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Biomedical subjects

Y Shibata

Publications and source records attributed to Y Shibata.

At least 325 records · Page 18Linked to original sources
PubMed1996

[Successful induction of immune tolerance and novel hemostatic effects in a hemophilia A with high-responder inhibitor by regular infusions of factor VIII].

A hemophilia A patient with high responder inhibitor had been treated by (activated) prothrombin complex concentrates (A) PCC and activated factor VII until the occurrence of intracranial bleeding at the age of 6 years. Since the inhibitor titer was decreased less than 1 Bethesda Units/ml, high dose of factor VIII was given followed by the infusions of factor VIII concentrates (100 units/kg) three times a week. In spite of previous episodes of anamnestic responses by factor VIII products before, the inhibitor titer did not increase and disappeared completely 6 months after the FVIII infusion therapy. The specific anti-factor VIII IgG subclasses of the inhibitor were IgG2 and IgG4. The inhibitor recognized both light and heavy chains. He have no bleeding episode for 6 months since the beginning of the prophylactic with factor VIII concentrates.

Blood Coagulation Factors↗
PubMed1996

Expression of heat shock protein 70 (HSP70) and EBV latent membrane protein 1 (LMP1) in Reed-Sternberg cells of Hodgkin's disease.

Tissue sections embedded in paraffin and fixed in formalin from 65 patients with Hodgkin's disease (HD) were examined for the presence of heat shock protein 70 (HSP70) and Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) using avidin-biotin immunoperoxidase complex technique. The staining results in Reed-Sternberg (R-S) cells and their variants were evaluated independently. HSP70 expression was found in R-S cells in 55 cases (85%) of HD examined and the frequency of HSP70 positive cases was significantly higher than that of HSP70 negative cases (P < 0.01). This protein was present in pathogenic cells in 9/12 cases (75%) of lymphocyte predominant Hodgkin's disease (LPHD), 21/27 cases (78%) of mixed cellularity Hodgkin's disease (MCHD), 10/10 cases (100%) of lymphocyte depleted Hodgkin's disease (LDHD) and 15/16 cases (94%) of nodular sclerosing Hodgkin's disease (NSHD). The association between HSP70 expression and HD thus appeared to be more frequent in patients wish LDHD and NSHD subtypes, although examples of HSP70-positive tumors were found in all histological subtypes. Studies of non-neoplastic lymphoid tissues demonstrated that centroblasts (large lymphocytes in germinal centers) were constantly positive; occasional histiocytes revealed variable reactivity for.

HSP70 Heat-Shock Proteins↗
PubMed1996

Immunohistochemical findings of arterial fibrinoid necrosis in major and lingual minor salivary glands of primary Sjögren's syndrome.

Arterial fibrinoid lesions in major salivary glands and lingual minor salivary glands from four autopsied patients with primary Sjögren's syndrome were studied histologically and immunohistochemically. On a morphological basis, the preceding arterial fibrinoid necrosis was regarded as medial damage, particularly of smooth muscle cells. The medial smooth muscle cells underwent vacuolated degeneration and disappeared, and resulted in full-blown fibrinoid arteritis. By means of the immunoperoxidase method the distribution of the immunoglobulins, fibrin, complement (C3), transferrin, ferritin, vimentin and lysozyme was studied. The normal arterial wall reacted with the lambda light chain of immunoglobulin, transferrin and vimentin Vacuolated degeneration of medial smooth muscle cells, regarded as the initial change in cases of vascular fibrinoid lesion, was positive for IgG, C3 and vimentin. We suggest that IgG antibody is a useful marker to detect the initial phase of arterial fibrinoid necrosis. In the foci of fibrinoid necrosis, fibrin, C3 and vimentin were detected. Among these three antibodies, only fibrin was negative in the normal arterial wall and vacuolated degenerates of medial smooth muscle cells. Mononuclear cells surrounding areas of fibrinoid necrosis stained strongly with antisera to immunoglobulins, transferrin, ferritin and vimentin, and negatively with fibrin, C3 and lysozyme antibodies.

Adult↗
PubMed1995

An abnormal fibrinogen Fukuoka II (Gly-B beta 15-->Cys) characterized by defective fibrin lateral association and mixed disulfide formation.

