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Biomedical subjects

C K Lai

Publications and source records attributed to C K Lai.

At least 91 records · Page 5Linked to original sources
PubMed1993

Serum concentration of soluble interleukin 2 receptors in asthma. Correlation with disease activity.

We evaluated whether serum soluble interleukin 2 receptor (sIL-2R), a marker of T lymphocyte activation in vivo, could be useful to monitor disease activity in asthma. Venous blood was collected from 26 patients with acute severe asthma prior to the commencement of systemic corticosteroid therapy (day 1), 15 with stable disease, and 13 normal control subjects. Serum sIL-2R level was significantly higher in acute asthma (462.7 +/- 36.1 U/ml; mean +/- SEM) than stable disease (328.5 +/- 30.4 U/ml, p = 0.013) which in turn, was significantly raised when compared with control subjects (239.0 +/- 22.9 U/ml; p = 0.0003 vs acute; p = 0.036 vs stable). Nevertheless, sIL-2R concentrations in 11 patients with acute and 11 with stable disease did not exceed the upper limit of normal, ie, mean +.2 SD of the value in control subjects = 404.4 U/ml. Repeated measurements of sIL-2R in 24 acute asthmatics on day 3 revealed no significant fall (464.6 +/- 37.2 U/ml, NS), although the reduction in sIL-2R was significantly correlated with the corresponding improvement in peak expiratory flow (r = -0.52, p = 0.005). Following resolution of the acute attack, further measurements performed in 11 of these subjects on day 28 showed a significant fall in sIL-2R (p = 0.016). Our data showed that although serum sIL-2R was raised in asthma and, to a certain extent, might reflect disease activity, the considerable overlap of values between asthma of differing severity and normal control subjects precludes its clinical use as an index of asthma severity.

Acute Disease↗
PubMed1993

Circulating adhesion molecules in tuberculosis.

Leucocyte-endothelial adhesion molecules have been implicated in the pathogenesis of inflammatory diseases. To evaluate their role as markers of disease activity in tuberculosis, we have used an antigen capture ELISA to measure the serum concentrations of circulating intercellular adhesion molecule-1 (cICAM-1), E-selectin (cE-selectin) and vascular cell adhesion molecule-1 (cVCAM-1) in 34 patients with active tuberculosis (27 with pulmonary disease and seven with lymph node disease) before the commencement of standard chemotherapy, 15 subjects who had previously completed treatment for pulmonary tuberculosis, and 27 healthy volunteers. Circulating ICAM-1 and E-selectin levels were significantly elevated in patients with active tuberculosis when compared to those with treated disease (P < or = 0.01), and healthy controls (P < 0.02). Circulating VCAM-1 was raised in patients with active or old pulmonary tuberculosis (P < 0.02 versus healthy controls) but not in those with tuberculous lymphadenitis. Significant correlations were observed between the levels of cICAM-1 and cE-selectin (p = 0.63, P = 0.0001), and between cICAM-1 and cVCAM-1 (p = 0.28, P = 0.016). Taking the mean +2 s.d. of the serum level in healthy controls as the upper limit of normal range, circulating ICAM-1 had the best discriminative power in identifying active tuberculosis, being elevated in about 80% of patients but was raised in only 6.7% of subjects with treated disease and in 3.7% of normal subjects. Our data support the possibility that three adhesion molecules may be involved in the pathogenesis of tuberculosis and cICAM-1 may be a useful marker of disease activity.

Adolescent↗
PubMed1992

Characterization of cytokine gene expression in CD4+ and CD8+ T cells after activation with phorbol myristate acetate and phytohaemagglutinin.

Cytokines are important mediators involved in the development of effector cells and in the regulation of immune responses. The gene expression of these mediators in T cell subset has yet to be fully elucidated. Using sensitive reverse transcription-polymerase chain reaction (RT-PCR), the kinetics of cytokine gene expression in human CD4+ and CD8+ T cells were examined. CD4+ T cells were more readily activated by phorbol myristate acetate (PMA) and phytohaemagglutinin (PHA) than CD8+ T cells in terms of the IL-2 receptor (IL-2R) mRNA expression. Quantitative differences in cytokine gene expression between CD4+ and CD8+ T cells were confirmed and higher levels of cytokine mRNAs were induced in CD4+ than in CD8+ T cells. Early induction of IL-2 mRNA was observed in both T cell subsets. The demonstration of different kinetics of cytokine gene expression illustrates one of the examples of the complexity of immunoregulation. The differential response of cytokine gene expression in different T cell subsets should be taken into consideration when clinical studies in cytokine production by peripheral blood mononuclear cells are interpreted.

