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Biomedical subjects

M Takeda

Publications and source records attributed to M Takeda.

At least 883 records · Page 49Linked to original sources

[Analysis of tolerable radiation dose on the oral mucosa and mandibular bone--external beam and/or brachytherapy].

Cooperative study from six institutes was made for the late radiation damage of oral mucosa and mandibular bone. Analysis was made for the selected patients with oropharyngeal cancer for external beam alone and with tongue cancer for interstitial implant. All of them were followed at least two years without recurrence having no secondary treatment after initial radiotherapy. As for external beam alone, frequency of the mucosal ulcer was not increased with high dose level, but tolerance dose for the oral mucosa was limited from associated mandibular damage. Late damages were not likely after brachytherapy alone.

Brachytherapy↗

Blocking effects of alinidine on negative chronotropic and inotropic responses to vagal stimulation and injected acetylcholine and carbachol in dogs.

The effects of alinidine on negative chrono- and inotropic responses to cholinergic interventions, i.e., intramural vagal nerve stimulation and an injection of acetylcholine (ACh) or carbachol, were investigated in isolated, blood-perfused canine atrial preparations perfused by arterial blood from donor dogs. Vagal nerve stimulation (5, 10 or 30 Hz) and an injection of ACh (0.17-1.65 nmol) or carbachol (0.05-0.55 nmol) induced frequency-dependent and dose-dependent negative chrono- and inotropic responses, respectively. These responses were reproducible in the same preparation. During the negative chrono- and inotropic responses to alinidine (85-854 nmol), cardiac responses to cholinergic interventions were depressed dose-dependently. The depressive effects of alinidine on the negative chronotropic responses were significantly (P less than .05) greater than those on the negative inotropic ones. However, alinidine did not affect adenosine-induced negative cardiac responses. Atropine (0.43-4.32 nmol) uniformly blocked responses to cholinergic intervention dose-dependently. The potency of the antimuscarinic effect of alinidine was approximately 1/200 to 1/500 of the potency of atropine at the 50% inhibition dose for responses to vagal stimulation, carbachol and ACh. Intravenous administration of alinidine (1 mg/kg) to the donor dog also suppressed cardiac responses to choline esters and vagal stimulation in the isolated atrium perfused by the donor's blood. These results suggest that alinidine has suppressive effects on the negative chrono- and inotropic responses to exogenous choline esters and endogenous ACh from parasympathetic nerve terminals at the post-junctional cholinergic muscarinic receptors in the dog heart.

Acetylcholine↗

Nuclear genes encoding the yeast mitochondrial ATPase complex. Analysis of ATP1 coding the F1-ATPase alpha-subunit and its assembly.

Mitochondria prepared from the yeast nuclear pet mutant N9-84 lack a detectable F1-ATPase activity. Genetic complementation of this mutant with a pool of yeast genomic DNA in the yeast Escherichia coli shuttle vector YEp13 restored its growth on a nonfermentable carbon source. Mitochondria prepared from the transformed host contained an 8-fold higher than normal level of the F1 alpha-subunit and restored ATPase activity to 50% that of the wild-type strain. Deletion and nucleotide sequence analysis of the complementing DNA on the plasmid revealed a coding sequence designated ATP1 for a protein of 544 amino acids which exhibits 60 and 54% direct protein sequence homology with the proton-translocating ATPase alpha-subunits from tobacco chloroplast and E. coli, respectively. In vitro expression and mitochondrial import experiments using this ATP1 sequence showed that additional amino-terminal sequences not present in the comparable plant and bacterial subunits function as transient sequences for import.

Amino Acid Sequence↗

Hemodynamics of the gastric mucosa and gastric ulceration in rats and in patients with gastric ulcer.

The microcirculation is the fundamental nutrient supply and waste removal system of all tissues. Recent improvements in spectrophotometric technique have made possible the noninvasive assessment of oxygen supply and utilization in the gastric mucosa. The authors have utilized such methods to assess gastric mucosal hemodynamics. The technique permitted further clarification of the roles of the gastric microcirculation, mucosal oxygenation, and acid secretion in the pathogenesis of stress ulcers in the stomach of rats. Furthermore, it provided important information on the function of gastric mucosal hemodynamics in the healing of gastric ulcers in man. The technique is described along with the authors' correlation studies between spectrophotometric data and other techniques for measuring gastric blood flow (hydrogen gas clearance and aminopyrine clearance methods and direct electromagnetic flowmeter techniques) and the prevention of ulcerogenesis.

