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Biomedical subjects

T Matsuda

Publications and source records attributed to T Matsuda.

At least 505 records · Page 28Linked to original sources

Na(+)-Ca2+ exchanger: physiology and pharmacology.

The Na(+)-Ca2+ exchanger in the plasma membrane is a bidirectional electrogenic ion transporter that couples the translocation of Na+ in one direction with that of Ca2+ in the opposite direction. This system is involved in regulation of intracellular Ca2+ concentration via the forward mode (Ca2+ extrusion) or the reverse mode (Ca2+ influx). There are two types of the plasma membrane Na(+)-Ca2+ exchanger in an animal, and they are called the cardiac type and rod outer segment type. In addition, there is an electroneutral Na(+)-Ca2+ exchanger present in mitochondria. Recent studies by the molecular biology technique show that there are at least 8 isoforms of the cardiac type (NCX1), and there are two other exchangers in the brain (NCX2 and NCX3). Due to new techniques of molecular biology and electrophysiology, much evidence is accumulating with respect to the structure, mechanism, regulation, and physiological and pathological roles of the Na(+)-Ca2+ exchanger. This review summarizes recent progress in this research field that is of pharmacological interest.

Animals↗

Central regulation of urine production by a selective mu-opioid agonist, [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin, in rats.

We have investigated opioid mechanisms concerning regulation of urine production in the hypothalamic supraoptic nucleus (SON). In this study, the effect of [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), a potent selective mu-opioid agonist, microinjected into the SON of anesthetized hydrated rats, on the urine outflow rate was examined. DAMGO caused a dose-dependent decrease in the urine outflow rate with no significant changes in blood pressure nor heart rate. The ED50 value for the antidiuresis was calculated to be 0.055 nmol from the dose-response curve. The antidiuresis elicited by DAMGO (0.1 nmol) was partially inhibited by intra-SON pre-injection of naloxone (3 nmol), a relatively mu-selective opioid antagonist, and timolol (100 nmol), a beta-adrenoceptor antagonist, but not by intra-SON pre-injection of phenoxybenzamine (20 nmol), an alpha-adrenoceptor antagonist, nor atropine (300 nmol), a muscarinic antagonist. Intravenous injection of d(CH2)5-D-Tyr(Et)VAVP (16.7 micrograms), a vasopressin receptor antagonist, did not influence the DAMGO-induced antidiuresis. These findings suggest that antidiuresis mediated through mu-opioid receptors in the SON involves beta-adrenoceptors in the nuclei, but does not involve an increase in vasopressin release.

Adrenergic alpha-Antagonists↗

Interaction of orally administered 5-[3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-benzodioxole (MKC-242) with 5-HT1A receptors in rat brain.

The present study was carried out to clarify whether orally administered 5-{3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy}-1,3-be nzodioxole (MKC-242), a serotonin1A (5-HT1A)-receptor agonist having potent anxiolytic-like and antidepressant-like effects in animal models, binds to 5-HT1A receptors in rat brain. Quantitative autoradiography showed that orally administered MKC-242 (0.1-0.5 mg/kg) caused a significant decrease in 3[H]8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) binding in the hippocampus and dorsal raphe nucleus sections. The decrease in the binding by MKC-242 was observed up to 4 hr after administration, and the effective doses were similar to those in its anxiolytic-like effect in the animal models. Repeated treatment of MKC-242 (0.5 mg/kg/day, p.o.) or buspirone (30 mg/kg/day, p.o.) for 2 weeks did not affect [3H]8-OH-DPAT binding in both sections. These results suggest that orally administered MKC-242 at the low doses that do not show 5-HT1A-receptor-mediated in vivo responses such as the hypothermic effect, adrenocortical effect and the decrease in 5-HT turnover passes the blood-brain barrier and subsequently binds to 5-HT1A receptors in rat brain. In addition, they indicate that repeated stimulation of the receptors by the agonists does not affect the number of the binding sites.

5,7-Dihydroxytryptamine↗

Inhibition by nitric oxide of the uptake of [3H]serotonin into rat brain synaptosomes.

