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Biomedical subjects

I Tanaka

Publications and source records attributed to I Tanaka.

At least 325 records · Page 18Linked to original sources

[Molecular biology and pharmacology of natriuretic peptide system].

The natriuretic peptide system comprises at least three endogenous ligands, namely, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), and three receptors for natriuretic peptides (NPR), that is, NPR-A, NPR-B and clearance receptor (NPR-C). Three natriuretic peptides derived from the distinct genes share a common ring structure with 17 amino acids formed by a disulfide linkage which confers the unique biological property on these peptides. ANP and BNP are elucidated to be the cardiac hormone mainly secreted from the atrium, and from the ventricle, respectively. CNP, first recognized as the neuropeptide, is now identified within the vascular wall, especially in endothelial cells and considered to be the peptidic endothelium-derived relaxing factor (EDRF). While NPR-A shows the high affinity to ANP and BNP, NPR-B is the selective receptor for CNP. These two types of "biologically active" NPR are the membrane-bound guanylate cyclase itself, and mediate the wide range of biological actions of natriuretic peptides through cyclic GMP-dependent cascade. The clearance receptor shows the ligand-binding affinity with the rank order of ANP > CNP > BNP and is considered to be involved in the clearance of the peptides. The natriuretic peptide system as an endocrine and paracrine/autocrine system serves as one of the key modulatory systems for blood pressure, body fluid homeostasis and vascular remodeling.

Amino Acid Sequence↗

Brain energy metabolites in mice after an acute exposure to carbon monoxide.

Brain energy metabolites were determined in mice over 8 days after an acute exposure to carbon monoxide (CO). The exposure of 0.5% CO for 15 min caused 33% mortality. Survived mice recovered completely within 30 min in room air. Lactate increased markedly immediately after the exposure, while glucose increased 30 min later. Four hours, 1 day, 4 days and 8 days after the exposure, the levels of brain energy metabolites including phosphocreatine and ATP did not differ from those of the control. Thus, energy metabolism in the whole brain in mice appears not to be impaired after they survive an acute CO intoxication.

Adenosine Triphosphate↗

Microsurgical scalp and skull reconstruction using a serratus anterior myo-osseous flap.

In reconstruction of large scalp and skull defects, the usefulness of microvascular free tissue transfer is manifest. We have performed 4 scalp and skull reconstructions by free serratus anterior osteomuscle flap transfer. The usefulness of serratus anterior osteomuscle flap for reconstruction of combined, extensive scalp and skull defects is emphasized.

Brain Injuries↗

5-Hydroxydecanoate inhibits ATP-sensitive K+ channel currents in guinea-pig single ventricular myocytes.

We investigated the effect of 5-hydroxydecanoate, a novel antiarrhythmic agent, on the electrical activity of guinea-pig ventricular myocytes. The outward K+ current increased by lowering the intracellular ATP concentration (0.5 mM) was efficiently blocked by 5-hydroxydecanoate when recording in the whole cell configuration with the application of voltage ramps. The increase in the time-independent outward K+ current induced by reducing intracellular ATP to 0 mM was also blocked by 5-hydroxydecanoate (10 or 100 microM) and by tolbutamide (1 mM). Using the single channel recording technique, we found that 5-hydroxydecanoate blocked ATP-sensitive K+ channels when its channel open probability was increased by 1 mM ATP together with 1 mM ADP or by an intracellular pH of 6.6. These conditions are well documented to reflect metabolic changes in the early stages of myocardial ischemic attack. These results suggest that 5-hydroxydecanoate could inhibit ATP-sensitive K+ channels, resulting in an antiarrhythmic effect specifically on ischemic hearts.

Adenosine Triphosphate↗

Enzyme-linked immunoassays for CRM positive hemophilia A using monoclonal antibodies with defined epitopes.

Sensitive, monoclonal antibody-based, enzyme-linked immunosorbent assays (ELISAs) for plasma factor VIII (FVIII) antigen have been developed. The assays used five monoclonal anti-FVIII antibodies with known epitopes in four different pairwise combinations. The sensitivity of the assays was increased by use of the ELISA amplification method described by Bobrow et. al. (J. Immunol Methods 125:279, 1989). These assays can distinguish between CRM positive, CRM reduced and CRM negative hemophilia A. A total of 94 plasma samples from 78 different patients were screened and generally consistent results were obtained among the different assays. Such assays are potentially useful in the phenotypic and genotypic analysis of hemophilia A.

Antibodies, Monoclonal↗

A new methyl bromide gas generator for inhalation toxicity studies.

A simple generator for methyl bromide gas has been newly developed by us. For inhalation toxicity studies, until now, there have been few generators capable of producing a constant and stable concentration of methyl bromide gas easily because of its high volatility. The principle of this new generator is based on gas-liquid equilibrium. The gas is generated from the surface of liquid methyl bromide in an evaporator made of a Teflon tube. The generator can produce up to 10,000 ppm of methyl bromide gas in a 0.1 m3 exposure chamber, and the concentration of this generated gas is able to be kept within +/- 0.8% over a long period of time. The generator has proved to be useful for investigating the effects of methyl bromide on health in inhalation toxicity studies.

