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Biomedical subjects

H Kido

Publications and source records attributed to H Kido.

At least 91 records · Page 5Linked to original sources
PubMed1995

Detection of tryptase TL2 and CD26 antigen in brain-derived cells non-permissive to T-cell line-tropic human immunodeficiency virus type 1.

Tryptase TL2 purified from MOLT-4 human T cells binds to the envelope protein of human immunodeficiency virus type 1 (HIV-1). Tryptase TL2 and CD26 antigen are supposed to play roles in HIV-1 entry into cells. Although CD4 is a principal receptor for HIV-1, brain cells expressing the CD4 antigen are not permissive to HIV-1 strains infectious to monocyte or T-cell lines. We examined whether the non-permissiveness of the brain-derived cells to standard HIV-1 strains could be explained by a lack of tryptase TL2 or CD26. Western blots showed that the amounts of tryptase TL2 expressed in cell lysates prepared from the brain-derived cells were similar to those prepared from various cells susceptible to HIV-1 strains. Furthermore, flow cytometry revealed the presence of the CD26 antigen on the cell surface of many types of cells. The resistance of the brain-derived cells to standard HIV-1 strains is not due to a lack of tryptase TL2 or CD26.

Brain↗
PubMed1995

Relationship of microparticles with beta 2-glycoprotein I and P-selectin positivity to anticardiolipin antibodies in immune thrombocytopenic purpura.

We investigated the association of beta 2-glycoprotein I and P-selectin with platelet-derived microparticles in 48 patients with immune thrombocytopenic purpura and 20 normal controls using two-color flow cytometric analysis. In addition, anticardiolipin antibodies were detected by an enzyme-linked immunosorbent assay. Platelet microparticles from the patients showed a higher positivity for beta 2-glycoprotein I than those from the normal controls (23.1 +/- 15.4% vs. 5.3 +/- 3.1%, p < 0.01), but this positivity was not related to the presence of platelet-associated IgG or to the severity of thrombocytopenia. In the 18 patients with more than 20% P-selectin-positive microparticles, beta 2-glycoprotein I positivity was significantly higher than in the 30 patients with less than 20% P-selectin-positive microparticles (37.1 +/- 20.5% vs. 21.5 +/- 17.3%, p < 0.01). In addition, anticardiolipin antibodies were detected in eight patients, and they had a significantly higher level of beta 2-glycoprotein I-positive microparticles than the patients without such antibodies (42.0 +/- 22.9% vs. 22.6 +/- 18.9%, p < 0.05). Our results suggest that anticardiolipin antibodies activate platelets in immune thrombocytopenic purpura and cause the generation of microparticles rich in beta 2-glycoprotein I and P-selectin. These microparticles may then act to regulate coagulation abnormalities in patients with anticardiolipin antibodies.

Adolescent↗
PubMed1995

Platelet-derived microparticles may influence the development of atherosclerosis in diabetes mellitus.

We investigated the association between low-density lipoprotein (LDL), triglycerides, and platelet activation in 18 patients with hypertension age 41-64 years and 18 with diabetes mellitus aged 43-70 years. Platelet P-selectin positivity and the microparticle level (indicators of activation) were both significantly higher in the diabetics than in healthy controls (P-selectin: 28.0% +/- 7.5% vs. 7.3% +/- 4.2%, P < 0.001; microparticles: 1900 +/- 966 vs. 526 +/- 158/10(4) platelets, P < 0.01). In contrast, there was no significant increase of either parameter in the patients with hypertension. Plasma microparticle levels were also significantly greater in the diabetics with high LDL levels than in those with low LDL levels (2375 +/- 949 vs. 1519 +/- 796/10(4) platelets, P < 0.05), and in those with high rather than low triglyceride levels (2188 +/- 845 vs. 1492 +/- 783/10(4) platelets, P < 0.05). However, platelet positivity for P-selectin was not significantly different between these two subgroups. Microparticle and P-selectin levels both showed no significant difference between the hypertensive patients with high and low LDL or triglyceride levels. These results suggest that platelet-derived microparticles may participate in the development or progression of atherosclerosis in patients with diabetes mellitus.

