Search PubMed⌕ Search

Biomedical subjects

F Yamauchi

Publications and source records attributed to F Yamauchi.

At least 37 records · Page 2Linked to original sources

Altered production of IgE and IgA induced by IL-4 in peripheral blood mononuclear cells from patients with IgA nephropathy.

In order to elucidate the factors responsible for altered immunoglobulin production in patients with IgA nephropathy (IgAN), the in vitro effects of IL-4 and interferon-gamma (IFN-gamma) on the synthesis of IgE and IgA by peripheral blood mononuclear cells (PBMC) were studied. Spontaneous IgE and IgA synthesis by PBMC was significantly increased in patients with IgA nephropathy compared with controls. The maximum amounts of IgA and IgE synthesis by PBMC after stimulation with IL-4 were almost the same both in patients with IgAN and in controls. The enhancement rate of IL-4-induced IgE and IgA synthesis was significantly lower in IgAN than in the controls, suggesting in vivo preactivation of PBMC in IgAN patients. IFN-gamma suppressed IgA and IgE synthesis by PBMC from IgAN patients as well as controls. However, the suppressive effect on IgE synthesis was less prominent in patients with IgAN. These results suggested that altered IL-4 action might be involved in the development of IgA nephropathy.

Adolescent↗

Prostaglandin D2 increases Cl secretion across canine tracheal epithelium through cyclo-oxygenase stimulation and cAMP production.

Prostaglandin (PG) D2 is one cyclo-oxygenase product of arachidonic acid metabolites that may play a role in the pathogenesis of asthma. To determine the effect of PGD2 on ion transport by airway epithelium and its mechanism of action, we measured bioelectric properties of canine cultured tracheal epithelium under short-circuit conditions in vitro. PGD2 (10(-7) M) increased short-circuit current (Isc) from 5.5 +/- 1.2 to 14.1 +/- 2.9 microA cm-2 (means +/- SE, P less than 0.01) when added to the mucosal solution, and to 22.2 +/- 3.8 microA cm-2 (P less than 0.001) when added to the submucosal solution, an effect that was accompanied by the corresponding increases in transepithelial potential difference and conductance. These effects were dose-dependent. The PGD2-induced increase in Isc was not altered by preincubation of cells with autonomic antagonists (phentolamine, propranolol, atropine), the lipoxygenase inhibitor AA-861, the protein kinase C inhibitor H-7, or the Na channel blocker amiloride, but it was inhibited by each of indomethacin, piroxicam, the Cl channel blocker diphenylamine-2-carboxylate, the Cl transport inhibitor furosemide, and Cl-free medium. Intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels were dose-dependently increased by PGD2. These results suggest that PGD2 may selectively stimulate airway epithelial Cl secretion via cyclo-oxygenase- and cAMP-dependent pathway.

Animals↗

Stimulation of Cl secretion by lactoferrin across canine airway epithelial cells in culture.

To investigate the effect of lactoferrin, an iron-binding glycoprotein in the respiratory tract, on ion transport function of airway epithelial cells, we measured bioelectric properties of canine cultured tracheal epithelium by Ussing's short-circuit technique. Addition of lactoferrin (60 micrograms/ml) to the mucosal side of epithelial sheet increased the short-circuit current (Isc) from 4.8 +/- 0.8 to 7.5 +/- 1.1 microA/cm2, and the submucosal addition likewise increased Isc from 3.8 +/- 0.6 to 5.6 +/- 0.7 microA/cm2 (p < 0.001, in each case). This effect was concentration dependent. The lactoferrin-induced increase in Isc was not altered by amiloride, indomethacin, or propranolol but was abolished by diphenylamine-2-carboxylate or substitution of Cl with iodide in the medium. Intracellular cyclic AMP levels were not increased by lactoferrin. These results suggest that lactoferrin may selectively stimulate Cl secretion across the airway mucosa, an effect that may not be dependent on prostaglandins, beta-adrenergic receptor or intracellular cyclic AMP.

