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Biomedical subjects

H Yoshida

Publications and source records attributed to H Yoshida.

At least 181 records · Page 10Linked to original sources
PubMed2001

XAFS study of the additive cation effect on the oxidation-resistance of platinum catalyst.

The additive cation effect on the oxidation-resistance of platinum supported on alumina was investigated by Pt L(III) and L(II)-edge XAFS. The white line intensity at Pt L(III)-edge of oxidized catalysts decreased with an increase in the electronegativity of the additive cation in the same way as the support effect previously reported: The addition of electrophilic cations make the supported platinum less oxidized state compared with the original Pt/Al2O3 and vice versa. Thus, it was revealed that the addition of more electrophilic cations provides the higher oxidation-resistance to platinum catalyst, even when platinum is supported on basic oxides.

Journal Article↗
PubMed2001

XANES analyses of silicon crystalline irradiated by nitrogen/oxygen ions.

X-ray absorption techniques have been applied to the characterization of 5 keV nitrogen / oxygen ions implanted silicon samples. The depth selective measurement of XANES by recording in PEY mode and the quantitative analysis by superposition of XANES spectra were carried out to elucidate the depth profile of implanted ions. It has been revealed that the silicon nitride phase were formed in silicon after prolonged N+ irradiation and it extended over the deep part of the damaged region from the surface. On the other hand, for the O+ irradiation, silicon dioxide phase were produced only in the shallow part of the damaged region, i.e., the silicon dioxide phase likely broke off during the irradiation.

Journal Article↗
PubMed2001

EXAFS study of crystal structures of (Ba1-xLax)2In2O5+x and their oxide ion conductivity.

Crystal structures of(Ba1-xLax)2In2O5+x (x=0.00, 0.20, 0.30, 0.40, 0.50) were analyzed by EXAFS and the powder X-ray Rietveld method. A Fourier transform of In K-edge EXAFS data from (Ba1-xLax)2In2O5+x showed a peak between 1.2 and 2.0 A attributed to the nearest oxide ions around In3+ cation. The peak as back-Fourier transformed, and the structural parameters were refined by the least square fitting. The coordination number of In3+ cation increases with increasing La3+ cation) content. This means oxygen is introduced at interstitial site by keeping an electroneutrality. As a result of the oxygen distribution, the oxide ion vacancies distribute randomly. The electrical conductivities of (Ba1-xLax)2In2O5 rapidly increased above 1203 K due to the order-disorder transition of oxygen vacancy. On the other hand, the electrical conductivities of (Ba1-xLax)2In2O5+x (x=0.20, 0.30, 0.35. 0.40, 0.45, 0.50) did not show the sharp discontinuity in the conductivity because the disorder phase of defective perovskite type structure was stabilized by doping La3+ cations at A-site even at low temperature.

Journal Article↗
PubMed2001

Desferrioxamine, an iron chelator, upregulates cyclooxygenase-2 expression and prostaglandin production in a human macrophage cell line.

Prostaglandins (PGs) play regulatory roles in a variety of physiological and pathological processes, including the immune response, cytoprotection and inflammation. Desferrioxamine (DFX), an iron chelator, is known to reduce free radical-mediated cell injury and to upregulate certain inflammatory mediators. We investigated the effects of DFX on the production of PGs and the expression of cyclooxygenase-2 (COX-2), the rate-limiting enzyme in the synthesis of PGs, using a human macrophage cell line, U937. Our results showed that COX-2 expression and PGE(2) production are upregulated by DFX treatment and that this upregulation is dependent on both COX-2 promoter activity and alteration of mRNA stability. COX-2 promoter activity may be, at least in part, mediated by activation of the extracellular signal-regulated kinase pathway. These findings suggest that iron metabolism may regulate inflammatory processes by modulating PGs as well as other inflammatory mediators.

Binding Sites↗
PubMed2001

Hepatitis C virus core protein activates nuclear factor kappa B-dependent signaling through tumor necrosis factor receptor-associated factor.

