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Biomedical subjects

K F Chung

Publications and source records attributed to K F Chung.

At least 73 records · Page 4Linked to original sources
PubMed2001

Interleukin-5 in growth and differentiation of blood eosinophil progenitors in asthma: effect of glucocorticoids.

1. There are increased numbers of circulating CD34(+) progenitor cells for eosinophils in patients with atopic asthma, with a further increase following allergen exposure or spontaneous worsening of asthma. We investigated the expression of IL-5 and IL-5Ralpha receptor in circulating CD34(+) progenitor cells in allergic asthmatics and the effects of corticosteroids. 2. Using double-staining techniques, up to 50% of CD34(+) cells expressed intracellular IL-5, and by RT - PCR, there was significant expression of IL-5 mRNA. When cultured in a semi-liquid methylcellulose medium, there were more eosinophil colony-forming units grown from asthmatic non-adherent mononuclear cell depleted of T cells in the presence of the growth factors GM-CSF, SCF and IL-3, but not of IL-5. 3. An anti-IL-5Ralpha receptor antibody and an anti-sense IL-5 oligonucleotide reduced the number of eosinophil colony forming units. No IL-5 mRNA or protein expression on T cells was observed in asthmatics or normal subjects. In the presence of growth factors including IL-5, there were significantly greater colony numbers with eosinophilic lineage grown from either asthmatics or normal subjects. 4. Dexamethasone (10(-6) M) suppressed IL-5 mRNA and protein expression in CD34(+) cells, and reduced eosinophil colony-forming units in asthmatics, but not in normal subjects. Dexamethasone did not change the expression of IL-5Ralpha on CD34(+) cells. 5. We conclude that there is increased expression of IL-5 on blood CD34(+) cells of patients with asthma and that this expression may auto-regulate eosinophilic colony formation from these progenitor cells. Corticosteroids inhibit the expression of IL-5 in circulating CD34(+) progenitor cells.

Adult↗
PubMed2001

Decreased T lymphocyte infiltration in bronchial biopsies of subjects with severe chronic obstructive pulmonary disease.

BACKGROUND: Studies on the inflammatory process in the large airways of patients with mild/moderate COPD have shown a prevalent T lymphocyte and macrophage infiltration of the bronchial mucosa. However, bronchial inflammation in more severe disease has not been extensively studied. OBJECTIVE: The aim of the present study was to characterize the lymphocyte infiltration in the bronchial mucosa of subjects with severe, compared to mild, COPD, and to examine the relationship between airflow limitation and T lymphocyte numbers in the bronchial mucosa. METHODS: We examined bronchial biopsies obtained from nine smokers with severe airflow limitation, nine smokers with mild/moderate airflow limitation and 14 smokers with normal lung function. Immunohistochemical methods on cryostat sections were used to assess the number of CD3+, CD4+, CD8+ cells and the number of CD3+ cells coexpressing the chemokine receptor CCR5 (CCR5+CD3+) in the subepithelium. RESULTS: Subjects with severe COPD had lower numbers of CD3+, CD8+ and CCR5+CD3+ cells than mild/moderate COPD (P < 0.012, P < 0.02 and P < 0.02, respectively) and control smokers (P < 0.015, P < 0.005 and P < 0.015, respectively). In subjects with airflow limitation the number of CD3+ and CD8+ cells was inversely correlated with the degree of airway obstruction (r = 0.59, P < 0.015 and r = 0.52, P < 0.032, respectively). CONCLUSIONS: Bronchial inflammation in severe COPD is characterized by lower numbers of CD3+ and CD8+ cells and decreased numbers of CD3+ cells coexpressing the chemokine receptor CCR5. T lymphocyte infiltration is inversely correlated with the degree of airflow limitation.

Aged↗
PubMed2001

Stimulus dose titration for electroconvulsive therapy.

