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Biomedical subjects

T Sone

Publications and source records attributed to T Sone.

At least 163 records · Page 9Linked to original sources

In vitro toxicity test of poisonous mushroom extracts with isolated rat hepatocytes.

Effects of poisonous mushroom extracts on isolated rat hepatocytes were studied. Though no significant decrease in the cell viability was observed during the incubation of hepatocytes with the extracts at a concentration of 5% (v/v) of Amanita abrupta, A. gymnopus, and A. virosa caused marked decreases in the intracellular glutathione content in sharp contrast to the extracts of A. volvata and A. flavipes. Comparative toxicity tests were carried out for the effects of the extract of A. abrupta, dl-propargylglycine, and alpha-amanitin. The extract of A. abrupta at a concentration of 1% (v/v) caused a marked decrease in the glycogen content, a noticeable elevation in the phosphorylase alpha activity, and a slight acceleration of lipid peroxidation in the hepatocytes. Although dl-propargylglycine decreased the intracellular glutathione content progressively with the incubation time, a significant effect of the chemical on lipid peroxidation and the glycogen content was observed only after prolonged incubation at a concentration of 5 mM. On the other hand, alpha-amanitin exerted a little effect on the hepatocytes at 1 microM. These results have indicated that the intoxication by the extract of A. abrupta on the hepatocytes might not due to independently each component, dl-propargylglycine and alpha-amanitin, but combined effect of these components or unidentified substances.

Alkynes↗

[Characterization of the asynergic myocardium in acute coronary syndrome using simultaneous dual radionuclide emission computed tomography].

The purpose of the present study was to evaluate the tissue characterization of the ischemic myocardium by dual single photon emission computed tomography (SPECT) with thallium-201 (Tl-201) and technetium-99m pyrophosphate (Tc-99m PYP) using the simultaneous collection method. The subjects consisted of 84 patients with acute coronary syndrome followed by protracted left ventricular asynergy. For precise interpretation of clinical scintigraphy, we used phantom experiments and the results were as follows: 1. The residual myocardium in the infarcted area could be evaluated to some extent from the severity of the defect on Tl-201 SPECT with optimal and unified image processing standardized by maximal pixel counts in the myocardium. 2. The influence of cross talk between two radionuclides on each tomographic image was negligible under usual clinical conditions. 3. In a subendocardial infarction model where the Tc-99m layer was located within 50% inside the phantom wall and the other space was filled with 201TlCl solution, the Tc-99m layer was clearly visualized inwardly as compared with the Tl-201 layer on dual SPECT with optimal image processing. 4. Transmural infarction could be visualized as a total defect on Tl-201 SPECT only when its diameter was greater than 2 to 2.5 cm. Taking these results into account, we evaluated clinical cases. According to the peak CK value and Tl-201 SPECT in the chronic phase, the subjects were categorized as transmural infarction (TMI), nontransmural infarction (NTMI) and unstable angina pectoris (UAP), and the scintigraphic characteristics of each group were compared. Short-axis tomographic features of all lesions were classified in nine types from 1A to IIIC by the combination of Tl-201 uptake grades (total defect: I, reduced uptake: II, normal: III) and the condition of Tc-99m PYP accumulation (negative: A, transmural: B, subendocardial: C). The relationship between recovery from asynergy and the dual scintigraphic findings was also evaluated and 17 patients in whom asynergy had nearly resolved in the chronic phase was especially classified in a reversible ischemic myocardial damage (RIMD) group. The clinical results were as follows: 1. In cases without reinfarction, a Tl-201 uptake in ischemically-injured lesions was variably improved in the chronic phase. In 9% of all the lesions of NTMI, a Tl-201 uptake showed total defects in the acute phase. 2. Type IIC lesions were most frequently observed, accounting for 43% of all lesions of NTMI.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

[Three operated cases of LMT-lesion with chief complaint of syncopal attack].

An urgent aorto-coronary bypass operation (AC-bypass) was made in three patients with unstable angina pectoris, suffering from stenosis of the left main trunk (LMT). All patients were admitted with chief complaints of chest discomfort and syncopal attack. Case 1 was a 71 year-old man who suffered with chest discomfort and syncopal attack. He was admitted to our emergency room by ambulance 40 minutes after the syncopal attack, on January 11, 1989. His blood pressure was 140/96; pulse 84 and regular. The electrocardiogram (ECG) showed right bundle branch block, ST elevation in aVR, aVL and ST depression in all other leads. Coronary arteriogram (CAG) was made urgently and showed 80% stenosis in LMT. The emergency AC-bypass operation was successfully carried out about 3 hours and 10 minutes after the onset of symptoms. Case 2 was a 51 year-old man who suffered from precordial oppression and syncopal attack. He was admitted to our emergency room by ambulance about 1 hour after the attack, on January 17, 1989. His blood pressure was 94/74; pulse 120 and irregular. Chest radiography showed a cardiothoracic ratio of 58% and the ECG disclosed atrial fibrillation, ST elevation in aVR and ST depression in I, II, III, aVF, V1-6. The echocardiogram revealed hypokinetic motion in the antero-lateral wall of the left ventricle. CAG was carried out without delay, and showed 70% stenosis with slit in LMT. An emergency AC-bypass operation was successfully carried out about 3 hours and 50 minutes after the onset of symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[A surgical case of aortic regurgitation with Behçet disease].

