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Biomedical subjects

T Matsuda

Publications and source records attributed to T Matsuda.

At least 955 records · Page 53Linked to original sources

Localization of CuZn-superoxide dismutase in the human male genital organs.

We performed an immunohistochemical analysis using a polyclonal antibody to determine the localization of CuZn-superoxide dismutase (SOD), a scavenger of superoxide anion radicals, in the human male genital organs. In the testis, intense immunoreactivity of CuZn-SOD was shown in both the cytoplasm and nucleus of the spermatogonia of the seminiferous tubules. Spermatocytes, further differentiated germ cells and Sertoli cells showed no or weak immunoreactivity. In the ductus epididymis, the principal cells showed no or weak immunoreactivity except for the stereocilial region, while the basal cells showed relatively intense immunoreactivity. In the ductus deferens, the prostate and the seminal vesicles, columnar and cuboidal epithelia showed CuZn-SOD immunoreactivity. The immunoreactivity was more intense in the epithelia of the ductus deferens than in the prostate or the seminal vesicles. Basal cells in the prostate also showed intense immunoreactivity. Collectively, the present immunohistochemical results suggest that CuZn-SOD in the male genital organs is localized where it could play an important role in cell differentiation, including spermatogenesis. The CuZn-SOD could also play a role in local defence mechanisms against tissue damage mediated through superoxide anion radicals, as well as in providing SOD to the seminal plasma.

Adult↗

Carbohydrate binding specificity of monoclonal antibodies raised against lactose-protein Maillard adducts.

Three hybridoma antibodies (L101, L104, and L117) specific for lactose-protein amino carbonyl products (Maillard adducts) were obtained by immunizing mice with the lactose-ovalbumin Maillard adduct and by screening with the lactose-bovine serum albumin (BSA) adduct. They reacted with the Maillard adducts of lactose with several different proteins, but not with the adducts of several other reducing sugars. L101 reacted well with the lactose-BSA adducts formed by 2- to 16-day incubation, whereas L104 and L117 reacted with the advanced stage reaction products but not with the adducts of 2-day incubation. The competitive inhibition of the antibody binding by several mono- and disaccharides showed that lactulose (4-O-beta-D-galactopylanosyl-D-fructose) was the best inhibitor for all three antibodies, and that L104 and L117 were inhibited by methyl-beta-D-galactoside more effectively than L101. These results suggested that different components produced during the progress of the Maillard reaction could be antigenic determinants, and that the carbohydrate moiety including the terminal galactosyl residue played an important role in the antibody binding to the lactose-protein Maillard adducts.

Animals↗

Evidence of a role for phosphatidylinositol synthesis in human amnion cell proliferation.

Phosphatidylinositol (PtdIns) is the key precursor of phosphoinositide-derived intracellular mediators. The effects of changing the rate of PtdIns synthesis on mitogenic activity of human amnion-derived WISH cells were investigated. Incubation of the cells with [3H]inositol caused a time- and dose-dependent PtdIns labeling. Exogenous Ca2+ inhibited [3H]inositol incorporation in a dose-dependent fashion; half-maximal inhibition occurred with 0.3-1.0 mM Ca2+. In contrast, removal of cytosolic Ca2+ by ionophore A23187 and 1 mM EGTA induced enhancement of the PtdIns labeling as a function of A23187 concentration, perhaps through release of inhibitory effects of endogenous Ca2+. The A23187-stimulated PtdIns labeling with [3H]inositol was not abolished by additional unlabeled inositol, suggesting that [3H]inositol labeling of PtdIns occurred mainly through de novo synthesis catalyzed by PtdIns synthase (EC 2.7.8.11). In cells with PtdIns synthase activity decreased by exogenous Ca2+, [3H]thymidine incorporation was also inhibited, while A23187 caused dose-dependent enhancement of thymidine incorporation. The changes in PtdIns synthase activity occurred in parallel with changes in mitogenic activity caused by increasing the dose of exogenous Ca2+ or A23187. A similar lowering of mitogenic activity was observed upon suppression of PtdIns synthase by pemirolast potassium (9-methyl-3-1H-tetrazol-5yl-4H-pyrido[1,2-a]pyridin-4-one potassium) via a Ca(2+)-independent mechanism. These data demonstrate that changes in PtdIns synthase activity by some agents acting via different mechanisms are associated with parallel changes in thymidine incorporation, and suggest that PtdIns production is tightly coupled to cell proliferation in human amnion cells.

