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Biomedical subjects

K F Chung

Publications and source records attributed to K F Chung.

At least 163 records · Page 9Linked to original sources
PubMed1997

Inducible nitric oxide synthase after sensitization and allergen challenge of Brown Norway rat lung.

1. We studied the effects of ovalbumin (OA) sensitization and challenge on inducible nitric oxide synthase (iNOS) gene and protein expression in Brown-Norway rats in vivo. 2. By use of Northern analysis, a 4.4-kb iNOS mRNA transcript was weakly observed in control rat lung but there was a 3 fold increase in lungs sensitized to OA alone (P<0.05). In sensitized rats, four hours after exposure to OA aerosol, there was a 6 fold increase in iNOS mRNA transcript (P<0.05), which returned to baseline at 24 h. 3. Immunostaining with an anti-mouse iNOS antibody revealed some patchy staining of airway epithelium in naive rats. There were no changes in sensitized rats exposed to saline, but sensitized and OA-exposed rats showed increased expression in iNOS staining in macrophages. 4. Electrophoretic mobility shift assays of lung nuclear extracts showed a marked increase in nuclear factor-kappaB (NF-kappaB)-binding activity at 2 h after allergen exposure with return to baseline at 6, 12 and 24 h. 5. We concluded that there is increased iNOS gene and protein expression associated with increased NF-kappaB DNA-binding in lungs of sensitized and challenged rats. The increase in iNOS expression may underlie the increase in exhaled NO found after allergen challenge and may contribute to the development of allergen-induced airway hyperresponsiveness.

Allergens↗
PubMed1997

Adoptive transfer of allergen-specific CD4+ T cells induces airway inflammation and hyperresponsiveness in brown-Norway rats.

Following allergen exposure, sensitized Brown-Norway rats develop airway hyperresponsiveness (AHR) and eosinophilic inflammation together with an increase in activated T cells (CD25+) in the airways. We tested the hypothesis that CD4+ T cells are involved directly in the acquisition of AHR. Spleen T cells from animals that were injected intraperitoneally on three consecutive days with ovalbumin/Al(OH)3, showed a dose-dependent proliferative response in vitro to ovalbumin, but not to bovine serum albumin, as measured by [3H]thymidine uptake. For total T-cell transfer, spleen cells obtained from donor rats 4 days after sensitization were depleted of adherent cells by a nylon wool column separation. CD4+ and CD8+ T cells were purified by immunomagnetic beads cell separation. Recipient naive rats were injected intravenously with 50 x 10(6) total T cells, 20 x 10(6) and 5 x 10(6) CD4+ cells, and 5 x 10(6) CD8+ cells, and were exposed to ovalbumin aerosol 24 hr afterwards. After a further 24 hr, airway responsiveness to acetylcholine (ACh) was measured and provocative concentration (PC) values PC100, PC200 and PC300) (the ACh concentration needed to achieve 100, 200 and 300% increase in lung resistance above baseline) were calculated. Airway responsiveness was significantly increased in recipients of sensitized total T cells compared with recipients of cells from saline-injected donor rats (P < 0.05). There were significantly increased eosinophil major basic protein (MBP)+ cell counts/mm2 in airway submucosal tissue in the hyperreactive rats and a significant correlation was found between the number of MBP+ cells and PC100 (r = 0.75; P < 0.03) in recipients of sensitized total T cells. Purified CD4+ T cells from sensitized donors induced AHR in naive recipients (P < 0.05), while sensitized CD8+ and naive CD4+ cells failed to do so. Our data indicate that T cells may induce AHR through an eosinophilic airway inflammation and that CD4+ T cells may have a direct effect in this process in Brown-Norway rats.

Adoptive Transfer↗
PubMed1997

Interaction of ozone exposure with airway hyperresponsiveness and inflammation induced by trimellitic anhydride in sensitized guinea pigs.

The effect of prior ozone (O3) exposure on airway hyperresponsiveness and inflammation induced by trimellitic anhydride (TMA) has been investigated in TMA-sensitized guinea pigs. Airway responsiveness was measured as the concentration of acetylcholine needed to increase baseline lung resistance (RL) by 300% (PC300). Ozone (3 ppm for 3 h) caused an increase in -log PC300 at 1 h after exposure, with return of -log PC300 to control levels at 8 h. Ozone also increased baseline RL at 8 h. TMA challenge increase -log PC300 in TMA-sensitized guinea pigs at 8 h after challenge from 3.85 +/- 0.09 to 4.11 +/- 0.09. Ozone exposure prior to TMA challenge prevented the induction of airway hyperresponsiveness with a mean -log PC300 of 3.51 +/- 0.20, which was not different from that of control TMA-sensitized group. Baseline RL was significantly higher in ozone-pretreated animals after TMA challenge when compared to those of either control or challenged with TMA alone. Ozone had no effect on TMA challenge-induced BAL eosinophilia and neutrophilia. We conclude that a single exposure to ozone inhibits the increase in airway responsiveness but increases the bronchoconstrictor response induced by TMA in TMA-sensitized guinea pigs; however, the inflammatory airway response to TMA is unchanged by preexposure to ozone.

