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Biomedical subjects

T Yoshimura

Publications and source records attributed to T Yoshimura.

At least 451 records · Page 25Linked to original sources
PubMed1993

Hypertrophic cranial pachymeningitis associated with mixed connective tissue disease; a comparison with idiopathic and infectious pachymeningitis.

This is the first report describing hypertrophic cranial pachymeningitis which developed in association with mixed connective tissue disease (MCTD). A 56-year-old man with a two-year history of MCTD gradually developed symptoms of headache and blurred vision. Bilateral papilledema and increased opening pressure and mild pleocytosis of the cerebrospinal fluid were noted. Magnetic resonance imaging of the brain revealed a diffuse thickening and a gadolinium-enhancement of the cranial dura mater. While five previous patients, diagnosed as idiopathic or infectious hypertrophic cranial pachymeningitis in our department, had either otitis media or sinusitis and showed multiple cranial nerve involvement, the present patient had neither otitis media nor sinusitis and did not show any cranial nerve involvement other than papilledema.

Adult↗
PubMed1993

Effect of synthetic protease inhibitor on histologic changes and free radical activity in hamsters with pancreatic cancer.

To investigate the effects of synthetic trypsin inhibitors on pancreatic cancer, camostat (FOY-305) was administered orally to hamsters with experimental pancreatic cancer induced by diisopropanol nitrosamine (DIPN). The effect of free radicals on carcinogenesis was examined by measuring the tissue levels of the scavengers superoxide dismutase (SOD) and glutathione peroxidase (GSX-Px), and pancreatic tissues were examined histologically. Cancers developed in all hamsters that survived 24 weeks in the DIPN group and the FOY group, but 80% of the cancers in the DIPN group were tubular adenocarcinomas, and 91% of those in the FOY group papillary adenocarcinomas. The SOD activity in the DIPN group was significantly lower in the cancerous area and the borderline region than in the non-cancerous region and normal tissue. SOD activity in the cancerous and borderline regions was higher in the FOY groups than in the DIPN group. GSH-Px levels in the borderline and non-cancerous regions were significantly higher in the FOY group than in the DIPN group. These results suggest that the synthetic protease inhibitor slows the progress of pancreatic cancer by its free radical scavenging activity.

Adenocarcinoma↗
PubMed1993

Electron spin resonance studies of free radicals in gamma-irradiated golden hamster embryo cells: radical formation at 77 and 295 K, and radioprotective effects of vitamin C at 295 K.

Formation of free radicals in golden hamster embryo (GHE) cells produced by gamma irradiation at 77 and 295 K has been studied by electron spin resonance (ESR) spectroscopy. The yields of free radicals in the gamma-irradiated frozen cells at 77 K increase linearly with increasing dose in the range from 8 Gy to 1.3 kGy, suggesting that the mechanism of radical formation at a dose of 8 Gy is the same as that at 1.3 kGy. When GHE cells are irradiated with 5 kGy gamma rays at 295 K and then the ESR spectrum is measured at 77 K, a part of the organic radicals produced can be observed clearly. The organic radicals survive in GHE cells for more than 24 h at room temperature. The formation of the organic radicals by gamma irradiation is suppressed upon the addition of vitamin C to the GHE cells. When an aqueous solution of albumin (0.1 kg dm-3) is gamma-irradiated with 5 kGy at 295 K, albumin radicals are observed by ESR. The formation of the albumin radicals is suppressed drastically upon the addition of vitamin C. The efficient radioprotection of vitamin C against radical formation has been interpreted in terms of the scavenging of albumin radicals by vitamin C.

Animals↗
PubMed1993

[Effects of polychlorinated biphenyls on regeneration of the peripheral nerve in rats].

The sciatic nerves was crushed at the mid-thigh level on the last day of 32 days oral administration of PCB. Nerve specimens were obtained from the crushed regions at 1, 2, 4 and 8 weeks after crushing. There was no significant difference between the experimental group and the control group in the density of regenerating fibers and distribution of fiber diameters at 1 and 2 weeks. At 4 and 8 weeks, however, the density of myelinated fibers was higher in the experimental group than in the control group. These results indicate that PCB may inhibit the regeneration of the crushed nerves. It is, however, still unknown that this adverse effects of PCB on the peripheral nerve depends on the disturbance of the remyelination or regeneration of the axon or both.

