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Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 991 records · Page 55Linked to original sources
PubMed1992

Tauro-beta-muricholate preserves choleresis and prevents taurocholate-induced cholestasis in colchicine-treated rat liver.

In recent clinical and animal experimental studies, ursodeoxycholic acid (UDCA) has been noted to have marked choleretic and cytoprotective actions. To define the mechanism and determine whether such favorable influence is specific to UDCA, the choleretic action of beta-muricholic acid (beta-MCA), which has a similar chemical structure, was studied using an isolated rat-liver-perfusion system. As a result, beta-MCA and taurine-conjugated beta-MCA (T beta-MCA) stimulated bile flow accompanied by elevation of bile acid output and phospholipid output, and beta-MCA caused an elevation in biliary HCO3- concentration in normal rat livers. After colchicine treatment, taurocholic acid (TCA) administration was associated with marked cholestasis while both beta-MCA and T beta-MCA still increased bile flow under the same conditions. Furthermore, simultaneous administration of beta-MCA or, more markedly, T beta-MCA reversed the effects of TCA alone in colchicine-treated rat liver; significant preventive effects against the cholestasis could be shown. These data suggest that beta-MCA and especially T beta-MCA can support choleresis even under conditions of colchicine-dependent microtubule dysfunction. The effects of T beta-MCA on organelle lipids and their intracellular transport may differ from those of TCA, presumably because of the anticholestatic and cytoprotective effects of T beta-MCA.

Animals↗
PubMed1992

Agonist- and subunit-dependent potentiation of glutamate receptors by a nootropic drug aniracetam.

GluR1 and GluR2 cDNAs encoding non-NMDA subtypes of glutamate receptor were isolated from a rat brain cDNA library by Boulter et al. (Science, 249 (1990) 1033-1037). Functional receptors activated by kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and glutamate were expressed in Xenopus oocytes injected with GluR1, GluR2 or a mixture of GluR1 and GluR2 RNAs. In GluR1-expressed oocytes, 1 mM aniracetam potentiated AMPA-induced currents by 99 +/- 10% (mean +/- S.E.M., n = 5) and glutamate-induced currents by 140 +/- 8% (n = 4), but little affected kainate-induced currents. Aniracetam was effective from a concentration of 0.1 mM, and it exhibited more conspicuous effects with the increase of the dose. In oocytes injected with GluR1 plus GluR2 RNAs, aniracetam more markedly potentiated current responses to AMPA and glutamate than those in oocytes injected with GluR1 RNA alone. For example, 1 mM aniracetam potentiated AMPA-induced currents by 396 +/- 76% (n = 4) and glutamate-induced currents by 970 +/- 65% (n = 5) in oocytes injected with 10% GluR1 and 90% GluR2 RNAs. In these oocytes, however, the potentiation of kainate-induced currents by 1 mM aniracetam was only 8 +/- 5% (n = 4). Thus, we conclude that the potentiation of the AMPA/kainate receptor by aniracetam depends on both species of agonists and subunit composition of the receptor.

Animals↗
PubMed1992

Deoxyspergualin, a novel immunosuppressant, markedly inhibits human mixed lymphocyte reaction and cytotoxic T-lymphocyte activity in vitro.

Deoxyspergualin (DSG) has demonstrated potent immunosuppressive activities in vivo. However, because of its lability in culture medium, the mechanism of activity has not yet been identified in vitro. In this study, a more stable analogue, deoxymethylspergualin (MeDSG), was used to investigate the in vitro immunosuppressive activity of DSG. MeDSG suppressed both human mixed lymphocyte reaction (MLR) and cytotoxic T-lymphocyte (CTL) activity at doses greater than 0.1 micrograms/ml in vitro. In kinetics studies, MeDSG was found to suppress a MLR when added on day 3 of a 7 day MLR incubation but cyclosporin A (CYA) suppressed a MLR only when added during the initial stage of a MLR (i.e. on day 1). In studies of cell surface phenotype in the MLR, MeDSG treatment decreased the numbers of CD8+ lymphocytes but those of CD4+ lymphocytes were not affected. In addition, MeDSG had no significant effect on interleukin-2 (IL-2) receptor expression or IL-2 production. These results suggest that MeDSG suppresses the T-cells which are proliferating competent cells such as cytotoxic T-cells (CD8+), but has a different mode of immunosuppressive action compared with CYA.

