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T Ohno

Publications and source records attributed to T Ohno.

At least 847 records · Page 47Linked to original sources

Studies on metabolism of tripamide. III. Metabolic fate of 14C-tripamide in rats and rabbits.

The metabolic fate of a new antihypertensive agent, tripamide (N-(4-aza-endo-tricyclo[5.2.1.0(2,6))]-decan-4-yl)-4-chloro-3-sulfamoylbenzamide), in rats and rabbits was studied using its 14C-labeled compound. The blood level of radioactivity in both species reached the maximum at 1 hr after oral administration, indicating the rapid absorption of the drug from the gastrointestinal tract. Following either oral or intravenous administration, a high concentration was observed in the liver of rats, but it was found in the kidney of rabbits. The major metabolite was 4-chloro-3-sulfamoylbenzoic acid in tissues, urine and feces; and in both species, the unchanged drug was only detected in the kidney. The pathway of excretion of radioactivity was via urine and feces in case of rats; but in rabbits, it was predominantly excreted via urine, although significant quantities of radioactivity were excreted with feces. The radioactivity excreted in feces was attributable to that which was excreted in bile, indicating the absorption of almost all the tripamide administered in both species. During the period of repeated dosing, though blood levels increased gradually and became about 1.5 times as high as that in the single dosing, radioactivity did not accumulate in most tissues and organs.

Animals↗

In vitro effect of LH-releasing factor on the content of cyclic cytidine 3' 5' monophosphate (c-CMP) in the rat anterior pituitary.

The effect of LH-RF on pituitary content of cyclic cytidine 3' 5' monophosphate (c-CMP), one of the newly detected cyclic nucleotides, was examined by the RIA procedure. In results showed that the pituitary content of c-CMP was lower than in various other organs of the rat. When incubated in vitro in the presence of 0.5 ng LH-RF/ml incubation medium, c-CMP content of the anterior pituitaries was reduced slightly, but the difference was not statistically significant when compared with the controls. No difference in c-CMP content was observed between the controls and the 5 ng LH-RF/ml group. C-CMP content in the rat anterior pituitary tissue did not change significantly during an in vitro time-course study (5, 15, and 30 min.) in the presence of 5 ng LH-RF/ml. In contrast, c-AMP content of the pituitary was significantly (P less than 0.05) elevated by the stimulation of 5 ng of LH-RF/ml at a 15 minutes of incubation. These data suggest that c-CMP content, unlike c-AMP, might not be changed significantly by hypothalamic gonadotropin releasing hormone.

Animals↗

Thermal and metabolic responses of temperature-acclimated rats during cold and heat exposures.

Some endocrine and metabolic responses to acute cold and heat exposures were observed in rats acclimated to cold, heat, or both cold and heat. Rats exposed to both cold (12 hr, 5 degrees C) and heat (12 hr, 34 degrees C) for 4 to 5 weeks (CHA) showed less fall of colonic temperature (Tc) in the cold (-5 degrees C) than heat-acclimated rats (34 degrees C, 4 to 5 weeks) (HA) and warm controls (WC), but a greater fall than cold-acclimated rats (5 degrees C, 4 to 5 weeks) (CA). CHA possessed a larger quantity of interscapular brown adipose tissue and showed greater cold-induced oxygen consumption (VO2) than WC and HA but less than CA. Blood glycerol levels rose similarly in all groups in the cold, while the increase in blood free fatty acids (FFA) levels was significantly greater in HA and smaller in CA than in WC and CHA. Acute cold exposure caused the elevation of plasma glucagon level in WC and HA, but not in CA and CHA. It lowered plasma insulin levels in HA, and the insulin/glucagon molar ratio (I/G) in WC, HA, and CHA. All groups showed the same increases in Tc during acute heat exposure (34 degrees C). However, the heat-induced increase in VO2 was greater in WC than in HA, CA, and CHA. Blood metabolite levels were not affected by acute heat exposure in all groups. Plasma glucagon levels decreased in CHA, while plasma insulin levels increased in WC and CA. I/G increased in WC and CHA. These results indicate that thermal and metabolic responses would be modified by previous exposures to cold, heat, and cold-heat.

Acclimatization↗

[Study on the functions of synthesis and release of gonadotropins of the pituitary gland in human subjects by LH-RH 2-step test].

