Effects of type I and type II phospholipase A2 on rat peritoneal mast cells.
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Biomedical subjects
Publications and source records attributed to C K Lai.
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Asthma is an inflammatory disease with a strong genetic predisposition. We have studied a group of unrelated asthmatic patients of southern Chinese origin on their HLA-DR and -DQ regions using molecular techniques and compared them with 104 healthy controls of the same ethnic origin. Restriction fragment length polymorphism (RFLP) was used to genotype the MHC class II DR beta, DQ alpha and DQ beta loci of the subjects. Polymerase chain reaction (PCR) using sequence specific primer (SSP) for DQ beta genes was also performed. No significant difference was found in the HLA-DQ and -DR loci between the patients and the controls. All patients had their serum IgE antibody levels measured, bronchial reactivity assessed by histamine broncho-provocation and cutaneous reactivity to common allergens determined by skin-prick tests to Dermatophagoides pteronyssinus, Dermatophagoides farinae, mixed grass pollens, Aspergillus fumigatus, cat fur and dog dander and they were classified respectively. The HLA-DR and -DQ genotypes of these subgroups of patients were compared. There was no significant difference among these subgroups of patients according to their serum IgE levels, the degree of bronchial reactivity and whether they were positive for the skin tests for the various allergens respectively. The results suggest that HLA-DQ and -DR genotypes are not associated with asthma in southern Chinese people.
BACKGROUND: Primary spontaneous pneumothorax (PSP) is a common clinical condition associated with high recurrence if no definitive treatment is given and could be life threatening if left untreated. The best treatment for this condition, however, remains controversial. AIMS: A prospective study of patients with PSP treated by video assisted thoracoscopic surgery (VATS) after a mean follow up of 16 months. METHODS: Between September 1992 and April 1994, 114 VATS procedures were performed on 110 patients with PSP (including four patients with bilateral presentation) by one surgical team from a single institution. Mechanical pleurodesis with Marlex mesh was performed on all patients. In addition, apical bullae were identified in 100 cases (88%) and these were resected. RESULTS: There was no mortality. The median hospital stay was three days. The procedure was well accepted by patients and this was reflected subjectively in a visual analogue scale and objectively in the requirement of postoperative analgesia. Complications included one wound infection, one bleeding, eight persistent air leaks over ten days. We had two failures with recurrence of pneumothorax occurring one week and two months postoperatively (mean follow up of 16 months). Late morbidity with intercostal neuropathy was identified in nine patients but only two of them required oral analgesics. CONCLUSION: VATS is a quick and effective treatment for PSP. We currently recommend VATS for patients with recurrent spontaneous pneumothorax, as well as first time pneumothoraces associated with tension, bilaterality, frequent travelling, unreliable follow up and persistent air leak over three days.
Soluble interleukin-2 receptor (sIL-2R) is a marker of T-lymphocyte activation. We have undertaken a study to examine the serum sIL-2R levels in patients with pulmonary tuberculosis (TB) and the changes following anti-TB chemotherapy. Forty four patients with pulmonary TB or tuberculous pleural effusion were recruited. Serum was collected from the patients before and at 1, 2, 4 and 6 months after initiation of anti-TB chemotherapy. Serum sIL-2R level was measured by an enzyme immunoassay. The mean sIL-2R level before treatment was 1,452 +/- 103 (SEM) U.ml-1, which was significantly higher than that of healthy control subjects (374 +/- 30 U.ml-1). There was no significant change in the sIL-2R level at 1 month, but there was a gradual reduction from the second month onwards. At the sixth month the mean sIL-2R level was 1080 +/- 81 U.ml-1, which was significantly lower than that before treatment. However, despite clinical improvement, the sIL-2R levels at the sixth month were still significantly higher than those of control subjects. We conclude that sIL-2R levels were elevated in patients with pulmonary TB and there was a gradual reduction following anti-TB chemotherapy. However, the sIL-2R levels were still higher than control subjects at completion of treatment, suggesting a delayed resolution of the inflammation in patients with pulmonary TB.
