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Biomedical subjects

C K Ng

Publications and source records attributed to C K Ng.

At least 55 records · Page 3Linked to original sources
PubMed1993

Increased plasma platelet-activating factor in children with acute asthmatic attacks and decreased in vivo and in vitro production of platelet-activating factor after immunotherapy.

BACKGROUND: To explore the possible role of platelet-activating factor (PAF) in the pathogenesis of bronchial asthma, circulating PAF and in vitro production of PAF were studied. METHODS: Radioimmunoassay kits were used in 15 children with acute asthmatic attacks, in 25 newly diagnosed asthmatic children, in 25 good and 18 poor responders to immunotherapy, and in 18 healthy controls. RESULTS: The results demonstrated the following: (1) PAF was present in the blood of healthy controls. (2) New patients had much higher circulating PAF than did healthy controls (p < 0.005), and the circulating PAF decreased after immunotherapy in good (p < 0.005) but not in poor responders. (3) The circulating PAF increased up to 20 times that of healthy controls during acute asthmatic attacks. (4) The spontaneous and allergen-stimulated secretion of PAF were markedly increased in new patients and decreased to normal after successful immunotherapy (p < 0.005). (5) No increased spontaneous and allergen-stimulated production of PAF was found during acute attacks, but granulocytes from those patients still produced the greatest amount of PAF when stimulated with calcium ionophore A23187. (6) Although a major portion of allergen-induced PAF was secreted, less than 10% of ionophore-induced PAF was secreted. CONCLUSION: The findings that the circulating PAF increased markedly during acute asthmatic attacks and the enhanced in vivo and in vitro productions of PAF decreased to normal after successful immunotherapy strongly suggest that PAF may be involved in the pathogenesis of bronchial asthma.

Acute Disease↗
PubMed1992

Effect of insulin-like growth factor-I on the synthesis and distribution of link protein and hyaluronan in explant cultures of articular cartilage.

Addition of 20% (v/v) fetal calf serum or insulin-like growth factor-I (IGF-I; 20 ng/ml) to the medium of explant cultures of adult articular cartilage resulted in an increased rate of synthesis of the three components of the proteoglycan aggregate-namely link protein, hyaluronan and aggrecan. Fetal calf serum also stimulated the synthesis of other matrix proteins by articular cartilage compared with tissue maintained in medium alone or medium containing IGF-I. Although addition of fetal calf serum or IGF-I to the culture medium of cartilage explant cultures stimulated both hyaluronan and aggrecan synthesis, no change in the distribution of these two macromolecules between tissue and medium was observed. Approx. 50% of the newly synthesized hyaluronan was retained by the tissue compared to 93% of the labelled aggrecan. Culture conditions had some influence on the distribution of link protein, in cultures maintained in medium alone or in medium containing IGF-I, less than 12% of the newly synthesized link protein was lost to the medium of the cultures. However, in cultures maintained with fetal calf serum between 25% and 19% of the radiolabelled link protein was lost from the matrix of the explants. This work suggests that the chondrocyte synthesizes the macromolecules that make up the proteoglycan aggregate in a co-ordinated manner, thereby retaining the relative amounts of each component of this functionally important complex.

Aggrecans↗
PubMed1992

The extracellular processing and catabolism of hyaluronan in cultured adult articular cartilage explants.

Hyaluronan was shown to have the same turnover time as aggrecan in explant cultures of adult bovine articular cartilage. Inclusion of fetal calf serum in the culture medium resulted in a similar decrease in the rate of catabolism of both hyaluronan and proteoglycan. Less than 9% of the hyaluronan lost from the explants in the course of the experiment was recovered from the culture medium as hyaluronan, suggesting that the catabolism of hyaluronan involves the uptake of this glycosaminoglycan by the chondrocytes. Analysis of the molecular size of the newly synthesized hyaluronan in these cultures showed that the hyaluronan was initially synthesized as large macromolecules that were gradually depolymerized with time within the extracellular matrix. The resulting size distribution of newly synthesized hyaluronan molecules after 12 days in culture was similar to that determined for the endogenous hyaluronan. The kinetics of depolymerization of the newly synthesized hyaluronan was consistent with a random fragmentation of the macromolecule. The rate constants for the depolymerization of hyaluronan indicate that oxygen-derived radicals may be involved in the fragmentation of this macromolecule. Inclusion of either cycloheximide or proteinase inhibitors in the medium of the explant cultures resulted in a marked decrease in the rate of loss of hyaluronan from the tissue and in the inhibition of the depolymerization of the newly synthesized macromolecule. This suggests that both the catabolism and the depolymerization of hyaluronan are cell mediated and depend on metabolically active cells.

