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Biomedical subjects

T Matsubara

Publications and source records attributed to T Matsubara.

At least 397 records · Page 22Linked to original sources
PubMed1988

Evidence for voltage-dependent block of cardiac sodium channels by tetrodotoxin.

The effects of tetrodotoxin (TTX) on cardiac sodium channels in guinea-pig ventricular muscle were investigated. Membrane potential was controlled using a single sucrose gap voltage clamp method, and the maximum upstroke velocity of the ventricular action potential (Vmax) was used as an indicator of drug-free sodium channels. Reduction of Vmax by TTX was found to be both voltage- and time-dependent, similar to the effects of many local anesthetic drugs, with the exception that TTX concentrations high enough to produce significant use-dependent block (e.g. 2 microM), also produced significant tonic block, even at potentials negative to -85 mV. The mechanism underlying use-dependent block was determined by defining the time course of block development at potentials between -40 and +20 mV, and the time course of recovery at -85 mV. In 2 microM TTX, the time course of block development at +20 mV contained two phases, a fast phase (tau less than 3 ms) having a mean amplitude of 8.1 +/- 3.2% of control Vmax, and a slow phase (tau = 429 +/- 43 ms) having an amplitude of 35 +/- 2% of control Vmax (n = 5). Recovery from use-dependent block at -85 mV occurred with a time constant of 324 +/- 58 ms (n = 5). The effects of TTX could be well-described by a modulated receptor model with an estimated 12 mV drug-induced shift of inactivation, and state-dependent dissociation constants of 10, 4 and 0.3 microM for rested, activated and inactivated channels. These same drug rate constants could also be used to adequately simulate the reported effects of TTX on plateau sodium currents in a variant model with slow inactivation kinetics.

Action Potentials↗
PubMed1988

Peripheral blood monocyte/macrophages and serum tumor necrosis factor in Kawasaki disease.

We analyzed the populations of peripheral blood monocyte/macrophages in 27 patients using a fluorescence-activated cell sorter, and investigated the possibility, in another 30 patients, that tumor necrosis factor (TNF) might be detectable in serum during the acute phase of Kawasaki disease (KD). Percentages of peripheral blood monocyte/macrophages among mononuclear cells and serum TNF levels were both seen to increase during the acute phase of the illness in patients with KD. The percentage of TNF positive cases in KD patients with coronary involvement was higher than that of patients without coronary involvement. These results suggest the possibility that immunological activation, accompanied by the secretion of TNF from monocyte/macrophages, is an important predisposing condition for the exacerbation of vascular damage in KD.

Antigens, Differentiation↗
PubMed1988

Comparative effects of captopril and nifedipine on split renal function in renovascular hypertension.

Comparative effects of angiotensin-converting enzyme inhibitor (ACEI) captopril and calcium entry blocker nifedipine on the split renal function were studied in six patients with renovascular hypertension (RVH) with unilateral stenosis (38 +/- 5 years). Both captopril and nifedipine showed potent antihypertensive effects; the mean arterial pressure was reduced from 131 +/- 16 to 105 +/- 8 mm Hg (P less than 0.001) by captopril, and from 128 +/- 15 to 109 +/- 11 mm Hg (P less than 0.001) by nifedipine. The glomerular filtration rate (GFR) in the stenotic kidney was 24 +/- 6 mL/min, which decreased to 11 +/- 2 mL/min (P less than 0.01) during captopril administration, and only slightly decreased (18.8 +/- 5 mL/min) during nifedipine administration. The effective renal plasma flow (ERPF) increased in the nonstenotic kidneys in response to both drugs. These results show that angiotensin II rather than renal perfusion pressure may be important for maintaining GFR in the stenotic kidney, and further suggest that nifedipine may be used relatively safely in treating patients with RVH, although caution should be exercised in terms of their ability to preserve the renal function in individual kidneys.

Adult↗
PubMed1988

Nitric oxide complex of cytochrome c' in cells of denitrifying bacteria.

Electron paramagnetic resonance (EPR) spectra at 77K have been measured for the dried cells of three groups of chemoheterotrophic bacteria cultured in the presence of nitrate: I, denitrifying bacteria containing cytochrome c' (Alcaligenes sp. NCIB 11015, Achromobacter xylosoxidans GIFU 543); II, denitrifying bacteria in which cytochrome c' has not been found (Alcaligenes faecalis IAM 1015, Bacillus firmus NIAS 237, Pseudomonas stutzeri ATCC 17641); III, non-denitrifying bacterium containing cytochrome c' (A. xylosoxidans GIFU 1055). A characteristic three-line EPR signal was detected only in the dried cells of group I, and was assigned to NO-cytochrome c' complex. The probable physiological role of the cytochrome c' in denitrifying bacteria is discussed.