Respiratory diseases can cause considerable disability in the elderly because of their limited respiratory reserve as a result of ageing. We have investigated the prevalence of respiratory symptoms and diseases in elderly Chinese in Hong Kong and compared these data with those in elderly Caucasian populations. Two thousand and thirty two (999 male and 1,033 female) subjects, selected by age-stratified random sampling from a register of Hong Kong residents aged 70 yrs and over were interviewed to complete a respiratory questionnaire. Total serum immunoglobulin E (IgE) was measured in 195 subjects. At least one respiratory symptom was reported by 56% of subjects. The most frequently reported symptoms were morning phlegm (26%), chronic cough with phlegm (10%) and wheeze in the past 12 months (8%). Of the self-reported diseases, the commonest was chronic bronchitis (7%), followed by asthma (5%), pulmonary tuberculosis (3%) and emphysema (2%). Of the 218 subjects with obstructive airway diseases, 128 (59%) had sought medical advice in the past 12 months. The most important determinants for respiratory symptoms and diseases were smoking and social class. Total serum IgE was significantly higher in current smokers than nonsmokers and also in those with chronic cough and phlegm than those without these complaints. Our study shows that respiratory ailments in Hong Kong elderly are as common as those reported in Sweden and the USA but less than those in England.
Salmeterol may be useful in the treatment of asthmatic patients requiring high-dose inhaled steroids, and there have been debates about its anti-inflammatory action. We have compared the efficacy and effects on serum inflammatory markers, including soluble interleukin 2R (sIL-2R), eosinophil cationic protein (ECP), and tryptase of salmeterol and albuterol in 20 patients with moderate to severe asthma who were all receiving high-dose inhaled corticosteroids and inhaled beta 2-agonist on demand. After a 2-week run-in period, they received, in a randomized, crossover, double-blind and placebo-controlled manner, either salmeterol, 50 micrograms twice a day, or albuterol 400 micrograms, four times a day, from a powder inhaler during two 2-week treatment periods, separated by a 2-week washout. Compared with albuterol, salmeterol treatment was associated with better morning and mean peak expiratory flow (p = 0.013 and 0.016, respectively), less daytime and nocturnal symptoms (p = 0.008 and 0.01, respectively), reduced requirement of rescue albuterol (p = 0.04), and better efficacy rating by patients (p = 0.04). However, serum concentration of sIL-2R was significantly higher during regular albuterol treatment (p = 0.014) but no differences were seen in the concentrations of ECP and tryptase between the two treatment periods. We conclude that inhaled salmeterol, 50 micrograms twice daily, confers a better control of asthma than albuterol, 400 micrograms four times daily, in patients with moderate to severe disease, and the latter treatment may be associated with increased T-lymphocyte activation.
The crystal structure of human platelet factor 4 (PF4) has been solved to a resolution of 2.4 A by molecular replacement and refined to an R-factor of 24.1%. The structure consists of four polypeptide chains which form a tetrameric unit. N-terminal residues, previously defined as a random coil or extended loop region, form antiparallel beta-sheet-like structures that form noncovalent associations between dimers. These antiparallel beta-sheet-like structures are positioned lateral to the beta-bilayer motif and stabilize the tetrameric unit. A positively charged ring of lysine and arginine side chains encircles the PF4 tetramer sphere, presenting multiple potential sites and orientations for heparin binding. The electrostatic interactions of multiply charged amino acid side chains and hydrogen bonding interactions at the AB/CD dimer interface serve to stabilize the tetrameric structure further.
The mast cell protective effects of the newly developed long-acting beta 2-agonists salmeterol and formoterol were compared with those of conventionally used beta 2-agonists, non-specific beta-agonists, disodium cromoglycate (DSCG) and theophylline. With the exception of DSCG, all the test agents inhibited ovalbumin-induced histamine release from enzymically dispersed guinea pig lung mast cells in a dose-dependent fashion. At the maximum concentration tested, theophylline produced the highest level of protection, inhibiting up to 90% of ovalbumin-induced histamine release whereas DSCG produced only 10% inhibition. The maximum inhibition produced by all the beta 2-agonists tested was around 45%. While salmeterol was equipotent with salbutamol, formoterol was at least a 100-fold more potent. Hence the present study confirmed the previously reported mast cell stabilizing actions of conventional beta 2-agonists and extended the observation to the newly developed long-acting analogues.
