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Biomedical subjects

T Matsuda

Publications and source records attributed to T Matsuda.

At least 1,009 records · Page 56Linked to original sources

Cough receptor sensitivity and bronchial responsiveness in normal and asthmatic subjects.

We examined whether airway cough receptor sensitivity correlates to nonspecific bronchial responsiveness. We measured cough threshold, the lowest concentration of inhaled tartaric acid eliciting five or more coughs, and the provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20FEV1) in 38 normal and 11 asthmatic subjects. All subjects were nonsmokers. The geometric mean value of PC20FEV1 was 25.7 mg.ml-1 (GSEM1.29) and 0.63 mg.ml-1 (GSEM1.29) and the geometric mean value of the cough threshold was 115 mg.ml-1 (GSEM1.20) and 95.5 mg.ml-1 (GSEM1.35) in normal and asthmatic subjects, respectively. The PC20FEV1 was significantly (p less than 0.01) lower in asthmatics than in normals but the cough threshold did not differ between them. No significant correlation was observed between the cough threshold and the PC20FEV1 in normal subjects or in asthmatics. These results indicate that cough sensitivity does not directly correlate to bronchial responsiveness in normal and asthmatic subjects.

Administration, Inhalation↗

[Felty's syndrome].

Felty's syndrome is a variant of rheumatoid arthritis with a triad of leukopenia, splenomegaly and typical rheumatoid arthritis, and often accompanies the other extraarticular symptoms, such as subcutaneous nodules, lymphadenopathy, anemia, thrombocytopenia, leg ulcers, fever and weight loss. In addition to the decreased number of leukocyte, impaired functions of leukocytes were also revealed. These changes were considered as the cause of repeated infections, which was the major cause of death in Felty's syndrome. Splenectomy is not fully effective for leukopenia and for the repeated infection. Glucocorticoid therapy can increase leukocyte count, at least tentatively. It has been reported that gold was effective for leukopenia, repeated infection and skin ulcer. However, the definitive way of treatment of this syndrome based on the pathogenesis of this syndrome, remains to be established.

Adolescent↗

[Arachidonic acid metabolism affected by cellular interactions regulating leukocyte adherence].

Increased leukocyte adherence to endothelium is recognized to be the first step following the development of unstable angina and cerebrovascular disease. In this paper, the methods to determine leukocyte adherence and the conditions which influence the result of the assay are discussed. We administered aspirin, TxA2 synthetase inhibitor or TxA2 receptor antagonist to healthy volunteers. Leukocyte adherence was inhibited following the administration of these antiplatelet agents. The effect on leukocytes may prevent thrombosis formation. Although the role of the leukocyte adherence in the pathogenesis of thrombosis has not been fully elucidated. Several forms of stimuli may cause expression of adhesive glycoproteins, which have a RGD sequence, on the surface of leukocyte and thus lead to thrombotic formation.

Arachidonic Acid↗

[Analysis of bronchoalveolar lavage fluid in patients before and after bone marrow transplantation].

We analysed BALF cell findings in 9 patients (group A: 5 patients without lung disease after bone marrow transplantation (BMT), group B: 4 patients with lung disease after BMT) before and after BMT. Before BMT, BALF cell findings in group A were almost normal, whereas a relative increase of lymphocytes was seen in group B. Although total cell counts and cell composition in group A changed little after BMT, CD4/CD8 ratios in BALF lymphocytes decreased. In contrast, a relative increase of lymphocytes and neutrophils was seen in group B and there was variation of CD4/CD8 ratios in BALF lymphocytes after BMT. We there studied the BALF lymphocytes of 3 patients in group A and 4 patients in group B after BMT by means of 2-color analysis. Among CD4+ cell populations, CDw 29+ cells were decreased in both groups after BMT. A relative increase of BALF-CD4+ HLA-DR+ cells and CD8+ HLA-DR+ cells was seen in group A, but was not seen in group B. These findings suggest that there is abnormality of local immunity in the lung after BMT.

