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Biomedical subjects

L Wong

Publications and source records attributed to L Wong.

At least 127 records · Page 7Linked to original sources
PubMed1995

Patterns and rates of growth of microcosm dental plaque biofilms.

Rates of growth in wet weight and changes in them over time were established for microcosm dental plaques cultured from the mixed salivary bacteria in an artificial mouth. Standardized conditions included a continuous supply of medium containing 0.25% mucin and 1.5 ml of 5% w/v sucrose in 6 min every 8 h. Plaques were weighed daily. Plaque wet weight and total protein were highly correlated. Plaque doubling times were 3-7 h over day 1 and 9-21 h over day 2, which is similar to in vivo plaques. Subsequently, growth curves were either linear or between a linear and exponential increase. Evidence was obtained for plaque blooms. Methyl paraben (0.2%) applied for 15 min (3.75 ml) 6 times daily inhibited growth but only for 3 days, after which the rate was similar to control plaques, indicating that selection for resistance had occurred. It was concluded that the regulation of plaque growth rates is complex and does not conform to simple growth pattern models. Detailed studies of plaque growth and the effects of antiplaque agents can be carried out using this experimental system.

Bacterial Proteins↗
PubMed1995

'Hospital hyperglycaemia'; perception or reality?

Patients' perceptions that clinic fasting blood glucose measurements in Type 2 diabetes are artefactually high were investigated. Eighteen men and 14 women in the Salford cohort of the United Kingdom Prospective Diabetes Study (UKPDS) with a median age of 51 (range 37-69) years measured their fasting blood glucose concentration at home with visually read sticks or meters; they then collected capillary blood into fluoride tubes both at home and in clinic after a median lapse of 77 (range 25-173) min. The clinic samples were measured immediately and after a time lapse equivalent to the time taken to reach clinic to control for continued glycolysis in the home sample. Mean fasting blood glucose was 5.9 +/- 1.9 mmol 1(-1) by the patients' own measurement and 6.0 +/- 1.8 mmol 1(-1) on the home collected sample compared with 6.2 +/- 2.0 mmol 1(-1) and 6.1 +/- 2.0 mmol 1(-1) on the hospital immediate and time-lapsed measurements, respectively (p > 0.05 for all comparisons between home and hospital measurements); although there were no systematic differences, occasional measurements differed more than 2 mmol 1(-1). These data support the use of the fasting blood glucose level as a stable, patient-independent measure of glycaemic control in Type 2 diabetes.

Adult↗
PubMed1995

Lipid composition of HDL subfractions in dog plasma and lymph.

We report the lipid composition of dog plasma and peripheral lymph lipoproteins as separated into pre-beta, alpha, and pre-alpha fractions by agarose gel electrophoresis. Plasma lipoproteins with alpha mobility have a composition different from that of plasma lipoproteins with pre-alpha mobility, having 9% versus 11% free cholesterol, 21% versus 17% cholesterol ester, 1% versus 16% triacylglycerol, and 69% versus 56% phospholipid. On the other hand, lymph alpha and pre-alpha lipoproteins have compositions that are quite similar (9% versus 7% free cholesterol, 17% versus 17% cholesterol ester, 2% versus 4% triacylglycerol, and 71% versus 71% phospholipid). The lipid compositions of plasma and lymph alpha lipoproteins are quite similar (9% versus 9% free cholesterol, 21% versus 17% cholesterol ester, 1% versus 2% triacylglycerol, and 70% versus 72% phospholipid). The lipid compositions of plasma and lymph pre-alpha lipoproteins are different (11% versus 7% free cholesterol, 17% versus 17% cholesterol ester, 16% versus 4% triacylglycerol, and 56% versus 71% phospholipid). Peripheral lymph lipoproteins with pre-beta mobility contained 15% cholesterol, 13% cholesterol ester, 10% triacylglycerol, and 61% phospholipid. Compared with plasma, peripheral lymph lipoproteins are free cholesterol-enriched in all fractions. Calculated stoichiometric ratios of lipid to apoA-I per particle, alpha lipoproteins have two molecules of apoA-I per particle, and pre-alpha lipoproteins have four molecules of apoA-I per particle.

