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Y Hashimoto

Publications and source records attributed to Y Hashimoto.

At least 91 records · Page 5Linked to original sources
PubMed2001

Novel immunosuppressive effect of FK506 by augmentation of T cell apoptosis.

We have recently reported the accumulation of oligoclonal activated T cells in the spontaneously developed autoimmune pancreatitis in aly/aly mouse. In this study, we examined the effects of FK506 in this mouse model in preventing autoimmune pancreatitis and investigated its action on calcium signalling apoptosis of alymphoplasia (aly) lymphocytes in vitro. Mice were treated with FK506 from 8 to 25 weeks of age. At the age of 15 weeks, minimal mononuclear cell infiltration was observed in the pancreas in both the FK506 treated group and the control group. Furthermore, a marked cell infiltration associated with destruction of acini and partial fatty changes were observed in 25-week-old control mice. In contrast, FK506 treated mice showed almost no tissue destruction or mononuclear cell infiltration at the age of 25 weeks. Furthermore, at 15 weeks of age, most mononuclear cells in FK506-treated mice were TUNEL positive, whereas only a few were positive in control mice. This augmentation of T cell apoptosis by FK506 was confirmed using naive splenocytes activated by PMA and ionomycin in vitro. Finally, a suppressive effect of FK506 on Bcl-2 production but not on Bax production was confirmed by Western blotting. This unique effect of FK506 on the augmentation of T cell apoptosis is probably one of the mechanisms explaining its beneficial effect on aly autoimmune pancreatitis.

Animals↗
PubMed2001

Zinc supplementation enhances the response to interferon therapy in patients with chronic hepatitis C.

We evaluated the synergistic effect of zinc supplementation on the response to interferon (IFN) therapy in patients with intractable chronic hepatitis C in a pilot study using natural IFN-alpha with or without zinc. No clinical differences were observed between patients treated with IFN alone (n=40) and IFN with polaprezinc (IFN + Zn, n=35). All patients were positive for HCV genotype Ib and had more than 105 copies of the virus/mL serum. Ten million units of natural IFN-alpha was administered daily for 4 weeks followed by the same dose every other day for 20 weeks. In the IFN + Zn group, patients received an additional dose of 150 mg/day polaprezinc orally throughout the 24-week IFN course. No additional side-effects of polaprezinc were noted but four out of 40 IFN alone treatment and three out of 35 IFN + Zn group withdrew because of side-effects. Complete response (CR) was defined as negative HCV RNA in the serum on PCR and normal aminotransferase level 6 months after therapy. Incomplete response (IR) was normal liver enzyme and positive serum HCV RNA. Both of them were evaluated at the 6 months after the completion of the treatment. Patients with higher levels of serum HCV (more than 5 x 105 copies/mL) had little response in both treatment groups. Patients with moderate amount of HCV (105 to 4.99 x 105/mL) showed high response rates in combination group (CR: 11/27, 40.7%; CR + IR 15/27, 64.3%), better than IFN alone (CR: 2/15, 18.2%; CR + IR: 2/15, 18.2%). Serum zinc levels were higher in patients with IFN + Zn group than in the IFN group. Our results indicate that zinc supplementation enhances the response to interferon therapy in patients with intractable chronic hepatitis C.

Adult↗
PubMed2001

Role of protein kinase C, K(ATP) channels and DNA fragmentation in the infarct size-reducing effects of the free radical scavenger T-0970.