Adult↗

[The relation between bronchial infiltration of eosinophils and bronchial hyperresponsiveness in two cases of eosinophilic pneumonia].

We evaluated the bronchial hyperresponsiveness to methacholine in the two cases of eosinophilic pneumonia with infiltration of eosinophils into bronchial mucosa. Bronchial responsiveness was not increased in either case in spite of marked infiltration of eosinophils into the bronchial mucosa and submucosa. Hypodense eosinophils are reported in the sputum of patients with bronchial asthma. This suggests that infiltration of activated eosinophils into the bronchial mucosa is an essential factor in bronchial hyperresponsiveness.

Adult↗

[Simple hypothermic retrograde cerebral perfusion for brain protection during aortic arch surgery].

We have recently found that retrograde cerebral perfusion can be performed by simply elevating central venous pressure to 15 mmHg in the Trendelenburg position when the aortic arch is open during aortic arch surgery. During deep hypothermic (15 degrees C) perfusion of the lower half of the body with the descending aorta occluded, and with single cannulation of the right atrium for drainage, oxygen-saturated venous blood perfuses the brain retrogradely, supplying it with oxygen. This method renders clamping of the aortic arch and the arch vessels unnecessary. Eleven cases of aortic arch aneurysm (9 males, 2 females; 5 true aneurysms, 5 dissecting aneurysms, one combined aneurysm; mean age, 63 years) were operated using this technique, whose clinical significance was then evaluated. Median sternotomy was performed in 4 cases, left thoracotomy in 7. Patch replacement was performed in 2 cases and graft replacement in 9 cases (the proximal arch in 2, the whole arch in 2, the distal arch in 5). In two cases coronary artery bypass surgery using the internal thoracic artery was performed simultaneously via lateral thoracotomy. Operation time was 517 +/- 139 min, pump time was 211 +/- 34 min, cardiac arrest time was 84 +/- 34 min and the lowest rectal temperature was 15.7 +/- 1.1 degrees C. In the venous return, PO2 was 188 +/- 136 mmHg, and SO2 97.5 +/- 2.9%, the respective values in the retrogradely perfused blood in the aortic arch being 46 +/- 12 mmHg and 68.8 +/- 18.8%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Thromboxane A2 synthetase inhibitor (OKY-046) improves abnormal mucociliary transport in asthmatic patients.

The effect of a thromboxane A2 synthetase inhibitor (OKY-046, 400 mg po/day) on mucociliary transport was investigated in 19 asthmatic patients. The nasal clearance time, as measured by the saccharin test, was prolonged in asthmatics (60.2 +/- 8.4 SE min) compared with normal controls (15.1 +/- 3.4 SE min). Within 4 weeks after OKY-046 administration, the nasal clearance time had improved (27.4 +/- 4.4 SE min, P less than .01) and the amount of sputum had decreased 30% (P less than .01). These results indicate that thromboxane A2 plays an important role in mucociliary transport in patients with asthma.

Aged↗

Na+ influx-induced decrease of (Na+ + K+)-ATPase activity in rat brain slices: role of Ca2+.

Treatment of rat brain slices with veratrine and monensin decreased (Na+ + K+)-ATPase activity in the membranes in a dose-dependent manner. The effect of monensin, like that of veratrine, was accompanied by a decrease of maximal binding sites for ouabain. The inhibitory effect of monensin on the enzyme activity was dependent on external Ca2+ at low concentrations, but not at a high concentration. The decreased enzyme activity induced by monensin was restored by subsequent incubation of the slices in a Ca(2+)-free medium containing 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester (BAPTA-AM), a chelator of intracellular Ca2+. The effect of monensin at a low concentration on enzyme activity was antagonized by amiloride (1 mM), bepridil (5 microM), quinacrine (30 microM) or verapamil (30 microM), but not by nifedipine (1 microM) or omega-conotoxin (1 microM). Furthermore, the inhibitory effect of monensin at a high concentration under Ca(2+)-free conditions was blocked by BAPTA-AM (30 microM) and by bepridil (100 microM) or diazepam (500 microM), inhibitors of mitochondrial Na(+)-Ca2+ exchange. Inhibitors of calmodulin, protein kinase C, phospholipase A2 and calpain did not affect the monensin-induced decrease of enzyme activity. Dithiothreitol (10 mM) blocked the effect of monensin on enzyme activity but did not affect the ionophore-induced influx of Ca2+ in the slices.