Animals↗

CD4 subsets in IgA nephropathy.

CD45RA+ (2H4+) and CD45RA-(CD29, 4B4+) antigenic expressions, recognized as a suppressor inducer and a helper inducer, respectively, on CD4+ and T alpha 4+ cells (Fc alpha receptor bearing CD4 T cells) were measured by three color flow cytometry in patients with IgA nephropathy (IgAN). The 4B4+ subsets of CD4 and T alpha 4 T cells were increased significantly in the patient group compared with the control group. The level of the 2H4+ subset did not differ between the two groups. No significant correlation was observed between the increase in the 4B4+ subset and disease severity, as estimated by measuring the proteinuria, levels of serum creatinine and immunoglobulins (Igs) or renal tissue damage. It was concluded that 4B4+ CD4+ and 4B4+ T alpha 4+ subsets might be involved in the mechanism of immunopathogenesis of IgA nephropathy.

Adult↗

Effects of angiotensin peptides on cholinergic neurotransmission in rabbit tracheal smooth muscle.

To determine the effects of angiotensins I, II, and III (A I, A II, and A III) on airway smooth muscle functions, we studied isolated tracheal segments from rabbits under isometric conditions in vitro. Addition of A II and A III but not A I potentiated the contractile response to electrical field stimulation (EFS) at 5 Hz in a dose-dependent fashion. The frequency-response curves for EFS were displaced to the left by A II and A III, whereas the contractile responses to exogenous acetylcholine remained unchanged. Angiotensin-induced potentiation of the response to EFS was further increased in the presence of physostigmine. These results suggest that A II and A III may prejunctionally potentiate the vagally-mediated contraction of airway smooth muscle.

Acetylcholine↗

[Airway epithelial beta 3-adrenergic receptor--effect on bioelectric properties and its mechanism of action].

To characterize the "atypical" beta-adrenergic receptor (beta 3-adrenergic receptor) and its action on ion transport across airway mucosa, we measured the bioelectric properties of canine cultured tracheal epithelium under short-circuited conditions in vitro. Submucosal but mucosal addition of BRL37344, a selective beta 3-adrenergic agonist, increased short-circuit current (Isc) in a dose-dependent fashion, the EC50 value being 30 fold higher than that of isoproterenol. This effect on Isc was accompanied by the accumulation of intracellular cyclic AMP, and it was abolished by diphenylamine-2-carboxylate, bumetanide, and Cl-free medium, but not by amiloride. Pretreatment of cell with beta 1- and beta 2-adrenergic antagonists greatly reduced the Isc response to isoproterenol, whereas it had little effect on the BRL37344-induced response. In addition, the increase in Isc produced by BRL37344 was competitively antagonized by cyanopindolol, but pA2 was significantly different from the case of isoproterenol. These results suggest that beta 3-adrenergic receptors exist on airway epithelium, and may stimulate Cl secretion across the airway mucosa via accumulation of intracellular cyclic AMP.

Adrenergic beta-Agonists↗

[Pharmacological evidence for the existence of beta 3-adrenergic receptors in canine airway smooth muscle].