Acetylcholine↗
PubMed1997

Interaction of ozone and allergen challenges on bronchial responsiveness and inflammation in sensitised guinea pigs.

BACKGROUND: Environmental pollutants such as ozone may interact with airway responses to allergen in sensitised individuals. METHODS: We examined the effects of a single exposure to ozone (1 ppm for 1 h) on bronchial responsiveness to acetylcholine (ACh) aerosol 3 and 24 h after single ovalbumin (OA) challenge in OA-sensitised anaesthetised guinea pigs. Broncho-alveolar lavage (BAL) was performed and protein content and differential cell counts were determined. RESULTS: Ozone increased bronchial responsiveness at 3 h but not at 24 h, while OA alone had no effect. At 3 h after ozone, OA induced further, but non-significant increases in bronchial responsiveness to ACh, but at 24 h after ozone, there was enhanced responsiveness. Neutrophil counts in BAL fluid increased at 3 and 24 h after exposure to ozone alone, but there were no further increases with ozone followed by OA exposure. Protein concentration was significantly increased in the ozone and OA groups at 3 and 24 h (163.4 +/- 25.6 and 128.7 +/- 7.4 mg/ml, respectively) compared to 54.0 +/- 18.1 mg/ml in the control group (p < 0.02 and p < 0.01, respectively). CONCLUSION: Our data demonstrate an interaction of OA with ozone exposure on bronchial responsiveness; one underlying mechanism could be through damage at the endothelial-epithelial barrier.

Acetylcholine↗
PubMed1997

Role of cytokine-induced neutrophil chemoattractant (CINC) in ozone-induced airway inflammation and hyperresponsiveness.

Cytokine-induced neutrophil chemoattractant (CINC) is a rat chemokine with potent chemoattractant effects on neutrophils. We determined the involvement of CINC in ozone-induced airway neutrophilia and bronchial hyperresponsiveness (BHR) in the rat. We found a marked increase in lung CINC messenger RNA (mRNA) within 2 h after cessation of ozone exposure (1 ppm for 3 h), as measured by Northern blot analysis, whereas rats exposed to room air had no detectable CINC mRNA. Ozone exposure induced a significant neutrophilia in bronchoalveolar lavage fluid (BALF) at 24 h after exposure (air-exposed rats: 4.2 +/- 2.0 x 10(4), versus ozone-exposed rats: 16.1 +/- 3.7 x 10(4)); prior treatment with a goat anti-CINC antibody (1 mg, intravenously) suppressed the neutrophilia (3.1 +/- 0.9 x 10(4)). When administered intratracheally, the antibody (230 micrograms) partially inhibited the influx of neutrophils. The increase in bronchial responsiveness to acetylcholine observed after ozone exposure was not inhibited by the anti-CINC antibody. The anti-CINC antibody (1 mg, intravenously) also inhibited BALF neutrophilia induced by exposure to a higher concentration of ozone (3 ppm, 3 h), without an effect on BHR. CINC is an important chemokine causing ozone-induced neutrophil chemoattraction, but is not involved in the induction of ozone-induced BHR. The neutrophil is unlikely to contribute to BHR in this model.

Acetylcholine↗
PubMed1997

Inhibition of PAF-induced gas exchange defects by beta-adrenergic agonists in mild asthma is not due to bronchodilation.

