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Biomedical subjects

M Horiuchi

Publications and source records attributed to M Horiuchi.

At least 289 records · Page 16Linked to original sources

Partially purified "activated" receptor-glucocorticoid complex from rat liver: regulation of nuclear, chromatin, and DNA-cellulose binding of "activated" complex by pyrophosphate and ATP.

The effects of PP1 and ATP on nuclear binding of the "activated" receptor-[3H]-triamcinolone acetonide (TA) complex purified about 3,000-fold from adrenalectomized rat liver were investigated. ATP at up to 5 mM did not affect nuclear binding of the "activated" complex, but PP1 at 2-7 mM greatly enhanced it. However, ATP in the presence of PP1 decreased nuclear binding dose-dependently. Similar results were obtained in the case of chromatin binding, but PP1 alone did not alter DNA-cellulose binding of the "activated" complex, suggesting that the binding sites for chromatin and DNA on the "activated" complex are different. Furthermore, PP1 enhanced ATP-agarose binding of the "activated" complex, indicating that the PP1 binding site(s) on the receptor is different from the ATP binding site(s). The physicochemical properties of the "activated" receptor-glucocorticoid complex bound with ATP and/or PP1 were examined by sucrose density gradient centrifugation and Sephadex G-150 gel filtration. There was no detectable change in the sedimentation coefficient or molecular weight (about 4.2S; Mr approximately equal to 98,000) on binding with ATP and/or PP1. These results suggest that the binding of PP1 and PP1 plus ATP to the "activated" complex caused some allosteric change of the acceptor binding sites of the receptor, resulting in increase or decrease in its binding to nuclei, chromatin, or DNA.

Adenosine Triphosphate↗

Induction of megamitochondria in the rat liver by N-propyl alcohol and N-butyl alcohol.

Propyl alcohol and butyl alcohol had similar effects to ethyl alcohol on ultrastructure of liver mitochondria. Rats were given 32% ethyl alcohol, 32% n-propyl alcohol, and 6.9% n-butyl alcohol in drinking water for up to three months. After one month, mitochondria in hepatocytes obtained from the experimental animals became elongated, constricted or cup-shaped with scanty cristae. After two months, mitochondria in some hepatocytes became gigantic. In extreme cases, the megamitochondria exceeded 10 micron in diameter. Coupling efficiencies of hepatic mitochondria obtained from alcohol-fed animals were well preserved despite their drastic morphologic changes.

1-Butanol↗

Membrane fusion in mitochondria. II. An ultrastructural interpretation of cristae-enriched megamitochondria induced by cuprizone.

Ultrastructure of megamitochondria in mouse hepatocytes induced by cuprizone was analyzed in the light of the fusion of inner mitochondrial membranes. Hepatic parenchymal cells of mice fed with a 0.5% cuprizone-diet for 7-8 days were characterized by megamitochondria with numerous cristae including disoriented, shorter ones than those of the control and those in vesicular configuration. After feeding the animals with cuprizone for 15-16 days, megamitochondria increased their sizes further and the number of cristae decreased drastically. Numbers of cristae based on a unit-mitochondrial area were 41.3 +/- 10.8 for the former type of cristae-enriched megamitochondria and 3.8 +/- 1.8 for the latter type of megamitochondria with the value of 23.9 +/- 6.2 for the control. Considering the content of cytochromes in megamitochondria previously reported, these results might suggest that the fusion and defusion of inner mitochondrial membrane take place along with the fusion of outer membranes during the megamitochondrial formation.

Animals↗

[Pharmacology of a 1H-1, 2, 4-triazolyl benzophenone derivative (450191-S), a new sleep-inducer (III). Behavioral study on interactions of 450191-S and other drugs in mice].

Interactions between 450191-S and other representative drugs which might be clinically used with 450191-S were behaviorally investigated in mice, and compared with the cases of nitrazepam, estazolam and triazolam. The potencies of 450191-S and nitrazepam in preventing pentetrazol convulsions were markedly decreased by aminopyrine, whereas that of estazolam was remarkably increased by phenytoin. Administration of nitrazepam with other drugs, except aminopyrine, or of estazolam together with haloperidol exhibited an anticonvulsive pattern different from the case of dosing with either drug alone. Only the effect of triazolam was not influenced by any drugs used. The potency of haloperidol against apomorphine-induced climbing behavior was significantly reduced by nitrazepam, and the pattern of the haloperidol effect was changed by treatment together with 450191-S or estazolam. However, triazolam had no influence on the effect of haloperidol. The antagonistic activity of imipramine to reserpine-induced hypothermia was slightly decreased by 450191-S, estazolam and triazolam, but little affected by nitrazepam. In the protection from maximal electroshock convulsions (MEC), the potency of phenytoin was significantly decreased by 450191-S and triazolam. Moreover, the anti-MES pattern of phenytoin was altered by nitrazepam. Estazolam exerted no significant influence on the effect of phenytoin. Analgesic activities of morphine and/or aminopyrine were potentiated by pretreatment with sleep-inducers, but not 450191-S. Thus, judging from the potency and stability of the anti-pentetrazol effect, 450191-S seems to be inferior to triazolam, but superior to nitrazepam and estazolam. Also, 450191-S may be differentiated from other sleep-inducers by the fact that only 450191-S did not potentiate the analgesic activities of morphine and aminopyrine.

