small intestine also participates in the metabolism of propofol.

Adult↗
PubMed2005

Suppression of Hall-term effects by gyroviscous cancellation in steady collisionless magnetic reconnection.

The formation of an ion-dissipation region, in which motions of electrons and ions decouple and fast magnetic reconnection occurs, is demonstrated during a steady state of two-dimensional collisionless driven reconnection by means of full-particle simulations. The Hall-term effect is suppressed due to the gyroviscous cancellation at scales between the ion-skin depth and ion-meandering-orbit scale, and thus ions are tied to the magnetic field. The ion frozen-in constraint is strongly broken by nongyrotropic pressure tensor effects due to ion-meandering motion, and thus the ion-dissipation region is formed at scales below the ion-meandering-orbit scale. A similar process is observed in the formation of an electron-dissipation region. These two dissipation regions are clearly observed in an out-of-plane current density profile.

Journal Article↗
PubMed2004

Protective effects of nef-deleted SHIV or that having IFN-gamma against disease induced with a pathogenic virus early after vaccination.

To clarify the involvement of primitive non-specific immune responses in the protective effects of a live, attenuated virus, each two rhesus macaques were intravenously immunized with an attenuated chimeric simian and human immunodeficiency virus (SHIV) in which the nef gene was deleted (SHIV-NI) or a SHIV having human IFN-gamma inserted into the deleted nef region (SHIV IFN-gamma). These immunized monkeys were intravenously challenged with a heterologous pathogenic SHIV (SHIV-C2/1) at four weeks post immunization (wpi). After vaccination, one of each SHIV-NI- or SHIV IFN-gamma-immunized monkeys showed a low level of SIV Gag-specific lymphocyte proliferative response but did not have neutralizing antibodies to both the parental and challenge viruses. After the challenge, the plasma viral RNA loads of the challenge virus were suppressed in all the immunized monkeys and the severe CD4+ T cell loss observed in the unimmunized monkeys was not found. Thus, both SHIV IFN-gamma and SHIV-NI infections could prevent from disease progression by a pathogenic virus early after immunization, suggesting that primitive non-specific immune response elicited by attenuated virus infection, in addition to highly acquired virus-specific immunity, contributes to the protective effect against a pathogenic virus.

AIDS Vaccines↗
PubMed2001

Ion dynamics in steady collisionless driven reconnection.

Steady collisionless driven reconnection in an open system is investigated by means of a new two-dimensional full-particle simulation. The reconnection rate is controlled by an external driving electric field. Ion-meandering motion plays an important role in ion dynamics which controls the spatial structures of ion quantities. Although the electric current is predominantly carried by electrons, the current layer has the half-width of the ion-meandering orbit scale because the density profile is controlled by massive-ion motion. Thus, the global dynamic behavior of reconnection is dominantly controlled by ion dynamics. An electrostatic field generated through the finite-Larmor-radius effect leads to electron acceleration in the equilibrium current direction in the ion-dissipation region and ion heating by intensifying meandering motion. Our results are in agreement with the recent experimental results of Yamada et al. [Phys. Plasmas 7, 1781 (2000)] and of Hus et al. [Phys. Rev. Lett. 84, 3859 (2000)].

Journal Article↗
PubMed2001

Acute cholestatic hepatitis caused by a probable allergic reaction to paracetamol in an adolescent.

We reported on an adolescent who suffered from cholestatic hepatitis after taking a low dose of paracetamol. It was suspected that the condition was brought about by an allergic reaction to paracetamol. Paracetamol is one of the representative intrinsic hepatotoxic drugs. There have been only a few reports on liver damage due to an allergic reaction to paracetamol. There is a need to call attention to this particular reaction.

Acetaminophen↗
PubMed1999

Xenopus cytosolic thyroid hormone-binding protein (xCTBP) is aldehyde dehydrogenase catalyzing the formation of retinoic acid.

