Search PubMed⌕ Search

Biomedical subjects

K Hiraga

Publications and source records attributed to K Hiraga.

At least 73 records · Page 4Linked to original sources

Respiratory responses to chest compression in human subjects.

To test the hypothesis that respiratory compensation for chest compression in the conscious state is different from that in the unconscious state, a range of chest compression was applied to eight conscious and eight anesthetized subjects. Chest compression was carried out by inflating a pneumatic cuff inserted under a chest corset and placed over the anterior chest wall for 5 min. Cuff inflation pressures were 25, 50, and 100 mm Hg: light, moderate, and heavy chest compression, respectively. In both conscious and anesthetized subjects, chest compression immediately caused a decrease in tidal volume (VT) and a concomitant increase in respiratory frequency (f). These changes stabilized within 2 min and remained nearly steady for the rest of the sustained chest compression. The decrease in VT was more prominent the greater the loads, and the change in f was in reverse proportion to the change in VT. In conscious subjects the increase in f was due to shortening of both inspiratory time (T1) and expiratory time (TE), whereas in anesthetized subjects the increase in f was due solely to shortening of TE. In conscious subjects, the values of minute ventilation (VI) and end-tidal PCO2 (PETCO2) during light and moderate chest compression were not different from the control values, whereas VI increased and PETCO2 decreased during heavy chest compression. In anesthetized subjects, the values of VI and PETCO2 were not different from the control values at any different magnitudes of chest compression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Abnormal metabolism of substances related to glycine and beta-alanine].

Glycine and serine are interconverted by serine hydroxymethyltransferase and hence share their metabolic pathways. In the rat the carbon skeleton of choline is derived from the alpha and beta carbons of serine through phosphatidylserine and is further converted to that of glycine through N-methylated molecules of glycine i.e. betaine, N-dimethylglycine, and sarcosine (N-methylglycine). Thus far, the production of a folate derivative of the active one carbon that is an essential material for purine nucleotides and thymidylate biosynthesis is the notable feature of this metabolic process. In the major degradative pathway for pyrimidine nucleotides, beta-alanine, one of omega-amino acids, is produced and further catabolized by beta-alanine: oxoglutarate transaminase which is suggested to be identical to that for gamma-aminobutyrate, another omega-amino acid. Disorders included in these metabolic pathways are succinctly reviewed.

4-Aminobutyrate Transaminase↗

cDNA cloning of a calcineurin B homolog in Saccharomyces cerevisiae.

We have isolated a cDNA clone encoding a homolog of mammalian calcineurin B (the regulatory subunit of calmodulin-dependent protein phosphatase) by screening a cDNA expression library of Saccharomyces cerevisiae with antiserum against bovine calcineurin B. The yeast calcineurin B homolog (YCNB) is composed of 175 amino acids with a calculated molecular mass of 19,639 daltons and contains four putative Ca(2+)-binding domains. The amino-acid alignment of YCNB with human calcineurin B demonstrates 53% sequence identity and 82% homology. Southern blot analysis indicates that the gene for YCNB is a single-copy gene. Thus, yeast calmodulin-dependent protein phosphatase apparently has a heterodimeric structure similar to that of the enzyme in mammalians.

Amino Acid Sequence↗

Partial structure of the human H-protein gene.

In a span of approximately 13 kb, two genomic fragments showing an obvious overlap encoded the 1,192 base pair (bp) cDNA sequence for human H-protein. Because of the close similarity in the genomic organization comprised of five exons to that for the chicken H-protein gene, this region was assigned to the true H-protein gene in human. Primer extension analysis suggested and S1 protection analysis confirmed that at least one additional exon for the 74 bases-long 5' untranslated region in H-protein mRNA exists as the presumable first exon. None of the 5.0- and 5.5-kb SacI and the 5.2-kb EcoRI fragments which were undetectable in the genomes of patients with nonketotic hyperglycinemia was included in the true H-protein gene.

Amino Acid Sequence↗

Isolation and sequence determination of cDNA encoding T-protein of the glycine cleavage system.

T-protein is a component of the glycine cleavage system and catalyzes the tetrahydrofolate-dependent reaction. A partial cDNA for chicken T-protein was isolated by screening a chicken liver cDNA library with oligonucleotide probes based on amino acid sequences. The clone (CT5C) contains a 675-base pair insert encoding the C-terminal half of the T-protein. Screening of a bovine liver lambda gt10 cDNA library with the insert of CT5C as a probe detected a clone, BT5A, with an insert of about 2 kilobase pairs. The 1191-base pair coding region encodes a precursor protein of 397 amino acids (Mr 42,852) comprised of a 22-residue mitochondrial targeting sequence and a 375-residue mature protein (Mr 40,534). The 33 amino acids immediately following the targeting sequence correspond exactly to those determined by sequence analysis of the amino terminus of the purified bovine T-protein. The mature protein contains several hydrophilic segments with a cluster of arginine and lysine. The T-protein cDNA probe hybridized to an mRNA species of about 2 kilobases in bovine brain, lung, heart, and liver. A probe for H-protein hybridized with two species of mRNA in these tissues and weak signals were also found in spleen. Although the enzymatic activities of T-protein and H-protein were found in these tissues where transcripts were found, activity of P-protein was detected only in liver and brain. Southern blot analysis of genomic DNA suggested that T-protein is a single copy gene.