Hepatitis C virus (HCV) core protein, a viral nucleocapsid, has been shown to affect various intracellular events including the nuclear factor kappaB (NF-kappaB) signaling supposedly associated with inflammatory response, cell proliferation, and apoptosis. In order to elucidate the effect of HCV core protein on the NF-kappaB signaling in HeLa and HepG2 cells, a reporter assay was utilized. HCV core protein significantly activated NF-kappaB signaling in a dose-dependent manner not only in HeLa and HepG2 cells transiently transfected with core protein expression plasmid, but also in HeLa cells induced to express core protein under the control of doxycycline. HCV core protein increased the DNA binding affinity of NF-kappaB in the electrophoretic mobility shift assay. Acetyl salicylic acid, an IKKbeta-specific inhibitor, and dominant negative form of IKKbeta significantly blocked NF-kappaB activation by HCV core protein, suggesting HCV core protein activates the NF-kappaB pathway mainly through IKKbeta. Moreover, the dominant negative forms of TRAF2/6 significantly blocked activation of the pathway by HCV core protein, suggesting HCV core protein mimics proinflammatory cytokine activation of the NF-kappaB pathway through TRAF2/6. In fact, HCV core protein activated interleukin-1beta promoter mainly through NF-kappaB pathway. Therefore, this function of HCV core protein may play an important role in the inflammatory reaction induced by this hepatotropic virus.

Cell Line↗
PubMed2001

Bradycardia-induced long QT syndrome caused by a de novo missense mutation in the S2-S3 inner loop of HERG.

Long QT syndrome is a congenital disorder that presents with a defective cardiac ion channel and is either associated with prolonged action potential or, more commonly, known as an acquired form in which "torsades de pointes" type arrhythmias specifically occur after secondary causes. We report a case of a novel HERG mutation (A490T) that caused a bradycardia-associated form of long QT syndrome. A 27-year-old woman exhibited recurrent syncope due to torsades de pointes associated with a disturbance of the cardiac conduction system. By using polymerase chain reaction and single strand conformational polymorphism analyses, we identified a heterozygous single nucleotide substitution of HERG (G to A at nt 1468). This mutational change was not present in 140 Japanese control individuals. Electrophysiological assays for the A490T mutant HERG channel were conducted in the heterologous expression system with COS7 cells. The mutant channel was found to reconstitute functional channel currents, suggesting the homomeric mutant channel was functional. The mutation did not change the properties of the activation gate and inward rectification, however the current density of this mutant channel was small compared with that of wild type HERG. Taken together, this mutant may cause subtle changes in HERG channel functions (I(Kr)) in vivo. In this case, genetic background and unexpected bradycardia may have contributed to the development of long QT syndrome.

Adult↗
PubMed2001

Des-gamma-carboxy prothrombin as a useful predisposing factor for the development of portal venous invasion in patients with hepatocellular carcinoma: a prospective analysis of 227 patients.

BACKGROUND: Portal venous invasion (PVI) in patients with hepatocellular carcinoma (HCC) is an important factor affecting prognosis. The objective of this study was to elucidate predisposing factors for the development of PVI. METHODS: Two hundred twenty-seven patients with HCC who did not show PVI and who received percutaneous ethanol injection therapy and/or microwave coagulation therapy at the time of their first hospital admission were enrolled between 1994 and 1996. After their HCC was treated, the patients were followed for a mean of 19 months. For the detection of HCC recurrence and/or development of PVI, ultrasonography was performed every 3 months, a computed tomography (CT) scan was performed every 6 months, and the biochemical parameters of the patients were measured every month. PVI was defined as protrusion of the tumor into the first and/or second branch or into the main trunk of the portal vein. RESULTS: Of the 227 patients, 24 (11%) later developed PVI. Tabular analysis was performed on these 24 patients and indicated that tumor size, albumin, total bilirubin, prothrombin time, alpha-fetoprotein (AFP) level, and des-gamma-carboxy prothrombin (DCP) level differed significantly between the time of initial admission and the time of PVI development. A univariate analysis performed on the 227 patients indicated that an increase in the numbers of tumors, the histologic tumor grade (differentiation), the AFP level, and the DCP level at the time of initial diagnosis of HCC had a significant correlation with the later development of PVI; and a stepwise, multivariate Cox regression analysis revealed that the DCP level was the strongest predisposing factor (P < 0.0010; risk ratio = 5.65) followed by the histologic grade of tumor differentiation. CONCLUSIONS: The results suggest that the serum DCP level is the most useful predisposing clinical parameter for the development of PVI.

Adult↗
PubMed2001

4-(6,7-Dihydro-5,8-dioxothiazolo[4,5-g]phthalazin-2-yl)benzoic acid N-hydroxysuccinimide ester as a highly sensitive chemiluminescence derivatization reagent for amines in liquid chromatography.

