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K Matsui

Publications and source records attributed to K Matsui.

At least 181 records · Page 10Linked to original sources
PubMed1998

Roles of the mutagenesis proteins SamA'B and MucA'B in chemically induced frameshift mutagenesis in Salmonella typhimurium hisD3052.

The mutagenesis induced by ultraviolet light and many chemicals in Escherichia coli is largely dependent upon the proteins encoded by the umuDC operon and their analogs. In Salmonella typhimurium, there are two sets of umuDC-like operons: the umuDC(ST) operon in the chromosome and the samAB operon located on the 60-MDa cryptic plasmid. The former operon, but not the latter, confers UV mutability on S. typhimurium. Nevertheless, the samAB operon, when carried on high-copy-number plasmids, can efficiently promote UV mutagenesis. In order to characterize the function of samAB in greater detail, we have compared the abilities of MucA'B and a putative activated form of SamAB, i.e. SamA'B, to promote chemically induced frameshift mutagenesis in S. typhimurium hisD3052. MucAB is an activated form of the products of mucAB, which is the most potent umuDC analog characterized so far. We have used four plasmids, each carrying samA', samB, mucA' or mucB with a lac promoter instead of their own promoters. The results indicated that under the conditions of elevated expression, SamA'B can promote chemically induced frameshift mutagenesis by furylfuramide, aflatoxin B1, 1-nitropyrene, and 1,8-dinitropyrene, with efficiencies comparable to, or even better than, MucA'B. Increase of the levels of expression enhanced the ability of SamA'B to promote the mutagenesis, while it decreased that of MucA'B. Surprisingly, the elevated expression of MucB alone significantly enhanced the frameshift mutagenesis induced by 1-nitropyrene and 1,8-dinitropyrene, whereas the elevated expression of SamB, MucA' and SamA' did not enhance it. These results suggest that the abilities of SamA'B and MucA'B to promote mutagenesis strongly depend on their levels of expression. The possible roles of these mutagenesis proteins in chemically induced frameshift mutagenesis are discussed.

Bacterial Proteins↗
PubMed1998

Cucumber root lipoxygenase can act on acyl groups in phosphatidylcholine.

A cDNA encoding cucumber root lipoxygenase was isolated and expressed in E. coli. The enzyme showed highest activity at pH 5.5 when alpha-linolenic acid dispersed with Tween 20 was used as a substrate but showed little activity at above pH 8.0. On the contrary, it showed the highest activity at pH 9.0 with trilinolenin emulsified with gum arabic. When the assay was performed with linolenic acid dispersed with different concentrations of Tween 20, little activity which could be seen up to the reaction solution became turbid as the linolenic acid/Tween 20 ratio increased, while the activity rapidly emerged afterward. The enzyme could also act on phosphatidylcholine, although the activity was strongly modified by freeze-thaw and sonication treatment on the lipid vesicles. Addition of deoxycholic acid to the phospholipid vesicles drastically enhanced the activity. Addition of free fatty acid was also revealed to be effective to enhance the activity. In the latter case, myristic acid exerted highest activity. Oleic acid enhanced the activity more highly than palmitic acid did. These lines of evidence suggested that the lipoxygenase strictly recognized a specific physical state of the phospholipid substrate in the reaction mixture. The enzyme was irreversibly inactivated as the reaction proceeded, however, the rate of the inactivation was much influenced by the additives. Furthermore, stoichiometry between consumed oxygen and formed conjugated diene could not be observed. (c) 1998 Elsevier Science B.V.

Amino Acid Sequence↗
PubMed1998

A Dumon stent inserted for bronchial stenosis causing a left bronchopericardial fistula: report of a case.