Amino Acid Sequence↗

The glycine cleavage system. Occurrence of two types of chicken H-protein mRNAs presumably formed by the alternative use of the polyadenylation consensus sequences in a single exon.

Several cDNAs encoding H-protein, a constituent of the glycine cleavage system, were cloned from chicken liver cDNA libraries with an antibody raised against rat H-protein or with a nick-translated cDNA of an immunoreactive clone. The structure of the H-protein cDNA consisting of 910 base pairs was determined using clones with an apparent overlap in the nucleotide sequence. The cDNA encodes the precursor form of H-protein that is comprised of 39 amino acid residues for a mitochondrial presequence and 125 amino acid residues for the mature protein, following a 5' untranslated region of 13 base pairs. There are two genuine consensus sequences for the cleavage/polyadenylation of the precursor H-protein mRNA in the 3' untranslated region of the cDNA sequence. We showed by comparison with the delta-aminolevulinate synthase gene that only one copy of the H-protein cDNA occurs in the haploid genome of the chicken. Nevertheless, two types of H-protein mRNAs, which differ by the length of their 3' untranslated region, are produced in liver. The chicken H-protein gene extends over 8 kilobase pairs on the genome and includes 5 exons that encode the entire cDNA sequence. Two AATAAA motifs are coded in the last exon of this gene, suggesting that the differently size H-protein mRNAs are produced by the alternative use of these motifs.

Amino Acid Oxidoreductases↗

The glycine cleavage system. Molecular cloning of the chicken and human glycine decarboxylase cDNAs and some characteristics involved in the deduced protein structures.

A cDNA encoding chicken glycine decarboxylase (pCP15b) was isolated using an antibody specific to this protein. Additional cDNAs were cloned with the aid of the genomic fragments obtained by using the pCP15b cDNA probe. No initiator methionine codon is found in the currently elucidated cDNA sequence, and an ATG codon in an exon is assigned to this role. The precursor glycine decarboxylase deduced from the 3514-base pair nucleotide sequence is comprised of 1,004 amino acids (Mr = 111,848). The 1,020 amino acid residues are encoded for the precursor form of human glycine decarboxylase (Mr = 112,869) in the 3,783-base long cDNA sequence of two 1.9-kilobase pair cDNAs with a pentanucleotide overlap. The pyridoxal phosphate binding site lysine and a glycine-rich region, which is suggested to be responsible for the attachment of the phosphate moiety of pyridoxal phosphate, are found in close proximity in both the chicken and human enzymes. This region essential for the enzyme action is suggested to be embedded in a segment rich in beta-turns and random coils and is surrounded by conserved and repetitive amino acid sequences. It is suggested that these structures are involved in the organization of the active site of glycine decarboxylase.

Amino Acid Oxidoreductases↗

The glycine cleavage system. The coupled expression of the glycine decarboxylase gene and the H-protein gene in the chicken.

Regulation of the transcription of the glycine decarboxylase gene and the H-protein gene was examined in chicken. Northern analysis suggested and run-off transcription confirmed that the glycine decarboxylase gene transcription is exclusively tissue-specific and takes place at different efficiencies in liver, kidney, and brain which are the chicken tissues exhibiting the glycine cleavage activity. No evidence for the glycine decarboxylase gene transcription was obtained in heart, spleen, and skeletal muscle. Basal and tissue-specific transcription of the H-protein gene can be distinguished. The tissue-specific transcription coordinates with transcription of the glycine decarboxylase gene in active tissues, while low abundance H-protein and its mRNA, products of the basal transcription, exist in inactive tissues together with small amounts of T-protein. Apparently, T-protein is synthesized by a process similar to that for H-protein. Glycine decarboxylase mRNA levels show a linear relationship with H-protein mRNA levels and with specific activities of the glycine cleavage reaction in active tissues. Tissue-specific distribution of the glycine cleavage activity is primarily determined by the expression of the glycine decarboxylase gene. The coordinate and tissue-specific transcription of the genes for the constituent proteins plays a key role in determining the magnitude of the glycine cleavage activity in chicken tissues and, thereby, the tissue-specificity of glycine metabolism.

Amino Acid Oxidoreductases↗

A cell line of human malignant astrocytoma producing autocrine growth factor.