Bacteria↗
PubMed1988

An autopsy case of primary angiosarcoma of the pericardium mimicking malignant mesothelioma.

The pathology of a rare case of primary diffuse angiosarcoma of the pericardium is reported. Grossly, the heart was entirely encased by the pericardial tumor, and the myocardium was only superficially invaded by the tumor. The tumor tissue extended directly to the mediastinum, where the great vessels were embedded in the tumor. A few minute distant metastases were found only in the bilateral lungs and pulmonary hilar lymph nodes. Microscopically, the tumor tissue was composed of malignant cells forming vascular channels admixed with solid areas. Histo- and immunohistochemically, no mesothelial characteristics were evident. Factor VIII-related antigen and Ulex europaeus I lectin were positive, implying that the tumor was of vascular origin. Grossly, and in part microscopically, this case resembled malignant diffuse mesothelioma, indicating that pericardial angiosarcoma may sometimes mimick malignant mesothelioma.

Adult↗
PubMed1988

Quinidine blocks cardiac sodium channels during opening and slow inactivation in guinea-pig papillary muscle.

1. In order to quantify the time- and voltage-dependent block of sodium channels by quinidine, we voltage clamped guinea-pig papillary muscles and measured the maximum upstroke velocity (Vmax) of the cardiac action potential. 2. Quinidine reduces Vmax presumably by blocking cardiac sodium channels. In therapeutic concentrations, quinidine causes a small amount of tonic block. Upon depolarization of the cardiac cell membrane, a use-dependent block develops. 3. A slow component of use-dependent block has time- and voltage-dependence similar to that of slow inactivation, develops for the duration of the depolarization or until a steady state is reached. 4. In addition, closely associated with the action potential upstroke, a fraction of the channels blocks very quickly. This represents block of activated or open channels. 5. Near the normal resting potential, channels recover from block with a time constant of 3 to 8 s. At more negative membrane potentials recovery from block occurs slightly faster, while at more positive potentials recovery from block proceeds somewhat more slowly. 6. In terms of the modulated receptor hypothesis, quinidine has a low affinity for the rested state, avidly blocks open sodium channels, but does not bind significantly to inactivated channels. In addition, quinidine blocks channels as they exhibit slow inactivation.

Animals↗
PubMed1988

Role of intestinal bacteria in the metabolism of aldosterone in man.

Urinary aldosterone metabolites were measured before and after the administration of 1 g/day of kanamycin, a nonabsorbable antibiotic, for 7 days, in 6 normal volunteers and in 11 patients with liver cirrhosis. Urinary excretion of 21-deoxytetrahydroaldosterone (21-deoxy-THAldo) decreased by 40 and 86% from the control values in normal volunteers and in patients, respectively (p less than 0.05), after kanamycin administration. Urinary excretion of 21-deoxyaldosterone (21-deoxy-Aldo) also fell by 48 and 89% in normal subjects and in patients, respectively, but the decrease was significant only in the normal subjects (p less than 0.05). In normal volunteers, urinary free aldosterone and THAldo remained constant, whereas the ratio of 21-deoxy-Aldo to aldosterone and 21-deoxy-THAldo to THAldo decreased from 10.2 to 3.7 and 2.1 to 0.3, respectively (p less than 0.01). These results indicate that intestinal bacteria participate in the metabolism of aldosterone during enterohepatic circulation in man.

Adrenal Cortex Hormones↗
PubMed1988

[Effect of the nonsteroidal anti-inflammatory drug 480156-S on hepatic drug-metabolizing activity and pharmacological action of diazepam and pentobarbital in rats].

Effect of the nonsteroidal anti-inflammatory drug 480156-S on liver drug-metabolizing activity was studied in rats, and its effect was compared with that of cimetidine. Cytochrome P-450-dependent 7-alkoxycoumarin O-dealkylase activity was not affected by a single administration of 480156-S, but the activity, especially the O-demethylase but not the O-depropylase, was suppressed dose-dependently by multiple administrations. Pretreatment of rats with phenobarbital caused a diminution of the inhibitory action of 480156-S. Treatment of rats with cimetidine resulted in a marked decrease in the activity, although it recovered 24 hr later. After the pretreatment of animals with 480156-S or reference drugs, the pharmacological action of diazepam was determined using muscle relaxation and inhibitions of electroshock-induced convulsion and pentetrazole-induced clonic convulsion as the indicators. Prolonged pharmacological activity of diazepam was observed when liver drug-metabolizing activity was lowered by the pretreatment. On the other hand, pentobarbital-induced anesthesia was prolonged by the pretreatment of rats with cimetidine, but the anesthesia was not modified by the administration of 480156-S. These results suggest the inhibitory action of 480156-S on a specific form(s) of P-450 isozyme.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1988

In vitro effects of various heterocyclic thiol compounds and beta-lactam antibiotics on vitamin K-dependent gamma-glutamylcarboxylation activity in liver microsomes.