Age Factors↗
PubMed1992

Effect of the chest wall and blood volume on pulmonary distensibility.

To determine the reason for increased pulmonary distensibility in excised lungs, we performed deflation pressure-volume (PV) studies in 24 dogs. Exponential analysis of PV data gave K, an index of distensibility. Lung volume was measured by dilution of neon. Compared with measurements obtained in the supine position, with the chest closed, and with esophageal pressure (Pes) to obtain transpulmonary pressure, K was not changed significantly with the chest strapped, with pleural pressure to obtain transpulmonary pressure, or with the chest open. From displacement of PV curves obtained in the supine position and with the chest closed or open, we estimated that Pes was 0.18 kPa greater than average lung surface pressure. An increase in K in the prone and head-up positions was attributed to a traction artifact decreasing Pes. Exsanguination increased K and produced a relative increase in gas volume. These results show that overall pulmonary distensibility is unaffected by an intact chest wall. An increase in K and gas volume after exsanguination probably reflects a decreased pulmonary blood volume, with collapse of capillaries increasing the alveolar volume-to-surface ratio.

Animals↗
PubMed1991

Decreased pulmonary distensibility and pulmonary barotrauma in divers.

Pulmonary distensibility, lung volume and conductance were measured in 14 men (mean age 22 (SD 3) years) who suffered pulmonary barotrauma (PBT) during shallow water diving. Exponential analysis of static pressure-volume date obtained during deflation of the lungs gave K, and index of distensibility. The pulmonary conductance-recoil pressure (GL-PL) relationship was also obtained during deflation. Total lung capacity (TLC) was measured in a body plethysmograph or by nitrogen washout. The results were compared with 34 male nonsmokers and 10 healthy male divers. Mean lung volumes and FEV1 did not differ significantly in the three groups. In the PBT group K was decreased and recoil pressure was increased; the slope of the regression of GL and PL was decreased indicating stiffer airways. Decreased K reflects a decreased airspace size. Smaller airspaces increase the surface component of recoil pressure which increases the stress in tissue fibres. Relatively stiff airways may magnify the elastic stresses in peribronchial alveolar tissue increasing the possibility of rupture of alveolar walls with interstitial gas dissection.

Adult↗
PubMed1991

Sensitivity of myocardial fluorodeoxyglucose lumped constant to glucose and insulin.

The lumped constant (LC) that relates the steady-state phosphorylation rate of 2-[18F]-fluoro-2-deoxy-D-glucose (2-FDG) to that of glucose was determined in an isolated working rat heart model by direct assay of phosphorylation product formation. Five conditions were tested: 5 and 30 mM glucose without insulin, and 2, 3.5, and 5 mM glucose + 10 mU/ml insulin, all at high external work load. Hearts were continuously perfused with 2-FDG and tritiated glucose without recirculation. The steady-state production of tritiated water was used to monitor the glucose phosphorylation rate. Perfused hearts were freeze-clamped and extracted in perchloric acid, and 2-FDG-6-phosphate was separated from 2-FDG with a formate column. The accumulation of 2-FDG phosphorylation products in tissue was also determined from the slopes of the total tissue radioactivity time courses measured by external gamma-ray detection. Without insulin, the LC value decreased 18% as perfusate glucose concentration was increased sixfold (0.94 +/- 0.06 at 5 mM vs. 0.77 +/- 0.17 at 30 mM). With insulin, the LC rose from 0.33 +/- 0.03 at 5 mM to 1.19 +/- 0.05 at 2 mM glucose concentration. The trends can be interpreted in terms of the concept of control strength; the LC value rises as glycolysis becomes rate limited by transport into cells. This potential variability of the LC must be addressed in the quantitative interpretation of myocardial deoxyglucose studies.

Animals↗
PubMed1990

Usefulness of physiologic dual-chamber pacing in drug-resistant idiopathic dilated cardiomyopathy.