A cell line was established from an anaplastic astrocytoma from a 69-yr-old female. The cells have been serially subcultured over 300 times for 6 yr without showing any sign of cell senescence. Their doubling time is about 36 h. The cells are fusiform and often hexagonal in sparse culture, but become spindle-shaped and formed mosaic structure in confluent culture. Under electron microscopy, intermediate filaments were randomly distributed in the cytoplasma, especially in the perinuclear space. The chromosome number was near tetraploid and varied from 86 to 94 chromosomes with a modal number of 91. The alpha and beta subunits of S-100 protein, vimentin, and glial fibrillary acidic protein (GFAP), which are reliable markers of astrocytic cells, were demonstrated in a large number of cells by immunoperoxidase staining. The results of immunoblotting showed that the expression of vimentin was much higher than that of GFAP. The tumorigenicity of the cells was revealed by xenografting into nude mice, which were X-irradiated before inoculation. Culture medium conditioned by the cells promoted growth of these cells in serum-free conditions and of normal rat glial cells in serum-depleted culture. The growth-promoting effect of conditioned medium was lost by trypsinization and reduced by boiling. These findings suggest that these cells are derived from neoplastic astrocytic cells and secrete a self-acting polypeptide growth-promoting factor into the culture medium.

Aged↗

Respiratory, laryngeal, and tracheal responses to nasal insufflation of volatile anesthetics in anesthetized humans.

In order to determine whether or not irritation of the nasal passage with commonly used volatile anesthetics can elicit airway reflexes, we investigated respiratory, laryngeal, and tracheal responses to nasal insufflation of three volatile anesthetics (enflurane, isoflurane, and halothane) in 13 patients anesthetized with flunitrazepam, pentazocine, and nitrous oxide. The trachea of each patient was intubated with a saline-filled double-cuffed endotracheal tube. Changes in breathing pattern were measured with a pneumotachograph while changes in laryngeal wall tension and tracheal wall tension were assessed by measuring changes in the proximal cuff pressure and the distal cuff pressure, respectively. In 8 of 13 patients, the dose-response relationship for each anesthetic was determined by administering different concentrations (1, 3, and 5%) of gas mixtures. In these patients, nasal insufflation of 1 and 3% of each anesthetic did not produce any reflex response, whereas reflex responses were evident during nasal insufflation of 5% enflurane, isoflurane, and halothane. In all 13 patients, nasal insufflation of all three anesthetics at a concentration of 5% invariably produced changes in breathing pattern characterized by prolongation of expiratory time (TE). However, prolongation of TE was the most pronounced for enflurane (from a control value of 2.1 +/- 0.5 to a maximum value of 4.8 +/- 2.2 s [mean +/- standard deviation]), less for isoflurane (from 2.2 +/- 0.5 to 3.9 +/- 1.7 s), and the least for halothane (from 2.2 +/- 0.6 to 2.9 +/- 0.9 s).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Inhibition of membrane Ca2(+)-ATPase of Saccharomyces cerevisiae by mating pheromone alpha-factor in vitro.

Plasma membrane Ca2(+)-ATPase of Saccharomyces cerevisiae was solubilized and partially purified by calmodulin-affinity chromatography. The activity of Ca2(+)-ATPase isolated from MATa cells was inhibited by physiological concentrations of the mating pheromone alpha-factor in a dose-dependent manner. The enzyme prepared from a receptor-deficient sterile mutant cells (delta ste-2) was similarly inhibited by alpha-factor, but the enzyme from MAT alpha cells was resistant to the mating pheromone. We suggest that the inhibition may be involved in the alpha-factor-induced increase of Ca2+ uptake reaction of MATa cells.

Bacterial Proteins↗

Coordination of swallowing and respiration in unconscious subjects.

We investigated the coordination of swallowing and breathing in 11 unconscious patients with an endotracheal tube in place during the recovery period from general anesthesia. Swallows occurred during both the inspiratory and expiratory phases with no preponderant occurrence during either phase. When a swallow occurred during inspiration, the inspiration was interrupted immediately and was followed by expiration, but the durations of both inspiration and expiration were progressively increased as the time from the onset of inspiration to the onset of swallowing was progressively delayed. A swallow coinciding with the expiratory phase progressively prolonged the duration of the expiration that had been interrupted as the timing of swallowing was progressively delayed. Repeated swallows invariably and in a predictable manner caused changes in the breathing pattern. Thus when the frequency of regularly repeated swallows was relatively high, the breathing pattern was characterized by regular, shallow, and rapid breaths. When the frequency of regularly repeated swallows was relatively low, the breathing pattern was characterized by regular, deep, and slow breaths. When the frequency of repeated swallows was irregular, the breathing patterns were characterized by inconsistent changes in tidal volume and respiratory frequency. Our results indicate that, in unconscious subjects, some mechanisms integrating respiration and swallowing are operative and responsible for changes in breathing patterns during swallowing.

Adult↗