There is increasing evidence for the existence of a third atypical beta-adrenergic receptor (beta 3-adrenoceptor) in various tissues including adipocytes, cardiac myocytes and intestinal smooth muscle preparations. In the present study, to determine whether beta 3-adrenoceptors also exist in the airway smooth muscle, we studied isolated bronchial segments from dogs under isometric conditions in vitro. Application of beta-adrenoceptor agonists produced a concentration-dependent relaxation of tissues precontracted with 10(-5) M acetylcholine, the order of potency being isoproterenol (1) > or = salbutamol, a beta 2-selective adrenoceptor agonist (0.95) > or = BRL 37344, a beta 3-selective adrenoceptor agonist, (0.83) >> norepinephrine (0.10). Under the condition in which alpha- and beta 1-adrenoceptors had been blocked by phentolamine and ICI 89406, respectively, the relaxant response to salbutamol was competitively antagonized by the beta 2-adrenoceptor antagonist ICI 118551, and the pA2 value was 7.01 +/- 0.25 (mean +/- SE), whereas the response to BRL 37344 was resistant, with of apparent pA2 value of 5.66. However, cyanopindolol, an antagonist atypical beta-adrenoceptors, antagonized BRL 37344-induced relaxation in a competitive fashion with a pA2 of 6.74 +/- 0.11. This pA2 value was lower than that when salbutamol was used as an agonist (p < 0.05). These results indicate that beta 3-adrenoceptors probably exist in canine bronchial smooth muscle, and that stimulation of this type of receptors produces potent bronchodilation. Therefore, a specific agonist for beta 3-adrenoceptors could be valuable in the treatment of asthma.

Acetylcholine↗

In vivo antibody response to mucosal (NASAL) and subcutaneous stimulation of influenza virus in patients with IgA nephropathy.

Anomalies in the production of antibodies have been postulated in the development of IgA nephropathy. In order to study the aberrant immune response in patients with IgA nephropathy (IgAN), an influenza virus vaccine was administered to healthy adults and patients with IgAN to demonstrate if there was any in vivo alteration in the antibody production to mucosal and non-mucosal antigenic stimulation in these groups. The vaccine was administered subcutaneously (s.c) or intranasally at a dose of 350 CCA or 1,050 CCA at an interval of 4 weeks, respectively. IgG, IgA, IgM class antibodies to influenza virus were determined using the enzyme linked immunosorbent assay (ELISA). Subcutaneous stimulation induced IgM antibody response in both groups. However, positive response to nasal stimulation was observed only in the patient group. Serum IgA and IgM responses in the patient group were significantly higher than those in the control group. These data suggested that patients with IgA nephropathy showed higher antibody response to mucosal stimulation than healthy controls.

Administration, Intranasal↗

Ambroxol inhibits Na+ absorption by canine airway epithelial cells in culture.

To study the effect of ambroxol on ion transport functions of airway mucosa, we measured bioelectric properties of canine cultured tracheal epithelium under short-circuit conditions in-vitro. Addition of ambroxol to the submucosal but not to the mucosal solution in an Ussing chamber decreased short-circuit current, transepithelial potential difference and cell conductance. The ambroxol-induced decrease in short-circuit current was not affected by bumetanide or diphenylamine-2-carboxylate, but it was abolished by pretreatment of cells with amiloride. These results suggest that ambroxol may selectively inhibit Na+ absorption by airway epithelium, thereby increasing water composition in airway surface fluid and reducing mucus viscosity.

Absorption↗

Effect of neutral endopeptidase inhibition on substance-P-induced increase in short-circuit current of canine cultured tracheal epithelium.

We studied the effect of substance P (SP) on the electric properties of cultured canine tracheal epithelium and its possible modulation by neutral endopeptidase (NEP) by Ussing's short-circuited technique in vitro. Addition of SP (5 x 10(-6) M) to the mucosal side increased short-circuit current (SCC) from 5.1 +/- 0.9 to 10.3 +/- 2.2 microA/cm2 (mean +/- SE; p less than 0.01), which was accompanied by increases in transepithelial potential difference and conductance. The effect of the mucosal SP on SCC was dose-dependent, with the maximal increase from the baseline value being 5.8 +/- 1.0 microA/cm2 observed at 5 x 10(-5) M. The NEP inhibitor phosphoramidon (10(-5) M) did not affect these responses. On the other hand, SCC was not altered by the addition of SP to the submucosal side. However, it was increased dose-dependently in the presence of phosphoramidon (10(-5) M) but not in the presence of captopril, bestatin or leupeptin. This stimulatory effect of submucosal SP was abolished by furosemide, diphenylamine-2-carboxylate and Cl-free medium, but not by amiloride. These results suggest that SP may selectively stimulate Cl secretion across the airway epithelium and that this effect may be modulated by submucosal NEP.

