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K Torii

Publications and source records attributed to K Torii.

15 recordsLinked to original sources

Age-related decrease in respiratory muscle mitochondrial function in rats.

The purpose of this study was to elucidate the effects of aging on diaphragmatic mitochondrial function. Diaphragm mitochondria were prepared from specific pathogen-free rats aged 7 wk (n = 7), 35 wk (n = 7), and 55 wk (n = 7). The activities of various portions of the mitochondrial electron transport chain, i.e., complexes I, II, III, and IV, were measured enzymatically. The specific activities of complex I decreased significantly (P less than 0.01) in 35-wk-old rats (726 +/- 90 nmol/min/mg protein) compared with 7-wk-old rats (1,018 +/- 121), and the decrease was more remarkable in 35-wk-old rats (565 +/- 64; P less than 0.01 versus 35-wk-old). The activities of complex IV also decreased significantly (P less than 0.01) in 55-wk-old rats (1,222 +/- 191) compared with 7-wk-old rats (1,797 +/- 208); however, no significant changes in complex IV activities between 7-wk-old rat and 35-wk-old rats were observed. In contrast, the activities of complex II and III were not affected by aging. Limb muscle, heart, and liver mitochondria were also prepared from the same rats. The same tendency was observed in limb muscle mitochondria; however, in heart and liver mitochondria, activities of all four complexes were not changed in rats of all age groups. These results indicate that vulnerability of mitochondrial electron transport chain to aging differs from organ to organ and that it also differs from portion to portion in the electron transport chain and the most vulnerable site was complex I.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Aging-associated deletions of human diaphragmatic mitochondrial DNA.

It is known that respiratory function deteriorates with age. Endogenous damage to DNA is thought to contribute to the aging process. The mitochondrial oxidative phosphorylation system, a bio-engine, consists of five complexes, and 13 subunits of those complexes are biosynthesized from information encoded in mitochondrial DNA. Mitochondrial DNA is shown to have a much higher mutation rate than nuclear DNA. We examined the diaphragms obtained at autopsy from 34 humans, 23 men and 11 women, ranging in age from 25 to 85 yr, for mitochondrial DNA deletions using the polymerase chain reaction method. Multiple mitochondrial DNA deletions were detected particularly among the elderly; the number of deletions in those over age 70 was significantly higher than in those under age 40. The occurrence of a 3.4-kbp deletion of mitochondrial DNA increased with age, i.e., 0% of those under age 30, 20.0% of those in their forties, 25.0% of those in their fifties, 28.6% of those in their sixties, 72.7% of those in their seventies, and in all of those over age 80. The mutation was based on the directly repeated sequence, 5'-TCACCCC-3', which exists in both the CO3 gene and the ND5 gene. Replication impairment occurred at that directly repeated sequence, which caused the elimination of a genome between the CO3 gene and the ND5 gene, and information for biosynthesis of four subunits in complex I (ND3, ND4L, ND4, and ND5), one in complex IV (CO3), and five transfer RNA genes was missing.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

[In vitro susceptibilities of Mycobacterium avium and Mycobacterium intracellulare to new macrolides, new quinolones, and antituberculous drugs on Dubos agar medium].

Mycobacterium avium and M. intracellulare were isolated from the sputum of patients infected with atypical mycobacteria using 1% Ogawa medium and identified by the DNA probe test. Then the MICs of various kinds of drugs against these mycobacterial species were determined on Dubos agar medium, and the drug susceptibilities were also determined on 1% Ogawa medium in parallel. The drugs tested were new macrolides, such as clarithromycin (CAM) and roxithromycin (RXM), new quinolones, such as ofloxacin (OFLX) and ciprofloxacin (CPFX), and antituberculous drugs, such as isoniazid (INH), rifampicin (PFP), streptomycin (SM), and ethambutol (EB). The MICs of the drugs tested, especially those of CAM, OFLX, and RFP, when determined on Dubos agar medium, were generally lower against M. intracellulare than against M. avium. The susceptibilities of the mycobacterial isolates tested to RFP and SM determined on Dubos agar medium were markedly different from those determined on 1% Ogawa medium. Such discrepancies may be accounted for by absorption of these drugs to the egg medium and instability of RFP in the egg medium. Overall, our results indicate that the new macrolides and new quinolones are effective against atypical mycobacteria.

4-Quinolones

Age-associated accumulation of 8-hydroxydeoxyguanosine in mitochondrial DNA of human diaphragm.