IgA nephropathy (IgAN), characterized by glomerular deposition of IgA and frequently elevated plasma IgA levels, has increased T helper cell activity. In vitro measurement of cytokines in supernatant of cultured peripheral lymphocytes revealed conflicting findings. We examined the profile of cytokine mRNA expressed in purified CD4+ cells in patients with IgAN in order to study their pattern of Th1 (releases IL-2 and interferon-gamma (IFN-gamma)) and Th2 (releases IL-4 and IL-5) T cell response. We assessed the circulating CD4+ T cells in patients and normal controls by the expression of messenger RNA (mRNA) for IL-2, IL-4, IL-5 and IFN-gamma. The cytokine mRNAs were analysed with reverse transcription-polymerase chain reaction and were measured semiquantitatively by using a housekeeping gene, beta-actin. Compared with the control subjects, CD4+ T lymphocytes from patients with IgAN expressed a higher level of IL-2 mRNA (P = 0.007), IFN-gamma mRNA (P = 0.04), IL-4 mRNA (P = 0.048), and IL-5 mRNA (P = 0.016). Within these patients with IgAN, a good correlation was demonstrated between the gene expression of cytokines in Th1 or Th2 cells. The IL-2 mRNA levels in Th1 cells from these patients with IgAN also correlated significantly with the IL-4 or IL-5 mRNA levels in their Th2 cells. Our study revealed IgAN is associated with activation in circulating lymphocytes of the IL-2, IFN-gamma, IL-4 and IL-5 gene cluster, a pattern compatible with activation of both the Th1- and Th2-like T lymphocyte population. The increased transcription of these cytokines genes may be contributory to the immunopathologic findings in IgAN.
Video-assisted thoracoscopy (VAT) offers a new approach to the diagnosis and treatment of many thoracic conditions. From September 1992 to August 1993, a total of 163 VAT procedures were successfully performed on 108 patients (87 male, 21 female; age range from 12 to 77) which consisted of 42 bleb eliminations and 64 mechanical pleurodesis for spontaneous pneumothorax, 11 wedge resections for pulmonary nodules, three wedge biopsies for diffuse pulmonary infiltrate, four thoracic sympathectomies, resections of two mediastinal masses, three pericardial windows, 10 guided pleural biopsies for undiagnosed effusions, six guided drainage of empyema and haemothorax, 16 staging of intrathoracic tumours and two explorations for penetrating thoracic trauma. There was no procedure-related mortality. Complications included one recurrence for spontaneous pneumothorax, one re-exploration for bleeding (also by VAT approach), one wound infection, and six persistent air leaks for more than 10 days. The median duration of postoperative chest tube drainage was 2 days and the median hospital stay was 4 days. It was concluded that VAT is a safe and effective approach in thoracic surgery and with further refinement in instrumentation even more procedures will be technically feasible. The long-term results of VAT are being awaited in order to define its true merits in thoracic surgery.
There is accumulating evidence that leukocyte-endothelial adhesion molecules are important in inflammatory injury in being involved in the primary step of entrapment and migration of leukocytes to the site of inflammation. We have used an antigen capture ELISA to measure the levels of circulating intercellular adhesion molecule-1 (cVCAM-1), vascular cell adhesion molecule-1 (cVCAM-1) and E selectin (cE selectin) in the peripheral blood of 33 patients with IgA nephropathy (IgAN) during clinical quiescence and 24 healthy controls. The serum levels of cICAM-1 and E selectin in IgA-nephritic patients were not different from that of healthy controls but the cVCAM-1 level was significantly elevated in IgAN despite a lack of clinical activity (p = 0.008). The differential rise of circulating leukocyte-endothelial adhesion molecules in IgAN probably reflects the origins and nature of these molecules as well as the specific immunological profile of IgAN. There was no correlation between the levels of these three circulating adhesion molecules. When the patients with IgA nephropathy were stratified according to the severity of their glomerular and interstitial lesions, there was an apparent increase in cE selectin and cVCAM-1 associated with increased histopathologic grading. The changes in endothelial adhesion molecules during clinical exacerbation were studied in 10 patients. Coinciding with synpharyngitic macrohematuria, there was a significant rise of cVCAM-1 and cE selectin (p = 0.046 and p = 0.016, respectively) but no similar rise was observed in cICAM-1.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of two recently developed long-acting beta 2-adrenoceptor agonists, formoterol and salmeterol, on mast cells from different sources were compared with those of the prototype short-acting analogue, salbutamol. With the exception of high concentrations of salmeterol (> 10(-5) M), none of the tested beta 2-adrenoceptor agonists inhibited the anti-IgE-induced histamine release from rat peritoneal mast cells. In contrast, all three compounds dose dependently inhibited the immunologically induced histamine release from isolated lung mast cells of guinea pig and human at concentrations < or = 10(-5) M.