Animals↗

The amino terminus of the yeast F1-ATPase beta-subunit precursor functions as a mitochondrial import signal.

The ATP2 gene of Saccharomyces cerevisiae codes for the cytoplasmically synthesized beta-subunit protein of the mitochondrial F1-ATPase. To define the amino acid sequence determinants necessary for the in vivo targeting and import of this protein into mitochondria, we have constructed gene fusions between the ATP2 gene and either the Escherichia coli lacZ gene or the S. cerevisiae SUC2 gene (which codes for invertase). The ATP2-lacZ and ATP2-SUC2 gene fusions code for hybrid proteins that are efficiently targeted to yeast mitochondria in vivo. The mitochondrially associated hybrid proteins fractionate with the inner mitochondrial membrane and are resistant to proteinase digestion in the isolated organelle. Results obtained with the gene fusions and with targeting-defective ATP2 deletion mutants provide evidence that the amino-terminal 27 amino acids of the beta-subunit protein precursor are sufficient to direct both specific sorting of this protein to yeast mitochondria and its import into the organelle. Also, we have observed that certain of the mitochondrially associated Atp2-LacZ and Atp2-Suc2 hybrid proteins confer a novel respiration-defective phenotype to yeast cells.

Amino Acid Sequence↗

Correction of abnormal matrix formed by cmd/cmd chondrocytes in culture by exogenously added cartilage proteoglycan.

The cartilage matrix deficiency (cmd/cmd) mouse fails to synthesize the core protein of cartilage-characteristic proteoglycan (cartilage PG). Chondrocytes from the cmd/cmd cartilage cultured in vitro produced nodules with greatly reduced extracellular matrix. Immunofluorescence staining revealed that the nodules of mutant cells differed from the normal in lacking cartilage PG and in uneven and reduced deposition of type II collagen. Exogenously added cartilage PG prepared from either normal mouse cartilage or Swarm rat chondrosarcoma to the culture medium was incorporated exclusively into the extracellular matrices of the nodules, with a concurrent correction of the abnormal distribution pattern of type II collagen. The incorporation of cartilage PG into the matrix was disturbed by hyaluronic acid or decasaccharide derived therefrom, suggesting that the incorporation process involves the interaction of added proteoglycan with hyaluronic acid. Both the hyaluronic acid-binding region and the protein-enriched core molecule prepared from rat chondrosarcoma cartilage PG could also be incorporated but, unlike the intact cartilage PG, they were distributed equally in the surrounding zones where fibroblast-like cells predominate. The results indicate that the intact form of cartilage PG is required for specific incorporation into the chondrocyte nodules, and further suggest that cartilage PG plays a regulatory role in the assembly of the matrix macromolecules.

Animals↗

Isolation, and catalytic and immunochemical properties of cathepsin D-like acid proteinase from rat erythrocytes.

An erythrocyte membrane-associated cathepsin D-like acid proteinase, termed "EMAP," was purified to homogeneity from freshly collected rat blood in a yield of 60-65%. The molecular weight of the enzyme was determined to be 80,000-82,000 by Sephadex G-100 gel filtration. The enzyme was inhibited strongly by pepstatin and partially by HgCl2, Pb(NO3)2, and iodoacetic acid. The preferred substrate for the enzyme was hemoglobin. The enzyme also hydrolyzed serum albumin and casein, but to lesser extents, with an optimum pH of 3.5-4.0. However, it could not hydrolyze leucyl-2-naphthylamide, benzyloxycarbonyl-Phe-Arg-4-methyl-7-coumarylamide or other synthetic substrates at pH values ranging from 3.5 to 9.5. The enzyme was very similar to human EMAP in a number of enzymatic properties, whereas it differed from rat cathepsin D in several respects, such as pH stability, molecular weight, isoelectric point, and chromatographic properties. Immunologically, the enzyme cross-reacted with the rabbit antibody prepared against human EMAP. The patterns of immunoelectrophoresis, immunoblotting, and immunoprecipitation of the enzyme were remarkably similar, if not identical, to those of human EMAP. In contrast, rat EMAP showed no reaction with the rabbit antibody raised to rat spleen cathepsin D. These results indicate that EMAP is a unique cathepsin D-like acid proteinase different from ordinary cathepsin D.

Animals↗

Serum haloperidol levels of schizophrenics receiving treatment for tuberculosis.