Animals↗
PubMed1995

Late-onset X-linked sideroblastic anemia. Missense mutations in the erythroid delta-aminolevulinate synthase (ALAS2) gene in two pyridoxine-responsive patients initially diagnosed with acquired refractory anemia and ringed sideroblasts.

X-linked sideroblastic anemia (XLSA) is caused by mutations of the erythroid-specific delta-aminolevulinate synthase gene (ALAS2) resulting in deficient heme synthesis. The characteristic hypochromic, microcytic anemia typically becomes manifest in the first three decades of life. Hematologic response to pyridoxine is variable and rarely complete. We report two unrelated cases of highly pyridoxine-responsive XLSA in geriatric patients previously diagnosed with refractory anemia and ringed sideroblasts. A previously unaffected 77-yr-old male and an 81-yr-old female were each found to have developed severe hypochromic, microcytic anemia with ringed sideroblasts in the bone marrow, which responded dramatically to pyridoxine with normalization of hemoglobin values. Sequence analysis identified an A to C transversion in exon 7 (K299Q) of the ALAS2 gene in the male proband and his daughter. In the female proband a G to A transition was identified in exon 5 (A172T). This mutation resulted in decreased in vitro stability of bone marrow delta-aminolevulinate synthase activity. Each patient's recombinant mutant ALAS2 enzyme had marked thermolability. Addition of pyridoxal 5'-phosphate in vitro stabilized the mutant enzymes, consistent with the observed dramatic response to pyridoxine in vivo. This late-onset form of XLSA can be distinguished from refractory anemia and ringed sideroblasts by microcytosis, pyridoxine-responsiveness, and ALAS2 mutations. These findings emphasize the need to consider all elderly patients with microcytic sideroblastic anemia as candidates for XLSA, especially if pyridoxine responsiveness is demonstrated.

5-Aminolevulinate Synthetase↗
PubMed1995

Effects of fluoride-supplemented sucrose on experimental dental caries and dental plaque pH.

Sucrose, 5% and 10% (w/v), supplemented with between 0 and 5 ppm fluoride (F), was tested for its influence in vitro on plaque-induced experimental in vitro enamel caries and plaque pH. Plaque growth on bovine enamel was initiated from saliva inocula and sustained in a multiple plaque growth system for up to 31 days by means of a basal medium with periodic applications of sucrose or sucrose supplemented with F. Change in enamel mineralization was assessed, before and after plaque growth, by microhardness testing and microradiography; pH was monitored with microelectrodes. It was found that enamel demineralization was inversely related to the F concentration in the range 2 to 5 ppm, for both 5% and 10% sucrose. Plaque pH responses were unaffected by the F supplements.

Analysis of Variance↗
PubMed1995

Genetic variation in plasma androgens and ovarian aromatase activity during mouse pregnancy.

Genetic variation in fetal survival, maternal plasma androgen levels, and ovarian aromatase activity was examined mid (Day 9) and late gestation (Day 16) in strains of mice that differ in reproductive performance (A/J, C57BL/6J, C8/JIs, C17/JIs, and S15/JIs). At both gestational stages, females selected for large litter size (S15/JIs) carried more fetuses than any of the other strains examined. Particularly at midpregnancy, S15/JIs females also maintained higher plasma levels of androstenedione and testosterone relative to both control strains, C8/JIs and C17/JIs. Consistent with previously reported changes in peripheral estrogen levels during mouse pregnancy, aromatase activity was higher on Day 16 than on Day 9. This study demonstrates genetic variation in fetal survival that is correlated with increased maternal androgen levels. A stage-specific gestational increase in aromatase activity occurs in several strains of mice and is associated with elevated plasma estrogen during the second half of pregnancy.

Androgens↗
PubMed1995

Bcl-2 protein expression in normal human bone marrow precursors and in acute myelogenous leukemia.