Aminopyrine↗

[Pharmacological studies on drug dependence. (III): Intravenous self-administration of some CNS-affecting drugs and a new sleep-inducer, 1H-1, 2, 4-triazolyl benzophenone derivative (450191-S), in rats].

The present study examined comparative self-administration of some typical CNS-affecting drugs with a new sleep-inducer, 450191-S, in rats, Most animals self-administered both methamphetamine and cocaine in an extremely stable and invariable fashion with cycles of alternating responding and non-responding periods during the day and at night. Response frequency increased in proportion to a fixed-ratio value. An initial increase in response rate followed by cessation of the responding was observed during extinction. Sixty-five percent of the rats tested self-administered morphine in a relatively variable and less stable fashion. Total daily morphine intake was directly related to the unit dose. Eighty-three percent of the rats self-administered pentazocine. Fifty and sixty-four percent of the rats maintained self-administration of phenobarbital and diazepam, respectively, with higher intake at night than during the day. Responding persisted at a low rate for several days during extinction. Abrupt withdrawal of 450191-S caused the same slight weight loss and moderate decrease in food intake as those seen with diazepam and nitrazepam, and cross-physical dependence between 450191-S and diazepam was found. Self-administration of 450191-S at 0.5-2.5 mg/kg/infusion was observed with 2 out of 11 rats, which was much less than that found with diazepam. These results suggest that 450191-S possesses little, if any, drug dependence liability of the tranquilizer type.

Animals↗

Induction of megamitochondria in the mouse and rat livers by hydrazine.

The correlation between structures of chemicals and their inducibility for megamitochondrial formation was investigated. Since the chemical structure universal to the inducers of megamitochondria previously reported (cuprizone and isonicotinic acid derivatives) is the carbazoyl group (-CONHNH2), semicarbazide (NH2NHCONH2) was tested first. Then, hydrazine (NH2NH2) was tested, replacing the carbazoyl group of semicarbazide by an amino group (-NH2). The present study demonstrates that (1) megamitochondria were induced in mouse and rat hepatocytes by feeding the animals with a diet containing semicarbazide or hydrazine, suggesting that the carbazoyl group was not essential for megamitochondrial formation; (2) hydrazine-induced megamitochondrial formation was a reversible process. Coupling efficiencies and activities of ATPase and cytochrome oxidase of megamitochondria induced by hydrazine were slightly decreased, while the activity of monoamine oxidase was moderately decreased. Freeze-fracture electron microscopy revealed particle-free regions in the outer membranes of megamitochondria fixed with glutaraldehyde at 22 degrees C; the regions disappeared at 25 degrees C, indicating that the temperature of the liquid crystalline to gel state lipid phase transition in the megamitochondrial outer membrane was elevated. It is speculated that chemical structure of inducer of megamitochondria could be simplified to NH2-G (G, substituting group).

Aging↗

Effect of nigericin on distribution of sodium, potassium and calcium ion in rabbit lens.

Nigericin, a carboxylic monovalent cation ionophore, induced opacification in the rabbit lens within 2 hr of incubation at 37 degrees C at a concentration of 10(-7)M. The opacification was in the subcapsular region where a marked degree of Ca2+ accumulation and change in the monovalent cation balance occurred. Nigericin may accumulate and act locally at the surface region of the lens, presumably due to the high lipid solubility of nigericin. Nigericin induced an opacification of the lens when applied either to the anterior chamber or to the vitreous of rabbit eye.

Animals↗

Alteration in the inducibility by dexamethasone of the activity of tyrosine aminotransferase and tryptophan oxygenase in regenerating rat liver after partial hepatectomy.