Amino acid sequencing of an internal peptide fragment derived from purified Xenopus cytosolic thyroid hormone-binding protein (xCTBP) demonstrates high similarity to the corresponding sequence of mammalian aldehyde dehydrogenase 1 (ALDH1) (Yamauchi, K., and Tata, J. R. (1994) Eur. J. Biochem. 225, 1105-1112). Here we show that xCTBP was co-purified with ALDH and 3,3',5-triiodo-L-thyronine (T3) binding activities. By photoaffinity labeling with [125I]T3, a T3-binding site in the xCTBP was estimated to reside in amino acid residues 93-114, which is distinct from the active site of the enzyme but present in the NAD+ binding domain. The amino acid sequences deduced from the two isolated xALDH1 cDNAs (xALDH1-I and xALDH1-II) were 94.6% identical to each other and very similar to those of mammalian ALDH1 enzymes. The two recombinant xALDH1 proteins exhibit both T3 binding activity and ALDH activity converting retinal to retinoic acid (RA), which are similar to those of xCTBP. The mRNAs were present abundantly in kidney and intestine of adult female Xenopus. Interestingly, their T3 binding activities were inhibited by NAD+ and NADH but not by NADP+ and NADPH, whereas NAD+ was required for their ALDH activities. Our results demonstrate that xCTBP is identical to ALDH1 and suggest that this protein might modulate RA synthesis and intracellular level of free T3.

Aldehyde Dehydrogenase↗
PubMed1998

Alterations in the enzyme activity and protein contents of protein disulfide isomerase in rat tissues during fasting and refeeding.

Protein disulfide isomerase (PDI) is an enzyme that participates in the formation of disulfide bonds. It is also known to be the subunits of some enzymes and the membrane-associated thyroid hormone-binding protein. In this study, we measured the quantitative distribution of PDI protein in rat tissues and examined the relationship between protein level and enzyme activity in PDI during fasting and refeeding. Western blotting with specific anti-PDI antiserum detected the PDI protein band of 55 kd. Among several tissues, liver contained the largest amount of PDI protein, followed by kidney and fat, in which one-third to one-fourth of the hepatic PDI protein existed. The PDI protein band was also detected in heart and muscle. Fasting for 3 days decreased PDI protein levels in rat liver by 40%; control levels were recovered after 3 days of refeeding. The same change was observed in kidney. PDI activity, measured by the scrambled ribonuclease method, did not show the parallel alteration to PDI protein level in liver and kidney. Isomerase activity decreased to 50% of control values during fasting, but did not recover by refeeding. Thyroidal status did not affect either PDI protein level or isomerase activity. These findings show that fasting and refeeding affect PDI protein and enzyme activity, and that PDI protein level does not always reflect PDI activity.

Animals↗
PubMed1997

Rat hepatoma Reuber H-35 cells produce factors that promote the hatching of mouse embryos cultured in vitro.