We present herein the case of a 59-year-old man in whom a Dumon stent, inserted as treatment for stenosis of the left main bronchus, caused a left bronchopericardial fistula. The patient initially presented with severe dyspnea caused by main bronchial stenosis of unknown origin for which a Dumon stent was inserted at a local hospital. The Dumon stent migrated to the endobronchus through the stenosis of the left main bronchus a few days later, and his dyspnea remained unresolved. He was subsequently referred to our department 6 months later, where a left pneumonectomy under supportive cardiopulmonary bypass through the femoral artery and vein was performed, and a postoperative pathological diagnosis of bronchial leiomyosarcoma was made. For this rare group of malignant tumors, early diagnosis permits complete surgical resection of the mass and offers the best prognosis. Excision of the tumor should be performed under cardiopulmonary bypass through the femoral vessels when a risk of sudden rupture of the pulmonary artery or vein exists for any reason.

Bronchi↗
PubMed1998

Developmental characteristics of vessel density in the human fetal and infant brains.

We demonstrated the developmental characteristics of vessel density in the human brain, using an antibody against CD31, which specifically reacts with endothelium. In the cerebral cortex and subcortical white matter, the vessel density was low at 16-28 weeks of gestation (GW), and then increased after 36 GW. In the deep white matter, the vessel density was high in the middle fetal period (16-24 GW), and then transiently decreased at 28-36 GW, and increasing after 39 GW. In the putamen, the vessel density was high at 20-21 GW, remained high throughout the fetal period, and then rapidly increased after birth. In the basis pontis, the number of vessels increased after 28 GW, and after 32 GW was greater than in the pontine tegmentum. These alterations in vessel density may correlate with the pathogenesis of perinatal brain injury. Thus, the transient decrease of vessel density in the deep white matter may predispose to periventricular leukomalacia in cerebral hypoperfusion. Similarly, the well-developed vascularity in the basis pontis may predispose its relatively immature neurons to neuron necrosis produced by free radical injury.

Aging↗
PubMed1998

Induction of antitumor cytotoxic activity using CD34+ cord blood cell-derived and irradiated tumor cell-primed dendritic cells.

Dendritic cells (DCs) are the most powerful antigen-presenting cells in the immune system. They can activate immunologically naive T cells and improve the efficacy of immunotherapy against tumors. In the present study we investigated whether CD34+ cord blood cell-derived DCs are capable of inducing antitumor cytotoxic cells, such as cytotoxic T lymphocytes (CTLs), NK cells, and monocytes. Cord blood T cells stimulated by DCs pulsed with irradiated K562 major histocompatibility complex (MHC) class I+ cells were highly effective in eliciting a selective killing response against K562 class I+ cells. This killing activity was almost completely abrogated by antibodies to CD8 or MHC class I, but not to CD4. This suggests that tumor cell-pulsed DCs generated from CD34+ cord blood cells are able to induce tumor specific CTLs against corresponding tumor cells from cord blood T cells, and that these CTLs are CD8+ T cells which may recognize tumor cells via MHC class I molecules. This observation has potentially important implications for the use of DCs in clinical immunotherapy in cord blood transplantation.

Antigen Presentation↗
PubMed1998

Phase II trial of carboplatin plus oral etoposide for elderly patients with small-cell lung cancer.

A phase II trial was conducted to evaluate the efficacy and toxicity of the Egorin's carboplatin dosing formula with 14-day oral etoposide in 38 elderly patients with small-cell lung cancer (SCLC). The overall response rate was 81%. Median survival times were 15.1 months for 16 limited-disease (LD) and 8.6 months for 22 extensive-disease (ED) patients. Myelosuppression was the principal side-effect. This regimen is an active regimen in the treatment of elderly SCLC patients.

Aged↗
PubMed1998

JTT-501, a novel oral antidiabetic agent, improves insulin resistance in genetic and non-genetic insulin-resistant models.