Administration, Inhalation↗

Lateral interactions of pig apolipoprotein A-1 with egg yolk phosphatidylcholine and with cholesterol in mixed monolayers at the triolein-saline interface.

Interfacial tensions of egg yolk phosphatidylcholine (PC) and cholesterol monolayers adsorbed at the triolein-saline interface were measured in the presence and absence of pig apolipoprotein A-1 (apoA-1) in the saline phase. In the absence of apoA-1, the adsorptions of PC and cholesterol at the interface from the triolein phase are cooperative, showing large lateral attractive interactions between the PC molecules and the cholesterol molecules in the monolayer. In the presence of apoA-1, the PC adsorption is anti-cooperative, indicating strong lateral attractive interactions between the PC and the apoA-1 molecules, i.e., apparently, repulsive lateral interactions between the PC molecules. On the other hand, lateral interactions of very low magnitude are observed between the cholesterol and apoA-1 molecules in the monolayer. Values of the lateral interaction energy are evaluated from the adsorption data by the Defay-Prigogine-Flory theory of monolayers. The large difference in lateral interaction energy with apoA-1 between PC and cholesterol in a mixed monolayer is discussed in connection with current problems in lipoprotein catabolism: reverse cholesterol transport, alterations in affinity of lipid particles to apoA-1, and formation of high-density lipoproteins and abnormal lipoproteins.

Adsorption↗

A cAMP-dependent protein kinase inhibitor modulates the blocking action of ATP and 5-hydroxydecanoate on the ATP-sensitive K+ channel.

We studied the blocking mechanism of 5-hydroxydecanoate, a novel antiarrhythmic agent, on the ATP-sensitive K+ channel in the single ventricular myocytes using the inside-out patch clamp technique. The channel activity in response to 5-hydroxydecanoate varied with each membrane patch corresponding to the sensitivity to ATP. In this condition the exogenous application of cAMP or cAMP-dependent protein kinase (PKA) obviously recovered the ATP-sensitive K+ channel activity after channel deactivation. By contrast, in membrane patches exhibited low sensitivity to ATP, endogenous cAMP-dependent protein kinase inhibitor (PKI) depressed the channel activity and restored the inhibitory action of 5-hydroxydecanoate and ATP on the channel. These results suggest that PKA-PKI system is involved in the regulatory mechanism of gating activity of the ATP-sensitive K+ channel and the blocking action of 5-hydroxydecanoate and ATP appears to be exerted by potentiating the inhibitory action of PKI on the channel.

Adenosine Triphosphate↗

Gene introduction into granulocyte-macrophage progenitor cells by electroporation: the relationship between introduction efficiency and the proportion of cells in S-phase.

Our previous study demonstrated the positive relationship between the gene introduction rate into hematopoietic cell lines by electroporation and the percentage of cells in S-phase. In the present study, granulocyte-macrophage progenitor cells (CFU-C) rich marrow cell fraction were cultured in suspension with IL-3, GM-CSF and G-CSF for 4 days. The number of CFU-C were increased three times after the culture, and 3H-thymidine suicide tests of cultured cells demonstrated that the proportion of CFU-C in S-phase was increased by two to four times. The efficiency of gene transfer into CFU-C with the plasmid pMoZtk (containing the beta-galactosidase gene) by electroporation was nearly doubled by culturing marrow cells with these growth factors. These findings confirm that the introduction rate of the gene into CFU-C by electroporation is more efficient in cell populations with a higher percentage of CFU-C in S-phase.

Cell Count↗

Purification and cDNA cloning of a novel factor produced by a human T-cell hybridoma: sequence homology with animal lectins.

We have purified a novel immunoregulatory factor (BMPG: bone-marrow proteoglycan) produced by a T-cell hybridoma, with a monoclonal antibody column. Using an oligonucleotide probe corresponding to the partial amino acid sequence of BMPG, we cloned, sequenced, and expressed a cDNA for BMPG. BMPG has 222 amino acid residues with a 16 N-terminal signal sequence, so the mature form has 206 amino acid residues. BMPG was found to have unique characteristics: it has three types of sugar chains and it shows a marked homology with animal lectins including the human asialoglycoprotein receptor, chicken hepatic lectin and the homing receptor of lymphocytes.

Amino Acid Sequence↗

Adsorption characteristics of organic solvent vapor on activated carbon under fluctuating vapor concentrations.

Air containing organic solvent vapor was introduced into a glass column packed with activated carbon particles under the conditions of rectangularly fluctuating vapor concentration. All the experiments were started from an adsorption cycle and were succeeded by a nonadsorption cycle. These cycles were repeated at the same intervals under a constant flow rate. The experimental breakthrough curves and the breakthrough times were compared with those obtained under a constant vapor concentration. The breakthrough curves at the fluctuating vapor concentration were oscillated and the breakthrough times were sometimes significantly shorter than those at the constant vapor concentration when the designed average vapor concentration, i.e., the concentration averaged over an equal number of on and off cycles, was equal. This tendency was greater for the solvents that have higher saturated vapor pressures, such as acetone, methyl acetate, and methyl chloroform, especially when the fluctuating time interval was long. Because the vapor concentrations in the work environments are fluctuating, the effective time of charcoal tubes and respirator cartridges may become shorter than the expected values, which are based on the constant vapor concentration laboratory studies.

