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Biomedical subjects

T Tsuchiya

Publications and source records attributed to T Tsuchiya.

At least 523 records · Page 29Linked to original sources

[An erythremia with acquired HbH disease and chromosomal abnormality].

A 56-year-old male was admitted to the Nihon University Hospital because of general fatigue and anemia on September 21st, 1985. He had mild hepato-splenomegaly. Hematological findings showed RBC 286 x 10(4)/microliters, Hb 6.0/dl, reticulocyte count 2.5%, platelet count 9.3 x 10(4)/microliters and WBC 2,400/microliters. An erythroblast per 100 leukocytes counted in a blood film was found. Bone marrow was erythroid hyperplasia with megaloblasts. The erythroblasts were PAS positive but not ringed sideroblasts. Other laboratory data including hemolysis were all negative. This case seemed to be diagnosed as refractory anemia (RA) according to the FAB classification. Chromosomal analysis of marrow cells, however, all revealed 46, XY, 20q- at diagnosis and 46, XY, 7q- 20q- after 22 months. Furthermore, Hb electrophoresis ahd family study indicated the presence of acquired HbH disease. Neither erythroid bursts (BFU-e) nor late erythroid progenitors (CFU-e) were detected. He has had progressive anemia without proliferation of blasts for over 2 years. From these findings, we postulate that the entity of erythremia should be distinguished from RA including many heterogeneous diseases.

Chromosome Deletion↗

[Perioperative hemodynamic changes and management of hemodialysed patients].

Perioperative hemodynamic changes of hemodialysed patients were investigated and the changes of emergency cases (group E, n = 8) were compared with those of scheduled ones (group S, n = 13). By preoperative hemodialysis (HD), the values of blood urea nitrogen, serum creatinine, serum potassium, serum bicarbonate, and hematocrit were adjusted within normal range in group E, with no significant difference from those of group S. On the other hand, concerning the effect of preoperative removal of body water by HD, cardio-thoracic ratio (CTR, 53.6 +/- 3.1%) and pulmonary artery diastolic pressure (PADP, 11.6 +/- 5.0 mmHg) of group E were significantly higher than those of group S (CTR = 46.9 +/- 4.5%, PADP = 7.8 +/- 3.0 mmHg), indicating that the removal of body water by preoperative HD might be less in group E. However, group E patients required more administration of fluid and pressor agents in order to maintain their blood pressure and/or cardiac output during operation. Although with less water removal preoperatively and more fluid intraoperatively, postoperative PADP was significantly reduced (8.3 +/- 3.0 mmHg) in group E, suggesting that the requirement of perioperative water is more in group E. We conclude that the safe perioperative hemodynamic management for emergency surgery of hemodialysed patients requires following points; (1) The excessive removal of body water by preoperative HD should be avoided. (2) Intraoperative fluid infusion should be adequate so that they do not fall into hemodynamic collapse.

Adult↗

[Intraoperative coronary artery spasm--retrospective review of 10 cases].

Ten cases of intraoperative coronary artery spasm were reviewed retrospectively. Four cases were open heart surgeries, one was a surgery for aortic dissecting aneurysm, and the other five were abdominal ones. In the cases of open heart surgery under anesthesia with high dose fentanyl, coronary artery spasm occurred at weaning period from cardio-pulmonary bypass. In the cases of abdominal surgery, all under neuroleptanesthesia with continuous epidural block, coronary artery spasm occurred within one hour after the beginning or before the end of operation. In four of five abdominal surgeries, systolic blood pressure became less than 90 mmHg when coronary artery spasm occurred. Coronary artery spasm brought severe depression of myocardial contractility and life threatening arrhythmias by which weaning from cardiopulmonary bypass became difficult during open heart surgery. There was a case which required several hours before hemodynamics became stable also in abdominal surgery. It was suggested that general anesthesia with continuous epidural block could be a triggering factor of coronary artery spasm when hypotension and insufficient depth of general anesthesia are present simultaneously.

Aged↗

Correlations among chemical constituents, cytotoxicities and tissue responses: in the case of natural rubber latex materials.

Natural rubber latex films obtained from 40 different brands of rubber gloves were tested by quantitative chemical analyses, two cytotoxicity tests (agar-diffusion assay using L929 cells and colony assay using V79 cells) and 7-day implantation test in the rabbit muscle. Multiple regression analysis of these data showed that dithiocarbamate accelerators caused the toxicities whereas antioxidants did not. Thickness of inflammatory layer was the most useful parameter to evaluate tissue response among 13 histological parameters investigated. There were good correlations between the cytotoxicity indices and the thickness of inflammatory layer.