The expression of bcl-2 protein that is involved in preventing apoptosis in hemopoietic and other cells was evaluated by quantitative flow cytometry in various subpopulations in the normal fetal bone marrow (FBM) and in different types of acute myelogenous leukemias (AML). In the FBM the highest bcl-2 levels (mean antibody binding capacity 51 x 10(3) molecules/cell) were found in CD34+ intermediate sized blasts and myeloblasts, while a CD34+ subset of CD10+ lymphoblasts had low bcl-2 content (8-10 x 10(3) molecules/cell) and the CD34-, CD10+ lymphoblasts were, as expected from previous studies, bcl-2- (< 5 x 10(3) molecules/cell). Variable levels of bcl-2 (5.1-222 x 10(3)) were found in 43 tested cases of AML. The bcl-2 levels decrease with granulocytic and monocytic differentiation and, accordingly, cases of AML with M1 and M2 features showed significantly higher mean bcl-2 levels than the leukemias with promyelocytic (M3) or myelo-monocytic (M4/M5) features. Nevertheless, in seven cases of AML the bcl-2 levels were higher than seen in the normal FBM cells and none of these patients remain in remission after 2 years. Furthermore, in several AML cases intraclonal heterogeneity was observed. The undifferentiated smaller blasts with Class-IIdim display had higher bcl-2 content than the more differentiated larger blasts with more granular side scatter and Class-bright expression. In the same subsets of AML blasts the proliferative S-G2-M fractions showed a reciprocal correlation to bcl-2 content. Thus the higher bcl-2 levels may give a survival advantage and confer some degree of drug resistance to the least differentiated blast populations. The multi-parameter analysis described in this paper, including a combined bcl-2 and cytokinetic analysis of phenotypically defined subgroups of AML blasts, may detect early population shifts during relapse and also guide combination drug therapy.

Antigens, CD↗
PubMed1995

Incontinence has different meanings for different people.

This study used a multi-method approach to examine older patients' attitudes to, and feelings about, their incontinence. The results indicate that patients did not necessarily accept incontinence as a normal aspect of the ageing process and that they used various strategies to cope with incontinence. Some patients found incontinence too stressful to discuss but most welcomed health professionals' initiation of discussion and saw such consultation as contributing to the effectiveness of continence management. Further study is needed to identify the reasons why some patients who have little professional assistance have positive attitudes to their incontinence and others do not.

Aged↗
PubMed1995

The many uses of allograft skin.

Although allografts have traditionally been used on burn patients as temporary covers for large surface area burns before placement of autografts, recent investigations suggest other applications in wound healing. The purpose of this article is to discuss some of the applications for allograft skin, present illustrative examples of its usefulness, and explore possibilities for future research, including tissue banks, rejection of allograft skin, and cultured epithelial allografts. These applications and possibilities support the use of allograft skin as a true "biologic dressing."

Culture Techniques↗
PubMed1994

Heparan sulfate is essential to amphiregulin-induced mitogenic signaling by the epidermal growth factor receptor.

Human amphiregulin (AR) is a heparin-binding growth factor which functions by binding to and activating the epidermal growth factor (EGF) receptor tyrosine kinase. AR contains an EGF-like domain (residues 44-84) and a Lys/Arg-rich NH2-terminal extension (residues 1-43). Synthetic peptides corresponding to residues 8-26, 26-44, and 68-84 of AR were tested for their ability to compete for the binding of AR to immobilized heparin. AR8-26 and AR68-84 had no significant effect on the binding of AR to heparin, whereas AR26-44 bound to heparin and blocked the binding of AR to heparin. Both soluble heparin and heparan sulfate inhibited AR-induced mitogenesis in MCF-10A human mammary epithelial cells with an IC50 of 5 and 2 micrograms/ml, respectively, whereas soluble chondroitin sulfate had only a slight inhibitory effect. When MCF-10A cells were grown in the presence of chlorate, an inhibitor of sulfation, or exposed to the glycosaminoglycan-degrading enzymes heparitinase or heparinase, the ability of AR to evoke mitogenesis in these cells was lost. Chlorate, heparitinase, or heparinase treatment inhibited AR-induced autophosphorylation of tyrosine residues in the EGF receptor. None of these treatments had any significant effect on EGF-triggered mitogenic signaling by the EGF receptor. These results indicate that extracellular heparan sulfate glycosaminoglycan is essential to AR-induced mitogenic signaling by the EGF receptor tyrosine kinase.