A case of Behçet disease associated with aortic valve regurgitation treated with aortic valve replacement is reported. The patient was treated successfully with special surgical techniques for prevention of post operative paravalvular leakage and occurrence of pseudo aneurysm because the patient was under long-term steroid therapy for Behçet disease.

Aortic Valve↗

[Rapid measurement of human parathyroid hormone-(1-84) by immunoradiometric assay for use in intraoperative determination of hyperfunctioning parathyroid glands].

Rapid measurement of serum intact parathyroid hormone concentration was achieved by modification of an immunoradiometric assay for the hormone. Incubation of serum samples for 15 min at 37 degrees C under shaking gave optimal results in terms of assay variance and reproducibility: intra-assay CVs were less than 10% over the hormone concentrations of 11-1,600 pg/ml; intra- and inter-assay CVs for two control sera at different hormone levels were less than 12%. The minimal detectable hormone concentration was found at 27.8 pg/ml. The serum hormone levels of 43 subjects (31 health subjects, 9 patients with primary hyperparathyroidism, and 3 patients with secondary hyperparathyroidism) determined by either rapid or regular assay well correlated with each other (r2 = 0.979, p less than 0.001). In two patients with parathyroid adenoma serum intact PTH levels fell rapidly to 12.1% of the preoperative values 20 min after ligation of the vascular pedicle to the hyperfunctioning glands. We conclude that the modified assay protocol allows rapid, accurate, and simple estimation of intact PTH concentrations, and can be used as an intraoperative measure to aid both diagnosis and surgical cure of hyperparathyroidism.

Chi-Square Distribution↗

Mutant vitamin D receptors which confer hereditary resistance to 1,25-dihydroxyvitamin D3 in humans are transcriptionally inactive in vitro.

Hereditary 1,25-dihydroxyvitamin D3-resistant rickets is a human syndrome that arises as a result of heterogeneous molecular defects in the vitamin D3 receptor. Recent studies have identified single unique point mutations within the second or third exons that encode the DNA-binding domain of the vitamin D receptor (VDR) gene in two families with this syndrome. In the experiments reported here, these mutations were introduced into the normal VDR cDNA by site-directed mutagenesis and the mutant products evaluated for hormone, nuclear, and DNA-binding characteristics. Each mutant VDR was expressed in COS-1 cells at equivalent levels, and saturation analysis of cell cytosol revealed normal affinity for the 1,25-dihydroxyvitamin D3 hormone. Incubation of transfected cells with radiolabeled hormone followed by lysis and extraction suggests a lowered salt dependence for solubilization of the mutant VDR. Concomitantly, mutant receptors exhibited reduced affinity for immobilized calf thymus DNA. While cotransfection of the wild type receptor together with a vitamin D-inducible (osteocalcin) chloramphenicol acetyltransferase reporter gene construction in CV-1 cells resulted in strong induction by 1,25-dihydroxyvitamin D3, neither mutant receptor was capable of directing significant activity either as a function of receptor or hormone concentration. These data suggest that the unique point mutations identified in each of these two families are responsible not only for the phenotype originally ascribed to the abnormal receptor but also severely compromise each protein's ability to activate transcription.

Animals↗

Production of interleukin 1 beta, a potent bone resorbing cytokine, by cultured human myeloma cells.

Supernatants of freshly isolated human myeloma cell cultures were examined both for bone-resorbing activity (BRA) in vitro using newborn mouse calvaria, and for identification of the causal substances of the BRA. Eight of 14 culture supernatants of myeloma cells had BRA. All of these BRA-positive supernatants were from patients with marked destructive bone lesions of multiple myeloma. The presence of interleukin 1 (IL-1), especially IL-1 beta, was demonstrated in seven of these BRA-positive supernatants but not in BRA-negative supernatants. The concentrations of IL-1 beta were high enough to induce bone resorption in the newborn mouse calvaria assay and the BRA was totally abolished by pretreatment of the supernatants with anti-IL-1 beta antibody but not with either anti-IL-1 alpha antibody or normal serum. Other bone resorbing cytokines such as tumor necrosis factor or lymphotoxin were not present in high enough concentrations to stimulate bone resorption and their levels did not correlate with the BRA. IL-1 beta mRNA was also identified in BRA-positive myeloma cells. These results demonstrate that IL-1 beta is the principal agent of BRA present in supernatants of myeloma cell cultures, and also identify a possible role of IL-1 beta in destructive bone lesions in patients with multiple myeloma.