Adult↗
PubMed1995

Calcium requirement and inhibitor spectrum for intracellular HIV type 1 gp160 processing in cultured HeLa cells and CD4+ lymphocytes: similarity to those of viral envelope glycoprotein maturase.

We recently purified the calcium-independent processing protease named viral envelope glycoprotein maturase (VEM), that converts human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein precursor gp160 to gp120 and gp41, from the human CD4+ T cell line, Molt-4 clone 8 [Kido, H., Kamoshita, K., Fukutomi, A., and Katunuma, N. (1993) J. Biol. Chem. 268, 13406-13413]. In this report, we deal with the inhibitor specificity and calcium requirement for intracellular gp160 processing in cultured HeLa cells and human CD4+ lymphocytes. Processing of gp160 in these cells infected with recombinant vaccinia virus encoding the gp160 gene was not affected by intracellular calcium depletion induced by the calcium ionophore A23187 and EGTA or by intracellular calcium administration. Processing of gp160 by the purified VEM in vitro was not inhibited by EDTA, EGTA, or the metallo-protease inhibitor phosphoramidon, but was specifically inhibited by a substrate analog, decanoyl-RVKR-chloromethylketone, and the trypsin-type protease inhibitors aprotinin, HI-30, and diisopropyl fluorophosphate (DFP). It was also inhibited by E-64 and thiol reagents. But intracellular gp160 processing was inhibited only by permeable, low molecular mass inhibitors of VEM, such as DFP, E-64, and thiol reagents. Syncytium formation induced by cell surface gp120 was also inhibited by permeable inhibitors of VEM. Taken together, our results indicate that calcium ions may not be essential for intracellular gp160 processing and so HIV-1 gp160 induced by recombinant vaccinia virus may be processed mainly by a protease(s) that does not require calcium ions, such as VEM in these cells.

Amino Acid Sequence↗
PubMed1995

Systematic approach to a dosage regimen for phenytoin based on one-point, steady-state plasma concentration.

A systematic approach to individualizing the phenytoin (PHT) dose from a previous dose (D) and steady-state concentration (Css) pair was established by the combined use of two methods based on recently reported population pharmacokinetic parameters. This system applies the Michaelis-Menten equation to the initial data pair (D1-Css1) and solves for (a) maximum metabolic rate constant (Vmax) assuming the population mean for the Michaelis constant (Km) (method 1), and (b) Km assuming the population mean for Vmax (method 2). The derived estimates of Vmax and Km are then put through a series of filters, which results in the selection of method 1 and/or method 2 or allocation of a third category that needs further evaluation. A simulation study was performed to find a series of filters. The presented approach was applied retrospectively to the patients' data of 35 sets. Accurate predictions of the Css error within 5 micrograms/ml were obtained in 84% of the 25 cases, and in 30% of the 10 cases excluded. This systematic approach gives better prediction performance in mean error, mean absolute error, and root mean square error than a Bayesian feedback method.

Adult↗
PubMed1995

Significance of cytokines and CD68-positive microparticles in immune thrombocytopenic purpura.

We investigated the significance of cytokines (soluble interleukin-2 receptor, granulocyte-macrophage colony-stimulating factor, interleukin-6, and interferon-gamma) and CD68-positive microparticles in immune thrombocytopenic purpura. Cytokines were measured by enzyme-linked immunosorbent assay and microparticles were detected by flow cytometry. CD68 expression by histiocytic U937 cells incubated with lipopolysaccharide or cytokines was also assessed in a control study. The level of CD68-positive microparticles was significantly higher in the patients with thrombocytopenia than in normal controls (p < 0.01). The soluble interleukin-2 receptor level was also significantly higher in patients than in controls (p < 0.01), but the other cytokines did not show a significant difference. However, patients with severe thrombocytopenia (platelet count > 20,000/microliters) had significantly higher levels of granulocyte-macrophage colony-stimulating factor and interleukin-6 than the controls (p < 0.05). When opsonized platelets were incubated with activated U937 cells, lipopolysaccharide and granulocyte-macrophage colony-stimulating factor caused an increase of CD68-positive microparticles in the supernatant. These results suggest that granulocyte-macrophage colony-stimulating factor is released by activated T cells in immune thrombocytopenic purpura and activates monocyte/macrophage phagocytosis, resulting in an increase of circulating CD68-positive microparticles and enhanced platelet destruction.

