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Biomedical subjects

G Wong

Publications and source records attributed to G Wong.

At least 55 records · Page 3Linked to original sources
PubMed1999

Artificial human skin: cytokine, prostaglandin, Hsp70 and histological responses to heat exposure.

Artificial human skin, Skin2 (keratinocytes and fibroblasts) and EpiDerm (keratinocytes), was used to determine heat-induced release/accumulation of mediators of injury and repair. Skin2 was exposed to 37 or 41-45 degrees C for 90 min, followed by 37 degrees C for 22.5 h. Media were analyzed for interleukin-1alpha (IL-1alpha), prostaglandin-E2 (PGE2), thromboxane-B2 (TxB2) and nuclear matrix apparatus protein (NMAP, viability). Specimens were taken for microscopy. Media and lysates from Skin2 and EpiDerm (37 and 45 degrees C) were analyzed for IL-1alpha, its soluble receptor (sIL-1RII), receptor antagonist (IL-1Ra), interleukin-6 (IL-6) and heat shock protein-70A (lysates only). Significant release of IL-1alpha and PGE2 was detected only above 43 degrees C, where viability deteriorated and histological damage (especially to keratinocytes) was observed. With both skin products, sIL-1RII release was heat-depressed. IL-1alpha and IL-1Ra were elevated in media and IL-1Ra appeared to lower the bioactivity of IL-1alpha. Heat depressed IL-6 release from Skin2 fibroblasts. IL-6 production and release were negligible with EpiDerm. Heat increased Hsp-70A in both products. We conclude keratinocytes and fibroblasts are not primary cytokine and prostaglandin sources in heatstroke (< 44 degrees C) but could be in evaporative cooling failure, focal hot spots, or systemic responses. Levels of IL-1Ra, PGE2 and Hsp70A may be important markers of cell status.

Antigens, Nuclear↗
PubMed1999

Does local anaesthetic affect the success rate of intravenous cannulation?

We aimed to assess whether subcutaneous lignocaine affects the success rate of intravenous cannulation using a randomized clinical trial. Pre-prepared cannulation packs, 50% containing local anaesthetic, were used to cannulate consecutive consenting patients presenting to the Emergency Department who required cannulation as part of their routine treatment. Doctors with less than four years postgraduate experience randomly selected a pack to perform cannulation and completed a data collection form after each cannulation. Eighty-seven patients received lignocaine with 73 (83.9%) successfully cannulated on the first attempt, 79 patients were cannulated without lignocaine with 64 (81%) successfully cannulated on the first attempt. Subcutaneous lignocaine did not significantly affect the success rate of intravenous cannulation on the first attempt (P = 0.5). Subcutaneous lignocaine has been shown to significantly reduce the pain of intravenous cannulation. This study supports the use of local anaesthesia for all routine venous cannulation.

Anesthesia, Local↗
PubMed1999

Identification of the Escherichia coli enzyme I binding site in histidine-containing protein, HPr, by the effects of mutagenesis.

The structure of the N-terminal domain of enzyme I complexed with histidine-containing protein (HPr) has been described by multi-dimensional NMR. Residues in HPr involved in binding were identified by intermolecular nuclear Overhauser effects (Garrett et al. 1999). Most of these residues have been mutated, and the effect of these changes on binding has been assessed by enzyme I kinetic measurement. Changes to Thr16, Arg17, Lys24, Lys27, Ser46, Leu47, Lys49, Gln51, and Thr56 result in increases to the HPr Km of enzyme I, which would be compatible with changes in binding. Except for mutations to His15 and Arg17, very little or no change in Vmax was found. Alanine replacements for Gln21, Thr52, and Leu55 have no effect. The mutation Lys40Ala also affects HPr Km of enzyme I; residue 40 is contiguous with the enzyme I binding site in HPr and was not identified by NMR. The mutations leading to a reduction in the size of the side chain (Thr16Ala, Arg17Gly, Lys24Ala, Lys27Ala, and Lys49Gly) caused relatively large increases in Km (>5-fold) indicating these residues have more significant roles in binding to enzyme I. Acidic replacement at Ser46 caused very large increases (>100-fold), while Gln51Glu gave a 3-fold increase in Km. While these results essentially concur with the identification of residues by the NMR experiments, the apparent importance of individual residues as determined by mutation and kinetic measurement does not necessarily correspond with the number of contacts derived from observed intermolecular nuclear Overhauser effects.