Adult↗

5-Isoquinolinesulfonamide derivatives. 1. Synthesis and vasodilatory activity of N-(2-guanidinoethyl)-5-isoquinolinesulfonamide derivatives.

Two novel series of N-(2-guanidinoalkyl)-5-isoquinolinesulfonamides, 2 and 3, were prepared. Many of the compounds possessed vasodilatory activity when injected locally into the femoral artery of dogs. The most potent compound, 1-amidino-4-(5-isoquinolylsulfonyl)-1,4-perhydrodiazepine, 33, was comparable to diltiazem, which is used clinically as a vasodilator.

Animals↗

5-Isoquinolinesulfonamide derivatives. 2. Synthesis and vasodilatory activity of N-(2-aminoethyl)-5-isoquinolinesulfonamide derivatives.

A new series of aromatic sulfonamides, the N-(2-aminoethyl)-5-isoquinolinesulfonamide derivatives, 3, was synthesized from 5-isoquinolinesulfonic acid and shown to possess vasodilatory action. Vasodilatory activity was evaluated in vivo in terms of increases in arterial blood flow in dogs after local injection in the femoral and/or vertebral arteries. When the alkylene group between the two nonaromatic nitrogen atoms was ethylene, the most potent activity was obtained. Alkylations of either of the two nonaromatic nitrogens yielded more active compounds, although bulky or excessively long alkyl groups reduced the potency. Among these derivatives, 27 and 47 were equipotent to diltiazem, which is used clinically as a cardiovascular drug. These two compounds also had antihypertensive and vasodilatory activities when administered intravenously, although the activities were less than that of diltiazem when given by this route.

Animals↗

7-ethenyloxycoumarin as a new substrate for fluorophotometric assay of hepatic microsomal epoxidizing activities.

7-Ethenyloxycoumarin (7-vinyloxycoumarin, VOC) was metabolized by rat liver microsomes in the presence of a reduced nicotinamide adenine dinucleotide phosphate-generating system to 7-hydroxycoumarin (HOC) and glycolaldehyde via the unstable epoxide, 7-(epoxyethoxy)coumarin, as an obligatory intermediate which had a half life of 5.4 min in 0.1 M phosphate buffer, pH 7.4, at 37 degrees C. The epoxide of VOC accumulated in the microsomal incubation mixture in the presence of the epoxide hydrolase inhibitor, 3,3,3-trichloropropene 1,2-oxide, was isolated and identified. HOC and glycolaldehyde were auto-decomposition products of the putative highly unstable intermediate, 7-(1',2'-dihydroxyethoxy)coumarin, mostly formed by microsomal epoxide hydrolase from the epoxide. Direct fluorophotometry of HOC made it possible to determine epoxidizing activities of very small quantities of the microsomes from untreated rat liver (greater than or equal to 5 micrograms protein). VOC was epoxidizied by rat liver microsomal cytochrome P-450, inducible by 3-methylcholanthrene (3-MC) and phenobarbital (PB), and the microsomal epoxidation reactions were inhibited by IgG preparations raised against the major cytochrome P-450 components isolated from 3-MC- and PB-pretreated rat liver microsomes. In the untreated, 3-MC- and PB-pretreated rat liver microsomes, at least two monooxygenase components with different affinity were strongly suggested by a kinetic study, carried out using the antibodies, to be involved in the epoxidation of VOC.

Animals↗

Comparative studies on the metabolism and mutagenicity of vinyl ethers.

4-Nitrophenyl vinyl ether (1), umbelliferyl vinyl ether (2), 4-cyanophenyl vinyl ether (3), and 4-acetylphenyl vinyl ether (4) were mutagenic toward Salmonella typhimurium TA100 and TA100NR in the presence of the hepatic 9000 x g supernatant fraction fortified with a reduced nicotinamide adenine dinucleotide phosphate generating system (S9mix), but no significant mutagenicity of 4-chlorophenyl vinyl ether (5), phenyl vinyl ether (6), n-butyl vinyl ether (7), and ethyl vinyl ether (8) was found. The epoxides of 1-4 were highly mutagenic toward the bacteria without the S9mix. Also, epoxides of 5 and 6 showed relatively weak mutagenicity. Studies on the metabolism of 1 showed that the epoxide (1a) formed from 1 by microsomes behaved as a labile intermediate in the incubation mixture. Untreated rat hepatic microsomes accumulated 1a and induced mutagenicity of 1 most effectively among the activation systems used. Mutagenic activities of vinyl ethers in the presence of the S9mix were correlated with stabilities of their epoxides. From these results, it is suggested that the critical factor for the mutagenicity of vinyl ethers is the formation and stability of epoxide intermediate in the biological system.