The pituitary gonadotropin response of synthesis and release to two step stimulation by 100 micrograms of LH-RH at 60 minutes interval was studied by radioimmunoassay of LH and FSH in normal menstrual cycling and menopause women and adult males. The blood samples were collected before LH-RH stimulation and 30, 60, 90, 120 minute after the first stimulation, respectively. The value of delta 1 was defined as either higher value at 30 or 60 minute minus the value at 0 minute. The value of delta 2 was defined as either higher value at 90, 120, or 180 minute minus the value of 60 minute. delta 1 Was explained as the release of pituitary gonadotropin and delta 2 standed for the release and synthesis of pituitary gonadotropin. delta 1 delta 2 Ratio was expressed as delta 2/delta 1 100%. If delta 2 was higher than delta 1, subsequently the value of delta 1 delta 2 ratio was larger than 100. When delta 1 was more than delta 2, then the value of delta 1 delta 2 ratio was smaller than 100. In normal menstrual women delta 1 of LH were as Preovulatory phase greater than Follicular phase greater than or equal to Luteal phase, delta 2 were as Preovulatory phase greater than Luteal phase greater than Follicular phase. The value of both delta 1 and delta 2 of FSH were Preovulatory phase greater than Follicular phase greater than Luteal phase. The delta 1 of serum LH of menopause women and adult males were higher whereas delta 2 of both serum LH and FSH of adult males were extremely low in value. delta 1 And delta 2 of serum FSH in menopause women showed higher values than those of others. delta 1 delta 2 Ratio of LH and FSH of both follicular phase and luteal phase were more than 100, indicating dominant pattern of synthesis of gonadotropin. The delta 1 delta 2 ratio of LH at preovulatory phase and of both LH and FSH in menopause women and adult males were smaller than 100, suggesting dominant pattern of release of pituitary gonadotropin. These dates suggest that our LH-RH two step test was more useful to clarify anterior pituitary function in terms of both synthesis and release of gonadotropin.

Female↗

[Development of a fetoscope and its clinical application].

One of the major goals in modern obstetrics is to provide more detailed informations of prenatal fetal physiology. Since 1972, more than 200 amniocentesis were performed in our hospital and the importance of prenatal genetic diagnosis has been recognized. But amniocentesis has the limitations which are 1) the lack of expression of many single gene hereditary disorders in amniotic fluid and its cells, 2) the large percentage (90%) of nonviable fetal cells in any given sample, 3) the length of time required to culture fetal cells. Accordingly the necessity of development of other methods to obtain further direct data on the fetus from the uterine cavity has been indicated. Among gynecological endoscopies, fetoscopy which is direct visualization of the fetus by introduction of an endoscope into the amniotic cavity is expected to obtain direct information from the uterine environment in pregnant women. By our newly developed fetoscope, we investigated clinical indications and contraindications of fetoscopy as well as future possibilities of this endoscope. Our present study indicates that further developments and future benefits of fetoscopy entirely depend on the progress of laboratory techniques which can provide more accurate data through specimens obtained fetoscopy.

Adult↗

Spleen colony-forming cell as common precursor for tissue mast cells and granulocytes.

The haematopoietic stem cells which produce colonies in the spleen of irradiated mice (CFU-S) can differentiate into erythrocytes, granulocytes, megakaryocytes and B lymphocytes. Although mast cell precursors are known to be present in the bone marrow, spleen, fetal liver and peripheral blood of mice, the relationship between the mast cell precursor and CFU-S has remained unclear. We have now made use of mice of two mutant genotypes to determine whether or not the tissue mast cell is a progeny of CFU-S. Giant granules of beige (C57BL/6-bg/bg, Chediak-Higashi syndrome) mice can be used for identification of the origin of both tissue mast cells and granulocytes, and WBB6F1-W/Wv mice are useful recipients because they lack tissue mast cells owing to a defect in mast cell precursors. We injected the cells from a single spleen colony into each WBB6F1-W/Wv mouse and demonstrated directly that the tissue mast cell is a progeny of CFU-S.

Animals↗

Nucleotide sequence of a cloned cDNA copy of TMV (cowpea strain) RNA, including the assembly origin, the coat protein cistron, and the 3' non-coding region.

The cloned cDNA derived from the 3' end of cowpea strain (Cc) RNA of tobacco mosaic virus (TMV) has been sequenced. Substantial sequence information of 1,060 nucleotides from the 3' end of the RNA reveals some interesting features: (1) the coat protein cistron corresponds to residues 210-701 from the 3' end. Some errors in the amino acid sequence previously reported have been corrected and the revised total length of the coat protein is 162 amino acid residues. The capping site of the coat protein mRNA is at residue 711 from the 3' end of genome RNA. (2) The assembly origin of reconstitution is positioned within the coat protein cistron at residue 369-461 which can be formed into a highly base-paired hairpin loop structure. The sequence, GAXGUUG, in the loop region and a triplet-repeated purine base tract surrounding the loop are found. These structural features are common to assembly origins of both Cc and vulgare strains. (3) We find the sequence highly homologous to, but distinct from, the genuine assembly origin. It will be called the pseudo-assembly origin, which is located in the corresponding region to the assembly origin of the vulgare strain, outside the coat protein cistron. There is also the sequence, GAXGUUG, in the middle of the region. (4) In the 5' flanking region of the coat protein cistron, a long reading frame, probably of 30 K protein, is found. The coding region is terminated in the coat protein cistron and thus the 30 K protein and the coat protein cistrons overlap. (5) The 3' non-coding region is 209 residues long and can be folded into a possible tRNA-like structure. Surprisingly, we find that the 3' terminal sequence of Cc RNA is not very similar to that of vulgare RNA but extensively homologous to that of turnip yellow mosaic virus (TYMV) RNA.