UNLABELLED: Stimulus dose titration for electroconvulsive therapy (ECT), the method to determine seizure threshold accurately, has not been commonly practiced. We describe our early experience of dose titration in 22 Chinese patients and compare seizure thresholds measured by dose titration with values predicted by the formula-based 'half-age' METHOD: Seizure thresholds, as measured by dose titration, varied fourfold among our sample and the average value was 105.5 mC or 16.7 J. At the titration session, 27% of patients had seizures after a single stimulation and 37% had seizures after two stimulations. Only one patient required four stimulations to induce a seizure. No patient had significant adverse events associated with the dose titration procedure. The 'half-age' method in average overestimated seizure thresholds by 44% when compared with that measured by dose titration and in 23% of our sample, the overestimation was more than 100%. The pros and cons of dose titration and 'half-age' prediction method will be discussed. Our early experience suggests that dose titration could be performed in the majority of patients receiving ECT.

Adult↗
PubMed2001

Protease-activated receptors in human airways: upregulation of PAR-2 in respiratory epithelium from patients with asthma.

BACKGROUND: Protease-activated receptors (PARs), which are G protein-coupled receptors that are activated after proteolytic cleavage of the amino terminus of the receptor, are likely to play a major role in airway inflammation. PARs are activated by endogenous proteases, including thrombin (PAR-1, -3, and -4) and tryptase (PAR-2 and -4), both of which are present in inflamed airways. OBJECTIVE: The purpose of this study was to compare the expression and distribution of PARs in biopsy specimens obtained from asthmatic and normal subjects and to examine the effect of inhaled corticosteroids on PAR expression. METHODS: Biopsy specimens were obtained from 10 normal and 20 asthmatic patients, and sections were stained for PAR-1, -2, -3, and -4 through use of specific antibodies. Staining was scored semiquantitatively for both intensity and distribution. RESULTS: Staining for all PARs was seen on the epithelium and smooth muscle in biopsy specimens from both normal and asthmatic subjects. In the epithelium, PAR-1 and -3 staining appeared to be apically concentrated, whereas PAR-2 and -4 staining was more diffuse. In normal subjects, epithelial staining intensity of PAR-1 and -3 was significantly greater than for PAR-4 (P < .05). Staining for PAR-1, -3, and -4 in biopsy specimens from asthmatic subjects was similar to that in specimens from normal subjects, irrespective of whether the former were using inhaled corticosteroids. However, PAR-2 staining in asthmatic epithelium was significantly increased in comparison with normal epithelium. Expression of PARs in airway smooth muscle did not differ between groups. CONCLUSION: Asthma per se is associated with increased PAR-2 expression in bronchial epithelium. Importantly, staining was not influenced by inhaled corticosteroids. These results suggest that PAR-2 might be involved in airway inflammation.

Administration, Inhalation↗
PubMed2001

Initial seizure threshold of bilateral electroconvulsive therapy in Chinese.

INTRODUCTION: This preliminary study examined the initial seizure threshold for bilateral electroconvulsive therapy (ECT) in Chinese and the correlates of this seizure threshold. METHOD: Fifty-four patients underwent stimulus dose titration in a standardized protocol. RESULTS: The mean initial seizure threshold was 117 mC (range 48-403 mC). Stepwise regression analysis showed that age, body mass index, and gender were independently related to seizure threshold and accounted for 36, 7, and 6% of its variance, respectively. Determination of a relationship between gender and seizure threshold was limited by the higher starting electrical dosage in men. DISCUSSION: This preliminary study suggests that the seizure threshold for bilateral ECT in Chinese is comparable with that in the Western population. Our finding that body mass index is related to seizure threshold has not been reported previously. We also propose several differences between bilateral and unilateral ECT in the determinants of seizure threshold.

Adolescent↗
PubMed2001

Evidence for systemic rather than pulmonary effects of interleukin-5 administration in asthma.