Bacterial Proteins↗
PubMed1998

Embryonic rat hippocampal neurons and GABAA receptor subunit-transfected non-neuronal cells release GABA tonically.

We used patch-clamp recording techniques to investigate the contribution of GABA to baseline membrane properties in cultured embryonic rat hippocampal neurons. Almost all of the neurons recorded with Cl--filled pipettes and clamped at negative potentials exhibited baselines that were noticeably noisy, with microscopic fluctuations superimposed on the macroscopic holding current. A gentle steam of saline applied to the neuronal surface rapidly and reversibly reduced the baseline current and fluctuations, both of which were completely eliminated by bicuculline. Fluctuation analysis showed that the variance in the baseline current signal was exponentially distributed with estimated kinetics comparable to those activated by submicromolar concentrations of exogenous GABA. The kinetics of Cl- channels activated by endogenous GABA displayed a potential sensitivity comparable to those activated by exogenous GABA. Non-neuronal cells stably transfected with alpha1 and gamma2 GABAA receptor subunits exhibited little baseline current variance when recorded with Cl--filled pipettes. Addition of micromolar GABA to the extracellular saline or to the pipette solution induced a saline- and bicuculline-sensitive baseline current signal comparable to that recorded in hippocampal neurons. Thus, both intra- and extracellular sources of GABA could contribute to the baseline properties recorded in these cultured neurons.

Animals↗
PubMed1998

Sonographic assessment of the cervix in pregnancy.

Recent studies using transvaginal and transperineal sonography to monitor the cervix have dramatically increased our knowledge of morphological changes of the cervix throughout pregnancy. Knowledge of the normal and abnormal appearance of the cervix gives insight into the processes of premature labor and cervical incompetence. The finding of a short cervix can be used to identify (and possibly treat) patients at risk for premature delivery. This article reviews the use of cervical sonography in obstetric care, including the diagnosis of incompetent cervix, the detection and monitoring of premature labor, and the evaluation of placenta previa.

Cervix Uteri↗
PubMed1998

TNF is a potent anti-inflammatory cytokine in autoimmune-mediated demyelination.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by localized areas of demyelination. Although the etiology and pathogenesis of MS remain largely unknown, it is generally assumed that immune responses to myelin antigens contribute to the disease process. The exact sequence of events, as well as the molecular mediators that lead to myelin destruction, is yet to be defined. As a potent mediator of inflammation, the cytopathic cytokine, tumor necrosis factor (TNF) has been considered to be a strong candidate in the pathogenesis of MS and its animal model, experimental autoimmune encephalomyelitis (EAE). However, its role in immune-mediated demyelination remains to be elucidated. To determine the contribution of TNF to the pathogenesis of the MS-like disease provoked by the myelin oligodendrocyte glycoprotein (MOG), we have tested mice with an homologous disruption of the gene encoding TNF. Here we report that upon immunization with MOG, mice lacking TNF develop severe neurological impairment with high mortality and extensive inflammation and demyelination. We show further that inactivation of the TNF gene converts MOG-resistant mice to a state of high susceptibility. Furthermore, treatment with TNF dramatically reduces disease severity in both TNF-/- mice and in other TNF+/+ mice highly susceptible to the MOG-induced disease. These findings indicate that TNF is not essential for the induction and expression of inflammatory and demyelinating lesions, and that it may limit the extent and duration of severe CNS pathology.

Animals↗
PubMed1998

Jarcho-Levin syndrome: two consecutive pregnancies in a Puerto Rican couple.

