Biomedical subjects

H P Kuo

Publications and source records attributed to H P Kuo.

15 recordsLinked to original sources

PubMed1995

Neurogenic goblet cell secretion and bronchoconstriction in guinea pigs sensitised to trimellitic anhydride.

Trimellitic anhydride is a cause of occupational asthma in humans. We have previously found that tracheal instillation of trimellitic anhydride conjugated to guinea pig serum albumin induces acute bronchoconstriction and airway plasma exudation in sensitised animals, responses mediated primarily via histamine release. In the present study, neural mechanisms mediating bronchoconstriction and goblet cell secretion were determined in trimellitic anhydride-sensitised guinea pigs using the ganglionic blocker hexamethonium to eliminate efferent reflex mechanisms, pretreatment with capsaicin to eliminate afferent mechanisms, or cimetidine and mepyramine to eliminate histamine-mediated mechanisms. The magnitude of secretion of intracellular mucus from tracheal goblet cells was quantified morphometrically as a mucus score which is inversely related to the degree of discharge. Guinea pigs were injected intradermally either with 0.1 ml 0.3% trimellitic anhydride in corn oil or with corn oil alone as control. Fourteen to eighteen days later all sensitised animals had developed specific immunoglobulin (Ig) G1 antibodies whereas the controls had not. Tracheal instillation of conjugated trimellitic anhydride in anaesthetised animals significantly increased airway lung resistance (RL) 24-fold in sensitised guinea pigs (34.3 +/- 7.9 cm H2O.ml-1.s) compared with controls (1.4 +/- 0.1 cm H2O.ml-1.s). Mucus score was significantly reduced by 51% (indicating goblet cell secretion) in sensitised guinea pigs (183 +/- 22 mucus score units) compared with controls (372 +/- 41 mucus score units). The antihistamines significantly inhibited conjugated trimellitic anhydride-induced bronchoconstriction by 89%, but did not significantly affect goblet cell discharge. Hexamethonium alone did not significantly affect conjugated trimellitic anhydride-induced bronchoconstriction or goblet cell secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

PubMed1995

Effects of CIS-19, a novel PAF receptor antagonist, on PAF-induced eosinophil recruitment and enhancement of superoxide anion generation in guinea-pigs.

We examined the effects of a novel platelet-activating factor (PAF) receptor antagonist, CIS-19 [cis-2-(3,4-dimethoxyphenyl)-6-isopropoxy-7-methoxyl-1-(N-methylforma mido)- 1,2,3,4-tetrahydronaphthalene], on PAF-induced inflammatory cells recruitment into airways and enhancement of superoxide anion (O2-) generation from cells retrieved by bronchoalveolar lavage (BAL) in urethane-anesthetized guinea-pigs. Administration of PAF (30 ng/kg, i.v.) produced a selective increase of eosinophils into airways, but no significant increase of the number of macrophages, neutrophils or lymphocytes. CIS-19 (2.5 and 5 mg/kg, i.v.) significantly inhibited the eosinophil recruitment induced by PAF. In vitro, PAF, phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) directly stimulated generation of O2- from BAL cells in a concentration-dependent manner. CIS-19 (10(-7)-10(-4) M) inhibited production of O2- induced by PAF (10(-7) M) in a concentration-dependent manner with an EC50 value of 0.84 microM, but not induced by PMA (0.5 microgram/ml) or FMLP (10(-7) M). Administration of PAF (5 ng/kg, i.v.) enhanced markedly PMA (0.5 microgram/ml) and FMLP (10(-7) M)-induced generation of O2- by 80.2% and 51.3%, respectively. The enhancing effect of PAF was maximal in cells harvested 5 min after the addition of PAF and then declined to baseline level at 60 min. These responses were inhibited by administration of CIS-19 (0.5-2.5 mg/kg, i.v.) or BN 52021 (5 mg/kg, i.v.). The results indicate that CIS-19 is potent in inhibition of PAF-induced airway inflammatory response and may have therapeutic potential as an anti-inflammatory drugs.

Animals↗

PubMed1995

Sensory neuropeptides modulate cigarette smoke-induced decrease in neutral endopeptidase activity in guinea pig airways.