Animals↗

[Annual changes of THI (Todai Health Index) scores of workers in a large-sized enterprise].

To develop a well controlled working environment including a mental health supporting system, it is important to survey the health status of workers. The authors analyzed results of the Todai Health Index (THI), which was administered to employees of a large-sized enterprise in Osaka in 1984, 1986, and 1987. The results were as follows: 1) Female workers had more complaints of "eye and skin", "many subjective symptoms", "mental instability", and "psychosomatic disorder" than males. Male workers complained more of "aggressiveness", "lie scale", and "arousal" than females. 2) The authors could not detect any annual changes of each scale during the 3 years. These results are similar to previous reports. 3) Some people had continuous complaints of "psychosomatic disorder" and "neurosis". These results indicate that THI is useful in obtaining information regarding mentally high risked workers.

Adult↗

Neurite outgrowth from mouse neuroblastoma and cerebellar cells induced by the protein kinase inhibitor H-7.

The protein kinase inhibitor H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride) or staurosporine was found to induce neurite outgrowth from mouse neuroblastoma N18TG2 cells and cultured cerebellar cells by light microscopy. Examination by electron microscopy revealed some morphological differences between the neurites of N18TG2 cells induced by H-7 and dB-cAMP, in which H-7 formed longer and thinner neurites and more abundant localized varicose structures along neurites than dB-cAMP. These results indicate that protein kinase inhibitor itself can act as a potent stimulus for inducing neurite outgrowth in a different manner from dB-cAMP.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

[Clinical results of hyperthermia alone in the treatment of refractory human tumors].

Retrospective analysis of patients with refractory tumors which were treated with hyperthermia alone in five institutions was performed. Hyperthermia was applied to 30 refractory tumors including 19 deep-seated tumors for a total of 427 sessions by 8 MHz or 13.56 MHz radiofrequency capacitive heating devices. Of the 30 tumors treated, 3 (10%) showed complete regression and 2 (7%) more than 50% regression. Although tumor regression was observed in small tumors, large deep-seated tumors did not respond to heat alone. Thus, response rate of hyperthermia alone was lower than expected, although subjective improvement by hyperthermia was noted in 53% patients. We consider that hyperthermia should be combined with radiation or chemotherapy whenever possible.

Adult↗

Long-term tissue distribution and steady state activity ratios of 232Th and its daughters in rats after intravascular injection of Thorotrast.

To estimate the absorbed dose in the critical organs of Thorotrast patients, it is necessary to know not only the distribution and concentration of 232Th but also its daughter nuclides in the body. The present investigation was undertaken in order to clarify the long-term 232Th tissue distribution and steady state activity ratios between subsequent daughters in the critical tissues using about 30 Wister male rats, as a basis for estimating absorbed doses. The tissue distribution of thorium was examined by means of an autoradiography of the whole body and/or the gamma-ray spectrometry at various times during 2 to 24 months following injection. The concentrations of daughter nuclides in tissues were determined by repetitive gamma examination over a period from 1 hr to 35 days after being sacrificed. The data indicate (1) that approximately 90% of injected Thorotrast is retained in the body for a prolonged period, but about 50% of radium and 10% of radon produced from thorium are eliminated from the body, (2) that the mean steady state activity ratios of 224Ra and 212Pb to 228Th for liver are 0.56 and 0.28, and 0.54 and 0.16 for spleen, 0.58 and 0.82 for lungs, respectively, and (3) that the parent 228Th is translocated to the bone.

Animals↗

Identification and characterization of adipokinetic hormone (Locusta migratoria)-like immunoreactivity in the human cerebrospinal fluid.

Using an antiserum raised against locust adipokinetic hormone I, considerable quantity of adipokinetic hormone-like immunoreactivity was demonstrated in the human cerebrospinal fluid. The immunoreactivity was characterized by gel permeation and high performance liquid chromatography. The main immunoreactive component in the cerebrospinal fluid coeluted with adipokinetic hormone I. These results suggest that adipokinetic hormone may contribute to the neuronal function in the human central nervous system.

Chromatography, Gel↗

A respiratory-driven and an artificially driven ATP synthesis in mutants of Vibrio parahaemolyticus lacking H+-translocating ATPase.

