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Biomedical subjects

K Wong

Publications and source records attributed to K Wong.

At least 19 recordsLinked to original sources
PubMed1992

The influence of cholesterol 3-sulphate on phase behaviour and hydrocarbon order in model membrane systems.

Cholesterol 3-sulphate (CS) is a component of the intercellular lipid found in the uppermost layer of human epidermis (the 'stratum corneum') and is thought to play an important role in tissue cohesion. In this investigation we have compared the influence of cholesterol (CH) and CS on the gel-to-liquid crystalline phase behaviour, the polymorphic phase behaviour, and the hydrocarbon order profile in selected model membranes. It is shown that in sphingomyelin (SPM) systems, the presence of equimolar amounts of either CH or CS eliminates the gel-to-liquid crystalline transition as detected by calorimetry. Similarly, in 1-palmitoyl,2-oleoyl-phosphatidylethanolamine (POPE) dispersions containing a perdeuterated palmitoyl chain (POPE-d31), it is shown that both CH and CS exert an ordering effect as determined by 2H-NMR techniques, however, CS is less potent at temperatures both above and below that of the main transition for the native phospholipid. Alternatively, in mixed systems containing dioleoylphosphatidylethanolamine (DOPE) and SPM (DOPE/SPM, 6:1 mol/mol) CH promotes thermotropic L alpha-->HII phase transitions, whereas CS stabilizes the bilayer organization. These bilayer stabilization effects can be diminished by addition of Ca2+. These effects are consistent with a larger area per molecule of CS as compared to CH, presumably related to the presence of the negatively charged sulphate moiety of CS.

Cell Membrane↗
PubMed1992

Staurosporine clamps cytosolic free Ca2+ concentrations of human neutrophils.

The present studies indicate that 50 nM-10 microM-staurosporine increased cytosolic free Ca2+ concentrations ([Ca2+]i) of fura-2-loaded neutrophils in a non-linear manner. The rise in [Ca2+]i was rapid, reaching a plateau (e.g. to 0.4 microM with 1 microM-staurosporine) within 30 s, and was maintained for more than 20 min. Pretreating cells with pertussis toxin had no effect on this reaction. The elevation of [Ca2+]i was insensitive to extracellular Ca2+ concentrations and was due entirely to mobilization of intracellular Ca2+ stores. Mn(2+)-quench studies confirmed the absence of Ca2+ influx. No Ca2+ efflux occurred in staurosporine-treated cells. In combination studies, staurosporine potentiated Ca2+ influx induced by N-formylmethionyl-leucyl-phenylalanine (FMLP) and did not block Ca2+ efflux associated with peptide stimulation of neutrophils. Studies with permeabilized cells showed that staurosporine did not directly release intracellular Ca2+ stores, nor did it affect the sequestration of Ca2+ by a Ca2+/ATPase pump. A radioligand-binding assay failed to detect changes in the level of inositol 1,4,5-trisphosphate in neutrophils incubated with less than or equal to 1 microM-staurosporine, but in cells treated with 10 microM-staurosporine the assay recorded a transient increase in this second messenger similar to that induced by FMLP. Finally, lysozyme, but not beta-glucuronidase, was released from staurosporine-treated cells. The present results suggest that staurosporine increased [Ca2+]i by indirectly mobilizing internal Ca2+ stores. Staurosporine suppression of Ca2+ efflux and generation of a persistent signal may account for the maintained elevation of [Ca2+]i.

Alkaloids↗
PubMed1992

Competition between cell-substratum interactions and cell-cell interactions.