Adsorption↗

Crystallization and preliminary X-ray structure analysis of pigeon egg-white lysozyme.

Calcium binding lysozyme from pigeon egg-white was crystallized by the hanging drop vapor diffusion technique using ammonium sulphate as a precipitant. The crystals belong to the orthorhombic system, space group P2(1)2(1)2(1), and have unit cell dimensions of a = 34.2 A, b = 34.8 A, and c = 99.4 A. One asymmetric unit contains one molecule of the pigeon lysozyme. The crystals diffract X-rays at least to 2.0 A resolution and are suitable for high resolution structure analysis. The diffraction data up to 3.0 A resolution were collected with a diffraction image processor, DIP100, using a Fuji imaging plate as an area detector. The structure was solved by the molecular replacement technique and refined to an R factor of 0.216. Least-squares fitting of the main-chains of pigeon egg-white lysozyme with those of chicken egg-white lysozyme and baboon alpha-lactalbumin showed that the main-chain folding of pigeon lysozyme is more similar to that of chicken lysozyme than that of alpha-lactalbumin. The largest differences between the pigeon and chicken lysozymes are in the surface loop regions.

Amino Acid Sequence↗

Possible inspiratory off-switch neurones in the ventrolateral medulla of the cat.

The location and axonal projection of a type of respiratory neurones (termed bIE neurones), which show burst firing at the time of phase transition from inspiration to expiration, were studied in Nembutal-anaesthetized, paralysed and artificially ventilated cats. The bIE neurones showed maximum firing at the sharp decline of inspiratory activity. All of the bIE neurones tested projected to medullary respiration-related areas of the ventral respiratory group (VRG), the dorsal respiratory group (DRG), and the Bötzinger complex (BOT). The bIE neurones were distributed in the dorso-medial border of the main assembly of respiratory neurones of the VRG and BOT. The possibility that these bIE neurones participate in inspiratory termination is discussed.

Animals↗

Increased level of atrial natriuretic peptide messenger RNA in the hypothalamus and brainstem of spontaneously hypertensive rats.

OBJECTIVE: The aim of this study was to investigate atrial natriuretic peptide (ANP) gene expression in the central nervous system (CNS) during hypertension. METHODS: We measured and compared immunoreactive atrial natriuretic peptide (irANP) and ANP messenger RNA (mRNA) in the hypothalamus and brainstem of 17-week-old spontaneously hypertensive rats (SHR) with those of age-matched Wistar-Kyoto (WKY) rats using ribonuclease (RNase) protection assay for ANP mRNA and a specific radioimmunoassay for irANP. RESULTS: RNase protection assay revealed that the concentrations of ANP mRNA in the hypothalamus and brainstem of SHR were higher than those of WKY rats. IrANP concentrations in the hypothalamus and brainstem of SHR were determined by a specific radioimmunoassay and found to be higher than those of WKY rats. Elevated mRNA levels in the hypothalamus and brainstem of SHR indicated that increased level of irANP in the CNS resulted from increased synthesis of ANP. CONCLUSION: We propose that increased synthesis of brain ANP in SHR may reflect a compensatory mechanism induced by hypertension.

Animals↗

Modulation of pancreatic exocrine function in rodents by treatment with pancreatic polypeptide.

The in vivo and in vitro treatment effects of pancreatic polypeptide (PP) were characterized by studying agonist-stimulated enzyme secretion in pancreatic acini prepared from 8-week-old mice treated for 2 days with PP (200 micrograms kg-1 day-1) and in pancreatic lobules from untreated male rats. In the mouse studies, enzyme secretion was evaluated on the basis of percentage total amylase released, amylase released per unit of DNA, and amylase released per unit of protein. When expressed as percentage total amylase released, the acini from mice treated with PP were significantly less responsive to pancreatic secretagogues than were acini from control animals. Chronic treatment with bovine PP lowered the maximal response to carbachol (12.3 +/- 0.3 vs. 9.0 +/- 0.3% total amylase release in control and PP treated, respectively), decreased the magnitude of the difference between basal and maximal amylase release (10.6 +/- 0.4 vs. 6.2 +/- 0.5% total amylase release in control and PP treated, respectively), and affected these changes without modifying the dose of carbachol producing half-maximal amylase release. Similarly, the percentage of total amylase released in response to all doses of cholecystokinin octapeptide (1-100 pM) was reduced by chronic treatment with PP. However, when amylase release was expressed relative to protein or DNA, no differences in enzyme release were detected between treatments with either secretagogue. Chronic treatment with PP increased the total amount of amylase in the acini (per unit DNA or protein), but the increased amylase appeared to be unavailable for release since the actual amount (per microgram DNA or milligram protein) released in response to agonists did not differ between treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