Biomedical subjects

Y Oyama

Publications and source records attributed to Y Oyama.

At least 55 records · Page 3Linked to original sources

PubMed2001

Future strategies in hematopoietic stem cell transplantation for rheumatoid arthritis.

Patients with coincidental rheumatoid arthritis (RA) treated by allogeneic hematopoietic stem cell transplantation (HSCT) for drug induced aplastic anemia have been fortuitously cured of RA. Other than these examples with allogeneic HSCT, there is no known curative therapy for RA. Despite its potential to cure, allogeneic transplantation is not being offered to patients with RA due to transplant related mortality. Advances in HSCT conditioning regimens and better prevention of graft-versus-host disease should allow consideration of allogeneic HSCT as therapy for severe RA. We propose a new, well tolerated, nonmyeloablative allogeneic stem cell transplant regimen as treatment for RA.

Arthritis, Rheumatoid↗

PubMed2000

Tri-n-butyltin-induced change in cellular level of glutathione in rat thymocytes: a flow cytometric study.

Since some of organotins, accumulated in edible mollusks of aquatic environments, exert a variety of toxic actions on experimental animals, it causes concern for the health of humans. We examined the effects of tri-n-butyltin chloride (TBT) and other organotins (triethyltin chloride, trimethyltin chloride, triphenyltin chloride and tetrabutyltin) on cellular content of glutathione (GSH) in rat thymocytes using a flow cytometer to further characterize the toxicity of TBT. When the cells were incubated with TBT at concentrations of 3 nM or more for 15 min, the cellular content of GSH dose-dependently decreased. However, it completely or partly recovered until 180 min even in the continued presence of TBT. This recovery was temperature-sensitive, suggesting an involvement of metabolic process. The efficacy of TBT to decrease the cellular content of GSH was greater than those of other organotins. Results suggest that TBT and some organotins at environmentally relevant (nanomolar) concentrations significantly reduce the cellular content of GSH, suggesting that they increase the vulnerability to some biological and chemical insults.

Animals↗

PubMed2000

Tachycardia-dependent right bundle-branch block with supernormal conduction.

This paper reports the case of a 76-year-old man in whom atrial flutter with varying atrioventricular block and intermittent right bundle-branch block was found. This is the first report on tachycardia-dependent right bundle-branch block associated with supernormal conduction in a case of atrial flutter. When an impulse is conducted to the ventricles beyond 0.72 s after a QRS complex of right bundle-branch block configuration, the impulse falls after the abnormally long effective refractor period of the right bundle branch and passes through the right bundle branch. When the conducted impulse occurs within 0.72 s after a QRS complex of right bundle-branch block configuration, the impulse usually falls in the refractory period and is blocked in the right bundle branch; however, only when the impulse occurs 0.48 or 0.49 s after that does it fall in the supernormal period and passes through the right bundle branch. The findings in the present report strengthen our previous suggestion that the presence of supernormal conduction plays an important role in the initiation of reentrant ventricular tachycardia.

Aged↗

PubMed2000

Ultrastructural characteristics of diabetic nephropathy.

Diabetic nephropathy is a major cause of chronic renal failure in Japan, and the prevalence rate has markedly increased during the past decade. Diabetic nephropathy shows various specific histological changes not only in glomeruli but also in the interstitial region. Nodular, diffuse, and exudative lesions, so-called diabetic glomerulosclerosis, are well known as glomerular lesions. At first, they were historically evaluated only by light microscopy, and thus which components of the glomeruli were modified was not sufficiently clear. Subsequent electron microscopic studies clarified that the expansion of the mesangial matrix was the true form of nodular and diffuse lesions, and that insudated serum substance was the real appearance of an exudative lesion. Interstitial lesions also exhibit specific features in diabetic nephropathy. In electron microscopic studies, it was proved that the size of mitochondria and thickness of the tubular basement membrane were increased in diabetic nephropathy. In this review, we introduce typical electron microscopic findings in diabetic nephropathy and recent opinions on the progression of diabetic nephropathy.

Diabetic Nephropathies↗

PubMed2000

Sinus escape-capture bigeminy and sinus extrasystolic bigeminy.