Base Sequence↗
PubMed1992

Acute effect of inhaled bradykinin on tracheobronchial clearance in normal humans.

BACKGROUND: Bradykinin, a nonapeptide that contributes as a mediator to the pathogenesis of asthma, may affect lung mucociliary clearance, as it has been shown to be a potent secretagogue in canine airways and in human nasal mucosa in vivo. To evaluate this possibility the effect of inhaled bradykinin on mucociliary clearance has been studied in 10 healthy volunteers. METHODS: Subjects attended the laboratory on two occasions to take part in tracheobronchial clearance studies using a non-invasive radioisotopic technique. Inhalation of radioaerosol was followed 30 minutes later by inhalation of either bradykinin (8 mg/ml) or vehicle placebo in a randomised, double blind fashion. After each inhalation the number of coughs was recorded. Whole lung radioactivity was measured every half hour for six hours with two collimated scintillation counters, and a tracheobronchial clearance curve was plotted for each subject on each occasion. RESULTS: Mucociliary clearance, expressed as the area under the tracheobronchial radioaerosol retention curve calculated for the first six hours (AUC0-6h), was greater in nine out of 10 subjects after inhalation of bradykinin than after placebo. The median values (range) for AUC0-6h were significantly reduced from 126% (78-232%)/h with placebo to 87% (51-133%)/h with bradykinin. CONCLUSION: It is concluded that acute exposure to inhaled bradykinin accelerates tracheobronchial clearance in normal human airways.

Administration, Inhalation↗
PubMed1992

Effect of inhaled platelet-activating factor on bronchial inflammation in atopic non-asthmatic subjects.

We have investigated the effect of inhaled platelet-activating factor (PAF) on bronchial mucosal inflammation in 6 atopic non-asthmatic subjects in a double-blind, placebo-controlled, randomised and crossover study. On 2 study periods at least 4 weeks apart, fiberoptic bronchoscopy was performed 24 h after inhalation of either 200 micrograms PAF or methacholine (control) to obtain endobronchial biopsies. Immunocytochemistry using antibodies for trypase (AA1) and eosinophil cationic protein (EG2) was performed to enumerate mast cells and eosinophils, respectively, in the bronchial submucosa. Median values of AA1+ cells and EG2+ cells did not differ significantly after inhalation of PAF or control (23.8 vs. 39 and 6 vs. 8/mm2, respectively, PAF vs. control, non-significant). Our findings suggest that within 24 h of inhaling a bronchoconstrictor dose of PAF, this agonist does not induce bronchial hyperresponsiveness or mucosal inflammation in atopic non-asthmatic subjects. However, because of the small number of subjects studied, these preliminary data should be interpreted with caution.

Administration, Inhalation↗
PubMed1992

Bronchial mucosal manifestations of atopy: a comparison of markers of inflammation between atopic asthmatics, atopic nonasthmatics and healthy controls.

We studied the role of atopy, as defined by positive skin tests to common inhalant allergens, in allergic bronchial inflammation. Endobronchial biopsies were taken via the fibreoptic bronchoscope in 13 symptomatic atopic asthmatics, 10 atopic nonasthmatics, and 7 normals. The numbers of mast cells, identified in the submucosa by immunohistochemistry using the AA1 monoclonal antibody against tryptase, were no different between the three groups, but electron microscopy showed that mast cell degranulation, although less marked in atopic nonasthmatics, was a feature of atopy in general. The numbers of eosinophils, identified by immunohistochemical staining using the monoclonal anti-eosinophil cationic protein antibody, EG2, were greatest in the asthmatics, low or absent in the normals and intermediate in the atopic nonasthmatics. In both atopic groups eosinophils showed ultrastructural features of degranulation. Measurements of subepithelial basement membrane thickness on electron micrographs showed that the collagen layer was thickest in the asthmatics, intermediate in the atopic nonasthmatics and thinnest in the normals. The results suggest that airways eosinophilia and degranulation of eosinophils and mast cells, as well as increased subepithelial collagen deposition, are a feature of atopy in general and suggest that the degree of change may determine the clinical expression of this immune disorder.