Cigarette smoke (CS) inhalation stimulates C-fibers to release sensory neuropeptides which mediate airway reflex responses to prevent irritants from entering the lower airways. When CS is inhaled via the upper airways, these airway defense responses may modulate the effect of CS on airway NEP activity and related airway hyperresponsiveness. To examine this possibility, we exposed guinea pigs to 1:10 diluted mid-tar cigarette smoke 100 puffs per day for 7 days and recorded pulmonary resistance of cumulative doses of neurokinin A (NKA, 10(-12)-10(-8) mol/kg, i.v.) or methacholine (Mch, 1-50 micrograms/kg, i.v.). NEP activity in the tracheobronchi was measured using fluorometric assay. Exposure of CS alone failed to alter the dose-response to NKA or Mch compared with air control. NEP activity in the airways after CS exposure was slightly but significantly lower than that of air control. Capsaicin pretreatment 1 week before CS exposure significantly shifted the dose-response curves of NKA, but not Mch, to the left and decreased NEP activity in the airways to a greater extent compared with CS exposure alone group. Capsaicin pretreatment alone failed to alter the responsiveness to NKA or NEP activity. CS also induced a significant increase in neutrophil counts in airways. Capsaicin pretreatment enhanced the effect of CS on neutrophil recruitment. We conclude that sensory neuropeptides may have a protective role in modulation of airways NEP activity downregulation induced by CS, probably by preventing CS from entering the lower airways or the chronic release of sensory neuropeptides induced by CS providing increased amount of substrata for NEP upregulation, and therefore modify the direct effect of CS on NEP activity and related airway hyperresponsiveness.

Airway Resistance↗

PubMed1995

Effect of nasal continuous positive airway pressure on methacholine-induced bronchoconstriction.

Bronchial hyper-responsiveness is a cardinal feature of asthma. To determine whether nasal continuous positive airway pressure (NCPAP) influences airway smooth muscle in response to exogenous stimuli, we examined the effect of NCPAP on aerosolized methacholine-induced bronchoconstriction in 16 stable asthmatic patients. The dose-response curve for each subject was measured by a log transformation and linear regression analysis as well as a formula fitted to the data points to obtain values for a (slope) and b (position). The PD20FEV1 significantly increased in patients receiving 8 cmH2O of NCPAP by one doubling dose compared with that in patients using sham pressure. NCPAP shifted the dose-response curves to be flatter, deviated upwards and to the right. The coefficient a, indicating bronchial reactivity, was significantly lower in patients receiving NCPAP. The coefficient b, indicating the bronchial sensitive threshold, was higher after applying NCPAP. In contrast, coefficients a and b did not change in subjects with sham pressure. NCPAP also significantly enhanced the bronchodilator effect of inhaled salbutamol in response to methacholine-induced bronchoconstriction. In summary, we have shown that NCPAP therapy improves bronchial smooth reactivity with an increase in PD20FEV1 and a reduction in the bronchial reactivity and bronchial sensitivity. Therefore, NCPAP may provide an adjuvant therapy in patients with acute bronchial asthma.

Acute Disease↗

PubMed1995

Multiple brushings with immediate Riu's stain via flexible fibreoptic bronchoscopy without fluoroscopic guidance in the diagnosis of peripheral pulmonary tumours.

BACKGROUND: Accurate diagnosis of peripheral pulmonary lesions usually relies on fluoroscopic guided procedures. As fluoroscopy is not routinely available in many respiratory units, an approach not using fluoroscopy but with a high diagnostic yield is highly desirable. METHODS: Immediate cytological examination of multiple brushings using Riu's stain, a modified Wright's stain, was performed in 38 patients with peripheral pulmonary lesions not visible at bronchoscopy. The results were compared with the final diagnoses determined by histological examination or subsequent Papanicolaou staining of cytological specimens and clinical course. RESULTS: Of the 38 patients 29 were subsequently confirmed to have a malignant tumour. Our method provided a diagnosis of malignancy in 86% of these lesions. The accuracy (91%) and sensitivity (88%) were higher for lesions > 3 cm in diameter than for those of diameter < or = 3 cm (87% and 83%). There were no false positive results. The 29 lesions correctly diagnosed as malignant by Riu's stain required significantly fewer brushings (mean (SD) 3 (2)) than the nine benign lesions (5 (4)). CONCLUSIONS: This technique provides a high diagnostic yield, avoids the need for fluoroscopy, and is probably safer than percutaneous biopsy.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed1995

Relation of bronchoalveolar lavage T lymphocyte subpopulations to rate of regression of active pulmonary tuberculosis.