This is the first report that age-associated accumulation of 8-hydroxydeoxyguanosine (8-OH-dG) does occur in human mitochondrial DNA (mtDNA) in muscle of diaphragm. We extracted mtDNA from human diaphragm muscles from differing age groups, and determined the amount of 8-OH-dG by ultramicro-high performance liquid chromatography/mass-spectrometry system. With the same specimen, multiple deletions of mtDNA were detected by electrophoresis after amplification by the polymerase chain reaction method. In subjects below age 55, the level of 8-OH-dG in mtDNA was below 0.02% of the total deoxyguanosine (dG), whereas, in subjects over age 65, the level of 8-OH-dG increased with age at a rate of ca. 0.25% per 10 years, reaching 0.51% at age 85. Moreover, a concomitant increase in multiple deletions was detected with the increase in age. These results suggest that, in younger diaphragms, replication of mtDNA dilutes out 8-OH-dG being not detectable. In the elderly subjects aged over 65, the replication rate might be slowed down leading to the accumulation of 8-OH-dG in mtDNA, which would accelerate the age-associated multiple deletions of mtDNA observed among the subjects.

8-Hydroxy-2'-Deoxyguanosine

Involvement of 5-hydroxytryptamine 3 receptors in regulation of interdigestive gastric contractions by motilin in the dog.

The effects of IV injection of 5-hydroxytryptamine 3 receptor antagonists (BRL 43694 and GR38032F) on gastrointestinal contractile activity were studied in dogs with vagally denervated fundic pouch in the conscious state by means of chronically implanted force transducers in the gastrointestinal tract and the pouch. In the interdigestive state, 5-hydroxytryptamine 3 receptor antagonists (0.01-0.1 mg/kg), if given during phase III contractions, instantly and dose-dependently inhibited the spontaneous and motilin-induced phase III contractions in the intact stomach and altered the duodenal phase III contractions to a pattern of continuous contractions, the contractile force which was 65% of the spontaneous phase III contractions in the duodenum and caused immediate caudad migration of phase III contractions along the small intestine. However, the spontaneous and motilin-induced phase III-like contractions in the denervated pouch were not affected at all by 5-hydroxytryptamine 3 receptor antagonists. When 5-hydroxytryptamine 3 receptor antagonists (0.1-3.0 mg/kg) were given during the phase I period, they did not directly stimulate gastrointestinal contractions. The cyclic fluctuation of the plasma motilin concentration with phase III activity in the stomach was also not influenced by 5-hydroxytryptamine 3 receptor antagonists, but the next phase III contractions in the stomach were inhibited. During the digestive state, however, 5-hydroxytryptamine 3 receptor antagonists (0.1-3.0 mg/kg) did not influence contractile activity in the gastrointestinal tract and in the vagally denervated fundic pouch. On the basis of recent pharmacological studies showing that the distribution of 5-hydroxytryptamine 3 receptors is recognized in the area postrema, peripheral neurons of vagal afferents, and the enteric nervous system, the results of the current study provide a basis for a hypothesis that 5-hydroxytryptamine 3 receptor antagonists are most likely to block motilin-induced signals at 5-hydroxytryptamine 3 receptors on the vagal afferents. In conclusion, the present findings suggest the possible involvement of 5-hydroxytryptamine 3 receptors on vagal afferents especially in terms of endogenous release of acetylcholine in the control of interdigestive phase III activity in the stomach by motilin.

Acetylcholine

Amino acid and NaCl appetite, and LHA neuron responses of lysine-deficient rat.

Rats' preferences for amino acids and NaCl in their drinking behavior were noted when they were fed either a control diet of gluten plus 20% purified egg protein, or (same rats, different time) a lysine-deficient diet. In control, the order of the rats' preferences was arginine greater than saline greater than monosodium L-glutamate (MSG, umami) greater than glycine greater than water greater than threonine greater than histidine greater than lysine. When fed a lysine-deficient diet the order of preference was lysine greater than saline greater than MSG greater than glycine greater than threonine greater than water greater than arginine greater than histidine. To relate neural activity with preference for amino acids and NaCl, activity of lateral hypothalamic (LHA) neurons was recorded during ingestion of MSG, lysine, arginine, glycine, saline, glucose, or water by the control and lysine-deprived condition, following a different cue tone. When the diet was lysine deficient, some neurons responded specifically to lysine ingestion. More neurons responded nondifferentially during licking in control, and responded to lysine, but fewer to other amino acid ingestion during lysine deficiency. Responses to cue tone were associated with those during licking. The present results suggest that preference for deficient amino acids might be mediated in the LHA.

Amino Acids

Taste preference and protein nutrition and L-amino acid homeostasis in male Sprague-Dawley rats.