[3H]Serotonin (5-HT) uptake by synaptosomes of rat brain was dose-dependently inhibited by nitric oxide (NO) donors such as sodium nitroprusside (SNP), 3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamin e, 3-morpholinosydnonimine and S-nitroso-L-cysteine (NO-CYS). The inhibitory effect was blocked by reduced hemoglobin. The effect was not mimicked by ferrocyanide and ferricyanide. 8-Bromoguanosine 3',5'-cyclic monophosphate (8-bromo cGMP) did not affect [3H]5-HT uptake into rat cortical synaptosomes. The reduced activity of [3H]5-HT uptake into the cortical synaptosomes pretreated with NO-CYS was partially reversed by washing the preparation after the treatment. Kinetic analysis showed that NO-CYS (100 microM) decreased the Vmax value without any change in the Km value. NO-CYS did not affect the specific binding of [3H]paroxetine, a ligand that binds to the 5-HT transporter, in membranes. NO-CYS and SNP, like iodoacetic acid and sodium cyanide, decreased the ATP content in cortical synaptosomes, but the effect on ATP content was not related to that on [3H]5-HT uptake. These findings suggest that NO inhibits reversibly [3H]5-HT uptake into rat brain synaptosomes without affecting the recognition site of the 5-HT transporter in a cGMP-independent manner, and the observed effect is not due to its metabolic effect.

Adenosine Triphosphate↗

Pituitary adenylate cyclase-activating polypeptide (PACAP) receptor mRNA in the rat adrenal gland: localization by in situ hybridization and identification of splice variants.

The distribution of mRNA for pituitary adenylate cyclase-activating polypeptide receptor (PACAP-R) was examined by in situ hybridization in rat adrenal gland. In the adrenal medulla, PACAP-R mRNA was expressed in almost all chromaffin cells without any significant expression in the cortical region. Using the reverse transcription-polymerase chain reaction, we analyzed the mRNA expression of PACAP-R splice variant forms in the adrenal gland. The predominant forms observed were the variant having a 28-amino acid insert in the third intracellular loop (termed PACAP-R-hop1). As PACAP is localized in the noradrenaline secreting cells of the adrenal chromaffin cells, and stimulates catecholamine release, the present results suggest that PACAP may serve as a paracrine or autocrine regulatory factor for the chromaffin cells through PACAP-R.

Adrenal Glands↗

Aeromonas bacteremia in patients with hematologic diseases.

Over a 23-year period, 17 patients with hematologic diseases developed Aeromonas bacteremia while in our hematology ward. Male predominance (14 patients, 82%) was seen, with a predilection for the elderly. Hematologic malignancies, especially acute leukemia, accounted for 15 (88%) of all patients. Cancer chemotherapy and neutropenia (15 patients each) were the most common preceding host conditions. Aeromonas bacteremia generally occurred in the second half of the year (July-December), with no exposure to water or fish. Seven recent isolates comprised Aeromonas sobria (five isolates) and Aeromonas hydrophila (two isolates). Twelve patients (71%) showed a clinical picture ranging from mild gastroenteritis to severe enterocolitis. Anorectal and hepatobiliary infections were also noted in a few patients. The overall mortality rate was 35%. Ten (77%) of the 13 patients who were treated with aminoglycoside plus cephalosporin or carbapenem survived in association with marrow recovery.

Acute Disease↗

Pneumonitis caused by saikokeisikankyou-tou, an herbal drug.

A 57-year-old man was admitted to our hospital because of dyspnea and abnormal shadow on chest roentgenogram. He had received two herbal drugs: Saikokeisikankyou-tou (SKT) for one month and Licium Halimifolium Mil (LHM) for two weeks. After admission, all medication was stopped and his symptoms were gradually diminished. Transbronchial lung biopsy specimens showed interstitial pneumonia. Lymphocyte stimulation test, skin test and challenge test were positive to these herbal drugs. We diagnosed him as drug-induced pneumonitis. This is the first report on pneumonitis caused by Saikokeisikankyou-tou diagnosed by lymphocyte stimulation test, skin test and challenge test.

Biopsy↗

Apheresis therapy for prolonged red cell aplasia after major ABO-mismatched bone marrow transplantation.

Two cases of leukemia were treated successfully with apheresis for delayed recovery of erythropoiesis due to antibody-mediated red cell aplasia after ABO-mismatched bone marrow transplantation (BMT). A 25-year-old female (ABO group O) underwent BMT from her brother (group A). Immunoadsorption using Biosynsorb A performed on day 146 after BMT followed by double filtration plasma pheresis (DFPP) reduced anti-A antibody titers from 1:32 to 1:2. Anemia improved dramatically within 2 weeks. A 49-year-old female (group O) underwent BMT from her mother (group A). She was treated with DFPP on day 131 after BMT. Anti-A antibody titers dropped from 1:16 to 1:1 and anemia improved gradually.

ABO Blood-Group System↗

Detection of eosinophils in hypertonic saline-induced sputum in patients with chronic nonproductive cough.