Amiloride↗

Relationship between the limited proteolysis of glycinin and its conformation.

The relationship between the limited proteolysis and conformation of native glycinin was studied by the following methods: analyses of the proteolytic digestion of chemically modified glycinin, circular dichroism (CD) measurements, a secondary structure prediction from the amino acid sequence and a hydropathy index analysis. The locations of tryptic fragments of glycinin were confirmed from the N-terminal amino acid sequences of the fragments. T fragments and P fragments were located at the N-terminal and central area of the acidic polypeptide chains, respectively. One of the cleavage sites was the Arg residue of around the 100th from the N-terminal side. The regions digested by limited trypsinolysis were presumed to be flexible, hydrophilic and near the surface of the molecule by prediction methods from the amino acid sequence. The other regions were predicted to be compact and beta-sheet in nature, almost 40-50% of the amino acid residues being predicted as beta-sheet from the amino acid sequence and from CD data.

Amino Acid Sequence↗

[Effect of roxithromycin on ciliary motility of rabbit tracheal epithelium in culture].

Mucociliary transport plays an important role in the lung defense mechanism by clearing inhaled particles and bacteria from the respiratory tract. In the present study, we tried to determine whether roxithromycin (RXM), a new semisynthetic macrolide, can affect airway mucociliary functions and, if so, what the mechanism of its action is. To do so we measured ciliary beat frequency (CBF) of rabbit cultured tracheal epithelium by a photoelectric method. Addition of RXM (10(-4) M) to a Rose chamber containing epithelial cells caused a rapid increase in CBF from 12.1 +/- 0.6 to 16.2 +/- 0.8 Hz (mean +/- SE, p less than 0.001) within 5 min. This effect was dose-dependent, the maximal increase from the baseline CBF and EC50 being 34.6 +/- 5.0% and 3 x 10(-6)M, respectively. The increase in CBF produced by RXM (3 x 10(-6)M) was not influenced by pretreatment of cells with the beta-adrenergic blocker propranolol, the lipoxygenase inhibitor AA-861, or the Ca(2+)-channel blocker verapamil, but it was partially reduced by the cyclooxygenase inhibitor indomethacin (p less than 0.05). Intracellular cyclic AMP levels were increased by 10(-4)M RXM from 42.3 +/- 8.7 to 72.7 +/- 7.0 pmoles/mg protein (p less than 0.05). These results indicate that RXM stimulates ciliary motility; an effect that may be attributed at least in part to the synthesis of cyclooxygenase products and cyclic AMP, and suggest that this macrolide could be useful in treating patients with impaired mucociliary transport in the airway.

Animals↗

[A case of Ramsey Hunt syndrome with multiple cranial nerve paralysis and acute respiratory failure].

The authors report a 56-year-old woman with Ramsey Hunt syndrome with multiple cranial nerve paralysis and acute respiratory failure. Five days before admission, she experienced right otalgia and right facial pain and consulted an otolaryngologist of our hospital, who diagnosed the illness as acute parotitis and laryngopharyngitis. One day before admission, she experienced mild dyspnea and general fatigue and came to our hospital emergency room. A chest X-ray film revealed no abnormalities but some blisters were observed around her right ear. The next day, her dyspnea became more severe and she was admitted. A chest X-ray film on admission revealed right lower lobe consolidation, and neurological examination disclosed multiple cranial nerve paralysis, i.e., paralysis of the right fifth, seventh, eighth, ninth, tenth, eleventh, twelfth and left tenth cranial nerve. The serum titer of anti-herpes zoster antibody was elevated to 1,024, and the patient was diagnosed as having Ramsey Hunt syndrome with multiple cranial nerve paralysis. Arterial blood gas analysis revealed hypoxemia with hypercapnea, which was considered to be due to aspiration pneumonia and central airway obstruction caused by vocal cord paralysis. Mechanical ventilation was soon instituted and several antibiotics and acyclovir were administered intravenously, with marked effects. Three months after admission, the patient was discharged with no sequelae except mild hoarseness. Patients with herpes zoster oticus, facial nerve paralysis and auditory symptoms are diagnosed as having Ramsey Hunt syndrome. This case was complicated by lower cranial nerve paralysis and acute respiratory failure, which is very rare.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Studies on the metabolic fate of sucrose esters in rats.