Adult↗
PubMed1991

Effect of azelastine and ketotifen on the bronchial and skin responses to platelet-activating factor in humans.

In a randomized, double-blind placebo-controlled study we investigated the effect of single oral doses of 8 mg azelastine and 2 mg ketotifen on the immediate response to platelet-activating factor (PAF) inhalation and to increasing doses of PAF injected intradermally. Bronchial provocation with 100 micrograms of PAF resulted in marked bronchoconstrictor responses, but neither azelastine nor ketotifen had any significant effect on these responses. Intradermal injection of PAF (100, 200 and 400 ng) resulted in a dose-related weal and flare response. Azelastine and ketotifen both caused significant reductions in this response (P less than 0.002-P less than 0.01). There was no significant difference between the effect of the two drugs.

Adult↗
PubMed1991

Binding of brain and atrial natriuretic peptides to cultured mouse astrocytes and effect on cyclic GMP.

125I-Porcine brain natriuretic peptide (125I-pBNP) bound to mouse astrocytes in primary culture in a time-dependent manner (t1/2 = 4.5 min), similar to 125I-human atrial natriuretic peptide (125I-hANP) (t1/2 = 5 min). Binding was saturable and reached equilibrium after 90 min at 22 degrees C for both radioligands. Scatchard analysis suggested a single class of binding sites for pBNP with a binding affinity and capacity (KD = 0.08 nM; Bmax = 78.3 fmol/mg of protein) similar to those of hANP1-28 (KD = 0.1 nM; Bmax = 90.3 fmol/mg of protein). In competition binding studies, pBNP or human/rat atrial natriuretic peptide (ANP) analogues [hANP1-28, rat ANP1-28 (rANP1-28), and rANP5-28] displaced 125I-hANP, 125I-pBNP, and 125I-rANP1-28 completely, all with IC50 values of less than nM (0.14-0.83 nM). All four peptides maximally stimulated cyclic GMP (cGMP) production by 10 min at 22 degrees C at concentrations of 1 microM with EC50 values ranging from 50 to 100 nM. However, maximal cGMP induction by brain natriuretic peptide (BNP) (25.9 +/- 2.1 pmol/mg of protein) was significantly greater than that by hANP1-28 (11.5 +/- 2.2 pmol/mg of protein), rANP1-28 (16.5 +/- 2.0 pmol/mg of protein), and rANP5-28 (15.8 +/- 2.2 pmol/mg of protein). These studies indicate that BNP and ANPs act on the same binding sites and with similar affinities in cultured mouse astrocytes. BNP, however, exerts a greater effect on cGMP production. The difference in both affinity and selectivity between binding and cGMP production may indicate the existence of receptor subtypes that respond differentially to natriuretic peptides despite similar binding characteristics.

Animals↗
PubMed1991

Effect of inhaled 15-(s)-hydroxyeicosatetraenoic acid on tracheobronchial clearance in normal human airways.

15-(s)-Hydroxyeicosatetraenoic acid (15-HETE) is the predominant metabolite of arachidonic acid in normal and asthmatic human airways and a potent mucus secretagogue in canine and human airways. A study was carried out on the effect of inhaled 15-HETE on tracheobronchial clearance, measured for six hours by a radioaerosol technique, in 10 normal subjects. Subjects inhaled 80 nmol 15-HETE or the diluent (sodium phosphate buffer) on two occasions at least two weeks apart in a double blind and randomised fashion (20 minutes after radioaerosol inhalation. Tracheobronchial clearance after inhaled 15-HETE was almost identical to that after placebo for all measurements up to six hours. It is concluded that 15-HETE has no effect on tracheobronchial clearance in normal human airways and is unlikely to account for the impaired mucociliary clearance seen in asthma.

Administration, Inhalation↗
PubMed1991

Atrial natriuretic peptide in the central nervous system.

Atrial natriuretic peptide (ANP), first isolated from rat atrial cardiocytes, is a potent natriuretic, diuretic and vasorelaxant hormone when given intravenously. In keeping with increasing evidence that many bioactive peptides that were first discovered in peripheral organs, are often present in the central nervous system, ANP and its binding sites have been localized on neurons in different regions of the brain. Further, ANP binding sites have been found on primary astrocyte and glial cell lines and ligand binding results in cyclic GMP production. In this review, we shall discuss the possible role of ANP as a neuromodulator and its effects on astrocytes, the most numerous cell type in mammalian brain.

