Biomedical subjects
Publications and source records attributed to M Horiuchi.
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Preventive and therapeutic effects of tiopronin (2-mercaptopropionylglycine) and glutathione on ethionine induced liver damage were studied. Administration of 1 g/kg ethionine resulted in significant differences in the degree of liver damage, and such was dependent on the feeding conditions of the animals. The present experiment was performed under the conditions where the most serious liver damage was observed. In the experiment on the preventive effects, serum GOT and GPT were markedly elevated by ethionine, but such elevation could be suppressed by administering tiopronin or glutathione 10 min before ethionine administration. Liver nonprotein thiol (NPSH) content decreased by 40--60% of the normal level 16 hr after ethionine adminstration, but increased by 30--45% 24 hr later. Administration of tiopronin suppressed the initial fall of liver NPSH content caused by ethionine, but this tendency was not observed in the glutathione treatment. Both liver cholesterol and triglyceride increased in the ethionine treated rats, and triglycerides in particular decreased with administration of tiopronin or glutathione. In the experiment on the therapeutic effects, the maximal values of serum GOT and GPT brought by ethionine were suppressed by the thiol compounds given 16 hr after ethionine administration, but liver NPSH content and liver lipids were not influenced. Thus, tiopronin and glutathione are considered to have preventive and therapeutic effects on liver damage induced by ethionine.
S-GPT elevated due to ethionine (Eth) administration was suppressed by thiol compounds such as tiopronin (2-mercaptopropionylglycine), glutathione, cysteine, in which tiopronin proved to be more effective than glutathione or cysteine. In thin-layer chromatography of urinary metabolites, Eth and ethionine sulfoxide were detected with administration of Eth, and S-ethyltiopronin plus Eth and ethionine sulfoxide by the administrations of Eth and tiopronin. These S-ethyl derivatives were not detected in the urine with administration of Eth and glutathione or cysteine. In the analysis of Eth and its metabolites by gas chromatography, cumulative urinary excretion of Eth within 72 hr after Eth administration was 40.7% in the Eth administered group, 23.6% in the Eth-tiopronin administered group and 38.2% in the Eth-glutathione administered group, respectively. In the urine of the Eth-tiopronin administered group, S-ethyltiopronin was excreted by 13.6%. Detoxicating effect of tiopronin on Eth induced liver damage was considered to involve the following mechanism. Tiopronin is considered to excrete part of Eth as S-ethyltiopronin by being an acceptor of transfer reaction of the ethyl group of Eth. Neither glutathione nor cysteine was an acceptor of the ethyl group and a detoxicating effect on Eth was not observed.
An investigation of laryngeal reflex maturation was undertaken in the dog to identify its period of most rapid postnatal differentiation. The canine model was selected because of its laryngeal reflex similarity to that of the human being. Observations in the dog indicate maximum differentiation to occur 1 to 1 1/2 months postnatally, based on measurements of recurrent laryngeal nerve myelination and conduction velocity. Latency and threshold analyses of evoked laryngeal responses additionally confirm this viewpoint. The importance of these observations rests in an understanding of developmental upper respiratory tract mechanisms that may be chronologically related to causes of fatal ventilatory events producing unexplained infant death. Such a correlation, requiring further confirmation, is based on the assumption that a critical period of most rapid development allows a transient susceptibility to noxious influences that can cause a disruption in organ function and even death of that organism itself.
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The clinical observation of aspiration following prolonged tracheostomy prompted a neurophysiologic investigation of the glottic closure reflex in dogs longitudinally evaluated after permanent tracheostomy. The data support significant alterations in the central organization of the protective closure reflex heretofore considered phylogenetically primitive and therefore physiologically stable over wide ranges of functional demand. The data indicate that chronic upper airway bypass results in: 1. increased threshold of the evoked adductor response; 2. random shifts in its latency; 3. rapid attenuation of the primary evoked response to repetitive SLN stimulation; and 4. reduced after-discharge activity, all of which contribute to a weakened, ill-coordinated closure respons.
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Conditioned medium containing a differentiation-stimulating factor (D-factor) for M1 cells (myeloid leukemia cell line) was recovered over a period of several weeks by culturing mouse secondary embryo cells in serum-free medium but supplemented with bovine serum albumin. Incubation of M1 cells with the conditioned medium for 48 hr or less resulted in differentiation of 60 to 80% of the cells. From the conditioned medium, D-factor was partially purified by preparative electrophoresis on a Pevikon block and the specific activity was increased 50 approximately 60-fold. The partially purified D-factor was capable of differentiating 30% of the M1 cells at a protein concentration of 2 approximately 3 microgram/ml. Half-logarithmic plots of phagocytosis-inducing activity vs. protein concentration yielded a sigmoid dose-response curve. D-factor is considered to be a glycoprotein with a molecular weight of 40,000 approximately 50,000 and an electrophoretic mobility of alpha-globulin. It is resistant to different protein-denaturing treatments. Since the nature of D-factor differs from that of the colony-stimulating factor for mouse bone marrow cells, it appears that these two activities are due to different substances.
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A clinical and genetic study on 25 twin pairs with at least one deaf member was performed. Concordance rate of hearing loss was 0.88 in MZ and 0.50 in DZ pairs, with an almost complete penetrance (P = 0.94). Consanguinity was found in 32% of cases, corresponding to five times the average population rate in Japan.
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General pharmacological properties of penfluridol (TLP-607) a long-acting antipsychotic drug, were examined in experimental animals and the following results were obtained. 1) TLP-607 produced a lowering of arterial blood pressure and bradycardia but had almost no effect on respiration and peripheral blood flow. 2) TLP-607 slightly hypertension induced by dopamine, adrenaline and noradrenaline, but had no effect on hypotension induced by acetylcholine and histamine. 3) Antagonistic actions of TLP-607 on such spasmogens as acetylcholine, histamine and barium chloride were slightly stronger than those of haloperidol and chlorpromazine. 4) TLP-607 had neither ganglionic nor neuromuscular blocking action. 5) TLP-607 had a slight or no effect in the following experiments; protection against stomach ulcer, activity of ileum and uterus in vivo and in vitro, urinary volume and electrolytes excretion, and gastro-intestinal propulsion. These results suggest that TLP-607 has no striking peripheral actions in experimental animals.
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