Amphiregulin↗
PubMed1994

Modulation of transforming growth factor beta receptors of rat lipocytes during the hepatic wound healing response. Enhanced binding and reduced gene expression accompany cellular activation in culture and in vivo.

Activation of lipocytes, characterized by increased proliferation and fibrogenesis, is a central feature of the hepatic wound healing response. We have examined whether modulation of receptors for transforming growth factor beta (TGF-beta) contributes to the fibrogenic behavior of activated lipocytes. Isolated lipocytes were maintained in a quiescent state by culturing the cells in suspension, where they displayed minimal specific binding for TGF-beta 1 and only a small amount of type III (betaglycan) receptor by affinity labeling. In contrast, lipocytes activated by growth on uncoated plastic displayed saturable binding of TGF-beta 1 (Kd = 28 pM, 7,730 receptors/cell), and receptors types I, II, and III. Binding activity in quiescent and activated cells correlated with responsiveness to TGF-beta 1; TGF-beta 1 induced cellular fibronectin mRNA expression only in activated and not quiescent cells. Despite the absence of binding in quiescent cells, type II receptor was detectable by immunoblot. By RNase protection assay, mRNAs for receptor types II and III were greater in quiescent than activated cells. In freshly isolated lipocytes from animals with liver injury caused by the administration of carbon tetrachloride, a rapid but transient increase in mRNA for receptor types I (approximately 3.2-fold), II (approximately 1.5-fold), and III (approximately 3-fold) was observed with peaks at 12 h for type I receptor, 1 h for type II receptor, and 6 h for type III receptor; mRNA induction was followed by down-regulation for all receptors. The modest changes in mRNAs compared with marked alterations in binding activity during mesenchymal cell activation suggest that TGF-beta receptors may be regulated in vivo in part by a post-translational mechanism.

Adipocytes↗
PubMed1994

Differentiation of intrahepatic membrane-bound and secretory apolipoprotein B by monoclonal antibodies: membrane-bound apolipoprotein B is more glycosylated.

Most apolipoprotein B (apoB) in rat hepatocytes membrane is membrane-bound. The purpose of this study was to determine whether differences existed between membrane-bound and plasma apolipoprotein B, which could be detected using monoclonal antibodies. Detergent-solubilized microsomal membrane-bound apoB was probed with two previously characterized monoclonal antibodies (LRB 200, LRB 220) and compared to a monospecific polyclonal antibody. LRB 200 (capable of binding 71% of plasma apoB) was able to recognize less than 20% of microsomal apoB compared to LRB 220 (a pan-apoB monoclonal antibody capable of binding 100% plasma apoB). To test the hypothesis that the immunologic difference detected by the monoclonal antibodies was due to increased glycosylation of the membrane-bound apolipoprotein B, plasma lipoproteins were incubated with neuraminidase. A progressive increase was found in antibody binding by LRB 200 but not by LRB 220 or the polyclonal antibodies. Inhibition of N-glycosylation by tunicamycin also increased the binding of monoclonal antibody LRB 200 to hepatocyte apoB. Inhibition of trimming of N-linked sugar by incubating hepatocytes with the inhibitors of glucosidase I and mannosidase I eliminated antibody binding by LRB 200 but not by LRB 220 or the polyclonal antibody. When N-linked sugars were removed by peptide: N-glycosidase F, antibody binding by monoclonal antibody LRB 200 was increased. Double-labeling experiments using 3H-mannose and 35S-methionine showed that cellular apoB contained twice the amount of mannose as medium apoB. These data suggest that membrane-bound apoB is more glycosylated than plasma lipoprotein apoB.

Amidohydrolases↗
PubMed1994

Monte Carlo and Poisson-Boltzmann calculations of the fraction of counterions bound to DNA.