The effects of coculture and conditioned medium of rat hepatoma Reuber H-35 cells on the subsequent in vitro development and hatching of mouse 2-cell embryos were examined. The hatching of embryos obtained from CD-1 mice was accelerated by coculture with Reuber H-35 cells in the presence of 3 mg/ml BSA. The promoting effect on complete hatching from zona pellucida was evident even in cell-conditioned medium containing 60 micrograms/ml BSA. In the presence of 60 micrograms/ml BSA, more than 20% of embryos completely hatched, whereas none hatched in the control culture. The promoting activity was also found in both the M(r) < 10,000 and the M(r) > 10,000 subfractions of the conditioned medium separated by ultrafiltration. The cell number per blastocyst was increased to 1.1- to 1.3 times the control by culturing embryos from the 2-cell stage with the conditioned medium or its subfractions. The effective target of promoting factors for complete hatching was after the morula stage, and blastocysts hatched completely even when incubated in conditioned medium for 6 h. Inhibitors of DNA polymerase alpha, protein synthesis, and protein kinase partially reduced (40-90% inhibition) the promoting effect of the conditioned medium. On the other hand, protease inhibitors showed no effect. In a caseinolytic assay, protease activity was undetectable in the conditioned medium. Incubating the 125I-labeled proteins derived from the M(r) > 10,000 fraction with blastocysts revealed that at least 9 proteins with apparent molecular masses of 76, 60, 49, 38, 34, 31, 24, 22, and 18 kDa specifically bound to or accumulated in the embryos. Moreover, reverse-transcriptase polymerase chain reaction showed that Reuber H-35 cells expressed mRNAs for epidermal growth factor, transforming growth factors alpha and beta 1, and stem cell factor. These results indicated that embryonic development and the process of zona hatching was accelerated by factors synthesized by Reuber H-35 cells. This and other studies demonstrated that Reuber H-35 cells exert positive (later than 2-cell stage) and negative (at 2-cell stage) effects upon the development of mouse embryos at different embryonic stages. These factors will serve as valuable tools to clarify the proliferating and differentiating mechanisms of the preimplantation embryo.

Animals↗
PubMed1996

Rat hepatoma reuber H-35 cells produce a 2-cell stage-specific inhibitor of the cleavage of mouse embryos.

We purified an embryonic stage-specific inhibitor produced by rat hepatoma Reuber H-35 cells against cleaving mouse 2-cell embryos and defined its biological properties. Zygotes obtained from CD-1 mice (a strain that shows a 2-cell block in vitro) or C57BL/6 and B6C3F1 mice (strains that do not) were cultured in media with and without 50 microM EDTA, respectively. The development of the zygotes from all strains was arrested at the 2-cell stage when zygotes were cocultured with Reuber H-35 cells. However, the embryos from C57BL/6 and B6C3F1 were less sensitive than those from CD-1 against the inhibitory effects of development. This inhibitory effect was also evident in medium conditioned with the Reuber H-35 cells. The factor from the conditioned medium was separated into its < 10 000 M(r) fraction by ultrafiltration and was further purified in fraction B-25 as a single peak by reverse-phase column chromatography. An incubation as short as 3-h during the late 2-cell stage (G2 phase) with fraction B-25 suppressed cleavage in 61.5% of the CD-1 embryos (30.3% in control culture). Although the inhibitory effect was reversible, embryos that cleaved again either degenerated or were retarded at various stages in their subsequent development. Additionally, a long-term incubation of developing zygotes with the inhibitory factor caused a significant reduction in [3H]thymidine (TdR) incorporation into the DNA of CD-1 2-cell embryos as well as developmental arrest at the interphase of the 2-cell stage. These results indicated that this factor will serve as a valuable tool with which to clarify the proliferating mechanism of the preimplantation embryo.

Animals↗
PubMed1995

Sialyllactose-mediated cell interaction during granulosa cell differentiation. Identification of its binding proteins.

The present study was designed to prove the carbohydrate-binding proteins interacting with cell surface sialyllactosylceramide (GM3, NeuAc alpha 2-->3Gal beta 1-->4Glc beta 1-->1'Cer), which is highly expressed during differentiation of rat ovarian granulosa cells. As a specific ligand for the sialyllactose (SL)-binding proteins on granulosa cells, we used a radioiodinated multivalent SL-linked albumin (Alb-(SL)17). The specific association of the ligand to the putative proteins on the intact cells was competitively inhibited by GM3 more effectively than other gangliosides, sialyllactotetraosylceramide, sialylneolactotetraosylceramide, and several glycoproteins with N-linked oligosaccharides. However, the proteins had no specificity for the side chain (N-acetyl or N-glycolyl forms) of sialic acid in GM3. Scatchard analysis of Alb-(SL)17 binding showed high (Kd = 6.4 x 10(-10)M) and low (Kd = 3.1 x 10(-8)M) affinity population of binding sites. By direct binding of 125I-Alb-(SL)17 to SL-binding proteins on Western blots, the putative proteins with molecular masses of 35, 18, and 14 kDa were detected. The interaction of the multivalent derivative with these binding proteins was differently modulated by Ca2+ and Mn2+. The SL-binding proteins occurred in immature granulosa cells and progressively decreased during differentiation, whereas their endogenous ligand GM3 increased. These results indicate that relatively low molecular weight SL-binding proteins exist on the surface of immature granulosa cells and that they may serve as receptor sites for newly synthesized GM3 during differentiation.