The beneficial effects of physiologic dual-chamber (DDD) pacing in the treatment of end-stage idiopathic dilated cardiomyopathy were evaluated in 16 patients in whom conventional drug therapy had failed. Candidates for cardiac transplantation as well as patients not accepted for transplantation participated. During DDD pacing at an atrioventricular delay of 100 ms, left ventricular ejection fraction increased from 16.0 +/- 8.4 to 25.6 +/- 8.6% (p less than 0.001) accompanied by a striking improvement in clinical symptoms, such as severe dyspnea at rest and pulmonary edema. The New York Heart Association class decreased from 3.6 +/- 0.4 to 2.1 +/- 0.5 (p less than 0.001). The decrease in cardiothoracic ratio from 0.60 +/- 0.06 to 0.56 +/- 0.05 (p less than 0.001) coincided with a decrease in left atrial and right ventricular echocardiographic dimensions, indicating a decrease in preload. Systolic blood pressure increased from 108 +/- 29 to 126 +/- 21 mm Hg (p less than 0.01) and diastolic blood pressure from 67 +/- 15 to 80 +/- 11 mm Hg (p less than 0.01). Normalization of heart rate was achieved. No major complications developed as a consequence of DDD pacing. All patients could be discharged from the hospital within 3 weeks after pacemaker implantation and return to a relatively normal life. Within 1 year after onset of DDD pacing only 4 of the patients died (from either sudden death or stroke). DDD pacing could represent an alternative approach to the management of chronic heart failure due to dilated cardiomyopathy, especially for heart transplant candidates and patients who are not accepted for cardiac transplantation, but no longer respond to drug therapy.

Adult↗
PubMed1990

Characterization and synthesis of macromolecules by adult collateral ligament.

Bovine collateral ligament was found to have a water content of 67.5 +/- 2.5%, the tissue was highly collagenous containing 100.3 +/- 15.1 micrograms hydroxyproline/mg dry weight. Type I collagen was the major collagen present with small amounts of Type III and V. The hexuronate content of the tissue was found to be 2.62 +/- 0.40 micrograms hexuronate/mg dry weight of tissue. On incubation in vitro collateral ligament incorporated [35S]sulfate and [3H]acetate into proteoglycans and [3H]acetate into hyaluronate and glycoproteins. The rate of synthesis of proteoglycans by collateral ligament was shown on a weight basis to be greater than that of tendon but lower than that of articular cartilage. Analysis of the proteoglycans present in collateral ligament showed two populations of proteoglycans to be present. Approx. 20% of the total proteoglycans present were large chondroitin- and keratan sulfate-containing proteoglycans capable of forming aggregates with hyaluronate. The major species of proteoglycan present were small dermatan sulfate proteoglycans made up of a core protein with a molecular mass of 45,000 daltons with one dermatan/chondroitin sulfate glycosaminoglycan chain of 30,000 daltons attached. The N-terminal amino acid sequence of the core protein of this proteoglycan showed it to be analogous to the core protein of dermatan sulfate proteoglycan II.

Amino Acid Sequence↗
PubMed1989

Synthesis of hyaluronate in cultured bovine articular cartilage.

The synthesis and distribution of hyaluronate and proteoglycan were studied in bovine articular cartilage in short-term explant culture with [3H]acetate and H2(35)SO4 as precursors. The incorporation of [3H]acetate into hyaluronate and sulphated glycosaminoglycans was linear with time, except that hyaluronate synthesis showed a marked lag at the beginning of the incubation. [3H]Hyaluronate represented 4-7% of the total [3H]glycosaminoglycans synthesized over a 6 h period. However, the distributions of [3H]hyaluronate and 3H-labelled sulphated glycosaminoglycans were different: about 50% of the newly synthesized [3H]hyaluronate appeared in the medium, compared with less than 5% of the 3H-labelled sulphated proteoglycans. A pulse-chase experiment revealed that the release of newly synthesized [3H]hyaluronate from cartilage was rapid. No difference was observed in the distribution of [3H]hyaluronate between medium and tissue by cartilage from either the superficial layer or the deep layer of articular cartilage. When articular cartilage was incubated with 0.4 mM-cycloheximide, proteoglycan synthesis was markedly inhibited, whereas the synthesis of hyaluronate was only partially inhibited and resulted in more of the newly synthesized hyaluronate being released into the medium. Analysis of the hydrodynamic size of [3H]hyaluronate isolated from cartilage on Sephacryl-1000 revealed one population that was eluted as a broad peak (Kav. less than 0.7), compared with two populations (Kav. greater than 0.5 and less than 0.5) appearing in the medium of cultures. These data suggest that hyaluronate is synthesized in excess of proteoglycan synthesis and that the hyaluronate that is not complexed with proteoglycans is rapidly lost from the tissue.

Animals↗
PubMed1989

beta-Methyl-15-p-iodophenylpentadecanoic acid metabolism and kinetics in the isolated rat heart.