BACKGROUND: Interleukin 5 (IL-5) has an important role in mobilisation of eosinophils from the bone marrow and in their subsequent terminal differentiation. A study was undertaken to determine whether inhaled and intravenous IL-5 could induce pulmonary eosinophilia and bronchial hyperresponsiveness (BHR) independently of these effects. METHODS: Nine mild asthmatics received inhaled (15 microg) or intravenous (2 microg) IL-5 or placebo in random order in a double blind, crossover study. Blood samples were taken before and at 0.5, 1, 2, 3, 4, 5, 24, and 72 hours following IL-5 or placebo, and bronchial responsiveness (PC(20) methacholine) and eosinophil counts in induced sputum were determined. RESULTS: Serum IL-5 levels were markedly increased 30 minutes after intravenous IL-5 (p=0.002), and sputum IL-5 levels increased 4 and 24 hours after inhaled IL-5 (p<0.05). Serum eotaxin was raised 24 hours after intravenous IL-5 but not after inhaled IL-5 or placebo. Blood eosinophils were markedly reduced 0.5-2 hours after intravenous IL-5 (p<0.05), followed by an increase at 3, 4, 5, and 72 hours (p<0.05). Sputum eosinophils rose significantly in all three groups at 24 hours but there were no differences between the groups. Bronchial responsiveness was not affected by IL-5. CONCLUSION: The effects of IL-5 appear to be mainly in the circulation, inducing peripheral mobilisation of eosinophils to the circulation without any effect on eosinophil mobilisation in the lungs or on bronchial responsiveness.

Administration, Inhalation↗
PubMed2001

Effects of prostaglandin E2 and cAMP elevating drugs on GM-CSF release by cultured human airway smooth muscle cells. Relevance to asthma therapy.

Human airway smooth muscle (HASM) cells release granulocyte macrophage-colony stimulating factor (GM-CSF) and express cyclooxygenase (COX)-2 (resulting in the release of prostaglandin [PG] E2) after stimulation with cytokines. Because COX-2 activity can regulate a number of inflammatory processes, we have assessed its effects, as well as those of agents that modulate cyclic adenosine monophosphate (cAMP), on GM-CSF release by HASM cells. Cells stimulated with a combination of proinflammatory cytokines (interleukin-1beta and tumor necrosis factor-alpha each at 10 ng/ml) for 24 h released significant amounts of PGE2 (measured by radioimmunoassay) and GM-CSF (measured by enzyme-linked immunosorbent assay). Indomethacin and other COX-1/COX-2 inhibitors caused concentration-dependent inhibitions of PGE2 concomitantly with increases in GM-CSF formation. Addition of exogenous PGE2 or the beta2-agonist fenoterol, which increase cAMP, to cytokine-treated HASM cells had no effect on GM-CSF release unless COX activity was first blocked with indomethacin. The type 4 phosphodiesterase inhibitors rolipram and SB 207499 both caused concentration-dependent reductions in GM-CSF production. Thus, when HASM cells are activated with cytokines they release PGE2, which acts as a "braking mechanism" to limit the coproduction of GM-CSF. Moreover, agents that elevate cAMP also reduce GM-CSF formation by these cells.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

University students' attitudes towards mental patients and psychiatric treatment.

BACKGROUND: Public attitudes towards mental patients and psychiatric treatment are mostly unfavorable. Mental patients tend to conceal their illness or selectively disclose their treatment histories to someone they trust. AIMS: To examine the university students' attitudes towards different information regarding a person labeled as mentally ill. METHODS: We designed seven descriptions of a mentally ill person of varying past and current treatment histories and randomly assigned 308 university undergraduates to read one of the descriptions. Subjects rated their willingness to interact with the hypothetical case using a 19-item social distance scale. RESULTS: Greater social distance was associated with non-medical field of study, no previous contact with the mentally ill and female gender. Subjects without previous contact with mentally ill individuals kept greater distance from a discharged mental patient receiving psychiatric care than a mental patient who did not require medications nor psychiatric follow-up. In contrast, respondents who had previous contact with the mentally ill were more willing to interact with a discharged mental patient receiving psychiatric care comparing with a person labeled as mentally ill alone and a mental patient who had never been admitted to hospital. CONCLUSIONS: Implications of our findings in clinical management and designing stigma-reducing programme are discussed.

