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M Yamanaka

Publications and source records attributed to M Yamanaka.

At least 19 recordsLinked to original sources
PubMed1992

Lithocholate binding by Y and Y' proteins in bovine small intestine.

Cytosolic proteins may play an important role in the intracellular transport of bile acids in enterocytes. The lithocholate binding properties of cytosolic protein from bovine small intestine were studied. Lithocholate binding was observed in the Y (45-50 kDa), Y' (30-35 kDa), and Z fractions (10-15 kDa) following gel filtration of cytosol. A Y protein with glutathione S-transferase activity (46 kDa) was purified by S-octyl-glutathione affinity chromatography and chromatofocusing (eluted at pH 7.5) of the Y fraction. Two Y' bile acid binding proteins with dihydrodiol dehydrogenase activity were partially purified from the Y' fraction by chromatofocusing and hydroxyapatite-HPLC. The lithocholate binding affinity of Y' protein (Kd < 0.35 microM) was higher than that of Y protein (Kd = 2 microM) and was comparable to that of Z protein (Kd = 0.2 microM). The binding affinity of Y protein was higher for bilirubin (Kd = 2.5 microM) than that for BSP (Kd = 200 microM). This was comparable to the binding affinity of bovine hepatic Y protein. These data indicate that Y' and Z proteins participate in the intracellular transport of bile acids from the brush border to the basolateral pole in enterocytes.

Animals↗
PubMed1992

Purification of 3 alpha-hydroxysteroid and 3 beta-hydroxysteroid dehydrogenases from human liver cytosol.

We previously reported that the human Y' bile acid binder, which has higher bile acid binding affinities than rat Y' binders (3 alpha-hydroxysteroid dehydrogenases), has dihydrodiol dehydrogenase activity and is different from 3 alpha-hydroxysteroid dehydrogenases. In this study, 3 alpha-hydroxysteroid dehydrogenases and 3 beta-hydroxysteroid dehydrogenase were purified from human liver, and bile acid binding affinities and enzyme kinetics of the 3 alpha-hydroxysteroid dehydrogenases were studied. On chromatofocusing of pooled Affigel blue fraction of the Y' fraction, three 3 alpha-hydroxysteroid dehydrogenase peaks eluted at pH 6.0, 5.7 and 5.4. These peaks did not bind bile acids, and further purification by hydroxyapatite-high-performance liquid chromatography gave pure 3 alpha-hydroxysteroid dehydrogenases with identical M(r) (36,000) having dihydrodiol dehydrogenase activity. 3 beta-Hydroxysteroid dehydrogenase was eluted together with Y' bile acid binder at pH 7.2 on chromatofocusing and was separated from Y' bile acid binder on hydroxyapatite-high-performance liquid chromatography as a pure protein with M(r) 32,000. The apparent Kms of 3 alpha-hydroxysteroid dehydrogenases were similar to those of rat enzymes. In conclusion, we purified human hepatic 3 alpha-hydroxysteroid dehydrogenases, which have similar characteristics to rat enzymes, but do not bind bile acids or reduce bile acid precursors. These data further support the importance of human bile acid binder in intracellular bile acid transport in the human liver.

3-Hydroxysteroid Dehydrogenases↗
PubMed1992

Binding of bile acids, organic anions, and fatty acids by bovine intestinal Z protein.

Z protein from bovine small intestinal mucosa was purified and its binding affinities for bile acids, organic anions, and fatty acids were compared with those of bovine hepatic Z protein. Purification of Z protein from intestinal and hepatic cytosol was performed by gel filtration, chromatofocusing, and hydroxyapatite chromatography. Both purified proteins had the same molecular weight (Mr 14,000) and eluted from a chromatofocused gel at about pH 10. Binding studies were performed by the competitive displacement of 8-anilinonaphthalene-1-sulfonic acid and by equilibrium dialysis. Binding affinities for bile acids, organic anions, and fatty acids were very similar between intestinal and hepatic Z proteins. Although the real physiologic role of Z protein remains to be further elucidated, these data indicate that intestinal Z protein participates in the mechanism of intracellular bile acid transfer in enterocytes.