The use of 15-p-iodophenyl-beta-methyl-pentadecanoic acid (beta Me-IPPA) as an indicator of long chain fatty acid (LCFA) utilization in nuclear medicine studies was evaluated in the isolated, perfused, working rat heart. Time courses of radioactivity (residue curves) were obtained following bolus injections of both beta Me-IPPA and its straight chain counterpart 15-p-iodophenyl-pentadecanoic acid (IPPA). IPPA kinetics clearly indicated flow independent impairment of fatty acid oxidation caused by the carnitine palmitoyltransferase I inhibitor 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). In contrast, beta Me-IPPA kinetics were insensitive to changes in fatty acid oxidation rate and net utilization of long chain fatty acid. Analysis of radiolabeled species in coronary effluent and heart homogenates showed the methylated fatty acid to be readily incorporated into complex lipids but a poor substrate for oxidation. POCA did not significantly alter metabolism of the tracer, suggesting that the tracer is poorly metabolized beyond beta Me-IPPA-CoA in the oxidative pathway.

Animals↗
PubMed1989

Kinetics of [18F]1-fluoro-2,4-dinitrobenzene, a potential probe for the glutathione detoxification system, in perfused working rat heart.

[18F]1-Fluoro-2,4-dinitrobenzene (FDNB), a substrate for the detoxification enzyme glutathione-S-transferase, was prepared by 18F-Cl exchange. It was administered as a rapid bolus in the perfused working rat heart and the kinetics of the label were followed by external coincidence detection and by analysis of the coronary effluents and tissue homogenates. The data suggest that part of the extracted tracer was released, part was dehalogenated and part was reversibly incorporated into a large tissue pool of FDNB that was not a substrate for defluorination. The rates of the specific processes, estimated from the residue data, may be sensitive to changes in the glutathione detoxification system and therefore applicable to investigation of the compromised myocardium.

Animals↗
PubMed1989

Measurement of O2 consumption in isolated organs without venous cannulation.

A new two-sensor technique for measurement of O2 consumption in isolated organs without venous cannulation was successfully applied to the isolated rat heart. Because this technique eliminates the net exchange of O2 between venous effluent and the environment, measurement of the O2 concentration is conveniently made by use of a polarographic sensor in a collected pool of effluent at the bottom of a closed organ chamber. The method was validated against conventional techniques using cannulation of the pulmonary artery. The two-sensor technique allows O2 consumption measurements to be made in isolated organ preparations in which representative venous cannulation is prohibitively difficult, for example in organs with multiple venous drains, or those in which cannulation would be expected to cause excessive perturbation of physiological status.

Animals↗
PubMed1989

Quantitative analysis of myocardial kinetics of 15-p-[iodine-125] iodophenylpentadecanoic acid.

Myocardial extraction and the characteristic tissue clearance of radioactivity following bolus injections of a radioiodinated (125I) long chain fatty acid (LCFA) analog 15-p-iodophenylpentadecanoic acid (IPPA) were examined in the isolated perfused working rat heart. Radioactivity remaining in the heart was monitored with external scintillation probes. A compartmental model which included nonesterified tracer, catabolite, and complex lipid compartments successfully fitted tissue time-radioactivity residue curves, and gave a value for the rate of IPPA oxidation 1.8 times that obtained from steady-state release of tritiated water from labeled palmitic acid. The technique was sensitive to the impairment of LCFA oxidation in hearts of animals treated with the carnitine palmitoyltransferase I inhibitor, 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). IPPA or similar modified fatty acids may be better than 11C-labeled physiological fatty acids such as palmitate in this type of study, because efflux of unoxidized tracer and catabolite(s) from the heart are kinetically more distinct, and their contributions to the early data can be reliably separated. This technique may be suitable for extension to in vivo measurements with position tomography and appropriate modified fatty acids.

Animals↗
PubMed1988

Comparison of 16-iodohexadecanoic acid (IHDA) and 15-p-iodophenylpentadecanoic acid (IPPA) metabolism and kinetics in the isolated rat heart.