1. We investigated whether JTT-501 (4-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzyl]-3,5-isoxa zolidinedione) would improve insulin resistance in genetic (Zucker fatty rats) and non-genetic (high-fat fed rats) rodent models of obesity. 2. JTT-501 (10-100 mg kg(-1) day(-1)) was administered orally to Zucker fatty rats for 7-21 days. In the high-fat fed rat model, JTT-501 (100 mg kg(-1) day(-1) was administered orally for 7 days. In both models, JTT-501 improved metabolic abnormalities by enhancing insulin action during the glucose tolerance test and the euglycaemic-hyperinsulinaemic clamp study. In ex vivo assays, JTT-501 ameliorated the impaired insulin-sensitive glucose oxidation and lipid synthesis in peripheral tissues. Furthermore, JTT-501 enhanced insulin receptor autophosphorylation in hindlimb muscle. 3. JTT-501 reduced serum leptin concentrations in both models, but did not affect body weight or epididymal fat weight. 4. Our observations indicate that JTT-501 improves the metabolic abnormalities in both genetic and non-genetic insulin-resistant models by enhancing insulin action in peripheral tissues. These effects of JTT-501 are due, at least in part, to enhanced insulin receptor autophosphorylation. In addition, JTT-501 is able to reduce serum leptin concentrations in hyperleptinaemia of the insulin-resistant model. We expect JTT-501 to show promise for treating non-insulin dependent diabetes mellitus patients with insulin resistance.

Animals↗
PubMed1998

Altered anionic GBM components in monoclonal antibody against slit diaphragm-injected proteinuric rats.

BACKGROUND: We previously reported that monoclonal antibody (mAb) 5-1-6 bound to renal filtration slits induces massive proteinuria without causing ultrastructural changes in the glomerulus. This study evaluated the underlying mechanisms of the increase in glomerular permeability. METHODS: The distribution of endogenous albumin and IgG in the glomerular basement membrane (GBM) was studied in in situ drip-fixed glomeruli of Munich-Wistar rats by use of immunogold immunocytochemistry in the presence and absence of mAb 5-1-6. The density of foot process glycocalyx components was estimated by labeling with Limax fluvus lectin- or Helix pomatia lectin-gold complexes. Anionic sites in the GBM were examined by labeling with cationic gold at pH 2.0 or 7.4. Carboxyl groups, which also furnish an anionic charge to the GBM, were examined by specific biotinylation and colloidal gold probe methods. In addition, the infusion-staining of anionic sites was performed by use of ruthenium red in both Munich-Wistar and Wistar rats. RESULTS: The urinary excretion of albumin and IgG was increased markedly in the treated rats, indicating a non-selective barrier defect. In the control rats, albumin and IgG molecules were mainly located along the inner half of the GBM, and to a lesser degree in the lamina rara externa. In the treated rats, the albumin and IgG moieties were more equally distributed throughout the width of the GBM. Newly appearing, small dense peaks at the outer side of the GBM were evident, indicating a barrier function of outer zone of the GBM and/or epithelial cell layer. No intergroup differences in the density of lectin binding sites on foot processes were seen. The reduction in the number of ruthenium red-positive anionic sites and cationic gold (pH 2. 0)-labeled anionic sites in the lamina rara externa was significant in the treated rats at day 3, indicating a possible alteration of charged proteoglycan in the lamina rara externa. No such changes were seen with cationic gold (pH 7.4)-labeled anionic sites in the GBM. The density of labeled carboxyl groups was significantly reduced in the treated rats relative to the controls. CONCLUSIONS: These results show that the injection of mAb 5-1-6 induced a perturbation of the charge- and probably the size-selective glomerular filtration barrier. The observed reduction in the levels of various negatively charged substances resulted in massive proteinuria, implying that alteration of target antigens can affect the integrity of the GBM constituents maintaining the normal barrier function.

Albuminuria↗
PubMed1998

Activation-induced apoptosis of mature T cells is dependent upon the level of surface TCR but not on the presence of the CD3 zeta ITAM.