Blocking conduction between the sinus node and the atria (SA block) can be responsible for symptomatic rhythm problems. However, in atrial escape-capture bigeminy with SA block, when atrial escape P waves originate in a site within or close to the sinus node, the diagnosis of SA block is not easy. Electrocardiograms were selected from 7 people with atrial bigeminy because (1) all atrial deflections (P waves) were almost the same in shape and in length of PR intervals, (2) comparatively long PP intervals alternated with comparatively short PP intervals, and (3) occasionally the atrial bigeminy changed to normal regular sinus rhythm in which 2 or more sinus P waves were found in succession. An attempt is made to clarify the mechanism for these cases. When regular sinus rhythm changed to bigeminal rhythm, the long PP interval introduced the bigeminy in 3 cases, indicating the presence of "sinus" escape-capture bigeminy; whereas the short PP interval introduced the bigeminy in the other 4 cases, indicating the presence of "sinus" extrasystolic bigeminy. In cases of sinus escape-capture bigeminy associated with SA block, the cases may occasionally be diagnosed wrongly as ordinary sinus arrhythmia not associated with SA block. Therefore, it seems that sinus escape-capture bigeminy is not so rare as is generally believed. Patients with SA block often require implantation of the artificial pacemaker. Thus, the authors believe that differentiation of sinus escape-capture bigeminy from other forms of "sinus" bigeminy is clinically important.

Adult↗

PubMed2000

Concealed conduction in the reentrant pathway as a mechanism of stable ventricular quadrigeminy.

This is the first report on the stable occurrence of ventricular quadrigeminy as a manifestation of concealed bigeminy in a case of fixed and late coupled ventricular extrasystoles. A 46-year-old man is reported in whom the period of ventricular bigeminy alternated with the period of ventricular quadrigeminy. Coupling intervals of the extrasystoles were fixed and much longer than sinus QT intervals. When the heart rate is decreased, the period of bigeminy changed to the period of quadrigeminy without gradual decrease in coupling of the preceding extrasystoles. Once such a change occurred, stable quadrigeminy is maintained for a period. These findings suggest the possibility that concealed electrotonic conduction of blocked impulses and interference of conducted impulses may occur in the reentrant extrasystolic pathway as a mechanism of stable ventricular quadrigeminy.

Electrocardiography↗

PubMed2000

Extensive intraglomerular thrombi of monoclonal IgM-kappa in a patient with malignant lymphoma.

We describe an 80-year-old man who developed malignant lymphoma (ML) complicated by extensive intraglomerular thrombi of immunoglobulin M (IgM)-kappa monoclonal immunoglobulin. The clinical picture was characterized by nephrotic syndrome and systemic lymphadenopathy. Laboratory examination showed mild anemia and a small amount of monoclonal IgM-kappa in the blood. The histopathologic findings and surface immunoglobulin analysis of the lymph node biopsy specimen were consistent with CD5-positive diffuse large B-cell (type, IgM-kappa) lymphoma. The subsequent renal biopsy showed a massive deposition of amorphous material in the glomerular capillary lumens, subendothelial areas, and mesangium. Nodular glomerulosclerosis was not found. An immunofluorescent study showed that the deposits consisted of IgM-kappa monoclonal immunoglobulin. Ultrastructurally, the deposits were composed of granular electron-dense material. Chemotherapy was effective for both the ML and nephrotic syndrome, and the patient's urine analysis results returned to normal. The histopathologic manifestations of this case are rare, and the pathogenesis of these glomerular lesions was obviously associated with ML.

Aged↗

PubMed2000

Toxicity of methylmercury conjugated with L-cysteine on rat thymocytes and human leukemia K562 cells in comparison with that of methylmercury chloride.

