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Biomedical subjects

K Hiraga

Publications and source records attributed to K Hiraga.

At least 109 records · Page 6Linked to original sources

Nasal constant positive airway pressure inhibits the swallowing reflex.

The effects of constant positive airway pressure applied via a nose mask through the nares (nasal CPAP) on the swallowing reflex were studied in eight adult humans. The swallowing reflex was induced by bolus injections of a small amount of distilled water (0.5 ml) into the pharynx at four different values of endexpiratory airway pressure (0,5,10, and 15 cm H2O CPAP) or by continuous infusion of water (3 ml/min) at two different values of endexpiratory airway pressure (0 and 15 cm H2O CPAP). The latency of response from the time of bolus injection of water to the occurrence of the first swallow as well as the number of swallows elicited during the period of 10 s immediately following the water injection were measured. Our results showed that increases in endexpiratory airway pressure progressively prolonged the latency of response and decreased the number of swallows. Also, the frequency of swallows decreased greatly at nasal CPAP of 15 cm H2O during continuous infusion of water. These results indicate that nasal CPAP exerts an inhibitory influence on the swallowing reflex.

Adult↗

[Reflex depression of respiration induced by baroreceptor stimulation during enflurane-nitrous oxide anesthesia].

Inhibition of respiration in response to arterial baroreceptor stimulation was studied in 7 patients with no evidence of respiratory or cardiovascular disorders under enflurane-nitrous oxide anesthesia. The arterial baroreceptors were stimulated by a bolus injection of phenylephrine (0.1mg, i.v.). A rise in blood pressure following administration of phenylephrine caused decreases in heart rate and tidal volume, suggesting the presence of cardiovascular and respiratory reflexes from baroreceptors in anesthetized humans. However, despite the statistical significance, the depression of respiration is too small to be clinically important.

Adult↗

Structure, turnover, and heme-mediated suppression of the level of mRNA encoding rat liver delta-aminolevulinate synthase.

lambda gt11 cDNA libraries were constructed with poly(A)+ RNA preparations from both porphyric chicken and rat livers. A cDNA which encodes chicken hepatic delta-aminolevulinate synthase was cloned by screening with an anti-chicken liver delta-aminolevulinate synthase antibody. Using this cDNA as a probe, cDNAs encoding the entire protein coding sequence of rat hepatic delta-aminolevulinate synthase were then cloned. The complete nucleotide sequences of the cDNAs have been determined. The result predicts that the rat hepatic pre-delta-aminolevulinate synthase comprises 642 amino acids. We measured the half-life of the hepatic delta-aminolevulinate synthase mRNA by RNA blot hybridization analysis using allylisopropylacetamide-induced porphyric rats as an experimental model and the rat cDNA as a hybridization probe. The half-life of the mRNA determined by the injection of alpha-amanitin is as short as 20 min. This value is significantly shorter than the estimated half-lives of most other mRNAs in the differentiated tissues of animals. The effect of hemin administration on the level of hepatic delta-amino-levulinate synthase mRNA was also examined. The half-disappearance time of the mRNA after the hemin administration was essentially the same as that determined by alpha-amanitin or actinomycin D, and no additive effect was observed between alpha-amanitin and hemin on the half-life determination. The results provide convincing evidence that heme inhibits the transcription of delta-aminolevulinate synthase mRNA.

5-Aminolevulinate Synthetase↗

The impaired expression of glycine decarboxylase in patients with hyperglycinemias.

Glycine decarboxylase, a constituent of the glycine cleavage system, in patients with either nonketotic or ketotic hyperglycinemia (NKH and KH) was examined using an anti-chicken glycine decarboxylase antibody. Patients with NKH who have lesion in glycine decarboxylase are differentiated by its expressed level in the liver. One group is cases of the neonatal onset type who have neither activity of the enzyme nor protein reactive to the antibody. The other is a case of the late onset type who shows low but detectable activity of the enzyme and the desirable amount of the immunoreactive material. In the liver of a patient with KH not showing the appreciable activity of H-protein, ubiquitous amount of protein reactive to anti-H-protein IgG is detected and amount of glycine decarboxylase has also been lowered. It is suggested that several mechanisms may be involved in determining the expressed level of glycine decarboxylase in patients with hyperglycinemias.

Adult↗

Cloning of cDNA encoding human H-protein, a constituent of the glycine cleavage system.