4-(6,7-Dihydro-5,8-dioxothiazolo[4,5-g]phthalazin-2-yl)benzoic acid N-hydroxysuccinimide ester was synthesized as a highly sensitive and selective chemiluminescence derivatization reagent for primary and secondary amines in liquid chromatography. Methyl-n-octylamine, n-nonylamine and n-decylamine were used as model compounds to optimize the derivatization, separation and chemiluminescence reaction conditions. This reagent reacts selectively with amines in the presence of triethylamine to give the highly chemiluminescent derivatives, which produce chemiluminescence by reaction with hydrogen peroxide in the presence of potassium hexacyanoferrate(III) in an alkaline medium. The chemiluminescent derivatives of the three amines can be separated within 20 min by reversed-phase liquid chromatography with isocratic elution, followed by chemiluminescence detection. The detection limits (signal-to-noise ratio=3) for primary and secondary amines are at sub-fmol levels for a 20-microl injection. Furthermore, this method was applicable to the determination of amantadine in human plasma.

Adult↗
PubMed2001

Analysis of the accumulation of mutants in Sabin attenuated polio vaccine viruses passaged in Vero cells.

To confirm the safety of oral poliomyelitis vaccine (OPV) cultured in Vero cells, the genetic stability of cultured polio vaccine viruses was analysed by MAPREC (mutant analysis by PCR and restriction enzyme cleavage). The rates of mutant accumulation of the viruses passaged in Vero cells under a low multiplicity of infection (MOI) condition (approximately 10(-3.5)CCID50/cell; the same as under usual OPV production conditions) were higher than those passaged in secondary cultured monkey kidney cells. However, the rates of mutant accumulation were restrained when the viruses were cultured under a high MOI condition (approximately 10(-1.5)CCID50/cell) in Vero cells. Furthermore, neurovirulence of the passaged viruses in pollovirus susceptible transgenic mice PVR-Tg21 was shown to correlate highly with the results of MAPREC. It is expected that our results will contribute to the large scale preparation of safe and effective OPV using Vero cells.

Animals↗
PubMed2001

Purification of activins from androgen-independent Shionogi carcinoma cells demonstrates enhanced expression of activin betaB-subunit under androgen-depleted cell conditions in vitro and in vivo.

Here, we report characterization of growth factors secreted from androgen-independent mouse mammary Shionogi carcinoma cells. Previous isolation of fibroblast growth factor 8 (FGF8) from androgen-dependent Shionogi carcinoma SC-3 cells prompted us to characterize growth factors secreted from the androgen-independent cells. After several purification procedures, mitogens for NIH3T3 cells from the androgen-independent cells were identified as activins on the grounds that activin betaA- and betaB-subunits are detected in the active fractions by Western blotting and that the growth-promoting effects by the active fractions are specifically inhibited in the presence of follistatin. In addition, exogenous activins, but not inhibin, stimulated the growth of NIH3T3 cells in a dose-dependent manner. Interestingly, transcripts of activin betaB-subunit were predominantly found in the androgen-independent cells while its betaA-subunit was universally expressed in both androgen-dependent and -independent Shionogi carcinoma cells. In concordant with this in vitro finding, transcripts of activin betaB-subunit were enhanced in murine prostates after castration. Therefore, expression of activin betaB-subunit, but not its betaA-subunit, is likely to be related with androgen-depleted cell conditions in prostates, and possibly in androgen-related cancers.

3T3 Cells↗
PubMed2001

Cerebrospinal fluid amyloid beta(1-42) levels in the mild cognitive impairment stage of Alzheimer's disease.

Cerebrospinal fluid (CSF) levels of amyloid beta-protein ending at amino acid position 42 (CSF-A beta(1-42)) and CSF-tau levels were quantified by sandwich ELISAs in 19 patients with mild cognitive impairment (MCI) who eventually developed Alzheimer's disease (AD) on follow-up as well as in 15 age-matched normal controls and 54 AD patients at diverse stages of the disease. In the present study, the annual conversion rate was approximately 15%. The CSF-A beta(1-42) levels did not differ significantly between the normal control group and the MCI group, however, these values declined significantly once AD became clinically overt. In contrast to CSF-Abeta(1-42), CSF-tau levels were significantly increased in the MCI stage, and these values continued to be elevated thereafter, indicating that increased levels of CSF-tau may help in detecting MCI subjects who are predicted to develop AD. We propose that CSF-tau and CSF-A beta(1-42) must be used as two distinct biomarkers that should be applied appropriately in clinical settings.