Salbutamol inhibits neutropenia, increased airway resistance, and gas exchange abnormalities provoked by platelet-activating factor (PAF) challenge in normal persons. To further explore the intriguing dissociation between spirometric abnormalities and gas exchange defects shown in patients with asthma, we investigated whether the salbutamol-induced improvement in gas exchange disturbances after PAF is the result of bronchodilation by comparing this effect with that of ipratropium bromide. We hypothesized that ipratropium bromide, an anticholinergic agent without vascular effects, should block PAF-induced bronchoconstriction but not interfere with its systemic, neutropenic, and gas exchange effects. We studied eight nonsmokers with mild asthma (26 +/- 2.0 SE yr of age) who, prior to PAF challenge (18 micrograms), inhaled either ipratropium bromide (80 micrograms) or salbutamol (300 micrograms) in a randomized, double-blind, crossover fashion 1 wk apart. Peripheral blood neutrophils, respiratory system resistance (Rrs), arterial blood gases and ventilation-perfusion (VA/Q) inequalities were measured 5, 15, and 45 min after PAF. Compared with pretreatment with salbutamol, ipratropium bromide also blocked the increase of respiratory system resistance (Rrs) but did not prevent facial flushing and neutropenia (p < 0.03) at 5 min nor the decrease of PaO2 (p = 0.08 and 0.05), the increase of AaPO2 (p < 0.02 each), and the deterioration of VA/Q relationships (p < 0.05 each) at 5 and 15 min, respectively. This functional pattern was similar to that observed previously in normal subjects and in nonpremedicated asthmatic patients after PAF, with return to baseline values at 45 min. By contrast, salbutamol blocked PAF-induced increased Rrs, in addition to all the other PAF-induced abnormalities. These findings indicate that, in patients with mild asthma, salbutamol inhibits PAF-induced neutropenia and gas exchange abnormalities by mechanisms involving other than airway smooth muscle narrowing, possibly by acting on both the bronchial and pulmonary circulations.

Adrenergic beta-Agonists↗
PubMed1997

Kyphoscoliosis and bronchial torsion.

STUDY OBJECTIVE: Severe idiopathic scoliosis is associated with respiratory failure. This usually is secondary to restrictive airway disease and reduced vital capacity. Patients may also suffer from an increase in airway resistance when severe kyphoscoliosis is present. SETTING: Three patients (two of whom required assisted ventilation) with varying degrees of kyphoscoliosis presented with moderate to severe breathing difficulties. INTERVENTION: Bronchoscopic examination of these patients showed evidence of torsion with secondary obstruction of the central airways. RESULTS: The airway obstruction was notable for its slit-like appearance, for the normality of the mucosa at the site of the obstruction, for the relative ease through which an instrument could traverse the obstruction, and once the retained secretions had been cleared, for the preservation of normal anatomy of the distal airways. The insertion of metal prostheses to stent the areas of obstruction prompted an impressive improvement in respiratory status, radiologic findings, and spirometric criteria in each case. Improvement has been maintained over a maximum follow-up period of 4 years. CONCLUSION: Severe kyphoscoliosis can lead to bronchial torsion and obstruction of the central airways. Patients should be assessed by bronchoscopy to exclude this deformity or any other cause of obstruction. The use of a metal endobronchial stent has been effective in both the immediate and long-term period.

Adult↗
PubMed1997

How are psychotic symptoms perceived? A comparison between patients, relatives and the general public.

OBJECTIVE: The aim of this study is to compare patients with schizophrenia with their relatives and the general public in their attitudes towards schizophrenic psychotic symptoms. METHOD: We used a case vignette depicting a person with typical schizophrenic psychotic symptoms and compared the attitudes of 44 inpatients and 47 outpatients with schizophrenia, 48 of their relatives and 43 members of the general public. We also compared the attitudes of patients with schizophrenia to their own symptoms and the symptoms described in the vignette. RESULTS: Subjects from the general public tended not to recognise psychotic symptoms as features of mental illness and tended not to consider drug treatment and hospitalisation as required. Sex, education level as well as previous contact with the mentally ill were found to be significant determinants of attitude. The levels of symptom awareness in patients with schizophrenia and their relatives are higher but still relatively low. In addition, we found that patients with schizophrenia who correctly appraised psychotic symptoms in another person were also aware of their own mental symptoms and need of treatment. CONCLUSIONS: The level of recognition of psychotic symptoms and awareness of a need for treatment are low in the general public, as well as in patients with schizophrenia and their relatives. These findings are discussed in relation to the assessment of insight in patients and a need for psychoeducational programs for each group.

Adolescent↗
PubMed1997

Benzodiazepine prescribing trend after its inclusion as a dangerous drug under the Hong Kong Dangerous Drugs Ordinance.