Amiloride↗

Endogenous basic fibroblast growth factor-dependent induction of collagenase and interleukin-6 in tumor necrosis factor-treated human microvascular endothelial cells.

Tumor necrosis factor-alpha (TNF-alpha) has been shown to enhance the synthesis of interleukin-6 (IL-6) and collagenase in human omental microvascular endothelial (HOME) cell (Mawatari, M., Kohno, K., Mizoguchi, H., Matsuda, T., Asoh, K., Van Damme, J. V., Welgus, H. G., and Kuwano, M. (1989) J. Immunol. 143, 1619-1627). In the present study, we have examined whether the TNF-alpha-induced synthesis of IL-6 or collagenase in HOME cells is mediated by an inducible growth factor. Among several growth factors examined, we found that the expression of basic fibroblast growth factor (bFGF) mRNA was the one most prominently enhanced when HOME cells were treated with TNF-alpha. The increase of bFGF mRNA by TNF-alpha in HOME cells was observed in both a dose- and time-dependent manner when assayed by Northern blot analysis. The induction of bFGF mRNA was observed by 3 h after incubation with TNF-alpha, and the maximal increase of 5-fold was obtained after 12 h of incubation with 100 units/ml TNF-alpha. Western blot analysis confirmed the enhanced synthesis of bFGF by TNF-alpha. Metabolic labeling and immunoprecipitation assays of bFGF showed that exposure to TNF-alpha enhanced secretion of bFGF into culture medium and also that TNF-alpha stimulated the production of bFGF molecules with molecular masses of 18, 21, and 22.5 kDa in HOME cells. TNF-alpha induced the expression of collagenase mRNA and IL-6 mRNA in HOME cells as well, and the coadministration of neutralizing anti-bFGF antibody almost completely blocked the effects of TNF-alpha. The treatment of HOME cells with exogenous bFGF significantly stimulated the expression of collagenase mRNA and IL-6 mRNA in HOME cells. Therefore, the biological effects of TNF-alpha on HOME cells may be mediated, at least in part, by TNF-alpha-induced bFGF.

Blotting, Northern↗

M3 cholinoceptors and P2y purinoceptors mediating relaxation of arteries in spontaneously hypertensive rats at prehypertensive stages.

Muscarinic cholinoceptor and purinoceptor subtypes were determined in femoral and mesenteric artery strips from spontaneously hypertensive rats (SHR) at prehypertensive stages. Acetylcholine (ACh), carbachol and oxotremorine induced endothelium-dependent relaxations during contractions evoked by 5-hydroxytryptamine. The order of relative potency of the agonists was ACh greater than carbachol = oxotremorine in the prehypertensive SHR and Wistar Kyoto rats (WKY). Schild plot data for muscarinic cholinoceptor antagonists obtained with carbachol or oxotremorine as agonist indicated that the arteries of prehypertensive SHR and WKY possessed M3 cholinoceptors mediating relaxation. The relaxation responses of the prehypertensive SHR and WKY arteries to ATP were inhibited by reactive blue 2 but not altered after P2x purinoceptors had been desensitized by alpha,beta-methylene ATP, which suggests that the arteries possessed P2y purinoceptors mediating relaxation. The responses of the femoral and mesenteric arteries from prehypertensive SHR to ACh, carbachol and ATP were similar to those of WKY arteries, although the response of the prehypertensive SHR artery to oxotremorine was significantly increased compared to that of the WKY artery. The results suggest that M3 cholinoceptor- and P2y purinoceptor-mediated relaxations are not changed in prehypertensive SHR arteries as compared to those in WKY arteries.