Mutants of Vibrio parahaemolyticus lacking the H+-translocating ATPase were isolated to evaluate both the role of this enzyme and the possibility of the involvement of other cation-translocating ATPase in the energy transduction in this organism. Dicyclohexylcarbodiimide-sensitive ATPase activity which represents the H+-translocating ATPase was not detected either in the membrane vesicles or in the cytosol of the mutants. Three major subunits, alpha, beta and gamma, of the H+-translocating ATPase were missing in the membranes of the mutants. Although ATP was synthesized in wild type cells when an artificial H+ gradient was imposed, little ATP was synthesized in the mutants. However, we observed a large ATP synthesis driven by the respiration not only in the wild type but also in the mutants. The respiratory-driven ATP synthesis in wild type was inhibited by an H+ conductor, carbonylcyanide m-chlorophenylhydrazone, by about 50%. On the other hand, the ATP synthesis in the mutants was not affected by the H+ conductor. Since this organism possesses a respiratory Na+ pump, Na+-coupled ATP synthesis might take place. In fact, we observed some ATP synthesis driven by an artificially imposed Na+ gradient both in the wild type and the mutant.

Adenosine Triphosphate↗

Determination of in vivo and in vitro radiosensitivity of mouse splenic T-lymphocytes using a T-cell cloning technique.

Recently the authors established a method for culturing mouse splenic T-lymphocytes with T-cell growth factor (TCGF) and feeder cells in vitro. Using this method, T-lymphocytes grow for approximately 14 days with population doubling times of 27-29 hr; cloning efficiencies (CEs) of mouse spleen cells ranged from three to twelve percent. Using this colony forming assay, in vivo and in vitro radiosensitivity of mouse splenic T-lymphocytes in the G0 phase and in vitro radiosensitivity of proliferating T-lymphocytes (cycling T-lymphocytes) were examined. For in vitro irradiation, the dose-survival curve of T-lymphocytes in G0 phase gave a D0 value of 0.99 Gy and a Dq value of 0.87 Gy and that of cycling T-lymphocytes gave a D0 value of 1.04 Gy and a Dq value of 0.19 Gy. For in vivo irradiation, the dose-survival curve of T-lymphocytes gave a D0 value of 1.01 Gy and a Dq value of 0.73 Gy. These results suggest that the recovering activity from sublethal damage of G0 T-lymphocytes was more effective than that of cycling T-lymphocytes. Furthermore, this colony forming assay system appears to be very useful for screening the effects of in vivo exposure to toxic and/or mutagenic agents and for comparing the effects of in vivo exposure with those of in vitro exposure to toxic agents as well as radiation.

Animals↗

Multi-copy introduction and high-level expression of interleukin-3 genes by retroviral vector superinfection.

We constructed a retroviral expression vector carrying multiple cloning sites. This vector was found to express efficiently the cloned gene. Using this vector and a helper virus-free system, a murine interleukin-3 (mlL-3) high-producing cell line was established by multiple cycles of infection with recombinant retroviruses carrying mlL-3 cDNA. The infected cells produced a considerable amount of mlL-3 and the concentration of mlL-3 in culture media increased as a function of the frequency of infection. High levels of mlL-3 cDNA, mRNA and protein in this cell line were confirmed by Southern, Northern and biological assays, respectively. These results suggest that artificial gene amplification is possible in a helper-free retroviral system. This should be applicable to efficient expression of bioactive molecules in a wide variety of mammalian cells including suspension cells.

Animals↗

Gas chromatographic assay and disposition of 6-chloro-2-pyridylmethyl nitrate, a new antianginal drug, in healthy volunteers.

Quantitative determinations of plasma concentrations of 6-chloro-2-pyridylmethyl nitrate, a new antianginal drug, and its urinary metabolite, 6-chloro-2-pyridinecarboxylic acid (metabolite 1), were obtained using GC with a 63Ni electron-capture detector. 6-Chloro-2-pyridylmethyl nitrate was extracted from plasma with n-pentane. Metabolite 1 was extracted from acidic urine with ethylacetate, back extracted with 0.1 M NaHCO3, and methylated with boron trifluoride methanol reagent. The internal standard for metabolite 1 determination was prepared by propylation of metabolite 1 with boron trifluoride n-propanol reagent. The formation of the esters was confirmed by the GC-MS results. These methods proved to be sensitive and reproducible. A single dose of 6-chloro-2-pyridylmethyl nitrate (5, 10, 20, 40, or 60 mg) was given perorally to healthy volunteers. From the data, a large interindividual variability in the apparent plasma clearance was apparent (85.5 +/- 123 L/min; CV 144%). However, metabolite 1 was the main metabolite in human urine, and the interindividual variation was slight (CV 13%).