This study was conducted to examine (1) whether an appropriate sputum can be obtained by inducing with inhalation of hypertonic saline in patients with chronic nonproductive cough and (2) whether eosinophils can be detected in the induced sputum. Appropriate samples were obtained by the induction in 25 of 31 patients with bronchial asthma (BA), 12 of 17 patients with cough-variant asthma (CVA), 17 of 20 patients with bronchodilator-resistant cough associated with atopy (atopic cough, AC), and 23 of 25 healthy subjects. Eosinophils were detected in the successfully induced sputum in 100%, 66.6%, and 88.2% of the patients with BA, CVA, and AC, respectively. Detection of eosinophils in induced sputum may be the initial diagnostic procedure for nonproductive cough of allergic nature.

Adolescent↗

A specific elevation of RANTES in bronchoalveolar lavage fluids of patients with chronic eosinophilic pneumonia.

Chronic eosinophilic pneumonia (CEP) is a rare, idiopathic lung disorder characterized pathologically by massive eosinophil infiltration into lung. In the bronchoalveolar lavage fluid (BALF) of patients with CEP, eosinophil numbers were markedly increased but returned to normal-levels upon the resolution of clinical symptoms, which suggests the crucial role of eosinophils in the pathogenesis of CEP. To clarify the mechanism of eosinophil accumulation in CEP, we determined the BALF levels of RANTES and macrophage inflammatory protein-1 alpha, two chemokines that predominantly exhibit in vitro eosinophil chemotactic activities. RANTES (106.7 +/- 27.2 pg/mg albumin; n = 16) concentrations in BALF from patients with CEP were significantly elevated in comparison with those of normal control subjects (1.4 pg/mg albumin; n = 13), whereas BALF macrophage inflammatory protein-1 alpha levels were not. In addition, eosinophils, lymphocytes, and macrophages in BALF were positively stained with a specific anti-RANTES antibody, which suggests that RANTES was produced locally in the lungs of CEP patients. Moreover, BALF-RANTES levels correlated significantly with the proportion of eosinophils in BALF. Furthermore, nearly half of the eosinophil chemotactic activities in BALF were abrogated by the anti-RANTES antibody in vitro. Collectively, these data suggest that locally produced RANTES is involved in eosinophil accumulation in the pulmonary alveolus and interstitium of patients with CEP.

Bronchoalveolar Lavage↗

[Metastatic tumor to the penis from lung and pancreas cancer: report of two cases].

Neoplasms metastasizing to the penis are uncommon, and occur at the end stage of carcinoma. We describe two patients with a metastatic lesion to the penis from lung squamous cell carcinoma and pancreatic adenocarcinoma. We reviewed 101 cases with secondary penile tumor. The prognosis of secondary penile tumor is extremely poor.

Adenocarcinoma↗

[Drug-induced pneumonitis associated PABRON-GOLD].

A 75-year-old man had for many years taken the commercially sold medicine PABRON-S whenever he caught a cold. He caught a cold and took the drug six days before admission. When PABRON-S was not available, he took PABRON-GOLD and experienced dyspnea the next day. A roentgenogram at another hospital revealed bilateral diffuse lung shadows. He was referred to our hospital. A thoracic CT scan showed bilateral interstitial shadows. Bronchoalveolar lavage fluid contained inflammatory cells including neutrophils and lymphocytes. Examination of a transbronchial lung biopsy specimen showed infiltration of mononuclear cells into the thick alveolar wall and interstitum. A drug lymphocyte stimulation test with PABRON-GOLD was positive. Based on these findings, we believe that this patient had drug-induced pneumonitis caused by PABRON-GOLD. He was treated with a steroid hormone and his symptoms resolved immediately, the abnormal roentgenographic shadows remained longer.

Acetaminophen↗

[Cough-variant asthma successfully treated with a peptide leukotriene receptor antagonist].

A 47-year-old woman complained of coughing for over 5 weeks. The coughing was not relieved by bronchodilators (theophylline, beta 2-adrenoceptor agonist; procaterol), anti-allergic agents (azelastine, ozagrel), an inhaled corticosteroid (beclomethasone dipropionate), a macrolide antibiotic (clarithromycin), or codeine phosphate. A peptide leukoriene receptor antagonist (pranlukast) completely abolished the coughing and increased the cough threshold to capsaicin. The patient was given a diagnosis of cough-variant asthma because her sputum contained many eosinophils and her airway responsiveness to methacholine was slightly higher than normal. Peptide leukotriene may have contributed to the coughing. The fact that coughing associated with cough-variant asthma was abolished by a peptide leukotriene receptor antagonist is clinically important.