Serum haloperidol levels were studied in schizophrenic patients with and without antituberculosis therapy, and the effect of these agents on serum haloperidol level was evaluated. Rifampicin caused significant suppression of serum haloperidol levels in all cases studied (n = 7). The serum haloperidol clearance rate was accelerated in patients taking rifampicin, with a shortened half-life (4.9 h) compared with the control group (9.4 h). Among 18 schizophrenic patients receiving isoniazid, three showed significantly elevated serum haloperidol levels. It is possible that isoniazid can elevate haloperidol levels in some patients depending upon some unknown factors. The elevation of serum haloperidol level was though to be due to prolonged clearance of haloperidol secondary to isoniazid interaction with hepatic enzymes involved in drug metabolism. These observations suggest that haloperidol doses in schizophrenic patients receiving rifampicin or isoniazid must be carefully monitored.

Adult↗

The effect of ascorbate on the acetylcholine release from guinea-pig ileal myenteric plexus.

The effect of ascorbate on the release of acetylcholine from the longitudinal muscle-myenteric plexus preparation of the guinea-pig isolated ileum has been investigated using a bioassay and an isotopic technique. Ascorbate at 5 mM increased the spontaneous output of acetylcholine and enhanced DMPP-induced output of acetylcholine, while iso-ascorbate, 5 mM, did not. Ascorbate did not influence either the spontaneous or the DMPP-induced release of acetylcholine from synaptosomes of the ileal myenteric plexus. These results suggest that ascorbate promotes acetylcholine release from intramural cholinergic nerves.

Acetylcholine↗

Identity of rat liver mitochondrial asparagine-pyruvate transaminase with phenylalanine-pyruvate transaminase.

Identification of rat liver mitochondrial asparagine-pyruvate transaminase with phenylalanine-pyruvate transaminase has been done. When a mitochondria extract was subjected to isoelectric focusing, the two enzyme activities were identically focused. This procedure and DEAE-Sepharose chromatography revealed multiple forms of the enzyme, in which the main form was purified. In the various purification steps the two enzyme activities appeared in the same fraction. The enzyme of the final preparation step gave a single band in polyacrylamide gel electrophoresis in the presence and absence of sodium dodecyl sulfate. During the purification, a similar increase of the specific activity and yield were obtained in the two activities. Phenylalanine was found to be a competitive inhibitor of asparagine transaminase. These results suggest the identity of the two enzymes.

Animals↗

Photoperiodic control of diapause induction and termination in Ostrinia nubilalis: two different clocks?

Both diapause induction and diapause termination are under photoperiodic control in the lepidopteran, Ostrinia nubilalis. In the present study, induction of diapause was maximal in light-dark (LD) cycles that contained 12 hr of light alternating with 12 hr of darkness (LD 12:12). Termination of diapause was maximal in LD 16:8. Diapause termination also occurred rapidly in non-24-hr LD cycles that possessed an 8-hr dark phase. In each of these cases, the period of the LD cycle was not important. Diapause termination did not, however, occur rapidly in non-24-hr LD cycles that lacked an 8-hr dark phase. Thus, the clock mechanism underlying the termination response resembles an hourglass in its behavior. This is in contrast with what is known about induction of diapause. Here it has been demonstrated that the circadian system is somehow involved. It is thus possible that two different physiological clocks underlie these responses.

Animals↗

Insect photoperiodism: diversity of results in night-break experiments, including nonresponsiveness to light.

Three night-break experiment protocols were utilized in an attempt to help clarify the role of the circadian system in photoperiodic time measurement in the European corn borer, Ostrinia nubilalis. Larvae raised in a light-dark (LD) cycle consisting of 12 hr of light alternating with 12 hr of darkness (LD 12:12), at a constant temperature of 30 degrees C, enter a state of arrested growth and development known as diapause (Takeda and Skopik, 1985). In the present research (Experiment 1), the induction of diapause was prevented by 1-hr light pulses that systematically scanned the dark phase of LD 12:12. Thus, the importance of 12 hr of uninterrupted darkness for maximal induction of diapause is stressed. The same experimental protocol applied to larvae already in diapause (Experiment 2), however, resulted in a bimodal curve of diapause termination. Although this result is consistent with the proposition that a nonperiodic hourglass timer underlies this event (Skopik and Takeda, 1986), it does not rule out the circadian system. Like LD 12:12, a thermoperiod in constant darkness (12 hr at 4 degrees C alternating with 12 hr at 25 degrees C) also induces diapause. Scanning such a thermoperiod with 1-hr light pulses, however, resulted in only a small effect (reduction of diapause) when light fell in the early to middle part of the warm phase (Experiment 3). Thus, the time-measuring system, under these experimental conditions, showed only a weak response to light. This unexpected result is discussed with respect to Experiment 1 and two general models that have been proposed to account for photoperiodic time measurement in insects.