The in vitro effect of N-methyltetrazolethiol (NMTT), one of the common substituents at the 3'-position of the cephem in various beta-lactam antibiotics, on liver microsomal gamma-glutamylcarboxylation (gamma-carboxylation) activity was examined using solubilized rat liver enzyme. The enzyme activity was inhibited by coexisting with NMTT and NADH, and this inhibitory activity could be suppressed by the addition of a sulfhydryl compound such as dithiothreitol (DTT), glutathione or cysteine. Various five-membered heterocyclic thiol compounds exhibited concentration-dependent inhibition of microsomal gamma-carboxylation activity. These inhibitory actions diminished markedly in the presence of 1 mM DTT. In vitro gamma-carboxylation activity also decreases upon addition of various beta-lactam antibiotics at 1 or 10 mM, depending upon the concentration of the drug. Among the heterocyclic thiol compounds, there is a correlation between their inhibitory activities and hydrophobicities. Thus, the in vitro inhibitory activity of heterocyclic thiol compounds and beta-lactam antibiotics on microsomal gamma-carboxylation activity is not correlated with their molecular structures, but rather depends on their hydrophobicities and with the concentrations in the reaction mixture.

Animals↗
PubMed1988

Vitamin K-reversible hypoprothrombinemia in rats. I. Sex differences in the development of hypoprothrombinemia and the effects of beta-lactam antibiotics.

Male and female rats were fed an ordinary diet which contained about 500 ng vitamin K/g or a vitamin K-deficient diet containing less than 5 ng vitamin K/g. Hypoprothrombinemic changes such as prolongation of the prothrombin time (PT) and activated partial thromboplastin time (APTT) were detected in male rats within 4-6 days after feeding of the vitamin K deficient diet. Blood clotting factor VII and descarboxy prothrombin (PIVKA) levels changed rapidly, with maximum alteration at 2-4 days. Similar changes in factor VII and PIVKA levels were observed in female rats, but they appeared only after feeding of the K deficient diet for a long period. PT and APTT in female rats showed slight or no alteration even after 10 day feeding of the K-deficient diet. These results indicate that male rats are more susceptible to vitamin K deficiency than female rats. Administration of latamoxef led to a dose-dependent development of hypoprothrombinemia in vitamin K-deficient female rats. The hypoprothrombinemia in vitamin K-deficient female rats was caused by beta-lactam antibiotics with N-methyltetrazolethiol, thiadiazolethiol and methyl-thiadiazolethiol as the 3'-position substituent of the cephem nucleus.

Animals↗
PubMed1988

Comparison of the action of epinephrine and a respiratory chain uncoupler, 2,4-dinitrophenol, on Ca2+-mobilization in isolated hepatocytes and perfused livers.

The effects of epinephrine and dinitrophenol (DNP) on Ca2+-fluxes and energy metabolism were compared in isolated rat hepatocytes and perfused rat livers. Epinephrine increased the cytosolic free Ca2+ concentration ([Ca2+]i), with Ca2+ being extruded into the extracellular space. DNP also increased [Ca2+]i, but did not cause Ca2+ extrusion into the extracellular space. The maximal change of [Ca2+]i caused by DNP was much larger than that by epinephrine. In the absence of extracellular Ca2+, the transient increase of [Ca2+]i due to epinephrine declined rapidly, while the DNP-induced increase was not affected. Although increased oxygen consumption was detected after the addition of epinephrine or DNP, tissue ATP contents decreased markedly by DNP, but not by epinephrine, suggesting that the Ca2+ extrusion is energy-dependent. DNP could activate glycogenolysis even after the depletion of the epinephrine-responsive Ca2+ store in isolated perfused liver, indicating that this intracellular Ca2+ store differed from the DNP-responsive store.

2,4-Dinitrophenol↗
PubMed1988

In vitro effect of beta-lactam antibiotics and N-methyltetrazolethiol on microsomal vitamin K epoxide reductase in rats.

