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T Haga

Publications and source records attributed to T Haga.

At least 163 records · Page 9Linked to original sources
PubMed1985

Acute effects of cigarette smoke inhalation on peripheral airways in dogs.

We studied the acute effects of the inhalation of cigarette smoke on the central and peripheral airways of 35 open-chested and tracheotomized dogs by the direct measurement of central (Rc) and peripheral (Rp) airway resistances. Rc was calculated by dividing the pressure difference between a tracheal catheter and a retrograde catheter by mouth flow, and Rp was obtained by dividing the pressure difference between the retrograde catheter and a pleural capsule by mouth flow. The pleural capsule was attached to the pleural surface for alveolar pressure measurement. Rc and Rp were measured by the 2-Hz forced oscillation method. With lung inhalation of the smoke of two-thirds of one cigarette in vagi intact dogs, Rp increased to 239% of the control value and Rc increased to 112%. After bilateral vagotomy, Rp increased to 143% and Rc increased to 104%. Propranolol did not influence the results. Hexamethonium and atropine both blocked these responses when vagi were intact. When the upper trachea, larynx, and nasopharynx, which were completely blocked by vagotomy, were exposed to the smoke of two-thirds of a cigarette, Rp increased to 155% and Rc increased to 144%. We thus conclude that cigarette smoke causes a major increase in Rp, mainly via the vagal reflex and partially via the stimulation of parasympathetic ganglia (probably nicotine), and a minor increase in Rc via vagal reflex.

Airway Resistance↗
PubMed1984

Hydrodynamic properties of muscarinic acetylcholine receptors solubilized from rat forebrain.

Muscarinic receptors from rat forebrain have been solubilized by Lubrol PX, lysophosphatidylcholine (LPC), digitonin and cholate/1 M sodium chloride. The overall level of solubilization was characterized using receptors prelabelled with an irreversible antagonist. The recovery of nondenatured soluble binding activity was estimated using reversible tritiated antagonists. All these detergents solubilized 60-85% of the total binding sites. In Lubrol PX most of the receptors were recovered in a denatured form. In the other detergents 30-90% of the solubilized receptors were stable and capable of binding reversible [3H]-antagonists with high affinity. The hydrodynamic properties of the soluble receptors have been examined by gel filtration and sucrose gradient centrifugation in H2O and D2O. The soluble receptors in Lubrol PX, lysophosphatidylcholine and cholate were, in general, heterogeneous as regards their molecular size. Estimates of the molecular weight after correction for bound detergent, varied from 82,000 to 134,000. Conditions were identified under which the receptor was largely monodisperse, and the estimates of molecular weight agreed with values (ca. 83,000) from sodium dodecylsulphate (SDS) polyacrylamide gel electrophoresis. The amount of bound detergent could not be calculated for the digitonin-muscarinic receptor complex which had an estimated overall median molecular weight of about 290,000. It is concluded that a subpopulation of muscarinic receptors from the rat forebrain is capable of existing in a monomeric soluble form and binding ligands. There is also evidence that complexes with other proteins can exist, but their specificity and functional relevance are not known.

Animals↗
PubMed1983

Affinity chromatography of the muscarinic acetylcholine receptor.

A novel compound, 3-(2'-aminobenzhydryloxy)-tropane (ABT), and an ABT-agarose gel were synthesized and used for the purification of solubilized muscarinic receptors. ABT had a high affinity with an apparent dissociation constant (Kd) of 7 nM for the muscarinic receptors solubilized from the porcine brain by digitonin. An ABT-agarose gel was prepared by coupling ABT with epoxy-activated Sepharose 6B, and the degree of substitution to the gel was determined to be 4-5 mumol/ml of the gel by UV absorption spectrum. During affinity chromatography using 10 ml of the ABT-agarose gel and 100 ml of the digitonin-solubilized preparation, 70% of muscarinic receptors were adsorbed to the gel, in marked contrast with the adsorption of only 2% of proteins. Approximately 25% of muscarinic receptors applied to the gel were eluted biospecifically with 1 mM muscarinic ligands. The purified fraction showed a high affinity for [3H]quinuclidinyl benzylate with a Kd of 0.4 nM and similar specificity for muscarinic ligands to that of unpurified soluble receptors. The protein concentration of the purified fraction was too low to be determined accurately, but very approximately a purification of 10(3)-fold was indicated.

Animals↗
PubMed1983

Solubilisation and molecular characterisation of muscarinic acetylcholine receptors.

Stable, soluble preparations of rat brain muscarinic receptors can be prepared by extracting membranes with digitonin, or with combinations of sodium cholate and sodium chloride. The stability of the cholate/NaCl extract is enhanced by the addition of egg phosphatidylcholine, which, at the same time, suppresses the considerable dispersity apparent in the hydrodynamic behaviour of the solubilised receptor. The Stokes radius of the brain muscarinic receptor in cholate/NaCl/lecithin extracts is 6.7 nm, with very similar values in other detergents, including digitonin and sodium dodecyl sulphate. Its sedimentation coefficient is 3.78s, and its molecular weight approximately 110,000 after correction for detergent binding. The isoelectric point of the digitonin - solubilised receptor is approximately 4.5.

Animals↗
PubMed1983

A study of long-term oxygen therapy in Japan and other Asian countries.

