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Biomedical subjects

K Wong

Publications and source records attributed to K Wong.

At least 163 records · Page 9Linked to original sources
PubMed1991

Brain lesions and cognitive function in late-life psychosis.

Twenty-four patients who developed their first psychotic episode after the age of 45 were studied with MRI and comprehensive neuropsychological testing and compared with 72 healthy elderly subjects. The patients demonstrated more clinical abnormalities on MRI, were more likely to have large white-matter lesions or metabolic illness, and did more poorly on many neuropsychological tests, particularly those testing frontal-lobe and memory abilities. We conclude that structural brain injury is commonly associated with the late onset of psychosis. Neuroimaging investigations are a valuable component in the evaluation of this patient group.

Aged↗
PubMed1991

Ito cell activation induced by chronic ethanol feeding in the presence of different dietary fats.

Bronfenmajer et al. (1966) first studied Ito cells in alcoholic hepatitis (AH) by light microscopy (LM). The number of Ito cells and the number of fat droplets were increased. Okanoue et al. (1983) found that Ito cells were reduced by LM but increased by electron microscopy (EM) in scars in AH. Ito cells were activated in scars (increased RER and decreased fat in Ito cells with transition to fibroblasts). Minato et al. (1983) showed that increased RER in Ito cells correlated with increased collagen synthesis of liver biopsies in vitro. Mak et al. showed increased RER correlated with the degree of fibrosis in alcoholic baboons (1984) and alcoholic cirrhosis in man (1988). French et al. (1988b) showed morphometrically that Ito cell fat was decreased and RER was increased only in scars but not in normal sinusoids so that Ito cell activation was restricted to the scars. There was no correlation of sinusoidally located Ito cell fat or RER with the amount of perisinusoidal collagen. In rats fed ethanol and a nutritionally adequate diet including corn oil (25% of calories) by intragastric cannula for five months the fatty liver progressed to focal central fibrosis, and Ito cell activation (fat/RER) was increased. When tallow was substituted for corn oil the Ito cells were not activated and the liver histology was normal. Thus, the type of dietary fat and the local environment (scars) are important factors in the activation of Ito cells by alcohol in vivo.

Alcoholism↗
PubMed1990

Auranofin modulated cytoplasmic free calcium in neutrophils by mobilizing intracellular calcium and inhibiting protein kinase.

The effect of the lipophilic gold compound, auranofin (AUR) on the calcium homeostasis of human neutrophils treated with or without n-formyl-methionyl-leucyl-phenylalanine (FMLP) was investigated. In agreement with previous reports, FMLP induced a rapid release of intracellular Ca2+ stores followed by a smaller influx of extracellular Ca2+. AUR and staurosporine enhanced while phorbol 12-myristate 13-acetate suppressed the secondary influx of Ca2+. Mn2(+)-quenching-of-fluorescence studies indicate that phorbol 12-myristate 13-acetate incubation blocked cation entry. AUR or staurosporine potentiation of FMLP effects on cytoplasmic free Ca2+ [( Ca2+]i) was attributed to suppression of negative feedback effects of protein kinase C. AUR (5-45 microM) per se induced a slow release of internal Ca2+ stores followed by a delayed influx of extracellular Ca2+. Control studies showed that AUR did not induce the formation of inositol 1,4,5-trisphosphate, lyse cells, or promote dye leakage. Dithiothreitol suppressed the AUR effect. AUR triggered biphasic but smaller increases in [Ca2+]i of neutrophil cytoplasts. Studies with permeabilized neutrophils showed that AUR directly released Ca2+ from internal stores. By comparison, gold sodium thiomalate, which had no effect on intact cells, also released Ca2+ from permeabilized cells. Present results indicate that AUR modulated [Ca2+]i directly by mobilized Ca2+ from multiple storage sites and indirectly by inhibiting protein kinase C.

Auranofin↗
PubMed1990

Structural analysis of sulphated glycoprotein 2 from amino acid sequence. Relationship to clusterin and serum protein 40,40.