BACKGROUND: Effective host defence against mycobacterial infection chiefly depends on the interactions between macrophages and T lymphocytes. This study investigated the relation of cellular components and their activity of cells obtained by bronchoalveolar lavage (BAL) from the lower respiratory tract to disease regression in patients with active pulmonary tuberculosis without HIV infection. METHODS: Clinical indices including age, sex, the presence of diabetes, fever, the presence of resistant strains of mycobacteria, the bacterial load in sputum, and disease extent on chest radiography at presentation were assessed before commencing four-drug antituberculous therapy. Twenty two patients with active pulmonary tuberculosis were divided into rapid, intermediate, and slow regression groups. Subpopulations of alveolar macrophages separated using discontinuous Percoll density gradient centrifugation and T lymphocytes (with CD3, CD4, CD8, and CD25 monoclonal antibodies) were quantified. RESULTS: There were no differences among rapid, intermediate, and slow regression groups in terms of age, sex, the presence of diabetes, the presence of resistant strains of mycobacteria, or the bacterial load in sputum. No differences were found between the groups in terms of subpopulations of alveolar macrophages or numbers of CD3 and CD4 lymphocytes. By contrast, an increase in CD8 cells was shown in the slow regression group compared with the rapid and intermediate regression groups. CD25 cell numbers were increased in the rapid regression group compared with the slow regression group. The CD4/CD8 ratio was decreased in the slow regression group compared with the rapid and intermediate regression groups and the relation between the proportion of CD25 cells and the CD4/CD8 ratio in BAL fluid was significant. CONCLUSIONS: A decreased CD4/CD8 ratio with an increase in CD8 cells in the alveolar spaces was associated with slow disease regression in patients with active pulmonary tuberculosis without HIV infection, suggesting that the balance of T lymphocyte subsets may play a central part in the modulation of host defence against mycobacterial infection.

Antitubercular Agents↗

PubMed1995

Hypereosinophilia in hemodialysis patients.

Hypereosinophilia (EO) is frequently observed in hemodialysis patients without apparent etiology. We prospectively studied hemodialysis (HD) patients during the period between May 1989 and December 1992, and divided the patients into 3 groups: non-eosinophilic control (EOC), intermittent EO (EOI), and persistent EO (EOP), according to the longterm measurements of their blood eosinophil counts. There were 91 patients enrolled in the study which were followed up for 24 months with 23 patients (25.3%) in the EOC group, 53 patients (58.2%) in EOI group, and 15 patients (16.5%) in the EOP group. There were no significant contribution of the type or reuse of the hemodialyzer to the development of EO, neither were age, serum albumin, KT/V, protein catabolic rate (PCR), or the duration of HD. The functional studies of eosinophils showed no significant difference in hypodense eosinophil distribution or eosinophilic cationic protein (ECP) levels between EOP group and EOC group. The distribution of hypodense eosinophils and serum ECP levels before and after dialysis procedure were not uniform, increasing in some but decreasing in the others. Thus the cause of EO is not merely due to the uremic state or dialysis procedures.

Adult↗

PubMed1992

The effect of endogenous nitric oxide on neurogenic plasma exudation in guinea-pig airways.

We studied the effect of endogenous nitric oxide (NO) on vagally induced plasma exudation into guinea-pig trachea and main bronchi using 125I-albumin as a plasma marker. NG-Nitro-L-arginine methyl ester (L-NAME, 1-10 mg/kg) dose dependently inhibited neurogenic plasma exudation. Intravenous phenylephrine which simulated the vasopressor effect as L-NAME (10 mg/kg) was without effect. The effect of L-NAME (5 mg/kg) was reversed by L-arginine (50 mg/kg). These results suggest that endogenous NO may contribute to neurogenic inflammation in the airways.

Animals↗

PubMed1992

K+ channel activator inhibition of neurogenic goblet cell secretion in guinea pig trachea.

A potassium (K+) channel activator, BRL 38227, inhibited goblet cell secretion in guinea-pig trachea induced by either electrical stimulation of the vagus nerves or acute inhalation of cigarette smoke, two stimuli which activate both cholinergic nerves and capsaicin-sensitive sensory nerves. BRL 38227 failed to inhibit methacholine- or substance P-induced goblet cell secretion which suggests that K+ channel activators inhibit neurogenic goblet cell secretion via a prejunctional effect on cholinergic and sensory nerves.