Changes in taste preference were investigated in a choice paradigm using rats under various states of protein nutrition. A preference for the umami taste substances, monosodium L-glutamate (MSG) with or without 5'-ribonucleotide (5'-guanosine monophosphate), was induced when dietary protein was within the normal range, but a preference for NaCl occurred under its marginal deficiency. A preference for both NaCl and glycine was induced under severe protein malnutrition, possibly reflecting the body's negative nitrogen balance. The strength of this preference paralleled the body's requirement for protein, and thus, like the protein requirement for normal growth, declined with age. When animals with L-lysine (Lys) deficiency consumed a Lys solution and began to grow normally, their intake of taste stimulus solutions changed from preferring NaCl and glycine to preferring MSG. The regulatory mechanism of preference for L-amino acid (AA) in rats deficient of an essential AA was related to the pattern of AA in plasma and brain. Data suggest that umami taste perception plays an important role in protein metabolism, and in maintenance of AA and ammonia homeostasis within normal limits.

Amino Acids

Coexisting thymic carcinoid tumor and thymoma.

Thymic carcinoid tumors are unusual neoplasms that are different from thymomas. We report a case of coexisting thymic carcinoid tumor and thymoma associated with myasthenia gravis. The clinicopathological findings are discussed with a review of the literature.

Carcinoid Tumor

Dissociation of various biological activities of Clostridium perfringens alpha toxin by chemical modification.

The effect of N-acetylimidazole, tetranitromethane, maleic anhydride and N-ethylmaleimide on various biological activities of Clostridium perfringens alpha (alpha)-toxin was investigated. Treatment of the toxin with N-acetylimidazole, tetranitromethane or maleic anhydride resulted in significant reduction of lethal, hemolytic and platelet-aggregating activities and phospholipase C activity (EY activity), as measured by increased turbidity in egg yolk emulsions. However, EY activity was more resistant to these reagents than lethal, hemolytic or aggregating activities. Phospholipase C activity (PN activity) as measured by hydrolysis of p-nitrophenylphosphorylcholine was retained after treatment with N-acetylimidazole, tetranitromethane or maleic anhydride. The activities of the toxin were not inactivated by treatment with N-ethylmaleimide. These data suggest that alpha-toxin contains multiple sites for biological activities of the toxin.

Animals

[A comparative study on the responses of blood vessels of oral mucosa to thermal stimulation in dentulous and edentulous subjects].

The purpose of this experiment was to clarify the characteristic changes of vasculature in edentulous alveolar mucosa and the effect of wearing a complete denture during sleep. Thermal stimulations were applied to the oral mucosa of five normal subjects and five completely edentulous patients and the responses of blood vessels were observed using both Impedance Plethysmography (IMP) and Reflection Photoelectric Plethysmography (RPP). Quantitative comparisons were made between edentulous patients and dentulous normal subjects, and between patients wearing complete dentures during sleep and those who do not. The following results were obtained. 1) The responses of blood vessels were divided into four groups. Type 1 showed dilatation in IMP and RPP. Type 2 showed dilatation but had late initial rising in IMP. Type 3 showed initial contraction in either or both IMP and RPP, and followed by dilatation few seconds later. Type 4 showed no changes in RPP but dilatation in IMP. 2) There was definite difference between edentulous and dentulous subjects in the frequency of exhibition of each type. Especially for the edentulous patients type 4 was observed in all stimulation temperature. 3) For the dentulous subjects there were more cases showing responses of RPP in digital apex than those do not. This was most conspicuous at the 50 degrees C stimulation. However for the edentulous patients there were about equal number of each cases. 4) The responses of blood vessels for both dentulous and edentulous subjects became greater and blood volume increased both with time at each temperature and as the stimulation temperature were raised. However the increase in the response was greater for the edentulous patients when the stimulation temperature was raised from 0 degrees C to 50 degrees C. 5) The responses of blood vessels became greater after two weeks when complete dentures were worn during sleep at night. And when dentures were not worn during sleep the responses decreased to a level lower than what it used to be after three weeks. 6) From the above results it was suggested that oral mucosa of the edentulous patients were losing their sensitivity due to wearing complete dentures and were not receiving as much effect of the contractile control from body as the dentulous subjects. It was also suggested that wearing denture during sleep at night cause inflammation of oral mucosa and increase the metabolism of tissue in edentulous patients.

Denture, Complete

Studies on the binding of adenylyl-3', 5'-cytidine to ribonuclease.