Sulphated glycoprotein 2 (SGP-2) is the major secreted protein product of rat Sertoli cells; likewise, clusterin is a major constituent of ram rete testis fluid. Isolation and sequencing of the intact subunits and peptides derived from clusterin show that it is the ram homologue of rat SGP-2. Human serum protein 40,40 (SP-40,40), a component of the SC5b-9 complex of complement, has recently been reported to be the human homologue of rat SGP-2. Analysis of the amino acid sequences of rat SGP-2 and human SP-40,40 show that both of these proteins have a significant relationship to the heavy chain of myosin. The regions of highest sequence similarity correspond to the major amphipathic domains in SGP-2/SP-40,40 and the long alpha-helical-tail domain of myosin, which forms a rod-like structure. SGP-2 has anomalous sedimentation behaviour which indicates that it probably exists in an extended conformation. A putative dinucleotide-binding structure has been identified in the longest stretch of identity between SGP-2 and SP-40,40. Elucidation of these features of SGP-2 and SP-40,40 may help to direct future studies into the role of these proteins in the reproductive and complement systems.

Amino Acid Sequence↗
PubMed1990

Nonvisualized gallbladder on oral cholecystography: implications for lithotripsy.

Currently, most protocols evaluating the efficacy of gallstone lithotripsy require a visualized gallbladder on oral cholecystography (OCG). The primary purpose of the OCG is to establish that the cystic duct is patent. When the gallbladder is visualized on OCG, it can also be used to number and size gallstones accurately. Patients with non-visualization of the gallbladder on OCG are excluded from consideration for lithotripsy. The purpose of this study was to evaluate retrospectively the ultrasonographic findings (i.e., number and sizes of stones in 32 patients with nonvisualization on the OCG). In 11 patients (34%) ultrasound (US) did not detect any stone, and it is presumed that the gallbladder failed to visualize for other reasons. Six patients (19%) had one or two stones and 15 (47%) patients had more than three stones. This suggests that 20% of patients with nonvisualization of the gallbladder on OCG would otherwise be eligible for lithotripsy provided that patency of the cystic duct can be demonstrated by other means, such as computed tomographic (CT) examination with oral biliary contrast or cholescintigraphy.

Cholecystography↗
PubMed1990

Relative insensitivity of densitometric stenosis measurement to lumen edge determination.

Coronary artery stenosis measurement from coronary arteriograms is dependent on lumen edge determination. In theory, dependence may be minimized by densitometric integration of the entire lumen as compared with densitometric determination of edges alone coupled with calculation of lumen size by geometric formulas. To assess the impact of approximations of lumen border position when densitometric and geometric methods are employed, external, intermediate and internal borders were defined and used with each method to calculate lumen narrowing from images of contrast-filled, asymmetrically stenotic model vessels and from clinically generated coronary arteriograms. Actual cross-sectional area narrowing of models correlated almost perfectly with densitometric narrowing for each of the three border criteria (external: r = 0.99, n = 192; intermediate: r = 0.99, n = 192; internal: r = 0.99, n = 192). Lumen narrowing calculated by assuming a circular lumen geometry with a diameter equal to the distance between these identical borders correlated less well with true area narrowing (external: r = 0.79, n = 192; intermediate: r = 0.83, n = 192; internal: r = 0.78, n = 192); the residual variance of the densitometric regression was significantly less than that of the geometric regression for each of the three border criteria (external: 8.13 versus 372, p less than 0.001; intermediate: 7.39 versus 315, p less than 0.001; internal: 7.13 versus 531, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗
PubMed1989

Elevation of intracellular cyclic AMP concentration fails to inhibit adrenaline-induced hyperpolarization in amphibian sympathetic neurons.

1. The effect of drugs on the adenosine 3':5'-cyclic monophosphate (cyclic AMP) content of desmethylimipramine (DMI)-treated bullfrog paravertebral sympathetic ganglia was studied by radioimmunoassay. The adrenaline-induced hyperpolarization (Adh) in the tissue was recorded by means of the sucrose-gap technique. 2. In the presence of propranolol (1 microM) and DMI (0.5 microM), adrenaline (1 microM) significantly reduced the concentration of cyclic AMP in forskolin-treated ganglia. This effect was prevented by pertussis toxin (5 micrograms ml-1). 3. The relative potency for drugs which increased ganglionic cyclic AMP content was: 50 microM forskolin much greater than 5 mM fluoride greater than 2 mM fluoride greater than 2 mM isobutylmethylxanthine (IBMX) greater than 5 mM caffeine. In contrast, their relative potency for inhibition of the Adh was: 2 mM IBMX greater than 5 mM fluoride greater than 5 mM caffeine much greater than 2 mM fluoride greater than 50 microM forskolin. The Adh was unaffected by pertussis toxin (5 micrograms ml-1). 4. Although the Adh was slightly reduced by the extracellular application of 8-bromo (8-Br) cyclic AMP, the majority of the data suggest that the transduction mechanism underlying the Adh is independent of the intracellular cyclic AMP concentration and provide an example of an alpha 2-adrenoceptor-mediated response that occurs independently of inhibition of adenylate cyclase.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1989