Animals↗
PubMed1991

Air-driven nebulised high-dose salbutamol in severe chronic obstructive airways disease: is it safe?

The increasing use of air-driven nebulised bronchodilators by patients with airflow obstruction has raised concern about the safety of this practice. We have investigated the effects of 10 mg salbutamol, nebulised in air, on blood gas tensions, heart rate and plasma potassium (K+), when administered alone to 9 patients with severe chronic obstructive airway disease and then in combination with a therapeutic dose of oral sustained-release theophylline to 5 of them on 2 separate occasions. No significant reductions in PaO2 were observed with either treatments. Heart rate increased significantly from 77.8 +/- 3.7 beats/min (mean +/- s.e.m.) at baseline to a peak of 87.1 +/- 4.4 beats/min at 45 min (p less than 0.001) with salbutamol alone and there was a similar trend of increase after combined therapy. K+ decreased significantly from a baseline of 4.0 +/- 0.3 to a minimum of 3.6 +/- 0.2 mmol/l at 90 min (p less than 0.001) with combined therapy but did not change significantly with single therapy. No subject developed any significant cardiac arrhythmias on either occasion. Although the number of subjects studied is small, our data suggest that air-driven nebulised high-dose salbutamol may be safe in the treatment of severe chronic obstructive airway disease but when combined with oral theophylline, a significant fall in plasma potassium may occur. This could be of clinical significance in hypokalaemic patients. When combination treatment is used, monitoring of plasma potassium is recommended.

Aged↗
PubMed1991

The safety aspects of fiberoptic bronchoscopy, bronchoalveolar lavage, and endobronchial biopsy in asthma.

We have documented the physiologic effects of fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) and endobronchial biopsy performed under local anesthesia in 20 asthmatic subjects, 8 healthy nonatopic control subjects, and 8 atopic nonasthmatic subjects. Premedication consisted of nebulized albuterol (2.5 mg; except for the study of atopic nonasthmatic subjects), ipratropium bromide (500 micrograms), and intramuscular atropine (0.6 mg). Intravenous midazolam was given for mild sedation, and oxygen was delivered via a nasal cannula. FEV1 was measured before and after premedication, immediately postbronchoscopy, and after 2 h recovery. There was a significant fall in mean (+/- SD) FEV1 immediately postbronchoscopy in both the asthmatic (26.2 +/- 16.7%; p less than 0.001) and normal (9 +/- 4.7%, p less than 0.05) groups, which in the asthmatic subjects correlated inversely with the concentration of methacholine provoking a 20% fall in FEV1 (PC20) measured 5 days prebronchoscopy (r = -0.74, p less than 0.001) but not with symptom scores, albuterol use, or peak expiratory flow (PEF) variation recorded during 2 wk before the investigation. There was significant arterial hemoglobin O2 desaturation during biopsy in the asthmatic subjects (median 3%, range -1 to 17% fall from baseline; p less than 0.01), which was not related to any of the measured indices of asthma severity. PC20, measured 5 days before and 5 days after bronchoscopy in the asthmatic subjects and 2 days before and 1 day after bronchoscopy in the atopic nonasthmatic subjects was not significantly affected by the procedure. We conclude that fiberoptic bronchoscopy with BAL and endobronchial biopsy can be conducted safely in asthmatic subjects, but requires caution in those with very responsive airways.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

T lymphocyte activation in patients with active tuberculosis.

Soluble interleukin-2 receptor (sIL-2R) is a marker of T lymphocyte activation. We measured the amount of serum sIL-2R in 35 patients with active tuberculosis before the initiation of antituberculous treatment. Twenty had pulmonary parenchymal lesion, 8 had tuberculous pleural effusion, and 7 had tuberculous lymphadenitis. The serum sIL-2R values were markedly elevated in patients with pulmonary tuberculosis (parenchymal lesion and pleural effusion) compared with patients with tuberculous lymphadenitis (2,612 +/- 536 versus 538 +/- 121 U/ml, p = 0.023), old, inactive tuberculosis (335 +/- 23 U/ml, p = 0.001), and normal control subjects (376 +/- 38 U/ml, p = 0.001). No significant difference was found between patients with parenchymal lesion and those with tuberculous pleural effusion. There was a positive correlation between serum sIL-2R values and the extent of disease on chest radiograph (r = 0.58, p less than 0.001). We conclude that the amount of sIL-2R may be a useful marker of disease activity and extent of involvement in patients with active tuberculous lesions.