Cyclosporine↗
PubMed1992

In vitro effects of glycosylated insulin in perfused liver and hindquarter in rats.

Using the perfused liver and hindquarter of the rat, the uptake of glycosylated insulin and its effect on glucose output were investigated. Insulin was glycosylated in ambient high glucose concentration, and glycosylated insulin GI80 (insulin incubated with 0.08% glucose), GI350 (incubated with 0.35% glucose), and GI1000 (incubated with 1% glucose) were prepared. The liver and hindquarter were perfused with nonglycosylated insulin (N-GI) or glycosylated insulin at a concentration of 100 or 1000 microU/ml. There were no significant differences in the fractional uptake of insulin by perfused liver and hindquarter despite glycosylation. Insulin-induced decrement in glucose output was significantly lower in the liver perfused with GI1000 than that in the liver perfused with N-GI, GI80, and GI350 at an insulin concentration of 100 microU/ml. There were no significant differences in insulin-induced decrement in glucose output between the hindquarter perfused with N-GI, GI80, GI350, and GI1000. These results suggest that when insulin (100 microU/ml) is incubated with a markedly elevated concentration of glucose (1000 mg/dl) its biological activity is reduced in the liver, but not in the hindquarter.

Animals↗
PubMed1992

Extent of ischaemia caused by hepatic vascular exclusion as evaluated in a canine model.

1. The difference in the extent of liver ischaemia between a hepatic vascular exclusion model and an inflow occlusion model were investigated by determining Indocyanine Green retention and hepatic mitochondrial redox state during 2 h of ischaemia in 10 mongrel dogs. The splanchnic venous bed and/or the infra-hepatic inferior vena cava were decompressed by pump-driven veno-venous bypass. 2. The Indocyanine Green retention test revealed that there was no hepatic blood flow in the hepatic vascular exclusion model during ischaemia (96.8 +/- 0.73% retention of the dye after 20 min), whereas hepatic blood perfusion was still present significantly in the inflow occlusion model (78.1 +/- 1.19% retention of the dye after 20 min) (P less than 0.01). 3. The mitochondrial redox potential of the liver in the dogs with hepatic vascular exclusion decreased immediately after the induction of ischaemia and remained fixed at extremely low levels. By contrast, in the dogs with inflow occlusion the redox potential decreased gradually after induction and was maintained significantly higher than that in dogs with hepatic vascular exclusion during 2 h of ischaemia (P less than 0.01). 4. It is concluded that the extent of liver ischaemia in the hepatic vascular exclusion model with pump-driven shunt is significantly different from that in the inflow occlusion model with shunt.

Animals↗
PubMed1992

Adrenergic mechanism in hyperketonemia in thyrotoxic and starved rats.

To evaluate the possible role of the adrenergic mechanism in hyperketonemia in hyperthyroidism and starvation, the plasma concentrations of FFA, acetoacetate (AcAc), and beta-hydroxybutyrate (BOHB) were measured in thyrotoxic and starved rats for 96 hours. Thyrotoxemia was induced in rats by a daily subcutaneous thyroxine (100 micrograms/kg/day) injection carried out for 7 days. Some of the thyrotoxic and starved rats were administered subcutaneous phentolamine (2 mg/kg, twice daily) or propranolol (0.1 mg/kg, twice daily). Plasma levels of FFA, AcAc, and BOHB were significantly increased in thyrotoxic and starved rats compared with the control rats. Phentolamine and propranolol administration did not alter plasma levels of FFA, AcAc, and BOHB in thyrotoxic rats. In starved rats, propranolol did not alter plasma levels of FFA, AcAc, and BOHB, however, phentolamine did increase plasma levels of FFA, AcAc, and BOHB. These results indicate that the adrenergic mechanism may not contribute to the hyperketonemia in thyrotoxic rats, but may have a slight inhibitory effect on ketogenesis in starvation probably due to alpha-antilipolytic action.