Animals↗

PubMed1992

Differential inhibitory effects of opioids on cigarette smoke, capsaicin and electrically-induced goblet cell secretion in guinea-pig trachea.

1. Goblet cell secretion in guinea-pig airways is under neural control. Opioids have previously been shown to inhibit neurogenic plasma exudation and bronchoconstriction in guinea-pig airways. We have now examined the effects of morphine and opioid peptides on tracheal goblet cell secretion induced by either electrical stimulation of the cervical vagus nerves, exogenous capsaicin, or acute inhalation of cigarette smoke. The degree of goblet cell secretion was determined by a morphometric method and expressed as a mucus score which is inversely related to mucus discharge. 2. Morphine, 1 mg kg-1, completely blocked goblet cell secretion induced by electrical stimulation of the vagus nerves. Morphine also inhibited the response to cigarette smoke given either at a low dose (10 breaths of 1:10 diluted in air), which principally activates cholinergic nerves, or at a high dose (20 breaths of undiluted), which activates capsaicin-sensitive sensory nerves, by 100% and 73% respectively. In contrast, morphine had no significant inhibitory effect on capsaicin-induced goblet cell secretion. The inhibitory effect of morphine was reversed by naloxone. 3. Selective mu- or delta-opioid receptor agonists, [D-Ala2, NMePhe4, Glyol5]enkephalin (DAMGO) or [D-Pen2, D-Pen5]enkephalin (DPDPE) respectively, caused a dose-related inhibition of low dose cigarette smoke-induced goblet cell discharge, with DPDPE more potent than DAMGO. A kappa-receptor agonist, trans-3,4-dichloro-N-methyl-N-(2-(1-pyrollidinyl)cyclohexyl) benzeneacetamine (U-50,488H), had no inhibitory effect. DPDPE had no inhibitory effect on goblet cell secretion induced by exogenous methacholine. 4. DAMGO dose-dependently blocked the response to high dose cigarette smoke with a maximal inhibition of 95% at 2 x 10(-7) mol kg-1. Neither DPDPE nor U-50,488H had any significant inhibitory effect. The increase in goblet cell secretion induced by exogenous substance P was not affected by DAMGO.5. We conclude that opioids inhibit neurally-mediated goblet cell secretion via actions at prejunctional delta and mu-receptors on cholinergic nerves and at mu-receptors on sensory nerve endings, and that capsaicin activation of sensory nerves is via a different mechanism from that of electrical or cigarette smoke activation.

Animals↗

PubMed1992

Cigarette smoke-induced airway goblet cell secretion: dose-dependent differential nerve activation.

We studied the effect of acute inhalation of middle-tar cigarette smoke on airway goblet cell secretion in anesthetized guinea pigs. Secretion induced by a low dose of smoke (10 breaths diluted 1:10 in air) was blocked by either hexamethonium or by filtering out the particulate phase of the smoke. The response was partially inhibited by atropine but was not inhibited by propranolol, phentolamine, or capsaicin pretreatment. Cutting the nerve supply to the airways did not inhibit the response to low-dose smoke. In contrast, goblet cell secretion induced by a high dose of cigarette smoke (20 breaths undiluted) was inhibited by capsaicin pretreatment but not by autonomic receptor blockade nor by filtering out the particulate phase. Secretion induced by the vapor phase of the high dose of cigarette smoke was blocked by capsaicin pretreatment but was not inhibited by hexamethonium. We conclude that in guinea pig airways the particulate phase of low doses of smoke activates cholinergic nerves via stimulation of parasympathetic ganglia, whereas the vapor phase of high doses of smoke activates capsaicin-sensitive sensory nerves.

Animals↗

PubMed1990

Capsaicin and sensory neuropeptide stimulation of goblet cell secretion in guinea-pig trachea.