1. In the present study, we investigated the effect of 1-(3-tert-butyl-2-hydroxy-5-methoxyphenyl)-3-(3-pyridylmethyl) urea hydrocloride (T-0970), a novel water-soluble low-molecular weight free radical scavenger, on the generation of hydroxyl radicals in vivo and on myocardial infarct size in an in vivo model of myocardial infarction in rabbits. 2. T-0970 scavenged hydroxyl radicals generated in the myocardium during reperfusion, as assessed by using a microdialysis technique and HPLC in an in vivo model with 30 min coronary occlusion and 30 min reperfusion in rabbits. 3. Another group of rabbits was subjected to 30 min coronary occlusion and 48 h reperfusion. The control group (n = 10) was infused with saline for 190 min from 10 min before occlusion to 180 min after reperfusion. The treatment group (T-0970 group; n = 10) was injected with a bolus 2.5 mg/kg T-0970 and then infused with T-0970 for 190 min from 10 min before reperfusion to 180 min after reperfusion at a rate of 100 microg/kg per min. The T-0970 + CHE group (n = 5) was given chelerythrine (CHE; a selective inhibitor of protein kinase C (PKC); 5 mg/kg, i.v.) 10 min before the administration of T-0970. The T-0970 + 5-HD group (n = 5) was given 5-hydroxydecanoate (5-HD; an inhibitor of mitochondrial K(ATP) channels; 5 mg/kg, i.v.) 10 min before the administration of T-0970. The CHE and 5-HD groups were given CHE (5 mg/kg, i.v.) and 5-HD (5 mg/kg, i.v.) 20 min before reperfusion, respectively. After 48 h reperfusion, infarct size was measured histologically and expressed as a percentage of the area at risk (AAR). In another series of experiments, the control (n = 5) and T-0970 (n = 5) groups were killed 4 h after reperfusion following 30 min coronary occlusion and DNA fragmentation in myocytes was assessed using in situ dUTP nick end-labelling (TUNEL) at the light microscopic level. 4. Infarct size, as a percentage of AAR, in the T-0970 group was significantly reduced compared with the control group (21+/-4 vs 41+/-4%, respectively; P<0.05). This reduction of infarct size by T-0970 was abolished by pretreatment with CHE and 5-HD. Neither CHE nor 5-HD alone had any effect on infarct size. The percentage of infarcted myocytes with DNA fragmentation by TUNEL in the T-0970 group was significantly reduced compared with the number in the control group (4.0+/-1.5 vs 10.7+/-1.9%, respectively; P<0.05). 5. T-0970, a free radical scavenger, improved reperfusion injury. This effect seemed to be mediated by activation of PKC, the opening of mitochondrial K(ATP) channels and inhibition of DNA fragmentation.

ATP-Binding Cassette Transporters↗
PubMed2001

Morphological spectrum of cyclin D1-positive mantle cell lymphoma: study of 168 cases.

Immunostaining for cyclin D1 is essential for reliable diagnosis of mantle cell lymphoma (MCL). However, a small number of cyclin D1-positive lymphomas other than MCL have been encountered. Our goal was to investigate the morphological spectrum of MCL as a disease entity, based on cyclin D1 overexpression. We reviewed 181 biopsy specimens obtained from 168 cases of cyclin D1-positive MCL. Typical findings were the presence of nodular (53.9% of cases) or diffuse (46.1%) histological patterns, containing mantle zone patterns (16.8%), naked germinal centers (33.5%) and perivascular hyaline deposition (83.2%). Unusual findings of residual germinal centers with a mantle cuff (four cases) and follicular colonization (two cases) were seen. High magnification showed a monotonous proliferation of tumor cells with cytological diversity including small (3.0%), intermediate (43.1%), medium (34.1%), medium-large (13.2%) and large (6.6%) cells. Pleomorphic and blastic/blastoid variants were encountered in 9.6 and 7.2% of cases, respectively. Three cases had foci of cells of considerable size, with a moderately abundant pale cytoplasm resembling marginal zone B cells. Two cases showed an admixture of cells which appeared transformed and mimicked the histology of chronic lymphocytic leukemia/small lymphocytic leukemia. In one, neoplastic mantle zones were surrounded by sheets of mature plasma cells, resembling the plasma cell type of Castleman's disease. An admixture of areas characteristic of MCL and of other larger cells, indicating histological progression or a composite lymphoma, were observed in seven cases. In high-grade lesions of five cases, nuclear staining of cyclin D1 was rarely detected. In our experience, cyclin D1 expression was also found in nine lymphomas other than MCL (five plasma cell myelomas, three Hodgkin's disease and one anaplastic large cell lymphoma). The application of cyclin D1 staining prompted us to recognize the broad morphological spectrum of MCL. MCL can be diagnosed with the application of cyclin D1 immunostaining, if careful attention is given to architectural and cytological features.

Adult↗
PubMed2001

Large granular lymphocytes in the oviduct of developing and hormone-treated chickens.

1. In the present study the distribution of large granular lymphocytes (LGLs) and influence of oestrogen on these cells was investigated in the oviduct of chickens by the observation of H and E stained sections. 2. The LGLs first appeared in the oviduct at 9 weeks and their frequency of occurrence increased with age and was highest in the infundibulum and vagina from 21 to 32 weeks of age. The frequency of occurrence of LGLs from magnum to uterus (glandular part) was low. These cells were located at the base, middle and apical parts of the lining epithelium as well as in the sperm-storage glandular epithelium. 3. When chickens of 21 weeks were treated with DES, LGLs abundantly infiltrated in the oviducal epithelium in comparison to the control. 4. These results suggested that the development of LGLs in the oviduct of chickens correlates with oestrogen secretion.