Animals↗
PubMed1995

Actions of 3,5,3'-tri-iodothyronine on the synthesis and secretion of major plasma proteins by a human hepatoblastoma cell line (Hep G2).

We have elucidated the action of tri-iodothyronine (T3) on the synthesis and secretion of seven major plasma proteins in a human hepatoblastoma cell line, Hep G2, and established an in vitro experimental model of human liver cells for the study of the mechanism of the action of thyroid hormone. Hep G2 cells cultured in serum-free medium were treated with various concentrations of T3. During the first 24 h of T3 treatment, accumulation of alpha-fetoprotein in the medium was decreased in a dose-dependent manner (10(-11)-10(-8) M), and the inhibitory effect was enhanced during the second 24 h of T3 treatment. On the other hand, alpha 1-antitrypsin accumulation in the medium during the second 24 h of hormone treatment was decreased by T3 (10(-9)-10(-8) M), although no change in accumulation was observed during the first 24 h of T3 treatment. The newly synthesized [35S]Met-labelled alpha 1-acid glycoprotein was increased by T3 and reached 3.4-fold within 37 h of 10(-8) M T3 treatment. The stimulatory effect increased time-dependently (4.6-fold after 61 h). In contrast, the synthesis of alpha-fetoprotein was reduced to half of that of the control after T3 treatment for 37 h. Although the content of newly synthesized [35S]alpha 1-antitrypsin was not affected by 10(-8) M T3 treatment during 3 days of hormone treatment, the accumulation of alpha 1-antitrypsin in the medium decreased to 87%; in contrast, total cellular newly synthesized alpha 1-antitrypsin increased to 105-130% of that of the control.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Proteins↗
PubMed1995

A novel action of epidermal growth factor in rat granulosa cells: its potentiation of gonadotrophin action.

It is well known that epidermal growth factor (EGF) induces down-regulation of LH receptors and desensitization to gonadotrophin stimulation in gonadal cells, including granulosa cells. In a previous study we showed that EGF receptor levels in rat granulosa cells were increased up to fourfold after 96 h of culture with human GH in the presence of FSH, and the present study has evaluated the action of EGF on these cells. The induced EGF receptors were identical in size to the pre-existing receptors as assessed by affinity labelling with 125I-EGF. After 48 h in culture, various amounts of EGF (0.5-10 ng) were added and the cells were cultured for a further 48 h. The addition of EGF caused down-regulation of LH receptors in cells expressing high levels of EGF receptors. However, this down-regulation was less than that in control cells. After the cells were washed, cAMP synthesis in response to human chorionic gonadotrophin (hCG) increased by two to three times the control value and this increase was closely correlated with an increase in EGF receptor content. However, stimulation with cholera toxin or forskolin showed no such augmentation, indicating that it may not be due to quantitative alterations in G proteins and their effector systems. Induction of EGF potentiation required long-term exposure to EGF, for at least more than 24 h. In addition, progesterone synthesis was sensitive to stimulation with lower doses of hCG. These findings indicate that the activation of hGH-induced EGF receptors may potentiate gonadotrophin action in granulosa cells.

Animals↗
PubMed1994

Production of human protein disulfide isomerase by Bacillus brevis.