Animals↗
PubMed1993

[A family with MELAS whose main manifestations are maternally-transmitted deafness and diabetes mellitus].

A family with maternally-transmitted deafness and diabetes mellitus is described. Although the proband clinically exhibited MELAS-like symptoms such as sudden-onset cerebellar ataxia and weakness of the proximal portion of the limbs in addition to deafness and diabetes mellitus, the other three members of the family had only deafness and diabetes mellitus and no neurological manifestations. The analysis of mitochondrial DNA of the two members revealed an A-->G mutation of tRNA(leu(UUR)), a mutation commonly seen in patients with MELAS. According to the clinical histories and endocrinological investigations, the type of the diabetes mellitus in this family was considered to be IDDM, which may be attributed to the dysfunction of mitochondrial of the pancreas islet cells, resulting from the mutation of the mitochondrial DNA.

Adult↗
PubMed1992

Partial reactions of bacterial D-amino acid transaminase with asparagine substituted for the lysine that binds coenzyme pyridoxal 5'-phosphate.

In bacterial D-amino acid transaminase (EC 2.6.1.21) replacement of Lys-145, which is covalently linked to the coenzyme pyridoxal 5'-phosphate in the wild-type enzyme, by an Asn residue gave a mutant enzyme (K145N) that slowly performed each half-reaction, as determined by spectral measurements. With the wild-type enzyme, the kinetics of these events were so rapid that pre-steady-state conditions were needed for their determination. The internal aldimine between coenzyme and Lys-145 was rapidly reduced with NaCNBH3 in the wild-type enzyme, whereas in the mutant enzyme the coenzyme, which is not covalently linked to the protein, was more resistant to reduction; the reduced forms of both wild-type and mutant enzymes were inactive. With large amounts of the K145N mutant enzyme and either amino acid or keto acid substrate alone, the formation of some reaction intermediates, i.e., the external aldimine with D-alanine and the ketimine with alpha-ketoglutarate, can be measured by conventional spectroscopy. Suicide substrates also induced slow spectral shifts of the E-PLP form of the enzyme. For the K145N enzyme, exogenous amines affected only the rate of the transaldimination but not the removal of the alpha-proton of the substrate. These results suggest that in the mutant enzyme some amino acid side chain other than Lys-145 performs this function. In order to identify this site, the K145N mutant enzyme was completely inactivated by the radiolabeled suicide substrate D-serine. Peptide mapping of tryptic digests showed that Lys-267 was the modified site.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1992

Flow cytometric analysis of nuclear DNA content of duct cell carcinoma of the pancreas.

BACKGROUND: This study was designed to evaluate the efficacy of nuclear DNA content analysis in determining the prognosis of carcinoma of the pancreas. METHODS: Resected and paraffin-embedded specimens from 72 patients with duct cell carcinoma of the pancreas were examined, and flow cytometry was used to explore the relationship between DNA ploidy and TNM classification or histologic grade. RESULTS: DNA aneuploidy was found histologically in 42.9%, 56.8%, and 71.4% of Grade 1, 2, and 3 tumors, respectively. DNA ploidy showed a statistically significant correlation with T category and retroperitoneal invasion. The cumulative survival rate of patients with retroperitoneal invasion was shorter than that of those without retroperitoneal invasion. Among the patients with retroperitoneal invasion, those with DNA aneuploidy had a significantly shorter survival time than did those with DNA diploidy. CONCLUSIONS: The DNA ploidy pattern, in combination with the presence or absence of retroperitoneal invasion, appears to be useful in predicting the prognosis for duct cell adenocarcinoma of the pancreas.

Adult↗
PubMed1992

In vitro quantitative autoradiography of [125I]alpha-bungarotoxin binding at the motor end-plates of experimental autoimmune myasthenia gravis.

A quantitative evaluation was made of nicotinic acetylcholine receptors (AChR) at the motor end-plates in experimental autoimmune myasthenia gravis (EAMG). Female Lewis rats were immunized with AChR protein purified from electric organs of Narke japonica. The forelimb digit extensor muscle obtained in the chronic stage of the controls and EAMG were studied using [125I]alpha-bungarotoxin, in vitro and autoradiographically. The maximum binding capacity (Bmax) values of the controls and EAMG were calculated to be 237.7 +/- 13.0 fmol/mg (n = 4) and 42.0 +/- 4.1 fmol/mg (n = 4), respectively (P less than 0.001), and the dissociation constant (Kd) values were 11.7 +/- 1.6 nM and 7.6 +/- 0.9 nM, respectively. This in vitro autoradiographic method revealed a quantitative reduction of AChR at the motor end-plates in EAMG.