3-Hydroxybutyric Acid↗
PubMed1992

In vitro effects of glycosylated insulin and glucagon in perfused liver of the rat.

Using perfused liver of the rat, the hepatic uptake of glycosylated insulin (GI) and glucagon (GG) and its effects on hepatic glucose output were investigated. Insulin and glucagon were glycosylated in ambient high glucose concentration, and GI80 or GG80 (insulin or glucagon incubated with 0.08% glucose), GI350 or GG350 (incubated with 0.35% glucose), and GI1000 or GG1000 (incubated with 1% glucose) were prepared. The liver was perfused with the medium containing 1000 microU/ml insulin and 200 pg/ml glucagon or 200 microU/ml insulin and 1000 pg/ml glucagon. The fractional uptake of insulin or glucagon by perfused liver was not significantly altered by the glycosylation. In the liver perfused with 1000 microU/ml insulin and 200 pg/ml glucagon, glucose output was not changed by the glycosylation of the hormones, while in the liver perfused with 200 microU/ml insulin and 1000 pg/ml glucagon, GI1000 reduced its biological activity, as reflected by insulin-mediated decrease in glucose output. These results suggest that in the liver insulin incubated with markedly high concentration of glucose reduces its biological activity at a physiological concentration in the presence of high concentration of glucagon.

Animals↗
PubMed1992

Isolated sleep paralysis elicited by sleep interruption.

We elicited isolated sleep paralysis (ISP) from normal subjects by a nocturnal sleep interruption schedule. On four experimental nights, 16 subjects had their sleep interrupted for 60 minutes by forced awakening at the time when 40 minutes of nonrapid eye movement (NREM) sleep had elapsed from the termination of rapid eye movement (REM) sleep in the first or third sleep cycle. This schedule produced a sleep onset REM period (SOREMP) after the interruption at a high rate of 71.9%. We succeeded in eliciting six episodes of ISP in the sleep interruptions performed (9.4%). All episodes of ISP except one occurred from SOREMP, indicating a close correlation between ISP and SOREMP. We recorded verbal reports about ISP experiences and recorded the polysomnogram (PSG) during ISP. All of the subjects with ISP experienced inability to move and were simultaneously aware of lying in the laboratory. All but one reported auditory/visual hallucinations and unpleasant emotions. PSG recordings during ISP were characterized by a REM/W stage dissociated state, i.e. abundant alpha electroencephalographs and persistence of muscle atonia shown by the tonic electromyogram. Judging from the PSG recordings, ISP differs from other dissociated states such as lucid dreaming, nocturnal panic attacks and REM sleep behavior disorders. We compare some of the sleep variables between ISP and non-ISP nights. We also discuss the similarities and differences between ISP and sleep paralysis in narcolepsy.

Adolescent↗
PubMed1992

Protection of gastric mucosa against ethanol-induced injury by intragastric bolus administration of epidermal growth factor combined with hydroxypropylcellulose.

Orally administered epidermal growth factor (EGF) has been shown to protect the gastric mucosa against injury induced by noxious agents. However, EGF administered by intragastric bolus appears to have less effect on the gastric mucosa because of its rapid excretion from the gastric lumen. In this study, mouse EGF given to rats by gastric intubation was confirmed to remain in the stomach at significantly high concentrations when given in combination with hydroxypropylcellulose (HPC), an agent that retards drug release. The residual mouse EGF levels in the gastric luminal content and tissue 3 h after administration of 50 micrograms/kg of EGF dissolved in 1 ml of 2% HPC were 30 and 60 times higher, respectively, than those obtained after EGF alone. Pretreatment with intragastric bolus administration of EGF and HPC at the same dose for 3 h attenuated significantly the development of gastric lesions induced by absolute ethanol compared to that with HPC alone, EGF alone, or saline (mean values of ulcer index: EGF + HPC, 14.3; HPC, 52.8; EGF, 50.7; and saline, 63.2 mm). There were no significant differences between the ulcer index in the HPC, EGF, and saline groups. The present study indicates that exogenous EGF given as an intragastric bolus protects the gastric mucosa against injury when combined with HPC, which can bind to EGF and prevent its rapid excretion from the gastric lumen.