In adrenalectomized rats, the activity of tryptophan oxygenase in liver cytosol was increased 4 h after dexamethasone injection, with a peak on day 2. It then gradually decreased to the value obtained in normal animals treated with dexamethasone. In adrenalectomized, 70% hepatectomized rats, tryptophan oxygenase activity decreased significantly during the period of DNA synthesis after partial hepatectomy; it then increased to above the level existing before hepatectomy, reaching a maximum on day 5, and subsequently returned to the level before hepatectomy. These changes were well correlated with those of dexamethasone receptors at all times after adrenalectomy and partial hepatectomy. In adrenalectomized rats, tyrosine aminotransferase activity was increased 4 h after dexamethasone injection, reached a maximum on day 2, and then remained elevated. The level was increased by subsequent 70% hepatectomy, reached a maximum on day 5, and then began to decrease, but activity was still high on day 10 after hepatectomy when the receptor level had returned to the value existing before hepatectomy. When actinomycin D or cycloheximide was injected with dexamethasone, the induction of the two enzymes was completely inhibited. The activities of the two enzymes in regenerating liver of rats without adrenals and without glucocorticoid treatment were as low as those in adrenalectomized rats without glucocorticoid treatment. Thus, there was a good correlation between the dexamethasone receptor level and the induction of tryptophan oxygenase, but there was a dissociation between the receptor level and the induction of tyrosine aminotransferase after adrenalectomy and partial hepatectomy. The mechanism of this dissociation is unknown.

Adrenalectomy↗

Value of computed tomography for radiation therapy of tumors of the nasal cavity and paranasal sinuses.

The role of computed tomography (CT) in connection with irradiation was evaluated in 60 patients with malignant tumors of the nasal cavity and paranasal sinuses. The extent of the tumors was well demonstrated at CT. The infratemporal fossa was involved in 33 patients, extension to the intracranial cavity was found in 6, and in 16 extension to the contralateral side. Such information is of great help in radiation treatment planning. On the other hand, CT was less valuable for evaluating the effect of radiation therapy.

Carcinoma, Squamous Cell↗

[Studies on a neo-adjuvant chemotherapy for head and neck cancer].

A neo-adjuvant chemotherapy as a preoperative and preradiation chemotherapy was studied in 60 cases of the head and neck cancers. Out of 60, 29 cases were treated with peplomycin (PEP) and 31 with combination chemotherapies which include vincristine (VCR), methotrexate (MTX), bleomycin (BLM), mitomycin C (MMC); VCR, MTX, BLM (Mathé); VCR, MTX, BLM, 5-FU, hydrocortisone (Price-Hill A); hydoxyurea, adriamycin, BLM; VCR, MTX, PEP; cisplatin (CPDD), PEP. In the group treated with PEP, CR was achieved in one case and PR in 14 cases with a response rate of 52%. Five-year survival by Kaplan-Meier's method after all treatment was 34%. In the group treated with combination chemotherapy, CR was achieved in 5 cases and PR in 19 cases with a response rate of 77%. Three-year survival of this group was 82%. Responders to PEP as well as combination chemotherapy were more often rendered disease-free after all treatment than non-responders. We concluded that two courses of VMP therapy (VCR, MTX, PEP) would be appropriate for the outpatients with advanced stage I or stage II, meanwhile two courses of CP therapy (CPDD, PEP) was inpatients with stage III or stage IV as a neo-adjuvant chemotherapy.

Adult↗

Method for determination of angiotensin-converting enzyme activity in blood and tissue by high-performance liquid chromatography.

A simplified method for an angiotensin-converting enzyme activity assay in biological samples was developed. Samples were incubated with hippurylhistidylleucine, an artificial substrate of angiotensin-converting enzyme. The reaction was terminated by the addition of metaphosphoric acid and liberated hippuric acid in the supernatant was quantitated directly by reversed-phase high-performance liquid chromatography. Tissues were homogenized in the presence of Nonidet-P40, a detergent, and the resulting supernatant was used for the assay of tissue angiotensin-converting enzyme activity by high-performance liquid chromatography. The present procedure made it possible to determine angiotensin-converting enzyme activity in whole blood and the total activity in tissues. A comparative study of angiotensin-converting enzyme activity in plasma, kidney and lung of five experimental animals showed a high degree of variation from species to species.

Animals↗

Computed tomography of malignant tumors of the nasal cavity and paranasal sinuses.

Staging of malignant tumors of the nasal cavity and paranasal sinuses by computed tomography (CT) was studied in a total of 49 patients, 33 with squamous cell carcinoma and 16 with tumors of other histologic types. Involved sites by the tumor were studied, and clinical staging was made using CT findings alone according to AJC classification for maxillary sinus tumors. Surgical findings for comparison were available for most cases. Of 33 squamous cell carcinomas and of 16 tumors with other histologic types, the maxillary sinus was the site of origin in 29 and eight, respectively. Of these 37 maxillary sinus tumors, 11 were staged T3, 26, T4, and none was staged T1 or T2. None of these tumors were down staged, and one T3 was upstaged after surgical procedures, although all sinuses were not explored in some cases. Sinusitis due to obstruction was indistinguishable from the tumor without bone destruction. And the determination of the site of origin was difficult in some cases. Despite these, CT should be used for pretreatment evaluation of the tumors of these sites.

Adenocarcinoma↗