1. We studied the effect of capsaicin and sensory neuropeptides on tracheal goblet cell secretion in anaesthetized guinea-pigs using a semi-quantitative morphometric technique whereby the magnitude of discharge of stained intracellular mucus, expressed as a mucus score (MS), was related inversely to discharge. 2. Capsaicin (i.v.) induced goblet cell secretion: a decrease of 50% in MS below control (indicative of increased secretion) was maximal at 3.3 x 10(-9) mol/kg. 3. Capsaicin-induced secretion was unaffected either by prior vagus nerve section or by pre-treatment with atropine, propranolol and phentolamine which suggests that local axon reflexes with release of sensory neuropeptides are involved in the response. 4. Intravenous substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and calcitonin gene-related peptide (CGRP) produced dose-related increases in goblet cell secretion, with SP the most potent. Doses (mol/kg) causing a 50% decrease in MS from control were 3.5 x 10(-12) for SP; 72 x 10(-10) for NKA; 1.6 x 10(-9) for NKB; and 1.2 x 10(-8) for CGRP. The maximal increase in goblet cell secretion was 75% of control and occurred with SP at 10(-10) mol/kg. 5. SP-induced mucus discharge was not inhibited by atropine or the histamine receptor antagonists mepyramine or cimetidine. 6. We conclude that in guinea-pig trachea, goblet cell secretion is under the control of capsaicin-sensitive sensory nerves and release of neuropeptides from these nerves may induce mucus discharge via tachykinin receptors of the NK-1 subtype (indicated by an order of potency of SP greater than NKA greater than NKB).

Anesthesia, General↗

PubMed1990

Neural control of goblet cell secretion in guinea pig airways.

We studied the neural control of goblet cell secretion in the lower airways of anesthetized guinea pigs using a semiquantitative morphometric technique. The magnitude of discharge of intracellular mucus was determined in histological sections of the trachea and main bronchi stained for mucus glycoproteins. Bilateral electrical stimulation of the cervical vagus nerves induced goblet cell secretion. The magnitude of the effect was dependent on the frequency, voltage, and pulse width of the stimulus, and the duration of stimulation. At 10 Hz, 5 V, and 5 ms for 3 min, there was a 62% decrease in the amount of intracellular mucus below that with sham stimulation. The secretion was blocked either by atropine or by pretreatment with capsaicin but was not significantly inhibited by idazoxan, an alpha-adrenoceptor antagonist. The magnitude of goblet cell discharge in animals pretreated with propranolol was intermediate between that in controls and that with nerve stimulation, although not significant to either. These results demonstrate that goblet cell secretion is under neural control in guinea pig airways and suggest that cholinergic, nonadrenergic-noncholinergic, and possibly adrenergic neural pathways, may contribute to the secretion.

Adrenergic alpha-Antagonists↗

PubMed1989

Pleural mesothelioma--analysis of 12 cases in Chang-Gung Memorial Hospital.

Twelve cases of pathologically proved pleural mesothelioma collected from 1983 to 1987 were analyzed retrospectively. There were 9 males, and 3 females, aged 14-76 year-old (mean 54 year-old). Eight cases were malignant mesothelioma. Four cases were benign mesothelioma. The male to female ratio in malignant tumor was 1 to 7; in benign tumor it was 1 to 1. The mean age in malignant mesothelioma was 45 year-old, and in benign mesothelioma it was 58. Of the 8 cases with malignant mesothelioma, there were 2 cases (25%) of fibrous type, 1 case (12.5%) of epithelial type, and 5 cases (62.5%) of mixed type. Asbestos exposure history was not evident in our series. Definitive diagnosis was obtained in 10 cases by thoracotomy (83%). Two cases of malignant mesothelioma were verified by pleural biopsy. The diagnostic yield is 40% for pleural biopsy, and 100% for thoracotomy. Bronchoscopic examination, percutaneous biopsy, and pleural effusion analysis were useless in making a definitive diagnosis and distinguishing from metastatic adenocarcinoma in our opinions.

Adenocarcinoma↗

PubMed1989

[Cytomegalovirus pneumonitis in renal transplantation--a case report].

Cytomegalovirus pneumonitis is a severe complication of renal transplantation. It usually occurs in the first 3-4 months after transplantation. Herein, we describe a 21 year-old male patient with chronic renal failure who received a successful cadaveric renal transplantation after regular hemodialysis three times per week for 3 years. Cyclosporin A and Methylprednisone were used for immunosuppressants after operation. The allograft kidney function improved gradually in two weeks. Serum BUN and creatinine were lowered to 25 mg/dl and 1.7 mg/dl respectively. Bacterial pneumonia developed on the 16th postoperative day. The control of pneumonia rapidly improved after the use of broad spectrum antibiotics. However, bilateral diffuse pulmonary infiltrations developed 21 days later. He received transbronchoscopic diagnostic procedures including TBLB without definite diagnosis. The final diagnosis was obtained by open lung biopsy, in which intranuclear inclusion body was found. The patient expired on the 55th postoperative day despite adjustment of immunosuppresant dosage and use of antiviral therapy.

Adult↗