Aged↗
PubMed2001

Characterization and subcellular localization of KCNQ1 with a heterozygous mutation in the C terminus.

Numerous mutations in KCNQ1, a gene encoding the alpha -subunit of cardiac delayed rectifier potassium channels, have been found in long QT syndrome (LQTS). Among them, several mutations in the C terminus have been shown to cause autosomal recessive or subclinical autosomal dominant LQTS. Here, we report a heterozygous mutation, T587M, which is also in the KCNQ1 C-terminal domain. The same mutation was found in three independent probands that were clearly symptomatic with family history of cardiac sudden death. Functional assay using a heterologous expression system with a mammalian cell line (COS7 cells) revealed that the mutant displayed neither functional channels when expressed alone nor dominant-negative effect when co-expressed with wild-type (WT) KCNQ1. To examine the cellular trafficking of KCNQ1, green fluorescent protein (GFP) was tagged to the cytoplasmic C terminus of WT or mutant KCNQ1. This procedure did not affect the essential properties of expressed WT KCNQ1 channels. On confocal microscopic images, GFP-tagged WT KCNQ1 showed a plasma membrane fluorescence pattern, whereas the GFP-tagged mutant showed a perinuclear fluorescence pattern. Co-expression of the mutant with GFP-tagged WT KCNQ1 did not influence its normal cellular transport. Therefore, the T587M mutant cannot traffic to the plasma membrane and may form no subunit assembly with WT KCNQ1. These findings provide a novel molecular basis for the clinical finding that this C-terminal mutation produced a severe form of RWS-type LQTS.

Adolescent↗
PubMed2001

Optical recording of the neuronal activity in the brainstem-spinal cord: application of a voltage-sensitive dye.

Although there are several limitations, optical recording techniques are superior to multi-electrode mapping methods, as it is possible to record at large number of points in a small area without destroying the tissue and possible to know relative changes of membrane potentials. Optical recording techniques using voltage-sensitive dyes will be more importantly applied in the study of central respiratory control (e.g., mechanisms of respiratory rhythm generation) in the near future.

Animals↗
PubMed2001

Increased noradrenaline release from rat preoptic area during and after sevoflurane and isoflurane anesthesia.

PURPOSE: To study the effects of sevoflurane and isoflurane on noradrenaline release from the rat preoptic area (POA). METHOD: Sixteen male Wistar rats were studied. A microdialysis probe with a 2 mm long semipermeable membrane was implanted in the POA. Dialysates were collected at intervals often minutes. After obtaining five control samples for 50 min, 30 min inhalation of 3% sevoflurane or 1.8% isoflurane was performed. After cessation of the inhalation, five more samples were obtained for 50 min as recovery phase. Noradrenaline (NA) concentration in the dialysates was measured by high pressure liquid chromatography with an electrochemical detector. RESULTS: Both sevoflurane and isoflurane caused marked increases in NA release from the rat POA (sevoflurane 233% at 20 min, isoflurane 357% at ten minutes after the start of inhalation). The marked NA releases were also observed during the emergence from sevoflurane and isoflurane anesthesia (sevoflurane 269% at 20 min, isoflurane 368% at ten minutes in the recovery phase). CONCLUSION: This study suggests that enhanced release of NA in the POA during sevoflurane and isoflurane may explain the excitatory phase observed during the peri-anesthetic period with these agents.

Anesthesia↗
PubMed2001

Th1-cytokine induction and anti-tumor effect of 55 kDa protein isolated from Aeginetia indica L., a parasitic plant.