Adolescent↗
PubMed1995

Low incidence of hemorrhagic infarction following coronary reperfusion with nasaruplase in a canine model of acute myocardial infarction. Comparison with recombinant t-PA.

An examination was made of the coronary thrombolytic effects of nasaruplase in a canine model of acute myocardial infarction. The model was produced by selective injection of an artificial thrombus into the coronary artery stenosed by laser ablation. Intravenous nasaruplase (8 U/kg/min) showed an equivalent thrombolytic effect to a recombinant tissue-type plasminogen activator (rt-PA, 10,000 IU/kg/min) as assessed by reperfusion rate (78.6 versus 79.2%) and reperfusion time (37.4 +/- 5.2 versus 37.0 +/- 2.5 min). Nasaruplase decreased the plasma alpha 2-plasmin inhibitor (alpha 2-PI) level by 28% immediately after reperfusion, but hardly altered fibrinogen or plasmin-alpha 2-plasmin inhibitor complex (PIC) levels. By contrast, rt-PA significantly decreased plasma alpha 2-PI and fibrinogen levels, by 84% and 92% respectively, and, increased PIC level more than 70-fold. Hemorrhagic infarction occurred in 2 of 14 animals in the nasaruplase group and in 9 of 19 animals in the rt-PA group. In these animals, significant correlations were found between the ratio of the hemorrhagic infarction area to total infarct area and the plasma alpha 2-PI (r = -0.740, p < 0.05) or fibrinogen (r = -0.798, p < 0.05) concentrations, as well as between the recovery rate of left ventricular regional wall motion and the plasma alpha 2-PI (r = 0.924, p < 0.01) or fibrinogen (r = 0.864, p < 0.01) concentrations. It is concluded that nasaruplase is a potent thrombolytic agent which preserves left ventricular function with a lesser rate of hemorrhagic infarction than rt-PA. Further, nasaruplase administration results in recovery of left ventricular regional wall motion and systolic function, such as Vmax.

Animals↗
PubMed1995

[Detection of soluble interleukin-2 receptor in idiopathic thrombocytopenic purpura].

We measured soluble interleukin-2 receptor (sIL-2 R) in serum samples from 57 patients with idiopathic thrombocytopenic purpura (ITP). The sIL-2 R level was significantly increased in the ITP patients (481.3 +/- 378.5 U/ml) compared with controls (176.2 +/- 66.9 U/ml) (p < 0.001), and was significantly higher in 8 patients positive for hepatitis C virus (HCV) antibody positive (1,140.7 +/- 194.3 U/ml) than in 49 HCV-antibody negative patients (378.9 +/- 278.6 U/ml) (p < 0.0001). There was also a significant difference between the HCV-antibody negative ITP patients and the controls (p < 0.01). Elevated sIL-2 R levels correlated with the CD 4/8 ratio (p < 0.05), but not with the platelet count or the level of platelet-associated IgG. The increase of sIL-2 R in ITP may be related to the immunological abnormalities underlying this disease.

Adult↗
PubMed1994

Involvement of a cystatin-alpha-sensitive cysteine proteinase in the degradation of native L-lactate dehydrogenase and serum albumin by rat liver or kidney lysosomes.