Acetylcholine↗

Gonadectomy changes the pituitary-adrenocortical response in mice to 5-HT1A receptor agonists.

The effects of 5-HT1A receptor agonists such as 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), BP-554 and buspirone on the serum corticosterone level were significantly more pronounced in female than in male mice. A similar sex difference was observed for the effect of 8-OH-DPAT on the plasma ACTH level. Pretreatment with proadifen, an inhibitor of microsomal drug-metabolizing enzymes, did not affect the sex difference in the effect of 8-OH-DPAT. The corticosterone response to 8-OH-DPAT in female mice was attenuated by ovariectomy. The effect of 8-OH-DPAT in ovariectomized mice was enhanced by chronic estradiol and the enhancement was blocked by testosterone. In male mice the corticosterone response to 8-OH-DPAT increased at 5 weeks after castration but had not changed at 2 weeks. Chronic estradiol enhanced the corticosterone response to 8-OH-DPAT in castrated mice. There was no difference between sexes in [3H]8-OH-DPAT binding to membranes and in the contents of 5-HT and 5-hydroxyindoleacetic acid in the hypothalamus. Accumulation of 5-hydroxytryptophan after decarboxylase inhibition in the hypothalamus was however greater in female than in male mice.

5-Hydroxytryptophan↗

Prothrombin Himi; an abnormal prothrombin characterized by a defective thrombin activity.

An abnormal prothrombin has been detected in a 26-year-old female, who had no history of excessive bleeding. Prothrombin activity was approximately 10% when measured using either the classical one-stage assay or the assay with Echis carinatus venom, whereas prothrombin antigen level was normal. In keeping with current nomenclature practices, the abnormal prothrombin was designated "Prothrombin Himi". The electrophoretic behavior and calcium binding properties of Prothrombin Himi did not differ significantly from normal. Prothrombin Himi was isolated by chromatography on Q-Sepharose. Electrophoretic migration of the purified abnormal prothrombin on SDS-PAGE was normal. Upon prothrombin activation by Echis carinatus venom, the clotting activity produced from Prothrombin Himi was only 37% of the normal level after 90 minutes of the activation time, where as the amidolytic activity was almost the same as normal. The cleavage patterns of Prothrombin Himi by factor Xa or Echis carinatus venom investigated by SDS-PAGE, were found to be normal. These results indicate that Prothrombin Himi was characterized by a defective thrombin enzymatic activity.

Adult↗

Metallothionein content correlates with the sensitivity of human small cell lung cancer cell lines to cisplatin.

We have established cis-diamminedichloroplatinum(II) (cisplatin) resistant human small cell lung cancer cell lines, H69/CDDP0.2 and H69/CDDP, to investigate the mechanism of acquired resistance to cisplatin. H69/CDDP0.2 and H69/CDDP were 6- and 11-fold resistant to cisplatin compared with the H69 parental cell line. H69/CDDP was also resistant to cadmium chloride (2-fold), cis-diammine(glycolato)platinum (4-fold), 4-hydroperoxycyclophosphamide (3-fold) and 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosour ea (4-fold) if the drug concentrations that inhibit cell growth by 50% from growth inhibition assay were compared. There was no significant difference in the cisplatin accumulation among these cell lines. Although DNA interstrand cross-link formations, determined by filter elution assay in H69/CDDP0.2 and H69/CDDP, was decreased to 20 to 30% of that in H69 parental cells, the repair capacity of DNA interstrand cross-links was equivalent in all three cell lines. Intracellular glutathione content was equal in all cell lines. H69/CDDP had the highest glutathione S-transferase activity (H69, 11 nmol/min/mg protein, H69/CDDP0.2, 12 nmol/min/mg protein; H69/CDDP, 74 nmol/min/mg protein, respectively) and an overexpression of glutathione S-transferase pi mRNA. The drug concentrations that inhibit cell growth by 50% for cisplatin in all cell lines were decreased by treatment with ethacrynic acid, an inhibitor of glutathione S-transferase pi, but this did not alter the relative degree of resistance. Intracellular metallothionein content (H69, 14 pmol/mg protein, H69/CDDP0.2, 22 pmol/mg protein; H69/CDDP, 33 pmol/mg protein, respectively) and expression of metallothionein mRNA were correlated with the drug concentrations that inhibit cell growth by 50% of the three cell lines for cisplatin and cadmium chloride. The present study suggested the importance of metallothionein in the mechanisms of cisplatin resistance.