Animals↗
PubMed1992

Sequence analysis and editing of the phosphoprotein (P) gene of rinderpest virus.

We have cloned the cDNA of the phosphoprotein (P) gene of the virulent (Kabete "O") strain of rinderpest virus and provided a comparative analysis of its sequence with that of the P genes of measles, canine distemper, and phocid distemper viruses. The gene encodes two overlapping open reading frames of 1521 and 531 nucleotides. Use of the first ATG would produce a P polypeptide of 507 amino acids with a calculated molecular weight of 54,344. The second ATG would produce a C polypeptide of 177 residues with a predicted molecular weight of 19,927. In addition, the insertion of a G residue at position 740 generates an alternative mRNA potentially encoding the V polypeptide of rinderpest virus. The homology comparisons in P amino acid sequences between rinderpest and measles, between rinderpest and canine distemper, and between rinderpest and phocid distemper viruses are 60, 44, and 46%, respectively. A four-way comparison shows an identity of 34%. Similar homology comparisons with the C amino acid sequence between rinderpest and measles, rinderpest and canine distemper, and rinderpest and phocid distemper viruses are 56, 42, and 40%, respectively. A homology of 31% is found in a four-way comparison for the C polypeptide. From the point of the insertion of the G residue, there is a homology of 78% between the V polypeptides of rinderpest and measle viruses.

Amino Acid Sequence↗
PubMed1992

Effects of ursodeoxycholate, its glucuronide and disulfate and beta-muricholate on biliary bicarbonate concentration and biliary lipid excretion.

We previously reported that high-dose ursodeoxycholate (UDC) infusion in rats resulted in extensive glucuronidation of UDC, and speculated that the glucuronidation causes bicarbonate-rich hypercholeresis induced by UDC (Takikawa, H., Sano, N., Narita, T. and Yamanaka, M. Hepatology 1990; 11: 743-749). To test this hypothesis, UDC, UDC-3-O-glucuronide, UDC-3,7-disulfate and beta-muricholate were separately and intravenously infused into rats (1 mumol/min per 100 g), and biliary bicarbonate concentration was measured. The effects of these bile acids on biliary lipid secretion were also studied. All four bile acids increased bile flow and biliary bile acid excretion. UDC and beta-muricholate significantly increased biliary bicarbonate concentration, whereas UDC glucuronide and disulfate did not. Independence of UDC glucuronide excretion and biliary bicarbonate concentration was also confirmed in EHBR, a hyperbilirubinemic mutant Sprague-Dawley rat. In this case biliary bicarbonate concentration also increased in spite of the absence of UDC glucuronide in the bile after UDC infusion. Biliary phospholipid secretion was increased with UDC, unchanged with beta-muricholate, and decreased with UDC glucuronide and disulfate. Biliary cholesterol secretion was increased with UDC, unchanged with beta-muricholate and UDC glucuronide, and decreased with UDC disulfate. These data indicate that glucuronidation is not the cause of bicarbonate-rich hypercholeresis induced by UDC but that glucuronidation and sulfation change the effect of UDC on biliary lipid secretion.

Animals↗
PubMed1992

Imidazo[1,2-alpha]pyridines. III. Synthesis and bradycardic activity of new 5-imidazo[1,2-alpha]pyridin-6-ylpyridine derivatives.

Structural modification of the cardiotonic agent, loprinone (E-1020, 1), suggested by data that it has a less positive chronotropic effect than milrinone (15), led us to find novel bradycardic agents that were structurally different from homoveratryl amine derivatives. Alkyl-oxy, -thio, and -amino derivatives at the 2-position of the pyridine ring of 1 produced bradycardic activity without a significant effect on blood pressure and myocardial contractility. Aryloxy analogues also decreased heart rate, and members with an electron-withdrawing group at the ortho position of the phenyl ring showed higher activity. Replacement of the imidazo[1,2-alpha]pyridine with pyridine resulted in diminished activity. The mechanism of bradycardic activity of these compounds seems to be direct action on the sinus node.