Human protein disulfide isomerase (PDI; EC 5.3.4.1) was expressed and secreted into the culture medium using Bacillus brevis as host and pNU200 which codes the promoter and signal sequence of major cell wall protein of B. brevis as vector. The accumulation of recombinant human PDI (rhPDI) reached about 5 mg l-1 in the late exponential phase of the bacterial growth. The purified rhPDI was found to be exactly processed at the carboxyl terminus of the signal sequence. It was as active as natural PDI derived from human placenta as determined by its ability to reactivate scrambled ribonuclease that was a fully oxidized mixture containing randomly formed disulfide bonds. The activity was significantly accelerated in the presence of dithiothreitol or a mixture of reduced and oxidized glutathione. These indicate that the characteristics of rhPDI are similar to those reported for mammalian PDI and that it can be used for refolding inactive proteins having incorrect disulfide bonds.

Amino Acid Sequence↗
PubMed1994

Granulosa cell luteinizing hormone receptor expression is modulated by ganglioside-specific ligands.

The ganglioside GM1 (Gal beta 1-->3GalNAc beta 1-->4[NeuAc alpha 2-->3] Gal beta 1-->4Glc beta 1-->1Cer) was synthesized during granulosa cell development in vitro, and the effect of the interaction between cell-surface GM1 and its ligands on the luteinizing hormone (LH) receptor expression was investigated. GM1 synthesis, demonstrated by metabolic labeling of glycosphingolipids with [3H]galactose and binding studies using the 125I-B-subunit of cholera toxin, a specific ligand for GM1, was increased in follicle-stimulating hormone (FSH)-treated granulosa cells. When granulosa cells were cultured for 72 h in a medium containing the B-subunit of cholera toxin, FSH-induced LH-receptor contents determined by measuring the binding of 125I-deglycosylated human chorionic gonadotropin to intact cells, was augmented. The stimulatory effect of the B-subunit was dependent on the FSH concentration and culture duration. The augmentation was observed after culture for 48 h, and marked increases were evident after 72 h, which coincided with an increase of the 125I-B-subunit binding capacity. Scatchard analysis of the LH-receptor binding indicated that treatment with the B-subunit increased the number of LH-binding sites (6580 sites/cell after treatment with 20 ng/ml FSH; 11,290 sites/cell after FSH plus 100 ng/ml B-subunit), but did not alter the binding affinity. A specific antibody against GM1 mimicked the stimulatory effect of the B-subunit. The augmentation was not accompanied by granulosa cell proliferation. These findings suggest that binding of exogenous or possible endogenous ligands to cell-surface GM1 produces signals and modulates the cellular behavior during granulosa cell development.

Animals↗
PubMed1994

Basic fibroblast growth factor induces luteinizing hormone receptor expression in the presence of insulin-like growth factor-I in ovarian granulosa cells.

Effect of basic fibroblast growth factor (bFGF) on the expression of receptors for luteinizing hormone (LH), a marker of differentiation, was studied using estrogen-primed rat ovarian granulosa cells in primary culture. bFGF had no effect by itself but dose-dependently induced expression of functional LH receptors in the presence of insulin-like growth factor-I (IGF-I). The effect of a combination of bFGF and IGF-I was delayed in onset and the magnitude of the response was smaller when compared to the action of follicle-stimulating hormone (FSH). Scatchard analysis revealed that dissociation constant (Kd) and number of LH receptors induced by bFGF and IGF-I were 0.47 nM and 6.48 fmol/10(6) cells, respectively. Unlike FSH, bFGF plus IGF-I did not cause an immediate increase in cAMP release, however, considerable amount of cAMP release was observed in cells incubated for 72 h with bFGF plus IGF-I. Indomethacin, an inhibitor of cyclooxygenase, attenuated both LH receptor expression and cAMP release induced by bFGF plus IGF-I but had little effect on the action of FSH. Finally, a combination of bFGF and IGF-I increased production of prostaglandin E2 in granulosa cells. These results indicate that bFGF is capable of inducing LH receptor in the presence of IGF-I by a mechanism involving production of prostaglandin E2.

Animals↗