Age Factors↗
PubMed2001

Headspace constituents of the tree remain of Cinnamomum camphora.

The volatile ingredients isolated from a fresh tree of Cinnamomum camphora (camphor tree) and from a tree remain of C. camphora were collected by using headspace techniques and analyzed by means of gas chromatography/mass spectrometry (GC/MS). 99.77% of the constituents consisting 23 components from the fresh tree, 98.68% of the constituents consisting 24 components from the tree remain were identified. Of these ingredients, camphor was obtained as the most abundant component.

Gas Chromatography-Mass Spectrometry↗
PubMed2001

Tolerance of point substitution of methionine for isoleucine in hen egg white lysozyme.

X-ray structure determination of proteins by using the multiple-wavelength anomalous dispersion method targeting selenomethionine is now widely employed. Isoleucine was examined for the second choice of the substitution of methionine next to leucine. We performed a systematic mutational study of the substitutions of methionine for isoleucine. All mutated lysozymes were less stable than the wild-type by about 1 kcal/mol and it is suggested that this instability was caused by the change in residual hydrophobicity from isoleucine to methionine. The X-ray structures of all mutant lysozymes were very similar to that of the wild-type. In addition, both the accessible surface areas and the conformation of the side chain of methionine in all mutant lysozymes were similar to those of the side chain at the respective isoleucine in the wild-type. Therefore, it is suggested that the mutation from isoleucine to methionine in a protein can be considered as a "safe" substitution.

Amino Acid Substitution↗
PubMed2001

The successful management of thoracoscopic thoracic duct ligation in a compromised infant with targeted lobar deflation.

IMPLICATIONS: We describe the successful management of thoracoscopic thoracic duct ligation in a 2.5-kg compromised infant by using selective lobar-bronchial blockade. The technique reduces the risk of intraprocedural physiologic impairment, allowing the benefits of otherwise minimally invasive thoracoscopic procedures, even when the conditions of children are severely compromised.

Chylothorax↗
PubMed2001

Inhalation anesthetics induce apoptosis in normal peripheral lymphocytes in vitro.

BACKGROUND: The authors hypothesized that perioperative lymphocytopenia is partially caused by apoptosis of lymphocytes induced by inhalation anesthetics. Therefore, they evaluated whether sevoflurane and isoflurane induce apoptosis of normal peripheral lymphocytes. METHODS: Normal peripheral blood mononuclear cells were exposed to sevoflurane and isoflurane, and the percentages of apoptotic lymphocytes was measured by Annexin V-fluorescein isothiocyanate-7-amino actinomycin D flow cytometry after 24 h of exposure (0.5, 1.0, and 1.5 mm) and after 6, 12, and 24 h of exposure (1.5 mm). The percentages of lymphocytes with caspase 3-like activity were also measured after 24 h of exposure (1.5 mm). RESULTS: The percentages of apoptotic lymhocytes were increased in a dose-dependent manner (controls: 5.1 +/- 1.4%; sevoflurane: 7.3 +/- 1.3% [0.5 mm], 9.1 +/- 1.5% [1.0 mm], 12.6 +/- 2.1% [1.5 mm]; isoflurane: 7.5 +/- 1.6% [0.5 mm], 10.5 +/- 1.5% [1.0 mm], 16.3 +/- 2.7% [1.5 mm]) after 24 h of exposure and in a time-dependent manner (controls: 1.2 +/- 0.4% [6 h], 3.4 +/- 0.7% [12 h], 5.6 +/- 1.2% [24 h]; sevoflurane: 1.8 +/- 0.4% [6 h], 6.4 +/- 1.2% [12 h], 11.3 +/- 2.2% [24 h]; isoflurane: 2.6 +/- 0.5% [6 h], 8.8 +/- 1.5% [12 h],16.0 +/- 1.9% [24 h]) at the concentration of 1.5 mm. The percentages of lymphocytes with caspase 3-like activity were increased (controls: 10.0 +/- 1.1%; sevoflurane: 13.8 +/- 1.2%; isoflurane: 17.0 +/- 1.3%). CONCLUSIONS: Both sevoflurane and isoflurane induced apoptosis in peripheral lymphocytes in dose-dependent and time-dependent manners in vitro.

Adult↗
PubMed2001

Oblique wedge osteotomy for femoral diaphyseal deformity in fibrous dysplasia: a case report.

A patient with fibrous dysplasia who had a three-dimensional diaphyseal deformity in the left femur was treated using an oblique wedge osteotomy. The patient was 26-year-old man with a history of two pathologic fractures in the midshaft of the femur. A 22 degrees angular deformity in the coronal plane and 15 degrees anterior bowing were corrected. The results at a followup 2 years after surgery were satisfactory in functional and radiologic terms. The technique and advantages of the oblique wedge osteotomy are discussed.