A dysfibrinogenemia was attributable to a single amino acid substitution from glycine to cysteine at residue 15 of the B beta chain in a fibrinogen molecule designated as fibrinogen Fukuoka II. The fibrinogen Fukuoka II showed prolonged thrombin and reptilase times and impaired fibrinopeptide B release by thrombin, resulting in abolition of fibrin monomer repolymerization under physiological conditions. Repolymerization of the des-(B beta 1-42)-fibrin monomers, however, was not distinguished from the normal pattern of des-(B beta 1-42)-fibrin monomers, suggesting that no other abnormality existed in fibrinogen Fukuoka II. Although an additional cysteine was substituted at residue 15 of the B beta chain, fibrinogen Fukuoka II had no free sulfhydryl group within the molecule. Instead, fibrinogen Fukuoka II formed a disulfide bond with cysteine, albumin, another mutated B beta chain within the same molecule, or intermolecular dimeric fibrinogen Fukuoka II. The mutation in fibrinogen Fukuoka II was the same as that in fibrinogen Ise published previously (Yoshida, N., Wada, H., Morita, K., Hirata, H., Matsuda, M., Yamazumi, K., Asakura, S., and Shirakawa, S. (1991) Blood 77, 1958-1963). Fibrinogen Ise, however, has been described as having prolonged thrombin time but normal reptilase time. Reasons for the discrepancy were not clear. Analysis of the B beta 1-42 fragment showed that fibrinogen was heterogeneous at position 31 of the B beta chain with respect to proline or hydroxyproline.

Amino Acid Sequence↗
PubMed1995

Amino-acid sequence of rat liver kynureninase.

Amino-acid sequence of kynureninase purified from rat liver cytosol was determined by an amino-acid sequencer. The enzyme was degraded to small peptides with cyanogen bromide, TPCK-trypsin, endoproteinase Glu-C, lysyl endoprotease and alpha-chymotrypsin. The enzyme subunit consisted of 464 amino acids, and the molecular weight of subunit was determined to be 52,510. The coenzyme pyridoxal phosphate-binding residue was lysine of which position was 276, and the N-terminal residue was N-acetylmethionine. The homology search between this enzyme and the other pyridoxal phosphate-dependent enzymes showed that kynureninase was similar to mitochondrial aspartate aminotransferase, and also to cystathionine gamma-synthase and gamma-lyase to a lesser extent.

Amino Acid Sequence↗
PubMed1995

Induction of experimental autoimmune sialoadenitis by immunization of PL/J mice with carbonic anhydrase II.

Experimental autoimmune sialoadenitis was induced in PL/J (H-2u) mice by intradermal immunization with human carbonic anhydrase II (CAII) and adjuvant containing monophosphoryl lipid A and trehalose diorynomycolate. Mice immunized with CAII showed a significant increase in the number and size of foci with lymphocytic infiltration in the salivary gland compared with mice immunized with adjuvant alone and untreated mice. In mice immunized with CAII, lymphocytic foci were observed around intercalated and intralobular ducts in the salivary glands, resulting in atrophy and replacement of acinar units. The epithelial cells of salivary ducts adjacent to the lymphocytic foci showed both degenerative and regenerative changes. Similar lymphocytic infiltrations were observed in the pancreas and kidney of a few mice immunized with CAII. Among several mouse strains with different H-2 haplotypes (p, q, r, s, and u), strains bearing H-2s and H-2u were susceptible to CAII-induced sialoadenitis. These results indicate that sialoadenitis induced by the immunization of CAII in mice may serve as a disease model of Sjögren's syndrome and that CAII or its derived peptides in association with the MHC may be one Ag recognized by an autoimmune response in this syndrome.

Animals↗
PubMed1995

Classification of ion channels in the luminal and abluminal membranes of guinea-pig endocardial endothelial cells.