Increased incidence of thymoma in Chinese myasthenia gravis: possible relationship with Epstein-Barr virus.

Thymectomy was carried out for treatment of myasthenia gravis in 27 unselected Chinese patients and thymoma was found in 13 of them. This 48% incidence of thymomas is two to three times greater than in Japanese and European patients, respectively. The reason for the higher incidence of thymomas observed in Chinese patients may be related to the presence of the Epstein-Barr virus genome in thymoma. Furthermore, all of the thymomas in our patients were lymphoepithelial and histologically resemble nasopharyngeal carcinoma and undifferentiated carcinoma of the salivary gland. Both these tumours are closely linked to the Epstein-Barr virus and in Hong Kong, nasopharyngeal carcinoma is the third commonest cause of death from malignancy. We recommend early thymectomy for patients with myasthenia gravis particularly in geographical areas where there is a high incidence of nasopharyngeal carcinoma and undifferentiated carcinoma of the salivary gland.

Adolescent↗
PubMed1989

Effects of gold coordination complexes on neutrophil function are mediated via inhibition of protein kinase C.

Previous studies have shown that the gold compounds auranofin (AUR) and gold sodium thiomalate (GST) inhibit responses of various cells and tissues. We found that superoxide anion generation induced in human neutrophils by the chemotactic tripeptide fmet-leu-phe (1 microM), fluoride (18 mM), or phorbol myristate acetate (PMA, 100 nM) was inhibited by pretreatment of cells with 5-100 microM AUR. The extent of inhibition was dependent on AUR concentration and duration of the preincubation. GST was much less potent, inasmuch as only weak effects were observed at 5 times higher concentrations. The ineffectiveness of GST was attributed to its slower rate of penetration into cells, compared with AUR. The finding that mobilization of internal Ca2+ stores was not blocked in AUR-treated cells suggests that phospholipase C-mediated hydrolysis of polyphosphoinositides to inositol 1,4,5-trisphosphate was not inhibited by the drug. Because PMA is known to mimic the action of diacylglycerol in activating protein kinase C (PKC), we investigated the possibility that gold compounds might be interfering with signal transduction at this level. Enzymatic assays indicated that both gold compounds reduced the level of PKC activity associated with the cytosol; however, translocation of PKC to the plasma membrane was not found. Immunoblot analyses carried out with polyclonal anti-PKC antisera revealed that the gold compounds did not cause degradation of PKC or increase translocation to the membrane. Further studies indicated that enhanced endogenous protein phosphorylation resulting from PMA stimulation was attenuated in cells co-treated with AUR. Finally, in vitro enzymatic assays showed that both AUR and GST inhibited partially purified PKC in a concentration-dependent manner. It is suggested that modulation of PKC represents a mechanism of action of gold coordination complexes at the cellular level.

Auranofin↗
PubMed1989

Platelet-activating factor (PAF) stimulates phosphatidylinositol hydrolysis in human peripheral blood mononuclear leukocytes.

Human peripheral blood mononuclear leukocytes were labeled with myo-[3H]inositol and stimulated by platelet-activating factor (PAF). PAF-induced phosphatidylinositol hydrolysis and inositol-1,4,5-trisphosphate (IP3) formation in a dose-dependent manner. The response was very rapid and transient and parallels the time course of PAF-induced calcium mobilization in the same cells. However, the doses of PAF for inducing IP3 formation were much higher than those for calcium mobilization. PAF-induced IP3 formation was inhibited by PAF receptor antagonist, L-659, 989, but was not altered by either pertussis toxin or cholera toxin. These data suggest that PAF receptor in human peripheral blood mononuclear leukocytes may be coupled through a pertussis toxin-insensitive guanine nucleotide binding protein to a phosphoinositide-specific phospholipase C.