Adult↗
PubMed2001

Expression of GATA family of transcription factors in T-cells, monocytes and bronchial biopsies.

GATA-binding proteins are a subfamily of zinc finger transcription factors with six members (GATA-1-6) that interact with the GATA deoxyribonucleic acid (DNA) sequence. This sequence is found in the regulatory regions of many genes including those encoding T-helper 2 (Th2)-like cytokines, receptors, adhesion molecules and enzymes, which may be important in the pathogenesis of bronchial asthma. The expression of GATA-3, 4 and -6 was investigated in peripheral blood T-lymphocytes and monocytes and bronchial biopsies from 11 normal subjects and 10 steroid-naive asthmatic patients. Using Western blot analysis, T-cells from asthmatic subjects expressed 5 times the level of GATA-3 compared to that in normals. Confocal microscopy indicated that GATA-3 expression was both nuclear and cytoplasmic. GATA DNA binding complex containing GATA-3 was elevated in Th2 cells as determined by electrophorectic mobility shift assay. In contrast, monocytes from normal and asthmatic subjects expressed GATA-4 and -6 in equal amounts, but no GATA-3 was found. Using immunohistochemistry in bronchial biopsies, epithelial cells expressed high levels of GATA-3, GATA-4 and GATA-6 proteins. Comparison of Western blots of bronchial biopsies showed no significant differences between normal and asthmatic subjects. In conclusion, the increased expression of GATA-3 in asthmatic T-cells may underlie augmented T-helper 2-like cytokines in this disease. However, the unaltered GATA-3 expression in epithelial cells suggests a distinct role for GATA-3 in these cells unrelated to T-helper 2-like cytokine release. Finally, no evidence was found for an increased expression of GATA-4 and GATA-6 in asthma.

Adult↗
PubMed2001

"Haemoxygenase-1 induction and exhaled markers of oxidative stress in lung diseases", summary of the ERS Research Seminar in Budapest, Hungary, September, 1999.

In recent years, there has been increasing interest in noninvasive monitoring of airway inflammation and oxidative stress. Several volatile and nonvolatile substances can be measured in exhaled breath and have been suggested as potential biomarkers of these events. Exhaled gases, including carbon monoxide (CO), alkanes (ethane, pentane), and substances measured in breath condensate, such as hydrogen peroxide (H2O2) and isoprostanes were all suggested as potential markers of oxidative stress in the lung. A European Respiratory Society (ERS) International Research Seminar entitled "Haemoxygenase-1 induction and exhaled markers of oxidative stress in lung diseases" was organized by the Airway Regulation and Provocation Group of the Clinical Allergy and Immunology Assembly in Budapest, Hungary in September, 1999 to integrate the latest knowledge on these issues and accelerate further improvement in this area. During this 2-day event several issues were raised about: the use and standardization of measurements in exhaled breath; problems of measuring expired H2O2 and other mediators in breath condensate; role and regulation of haemoxygenase (HO)-1 in the lung; and conditions and factors influencing exhaled CO. This report is a summary of the main presentations at the seminar, together with the current areas of research in this rapidly expanding field.

Antioxidants↗
PubMed2001

A community study of sleep-disordered breathing in middle-aged Chinese men in Hong Kong.