Amnion↗

Changes in plasma levels of thrombomodulin during haemodialysis.

We studied the changes in plasma levels of thrombomodulin (TM) known to be present on vascular endothelial cells and released into circulating blood following damage to endothelial cells, during haemodialysis in 49 patients with end-stage chronic glomerulonephritis maintained on haemodialysis. After a single haemodialysis, plasma levels of TM were significantly elevated from 38.4 +/- 13.8 ng/ml to 46.8 +/- 14.6 ng/ml (p less than 0.05). Plasma levels of TM before haemodialysis were significantly higher in the cases of long-term haemodialysis than in those of short-term haemodialysis (p less than 0.01). From these observations, increased plasma levels of TM may be due to decreased clearance of TM by renal insufficiency, or damage to endothelial cells induced by the recurrent haemodialysis. In those patients with a greater residual blood volume in a dialyser, the changes in plasma levels of thrombin-antithrombin III complex and TM during a single haemodialysis were significantly higher. From these findings, it was suggested that endothelial cell damage is more severe in patients with greater residual blood volume.

Adult↗

DNA topoisomerase-targeting antitumor agents and drug resistance.

A review of the chemotherapeutic agents which have been developed by targeting DNA topoisomerase I and II is presented. Camptothecins as topoisomerase I-targeting agents and newly developed topoisomerase II-targeting agents with unique properties are expected to be promising anticancer agents in the near future. An important issue is how cellular sensitivity to these agents is controlled. One approach is to establish and characterize drug-resistant human cancer cell lines, which would provide powerful tools to understand their intracellular target sites and also the mechanisms for acquirement of drug resistance to topoisomerase inhibitors. Drug resistance to topoisomerase-targeting agents appears to be closely correlated with two events, namely decreased expression and point mutation of topoisomerase genes.

Antineoplastic Agents↗

Fungal melanonychia: ungual phaeohyphomycosis caused by Wangiella dermatitidis.

A 51-year-old female Japanese patient developed black pigmentation affecting both big toe-nails. Direct potassium hydroxide examination of the nail tissue demonstrated clusters of spherical dematiaceous cells, toruloid hyphae, and septate hyphae. Wangiella dermatitidis was repeatedly isolated from the affected toe-nail lesions. This case represents the first documented case of ungual phaeohyphomycosis, 'fungal melanonychia,' caused by the dematiaceous fungus W. dermatitidis. The patient was successfully treated with a topical solution of bifonazole.

Exophiala↗

Involvement of arachidonate cyclooxygenase products in bronchial hyperresponsiveness induced by subthreshold concentration of aerosolized thromboxane A2 analogue (STA2) in guinea pigs.

Effects of a thromboxane synthetase inhibitor (OKY-046) and a cyclooxygenase inhibitor (indomethacin) on bronchial hyperresponsiveness induced by subthreshold concentration of aerosolized thromboxane A2 analogue (STA2) were investigated in anesthetized, artificially ventilated guinea pigs in order to examine the role of the cyclooxygenase pathway in bronchial hyperresponsiveness. Pretreatment with aerosolized OKY-046 significantly inhibited the bronchial hyperresponsiveness to histamine, but pretreatment with intravenous indomethacin showed a tendency to potentiate bronchial hyperresponsiveness. These results suggest that subthreshold concentration of thromboxane A2 contributes to bronchial hyperresponsiveness through activating the cyclooxygenase pathway including thromboxane A2 synthesis, and that the released cyclooxygenase products have an inhibitory effect on the bronchial hyperresponsiveness in guinea pigs.

Aerosols↗

Demonstration of Ph1-negative host haemopoietic progenitor cells in an allogeneic marrow transplant recipient with chronic myelocytic leukaemia using polymerase chain reaction.

In an attempt to characterize host-derived haemopoietic cells in mixed haemopoietic chimeras, we studied bone marrow cells from male patients with chronic myelocytic leukaemia (CML) transplanted with marrow grafts from female donors. Amplification of a Y chromosome-specific sequence (YDNA) in DNA from marrow mononuclear cells using polymerase chain reaction (PCR) revealed persistence of host cells in 2 of 3 patients studied. On the other hand, persistence of Ph1-positive cells was unable to be demonstrated in the marrow cells from these patients using reverse transcription PCR (RT-PCR) for detecting bcr-abl chimeric messenger RNA. RT-PCR sensitivity for detecting minimal Ph1-positive cells in a background of Ph1-negative cells proved better than that of the PCR for detecting male cells among female cells. When bone marrow progenitor cells from one of the documented mixed chimeras were analyzed after an in vitro colony assay using PCR, 2 of 12 erythroid burst-forming units (BFU-E) proved to be YDNA-positive, i.e., of host origin, whereas none of them was shown to be Ph1-positive, although 12 BFU-E analyzed in the marrow cells obtained pretransplant from the same patient were all YDNA- and Ph1-positive. These findings indicate that, in some marrow transplant recipients with CML, a small number of host-derived normal haemopoietic progenitor cells may persist following lethal chemoradiotherapy and allogeneic bone marrow transplantation despite the fact that Ph1-positive clones can be eradicated.