Animals↗
PubMed1992

Presence of amelanotic melanocytes within the outer root sheath in senile white hair.

In order to determine whether amelanotic melanocytes are present in senile white hair, we attempted to detect tyrosinase mRNA and its protein using in situ hybridization and immunohistochemical staining. Specifically stained cells containing tyrosinase mRNA or its protein were detected by each technique in 7/23 (30.4%) or 4/14 (28.6%) senile white hairs, respectively. These cells were located in the outer root sheath between the hair-bulb and the infundibulum. Silver staining was used to determine whether melanin was present within the outer root sheath of the senile white hair. Because none of the 21 white hairs tested showed specific staining within the outer root sheath, the absence of melanin was confirmed. Thus our results suggest the presence of amelanotic melanocytes within the outer root sheath of senile white hair.

Adult↗
PubMed1992

High human IgG levels in severe combined immunodeficient mouse reconstituted with human splenic tissues from patients with gastric cancer.

We implanted normal peripheral blood lymphocytes (PBL) from healthy donors and splenic tissues from patients with gastric cancers into the severe combined immunodeficient (SCID) mouse, demonstrating that SCID mouse with splenic tissue can produce a high level of human immunoglobulin G (IgG). The normal PBLs at 10(7) and 10(8)/mouse were implanted intraperitoneally, and three splenic tissues with a size of 3 x 3 x 3 mm from gastric cancer patients were inoculated subcutaneously into the bilateral backs of the mice. At 2, 4, 6 and 8 weeks after inoculation, mice were killed, and the human IgG was assessed by an ELISA method. SCID mice with splenic tissue revealed high human IgG levels from 2 weeks after inoculation and approximately 2 mg of IgG per ml was observed at 8 weeks post-implantation, while the IgG levels in mice treated with PBLs were limited. Since the half life of the extrinsic human IgG was 10.2 days, the high level of human IgG in the SCID mice was supposed to be produced by human plasma cells in the splenic tissue from gastric cancer patients. This model was thought to be adequate for evaluating human immunological functions in vivo.

Animals↗
PubMed1992

Myeloprotective activity of deoxyspergualin: influence on splenic colony-forming cell injury and antitumor activity of mitomycin C in mice.

We have examined the efficacy of deoxyspergualin (DSG) in protecting splenic colony-forming cells (CFU-S) from mitomycin C (MMC)-induced damage. The main findings of the study are as follows. (1) When DSG was administered at doses of 1.5 and 3 mg/kg for 7 days before the MMC injection, the decrease of the femoral CFU-S caused by MMC was diminished on the day after the MMC injection. The optimal dose was found to be 3 mg/kg. (2) In animals receiving 3 mg/kg DSG for at least 3 days preceding the MMC injection, the femoral CFU-S was more than 200% of that in the MMC alone group one day after the MMC injection. (3) The number of femoral CFU-S in the mice which received 3 mg/kg DSG for 3 days prior to MMC was significantly restored day by day and reached 70% of normal at 5 days after the MMC injection, while it was only 13% of normal in the MMC alone group. Moreover, the prior DSG administration significantly diminished the MMC toxicity to circulating platelets. (4) DSG administration (3 mg/kg) 3 days prior to MMC did not weaken the antitumor activity against colon 26 adenocarcinoma or P388 leukemia when compared with MMC alone. These findings have shown the ability of DSG specifically to protect the animals against bone marrow toxicity caused by MMC without interfering with the antitumor activity.

Adenocarcinoma↗
PubMed1992

Four clinical types of panic disorders.