BACKGROUND: Sleep-disordered breathing (SDB) in Asian populations is being increasingly recognized. This study investigated the prevalence of SDB in Chinese middle-aged office-based male workers in Hong Kong. METHODS: Sleep questionnaires were distributed to 1,542 men (age range, 30 to 60 years), and 784 questionnaires were returned. Subsequently, full polysomnographic (PSG) examinations were conducted in 153 questionnaire respondents. Subjects with an apnea-hypopnea index (AHI) > or =5 were recalled for clinical assessment. RESULTS: Questionnaire respondents were similar in age and body mass index (BMI) to the general community in the target age range and gender. Habitual snoring was reported by 23% of this cohort and was associated with excessive daytime sleepiness (EDS), hypertension, witnessed abnormal breathing pattern, BMI, and leg movements during sleep. Allowing for subject bias in undergoing PSG, the estimated prevalence of SDB and obstructive sleep apnea syndrome (OSAS) (defined as SDB in the presence of EDS) at various AHI cutoff threshold values was 8.8% and 4.1% (AHI > or =5), 6.3% and 3.2% (AHI > or =10), and 5.3% and 3.1% (AHI > or =15). Multiple stepwise logistic regression analysis identified BMI, habitual snoring, time taken to fall asleep, and age as predictors of SDB at AHI > or =5. Analysis of anthropometric parameters indicated that the relative risk of OSAS attributable to obesity was less than in white subjects. CONCLUSION: This community-based study of sleep apnea among middle-aged men in Hong Kong using full PSG demonstrated an estimated prevalence of OSAS (AHI > or =5 and EDS) at 4.1%. Increasing BMI and age were associated with SDB, although factors other than adiposity may also have an important pathogenic role in OSA in Chinese subjects.

Adult↗
PubMed2001

Pathophysiological mechanisms of asthma. Application of cell and molecular biology techniques.

Asthma is a common increasing and relapsing disease that is associated with genetic and environmental factors such as respiratory viruses and allergens. It causes significant morbidity and mortality. The changes occurring in the airways consist of a chronic eosinophilic and lymphocytic inflammation, together with epithelial and structural remodeling and proliferation, and altered matrix proteins, which underlie airway wall narrowing and bronchial hyperresponsiveness (BHR). Several inflammatory mediators released from inflammatory cells such as histamine and cysteinyl-leukotrienes induce bronchoconstriction, mucus production, plasma exudation, and BHR. Increased expression of T-helper 2 (Th2)-derived cytokines such as interleukin-4 and 5 (IL-4, 5) have been observed in the airway mucosa, and these may cause IgE production and terminal differentiation of eosinophils. Chemoattractant cytokines (chemokines) such as eotaxin may be responsible for the chemoattraction of eosinophils to the airways. The initiating events are unclear but may be genetically determined and may be linked to the development of a Th2-skewed allergen-specific immunological memory. The use of molecular biology techniques on tissues obtained from asthmatics is increasing our understanding of the pathophysiology of asthma. With the application of functional genomics and the ability to transfer or delete genes, important pathways underlying the cause if asthma will be unraveled. The important outcome of this is that new preventive and curative treatments may ensue.

Animals↗
PubMed2001

Cytokines in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic obstruction of expiratory flow affecting peripheral airways, associated with chronic bronchitis (mucus hypersecretion with goblet cell and submucosal gland hyperplasia) and emphysema (destruction of airway parenchyma), together with fibrosis and tissue damage, and inflammation of the small airways. Cytokines are extracellular signalling proteins. Increased levels of interleukin (IL)-6, IL-1beta, tumour necrosis factor-alpha (TNF-alpha) and IL-8 have been measured in sputum, with further increases during exacerbations, and the bronchiolar epithelium over-expresses monocyte chemotactic protein (MCP)-1 and IL-8. IL-8 can account for some chemotactic activity of sputum, and sputum IL-8 levels correlate with airway bacterial load and blood myeloperoxidase levels. The expression of chemokines such as regulated on activation, normal T-cell expressed and secreted (RANTES) may underlie the airway eosinophilia observed in some COPD patients. Cytokines may be involved in tissue remodelling. TNF-alpha and IL-1beta stimulate macrophages to produced matrix metalloproteinase-9 (MMP-9), and bronchial epithelial cells to produce extracellular matrix glycoproteins such as tenascin. Increased expression of transforming growth factor-beta (TGFbeta) and of epidermal growth factor (EGF) occurs in the epithelium and submucosal cells of patients with chronic bronchitis. TGFbeta and EGF activate proliferation of fibroblasts, while activation of the EGF receptor leads to mucin gene expression. The cytokine profile seen in chronic obstructive pulmonary disease is different from that observed in asthma. The role of these cytokines needs to be defined and there is a potential for anticytokine therapy in chronic obstructive pulmonary disease.