Since January 1992, all benzodiazepines have been classified as dangerous drugs under the Dangerous Drugs Ordinance in Hong Kong. This legislative provision requires medical practitioners and pharmacists to keep a detailed record of their prescriptions of benzodiazepines The present study looks at the impact of the provision on prescribing trends in the Hong Kong population and in a general psychiatric clinic. A comparison of the 1991 (baseline level) and 1994 figures reveals a 50% and a 10% reduction in the average yearly number of benzodiazepine prescriptions per person in the Hong Kong population and in the general psychiatric clinic, respectively. In particular, triazolam prescriptions had the greatest reduction. The findings are discussed in light of the possible changes of prescribing practice by medical practitioners after the new legislative provision came into effect.

Journal Article↗
PubMed1997

Recurrent hypersomina: a case report with polysomnographic findings.

Recurrent hypersomnia is an uncommon clinical problem that can be misdiagnosed and mistreated. I report a case of idiopathic recurrent hypersomnia. The clinical features, differential diagnoses, polysomnographic findings, possible aetiologies, and treatment are discussed.

Journal Article↗
PubMed1996

[Pharmacological specificities and modalities of prescriptions for corticoids for asthmatic adults].

The efficacy of corticosteroids in asthma has been recognized over 40 years ago. Since that time, the advent of inhaled forms has further improved the therapeutic of these drugs which are now recognized as the fundamental treatment for asthma, and described in detail by national and international consensus. Based on a large body of literature, it can now be recommended to prescribe inhaled corticosteroids for symptomatic asthma patients. Long-term treatment is required and dosage not exceeding 1000 micrograms/d (beclometasone dipropionate equivalent) in adults are safe. Differences in the pharmacological characteristics of the various systematic and inhaled corticosteroids can be used to adapt treatment and administration route to each patient and achieve good patient compliance with optimal therapeutic efficacy.

Administration, Inhalation↗
PubMed1996

Mechanisms of impaired beta-adrenoceptor-induced airway relaxation by interleukin-1beta in vivo in the rat.

We studied the in vivo mechanism of beta-adrenergic receptor (beta-AR) hyporesponsiveness induced by intratracheal instillation of interleukin-1beta (IL-1beta, 500 U) in Brown-Norway rats. Tracheal and bronchial smooth muscle responses were measured under isometric conditions ex vivo. Contractile responses to electrical field stimulation and to carbachol were not altered, but maximal relaxation induced by isoproterenol (10(-6)-10(-5) M) was significantly reduced 24 h after IL-1beta treatment in tracheal tissues and to a lesser extent, in the main bronchi. Radioligand binding using [125I]iodocyanopindolol revealed a 32+/-7% reduction in beta-ARs in lung tissues from IL-1beta-treated rats, without any significant changes in beta2-AR mRNA level measured by Northern blot analysis. Autoradiographic studies also showed significant reduction in beta2-AR in the airways. Isoproterenol-stimulated cyclic AMP accumulation was reduced by IL-1beta at 24 h in trachea and lung tissues. Pertussis toxin reversed this hyporesponsiveness to isoproterenol but not to forskolin in lung tissues. Western blot analysis revealed an IL-1beta-induced increase in Gi(alpha) protein expression. Thus, IL-1beta induces an attenuation of beta-AR-induced airway relaxation through mechanisms involving a reduction in beta-ARs, an increase in Gi(alpha) subunit, and a defect in adenylyl cyclase activity.

Animals↗
PubMed1996

Pro-oxidant iron is present in human pulmonary epithelial lining fluid: implications for oxidative stress in the lung.

Bronchoalveolar lavage (BAL) provides a sample of lung surface lining fluid. Several pulmonary diseases appear to involve tissue damage caused by reactive oxygen species generated by inhaled oxidants or by phagocytic cells activated within the lung. We show that BAL from normal healthy controls contain chelatable redox active iron that is pro-oxidant towards free radical reactions. Adult patients with the acute respiratory distress syndrome (ARDS) are known to he under severe oxidative stress and to have high mortality rates. Patients who survived ARDS were found to have chelatable redox active iron in their lung fluid, whereas nonsurvivors had no such iron present. Severe lung leak in nonsurvivors was paradoxically associated with increased levels of transferrin and iron-binding antioxidant activity. We suggest that the presence of pro-oxidant iron in normal lung fluid is an important factor which makes the lung vulnerable to oxidative stress.

Adolescent↗
PubMed1996

Ozone induction of cytokine-induced neutrophil chemoattractant (CINC) and nuclear factor-kappa b in rat lung: inhibition by corticosteroids.