The interaction of adenylyl-3',5'-cytidine (ApC) with ribonuclease-A (RNAase-A) was studied by steady-state kinetics and ultraviolet difference spectroscopy. X-ray difference Fourier synthesis at 4 A resolution was also used to study the binding of ApC to RNAase-S. Unlike well-studied compounds like uridylyl-3',5'-adenosine, ApC binds in an unique way: (1) the cytidine moiety is bound to the B1 and R1 sites, (2) the adenosine moiety protrudes to the solution and is not fixed spatially and (3) the phosphate group is bound to the non-specific site (the "Po site") previously postulated (Sawada, F. and Irie, M. (1969) J. Biochem. (Tokyo) 66, 415--418) as the binding site for the 5'-phosphate of uridine 2',5'-diphosphate or uridine 3',5'-diphosphate. This conclusion is consistent with that derived for adenylyl-3',5' -4-thiouridine based on CD difference spectroscopy (White, M.D., Keren-Zur, M. and Lapidot, Y. (1977) Nucleic Acid Res. 4, 843--851). The "Po site" is most likely the epsilon-amino group of Lys 66.

Adenine Nucleotides

Relationship between polyamine contents and protease activity in the rat submaxillary gland.

The effect of polyamines on the protease activity in the submaxillary gland of castrated rats has been investigated in vivo. The protease activity, which is increased by testosterone, is also increased to a lesser degree by the subcutaneous administration of spermidine. The administration of putrescine was less effective than that of spermidine. The increase of polyamine contents in the submaxillary gland of the castrated rats administered either testosterone or spermidine was nearly parallel to the increase of the enzymatic activity. The administration of methylglyoxal bis(guanylhydrazone), a potent inhibitor of spermidine synthesis, with testosterone inhibited slightly the increase of the protease activity by testosterone, while the administration of the inhibitor with spermidine had essentially no effect on the increase of the enzymatic activity by spermidine. The administration of testosteorne also caused a slight increase of S-adenosyl-L-menthionine decarboxylase activity. These results suggest that spermidine synthesis may be necessary for the stimulation by testosterone of protease synthesis in the rat submaxillary gland.

Adenosylmethionine Decarboxylase

Crystal structure of monoclinic ribonuclease-S at 4 A resolution. The mode of binding of 4-thiouridylic acid and a fragment of folic acid, p-aminobenzoylglutamic acid.

A four-A electron density map was calculated for the monoclinic crystal of ribonuclease-S (RNase-S) based on two heavy-atom derivatives. Close geometrical similarity was found between the two crystallographically independent RNase-S molecules (called molecules ZA and ZB) in this crystal and that (called molecule Y) in the trigonal crystal. Using the rotational and translational parameters relating these three molecules, it was established that the crystallographic two-fold symmetry between the two molecules ZA in the monoclinic crystal was exactly identical to that between the two molecules Y in the trigonal crystal, suggesting the tendency of RNase-S molecules to associate in this way although the interaction is weak. The 4-A difference Fourier maps calculated for the monoclinic crystal established the following conclusions. (1) 4-Thiouridine-2'(3')-monophosphates binds to the B1 and R1 sites like other pyrimidine nucleoside-2'(3')-monophosphates as expected from previous spectrophotometric studies, but not to the B2 site even at the concentration of 20 mM. An attempt to visualize the photoproduct generated by irradiation of near-ultraviolet light in this complex failed. (2) p-Aminobenzoylglutamic acid, a fragment of folic acid, seems to bind to RNase-S with its benzene ring close to the B2 site and the alpha-carboxylate group close to the p1 site. The model is compatible with most of the chemical results obtained by Sawada et al. ((1977) Biochim. Biophys. Acta 479, 188-197).

4-Aminobenzoic Acid

Appetite and taste preference in growing rats given various levels of protein nutrition.

The cephalic gustatory stimuli during a meal yield nutritional information and aid in the efficient control of homeostasis. This study was focused on either appetite for flavored food or feeding behavior in growing male Sprague-Dawley rats under various states of protein nutrition. In fasted rats, endogenous protein degradation was suppressed by ingestion of glucose that was sufficient to meet energy needs. The decrease in the amount of diet intake was compensated by sugar ingestion, except for sucrose. Rats that ingested sucrose exceeded 115% of total energy intake, compared to ingestion of saccharin as a control. Appetite and meal size are primarily dependent upon the dietary protein level, whether it was beyond normal requirements or not and, thus, flavoring by certain taste material is effective for a diet sufficient in protein, but not for a deficient one. In addition, rats fed a diet containing amino acids preferred saccharin and monosodium L-glutamate (MSG) and grew normally. But, when L-tryptophan-deficient diet was offered, the preference for tryptophan was elicited, and then MSG intake was elevated and their growth became normal. However, preference for saccharin never occurred because the level of tryptophan in blood fluctuated and was not maintained within normal limits. The strong preference for sweetness that is evoked by starvation is directly regulated by the negative energy balance. The animals' primary concern was energy intake and their second concern was protein nutrition, regardless of flavoring.

Aging