A cDNA that encodes human H-protein, a constituent protein of the glycine cleavage system, was cloned with anti-rat H-protein antibody as a probe from a human liver cDNA library constructed with an expression vector, lambda gt11. The longest size of cDNA of the isolated clones was about 750 base long (lambda HH15B9). On the other hand, we determined the primary structure of human H-protein from the amino terminal Ser by the 12th Val, including a hexapeptide, -Glu-Lys-His-Glu-Trp-Val-. In addition to the finding that most cDNA inserts cloned hybridized with the synthetic DNA probe composed of the possible sequences for the hexapeptide, we confirmed that lambda HH15B9 encodes the partial primary structure of H-protein in an open reading frame.

Amino Acid Oxidoreductases↗

Breathing pattern of anesthetized humans during pancuronium-induced partial paralysis.

We investigated the breathing patterns of 17 subjects anesthetized with enflurane before and after partial muscle paralysis produced by pancuronium bromide. In the face of significant muscle weakness produced by pancuronium, breathing patterns are characterized by decreases in both tidal volume and respiratory frequency. The decreased tidal volume corresponded to the decrease in occlusion pressure, indicating that the decreased tidal volume results solely from a decreased contractile force of the respiratory muscles. The decreased respiratory frequency was due to prolongation of both inspiratory and expiratory time without changing the ratio of the inspiratory time to the total breath time. Withdrawal of phasic vagal influence by airway occlusion before partial muscle paralysis revealed that an active Breuer-Hering inflation reflex was operative in only 8 of all 17 subjects. Since the contribution of the Breuer-Hering inflation reflex alone does not seem to account for the consistent decrease in respiratory frequency, some other mechanisms modulating respiratory frequency might be involved in the characteristic breathing patterns during partial muscle paralysis under enflurane anesthesia.

Adult↗

Respiratory reflex responses to stimulation of tracheal mucosa in enflurane-anesthetized humans.

We investigated respiratory reflex responses to tracheal mucosa stimulation induced by injection of distilled water in 13 female patients under three different depths of enflurane anesthesia (0.7, 1.0, and 1.3 minimum alveolar concentration). Detailed analysis of the types of reflex responses revealed that there are at least six different responses: 1) the apneic reflex, 2) the expiration reflex, 3) spasmodic, panting breathing, 4) the cough reflex, 5) slowing of breathing, and 6) rapid, shallow breathing. Among these reflex responses, the cough reflex was the most sensitive and the apneic reflex followed by slowing of breathing was the most resistant to deepening anesthesia, whereas the sensitivity of other types of reflex responses was in between. Our results indicate that the types of respiratory reflex responses to tracheal mucosa stimulation are associated with depths of anesthesia and that the differences in sensitivity to anesthesia may be a valuable sign in clinical assessment of depth of anesthesia.

Adult↗

[Hyperglycinemias].

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Amino Acid Metabolism, Inborn Errors↗

Effects of pH on the carcinogenicity of o-phenylphenol and sodium o-phenylphenate in the rat urinary bladder.

The effects of an alkalizer or an acidifier on bladder carcinogenesis induced by OPP or OPP-Na were examined. Groups of 31 male F344/DuCrj rats were given 1.25% OPP in the diet (group 1), 1.25% OPP in the diet plus 0.4% sodium bicarbonate (NaHCO3) in drinking-water (group 2), 2% OPP-Na in the diet (group 3) or 2% OPP-Na in the diet plus 1% ammonium chloride (NH4Cl) in drinking-water (group 4) for 26 wk. Urinary bladder tumours, papilloma and carcinoma occurred in 12/31 (39%) of group 1, 20/31 (65%) of group 2, 22/31 (71%) of group 3 and 3/31 (10%) of group 4. Values of urinary pH after 25 wk of treatment were correlated with the tumour incidences. The results indicate that the administration of an alkalizer enhanced the carcinogenicity of OPP and the administration of an acidifer inhibited the carcinogenicity of OPP-Na to the rat urinary bladder. This suggests that the earlier finding that OPP-Na was more carcinogenic than OPP resulted from the higher alkalinity of OPP-Na.

Animals↗

Mechanism of synthesis and localization of mitochondrial and cytosolic fumarases in rat liver.