Adult↗
PubMed2001

Bronchoconstrictive and relaxant effects of lidocaine on the airway in dogs.

OBJECTIVE: Intravenous lidocaine commonly is used to treat ventricular arrhythmias and to attenuate reflex airway constriction and intracranial pressure elevation during airway manipulation in intensive care units. There is much controversy as to the actions of lidocaine on the airway, so the aim of this study was to compare, in detail, the actions of lidocaine with those of bupivacaine and procaine on airway caliber and the associated changes in plasma catecholamine concentrations in the dog. DESIGN: Prospective, randomized, controlled experimental in vivo and in vitro study. SETTING: A university research laboratory. SUBJECTS: Mongrel dogs. INTERVENTIONS: In the first experiment, we evaluated the effects of intravenous local anesthetics--lidocaine 0-10 mg/kg (n = 7), bupivacaine 0-2.5 mg/kg (n = 7), or procaine 0-20 mg/kg (n = 7)--on basal airway tone. In second experiment, histamine (10 microg/kg + 500 microg x kg(-1) x hr(-1), n = 6), serotonin (10 microg/kg + 500 microg x kg(-1) x hr(-1), n = 7), and methacholine (0.5 microg/kg + 300 microg x kg(-1) x hr(-1), n = 7) were infused to determine the effects of lidocaine (0-10 mg/kg) on agonist-induced bronchoconstriction. In addition, the actions of lidocaine on vagal nerve stimulation were examined (n = 7). MEASUREMENTS AND MAIN RESULTS: Bronchial cross-sectional area at the third bronchial bifurcation of dogs was monitored continuously through a fiberoptic bronchoscope. In the first experiment, all local anesthetics produced a dose-dependent decrease in basal bronchial cross-sectional area. In the second experiment, lidocaine significantly potentiated histamine and serotonin-induced bronchoconstriction. In contrast, lidocaine antagonized methacholine- and vagal nerve stimulation-induced bronchoconstriction. CONCLUSION: We have clearly demonstrated that lidocaine may produce direct bronchoconstriction and worsen some agonist-induced bronchoconstriction, but it prevents reflex airway constriction. Therefore, we suggest that this agent be used with caution in asthmatics.

Anesthetics, Local↗
PubMed2001

Structure of a new 'aspzincin' metalloendopeptidase from Grifola frondosa: implications for the catalytic mechanism and substrate specificity based on several different crystal forms.

Crystal structures of a peptidyl-Lys metalloendopeptidase (MEP) from the edible mushroom Grifola frondosa (GfMEP) were solved in four crystal forms. This represents the first structure of the new family 'aspzincins' with a novel active-site architecture. The active site is composed of two helices and a loop region and includes the HExxH and GTxDxxYG motifs conserved among aspzincins. His117, His121 and Asp130 coordinate to the catalytic zinc ligands. An electrostatically negative region composed of Asp154 and Glu157 attracts a positively charged Lys side chain of a substrate in a specific manner. A Tyr133 side chain located on the S1' pocket had different configurations in two crystal forms and was not observed in the other crystal forms. The flexible Tyr133 plays two roles in the enzymatic function of GfMEP. The first is to provide a hydrophobic environment with Phe83 in order to accommodate the alkyl part of the Lys side chain of a substrate and the second is as a 'proton donor' to the oxyanion of the tetrahedral transition state to stabilize the reaction transition state.

Amino Acid Sequence↗
PubMed2001

Phage display cloning and characterization of monoclonal antibody genes and recombinant Fab fragment against the CD98 oncoprotein.

The Fab gene of anti-CD98 heavy chain (h.c.) monoclonal antibody (mAb) HBJ127 was cloned and expressed as a recombinant Fab (rFab) fragment by means of a phage display system. The variable heavy and light chain genes of HBJ127 were found to be derived from VOx-1 and IgVk8-30 germline, respectively. Extensive somatic mutation was found in the heavy chain complementarity determining region 2. rFab fragment was purified homogeneously from crude bacterial lysates by Ni-chelate chromatography in a yield of 71.4 mg from 100 ml of culture. rFab fragment was reactive with the cell surface of CD98-positive cells irrespective of tissues of origin, but not with CD98-negative cells. The recognition site of the rFab fragment was identical to that of mAb since the binding of rFab fragment to HeLaS(3) cells was completely inhibited by pretreatment with an excess of mAb. The relative affinity values of rFab fragment and mAb were found to be 0.11 x 10(8) and 0.35 x 10(8) M(-1), respectively. Three-fold lower affinity of rFab fragment may be due to the difference of valency of the antibody preparation. Cell growth inhibition in vitro by rFab fragment preincubated with anti-Fab suggests that the rFab fragment produced by cloned gene-bearing Escherichia coli was identical to the Fab part of HBJ127 mAb. These results show that a small fragment with antigen binding activity similar to that of the parent mAb can easily be prepared by using a phage display system. To our knowledge, this is a first report of the production of anti-CD98 h.c. rFab fragment.