There is increasing evidence that leukocyte-endothelial adhesion molecules are important in inflammatory airway disease because of their involvement in the primary steps of entrapment and migration of leukocytes to the site of inflammation. Recently, circulating forms of these adhesion molecules have been described, although their origin, fate, and function are still unknown. We have used an antigen capture ELISA to measure the concentrations of circulating intercellular adhesion molecule-1 (cICAM-1), E-selectin (cE-selectin), and vascular cell adhesion molecule-1 (cVCAM-1) in the peripheral blood of 13 atopic and 16 non-atopic normal subjects, 29 patients with stable asthma, and inpatients with acute asthma on Day 1 (n = 38), Day 3 (n = 29), and Day 28 (n = 13) of an asthmatic episode. Circulating ICAM-1 and E-selectin levels were significantly raised in acute asthma on all three study days when compared with those observed in stable asthma, atopic normal, or nonatopic normal volunteers with no significant differences among the latter three groups. Circulating VCAM-1 was not significantly increased in any of the groups studied. There were no correlations among the concentrations of these three circulating adhesion molecules. The elevated concentrations of cICAM-1 and cE-selectin in acute asthma may reflect the extensive inflammatory response occurring in the airways during acute exacerbations of the disease with airway obstruction. It is possible that the cytokine and mediator profiles in acute asthma lead to the preferential synthesis and expression of these two circulating adhesion molecules in comparison with cVCAM-1.
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In this simple high-performance thin-layer chromatographic technique for evaluating porphyrin excretion, porphyrins rapidly extracted from urine or feces are separated on reversed-phase octadecylsilyl (C18)-bonded silica thin-layer chromatography plates. We observed > 12 distinct bands of different porphyrins by viewing the plates under long-wave ultraviolet light. Positive screening tests can readily be characterized by the relative fluorescence of various free porphyrins. The two patients presented in this paper are possibly the first two cases of porphyria cutanea tarda reported in Hong Kong Chinese.
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The efficacy of bronchodilator nebuliser solutions may be influenced by the presence of preservatives. In a double blind, randomised, crossover study the effect of preservatives in determining the airway responses to 5 mg of terbutaline was studied in a group of 21 atopic asthmatic patients. The presence of preservatives affected neither the bronchodilator action of terbutaline nor its protection against bronchoconstriction induced by histamine.
An epidemic of infection due to Mycoplasma pneumoniae occurred in Hong Kong in 1986-1988. One hundred and seventy-nine cases were identified at the Prince of Wales Hospital over this period. Clinically significant infection predominantly affected children under 12 years, with 32% of all infections occurring in children aged between 6 and 11 years, and 39% in children between 1 and 5 years. Ninety-seven percent of childhood infections were respiratory in nature, the other 4 presentations were neuropsychiatric. Adequate information was available on 36 of the 43 subjects over 12 years. One teenager presented with acute psychosis; all other cases (35) were respiratory. In these cases cough was universal, and fever was present in 34 (97%). A variety of non-specific symptoms (rigors/chills, malaise, headache, sore throat, sweating) were frequently noted. Sputum production was documented in 75% of cases, and was frequently purulent. Radiological consolidation was very common (95% of cases), but resolved fully after 4 weeks. Complications were rare and included acute pericarditis in 1 patient and haemolysis in another, and both patients recovered subsequently. Clinical recovery was otherwise rapid and complete in all other patients. Persisting dry cough was the only symptom documented at follow-up. Although infection due to M. pneumoniae in an ethnic Chinese population appears similar to that described in other populations, a higher incidence in younger children was recorded in this study.