Administration, Oral↗

Simultaneous high-performance liquid chromatography assay of two metabolites of 6-chloro-2-pyridylmethyl nitrate, a new antianginal drug, and its application to a pharmacokinetic study in rats.

An HPLC technique has been developed for the simultaneous determination of 6-chloro-2-pyridine methanol (5) and 6-chloro-2-pyridinecarboxylic acid (3), two metabolites of 6-chloro-2-pyridylmethyl nitrate, a new antianginal drug, in rat plasma. The plasma sample was placed on a Bond Elut C18 column and the compounds were eluted with 250 microL of the mobile phase. A 50-150-microL aliquot was injected onto the HPLC column. No interfering substances were observed in the plasma of a normal rat. The calibration curves for both 5 and 3 were linear from 0.1 to 50 micrograms/mL. However, the quantitative detection of the two additional metabolites, N-(6-chloro-2-pyridylcarbonyl)-glycine (1) and N-acetyl-S-(6-chloro-2-pyridylmethyl)-L-cysteine (2) was not satisfactory. The metabolic pathway of 6-chloro-2-pyridylmethyl nitrate in vivo was studied in male rats which were dosed separately with 6-chloro-2-pyridylmethyl nitrate, 5, and 3. After intravenous injection of 6-chloro-2-pyridylmethyl nitrate, the unchanged drug was determined by a GC method that was also developed by us and reported in another paper. 6-Chloro-2-pyridylmethyl nitrate was rapidly metabolized, and the metabolites were detected as early as 1 min after 6-chloro-2-pyridylmethyl nitrate administration. The parent compound then declined rapidly and 3 formation was confirmed in the rat plasma. 6-Chloro-2-pyridylmethyl nitrate is extensively metabolized to 3 via 5 formation, and 3 is the main metabolite in rat plasma.

Animals↗

Na+(Li+)/branched-chain amino acid cotransport in Pseudomonas aeruginosa.

A transport system for branched-chain amino acids (designated as LIV-II system) in Pseudomonas aeruginosa requires Na+ for its operation. Coupling cation for this system was identified by measuring cation movement during substrate entry using cation-selective electrodes. Uptakes of Na+ and Li+ were induced by the imposition of an inwardly-directed concentration gradient of leucine, isoleucine, or valine. No uptake of H+ was found, however, under the same conditions. In addition, effects of Na+ and Li+ on the kinetic property of the system were examined. At chloride salt concentration of 2.5 mM, values of apparent Km and Vmax for leucine uptake were larger in the presence of Na+ than Li+. These results indicate that the LIV-II transport system is a Na+(Li+)/substrate cotransport system, although effects of Na+ and Li+ on kinetics of the system are different.

Amino Acids, Branched-Chain↗

Effect of chemical modifications on freeze denaturation of lactate dehydrogenase.

Lactate dehydrogenase (LDH) was chemically ethyl-acetimidated (EA-), dimethyladipimidated (DMA-), carbamylated, acetylated, acetoacetylated, or succinylated in order to alter the ionic charges on the epsilon-amino group of lysine residues. Acetylation, acetoacetylation, and succinylation, which change the positive charge at the lysine side chains to a negative one, inactivated the enzymic activity, but the rest of the modifications exerted no such inactivating effects. The active modified enzymes were subjected to freeze denaturation study, using the enzymic activity as an indication of the degree of the denaturation. The active enzymes were diluted with deionized water and stored in a freezer (-23 degrees C) for 1-3 days. Enzymic activity was assayed immediately after thawing. All the modified enzymes retained their activity even after the 3-day frozen storage, while the control or native enzyme lost its activity within 1 day of storage. Furthermore, the modified LDHs freeze-stored in 0.2 M monosodium glutamate (MSG) or 0.2 M lysine-hydrochloride (Lys-HCl) retained their activity. The cryoprotective effects exerted by the modifications and by 0.2 M MSG seemed to be synergistic, whereas those exerted by the modifications and by 0.2 M Lys-HCl did not. The mechanisms of cryoprotection and freeze denaturation are discussed in relationship with the cryoprotective effect exerted by already known cryoprotectants, such as sucrose or dimethyl sulfoxide.

Animals↗