Amino Acid Sequence↗
PubMed2001

[Clinical evaluation of an immunochromatography test for rapid diagnosis of influenza].

We evaluated a rapid diagnostic kit that detects influenza type A and B viral antigens by immunochromatography, Quick Vue Influenza Test (Quidel Corp., San Diego, CA, USA), with 425 specimens collected from patients with influenza-like symptoms at three hospitals between January and March 2001. The specimens included 184 nasal aspirates, 140 nasal swabs, and 101 throat swabs. The test correctly identified 179 of the 204 culture positive specimens and 203 of the 221 culture negative specimens; the sensitivity and specificity compared with the culture were 87.7% and 91.9%, respectively. The sensitivity of the test was 92.6% (112/121) for nasal aspirates, 83.7% (41/49) for nasal swabs, and 76.5% (26/34) for throat swabs, which is similar to the results for conventional rapid enzyme immunoassay kits for influenza virus infection. The sensitivity and specificity of the QuickVue Influenza Test were equivalent to those of Flu OIA (BioStar, Inc., Boulder, CO, USA), with the agreement of 84.2%. Although the QuickVue Influenza Test does not differentiate between influenza A and B viruses, the easy-to-use kit detects both types in the physician's office, allowing physicians to make a decision on prescription of neuraminidase inhibitor therapy during the initial visit.

Evaluation Studies as Topic↗
PubMed2001

Extracellular synthesis, specific recognition, and intracellular degradation of cyclomaltodextrins by the hyperthermophilic archaeon Thermococcus sp. strain B1001.

A unique extracellular and thermostable cyclomaltodextrin glucanotransferase (CGTase) from the hyperthermophilic archaeon Thermococcus sp. strain B1001 produces predominantly (>85%) alpha-cyclomaltodextrin (alpha-CD) from starch (Y. Tachibana, et al., Appl. Environ. Microbiol. 65:1991--1997, 1999). Nucleotide sequencing of the CGTase gene (cgtA) and its flanking region was performed, and a cluster of five genes was found, including a gene homolog encoding a cyclomaltodextrinase (CDase) involved in the degradation of CDs (cgtB), the gene encoding CGTase (cgtA), a gene homolog for a CD-binding protein (CBP) (cgtC), and a putative CBP-dependent ABC transporter involved in uptake of CDs (cgtDE). The CDase was expressed in Escherichia coli and purified. The optimum pH and temperature for CD hydrolysis were 5.5 and 95 degrees C, respectively. The molecular weight of the recombinant enzyme was estimated to be 79,000. The CDase hydrolyzed beta-CD most efficiently among other CDs. Maltose and pullulan were not utilized as substrates. Linear maltodextrins with a small glucose unit were very slowly hydrolyzed, and starch was hydrolyzed more slowly. Analysis by thin-layer chromatography revealed that glucose and maltose were produced as end products. The purified recombinant CBP bound to maltose as well as to alpha-CD. However, the CBP exhibited higher thermostability in the presence of alpha-CD. These results suggested that strain B1001 possesses a unique metabolic pathway that includes extracellular synthesis, transmembrane uptake, and intracellular degradation of CDs in starch utilization. Potential advantages of this starch metabolic pathway via CDs are discussed.

Amino Acid Sequence↗
PubMed2001

Treatment with sheng-mai-san reduces myocardial infarct size through activation of protein kinase C and opening of mitochondrial KATP channel.

Sheng-mei-san (SMS), a traditional Chinese formulation comprising Radix Ginseng, Radix Ophiopogonis and Fructus Schisandrae, has long been used for more than 700 years for patients with coronary heart disease. We attempted to clarify 1) whether SMS reduces myocardial infarct size, and 2) whether the infarct size-reducing effect of SMS is related to activation of protein kinase C and the opening of the mitochondrial KATP channels in Japanese white rabbits without collateral circulation. The results indicate that three days treatment but not acute treatment with SMS reduces myocardial infarct size through activation of protein kinase C and opening of the mitochondrial KATP channels.

Analysis of Variance↗