1. The ion channels on both the luminal and abluminal membranes of endocardial endothelial (EE) cells were separately recorded using the patch clamp technique in the guinea-pig heart. 2. The major population consisted of two types of non-selective cation channels, which showed open probabilities of 0.21 and 0.33 at the resting potential, and conductances of 36 and 11 pS, respectively. 3. The next major class was Cl- channels with an ohmic conductance of 409 pS. The channel was quiescent in the cell-attached mode but was activated by strong depolarization after excising the patch membrane. 4. The channels activated by intracellular Ca2+ were mainly K+ channels showing a 34 pS slope conductance and, less frequently, Ca(2+)-dependent K+ channels having a large conductance (210 pS). The inward rectifier K+ channel (32 pS) was also observed. 5. The non-selective cation channels were recorded on the luminal membrane, but scarcely on the abluminal membrane, suggesting an active transport of K+ and Na+ across the endocardium. 6. The resting membrane conductance of the EE cells may be provided mostly by non-selective cation channels and 34 pS Ca(2+)-dependent K+ channels.

Animals↗
PubMed1995

Structural studies on the hexasaccharide alditols isolated from the carbohydrate-protein linkage region of dermatan sulfate proteoglycans of bovine aorta. Demonstration of iduronic acid-containing components.

Five major hexasaccharide alditols were isolated from the carbohydrate-protein linkage region of bovine aorta dermatan sulfate peptidoglycans after reductive beta-elimination and subsequent chondroitinase ABC digestion. These molecules account for at least 55.3% of the total linkage region. Their structures were analyzed by enzymatic digestion in conjunction with high performance liquid chromatography, electrospray ionization mass spectrometry, and 500-MHz one- and two-dimensional 1H NMR spectroscopy. Three of these compounds have the conventional hexasaccharide core; delta HexA alpha 1-3Gal-NAc beta 1-4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl-ol. One is nonsulfated, and the other two are monosulfated on C6 or C4 of the GalNAc residue. They represent at least 6.3, 5.2, and 28.8% of the total linkage region, respectively. The other two compounds have the following hitherto unreported hexasaccharide core with an internal iduronic acid residue in common; delta HexA alpha 1-3GalNAc beta 1-4IdoA alpha 1-3Gal beta 1-3Gal beta 1-4Xyl-ol. One is monosulfated on C4 of the GalNAc, and the other is disulfated on C4 of the GalNAc and of the galactose residue substituted by the iduronic acid residue. These two compounds account for 35% of the five isolated hexasaccharide alditols and at least 4.3 and 10.7% of the total linkage region, respectively. The latter two structures form a striking contrast to the currently accepted conception that heparin, heparan sulfate, and chondroitin/dermatan sulfate share the common linkage tetrasaccharide core GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl. The biological significance of the isolated structures is discussed in relation to the biological functions and the biosynthetic mechanisms of dermatan sulfate.

Animals↗
PubMed1995

Prostaglandin E2 release triggered by phagocytosis of latex particles. A distinct association with prostaglandin synthase isozymes in bone marrow macrophages.

Previous studies showed that murine bone marrow-derived macrophages (M phi) induced in vitro by IL-3 express cellular prostaglandin G/H synthase (PGHS)-1 but not PGHS-2. To induce PGHS-2 in this study, the M phi were primed further with IFN-gamma plus LPS. The expression of the PGHS isozymes was determined by cytometric analysis using Abs against PGHS-1 and PGHS-2. The expression of PGHS-2, but not PGHS-1, was dexamethasone-sensitive. To assess PGE2-releasing capacity, the primed M phi were triggered by challenge with calcium ionophore A23187, the protein kinase C (PKC) activator PMA, exogenous arachidonic acid, and 1.1-micron latex bead particles. Our results showed that the primed M phi expressed both isozymes and responded to all challenges used to release a substantial amount of PGE2 (> 10 ng PGE2/10(6) cells/ml), whereas the control unprimed M phi responded to A23187 and arachidonic acid but not to PMA or latex beads to release PGE2. However, the primed M phi did not release PGE2 when triggered with nonphagocytosable particles (> or = 40 microns) or when pretreated with cytochalasin D before they were challenged with 1.1-micron beads. Furthermore, staurosporine, a PKC inhibitor, did not inhibit the PGE2 release triggered by the beads. PMA-triggered PGE2 release by the primed M phi, in sharp contrast, was staurosporine-sensitive but cytochalasin D-resistant. Our data suggest that there are multiple or alternative pathways for triggering PGE2 synthesis and release distinctively associated with two PGH synthase isozymes. It is of special interest that the novel pathway triggered by interiorization of particles is associated with the expression of PGHS-2.