Adult↗

Thermal and PGE2 sensitivity of the organum vasculosum lamina terminalis region and preoptic area in rat brain slices.

1. The effects of local applications of prostaglandin E2 (PGE2) on the unit activity of fifty-one neurones in the organum vasculosum lamina terminalis (OVLT) region and fifty-eight neurones in the preoptic area (POA) were investigated in small tissue slices from the rat hypothalamus containing the OVLT and POA isolated from each other. 2. Of these, thirty OVLT and twenty-eight POA neurones were warm sensitive and increased their discharge rate in response to a rise in tissue temperature. One OVLT neurone and one POA neurone were cold sensitive and showed the opposite type of responses to changes in temperature. The thermosensitivity of these neurones was still observed in a Ca2+ free-high Mg2+ solution. 3. Perfusion with PGE2 in doses between 1 and 250 nM changed the discharge rate in forty-two of fifty-one OVLT neurones and in thirty-two of fifty-eight POA neurones in a dose-dependent manner. The responses to PGE2 were not lost during synaptic blockade. The threshold dose of PGE2 to alter the discharge rate of the OVLT neurones (4.8 +/- 1.1 (S.E.M.) nM, n = 16) was significantly lower than that of the POA neurones (40.9 +/- 12.2 nM, n = 16). 4. Fifteen of forty-two OVLT neurones exhibited the responses with a slower onset (latency 5-13 min) and a longer duration (20 min to 3 h), but such responses were observed in only one of thirty-two POA neurones. 5. The responses of OVLT and POA neurones to PGE2 (50-250 nM) were reversibly blocked by a concurrent application of AH6809, a prostanoid EP1 and/or a DP receptor antagonist. 6. While there was no clear correlation between the type of thermosensitivity and the type of response to PGE2 among the POA neurones, a significantly higher incidence of inhibitory response to PGE2 was found among the warm-sensitive neurones in the OVLT region. 7. The lower threshold responses to PGE2 and the higher incidence of PGE2 responsiveness among OVLT neurones are consistent with previous findings which showed that the highest density of PGE2 receptor binding and the highest pyrogenic sensitivity to microinjected PGE2 were observed in the OVLT region. The results provide further evidence for the critical involvement of the OVLT region in mediating the febrile responses to blood-borne endogenous pyrogen through the local release of PGE2.

Animals↗

Changing patterns of blood culture isolates from patients with acute leukemia: a review of twenty years' experience.

During the 20-year period, 1972-1991, 286 episodes of bacteremia occurred in 200 (45%) of 445 patients with acute leukemia in a hematology ward, giving an incidence of 482 episodes per 1,000 hospital admissions. The frequency of bacteremia was almost unchanged throughout the study period. The frequency of gram-negative bacilli decreased significantly, however, from 81% of all the isolates for the first half of the study period to 50% for the latter half. Despite the common use of ceftazidime and imipenem during the last 5-year period, Pseudomonas aeruginosa increased in frequency to be the most frequent organism. This was opposite to the decreased frequencies of Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae. The isolates of P. aeruginosa obtained during this period, all of which proved sensitive to ceftazidime and/or imipenem, were almost equally distributed among five serogroups, although a temporal preponderance of a limited number of serogroups was observed during the preceding 15-year period. On the other hand, the frequency of gram-positive cocci increased from 9% in the first decade to 35% in the latter decade. Staphylococcus epidermidis, Enterococcus species and, to a lesser extent, Staphylococcus aureus were ranked as major pathogens. Among the recent isolates of S. aureus, methicillin-resistant strains virtually replaced methicillin-sensitive ones. Therefore, until more effective means for control of P. aeruginosa bacteremia in particular become available, the occurrence of this infection will continue to limit the successful treatment of acute leukemia.

Acute Disease↗

Staphylococcus aureus bacteremia in patients with hematologic disorders.