Calcium Channels↗
PubMed1989

Effect of platelet-activating factor (PAF) on cytosolic free calcium in human peripheral blood mononuclear leukocytes.

Cytosolic free calcium concentration, [Ca2+]i, in human peripheral blood mononuclear leukocytes was increased by platelet-activating factor (PAF) dose-dependently. The response was transient and was attenuated by EGTA (2 mM) in the medium. Furthermore, pretreatment of the cells with pertussis toxin did not alter significantly the rise in [Ca2+]i after stimulation by PAF. The data suggest that elevation of [Ca2+]i in human mononuclear leukocytes induced by PAF depends on: (1) calcium influx through calcium channels in the plasma membranes and (2) calcium mobilization from internal stores mediated via pathway(s) that is insensitive to the action of pertussis toxin.

Benzofurans↗
PubMed1988

Spontaneous vesiculation of large multilamellar vesicles composed of saturated phosphatidylcholine and phosphatidylglycerol mixtures.

The influence of temperature and ionic strength on the vesiculation properties of large multilamellar vesicles containing various proportions of dimyristoylphosphatidylglycerol has been investigated. It is shown that at low ionic strengths preformed large multilamellar vesicles composed of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol (7:3) on incubation at the gel to liquid-crystalline transition temperature (Tc approximately 23 degrees C) spontaneously vesiculate to form predominantly unilamellar systems with a mean diameter of 120 nm. Such vesiculation is not observed for incubations at temperatures appreciably above or below Tc, and is also inhibited by higher ionic strengths. Stable large multilamellar vesicles are formed, however, in systems containing the dioleoyl species of phosphatidylcholine or phosphatidylglycerol and also for dimyristoylphosphatidylcholine/dimyristoylphosphatidylserine mixtures. The vesiculation properties of dimyristoylphosphatidylcholine/dimyristoylphosphatidylglycerol mixtures, therefore, appear to reflect an instability in the region of the Tc driven by surface potential effects which are specific for the glycerol headgroup.

Calorimetry, Differential Scanning↗
PubMed1988

Effect of sulfhydryl reagents on PAF binding to human neutrophils and platelets.

The effects of sulfhydryl reagents on the binding characteristics of platelet-activating factor (PAF) to PAF receptors in human neutrophils and platelets were examined. Simultaneous incubation of neutrophil or platelet membranes with radiolabeled PAF and N-ethylmaleimide (NEM), p-(chloromercuri)benzenesulfonic acid (PCMBS), or 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) resulted in a dose-dependent inhibition of PAF specific binding to the membranes. PCMBS, a membrane-impermeable compound, also inhibited PAF specific binding to intact neutrophils and platelets. In the presence of PCMBS (0.1 mM) or NEM (20 mM), the ability of PAF to displace bound [3H]PAF from neutrophil membranes was reduced. Scatchard analysis of data from saturation binding experiments using neutrophil membranes indicated that the inhibitions of PCMBS (0.1 mM) and NEM (20 mM) on PAF specific binding were due to a decrease in the receptor affinity with no significant change in the number of binding sites. The results suggest that free sulfhydryl group(s) may be associated with the agonist binding site of PAF receptors in human neutrophils and platelets.

Blood Platelets↗
PubMed1988

Specific binding of platelet-activating factor (PAF) by human peripheral blood mononuclear leukocytes.

Binding of platelet-activating factor (PAF) to human peripheral blood mononuclear leukocytes was time-dependent, reversible, and saturable. [3H]PAF binding to the cells was inhibited dose-dependently by unlabeled PAF and PAF receptor antagonists: L-659,989, triazolam, and alprazolam. Scatchard analysis of saturation binding data indicated one class of receptors for PAF with KD = 5.7 nM and Bmax = 18 fmol/10(6) cells (11,100 receptors/cell). PAF (10 nM) increased intracellular free calcium concentration in human lymphocytes and this effect was inhibited by L-659,989 dose-dependently. Our data suggest that human peripheral blood mononuclear leukocytes have specific receptors for PAF.

Alprostadil↗