Female↗
PubMed1991

The value of prescribed 'high-fibre' diets for the treatment of the irritable bowel syndrome.

The symptoms of 72 patients with irritable bowel syndrome were assessed by questionnaire before and 6 months after a high-fibre diet had been prescribed, to find whether those who achieved the highest fibre intake did any better than those with smaller intakes. Dietary fibre intakes were measured after 6 months by a 7-day weighed food inventory. There was a significant inverse association between the presence of symptoms and fibre intake for: incomplete defaecation, urgency and hard stools with total fibre intake; urgency and hard stools with cereal fibre intake; and borborygmi with fibre intake at breakfast. All patients with constipation, mucus, urgency or watery stools at the beginning of the study, and who were consuming more than 30 g fibre by the end, reported an improvement in these symptoms. Increasing intakes of fibre were not related in any way to abdominal distension, diarrhoea, flatulence or patient's feelings about the working of their bowels. Therefore, this study suggests that the symptoms which benefit most from the prescription of a high-fibre diet are hard stools, constipation and urgency.

Adult↗
PubMed1990

Role of atrial natriuretic peptide in the increase in glomerular filtration rate induced by a protein meal.

1. The increase in glomerular filtration rate after a protein meal is believed to be mediated by hormonal factors. Since natriuresis is often observed after a protein meal, it was postulated that the increase in glomerular filtration rate after a protein meal might be mediated by atrial natriuretic peptide. 2. Subjects were given a low, medium or high protein meal. Fluid intake was controlled so as to avoid significant extracellular fluid volume expansion. It was found that the creatinine clearance, the urea excretion, the fractional sodium excretion and the potassium excretion were elevated in all subjects after protein meals (P less than 0.05). These effects were not observed in subjects given a carbohydrate control meal. 3. The plasma atrial natriuretic peptide concentrations remained unchanged in all subjects except those given a high protein meal (P less than 0.05). There was no significant relationship between plasma atrial natriuretic peptide concentrations and creatinine clearance before or after a protein meal. 4. The data suggest that a high protein meal induces a minor increase in plasma atrial natriuretic peptide concentration, whereas a low or medium protein meal does not. It is unlikely that the change in creatinine clearance after a protein meal can be explained by a change in plasma atrial natriuretic peptide levels.

Adult↗
PubMed1990

Contribution of histamine and prostanoids to bronchoconstriction provoked by inhaled bradykinin in atopic asthma.

Bradykinin, a nonapeptide cleavage product of high molecular weight kininogen, is a potent bronchoconstrictor agonist in asthma; however, its mechanism of action is not known. Since bradykinin has been shown to stimulate mediator release from mast cells and augment the release of prostanoids, we have examined the effect of a selective histamine H1 receptor antagonist, terfenadine and a potent cyclooxygenase inhibitor, flurbiprofen on bronchoconstriction provoked by inhaled bradykinin in asthma. As a bronchial provocation procedure bradykinin challenge was repeatable to within 1 doubling dilution. In nine atopic asthmatic subjects, terfenadine 180 mg, when compared to placebo, increased the geometric mean provocation concentration of inhaled agonist required to reduce FEV1 by 20% of baseline (PC20) from 0.7 to greater than 22.9 mg/ml for histamine (P less than 0.01) and 0.3 to 0.5 mg/ml for bradykinin (P less than 0.01). In a further nine atopic asthmatics, flurbiprofen 150 mg when compared to placebo produced a small but significant protection of the airways against bradykinin, geometric mean PC20 increasing from 0.40 to 0.79 mg/ml (P less than 0.05). We conclude that bradykinin is a potent bronchoconstrictor agonist in asthma, being approximately 9.5 times more potent than histamine in molar terms. Pharmacological intervention with terfenadine and flurbiprofen led to a significant protection of the airways against the constrictor effect of bradykinin but the effect in each case was small. Thus, while histamine and prostanoids may contribute as mediators of bradykinin-induced bronchoconstriction, they are unlikely to account for the majority of the response.

Adult↗