During the 20-year period, 1972-1991, 27 episodes of Staphylococcus aureus bacteremia, including 10 with methicillin-resistant strains (MRSA), were documented in 26 patients with hematologic disorders, mainly acute leukemia and malignant lymphoma, representing 6% of all 433 episodes of bacteremia in a hematology unit. MRSA replaced methicillin-sensitive strains (MSSA) in the last four years. The skin and upper respiratory tract were the two most common primary foci. Most episodes occurred during neutropenia. Pharyngeal colonization often preceded the development of bacteremia. Antibiotic therapy predisposed to MRSA acquisition during hospitalization, whereas MSSA was mostly detected in admission cultures. Among 22 patients with monomicrobial bacteremia, 19 (86%) survived longer than one week, including all four with MRSA bacteremia who received vancomycin. The survival rate did not differ materially between MRSA and MSSA bacteremias. Secondary foci, chiefly located in the lung, were found in 30% of all patients with S. aureus bacteremia. Prolonged antibiotic therapy, therefore, seems warranted in patients with evident metastatic lesions, although abbreviated therapy is proposed in neutropenic cancer patients.

Adolescent↗

Effect of recombinant human granulocyte colony-stimulating factor (G-CSF) in the treatment of Pseudomonas aeruginosa bacteremia complicating hematologic malignancy--a preliminary study.

The efficacy of recombinant human granulocyte colony-stimulating factor (G-CSF) in the treatment of Pseudomonas aeruginosa bacteremia in cancer patients receiving intensive chemotherapy was studied retrospectively. In 14 of the 24 episodes of P. aeruginosa bacteremia, which occurred in 23 severely neutropenic patients with hematologic malignancies during a three-year period, G-CSF was given subcutaneously or intravenously at daily doses of 75 micrograms/body to 200 micrograms/m2 of body surface. Overall, survival at one week after onset was observed in 13 patients (54%). Treatment with G-CSF, however, had no statistically significant association with one-week survival, although a favorable outcome was well correlated with an increase in the neutrophil count during therapy. On the other hand, septic shock and appropriate antibiotic therapy were the major prognostic factors. The frequency of shock was reduced by appropriate therapy, but not by G-CSF treatment. These preliminary findings thus suggested that G-CSF should not be effective in the treatment of neutropenic cancer patients with P. aeruginosa bacteremia. No adverse effects of G-CSF were observed.

Adolescent↗

Effects of methacholine induced bronchoconstriction and procaterol induced bronchodilation on cough receptor sensitivity to inhaled capsaicin and tartaric acid.

BACKGROUND: The direct effect of bronchoconstriction on cough receptor sensitivity is unknown, and the antitussive effect of beta 2 adrenergic agonists in man has been controversial. This study was designed to throw light on these questions. METHODS: The threshold of the cough response to inhaled capsaicin, a stimulant acting on C fibre endings, and tartaric acid, a chemostimulant, was measured before and 10 minutes after inhalation of methacholine, which caused a nearly 20% fall in forced expiratory volume in one second (FEV1), in 14 normal subjects (study 1), and also before and 30 minutes after inhalation of procaterol (30 micrograms), placebo, and saline in eight normal subjects (study 2). Progressively increasing concentrations of capsaicin and tartaric acid solutions were inhaled for 15 seconds by mouth tidal breathing at one minute intervals and cough threshold was defined as the lowest concentration of capsaicin and tartaric acid that elicited five or more coughs. RESULTS: In study 1 the geometric mean values of the cough threshold of response to capsaicin and tartaric acid before methacholine callenge, 2.98 (GSE 1.30) micrograms/ml and 46.6 (1.22) mg/ml, were not significantly different from those of the response to methacholine inhalation, 3.45 (1.33) micrograms/ml and 32.9 (1.37) mg/ml. In study 2 the geometric mean value of the cough threshold of response to capsaicin before inhalation of procaterol (4.61 (GSE 1.84) micrograms/ml) was not different from that after inhalation of procaterol (4.61 (GSE 1.84) micrograms/ml), which had significant bronchodilator effects. The cough threshold was not altered by placebo or saline. CONCLUSIONS: These findings suggest that muscarinic receptor stimulation, bronchoconstriction, beta 2 receptor stimulation, or bronchodilation might have no direct effect on the sensitivity of the cough receptors in normal subjects.

Adult↗

Lactate in rat skeletal muscle after hemorrhage measured by microdialysis probe calibrated in situ.