A lysosomal cysteine proteinase plays a critical role in the lysosomal degradation of native L-lactate dehydrogenase. The effects of a recombinant cystatin alpha and other cysteine proteinase inhibitors on the degradation of unlabeled native L-lactate dehydrogenase by total lysosomal enzymes were examined in vitro. L-Lactate dehydrogenase was inactivated, its 35-kDa subunit disappeared and the final amino acid degradation products were produced during an incubation with disrupted lysosomes in vitro. These processes were all markedly suppressed by a small amount of cystatin alpha without inhibiting the activities of the known lysosomal cysteine proteinases, cathepsins B, H, L, and J. These results suggest that a cysteine proteinases, which is highly sensitive to cystatin alpha and distinct from other known lysosomal cysteine proteinases, is involved in the lysosomal degradation of native L-lactate dehydrogenase. An L-lactate-dehydrogenase-inactivating enzyme in the extracts of lysosomes was partially purified. It was separated from cathepsin J using a Sephacryl S-200 gel-filtration column and was further separated from cathepsin H by DEAE-Sephadex A-50 anion-exchange column chromatography. The inactivation and degradation of L-lactate dehydrogenase by this partially purified enzyme were all markedly suppressed by a low level of cystatin alpha without inhibiting the activities of both cathepsins B and L. The degradation of rat serum albumin by the partially purified enzyme was also inhibited by the same concentration of cystatin alpha. It is concluded that a cystatin-alpha-sensitive cysteine proteinase, other than cathepsins B, H, L and J, is present in lysosomes and functions in the lysosomal degradation of at least native L-lactate dehydrogenase and serum albumin.

Animals↗
PubMed1994

Close co-localization of CD4 and a serine esterase tryptase TL2 on the cell-surface of human monocytoid and CD4+ lymphoid cells.

Tryptase TL2, a serine esterase in the membrane of human monocytoid and CD4+ lymphoid cells, specifically binds to the V3 domain of HIV-1 gp120. Here we report that monoclonal antibodies against CD4 that recognize the epitope interacting with gp120 specifically blocked the immunostaining of cell-surface tryptase TL2, although the antibody does not cross-react with tryptase TL2. Down-regulation of cell-surface CD4 induced by HIV-1 Nef prevented this blocking effect. These data suggest that CD4 is closely co-localized with tryptase TL2 on the cell surface and that regulation of the expression of tryptase TL2 is not associated with that of CD4.

Antibodies, Monoclonal↗
PubMed1994

Chromaffin cells express Alzheimer amyloid precursor protein in the same manner as brain cells.

Amyloid precursor protein (APP) 695 is remarkably expressed in the brain as compared with APP751 and APP770 which are dominant in other tissues. This study showed that human and bovine adrenal medullae dominantly expressed mRNA of APP695 as do brain nerve cells, while the adrenal cortexes expressed mRNAs of APP751 and APP770 as in other non-neural tissues. In immunohistochemistry, chromaffin cells of young rat adrenal medullae and primary cultured bovine chromaffin cells were significantly stained with a monoclonal antibody (mAb) against the common domain of the amino-terminal side of human APPs. At higher magnification, the immunostained cells revealed that APP was granularly distributed not only in the perikaryon but also in the cell processes. These results suggest that primary cultured chromaffin cells representing the state of adrenal medulla in vivo are a useful model for studying the pathophysiological functions of APPs and the mechanism of processing of APPs as a model of neuronal systems.

Adrenal Cortex↗
PubMed1994

Inhibitors of chymotrypsin-like proteases inhibit eosinophil peroxidase release from activated human eosinophils.

Eosinophils contain many cytotoxic mediators including eosinophil peroxidase (EPO) in their granules; on degranulation, these mediators are released by various pathophysiological stimuli, resulting in severe tissue damage. However, little is known about inhibitors of degranulation. Here, we report that eosinophils isolated from patients with bronchial asthma have significant chymotrypsin-like serine protease activity in the high salt extract fraction. The protease partially purified and labeled with [3H]diisopropylfluorophosphate has an apparent molecular mass of 28 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The chymotrypsin-like protease was not immunoreactive with antibodies against chymase and atypical chymase from rat mast cells or with an antibody against cathepsin G from human neutrophils. Studies on the subcellular distribution of the chymotrypsin-like protease indicated that the enzyme is mainly localized with EPO in eosinophil granules. Chymostatin, an inhibitor of the chymotrypsin-like protease(s), but not an inhibitor of other types of proteases, markedly inhibited the EPO release from eosinophils that was induced by immunoglobulin G plus rIL-5 or platelet-activating factor, although it had no effect on the release of EPO induced by the calcium ionophore A23187. These results suggest that proteolytic activation by chymotrypsin-like serine protease(s) in eosinophils plays some role in the process of receptor-mediated EPO release from the granules.