This report describes two consecutive pregnancies in a Puerto Rican woman that were complicated by the autosomal recessive form of Jarcho-Levin syndrome (spondylothoracic dysplasia). This syndrome, with multiple vertebral and rib malformations, leads to respiratory insufficiency and early neonatal death. The prenatal sonographic appearance is characterized by the presence of fanned-out ribs from fused thoracic vertebral bodies. The features that distinguish spondylothoracic dysplasia and another subtype of Jarcho-Levin syndrome, spondylocostal dysplasia, are discussed. Prenatal diagnosis allows for parental counselling and the possibility of termination of pregnancy if the lethal type of spondylothoracic dysplasia is diagnosed prior to fetal viability.

Adult↗
PubMed1998

The mouse GalR2 galanin receptor: genomic organization, cDNA cloning, and functional characterization.

The diverse physiological actions of galanin are thought to be mediated through activation of galanin receptors (GalRs). We report the genomic and cDNA cloning of a mouse GalR that possesses a genomic structure distinct from that of GalR1 and encodes a functional galanin receptor. The mouse GalR gene consists of two exons separated by a single intron within the protein-coding region. The splicing site for the intron is located at the junction between the third transmembrane domain and the second intracellular loop. The cDNA encodes a 370-amino acid putative G protein-coupled receptor that is markedly different from human GalR1 and rat GalR3 (38 and 57%) but shares high homology with rat GalR2 (94%). In binding studies utilizing membranes from COS-7 cells transfected with mouse GalR2 cDNA, the receptor displayed high affinity (K(D) = 0.47 nM) and saturable binding with 125I-galanin (Bmax = 670 fmol/mg). The radioligand binding can be displaced by galanin and its analogues in a rank order: galanin approximately = M40 approximately = M15 approximately = M35 approximately = C7 approximately = galanin(2-29) approximately = galanin(1-16) >> galanin(10-29) approximately = galanin(3-29), which resembles the pharmacological profile of the rat GalR2. Receptor activation by galanin in COS-7 cells stimulated phosphoinositide metabolism, which was not reversed by pertussis toxin. Thus, the galanin receptor encoded in the cloned mouse GalR gene is the type 2 galanin receptor and is active in both ligand binding and signaling assays.

Amino Acid Sequence↗
PubMed1998

Corneal response to orthokeratology.

PURPOSE: The technique of orthokeratology produces a corneal response to the mechanical pressures exerted by rigid contact lenses. This paper reports a study which investigated the topographic and pachometric corneal changes induced by orthokeratology. METHODS: Six young myopic subjects (11 eyes) wore "accelerated orthokeratology" lenses (OK-74; Contex Inc., Sherman Oaks, CA) in a high Dk material (AirPerm; Dk = 88) for 28 days. Corneal and epithelial thickness were measured topographically using the Holden-Payor optical micropachometer, and corneal topography was monitored using the EyeSys system. RESULTS: Refractive error change reached 1.71 +/- 0.59 D reduction in myopia after 28 days. After 1 day of lens wear, statistically significant central corneal flattening was noted, which progressed to reach 0.22 +/- 0.07 mm (1.19 +/- 0.38 D) at 28 days. A trend toward central epithelial thinning was apparent, reaching statistical significance on day 28 (7.1 +/- 7.1 microm; 9.6%). Midperipheral corneal thickening was also found approximately 2.5 mm from the corneal center, which was statistically significant by day 14 (13.0 +/- 11.1 microm; 2.4%). Calculations using Munnerlyn's formula indicate that changes in corneal sagittal height based on topographical thickness changes across the flattened central 5.25-mm zone can account for the refractive changes observed. CONCLUSIONS: These findings suggest that the initial corneal response to orthokeratology may be explained by redistribution of corneal tissue, rather than by overall bending of the cornea.

Adult↗
PubMed1998

Glucocorticoids decrease c-fos expression in human nasal polyps in vivo.