Alkaloids↗
PubMed1995

Fatty acid hydroperoxide lyase is a heme protein.

Fatty acid hydroperoxide lyase (HPO lyase) is an enzyme that cleaves hydroperoxides of polyunsaturated fatty acids to form short chain aldehydes and omega-oxoacids. Spectrophotometric analyses of HPO lyase highly purified from green bell pepper fruits indicate that it is a heme protein. The heme species was revealed to be heme b (protoheme IX) from the absorption spectrum of the pyridine hemochromogen. Although the spectrum highly resembles that of a plant cytochrome P450, allene oxide synthase from flaxseed, CO treatment of the enzyme caused no appearance of a peak at 450 nm, which is an essential diagnostic feature of a cytochrome P450. Internal amino acid sequences determined with peptide fragments obtained from the lyase showed no homology with any reported sequences.

Aldehyde-Lyases↗
PubMed1995

An acute myeloid leukemia gene, AML1, regulates hemopoietic myeloid cell differentiation and transcriptional activation antagonistically by two alternative spliced forms.

The AML1 gene on chromosome 21 is disrupted in the (8;21)(q22;q22) and (3;21)(q26;q22) translocations associated with myelogenous leukemias and encodes a DNA binding protein. From the AML1 gene, two representative forms of proteins, AML1a and AML1b, are produced by alternative splicing. Both forms have a DNA binding domain but, unlike AML1b, AML1a lacks a putative transcriptional activation domain. Here we demonstrate that overexpressed AML1a totally suppresses granulocytic differentiation and stimulates cell proliferation in 32Dcl3 murine myeloid cells treated with granulocyte colony-stimulating factor. These effects of AML1a were canceled by the concomitant overexpression of AML1b. Such biological phenomena could be explained by our observations that (i) AML1a, which on its own has no effects as a transcriptional regulator, dominantly suppresses transcriptional activation by AML1b, and (ii) AML1a exhibits the higher affinity for DNA binding compared with AML1b. These antagonistic actions could be important in leukemogenesis and/or myeloid cell differentiation because more than half of myelogenous leukemia patients showed an increase in the relative amounts of AML1a.

Alternative Splicing↗
PubMed1995

Expression of tissue-type plasminogen activator and its inhibitor couples with development of capillary network by human microvascular endothelial cells on Matrigel.

Human omental microvascular endothelial (HOME) cells seeded on Matrigel begin to migrate within 1 h, forming honeycomb-like structures and capillary-like networks within 18 h. Cross-sections of the capillary networks show them to be tube-like structures. Northern blot analysis showed that tissue-type plasminogen activator (t-PA) mRNA synthesis increased from the initial state at 0 h after seeding on Matrigel, reaching a steady state after 4 h. This elevated cellular t-PA mRNA level decreased markedly at 24 h. In contrast, the cellular plasminogen activator inhibitor-1 (PAI-1) mRNA level demonstrated biphasic curves during the 24 h after seeding on Matrigel: the PAI-1 mRNA level was increased eightfold initially at 4 h over that at 0 h, then declined, and again secondarily increased to greater than tenfold at 18 h. Cellular levels of both 72 kD type IV collagenase and tissue inhibitor of metalloproteinase (TIMP-2) mRNA were increased only a slightly within 2-4 h. These elevated mRNA levels were maintained for 18 h, while the TIMP-1 mRNA level increased up to 18 h, reaching around three times the level at 0 h. However, on collagen-coated dishes, cellular levels of t-PA, PAI-1, 72 kD type IV collagenase, TIMP-1, and TIMP-2 mRNA were not greatly changed during incubation for 24 h. On Matrigel, the cellular t-PA mRNA level at 18 h after seeding was greatly increased when treated with specific anti-transforming growth factor-beta (TGF-beta) antibody. In contrast, both PAI-1 and TIMP-1 mRNA levels at 18 h were reduced in the presence of anti-TGF-beta antibody. Development of the capillary network on Matrigel was inhibited in the presence of anti-t-PA antibody. Epidermal growth factor (EGF) enhanced t-PA gene expression and TGF-beta inhibited its expression in HOME cells cultured on collagen-coated dishes. On the other hand, TGF-beta enhanced cellular expression of the PAI-1 gene. The formation of a capillary network by HOME cells on Matrigel appears to be balanced by angiogenic EGF and anti-angiogenic TGF-beta through modulation of PA activity.