Clusterin, a glycoprotein which elicits the aggregation of a wide variety of cells (Fritz, I. B., and Burdy, K.:J. Cell Physiol., 140:18-28, 1989), has been utilized to investigate some of the factors modulating the competition between cell-substratum interactions and cell-cell interactions. We compared the responses to clusterin by anchorage-independent cells (erythrocytes) with those by anchorage-dependent TM4 cells (a cell line derived from neonatal mouse testis cells). Cells were maintained in culture in the presence of various substrata chosen to enhance cell-substratum interactions (laminin-coated wells), or to diminish cell-substratum interactions (agarose-coated wells). Results obtained showed that the aggregation of erythrocytes elicited by clusterin was independent of the nature of the substratum. In contrast, clusterin addition resulted in aggregation of anchorage-dependent TM4 cells only when TM4 cell-substratum interactions were weak. Thus, clusterin did not aggregate TM4 cells plated upon a laminin substratum, but readily aggregated TM4 cells plated upon an agarose-coated substratum, independent of the sequence of addition of cells and clusterin to the culture dish. We utilized YIGSR, a peptide which competes with laminin for laminin receptors, to determine the possible role of laminin receptors on TM4 cells in the competition between cell-substratum interactions and cell-cell interactions. The presence of YIGSR did not alter responses of erythrocytes to clusterin under all conditions examined. In contrast, the responses of TM4 cells to clusterin were greatly changed. YIGSR addition resulted in the inhibition of aggregation of TM4 cells otherwise elicited by clusterin. YIGSR also prevented attachment of TM4 cells to a laminin-coated surface, but this was reversed by the presence of clusterin. We discuss the possible roles of clusterin and laminin in altering the balance in the competition between cell to cell interactions and cell to substratum interactions.

Animals↗
PubMed1992

Surgical management of invasive pulmonary aspergillosis in immunocompromised patients.

The treatment of haematological malignancies with intensive chemotherapy and bone marrow transplantation results in prolonged periods of immunosuppression. This is associated with an increased incidence of invasive pulmonary aspergillosis (IPA) with reported mortalities of 67-83%. The mainstay of treatment is medical therapy, surgery being reserved for patients with haemoptysis. Resection of focal sites of infection has not been routinely considered in view of the high morbidity and mortality reported from the surgery of aspergillomas in past series. After the death of two neutropenic patients from massive haemoptysis following IPA in 1986, we have resected localised pulmonary aspergillus lesions in 16 patients following IPA. Five patients had haemoptysis. The most common procedure performed was a lobectomy. All patients were granulocytopenic and excessive post-operative bleeding occurred in three patients, one of whom required a re-thoracotomy as a result. There was one post-operative death due to cytomegalovirus pneumonia. Surgery was otherwise uneventful. There were no recurrent pulmonary aspergillus infections on follow-up and three patients proceeded to bone marrow transplantation. The success of surgical resection encourages an aggressive policy in the management of IPA to prevent life-threatening haemoptysis and to allow patients to proceed with further chemotherapy and bone marrow transplantation.

Adolescent↗
PubMed1992

Angiomyolipoma of the kidney: a clinical enigma in diagnosis and management.

Renal angiomyolipomas are uncommon benign tumours which clinically mimic renal cell carcinoma. They have characteristic features on ultrasound and CT scanning which may enable their diagnosis preoperatively. We review our experience of six cases of renal angiomyolipoma. These cases highlight the difficulties in making a preoperative diagnosis despite the use of modern scanning. We advocate conservative resection when the diagnosis is made preoperatively and when technically possible, but radical nephrectomy should be performed if there is a possibility of a carcinoma.

Adult↗
PubMed1991

Differential effect of diltiazem and TA-3090 on calcium homeostasis of neutrophils.

The effects of diltiazem and TA-3090, an 8-chloro analog of diltiazem, on cellular responses and calcium homeostasis of human neutrophils were investigated. TA-3090, at 10 to 20 microM, enhanced lysozyme release and superoxide generation induced in neutrophils by n-formyl-methionyl-leucyl-phenylalanine (FMLP). Higher concentrations of TA-3090 inhibited responses at IC50s between 70 and 85 microM. Diltiazem by comparison inhibited responses at an IC50 of about 200 microM. The two drugs had little or no effect on early signaling events: inositol 1,4,5-trisphosphate formation triggered by FMLP was not affected. Moreover, 500 microM TA-3090 or diltiazem did not significantly affect FMLP-triggered Ca2+ transients. (Cytoplasmic free Ca2+ levels ([Ca2+]i) were monitored in fura-2-loaded neutrophils.) Diltiazem alone caused a limited influx of extracellular Ca2+ which increased basal [Ca2+]i by twofold. Internal Ca2+ stores were not released. TA-3090, in contrast, induced a biphasic rise in [Ca2+]i--an initial mobilization of intracellular Ca2+ stores was followed after 10-15 min by a persistent influx of extracellular Ca2+ which increased [Ca2+]i to 1.3 +/- 0.7 (SD) microM. Complementary studies with semipermeabilized neutrophils showed that TA-3090 but not diltiazem directly released Ca2+ from intracellular stores. In TA-3090-treated cells, lactate dehydrogenase release was correlated with delayed influx of extracellular Ca2+. The chelation of extracellular Ca2+ by EGTA prevented LDH release. Present results show that TA-3090 and diltiazem initially blocked cell signaling at steps subsequent to phospholipase C activity. With TA-3090-treated cells, elevated [Ca2+]i ensuing from prolonged incubations likely activated inappropriate reactions leading to cell lysis and death.