The counterion density and the condensation region around DNA have been examined as functions of both ion size and added-salt concentration using Metropolis Monte Carlo (MC) and Poisson-Boltzmann (PB) methods. Two different definitions of the "bound" and "free" components of the electrolyte ion atmosphere were used to compare these approaches. First, calculation of the ion density in different spatial regions around the polyelectrolyte molecule indicates, in agreement with previous work, that the PB equation does not predict an invariance of the surface concentration of counterions as electrolyte is added to the system. Further, the PB equation underestimates the counterion concentration at the DNA surface, compared to the MC results, the difference being greatest in the grooves, where ionic concentrations are highest. If counterions within a fixed radius of the helical axis are considered to be bound, then the fraction of polyelectrolyte charge neutralized by counterions would be predicted to increase as the bulk electrolyte concentration increases. A second categorization--one in which monovalent cations in regions where the average electrostatic potential is less than -kT are considered to be bound--provides an informative basis for comparison of MC and PB with each other and with counterion-condensation theory. By this criterion, PB calculations on the B form of DNA indicate that the amount of bound counterion charge per phosphate group is about .67 and is independent of salt concentration. A particularly provocative observation is that when this binding criterion is used, MC calculations quantitatively reproduce the bound fraction predicted by counterion-condensation theory for all-atom models of B-DNA and A-DNA as well as for charged cylinders of varying linear charge densities. For example, for B-DNA and A-DNA, the fractions of phosphate groups neutralized by 2 A hard sphere counterions are 0.768 and .817, respectively. For theoretical studies, the radius enclosing the region in which the electrostatic potential is calculated to be less than -kT is advocated as a more suitable binding or condensation radius than that enclosing the fraction of counterions given by (1 - epsilon-1). A comparison of radii calculated using both of these definitions is presented.

DNA↗
PubMed1994

The pH response to urea and the effect of liquid flow in 'artificial mouth' microcosm plaques.

This study examined in detailed the pH response of microcosm plaque biofilms to the application of 500 mmol/l urea, and the effect of modifying the flow rate of BMM (a basal medium containing 0.25% mucin). Microcosm plaques were cultured from the mixed salivary bacteria in a multi-plaque 'artificial mouth' supplied continuously with BMM at 3.6 ml/h per plaque, and periodically with sucrose (5 or 10%). Urea (500 mmol/l) induced a pH response that was the inverse of the Stephan pH curve induced by sucrose. In thicker plaques the ureolytic pH response was delayed and slower. With no BMM flow, the urea-induced pH curve reached a maximum and then slowly decreased indicating loss of ammonia. A flow of BMM reduced the magnitude of the pH response. Urea dilution explained (r2 = 0.97) the reduction in the maximum rate of pH rise caused by an increasing BMM flow. There were, however, additional flow-rate effects on the magnitude of the pH rise, the curve areas and the maximum rate of pH decrease back to the resting pH. These effects were greatest at low BMM flow rates, indicating that ammonia clearance may be limited at higher flow rates by the rate of intraplaque diffusion and metabolism. Application of 50 instead of 500 mmol/l urea reduced the rate of pH rise about 10-fold, and the area of the curve about seven fold. Metabolism of arginine (50 mmol/l) generated only about half the pH response of the same amount of urea.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonia↗
PubMed1994

pH gradients induced by urea metabolism in 'artificial mouth' microcosm plaques.

Evidence was sought for urea-induced pH gradients in dental plaque microcosm biofilms cultured from the mixed salivary bacteria in a multi plaque 'artificial mouth'. Application of 500 mmol/l urea for short periods (6 min) to 5-8 mm maximum-thickness plaques induced intraplaque pH gradients of up to 0.7 pH units with the surface alkaline relative to the inner plaque. These pH gradients persisted for more than 5 h in the absence of a flow of fluid. With 30-min urea applications and a flow of a basal medium containing mucin (BMM, pH 7.0), the pH of the inner (deeper) plaque regions also increased. Although the pH gradient initially formed was alkaline at the plaque surface, the BMM flow lowered the surface pH to neutrality whilst the inner layers were still alkaline, thereby reversing the pH gradient. In thick microcosm dental plaques, urea-induced pH gradients can therefore form and last many hours. They probably result from the significant time taken for urea to penetrate to the inner layers of plaque, its rapid metabolism by the outer plaque layers, and a rate-limiting clearance of ammonia. Even a slow BMM flow over the plaque greatly increased the rate of return to the resting pH, causing the gradients to change polarity.

Alkalies↗