In order to reveal the implication of use of methylmercury chloride (MeHgCl) in in vitro study, the effects of 10 µM MeHgCl on rat thymocytes and human leukemia K562 cells were compared with those of methylmercury conjugated with L-cysteine (10 µM MeHg-Cys) using a flow cytometer and fluorescent probes to monitor cellular physiological and pathological parameters. MeHgCl hyperpolarized membranes of thymocytes, followed by depolarization within a few minutes after the application, while MeHg-Cys persistently hyperpolarized them. MeHgCl increased intracellular concentration of Ca(2+), decreased cellular content of glutathione and increased generation of superoxide anion in the cells. The effects of MeHg-Cys were much less than those of MeHgCl. MeHgCl greatly increased both numbers of the cells undergoing apoptosis and dead cells in cell suspension containing thymocytes, while this was not the case for MeHg-Cys. MeHgCl reduced the cell viability of human leukemia K562 cells and completely inhibited the cell growth. The effects of MeHg-Cys on K562 cells were less than those of MeHgCl. It can be concluded that the effects of MeHgCl on rat thymocytes and K562 cells are different from those of MeHg-Cys. The results obtained from the in vitro studies using MeHgCl may be less implicit to elucidate the mechanism of MeHg intoxication in humans and experimental animals because MeHg are present in forms of MeHg-Cys and/or MeHg-S conjugate under the in vivo conditions.

Journal Article↗

PubMed2000

Hematopoietic cell transplantation-related nephropathy in Japan.

To clarify the incidence and characteristics of hematopoietic cell transplantation (HCT)-related nephropathy (HCT-N) in Japan, we sent questionnaire letters to 188 hematologic divisions of 91 hospitals and analyzed the responses. Of 2,136 Japanese hematopoietic cell transplant recipients, 51 patients (2.4%) had HCT-N. The early-onset (</=30 days after HCT), middle-onset (31 to 120 days after HCT), and late-onset (>180 days after HCT) groups included 20, 16, and 15 patients, respectively. The early-onset group mainly consisted of patients with acute renal failure (ARF) and hemolytic uremic syndrome and/or thrombotic thrombocytopenic purpura. ARF was the dominant type in the middle-onset group. The main phenotype of the late-onset group was nephrotic syndrome, which correlated with chronic graft-versus-host disease (P=0.008). The total amounts of irradiation for patients with chronic renal failure and urinary abnormality were significantly greater than those for patients with ARF (P=0.004). The survival rate of the early-onset and middle-onset groups was 47.2%, whereas 87% of patients in the late-onset group survived (P=0.002). HCT-N is expected to become a serious and important problem in Japan because of the increasing number of HCTs from unrelated donors.

Adolescent↗

PubMed2000

Troglitazone, a PPARgamma ligand, inhibits osteopontin gene expression in human monocytes/macrophage THP-1 cells.

Peroxizome proliferator-activated receptor-gamma (PPARgamma) is a member of the nuclear receptor family of transcription factors that regulate adipocyte differentiation. Recent studies indicate that liganded PPARgamma not only promotes differentiation but also inhibits the activation of macrophages. Osteopontin, a component of extracellular matrix, is synthesized by macrophages in atherosclerotic plaques. In this study, we examined whether PPARgamma ligand regulates osteopontin gene expression in THP-1 cells, a cell line derived from human monocytic leukemia cells which can differentiate to macrophage upon stimulation with phorbol ester PMA. Northern blot analysis showed that osteopontin expression is markedly induced in response to PMA. Troglitazone, a PPARgamma ligand, dramatically attenuated the PMA-induced osteopontin expression. Transient transfection assays of the human osteopontin promoter/luciferase construct which contains a 5'-flanking region between -1500 and +87 relative to the transcription start site demonstrate that either treatment with troglitazone or cotransfection of PPARgamma expression vector inhibits osteopontin promoter activity. These data indicate that troglitazone reduces osteopontin gene expression at transcriptional level through PPARgamma activation, and suggest the role of troglitazone in inhibiting the ability of macrophages to produce extracellular matrix, which is particularly relevant to atherosclerotic plaque formation.

Base Sequence↗

PubMed1999

Exposure of rat thymocytes to hydrogen peroxide increases annexin V binding to membranes: inhibitory actions of deferoxamine and quercetin.