Animals↗
PubMed1992

Serum progesterone concentrations using P-EIA kit in captive and free-ranging Hokkaido brown bears, Ursus arctos yesoensis.

Serum progesterone (P) concentrations using P-EIA kit (Ovucheck, Cambridge Life Science Co., Ltd.) were examined in 8 captive and 7 free-ranging female Hokkaido brown bears (Ursus arctos yesoensis). The intra- and inter-assay coefficients of variation were 8.9%, 12.6% and 16.6%, 22.7%, respectively, based on 2 serum samples. There was a significant correlation between EIA and radioimmunoassay results based on 64 serum samples (r = 0.725; p less than 0.01). Serum P concentrations were examined in 5 pregnant, 2 solitary non-pregnant bears and a lactating non-pregnant bear in captivity. Annual changes of P levels in pregnant bears were observed as a small elevation during the mating season (May-June), a re-elevation in September-October and a sharp elevation in November-December. The sharp elevation was suspected to reflect changes when implantation occurred. Annual changes of P levels in solitary non-pregnant bears were similar to those in pregnant bears. An annual change of P levels in a lactating non-pregnant bear maintained levels under 5 ng/ml. Two of 7 free-ranging bears exhibited P levels over 1 ng/ml and the birth of cubs was confirmed in the following year in 1 of the 2 bears. P concentrations of other free-ranging bears exhibited less than 1 ng/ml, and these bears were considered to be non-pregnant. It was concluded that P-EIA kit was available for measuring P concentrations in Hokkaido brown bears.

Animals↗
PubMed1992

Pathological studies on local tissue reactions in guinea pigs and rats caused by four different adjuvants.

We investigated pathological changes at the injection site in guinea pigs and rats for 16 weeks following a single intramuscular injection of one of the following oil adjuvant emulsions; oil adjuvant ISA-70, Freund's incomplete adjuvant, Freund's complete adjuvant, and aluminium phosphate gel. In the animals injected with ISA-70 emulsion prepared by manual shaking, grossly, there was partial thickening of subcutaneous tissue, discoloration of inter-muscular connective tissue, and swelling of the inguinal lymph nodes at 2 and 4 weeks post injection (PI). Histopathologically, ISA-70 injected sites revealed acute inflammatory changes at 72 hrs PI, and peak reactions consisting of macrophage accumulation around oil cysts and fibrosis were observed at 4 weeks PI. These changes were less severe and of shorter duration than those in the other three adjuvants. Guinea pigs and rats injected with materials containing inactivated Newcastle disease virus (NDV) antigen similarly showed an infiltration of plasma cells and lymphocytes in addition to the changes described above. ISA-70 containing NDV antigen induced similar hemagglutination-inhibition titer to that induced by Freund's incomplete adjuvant.

Adjuvants, Immunologic↗
PubMed1992

[Establishment of an outbred strain (Jic: SUN) in the house musk shrew, Suncus murinus].

Planned reproduction of the house musk shrew, Suncus murinus was investigated using 3,016 females for mating. The birth rate and the weaning rate attained were 77.2% and 82.3%, respectively. The average litter size was 3.4. The mean value of the productive index (number of weaned individuals/number of females mated) was estimated as 2.2. The highest value of the productive index, 2.6, was recorded when the fourth litter was used for reproduction. No seasonal fluctuation in the reproductive ability was observed through the course of the present breeding. In the present study, we have maintained the closed colony of the house musk shrew for six years. This colony is established as a outbred strain, and is designated as Jic: SUN.

Animals↗
PubMed1992

[Mechanism of amino acid transport at the liver plasma membrane].