We have isolated a 55 kDa protein from the seed extract of Aeginetia indica L. (AIL), a parasitic plant, by affinity chromatography on an N-hydroxysuccinimide-activated Sepharose High Performance column bound with F3, a monoclonal antibody that neutralizes the cytokine-inducing and anti-tumor effect of AIL. In the present study, we examined this protein (AILb-A) for cytokine induction and anti-tumor effects by animal study, using syngeneic Meth-A tumor-bearing BALB/c mice, in which the Th2 response is genetically dominant. AILb-A administration resulted in markedly increased levels of Th1 cytokines [interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-12 and IL-18] in the sera derived from Meth-A-bearing mice. The in vitro re-stimulation with AILb-A of splenocytes derived from AILb-A-primed mice also selectively induced Th1-type cytokines and antigen-specific killer cell activity. The neutralizing test using cytokine-specific antibodies revealed that AILb-A-induced IL-18 plays a most significant role for and killer cell-inducing activities. Furthermore, IL-12 and IL-18 induced by AILb-A inhibited specifically IL-10 and IL-4 production, respectively. Finally, we examined the anti-tumor effect of AILb-A in both Meth-A-bearing BALB/c mice and Meth-A-bearing nude mice with BALB/c background. AILb-A exhibited a striking anti-tumor effect in normal BALB/c mice inoculated with Meth-A cells. In athymic nude mice, the anti-tumor effect of AILb-A was relatively weak. These findings strongly suggested that AILb-A is a potent Th1 inducer and may be a useful immunotherapeutic agent for patients with malignant diseases.

Animals↗
PubMed2001

Enhancement of anti-cancer immunity by a lipoteichoic-acid-related molecule isolated from a penicillin-killed group A Streptococcus.

We isolated the lipoteichoic-acid-related molecule (OK-PSA) from OK-432, a streptococcal preparation, by affinity chromatography on CNBr-activated Sepharose-4B-bound monoclonal antibody TS-2, which neutralizes the interferon (IFN)-gamma-inducing activity of OK-432. We have previously reported that OK-PSA is a potent inducer of Th1-type cytokines in human peripheral blood mononuclear cells in vitro. In this study, we conducted an animal experiment to examine whether OK-PSA exhibits an anti-tumor effect in vivo by acting as a Th1 inducer in syngeneic Meth-A tumor-bearing BALB/c mice, in which the Th2 response is genetically dominant. It was found that OK-PSA induced Th1-type cytokines [IFN-gamma, tumor necrosis factor-alpha, interleukin (IL)-2, IL-12 and IL-18] in BALB/c mice bearing Meth-A tumor and caused a marked anti-tumor effect. Although it was suggested by an in vitro study. using spleen cells derived from the animals, that IL-18 plays the greatest role in the induction of the Th1-dominant state and tumor cell killing induced by OK-PSA, the in vivo experiments demonstrated that both IL-12 and IL-18 are essential in the anti-tumor effect exhibited by OK-PSA. These findings strongly suggest that OK-PSA is a major effector molecule of OK-432 and may be a useful immunotherapeutic agent, as a potent Th1 inducer, for cancer patients with a Th2-dominant state.

Adjuvants, Immunologic↗
PubMed2001

Mutated SEA-D227A-conjugated antibodies greatly enhance antitumor activity against MUC1-expressing bile duct carcinoma.

For the purpose of establishing a new adoptive immunotherapy for bile duct carcinoma (BDC), we have directed our attention to superantigens (SAgs), the most potent known activators of T lymphocytes. In our previous study, staphylococcal enterotoxin A (SEA) was conjugated chemically with MUSE11 mAb, which recognizes the MUC1 cancer-associated antigen, and shown to enhance the specific cytotoxic activity of T-LAK cells against MUC1-expressing BDC cells (TFK-1) in vitro and in vivo. However, it is probable that SEA might cause side-effects because of nonspecific binding to class II positive cells. In order to overcome these, we generated mutated SEA (mSEA) by changing Asp at position 227 of native SEA to Ala, which has reduced affinity to MHC class II molecules, but retains the potential for T cell activation. When mSEA-D227A was administered to rabbits to examine effects on blood pressure, 500 times more mSEA-D227A was tolerated than native SEA. This prompted us to construct a mSEA-D227A-conjugated mAb, reactive with MUC1. It augmented the antitumor activity of T-LAK cells significantly, and furthermore, mSEA-D227A could be conjugated to two bispecific antibodies, BsAb (anti-MUC1 x anti-CD3) and BsAb (anti-MUC1 x anti-CD28), which in combination had greater enhancing effects than mSEA-D227A-conjugated anti-MUC1 mAb, and combination of unconjugated BsAbs. These findings indicate a utility of mSEA-D227A-conjugated antibodies for targeted cancer immunotherapy.

Amino Acid Substitution↗