Liver microsomal vitamin K epoxide reductase activity was determined by measuring the formation of menaquinone-4 from the substrate menaquinone-4 2,3-epoxide. The enzyme was active when dithiothreitol (DTT) was used as a reducing agent, and the activity increased gradually with increasing concentrations of DTT. Glutathione and cysteine also functioned as reductants, but these physiological reductants showed less than 15% of the activity detected with 0.5 mM DTT. Addition of various beta-lactam antibiotics to the assay mixture for vitamin K epoxide reductase caused a slight inhibition of the activity. N-Methyltetrazolethiol (NMTT) and other heterocyclic thiol compounds also inhibited the enzyme activity in vitro depending on their concentrations. Most of these antibiotics and heterocyclic thiol compounds inhibited the enzyme activity only 10-25% in the in vitro assay system even when higher concentrations were added (5-10 mM). Among the compounds tested, methyl-thiadiazolethiol was the only compound that caused 50% inhibition of the enzyme activity. NMTT-induced inhibition was diminished gradually by increasing DTT concentrations. Kinetic analysis of the inhibitory action of heterocyclic thiol compounds showed competitive inhibition against the reductant DTT and non-competitive inhibition against the substrate. On the other hand, warfarin, a typical anticoagulant, showed different patterns in the inhibitory action: non-competitive inhibition against DTT and mixed-type inhibition against the substrate.

Animals↗
PubMed1988

Vitamin K reversible hypoprothrombinemia in rats. II. Efficacy of vitamin K on latamoxef-induced coagulopathy in rats.

Feeding of a vitamin K-deficient diet caused the development of hypoprothrombinemic changes in rats such as prolongation of prothrombin time (PT) and activated partial thromboplastin time (APTT), decreases in plasma prothrombin and clotting factor VII levels, and an increase in the descarboxyprothrombin (PIVKA) level in both plasma and liver. Successive administrations of latamoxef (LMOX) to the vitamin K-deficient rats resulted in the further enhancement of these changes. After the development of hypoprothrombinemia with LMOX, a single subcutaneous injection of vitamin K1 normalized most of these abnormalities in blood coagulation parameters within 6 hr. When vitamin K was given at 200 micrograms/kg, PT, APTT and the plasma PIVKA level showed normal values for at least 8 days even when the animals were fed a vitamin K-deficient diet and treated with LMOX during the recovery period. The amount of vitamin K required to maintain most of the blood coagulation parameters in the normal range was about 3 micrograms/kg/day. The plasma level of vitamin K was higher than 0.3-0.5 ng/ml when the blood coagulation parameters were maintained in the normal range.

Animals↗
PubMed1988

Lethal shock in partially hepatectomized rats administered tumor necrosis serum.

A minute dose of bacterial endotoxin is known to cause lethal shock in BCG (Bacillus Calmette Guérin)-sensitized mice and rats. To gain insight into the mechanism of this hypersensitivity to endotoxin, serum (tumor necrosis serum: TNS) was prepared from BCG-sensitized Lewis rats following endotoxin challenge and injected intravenously into Lewis rats 2 days after their partial hepatectomy. TNS injection caused lethal shock in Hpx (partially hepatectomized) rats but not in normally fed, fasted, or sham-operated rats. Hpx rats survived injection of serum prepared by either BCG sensitization or endotoxin challenge alone. Biochemical and histological examination of the Hpx rats injected with TNS indicated that profound hypoglycemia, hepatic and renal injury, and dysfunction of the coagulation system accompanied by hemorrhage were involved in the lethal shock. These experiments also suggested that serum component(s), probably monokine(s) derived from activated macrophages, might participate in the endotoxin shock in BCG-sensitized rats.

Animals↗
PubMed1988

[Early detection and differential diagnosis of metastatic lung tumor].

In general, the prognosis of cases with metastatic pulmonary tumor is extremely poor. However, in cases where primary lesion is well controlled and no distant metastasis except the lung is clinically found, the pulmonary metastasis could be curable through the early detection of metastasis followed by radical surgery equally to the case with primary lung tumor. The candidate of this curable metastasis is the case with of nodular metastasis with a small number. I discuss the X-ray figure, differential diagnosis, diagnostic accuracy of the number of metastasis, and the interval of follow-up care after treatment of primary malignancy.

Aged↗
PubMed1988

[Modified surgical methods in gastrointestinal and lung cancers].

There are such cancers as that they are rarely detected during an early stage, they show poor prognosis even though being small in size, and that it is difficult to perform reduced operation on them for the purpose of functional conservation. Cancers of the lung, esophagus, rectum, liver, gallbladder and pancreas are included in these cancers for the present. Bronchoplasty for lung cancer, nervous conservation for rectum cancer, and conservative operation to keep a natural anus have been widely performed. At the present time, it has been still difficult to undertake reduced operation for the treatment of esophageal cancer and liver-biliary-pancreatic cancer without damages to the radicalness. Unfortunately, anticancer agents or irradiation has shown no satisfactory effects on the above mentioned cancers. However, radial effects are now obtained from some techniques; they are, laser irradiation for very early cancer of the bronchus and esophagus, and plypectomy for small and early rectal cancer.

Bronchi↗