Animals↗
PubMed1992

Inactivation of dimeric D-amino acid transaminase by a normal substrate through formation of an unproductive coenzyme adduct in one subunit.

D-amino acid transaminase, which contains pyridoxal 5'-phosphate (vitamin B6) as coenzyme, catalyzes the formation of D-alanine and D-glutamate from their corresponding alpha-keto acids; these D-amino acids are required for bacterial cell wall biosynthesis. Under conditions usually used for kinetic assay of enzyme activity, i.e., short incubation times with dilute enzyme concentrations, D-alanine behaves as one of the best substrates. However, the enzyme slowly loses activity over a period of hours when exposed to substrates, intermediates, and products at equilibrium. The rate of inactivation is dependent on enzyme concentration but independent of substrate concentration greater than Km values. Continuous removal of the product pyruvate by enzymic reduction precludes the establishment of equilibrium and prevents inactivation. The formation of small but detectable amounts of a quinonoid intermediate absorbing at 493 nm is proportional to inactivation. Studies with [14C]-D-alanine labeled on different carbon atoms indicate that the alpha-carboxyl group of the substrate is absent in the inactive enzyme; such decarboxylation is not a usual function of this enzyme. The inactive transaminase contains 1.1 mol of [14C]-D-alanine-derived adduct per mole of dimeric enzyme; this finding is consistent with the 50% reduction in the fluorescence intensity at 390 nm (due to the PMP form of the coenzyme) for the inactive enzyme. Thus, inactivation of one subunit of the dimeric enzyme renders the entire molecule inactive. Inactivation may occur when a coenzyme intermediate, perhaps the ketimine, is slowly decarboxylated and then undergoes a conformational change from its catalytically competent location.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1992

Fusion of phospholipid vesicles induced by an amphiphilic model peptide: close correlation between fusogenicity and hydrophobicity of the peptide in an alpha-helix.

A model peptide with 51 amino acid residues consisting of tandem repeats of a Lys-Lys-Leu-Leu sequence and a turn sequence of Asn-Pro-Gly at the center of the molecule has a random conformation at neutral pH but adopts an amphiphilic alpha-helical form in the presence of various salts or nucleotides [Goto, Y., & Aimoto, S. (1991) J. Mol. Biol. 218, 387-396; Goto, Y., Okamura, N., & Aimoto, S. (1991) J. Biochem. (Tokyo) 109, 746-750]. The interaction of this model peptide with liposome membranes and the resulting alpha-helical conformational transition and membrane fusion as well as the effect of the nucleotide ATP on these events were examined at neutral pH. The peptide associated stoichiometrically with liposome membranes composed of phosphatidylserine (PS) and phosphatidylcholine (PC) in a molar ratio of 2:1, resulting in formation of an amphiphilic alpha-helix and induction of fusion of the liposomes. However, the final fusion level was not correlated with the amount of binding or the helix content and was found to increase on an increase in hydrophobicity of the peptide in the alpha-helical form by neutralization of its positive charges by the negative charges of PS. In contrast, in the presence of ATP, the peptide bound completely to the PS/PC membranes at a lower concentration of liposome and concomitantly induced membrane fusion, indicating that ATP cooperates with PS to neutralize the charges of the peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1992

Determination of conjugated bile acids in human urine by high-performance liquid chromatography with chemiluminescence detection.

A qualitative and quantitative analysis of the conjugated 1 beta- and 6 alpha-hydroxy bile acids, including common bile acids, in human urine using high-performance liquid chromatography with chemiluminescence detection is described. After extraction of urine with C18 silica cartridges, the bile acids were separated into non-conjugated, glycine, taurine and sulphate fractions by ion-exchange chromatography on a lipophilic gel. Solvolysis of the sulphate was carried out by treatment with trifluoroethanol in acetone containing hydrochloric acid, and the liberated amino acid conjugates were fractionated again. The individual bile acids were separated on a reversed-phase C18 column (Bile Pak II), with detection by an immobilized 3 alpha-hydroxysteroid dehydrogenase enzyme reactor and chemiluminescence reaction of the generated NADH using 1-methoxy-5-methylphenazinium methylsulphate-isoluminol-microperoxidase system. The assay method showed the detection limits ranging from 8 to 250 pmol for the bile acids tested. Analysis of urine samples obtained from newborns, non-pregnant women and women in late pregnancy showed a large difference in bile acid composition and conjugation mode, suggesting that bile acid metabolism is different during fetal and neonatal periods.