The interstitial lactate concentration in rat skeletal muscle was measured in the normal state and after hemorrhage using a microdialysis probe, and the values calculated by in vitro and in vivo calibration were compared. After withdrawal of 30% of the estimated total blood volume, the lactate concentration in the dialysate gradually increased and then maintained an almost constant level. It was found that interstitial lactate levels of skeletal muscle calculated by the in vitro calibration method were not significantly different from those calculated by in vivo calibration in both the normal state and after hemorrhage. These data indicate that the absolute lactate concentration in the muscle interstitium in the normal state and after acute hemorrhage can be practically measured by a microdialysis probe calibrated in vitro. From the comparison of lactate concentrations in blood and in the muscle interstitium, it was suggested that rat skeletal muscle functions as a lactate consumer, rather than as a lactate producer, after acute hemorrhage.

Acute Disease↗

Isometric biaxial tension of smooth muscle in isolated cylindrical segments of rabbit arteries.

Biaxial tension developed in the common carotid and femoral arteries of rabbits by the activation of smooth muscle was determined in vitro using cylindrical segments. While the smooth muscle was stimulated with 10(-5) M norepinephrine, the intraluminal pressure and axial force were measured under isometric conditions, i.e., keeping the diameter and length constant. The development of the active tension in the axial direction was roughly proportional to that in the circumferential direction. The ratio of the axial stress response to the circumferential one was positively correlated to the ratio of the axial stretch to the circumferential one. The axial response was larger than expected from the histological observation that the smooth muscle cells align almost circumferentially. This means that although smooth muscle cells are oriented almost circumferentially, the extracellular matrix transmitted the smooth muscle constriction force not only in the circumferential direction, but also in the longitudinal direction under isometric conditions.

Animals↗

Effect of a M1-selective muscarinic receptor antagonist (pirenzepine) on basal bronchomotor tone in young women.

To examine the role of muscarinic M1-receptors in vagally mediated basal bronchomotor tone, we studied the effects of inhaled pirenzepine, which is a M1-receptor antagonist, on basal bronchomotor tone in 8 young women. To obtain dose-response curves to inhaled pirenzepine, we measured partial and full flow-volume curves before and 30 min after inhalation of each concentration of pirenzepine (3.25-200 micrograms/ml). Maximum expiratory flow on partial flow-volume curve at 25% forced vital capacity (PEF25) was measured as an index showing basal bronchomotor tone. The dose-response curve of the percent increase in PEF25 by pirenzepine was biphasic in shape. PEF25 was significantly increased by 3.12 (14.5 +/- 5.8%), 6.25 (15.5 +/- 4.2%), 12.5 (20.0 +/- 0.29%) and 200 micrograms/ml (17.3 +/- 5.9%) of pirenzepine, but not by 25 (9.6 +/- 5.6%), 50 (9.4 +/- 6.2%) and 100 micrograms/ml (14.4 +/- 6.2%) of pirenzepine. The percent increase in PEF25 by 40 micrograms of ipratropium bromide was 66.2 +/- 14.2%. These results suggest that the role of M1-receptors in vagally mediated basal bronchomotor tone may be significant but little compared with M3-receptors in normal humans.

Adult↗

Argyrophilic proteins of the nucleolar organizer region in acute leukemias and its relation to the S-phase fraction of leukemic cells.

Nucleolar organizer regions (NORs) are loops of DNA which transcribes to ribosomal RNA. The NOR-related protein becomes visible in nucleus by a silver-staining technique under a light microscope, and it has been named argyrophilic protein of NOR (Ag-NOR). In various malignancies, the correlation between the proliferation potential of tumor cells or histological grade and the number of Ag-NORs has been reported. In this study, we investigated the Ag-NOR of acute leukemic cells and its relation to the in vivo proportion of bone marrow leukemic cells in DNA synthetic phase. The number of Ag-NORs in bone marrow leukemic cells was more than that in peripheral blood (means values 2.78 and 2.48, respectively, p less than 0.01). This result shows that the number of Ag-NORs reflects the vigorous proliferative potential of bone marrow leukemic cells. However, no significant correlation was obtained between the number of Ag-NORs and the bromodeoxyuridine-labeling indices (r = 0.2064). These results suggest that Ag-NOR might be one of the markers for cellular proliferation in leukemia, while DNA synthesis of leukemic cells do not seem to be directly related to Ag-NOR. In order to clarify the role of Ag-NOR in leukemia, further studies are needed.

Adolescent↗