Capillaries↗
PubMed1995

Apoptosis is induced in BHK cells by the tsBN462/13 mutation in the CCG1/TAFII250 subunit of the TFIID basal transcription factor.

A temperature-sensitive (ts) mutant of the BHK21 cell line derived from golden hamsters, tsBN462 has a mutation in the gene encoding the largest subunit of the TFIID complex, TAFII250/p230/CCG1, and arrests in the G1 phase at the nonpermissive temperature, 39.5 degrees C. We found that tsBN462 cells underwent apoptosis following growth arrest at 39.5 degrees C, suggesting a role for CCG1 as a repressor of apoptosis. By electron microscopic observation, tsBN462 cells at 39.5 degrees C showed characteristic features of apoptosis. Apoptosis was not suppressed by expression of Bc1-2 or the adenovirus E1B 19 kDa protein. Cell death was suppressed completely by expression of wild-type CCG1 and partially by wild-type p53, a growth suppressor protein. Cell cycle arrest induced by p53 may help survival of tsBN462 cells at 39.5 degrees C. Apoptosis was accelerated in SV40 large T antigen-transformed tsBN462 cells at 39.5 degrees C where SV40 large T antigen formed a complex with p53, implying that the apoptosis of tsBN462 cells at 39.5 degrees C occurred in a p53-independent manner. Our results suggest that CCG1/TAFII250 is required for the expression of factors regulating apoptosis.

Adenovirus E1B Proteins↗
PubMed1995

Carcinoma of the cystic duct protruding into the common bile duct: report of a case.

We report herein the case of 65-year-old man in whom a diagnosis of primary carcinoma of the cystic duct was made on the basis of Farrar's criteria. The patient was admitted with upper abdominal pain, and although there was no evidence of jaundice or a palpable mass, there was tenderness in his right upper quadrant. Carcinoma of the cystic duct was suspected on the basis of computed tomography and magnetic resonance imaging findings. Cholecystectomy with resection of the bile duct and lymph node resection was performed, and percutaneous transhepatic cholangiography revealed a filling defect in the common bile duct (CBD). The tumor was found to have arisen from the cystic duct and demonstrated papillary growth into the CBD intraluminally through the orifice of the cystic duct. Microscopically, the tumor was identified as papillary adenocarcinoma with invasion limited to the subserosal layer of the cystic duct. There were no signs of nodal metastasis.

Adenocarcinoma, Papillary↗
PubMed1995

Matrilysin: expression, purification, and characterization.

The expression vector pGEX-2T under the control of the IPTG-inducible tac promotor is effective for the production of a fusion protein of glutathione transferase (GST, 26 kDa) and promatrilysin (28 kDa) separated from the C-terminus of GST by a thrombin cleavage site. Zwittergen (palmityl sulfobetaine), 2%, solubilizes the fusion protein that is found associated with inclusion bodies. The solubilized fusion protein is purified by affinity chromatography on GSH agarose. Promatrilysin is obtained by thrombin cleavage either on the column or after GSH elution of the fusion protein. Mono S chromatography of the recovered protein yields homogeneous promatrilysin. The zinc content of promatrilysin and its activated enzyme product is slightly greater than 2 mol of zinc per mole of protein. The results indicate that the matrix metalloproteinases (MMPs) contain two metal-binding sites at which zinc is firmly bound and possibly a third site at which it is weakly bound. Primary sequence alignments for all the MMPs have a sequence homologous to the zinc-binding site of astacin, HExxHxxGxxH, suggesting one of the zinc sites is a catalytic one, in agreement with the known inhibition of these enzymes by chelators. However, the other zinc-binding site(s) likely reflect the different ways that astacin and the MMP subfamilies are stabilized, i.e., disulfides in astacin and metal ions in the MMPs.

Base Sequence↗