Activation-induced cell death (AICD) occurs primarily in recently activated T cells after a second TCR triggering. Since a threshold in the activation status may be critical for AICD, it is likely that the CD3 ITAM, docking sites for tyrosine kinases, regulate AICD. A 'threshold model' for AICD was tested by using two targeted mutant mouse strains lacking either the zeta chain (CD3zeta-/-) or the ITAM of the zeta chain (CD3zeta-/-:Tgzetadelta67-150). Although the T cells from the CD3zeta-/- mice express extremely low levels of surface TCR, a subpopulation (approximately 18%) of activated T cells could be induced to express TCR/FcepsilonRI gamma by using a powerful polyclonal activation protocol. These activated TCR/FcRI gamma T cells were capable of undergoing AICD, but its induction required 10 times as much anti-CD3epsilon mAb as that required for AICD of wild-type T cells. Thus, the intensity of AICD correlated with the level of CD3 expression and was less efficient with activated, CD3zeta(-/-)-derived T cells. By contrast, AICD of T cells from the CD3zeta-/-:Tgzetadelta67-150 mice could be induced with low doses of anti-CD3epsilon mAb and the extent of AICD was comparable to T cells from wild-type mice. The AICD induced in T cells from CD3-/-, CD3zeta-/-:Tgzetadelta67-150 and normal controls was specifically inhibited by Fas-Ig fusion proteins. Our data support the 'threshold model' of AICD by demonstrating that AICD is controlled by the strength of T cell activation.

Animals↗
PubMed1998

Resonance Raman study on reduced flavin in purple intermediate of flavoenzyme: use of [4-carbonyl-18O]-enriched flavin.

4-Carbonyl-18O]-enriched lumiflavin, riboflavin, and FMN were prepared by incubating each corresponding non-labeled flavin in 1 M Na18OH (H218O) at 25 degrees C. [4-Carbonyl-18O]FAD was prepared from the corresponding riboflavin by using FAD synthetase. Isotope effects by [4-carbonyl-18O]-labeling confirmed that the 1,709-cm-1 band in the IR spectrum of lumiflavin and the 1,711-cm-1 band in the Raman spectrum of FAD are mainly derived from C(4)=O stretching vibrational mode. The 1,605-cm-1 Raman band of the anionic reduced flavin in the purple intermediate of D-amino acid oxidase (DAO) with D-proline or D-alanine does not shift in DAO reconstituted with [4-carbonyl-18O]FAD, although it shifts with [4,10a-13C2]- or [4a-13C]FAD. Thus the band is mainly due to the C(4a)=C(10a) stretching vibrational mode and includes no contribution from C(4)=O stretching vibration. The band frequencies cover a fairly wide range (1,602-1,620 cm-1) depending on the enzymes. The frequencies of the reduced flavin in the purple intermediates of the dehydrogenases (medium-chain acyl-CoA, short-chain acyl-CoA, and isovaleryl-CoA dehydrogenases) are higher than those of the oxidases (DAO and L-phenylalanine oxidase). This indicates that the C(4a)=C(10a) bond order of reduced flavin in the dehydrogenases with the low reactivity for molecular oxygen is stronger than that in the oxidases with high reactivity. Therefore, the band frequency of C(4a)=C(10a) stretching may serve as an indicator of the reactivity of flavoprotein with molecular oxygen. Furthermore, strong hydrogen bonding of flavin at the N(1) moiety with the hydroxyl group of Thr136 in MCAD is probably responsible for the strong bond of the C(4a)=C(10a) of reduced flavin in the dehydrogenase.

Flavin Mononucleotide↗
PubMed1998

Salmonella infection-induced non-responsiveness of murine splenic T-lymphocytes to interleukin-2 (IL-2) involves inhibition of IL-2 receptor gamma chain expression.

In a previous study we demonstrated that Salmonella typhimurium-induced immunosuppression involved T-cell non-responsiveness to interleukin-2 (IL-2). In this study we observed that Salmonella-induced T-cell non-responsiveness to IL-2 was not reversed completely by treatment with N(G)-monomethyl-L-arginine, which is known to inhibit nitric oxide (NO) secretion by macrophages in culture. Furthermore, when purified splenic T-lymphocytes from Salmonella-infected mice were activated with an anti-CD3 antibody, the responsiveness of these T-cells to IL-2 was suppressed significantly. Results of flow cytometric analysis using an anti-IL-2 receptor gamma chain (IL-2Rgamma) antibody showed that IL-2Rgamma expression in mitogen-activated T-cells was down-regulated by Salmonella infection. These results suggest that Salmonella infection-induced T-cell non-responsiveness to IL-2 involves a defective function of T-cells themselves and appears to be regulated by inhibition of IL-2Rgamma expression in T-cells.