Effects of hydrogen peroxide (H(2)O(2)) on rat thymocytes were examined, using a flow cytometer and three fluorescent probes, annexin V-fluorescein isothiocyanate (annexin V-FITC) for detecting phosphatidylserine expressed on the membrane surface, ethidium bromide for estimating dead cells, and fluo-3-acetoxymethyl ester (fluo-3-AM) for monitoring changes in intracellular Ca(2+) concentration ([Ca(2+)](i)), to characterize H(2)O(2)-induced cytotoxicity. Exposure to H(2)O(2) (30 microM or more) increased the number of annexin V-positive live cells dose- and time-dependently while the number of dead cells increased at concentrations of 1 mM or more. H(2)O(2) (30 microM or more) increased [Ca(2+)](i) in a dose-dependent manner. Threshold concentration of H(2)O(2) to increase [Ca(2+)](i) was similar to that to increase annexin V binding to membranes. The H(2)O(2)-induced change in cell membranes was attenuated under Ca(2+)-free conditions. Therefore, it is likely that Ca(2+) is involved in the H(2)O(2)-induced cytotoxicity. Deferoxamine was effective to protect the cells suffering from H(2)O(2)-induced oxidative stress, suggesting a contribution of hydroxyl radicals generated by the Fenton reaction. Quercetin also exerted a potent protective action on cells suffering from H(2)O(2)-induced oxidative stress. The results indicate that the exposure of rat thymocytes to H(2)O(2) at micromolar concentrations increases annexin V binding to cell membranes in a Ca(2+)-dependent manner, suggesting the possibility that the oxidative stress caused by H(2)O(2) (and/or hydroxyl radicals) induces apoptosis via increasing [Ca(2+)](i).

Animals↗

PubMed1999

Hypothetical protein KIAA0079 is a mammalian homologue of yeast Sec24p.

The Sec23p-Sec24p complex is a component of COPII-coated vesicles that mediate protein transport from the endoplasmic reticulum in yeast. The mammalian hypothetical protein KIAA0079 (KIAA0079p) exhibits sequence similarity to yeast Sec24p. KIAA0079p was co-eluted with mammalian Sec23p on gel filtration. In vitro binding experiments revealed that the C-terminal region of KIAA0079p binds to the N-terminal region of mammalian Sec23p. Overexpression of KIAA0079p caused a defect in protein export from the endoplasmic reticulum. These results support the idea that KIAA0079p is a functional homologue of yeast Sec24p.

Animals↗

PubMed1999

Three distinct anti-allergic drugs, amlexanox, cromolyn and tranilast, bind to S100A12 and S100A13 of the S100 protein family.

To investigate the roles of calcium-binding proteins in degranulation, we used three anti-allergic drugs, amlexanox, cromolyn and tranilast, which inhibit IgE-mediated degranulation of mast cells, as molecular probes in affinity chromatography. All of these drugs, which have different structures but similar function, scarcely bound to calmodulin in bovine lung extract, but bound to the same kinds of calcium-binding proteins, such as the 10-kDa proteins isolated in this study, calcyphosine and annexins I-V. The 10-kDa proteins obtained on three drug-coupled resins and on phenyl-Sepharose were analysed by reversed-phase HPLC. It was found that two characteristic 10-kDa proteins, one polar and one less polar, were bound with all three drugs, although S100A2 (S100L), of the S100 family, was bound with phenyl-Sepharose. The cDNA and deduced amino acid sequence proved our major polar protein to be identical with the calcium-binding protein in bovine amniotic fluid (CAAF1, S100A12). The cDNA and deduced amino acid sequence of the less-polar protein shared 95% homology with human and mouse S100A13. In addition, it was demonstrated that the native S100A12 and recombinant S100A12 and S100A13 bind to immobilized amlexanox. On the basis of these findings, we speculate that the three anti-allergic drugs might inhibit degranulation by binding with S100A12 and S100A13.

Amino Acid Sequence↗

PubMed1999

Humanization of a mouse neutralizing monoclonal antibody against tumor necrosis factor-alpha (TNF-alpha).

An anti-human tumor necrosis factor-alpha (TNF-alpha) monoclonal antibody, designated as 3B10, inhibits the biological activity of human TNF-alpha. In the present study, we constructed humanized version of the antibody by grafting its complementarity-determining regions (CDRs) onto a human antibody, HBS-1. Using a molecular model of mouse 3B10, framework residues affecting the CDR conformation were identified. Thus, these residues were also introduced into the framework together with the CDRs in a stepwise manner, depending on the degree of the possible importance of the residues. As a result, one humanized version (h3B10-9) which possesses nine mouse framework residues showed the same binding activity as that of the chimeric version. This humanized anti-TNF-alpha antibody is expected to be less immunogenic and thus more suitable for possible clinical use.