Animals↗

The effects of 24% paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride) on hemodynamics, blood gases, plasma lactate and plasma catecholamines in dogs.

The cause of death after ingestion of a large dose of paraquat is unclear. We investigated the cardiovascular effects of paraquat injection in 7 dogs that were anesthetized with urethane and alpha-chloralose and maintained on controlled ventilation. After control measurements, paraquat (20 mg/kg) was injected iv. Average concentrations of plasma paraquat were 128 micrograms/ml at 15 min (point 1) and 44 micrograms/ml at 4 hr. The average time of survival was 5.5 +/- 2.2 hr. Comparison was made of control values, 15 min (point 1), and 2.5 +/- 1.0 hr before death (point 2). Pulmonary capillary wedge pressure (+33%) and pulmonary vascular resistance (PVR) (+28%) increased, but no change occurred in mean arterial pressure (MAP) or cardiac output (CO) at 15 min. Mean arterial pressure (-50%) and cardiac output (-61%) decreased, while total vascular resistance (+56%) and PVR (+256%) were increased at point 2. Arterial pH decreased from 7.394 and 7.307 (point 1) to 7.143 (point 2). The concentration of plasma catecholamines and lactic acid increased significantly at both points 1 and 2. Renal, adrenal and myocardial tissues were studied by light and electron microscopy. The outstanding feature was early swelling of mitochondria and disruption of the contents in the presence of intact mitochondrial membrane.

Animals↗

[Anesthesia for Shy-Drager syndrome; effects of elastic bandage, phenylephrine, and IPPV].

A 57-year-old man with Shy-Drager syndrome underwent plastic surgery for decubitus on the buttocks under general anesthesia. Before induction of anesthesia, an elastic bandage was applied to the legs, and its effects were examined by raising the upper body. The fall in mean blood pressure decreased from 49% to 39%, and the symptoms of cerebral hypoxia disappeared. However, the induction of anesthesia with 5 mg diazepam, 0.05 mg fentanyl, and 100 mg thiamylal reduced blood pressure abruptly from 150/88 mmHg to 95/68 mmHg. Continuous infusion of phenylephrine was then started, and blood pressure became stable at around 150/90 mmHg. In this state, IPPV did not reduce the blood pressure in the supine position, and did not intensify its fall when the upper body was raised. Anesthesia was maintained with nitrous oxide 70% in oxygen, fentanyl and pancuronium. During the surgery, ventilation was controlled, and phenylephrine was infused at the rate of 5-15 micrograms.min-1 to maintain systolic blood pressure above 100 mmHg. Phenylephrine was infused during the two postoperative days, because blood pressure fell whenever the patient's posture was changed to prevent pressure on the operative site.

Anesthesia↗

Interaction of human parathyroid hormone-related peptide with parathyroid hormone receptors in clonal rat osteosarcoma cells.

Synthetic peptides corresponding to the amino-terminal region of the human parathyroid hormone-related peptide (hPTHrp) were used to characterize the interaction of hPTHrp with parathyroid hormone (PTH) receptors in clonal rat osteosarcoma cells (ROS 17/2.8). Both hPTHrp-(1-34) and [Tyr40]hPTHrp-(1-40) showed full agonist activity in stimulating cyclic AMP accumulation in ROS cells; human PTHrp-(1-34) was approximately 2.5-fold as potent as hPTH-(1-34). Both [Tyr-40]hPTHrp-(3-40) and hPTH-(3-34) inhibited the cyclic AMP increase induced by either hPTHrp or PTH with parallel dose-inhibition curves. Binding to intact ROS cells of a 125I-labeled [Tyr40]hPTHrp-(1-40) (125I-[Tyr40]hPTHrp-(1-40)) which retains full biological activity was time- and temperature-dependent and reversible. Binding of 125I-[Tyr40]hPTHrp-(1-40) and 125I-labeled [Nle8, Nle18, Tyr34]bovine PTH-(1-34)NH2 to ROS cells was competed for, to the same extent and with the comparable potency, by either unlabeled hPTHrp or PTH peptides. The binding capacity and affinity of receptors in ROS cells were strikingly similar for hPTHrp and PTH. Affinity cross-linking with either radioligand resulted in high affinity, specific labeling of an apparently identical macromolecule centering at Mr = 80,000, which was detected in sodium dodecyl sulfate-polyacrylamide gel electrophoresis in both reducing and nonreducing conditions. The data indicate that hPTHrp and PTH, their amino-terminal fragments at least, interact with the identical receptors with regard to affinity, capacity, specificity, and physicochemical characteristics in osteoblastic ROS 17/2.8 cells.

Animals↗