In order to investigate the use of long-term oxygen therapy in Japan, I sent questionnaires to the national chronic disease hospitals and general hospitals that are known to frequently treat respiratory diseases. I found that 61% of the chronic disease hospitals that responded had patients receiving long-term oxygen therapy in the hospital, and 12% had patients receiving it at home. Of the general hospitals answering the questionnaire, 77% had inpatients on long-term oxygen and 39% had home patients receiving oxygen therapy. The majority of patients were on oxygen for treatment of tuberculosis, its sequelae, or obstructive lung diseases. The mean PaO2 for inpatients and outpatients on oxygen was 69 mm Hg and 65 mm Hg, respectively. The cannula is the most frequently used oxygen delivery appliance. Hospital piping systems are used for inpatients, and cylinders and concentrators are used by outpatients. Health insurance covers the cost of oxygen and equipment for hospitalized patients. Home oxygen and equipment are paid for by the patient himself, or at public expense. According to the results of my questionnaire, in Hong Kong long-term oxygen is administered in the hospital only. In Korea it is administered in the hospital and on rare occasion in the home. In Taiwan oxygen is not administered on a long-term basis.

Asia, Eastern↗
PubMed1983

Muscarinic receptors in porcine caudate nucleus. I. Enhancement by nickel and other cations of [3H]cis-methyldioxolane binding to guanyl nucleotide-sensitive sites.

Muscarinic acetylcholine receptors in the synaptic membrane fraction of porcine caudate nucleus were characterized by using a radiolabeled agonist, [3H]cis-methyldioxolane [( 3H]CD) and an antagonist, [3H]quinuclidinyl benzilate [( 3H]QNB). Scatchard analysis of the specific binding of [3H]CD gave a single equilibrium dissociation constant of 8.1 nM when a concentration of less than 80 nM [3H]CD was used. The binding capacity was 390 fmoles/mg of protein and corresponded to about 10% of the binding sites of [3H]QNB. Agonist/[3H]CD competition binding experiments indicated that [3H]CD was selectively bound to the sites with a high affinity for agonists. [3H]CD binding was inhibited by Na+, K+, Mg2+, and Ca2+ with the half-maximal effect at 10-50 mM. Nickel ion showed biphasic effects on [3H]CD binding: a 2- to 3-fold enhancement of binding at 0.1-10 mM and inhibition above 10 mM. Other cations, including Co2+, Mn2+, and Zn2+, at 1 mM also increased [3H]CD binding by a factor of 1.5-1.8. Among 18 cations examined, only Cd2+, Hg2+, and Cu2+ caused significant inhibition of [3H]CD binding at 1 mM. [3H]CD binding was decreased to about 20% of the control value in the presence of guanylyl-5'-imidodiphosphate (GppNHp), GTP, and GDP with the half-maximal effect at 1.3, 32, and 45 microM, respectively. [3H]CD binding in the presence of Ni2+ was decreased by GppNHp to a level obtained in the presence of GppNHp alone. The increase caused by Ni2+ in [3H]CD binding was due to the increase in the maximal binding capacity (Bmax) without changes in the affinity for [3H]CD. We conclude that Ni2+ increases the proportion of a muscarinic receptor subclass (or state) that is sensitive to guanyl nucleotide.

Animals↗
PubMed1983

Muscarinic receptors in porcine caudate nucleus. II. Different effects of N-ethylmaleimide on [3H]cis-methyldioxolane binding to heat-labile (guanyl nucleotide-sensitive) sites and heat-stable (guanyl nucleotide-insensitive) sites.

Heat treatment of membranes from porcine caudate nucleus (50 degrees for 7 min) caused a marked decrease in [3H]cis-methyldioxolane [( 3H]CD) binding without affecting seriously the binding of [3H]3-quinuclidinyl benzilate [( 3H]QNB). Approximately 20% of the [3H]CD binding at 5 nM [3H]CD remained after the heat treatment. The remaining binding was not affected by 0.1 mM guanylyl-5'-imidodiphosphate (GppNHp) or by nickel or other cations at concentrations below 10 mM. Treatment of the membranes with trypsin (30 micrograms/mg of protein) at 20 degrees for 20 min also caused a marked decrease in [3H]CD binding without affecting seriously the binding of [3H]QNB. About 20% of the original [3H]CD binding remained in the presence of trypsin at a high concentration of protein (90 micrograms/mg). N-Ethylmaleimide (NEM) affected [3H]CD binding in two different ways: (a) preincubation of the membranes with NEM caused a marked reduction in heat- and GppNHp-sensitive [3H]CD binding, and (b) treatment with NEM caused an enhancement of heat-, GppNHp-, and trypsin-insensitive [3H]CD binding. Neither of the NEM effects required the coexistence of agonists. The concentration of NEM required for the first effect was 10 times lower than that for the second effect, indicating the existence of two NEM-binding sites with different affinities for NEM. The equilibrium dissociation constant (Kd) for [3H]CD after NEM treatment was 33 nM and was not affected by GppNHp, Ni2+, or heat treatment; the Kd was only 4 times higher than that (8 nM) without NEM treatment. These findings indicated the existence of two kinds of [3H]CD binding sites with high affinities for agonists: one is sensitive to guanyl nucleotide and is abolished by NEM and the other is induced by NEM and insensitive to guanyl nucleotide.

Animals↗