BACKGROUND: Activated c-fos binds to jun proteins to form the activation protein 1 (AP-1) transcription factor that regulates cytokine and other proinflammatory genes. c-Fos may play a key role in nasal polyp formation. Glucocorticoids may exert their anti-inflammatory effects through an interaction of glucocorticoid receptors with AP-1 that leads to mutual inactivation of both factors, and a "default" termination of AP-1 mediated gene activation. This may explain the beneficial effects of glucocorticoids in the treatment of nasal polyps. METHODS: To test this hypothesis in humans in vivo the immunohistochemical expression of c-fos-immunoreactive material (c-fos-irm) was assessed in nasal polyps from eight steroid naive subjects, polyps from eight subjects treated with topical beclomethasone dipropionate (BDP), and normal inferior turbinate nasal mucosa (n = 6). RESULTS: mRNA for c-fos was detected in all nasal polyps and normal mucosa. In contrast, c-fos-irm was present in all steroid naive subjects but in only two of the eight subjects treated with BDP (p = 0.007, two-tailed Fisher's exact test). c-Fos-irm was expressed solely in epithelial cells and glandular structures; it was expressed in normal epithelium and glands, but the staining intensity was low. CONCLUSION: Glucocorticoids appear to modulate expression of c-fos-irm and possibly AP-1 in human airway epithelial cells in vivo.

Adult↗
PubMed1998

Could a cycloplegic agent be replaced by a fogging or a corrective lens in the biometric measurement of the crystalline lens?

This study investigated whether a fogging or a corrective lens could be used to replace a cycloplegic agent in the ultrasonic measurement of crystalline lens thickness in myopia. A group of 28 Hong Kong Chinese adults with myopia was recruited. The crystalline lens thickness of the examined eye was measured by A-scan ultrasonography while the fixating eye was in one of three conditions: fog (+2.00 D fogging lens), full corrective lens, or cycloplegia (50 minutes after instillation of 1% cyclopentolate HCl). We found that the mean lens thickness was significantly different between the three conditions in our myopic subjects. The mean crystalline lens thickness under fogging and corrective lens conditions was significantly greater than the cycloplegic condition by 0.09 mm and 0.11 mm, respectively. The 95% limits of agreement compared to cycloplegia (fogging: -0.32 to +0.14; corrective: -0.35 to +0.13) showed marked intersubject variability, indicating that there is a risk of overestimating the lens thickness when substituting cycloplegia with either a fogging or a corrective lens.

Accommodation, Ocular↗
PubMed1997

NMDA receptor 2C subunit is selectively decreased by MK-801 in the entorhinal cortex.

Administration of the non-competitive NMDA receptor antagonist MK-801 (5-methyl-10,11-dihydro-5H-dibenzo[1,d]cyclohepten-5,10-imine) produces paradoxical neurotoxicity in limbic cortical regions which includes the entorhinal cortex. The expression of NMDAR-2C but not -2A, -2B or -2D subunits was significantly decreased in rat entorhinal cortex layer III following MK-801 administration. These results suggest an important role for the NMDAR-2C subunit in the response to MK-801-induced neurotoxicity in brain regions highly vulnerable to injury.

Animals↗
PubMed1997

Diazepam enhancement of GABA-gated currents in binary and ternary GABAA receptors: relationship to benzodiazepine binding site density.

Although the predominant GABAA receptor isoform in the adult rodent central nervous system is a ternary complex composed of alpha 1 beta 2/3 gamma 2-subunits, small populations of binary receptors lacking beta-subunits (i.e., complexes containing alpha gamma-subunits) have also been identified. When expressed in HEK 293 cells, recombinant GABAA receptors composed of either alpha 1 beta 2/3 gamma 2- or alpha 1 gamma 2-subunits form benzodiazepine-responsive, GABA-gated chloride channels. The objective of this study was to compare the ability of a prototypic benzodiazepine (diazepam) to augment GABA-gated chloride currents in these binary and ternary receptor isoforms. The potency of GABA was characteristically increased by diazepam (1 microM) in both receptor isoforms, but this increase was significantly greater (p < 0.05) in receptors composed of alpha 1 beta 2 gamma 2-subunits (approximately five- to sixfold) compared to alpha 1 gamma 2-subunits (approximately 2.2-fold). At GABA concentrations approximating its EC50 value (5 microM), the greater augmentation observed in ternary receptors was attributable to a higher efficacy of diazepam. Radioligand binding studies revealed that the Bmax of [3H]flunitrazepam was increased approximately 1.8- and 3.5-fold in cells expressing alpha 1 beta 2 gamma 2- and alpha 1 beta 3 gamma 2-subunits, respectively, compared to cells expressing alpha 1 gamma 2-subunits. A similar increase (approximately 3.8-fold) in the Bmax of [3H]Ro 15-4513 was observed in HEK 293 cells transiently transfected with cDNAs encoding alpha 6 beta 3 gamma 2-compared to alpha 6 gamma 2-subunits. The Kd values of these radioligands were not different in binary and ternary receptor isoforms. It is hypothesized that the greater efficacy of diazepam in alpha 1 beta 2 gamma 2 compared to alpha 1 gamma 2 GABAA receptors results from the higher benzodiazepine binding site density produced by the formation of a ternary complex.