Affinity Labels↗
PubMed1994

Meprin is predominantly involved in parathyroid hormone degradation by the microvillar membranes of rat kidney.

Hydrolysis of fragments of the C-terminal and mid-portions of parathyroid hormone (PTH) by a phosphoramidon-insensitive metallo-endopeptidase, previously purified by us from the microvillar membranes of rat kidney, and by the microvillar membranes of rat kidney themselves were investigated using a reverse-phase HPLC, and the amino acid sequences of each produced PTH metabolite were compared after their determination with an automated gas-phase protein sequencer. The results showed that both the purified microvillar endopeptidase and the microvillar membranes of rat kidney limited hydrolyzed human (h) PTH-(39-84) and hPTH-(39-68) mainly at peptide bonds flanked by a hydrophilic amino acid residue, where are characteristic for the purified microvillar endopeptidase but not for other known endopeptidase including endopeptidase 24.11. In addition, most of PTH metabolites generated by the microvillar membranes were insensitive to phosphoramidon and had amino acid sequences identical to those generated by the purified microvillar endopeptidase, indicating that these metabolites were produced by the enzyme integrated in the membranes. Since analysis of the N-terminal amino acid sequence of the purified microvillar endopeptidase revealed that it was structurally identical to rat meprin (EC 3.4.24.18), these results indicate that the purified microvillar endopeptidase or meprin is predominantly involved in PTH degradation by the microvillar membranes of rat kidney as an integral membrane protein.

Amino Acid Sequence↗
PubMed1994

In vivo dopamine-D2 and serotonin-5-HT2 receptor binding study of risperidone and haloperidol.

An in vivo receptor binding technique was applied to evaluate the affinities of risperidone and haloperidol for dopamine-D2 receptors (D2) and serotonin-5-HT2 receptors (5-HT2) in rat brain with [3H]YM-09151-2 and [3H]ketanserin as selective ligands. Radioactivities were obtained in the striatum frontal cortex, and cerebellum of the rats treated with the ligands. Time course study of receptor occupancy at 25 to 250 min after single doses of the drugs (1 mg/kg, IP) showed higher 5-HT2 occupancy in the frontal cortex and lower D2 occupancy in the striatum by risperidone than by haloperidol. Dose-response analysis of receptor occupancy revealed risperidone demonstrated higher binding affinity for 5-HT2 than for D2, while the reverse was observed with haloperidol. It appeared that risperidone (1 mg/kg, IP), but not haloperidol (1 mg/kg, IP), demonstrated regional selectivity in D2 occupancy favouring frontal cortex more than the striatum. That risperidone displayed a higher ratio of 5-HT2 to D2 in occupancy than haloperidol is in agreement with the previous findings obtained in vitro.

Animals↗
PubMed1994

Time course of dopamine1,2 and serotonin2 receptor binding of antipsychotics in vivo.

An in vivo receptor binding technique was applied to evaluate the affinities of clozapine (20 mg/kg), RMI-81582 (20 mg/kg), and haloperidol (1 mg/kg) for dopamine D1, D2 and serotonin 5-HT2 receptors in rat brain with [3H]-SCH23390, [3H]-YM-09151-2, and [3H]-ketanserin as selective ligands. The time course study of receptor occupancy at 25 to 250 min after intraperitoneal administration of the drugs showed higher 5-HT2 and lower D2 receptor occupancies of clozapine and RMI-81582 than those of haloperidol both in the striatum and frontal cortex. The 5-HT2/D2 ratios of receptor occupancy for clozapine and RMI-81582 were about 6 to 8 times higher than that for haloperidol. Stable occupancies of D1 receptors were observed only with RMI-81582 and clozapine, the former demonstrating the higher occupancy. These findings are in agreement with the previous findings obtained under in vitro conditions and may account for some part of the properties of atypical antipsychotic drugs.

Animals↗