Antineoplastic Agents↗

Isolation and characterization of the human pyruvate kinase M gene.

Genomic clones containing the human pyruvate kinase M (PKM) gene, which encodes the M1-type and M2-type isozymes, were isolated and their exon sequences were determined. The gene is approximately 32 kb and consists of 12 exons and 11 introns. Exons 9 and 10 contain sequences specific to the M1 and M2 types, respectively, indicating that the human isozymes are produced from the same gene by alternative splicing as in the case of the rat gene. The exon-intron structure of the human PKM gene is identical to that of the rat gene, and the introns of both genes interrupt the exons at the same points. Introns 6 and 7 begin with GC dinucleotide instead of the consensus GT, but the other exon-intron boundaries are consistent with the GT-AG rule. The gene is transcribed from multiple start sites. The 5'-flanking region of the gene contains putative Sp1-binding sites, but no TATA box or CAAT box, and shows high sequence similarity to that of the rat M gene. Bacterial chloramphenicol acetyltransferase assay revealed that the upstream region between positions -493 and -51 contained a cis-acting element(s) that was essential for expression of the M gene in HeLa cells. Long stretches of conserved regions were found in the introns around the M1-specific and M2-specific exons, suggesting that these regions may be involved in the alternative splicing machinery.

Amino Acid Sequence↗

Alteration in L-type pyruvate kinase gene expression is not associated with the LF-B1 mRNA level.

The relation of expression of the LF-B1 gene with the L-type pyruvate kinase (L-PK) mRNA level in rat liver and hepatoma cells was investigated. The L-PK mRNA level in rat liver changed after partial hepatectomy, during development and on intake of a high carbohydrate diet, while the level of LF-B1 mRNA remained unchanged or altered reciprocally. Dedifferentiated AH-130 cells, which did not express L-PK mRNA, expressed LF-B1 mRNA. These results suggest that transcription of the pyruvate kinase L gene is not simply regulated by the level of LF-B1 mRNA.

Animals↗

Structural and functional roles of cysteine residues of Bacillus polymyxa beta-amylase.

Bacillus polymyxa beta-amylase contains three cysteine residues at positions 83, 91, and 323, which can react with sulfhydryl reagents. To determine the role of cysteine residues in the catalytic reaction, cysteine residues were mutated to construct four mutant enzymes, C83S, C91V, C323S, and C-free. Wild-type and mutant forms of the enzyme were expressed in, and purified to homogeneity from, Bacillus subtilis. A disulfide bond between Cys83 and Cys91 was identified by isolation of tryptic peptides bearing a fluorescent label, IAEDANS, from wild-type and C91 V enzymes followed by amino acid sequencing. Therefore, only Cys323 contains a free SH group. Replacement of cysteine residues with serine or valine residues resulted in a significant decrease in the kcat/Km value of the enzyme. C323S, containing no free SH group, however, retained a high specific activity, approximately 20% of the wild-type enzyme. None of the cysteine residues participate directly in the catalytic reaction.

Amino Acid Sequence↗