The metabolism in rats of sucrose esters of stearic acid and palmitic acid was studied in vivo and in vitro using esters labelled with 14C at the sucrose of fatty-acid moiety. In excretion studies, the ratio of expired radioactivity to absorbed radioactivity after oral administration of the sucrose esters labelled at the sucrose moiety was similar to that after the administration of [14C]sucrose. A similar correlation between the ester labelled at the fatty-acid moiety and the free [14C]fatty acid was also observed. No intact sucrose ester was detected in the urine. Studies in vitro using everted intestinal sacs showed that there was virtually no transport of 14C-labelled sucrose esters from the mucosal to the serosal solution through the intestinal tissues, and that the enzymes in the intestinal mucosa played a more important role in the hydrolysis of sucrose esters than did those in the digestive fluid. In studies of intestinal absorption through the mesenteric lymphatic system, during the 24 hr after ingestion 1.8% of the administered radioactivity was recovered in the lymph after dosing with [U-14C]sucrose monostearate whereas 20% was recovered in the lymph after dosing with sucrose [1-14C]monostearate. This difference in levels of recovery of administered radioactivity indicated that sucrose monostearate was absorbed only after hydrolysis. No intact ester was detected in the lymph or in the portal or femoral blood. The results of all of these experiments show that the sucrose esters are hydrolysed to sucrose and fatty acids prior to intestinal absorption.

Absorption↗

Relationship between molar refraction and n-octanol/water partition coefficient.

The n-octanol/water partition coefficient (Pow) for organic chemicals which do not form the hydrogen bond was considered on the basis of London's dispersion force, because the dispersion force is the main component of van der Waals-type attractive forces between solute and solvent molecules. The dispersion force is a function of both the ionization potential and the molar refraction. As the variation of the ionization potential is small in comparison with that of the molar refraction, the latter is the most important factor to determine the value of Pow. Thus the relationship between Pow and the molar refraction can be established. The relationship was confirmed for some halogenated alkanes, alkenes and aromatics, and polycyclic aromatic hydrocarbons by analysis of observed values of Pow and calculated values of the molar refraction. Estimation of Pow from the molar refraction is advantageous for the preliminary hazard assessment of new chemicals, because direct measurement of Pow is laborious and time consuming for lack of information about analytical methods.

1-Octanol↗

Non-steady-state equilibrium model for the preliminary prediction of the fate of chemicals in the environment.

Prediction of the fate of chemicals in the environment is essential to the assessment of the potential hazard of chemicals. The fate of a chemical in the environment depends mainly upon (1) transfer processes between environmental compartments due to physicochemical properties, (2) transformation processes in each compartment, and (3) characteristics of the environment. Many equilibrium or kinetic models have been proposed to predict the fate of chemicals in the environment. Though kinetic models are useful in predicting the concentration-time profile of a chemical at the non-steady state, they are rather complicated. In this work is proposed a simple and useful equilibrium model for prediction of the mass and concentration distribution fraction, mean residence time, and concentration-time profile of a chemical released into the environment, an advantage of our model. For the validation of this model, the results were compared with data from Neely's pond experiment and field data monitored by the Japanese Environment Agency. The results show that the equilibrium model is valuable for preliminary prediction of the fate of chemicals that are priority chemicals for hazard assessment in the environment.

Chemical Phenomena↗