Calcium↗
PubMed1991

Clustering of erythrocytes by fibrinogen is inhibited by carnitine: evidence that sulfhydryl groups on red blood cell membranes are involved in carnitine actions.

Carnitine is bound by intact red blood cells, by red blood cell ghosts, and by glutaraldehyde-fixed human erythrocytes in a non-saturable, temperature-dependent manner. Binding of carnitine by these preparations is blocked by sulfhydryl reagents. Incubation or preincubation of red blood cell preparations with carnitine inhibits the aggregation of erythrocytes otherwise elicited by fibrinogen. Identical effects are obtained with red blood cell ghosts. In contrast, choline, even at high concentrations, is inactive in preventing the aggregation of erythrocytes. We discuss possible mechanisms by which carnitine favors the dispersion of red blood cells, and we present data indicating that sulfhydryl groups on erythrocyte membranes are required to permit these carnitine actions to be manifested.

Carnitine↗
PubMed1991

Effect of dietary fat on Ito cell activation by chronic ethanol intake: a long-term serial morphometric study on alcohol-fed and control rats.

We studied the effects of long-term ethanol ingestion and dietary fat on Ito cell activation morphometrically in rats. Sixteen pairs of Wistar male rats were divided into two groups, one fed tallow and the other fed corn oil as the source of dietary fat. Each group of rats were pair-fed a nutritional adequate liquid diet containing either corn oil (CF) or tallow (TF) as fat as well as protein and carbohydrate. Half of each group received ethanol, the rest were pair-fed isocaloric amounts of dextrose via an implanted gastric tube for up to 5 months. Morphometric analysis of the change in fat and rough endoplasmic reticulum (RER) of Ito cells was performed on electron micrographs obtained from monthly biopsies including baseline. Ito cell activation was assessed by a decrease in the ratio of fat/RER in Ito cells. The ratio of fat/RER in Ito cells of alcoholic rats fed the CF diet (CFA) gradually decreased. The ratio was found to be lower than in the pair-fed control rats (CFC) at 5 months of feeding. CFA: 1.74 +/- 0.57, vs. 7.46 +/- 2.05, respectively, p less than 0.05, mean +/- SE). Ito cell fat also significantly decreased at 5 months of feeding (p less than 0.05). The fat/RER ratio in CFA significantly decreased only subsequent to the development of fatty change, necrosis, and inflammation followed by fibrosis of the liver. In contrast, the TFA rats did not show a significant decrease in the fat/RER ratio in the Ito cells throughout the study, while TFC rats showed an increase in the fat/RER ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Postprandial hypergastrinaemia in patients with colorectal cancer.

Gastrin is trophic to colon cancers that possess gastrin receptors. Whether fasting serum gastrin concentrations are high in patients with colon cancer is controversial. We therefore studied the effect of food on serum gastrin concentrations in patients with colon cancer and control subjects. Fasting serum gastrin was greater, though not significantly so, in patients with colon cancer before surgery (mean (SD) 17.4 (3.6) pmol/l, n = 16) compared with control subjects (12.6 (1.9) pmol/l, n = 14). Postprandial increases in serum gastrin were significantly and persistently higher than normal in the cancer patients. These increases were due to a subset of six patients with serum gastrin concentrations greater than the control mean + 2 SD at 20 and 40 minutes (62 pmol/l-146 pmol/l). Four of the six patients had intra-abdominal metastases. The extent of the increase may well correlate with that of the disease. Surgical resection of the tumour resulted in a fall in serum gastrin values and probably reflects the cause of the hypergastrinaemia. Hypergastrinaemia may, therefore, be an important aetiological factor in colon carcinogenesis.

Abdominal Neoplasms↗
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↗