3-Hydroxysteroid Dehydrogenases↗
PubMed1992

Demonstration that a human 26S proteolytic complex consists of a proteasome and multiple associated protein components and hydrolyzes ATP and ubiquitin-ligated proteins by closely linked mechanisms.

It is known that two types of high-molecular-mass protease complexes are present in the cytosol of mammalian cells; a 20S latent multicatalytic proteinase named the proteasome, and a large proteolytic complex with an apparent sedimentation coefficient of 26S that catalyzes ATP-dependent breakdown of proteins conjugated with ubiquitin. In this work, we first demonstrated that a low concentration of SDS was required for activation of the latent proteasome, whereas the 26S complex degraded substrates for proteasomes in the absence of SDS. Moreover, the 26S complex was greatly stabilized in the presence of 2 mM ATP and 20% glycerol. Based on these characteristics, we next devised a novel procedure for purification of the 26S proteolytic complexes from human kidney. In this procedure, the proteolytic complexes were precipitated from cytoplasmic extracts by ultracentrifugation for 5 h at 105000 x g, and the large 26S complexes were clearly separated from the 20S proteasomes by molecular-sieve chromatography on a Biogel A-1.5 m column. The 26S enzyme was then purified to apparent homogeneity by successive chromatographies on hydroxyapatite and Q Sepharose, then by glycerol density-gradient centrifugation. Electrophoretic and immunochemical analyses showed that the purified human 26S complex consisted of multiple subunits of proteasomes with molecular masses of 21-31 kDa and 13-15 protein components ranging in molecular mass over 35-110 kDa, which were directly associated with the proteasome. The purified 26S proteolytic complex degraded 125I-labeled lysozyme-ubiquitin conjugates in an ATP-dependent manner. The 26S enzyme also showed high ATPase activity, which was copurified with the complex. Vanadate and hemin strongly inhibited not only ATP cleavage, but also ATP-dependent breakdown of ubiquitinligated proteins, suggesting that the 26S complex hydrolyzes ATP and ubiquitinated proteins by closely linked mechanisms. These findings indicate that the 26S complex consists of a proteasome with proteolytic function and multiple other components including an ATPase that regulates energy-dependent, ubiquitin-mediated protein degradation.

Adenosine Triphosphatases↗
PubMed1992

The influence of labor on thrombotic and fibrinolytic systems.

Plasma fibrinopeptide A, thrombin-antithrombin III complexes, tissue-plasminogen activator and alpha 2-plasmin inhibitor-plasmin complexes were measured early in the first stage of labor, in the second stage of labor and at 15 min after placental separation. Fibrinopeptide A and thrombin-antithrombin III complex levels did not change from the first to the second stage of labor but increased significantly after placental separation. There was a significant increase of the tissue-plasminogen activator level between the early first stage of labor and the second stage of labor, and it remained high after placental separation. A significant increase in the level of plasma alpha 2-plasmin inhibitor-plasmin complexes was observed after placental separation. These findings suggest that activation of the thrombotic system occurs at the time of placental separation and that activation of the fibrinolytic system begins during labor before placental separation to compensate for the hypercoagulable state which develops at the time of delivery.

Adult↗
PubMed1992

Immunoelectron microscopic localization of antigens which react with islet cell cytoplasmic antibodies within human pancreatic beta cells.

The presence of circulating autoantibody to islet cell cytoplasm is considered to be an important marker of Type 1 (insulin-dependent) diabetes mellitus. In the present study using islet cell cytoplasmic antibody positive patient sera as the first antibody, we studied the intracellular distribution of its antigen at the electron microscopic level using the pre-embedding immunoperoxidase method. Specific immunoreactivity was found in the membranes of beta cell-secretory granules and cytoplasmic membranes. This result is compatible with the interpretation that the antigen(s) on the membranes of beta cell secretory granules is (are) the target of islet cell cytoplasmic antibody.

Autoantibodies↗