Animals↗
PubMed1998

DNA sequencing of the gene encoding Salmonella typhimurium-derived T-cell inhibitor (STI) and characterization of the gene product, cloned STI.

In a previous study, we found a novel protein which inhibited T-cell responsiveness to interleukin-2 (IL-2) in Salmonella typhimurium and called it S. typhimurium-derived T-cell inhibitor (STI). In this study, we analyzed the DNA sequence of the gene encoding STI. The STI gene was cloned into a plasmid vector, pUC118, and expressed in Escherichia coli JM109. Like native STI, the cloned STI inhibited IL-2-dependent CTLL-2 cell growth. Furthermore, this growth inhibition involved down-regulation of IL-2 receptor expression. These results indicate that the cloned STI expressed in E. coli was identical to native STI. Sequencing revealed that the STI gene contained an open reading frame of 2298 base pairs encoding a precursor form of 765 amino acid residues (molecular mass 83605) that is processed into a mature form of 745 amino acid residues with molecular mass 81 548. Homology analysis revealed that its amino acid sequence was highly homologous with that of the beta-glucosidase of E. coli K-12. We designated the gene encoding STI sti.

Amino Acid Sequence↗
PubMed1998

Limited-stage small cell lung cancer: local failure after chemotherapy and radiation therapy.

PURPOSE: To evaluate radiation therapy regimens for improvement in local control in patients with limited-stage small cell lung cancer. MATERIALS AND METHODS: Radical radiation therapy results in 117 patients with limited-stage small cell lung cancer were retrospectively reviewed. The protocols in 90 patients were 40 Gy in 20 fractions (n = 28), 50 Gy in 25 fractions (n = 32), and 45 Gy in 30 fractions (accelerated hyperfractionation, n = 30). The other 27 patients received thoracic irradiation (dose range, 20-60 Gy; median dose, 54 Gy). All patients underwent systemic chemotherapy. RESULTS: The 5-year Kaplan-Meier survival rates in the patients with N0, N1, N2, and N3 disease were 26%, 34%, 18%, and 0%, respectively; the rates of in-field relapse were 25%, 36%, 26%, and 25%, respectively; and the rates of marginal relapse were 0%, 9%, 15%, and 29%, respectively. In 56% of patients with marginal relapse, the relapse site was at the upper margin. The 4-year in-field control rates for the patients who underwent 40, 50, and 45 Gy were 51%, 70%, and 56%, respectively. CONCLUSION: Patients with N3 limited-stage small cell lung cancer should undergo a separate protocol, and the upper margin should be extended in patients with N2 or N3 disease.

Adult↗
PubMed1998

Combination of irinotecan and etoposide for treatment of refractory or relapsed small-cell lung cancer.

PURPOSE: To determine the response rate, survival, and toxicity of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with etoposide, a topoisomerase II inhibitor, in refractory or relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS: Twenty-five patients with refractory or relapsed SCLC were entered onto the trial. All 25 patients had been pretreated with some form of cisplatin-based combination chemotherapy and had also received previous etoposide- or anthracyclinecontaining chemotherapy. The median time off chemotherapy was 6.7 months (range, 0.9 to 23.5). Patients were treated at 4-week intervals using CPT-11 (a starting dose of 70 mg/m2 intravenously on days 1, 8, and 15) plus etoposide (80 mg/m2 intravenously on days 1 to 3), with a subsequent dose based on toxicity. In addition, recombinant human granulocyte colony-stimulating factor (rhG-CSF; 2 microg/kg/d) was given from day 4 to day 21, except on the days of CPT-11 administration. RESULTS: All patients were assessable for toxicity and survival. Twenty-four patients were assessable for response. There were 14 partial responses (PRs) and three complete responses (CRs), for an overall response rate of 71% (95% confidence interval, 53% to 89%). The median response duration was 4.6 months. Median survival was 271 days. Major toxicities were myelosuppression (predominantly leukopenia) and diarrhea. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 56% and 20% of patients, respectively. Grade 3 to 4 diarrhea was observed in 4%. There was one treatment-related death due to severe myelosuppression. CONCLUSION: A combination of CPT-11 and etoposide with rhG-CSF support is an active therapy against refractory or relapsed SCLC and deserves to be studied more extensively in a phase III trial.