We determined in rat lung whether ozone exposure was associated with the expression of the chemokine, cytokine-induced neutrophil chemoattractant (CINC), and of the transcription factor, NF-kappa B. CINC mRNA expression peaked at 2 h after cessation of ozone exposure, and returned to basal levels by 24 h. DNA-binding activity of NF-kappa B showed a marked increase after ozone, maximal at 2 h. Dexamethasone inhibited CINC mRNA and NF-kappa B expression, together with neutrophilic inflammation. Our data supports the concept that ozone leads to NF-kappa B activation which increases CINC mRNA expression. These series of events could lead to neutrophilic inflammation.

Animals↗
PubMed1996

The effect of inhaled K+ channel openers on bronchoconstriction and airway microvascular leakage in anaesthetised guinea pigs.

Since orally administered K+ channel openers may have cardiovascular side effects, it is possible that inhaled administration would be preferred for the treatment of asthma. We have investigated whether inhaled levcromakalim and HOE 234 inhibit histamine-induced bronchoconstriction and airway plasma exudation in anaesthetised guinea pigs. We have also investigated whether inhaled HOE 234 inhibits the bronchoconstriction and plasma exudation induced by vagus nerve stimulation, which is due to the release of tachykinins from sensory nerves. Lung resistance was measured by airway resistance (RL) computed from airway and transpulmonary pressures and plasma exudation by measurement of Evans blue dye extravasation. Inhaled levcromakalim (25 mu g/ml) had a short duration of action, being effective against histamine-induced bronchoconstriction 2 min after pretreatment, but not at 10 min. Inhaled HOE 234 (25 mu g/ml) was similarly effective against histamine-induced bronchoconstriction but had a longer duration of action. Inhaled levcromakalim partially attenuated histamine-induced plasma extravasation in small airways, but not in the trachea or main bronchi, whereas inhaled HOE 234 had no effect. HOE 234 protected against non-adrenergic non-cholinergic nerve-induced bronchoconstriction, but had no effect on neurogenic- or substance P-induced plasma extravasation in the airway. Inhaled K+ channel openers protect against induced bronchoconstriction, but provide little or no protection against plasma exudation, possibly because of an increase in airway blood flow. In addition, inhaled HOE 234 had no effect on neurogenic leakage, suggesting that its vagal inhibitory effect on bronchoconstriction was on airway smooth muscle, rather than on release of neuropeptides from sensory nerves.

Administration, Inhalation↗
PubMed1996

Lack of a role for bradykinin in allergen-induced airway microvascular leakage and bronchoconstriction in the guinea pig.

We have investigated the role of bradykinin in allergen-induced airway microvascular leakage and bronchoconstriction in sensitized guinea pigs. We used a selective bradykinin B2 receptor antagonist, HOE140, which has been shown to prevent the airway effects induced by bradykinin. Lung resistance (RL) was measured for 6 min after challenge with allergen. Extravasation of Evans blue dye into airway tissues was used as an index of the airway microvascular leakage. Aerosolized ovalbumin (5 mg/ml, 30 breaths) induced a significant increase in RL and leakage of dye in the trachea, main bronchi and intrapulmonary airways in the ovalbumin-sensitized guinea pigs. HOE140 given by inhalation (200 microM, 60 breaths) had no effect on the airway microvascular leakage and bronchoconstriction induced by the allergen. I.v. HOE140 (200 nmol/kg) did not significantly inhibit these airway responses. We conclude that bradykinin-mediated mechanism may not play a significant role in airway microvascular leakage or bronchoconstriction induced by allergen.

Administration, Inhalation↗
PubMed1996

Effects of nedocromil sodium on airway neurogenic mechanisms.

Evidence shows that nedocromil sodium has a major inhibitory effect on sensory nerve activation. Animal models in which inhibitory effects have been demonstrated include bradykinin- or ovalbumin-induced plasma extravasation; cigarette smoke- or sulfur dioxide-induced bronchial hyperresponsiveness and increase in inflammatory cells in the airway; and bradykinin-induced airway vasodilatation and nasal mucosal edema. Nedocromil sodium has prevented the edema in human skin induced by substance P and neurokinin A, and, in the isolated rabbit trachea, has prevented substance P-induced potentiation of cholinergic neural responses at preganglionic (but not postganglionic) sites. In vitro, the drug also has inhibited nonadrenergic noncholinergic bronchoconstriction in guinea pig bronchi. Although a protective effect against citric acid-induced cough in the dog has been reported, no data are available from models of enhanced cough reflex, such as that in asthma. Inhibition of sensory nerve activation and prevention of tachykinin release by nedocromil sodium probably contribute to its beneficial effects in the treatment of asthma.

Animals↗