Anti-Asthmatic Agents↗

Effect of surfactant inhalation on allergic bronchoconstriction in guinea pigs.

BACKGROUND: In the small airway, surfactant reduces surface tension, prevents liquid filling of bronchioles, thereby maintaining patency in the small airways. Recent reports demonstrated that surfactant dysfunction develops in experimental asthma in immunized guinea pigs. However, there are few reports concerning surfactant and lung function in an experimental asthma model. OBJECTIVE: To examine whether inhaled surfactant improves lung mechanics in antigen-induced bronchoconstriction in guinea pigs. METHOD: We developed a passively immunized guinea pig model for allergic bronchoconstriction induced by antigen inhalation. Using this model, we investigated the effect of inhaled exogenous surfactant, surfactant TA, on the airway opening pressure (Pao) after antigen challenge. RESULTS: Aerosol antigen challenge produced a gradual and long-lasting increase in Pao. Twenty minutes after antigen challenge, aerosolized surfactant TA, 20 mg/ml, was inhaled for 90 s, and it significantly reduced the Pao by 32.8% in 12 min, while a 10.2% reduction was observed in a control group in the same period. When surfactant TA was administered by 90-s inhalation before antigen challenge, it inhibited the Pao increase in a dose-dependent manner: mean inhibitory rates of Pao were 33.6% in surfactant TA 10 mg/ml and 61.9% in surfactant TA 20 mg/ml, respectively. CONCLUSION: Inhaled surfactant showed preventive and recovery effects on antigeninduced bronchoconstriction in an immunized guinea pig model.

Administration, Inhalation↗

Peptide leukotrienes mediate acetaldehyde-induced bronchial hyper-responsiveness in guinea-pigs.

BACKGROUND: We previously reported that inhaled acetaldehyde, a metabolite of ethanol and a main factor in alcohol-induced asthma, causes bronchial hyper-responsiveness (BHR) in asthmatics. However, the mechanisms are unclear. OBJECTIVE: The purpose of this study was to investigate a role of a peptide leukotriene (LT) in acetaldehyde-induced BHR. METHODS: Effects of LT antagonists, ONO-1078 (0.1-1.0 mg/kg) and ICI-198, 615 (0.03-0.3 mg/kg), on acetaldehyde-induced bronchoconstriction and BHR to inhaled methacholine were examined using a modified Konzett-Rössler method in guinea pigs. RESULTS: Acetaldehyde at 0.8 mg/ml, which failed to induce significant changes in Pao (pressure at the airway opening), enhanced an increase in Pao induced by subsequent inhalations of ascending doses (50-200 micrograms/ml) of methacholine, suggesting a potentiating effect of acetaldehyde on bronchial responsiveness. Although ONO-1078 had no inhibitory effect on bronchoconstriction caused by ascending doses (5.0-20 mg/ml) of acetaldehyde, ONO-1078 and ICI-198, 615 reduced the acetaldehyde-induced BHR. CONCLUSION: Acetaldehyde causes BHR via LT release in guinea-pigs.

Acetaldehyde↗

[Emulsification experiments with dimethylsiloxane/phenylmethylsiloxane copolymer].

We compared the emulsification tendency of dimethylsiloxane/phenylmethylsiloxane copolymer (DPC; 5%-phenylated, specific gravity 0.984) with that of silicone oil (dimethylsiloxane; SO, specific gravity 0.966) and fluorosilicone oil (methyl-3,3,3-trifluoropropylsiloxane; FSO, specific gravity 1.256), which are clinically used as an intraocular tamponade. After SO, DPC and FSO were placed in a glass container with an equal amount of albumin solution (1 mg/ml) or gamma-globulin solution (1 mg/ml), and shaken SO and DPC, with their specific gravities being closer to water, showed less emulsification than FSO. Following vitrectomy, DPC was injected into the rabbit vitreous cavity, but did not seem to show any severe histological damage. Highly-phenylated DPC, which is slightly heavier than water, may be useful to treat inferior retinal detachment in place of FSO.

Animals↗

[Clinical statistics on in-patients and operations during a 20-year period (1975-1994) at Department of Urology, Kansai Medical University].

The patients, diseases and operations experienced between 1975 and 1994 in our department were statistically analyzed. The numbers of in-patients and operations have been increasing since 1977. During these 20 years, endoscopic surgery has replaced many open surgical procedures. The introduction of extracorporeal shock wave lithotripsy has dramatically changed the therapeutic modality for urolithiasis, and decreased of the necessity of open surgery.

Female↗