Adult↗
PubMed1998

Epitope-specific antibodies to the 43-kD glomerular membrane protein podoplanin cause proteinuria and rapid flattening of podocytes.

The 43-kD integral membrane protein podoplanin is localized on the surface of rat podocytes, and transcriptionally downregulated in rat puromycin nephrosis. In this study, a single intravenous injection of polyclonal rabbit anti-podoplanin IgG resulted in selective binding of IgG to the entire podocyte's surface. Some IgG produced by different rabbits rapidly induced transient proteinuria (approximately 350 mg/24 h at day 1, normal levels around day 5), whereas other IgG were ineffective. All anti-podoplanin IgG shared a common binding site at amino acids 39 to 47 (DDMVNPGLE), whereas IgG inducing glomerular damage specifically bound to an additional epitope at amino acids 74 to 79 (PIEELP), as observed by a SPOTs analysis on overlapping synthetic peptides. Proteinuria was not prevented by complement depletion or by treatment with the oxygen radical scavenger dimethylthiourea. Injection of Fab fragments failed to induce glomerular pathology, indicating that dimerization of podoplanin by divalent IgG was required. Proteinuria was paralleled by extensive flattening of foot processes that was also induced by blood-free perfusion of isolated rat kidneys with anti-podoplanin IgG. Thus, glomerular changes were due to direct interaction of distinct epitope(s) of podoplanin and divalent IgG. These results provide evidence that podoplanin plays a role in maintaining the unique shape of podocyte foot processes and glomerular permeability.

Animals↗
PubMed1998

Expression of types I, II, and III TGF-beta receptors in human glomerulonephritis.

Protein and mRNA expression of transforming growth factor-beta (TGF-beta) receptor type I (TbetaRI), type II (TbetaRII), and type III (TbetaRIII) were studied in serial sections of kidney samples obtained from patients with glomerulonephritis. In minimal change disease, weak expression of TbetaRI and TbetaRII was observed mainly in glomerular endothelial cells, peritubular capillaries, and interstitial arteriolar endothelial cells, whereas TbetaRIII expression was found mainly in the interstitium. Expression of all three TGF-beta receptors (TbetaR) was increased remarkably in glomerular and Bowman's capsular cells comprising the tuft adhesions to Bowman's capsules in glomerulonephritis with increased matrix accumulation, including IgA nephropathy, lupus nephritis, focal and segmental glomerulosclerosis, myeloperoxidase-antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis, and membranoproliferative glomerulonephritis. Increased expression of the three TbetaR was also seen in glomerular epithelial cells in the vicinity of glomerulosclerotic lesions, in crescent cells, and in some tubules and infiltrative mononuclear cells found in the periglomerular and tubulointerstitial lesions with increased matrix deposition. In contrast, no remarkable TbetaRII expression was noted in mesangial proliferative lesions in IgA nephropathy, lupus nephritis, and membranoproliferative glomerulonephritis. These data suggest that distinctive modulation of TbetaR expression may be involved in the development of adhesive, sclerotic, and proliferative renal lesions in human glomerulonephritis.

Activin Receptors, Type I↗
PubMed1998

Effective irradiation of a metastatic region of the lung in a patient with extraskeletal myxoid chondrosarcoma.

Complete obstruction of the right main bronchus occurred in a 76-year-old woman due to pulmonary metastasis from the extraskeletal myxoid chondrosarcoma (EMC) which had been detected 5 years earlier. Treatment with Nd-YAG laser and biopsy forceps opened up the lumen of the right main bronchus 90%, and then X-irradiation was given toward the remaining tumor. The tumor disappeared almost completely following radiotherapy and such a state had lasted for several years until she died of old age at the age of 81. We judged that radiotherapy had been effective for this tumor. To date, the information concerning the effect of radiotherapy on this disease is insufficient.

Aged↗