Several amino acid transport systems have been known in the liver: sodium-dependent systems A, ASC and N for neutral amino acids, a sodium-dependent system for glycine (system Gly), sodium independent systems L1 and L2 for neutral amino acids, and sodium dependent systems for anionic amino acids. Recent studies with isolated sinusoidal and canalicular membrane vesicles have revealed that sodium dependent transport of an anionic amino acid, glutamate, and glycine occurs at the canalicular membrane, not at the sinusoidal membrane. Furthermore, solubilization and reconstitution of systems A and N has been reported and a 100 kD protein responsible for system N transport has been identified in the rat liver.

Adaptation, Biological↗
PubMed1992

[A case of flomoxef-induced pneumonitis].

We report a case of flomoxef-induced pneumonitis. A 22-year-old man was treated with flomoxef following liver biopsy. A few days later he developed a high fever and severe dyspnea, and his chest X-ray film revealed diffuse reticulo-nodular shadows in both lung fields. We suspected interstitial pneumonitis due to flomoxef, and pulse therapy with methylprednisolone was started. He showed rapid recovery of symptoms and marked regression of pulmonary infiltration in his chest X-ray. Lymphocyte stimulation test was positive to flomoxef, which was compatible with the diagnosis of drug-induced pneumonitis. To our knowledge, there has been no previous case of pulmonary hypersensitivity to flomoxef reported in Japan.

Adult↗
PubMed1991

Cytotoxic effect and uptake mechanism by isolated rat hepatocytes of lithocholate and its glucuronide and sulfate.

The hepatotoxicity and uptake mechanism of lithocholate and its glucuronide and sulfate were studied using isolated rat hepatocytes. Cytotoxicity was in the order of lithocholate greater than lithocholate-glucuronide greater than lithocholate-sulfate; their 50% cytotoxic concentrations on hepatocytes were 50, 150 and 700 microM, respectively. Thus, glucuronidation as well as sulfation acted to detoxify lithocholate, not relating to the previously reported higher cholestatic effect of lithocholate-glucuronide than lithocholate. Lithocholate uptake was linear up to 50 microM, whereas the uptakes of lithocholate-glucuronide and sulfate were saturable with an apparent Km and Vmax of 32 microM and 6.4 nmol/min per 10(6) cells for lithocholate-glucuronide and 26 microM and 11.8 nmol/min per 10(6) cells for lithocholate-sulfate. Na+ replacement by choline+ had no effect on the uptake of lithocholate and lithocholate-glucuronide, whereas it slightly inhibited lithocholate-sulfate uptake. Lithocholate-glucuronide uptake was inhibited by lithocholate-sulfate and sulfobromophthalein, whereas lithocholate-glucuronide and sulfobromophthalein had no effect on lithocholate-sulfate uptake. These data indicate that hepatic lithocholate uptake is mediated by simple diffusion, and that hepatic uptake of lithocholate-glucuronide and sulfate is mainly mediated by a Na(+)-independent carrier.

Animals↗
PubMed1991

Cholestasis induced by lithocholate and its glucuronide: their biliary excretion and metabolism.

We studied the effects of the infusion of lithocholate and lithocholate-3-sulfate and 3-glucuronide in rats (0.29 mumol/min per 100 g body weight for 40 min) on bile flow, together with their biliary excretion and metabolism. Lithocholate-glucuronide had a higher cholestatic effect than lithocholate, whereas lithocholate-sulfate had almost no effect on bile flow. Lithocholate was mainly converted to taurine or glucuronide conjugates in the bile, serum and liver and hydroxylation of the tauro-conjugate proceeded. Lithocholate-sulfate was almost completely excreted in the bile, mainly as tauro-conjugate. Lithocholate-glucuronide was excreted in bile almost without conjugation, while some taurine conjugation occurred in the serum and liver. These results suggest that the poor biotransformation of lithocholate-glucuronide is related to its higher cholestatic potency than lithocholate.

Alanine Transaminase↗