Fumarases in the mitochondrial and cytosolic fractions of rat liver were separately purified and crystallized. These two fumarases were not distinguishable in physicochemical, catalytic, or immunochemical properties. The sequences of seven amino acids in the C-terminal portions of the two fumarases were shown using carboxypeptidase P to be identical, i.e.-Val-Asp-Glu-Thr-Ala-Leu-Lys-. The amino acid sequence of the N-terminal portion of the mitochondrial fumarase was determined by the Edman method as Ala-Gln-Gln-Asn-Phe-Glu-Ile-Pro-Asp-, but that of the cytosolic fumarase could not be determined by the Edman method, since the N-terminal amino acid was blocked. The N-terminal amino acid of the cytosolic fumarase was identified as N-acetyl-alanine by analysis of the acidic amino acid produced by digestion of the enzyme protein with pronase E, carboxypeptidase A and B. Then the sequence of five amino acids in the N-terminal portion was determined by analyzing the acidic peptide obtained by limited proteolysis of the enzyme protein with carboxypeptidase A as Ac-Ala-Ser-Gln-Asn-Ser-. Peptide mapping of the tryptic peptides obtained from the mitochondrial and cytosolic fumarases showed no difference in the amino acid sequences of the two except in their N-terminal portions. The turnover rates of the mitochondrial and cytosolic fumarases were determined by injecting L-[U-14C]leucine into rat and following the decay of specific radioactivity incorporated into immunoprecipitates from the partially purified enzyme. The half-life of the cytosolic fumarase was estimated as 4.8 days from the decay curve of its specific radioactivity. The decay curve of the specific radioactivity of the mitochondrial fumarase, obtained after a single injection of L-[U-14]leucine, was quite unusual: its specific radioactivity remained constant for about 7 days after pulse labeling, and then decreased exponentially with a half-life of 9.7 days. Similar amounts of cytosolic and mitochondrial fumarase were found in the livers of the rat, mouse, rabbit, dog, chicken, snake, frog, and carp, respectively. Similar subcellular distributions of the enzyme were also found in the kidney, heart, and skeletal muscle of rats, and in hepatoma cells (AH-109A). However, in rat brain no fumarase activity was detected in the cytosolic fraction. Two putative precursor polypeptides of rat liver fumarase were synthesized when rat liver RNA was translated in vitro in a rabbit reticulocyte lysate system.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Enhancing effect of thiabendazole on urinary bladder carcinogenesis induced by sodium o-phenylphenate in F344 rats.

Sodium o-phenylphenate (OPP-Na), a urinary bladder carcinogen in rats, and another fungicide, thiabendazole (TBZ) were fed separately or simultaneously to F344/DuCrj rats of both sexes. The rats were fed one of six diets, either the basal (control) diet or basal diet containing 0.2% TBZ (group T), 1% OPP-Na (1% SO), 2% OPP-Na (2% SO), 1% OPP-Na plus 0.2% TBZ (1% SO-T) or 2% OPP-Na plus 0.2% TBZ (2% SO-T) for 13 or 65 wk. In the 13-wk study, in which groups of ten rats of each sex were used, urinary bladder tumours appeared in 8/10 males in each of three groups--the 2% SO, 1% SO-T and 2% SO-T groups--but not in the remaining animals. Of these tumours, carcinoma accounted for 3/8 tumours in the 2% SO group, 2/8 in the 1% SO-T group and 8/8 in the 2% SO-T group. In the 65-wk study, in which groups of 15 rats were used, the tumour incidence in males was 1/15 in the T group and 15/15, 12/15 and 14/15 in the 2% SO, 1% SO-T and 2% SO-T groups, respectively, while in the females, tumours were found in 2/15, 1/15 and 12/15 animals in the 2% SO, 1% SO-T and 2% SO-T groups, respectively. Of these tumours, carcinoma accounted for 10/15, 11/12 and 10/14 in the males of the 2% SO, 1% SO-T and 2% SO-T groups, respectively, and for 1/2 and 6/12 in the 2% SO and 2% SO-T females, respectively. The tumour incidences in the 1% SO-T males in the two studies and in the 2% SO-T females in the 65-wk study showed a statistically significant increase over those in the 1% SO males or the 2% SO females. Thus, TBZ apparently enhanced the carcinogenic effects of OPP-Na in the rat urinary bladder.

Animals↗

[Comparison of characteristics between F344 and Slc:Wistar rats--Slc:Wistar rats cannot be distinguished from the F344 strain].

With respect to F344/DuCrj and Slc: Wistar rats, both widely used in Japan, it was found that there is a close similarity in the changes of body weights and survival rates, and in the organ distribution and incidence of spontaneous tumors. To examine the degree of homozygosity between F344 and Slc: Wistar strains, tumor transplantation and skin grafting were performed. The bladder carcinomas that originated from F344/DuCrj rats grew subcutaneously in the other F344 strains and Slc: Wistar rats, but did not grow in the other Wistar-derived strains. The skin grafts between F344/DuCrj or F344/NSlc and Slc: Wistar rats were accepted, but those between F344/DuCrj or Slc: Wistar and the other Wistar-derived strains were rejected. These results suggest that Slc: Wistar rats cannot be distinguished genetically from the F344 strain of rats.

Animals↗