The authors attempted to classify panic disorders into four types according to a clinical course and accompanying neurotic or depressive symptoms. The characteristics of each type are as follows; type I: a single panic attack is the only symptom, type II: only panic attacks occur frequently without any accompanying neurotic or depressive symptoms, type III: a recurrence of panic attacks and the gradual development of neurotic symptoms, such as anticipatory anxiety, generalized anxiety, agoraphobia, or hypochondriasis, type IV: depressive symptoms develop in the course of recurring panic attacks. Type IV is further divided into three subtypes. Type IV-1: depressive symptoms develop secondary to panic attacks and major depression later coexists with panic disorder. Type IV-2: panic disorder continuously changed into major depression. Type IV-3: panic attacks and depressive symptoms are seen independently. The most common types are type III and type IV-1, and seem to be a core group of the panic disorder. Typical cases of each type are presented and underlying psychopathology is discussed.

Adult↗
PubMed1992

Postnatal growth curves of very low birthweight Japanese infants.

To construct standard growth curves for Japanese infants of very low birthweight, longitudinal data provided by 47 neonatal centers in Japan were reviewed. Data were collected on the growth of infants admitted to those units during 1986 and 1987 and who survived beyond 3 years of age. A total of 379 singleton infants, who were free of neurological sequelae and appropriate for gestational age, were enrolled. Those whose birthweights were more than 600 g and less than 1,500 g were grouped into nine weight categories separated by increments of 100 g. Data on the increase in weight and head circumference were compiled and analyzed until more than half the infants in each weight category had been discharged from each site. Growth curves of bodyweight and head circumference in the nine groups were constructed using polynomial regression analysis to define the curve of best fit. With increasing prematurity, significant trends of greater weight loss (P < 0.05), longer time to reach the lowest weight (P < 0.01) and a longer time to regain birthweight (P < 0.01) were observed. In addition, there was a significantly higher incidence of chronic lung disease in such groups (P < 0.0001). Growth curves were characterized by the average clinical profiles in each of the nine groups. We believe that these data will be useful in evaluating the growth of very low birthweight infants being cared for in modern neonatal intensive care units in Japan.

Birth Weight↗
PubMed1992

Isolation and characterization of a chicken tyrosinase cDNA.

Complementary DNA clones coding for chicken tyrosinase were isolated from retinal pigmented epithelium of chicken embryo. Sequence analysis shows that one of the cDNA clones consisting of 1,997 nucleotides has an open reading frame coding for 529 amino acids. The deduced protein has nine N-glycosylation sites and a transmembrane region. A sequence comparison of the deduced chicken tyrosinase with the mouse and human homologues revealed that amino acid sequences are conserved for the entire polypeptides. Seventy-two percent and 73% of amino acids in the chicken sequence are identical to that of the mouse and human tyrosinases, respectively. Histidines neighboring the postulated copper-binding sites and the cysteines are well conserved. RNA blotting analysis showed that a major transcript of 2.5 kb is detected in retinal pigmented epithelium of a 9-day-old chicken embryo.

Amino Acid Sequence↗
PubMed1992

Phylogeny of regulatory regions of vertebrate tyrosinase genes.

Highly homologous DNA elements were found to be shared by the upstream regions of the mouse tyrosinase and tyrosinase related protein (TRP-1) genes. Several nuclear proteins were shown to bind to both of these upstream regions. Shared homologous DNA elements were also found in the 5' flanking sequences of Japanese quail and snapping turtle tyrosinase genes. Shared homologous nucleotide sequences were found to be scattered like an archipelago in the 5' upstream regions of mouse and human tyrosinase genes. Comparisons between Japanese quail and snapping turtle tyrosinase genes gave similar results. On the contrary, mammalian (mouse and human) and nonmammalian (quail and snapping turtle) tyrosinase genes did not show significant homology in their 5' upstream regions. In contrast, coding sequences in the first exons of vertebrate tyrosinase genes and their deduced amino acid sequences were found to be highly conserved except for their putative leader sequence-coding regions.

Amino Acid Sequence↗