Animals↗
PubMed1997

Localization and pharmacological characterization of pigeon diazepam-insensitive GABAA receptors.

Transduction mechanisms associated with ligand binding at diazepam-insensitive subtypes of GABAA receptors remain largely unknown, but unique behavioral effects of ligands binding at these sites have been reported in pigeons. The present study further evaluated the pharmacological characteristics of diazepam-insensitive GABAA receptors in pigeon brain, using [3H]Ro 15-4513. Autoradiography detected diazepam-insensitive benzodiazepine sites on GABAA receptors in a number of brain regions, with the highest densities present in the olfactory bulb, hippocampus, thalamic nuclei and cerebellar granule cell layers, with densities of approximately 10-20% of total benzodiazepine receptor binding. Saturation analysis revealed significant densities (approximately 10% of total benzodiazepine receptor binding) of extracerebellar diazepam-insensitive benzodiazepine receptors in optic lobe, hippocampus, and brainstem compared to 27% in cerebellum. As reported for mammalian diazepam-sensitive benzodiazepine receptors, GABA (50 microM) generally increased the affinities of agonists and partial agonists, had little effect on the affinities of antagonists, and decreased the affinity of an inverse agonist for pigeon cerebellar diazepam-sensitive benzodiazepine receptors. GABA modulation of ligand binding to diazepam-insensitive benzodiazepine receptors was less than that observed for diazepam-sensitive sites, and no positive modulation was observed. These results demonstrate the presence of cerebellar and extracerebellar diazepam-insensitive benzodiazepine receptors in pigeon brain, with distribution patterns and pharmacology similar to those reported in mammals. The comparable central localization and pharmacological properties of drugs at diazepam-sensitive and -insensitive benzodiazepine receptors in pigeons and rats attests to the evolutionary conservation of GABAA systems.

Affinity Labels↗
PubMed1997

Prodromes, coping strategies, insight and social functioning in bipolar affective disorders.

BACKGROUND: Patients suffering from bipolar affective disorders are generally reported to be able to detect prodromes. Insight is also said to be desirable for a good outcome. However, very little is known about the effect of insight and patients' spontaneous strategies for coping with prodromes on their social functioning. METHOD: In a cross-sectional study 40 bipolar patients, who were not in an acute episode, were interviewed about their prodromes of depression and mania, their coping strategies for these prodromes, their levels of insight and their levels of social functioning. RESULTS: A quarter of subjects reported that they could not detect any early warnings of depression compared with only 7.5% of subjects who reported that they could not detect prodromes of mania. Subjects reported both spontaneous cognitive and behavioural strategies for coping with prodromes of depression but only behavioural strategies for prodromes of mania. Subjects' current levels of depression, how they coped with prodromes of mania and their ability to recognize early warnings for depression contributed significantly to their level of social functioning. Insight also had a weaker but significant contribution. CONCLUSION: No causal link was made in this study. However, it did show that patients' level of social functioning was related to their level of insight, and to how well they coped with the prodromes of mania and whether they could detect prodromes of depression. The results suggest that it is worth exploring ways of teaching patients to monitor their moods and to promote insight and good strategies for coping with their prodromes.

Adaptation, Psychological↗