Cytokines↗
PubMed2000

Ceramide induction of COX-2 and PGE(2) in pulmonary A549 cells does not involve activation of NF-kappaB.

Ceramide is generated by the hydrolysis of membrane sphingomyelin by sphingomyelinase (SMase) and is implicated in multiple signaling pathways, including activation of NF-kappaB. As NF-kappaB is pivotal in the expression of numerous genes associated with airway inflammation and asthma, the effects of ceramide and SMase were examined in human pulmonary A549 cells. Ceramide and SMase both induced cyclooxygenase (COX)-2 protein expression and stimulated PGE(2) release. However, neither ceramide nor SMase induced NF-kappaB DNA-binding, loss of IkappaBalpha, or NF-kappaB-dependent transcription. Both ceramide and SMase were efficient inducers of the extracellular regulated kinase (ERK), but not Jun N-terminal kinase (JNK) or p38 mitogen-activated protein kinase. Since ERK is implicated in arachidonic acid availability, these data partly explain the ability of ceramide to induce PGE(2) release. However, as ERK is not required for IL-1beta-dependent induction of COX-2, the mechanism of ceramide and SMase induction of COX-2 remains unclear.

Bridged-Ring Compounds↗
PubMed2000

Involvement of haemoxygenase-1 in ozone-induced airway inflammation and hyperresponsiveness.

Haemoxygenase catalyses the degradation of haem to bilirubin, and the inducible form of haemoxygenase, haemoxygenase-1, is highly induced in response to oxidative stress in vitro. The effect of haemoxygenase-1 in oxidant stress in vivo is not known. We determined the effect of exposure to ozone on haemoxygenase-1 expression, and the modulation of haemoxygenase-1 expression on ozone-induced lung neutrophilia and bronchial hyperresponsiveness in rats. Ozone caused a significant induction of lung haemoxygenase-1. Pretreatment of rats with haemoglobin, a potent inducer of haemoxygenase-1, resulted in a large induction of haemoxygenase-1 expression, and inhibited ozone-induced neutrophilia and bronchial hyperresponsiveness. Tin protoporphyrin, a competitive inhibitor of haemoxygenase, reduced the expression of haemoxygenase-1 induced by haemoglobin. It enhanced ozone-induced neutrophilia, but not the bronchial hyperresponsiveness, and reduced the protective effect of haemoglobin. Overall, there was an association between bronchial hyperresponsiveness and the neutrophilic response. These data indicate that haemoxygenase-1 plays an important role in modulating the effects of an oxidant, such as ozone in the lungs.

Acetylcholine↗
PubMed2000

Use of the Epworth Sleepiness Scale in Chinese patients with obstructive sleep apnea and normal hospital employees.

OBJECTIVE: To determine the use of the Epworth Sleepiness Scale (ESS) in Chinese patients with obstructive sleep apnea syndrome (OSA) and normal hospital employees. METHODS: Our sample consisted of 61 healthy controls and 100 patients with OSA. The test-retest reliability, internal consistency, and concurrent validity of the Chinese version of the ESS were analyzed. We also compared the ESS scores between controls and patients, studied the association between the ESS score and the apnea-hypopnea index (AHI) and minimum oxygen saturation (mO(2)), and examined to what extent the ESS score was predictive of mean sleep latency of the Multiple Sleep Latency Test (MSLT). RESULTS: The Chinese version of the ESS was found to have satisfactory reliability and validity. The mean+/-S.D. of ESS scores in normals was 7.5+/-3.0; in patients, it was 13.2+/-4.7. The ESS score had a negative association with mean sleep latency of the MSLT (rho=-0.42, P=0.0001) but no correlation with the AHI and mO(2). ESS scores of 14 and above significantly predicted a low mean sleep latency of the MSLT. CONCLUSION: The ESS should be included as one of the methods for assessing sleepiness in clinic samples of patients with OSA. Our data showed that the ESS was useful to separate patients with and without pathological degree of objective daytime sleepiness as determined by the MSLT.

Adult↗