Amino Acid Sequence↗

PubMed1999

Purification of bovine S100A12 from recombinant Escherichia coli.

S100A12, a member of the S100 family of EF-hand calcium-binding proteins, was purified from Escherichia coli cells expressing the corresponding cDNA. The procedure involved washing induced E. coli cells with EDTA-containing hypotonic solution, ion-exchange chromatography, and HPLC. Recombinant S100A12 was purified to homogeneity with the final yield around 6.7 mg per 20 ml of culture. The purified protein was identical to native S100A12 in the N-terminal amino acid sequence, lysylendopeptidase peptide mapping, mass spectrum, and Ca2+-dependent binding affinity to amlexanox, an antiallergy drug. However, the N-terminal methionine residue of the purified protein was not cleaved off as in the native protein. The method used in the present study permits the purification of recombinant S100A12 in large quantities and may also be applicable to preparation of other S100 family proteins.

Amino Acid Sequence↗

PubMed1999

A new method for crosstalk correction in simultaneous dual-isotope myocardial imaging with Tl-201 and I-123.

We have developed a new method of crosstalk correction in simultaneous dual-isotope imaging with Tl-201 and I-123 by using crosstalk ratios and a blurring filter. Single isotope myocardial studies (10 for Tl-201 and 7 for I-123) were performed with a dual energy window acquisition mode and two low energy general-purpose collimators. Then two planar images acquired with dual energy windows for a Tl-201 line source and an I-123 line source were obtained to measure line spread functions (LSFs) and crosstalk ratios for each image. The line source experiments showed that the LSFs for the Tl-201 imaging window from the single Tl-201 source were very similar to those for the I-123 imaging window from the single Tl-201 source, but the LSFs for the Tl-201 imaging window from the single I-123 source had broad shapes which differed from those for the I-123 imaging window from the single I-123. To obtain accurate I-123 crosstalk images in the Tl-201 imaging window from the I-123 images in the I-123 imaging window, we designed a low-pass blurring filter. In 7 clinical I-123 MIBG studies, I-123 window images processed with this filter became very similar to the Tl-201 window image from the single I-123 source. The method proposed in this study can accurately correct the crosstalk in dual isotope studies with Tl-201 and I-123 and is easily applicable to conventional gamma camera systems with any dual energy window acquisition mode.

3-Iodobenzylguanidine↗

PubMed1999

Effects of exercise and standing on atrial parasystole: prolongation and shortening of the parasystolic cycle length.

In recently reported cases of ventricular parasystole, it was shown that after exercise the parasystolic cycle length is prolonged, in contrast to a shortening of the sinus cycle length, whereas during standing the parasystolic cycle length and the sinus cycle length both shortened. In this report, to explore whether the same features as occur in ventricular parasystole are seen in atrial parasystole, effects of exercise and standing on the parasystolic cycle length were investigated in two men with atrial parasystole. The atrial parasystolic cycle length was prolonged after exercise, whereas it shortened during standing, similar to what occurs in ventricular parasystole. This is the first report to show such changes of cycle length in atrial parasystole. These findings suggest that in atrial parasystole, as in ventricular parasystole, influences on the parasystolic cycle length do not always act in the same direction as those on sinus cycle length.

Adult↗

PubMed1999

Evaluation of the antioxidant activity of environmental plants: activity of the leaf extracts from seashore plants.

The antioxidant activity of the methanolic extracts of the leaves of 39 plant species was examined. These leaves were collected from the plants growing on subtropical seashores. The activity was evaluated by three kinds of assay methods, which included the DPPH radical scavenging assay, linoleic acid oxidation assay, and oxidative cell death assay. Two extracts from Excoecaria agallocha and Terminalia catappa showed remarkably potent activity in all assay systems. The HPLC analysis of the extracts indicated the presence of the same antioxidant and isolation work for the compound identified ellagic acid. The isolated ellagic acid showed strong antioxidant activity in the assay systems used.

Antioxidants↗