Animals↗

Adrenoceptor blocking and cardiovascular effects of the optical isomers of amosulalol (YM-09538), a combined alpha- and beta-adrenoceptor blocking agent, and the corresponding desoxy derivative (YM-11133) in rats.

The pharmacological activities of the enantiomers of amosulalol (YM-09538), a combined alpha- and beta-adrenoceptor antagonist, and the corresponding desoxy derivative (YM-11133) were investigated in the cardiovascular system of rats. The optical isomers of amosulalol and YM-11133 antagonized the vasopressor effect of phenylephrine and the positive chronotropic effect of isoproterenol in normotensive pithed rats. Based on DR2 values (micrograms/kg, i.v.) obtained from Schild plots, (+)-amosulalol and YM-11133 (DR2 = 30) were approximately 10 times more potent than (-)-amosulalol (DR2 = 324) in blocking alpha 1-adrenoceptors. For beta 1-adrenoceptors, in contrast, (-)-amosulalol (DR2 = 107) was approximately 60 times more potent than (+)-amosulalol (DR2 = 6460), which was almost equipotent with YM-11133 (DR2 = 3250). The results indicate that the optical isomers of amosulalol interact differently with alpha 1- and beta 1-adrenoceptors. The effects of these phenethylamines on blood pressure and heart rate were studied in urethane-anesthetized rats (i.v.). The rank order of hypotensive potency in anesthetized rats [+)- = desoxy greater than (-)-form) was consistent with the rank order of alpha 1-adrenoceptor antagonism in pithed rats. In contrast, (-)-amosulalol having a more potent beta 1-adrenoceptor antagonist activity than (+)-amosulalol and YM-11133 only produced dose-dependent bradycardia at the hypotensive doses. The results indicate that the vascular alpha 1- and cardiac beta 1-adrenoceptor blocking activities of the optical isomers of amosulalol contribute to their hypotensive and bradycardia, respectively. Thus, the racemate of amosulalol appears to exert an overall activity reflecting the activities of the individual isomers.

Adrenergic alpha-Antagonists↗

Significant regression of the tumor combined with the high level of plasma cortisol by low-dose administration of O, p'-DDD in a case with Cushing's syndrome caused by adrenocortical carcinoma.

The effect of o, p'-DDD on a functioning adrenocortical carcinoma is described. A 52-year-old woman, who had a huge adrenocortical carcinoma and pulmonary metastasis, was treated by a low-dose administration of o, p'-DDD, which reduced the tumor size. The excretion of urinary 17-OHCS was decreased, whereas plasma cortisol was not decreased but rather increased. This was considered to be caused that o, p'-DDD functioned as a cytotoxic factor which did not improve the states of hyperkalemia, hyperglycemia and hypertension. This suggested that monitoring to measure multiple steroids in addition to plasma cortisol and urinary 17-OHCS was useful for recognizing the general conditions of patients with adrenocortical carcinoma receiving o, p'-DDD therapy.

Adrenal Cortex Neoplasms↗

[Clinical effects of allylestrenol on benign prostatic hypertrophy by double-blind method].

A double blind comparative clinical trial was performed with allylestrenol (AE) and chlormadinone acetate (CMA) to investigate the clinical efficacy of AE on prostatic hypertrophy. Both drugs were administered orally for 12-16 weeks in a daily dose of 50 mg. With both drugs marked improvement of disorders of micturition and a slight decrease in the size of the hypertrophied prostatic node were observed. No significant difference was observed between the two drugs in the overall efficacy of the treatments. Significant improvement of practically all parameters used for evaluation of results was observed with both drugs following treatment. Ultrasonotomographic examination revealed diminution of the size of the prostatic node and x-ray examination of the ureter showed improvement in elevation of the fundus of the bladder. These improvements were better after CMA treatment than after AE treatment. With all other parameters used no significant difference was observed between the two drugs. Mild adverse effects such as loss of sexual desire and potency were observed in a few cases. The incidence of side-effects was lower following AE treatment, and the incidence of loss of sexual desire and potency was significantly lower after AE than after CMA. Taking into consideration efficacy and safety of the treatments, no significant difference was observed in usefulness between the two drugs, and we were able to confirm the usefulness of AE for the conservative treatment of prostatic hypertrophy.

Administration, Oral↗