Time courses of radioactivity (residue curves) were obtained following bolus injection into working rat hearts of two 125I-labeled long chain fatty acids: 16-iodohexadecanoic acid (IHDA) and 15-p-iodophenylpentadecanoic acid (IPPA). Residue curves were analyzed in terms of a rapid vascular washout component, an early tissue clearance component, and a very slow late component. For IHDA and IPPA in control hearts, early myocardial clearance kinetics were rate limited by the diffusion of catabolites. Sensitivity of the kinetics to impaired fatty acid oxidation was examination by pretreatment of animals with 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). Decreased fatty acid oxidation was indicated in IHDA and IPPA residue curves by a decrease in the relative size of the early clearance component. Analysis of radiolabeled species in coronary effluent and heart homogenates showed that back diffusion of IPPA was slower than that of IHDA; this discrepancy was most apparent in POCA hearts. In vitro binding assays suggested higher tissue:albumin relative affinity for IPPA than for IHDA. Thus, IPPA early clearance kinetics were more closely related to the clearance of labeled catabolite(s) and were therefore more sensitive to the oxidation rate of long chain fatty acids.

Animals↗
PubMed1988

Rate of increase in pulmonary distensibility in a longitudinal study of smokers.

To examine the hypothesis that an abnormally rapid increase in pulmonary distensibility occurs in cigarette smokers, 39 adult smokers (24 men), mean age 47 (SD 8) years, who were not disabled were studied on two occasions over a mean interval of 3.5 (SD 0.5) years. Exponential analysis of static pressure-volume data obtained during deflation of the lungs gave the exponent K, an index of distensibility. Total lung capacity (TLC) was measured in a body plethysmograph. At entry into the longitudinal study means values for K and static recoil pressure in the 39 smokers available for follow up were similar to those obtained in the original group of 101 smokers (73 men), mean age 42 (SD 11) years, in the cross sectional study. Over the interval of the study, ln K and TLC increased and FEV1 decreased at rates greater than those found in a previous longitudinal study of 34 non-smokers (24 men), mean age 42 (SD 15) years. In the longitudinal study of smokers the observed changes in K and in recoil pressure over the interval of study were greater than the values obtained from the regression slopes found in the cross sectional study of smokers. On the basis of the regression model used previously in the longitudinal study of non-smokers, the age coefficient for ln K was greater than that found in the non-smokers (p less than 0.01). The regression model also showed that the slope of ln K on age increased in older subjects. Because K is related to peripheral airspace size, a rapid rate of increase in K identifies smokers in whom airspace size is increasing abnormally rapidly. In this study the rate of increase in K and the variation between subjects was sufficient to explain the magnitude of the increased pulmonary distensibility found in cigarette smokers who present with emphysema.

Adult↗
PubMed1986

A longitudinal study of pulmonary distensibility in healthy adults.

To assess changes in pulmonary distensibility with age in a longitudinal study, 34 healthy non-smoking adults were examined on two or more occasions over an interval of 6.0 +/- 1.8 yr (mean +/- SD). Exponential analysis of static pressure-volume data obtained during deflation of the lungs gave the exponent, K, an index of distensibility. Total lung capacity (TLC) was measured in a body plethysmograph and increased over the interval of study. The results were compared with findings in a previous cross-sectional study of 124 subjects. At entry into the longitudinal study, mean values for K and static recoil pressure were similar to those obtained for subjects in the cross-sectional study. Over the interval of study, K increased more in subjects with higher values for K (older subjects) supporting the use of a logarithmic analysis of K on age. Using a statistical model which allowed for a variable number of observations and for variance of K between subjects, the increase in ln K with age was similar to that found in the cross-sectional study. From the relationship between K and the average size of airspaces (mean linear intercept, Lm) demonstrated previously in excised lungs, it is shown that the reported increase in Lm with age suffices to explain the increase in K with age in intact subjects.

Adult↗
PubMed1984

Phosphorylation of glucose analog 3-O-methyl-D-glucose by rat heart.

When isolated rat hearts were perfused with medium containing 3-O-methyl-D-glucose (3MG) a compound with the chromatographic behavior expected for 3MG-6-phosphate was formed. This assignment is supported by the action of alkaline phosphatase and by production of an identical peak on incubation of 3MG with yeast hexokinase in a buffer containing adenosine triphosphate and Mg++ ions. The clearance of labeled 3MG from isolated perfused rat hearts was biphasic and eventually total. Since sugar phosphates do not cross cellular membranes, this behavior is consistent with both formation and dephosphorylation of 3MG-6-phosphate, with dephosphorylation rate-limiting the slow phase of the clearance. Phosphatase activity was also indicated by a decrease in 3MG-6-phosphate when hearts were not chilled and homogenized immediately after perfusion. The common assumption that 3MG is not metabolized after transport into cells is shown by these experiments to be erroneous.

3-O-Methylglucose↗