Amino Acid Sequence↗

Kernicterus: enzymatic evidence for difference between the development of cholinergic and GABAergic innervations in the brain of the Gunn rat.

The activities of choline acetyltransferase (CAT) and glutamic acid decarboxylase (GAD), markers of cholinergic and GABAergic terminals, were measured in growing and adult Gunn rats, which possess an autosomal recessive gene for jaundice or kernicterus. In the olfactory tubercle, hippocampus, neostriatum, thalamus, and hypothalamus of the animals with kernicterus, the development of the cholinergic pathways was delayed, but by the adult stage it was normal, while there was practically no action on the innervation by GABAergic neurons, at least as indicated by the chemically measured parameters.

Acetylcholine↗

Changes in plasma glucagon levels to stressful environmental temperatures.

Effects of temperature stimuli on plasma glucagon levels were studied in fasted (18 hr) and shorn rats. Plasma glucagon levels rose significantly on exposures to both cold (-5 degrees C, 60 min) (p less than 0.001) and heat (36 degrees C, 60 min) (p less than 0.001) from that in control rats at 25 degrees C. Cold stimulus increased blood FFA level (p less than 0.001) and both cold and heat stimuli increased blood glycerol levels (p less than 0.05-0.001). FFA/glycerol molar ratio decreased to a similar extent on both cold and heat exposures (p less than 0.02-0.01). It was noted that plasma glucagon, blood FFA and glycerol levels increased significantly more in cold-exposed rats (p less than 0.001) than in heat-exposed ones. There were positive relations of plasma glucagon levels to blood FFA and glycerol levels (p less than 0.001), while an inverse relation of plasma glucagon level to FFA/glycerol molar ratio was observed in all experimental rats (p less than 0.05). Cold exposure reduced blood glucose level (p less than 0.001), while heat exposure did not affect it. Cold-induced increases of plasma glucagon and blood FFA levels were diminished significantly in cold-acclimated rats as compared with those in controls (p less than 0.05-0.001). Blood glycerol increased and FFA/glycerol molar ratio decreased to a similar extent on cold exposure in both control and cold-acclimated rats. Correlation between plasma glucagon and FFA/glycerol molar ratio was inversely significant in controls, but not significant in cold-acclimated rats. Blood glucose level was not altered on cold exposure in cold-acclimated rats. It was concluded that acute exposures to temperature stimuli, especially to cold, stimulate glucagon release, accompanied by increased utilization and mobilization of FFA and glucose, and plasma glucagon response to cold is diminished due to cold acclimation.

Acclimatization↗

Studies on the metabolism of tripamide, a new antihypertensive agent. I. Characterization of metabolites in rats.

1. Tripamide (N-(4-aza-endo-tricyclo[5.2.1.0(2,6)]decan-4-yl)-4-chloro-3-sulphamoyl [carbonyl-14C]benzamide) was metabolized in rat to yield five metabolites which were separated by chromatography, and characterized by mass spectrometry and reverse isotope dilution analysis. 2. The five metabolites were identified as follows; N-(3(or 5)-hydroxy-4-aza-endo-tricyclo[5.2.1.0(2,6)]decan-4-yl)-4-chloro-3-sulphamoylbenzamide (3-hydroxy-tripamide); N-8(or 9)-hydroxy-4-aza-endo-tricyclo[5.2.1.0(2,6)]decan-4-yl)-4-chloro-3-sulphamoylbenzamide (8-hydroxy-tripamide); 4-chloro-3-sulphamoylbenzamide; 4-chloro-3-sulphamoylbenzoic acid; and 4-chloro-3-sulphamoylbenzoic acid-(N'-acetyl)hydrazide. 3. Tripamide was metabolized rapidly and the major metabolite was 4-chloro-3-sulphamoylbenzoic acid in rat blood. 4. After intravenous injection, the excretion rate of the hydroxylated tripamide into bile was about 2-3 times faster than that into urine.

Animals↗