Biomedical subjects

Victor Wong

Publications and source records attributed to Victor Wong.

15 recordsLinked to original sources

PubMed2006

Loss of the astrocyte glutamate transporter GLT1 modifies disease in SOD1(G93A) mice.

Recent studies have highlighted the role of astrocytes in the development of motor neuron disease in animal models. The astrocyte glutamate transporter GLT1 is responsible for a significant portion of glutamate transport from the synaptic cleft; regulating synaptic transmission and preventing glutamate excitotoxicity. While previous studies have demonstrated reductions in GLT1 with SOD1-mediated disease progression, it is not well established whether a reduction in this astrocyte-specific transporter alters the pathobiology of motor neuron degeneration in the SOD1(G93A) mouse. In order to address this possible astrocyte-specific influence, we crossed the SOD1(G93A) mouse line with a mouse heterozygous for GLT1 (GLT1+/-) exhibiting a significant reduction in transporter protein. Mice that carried both the SOD1 mutation and a reduced amount of GLT1 (SOD1(G93A)/GLT1+/-) exhibited an increase in the rate of motor decline accompanied by earlier motor neuron loss when compared with SOD1(G93A) mice. A modest reduction in survival was also noted in these mice. Dramatic losses of the GLT1 protein and reduced glutamate transport in the lumbar spinal cords of the SOD1(G93A)/GLT1+/- animals were also observed. GLT1 was not significantly changed in cortices from these animals suggesting that the effect of mutant SOD1 on GLT1 production/function was largely targeted to spinal cord rather than cortical astrocytes. This study suggests that astrocytes, and the astrocyte glutamate transporter GLT1, play a role in modifying disease progression and motor neuron loss in this model.

Amino Acid Transport System X-AG↗

PubMed2006

Management of stigma and disclosure of HIV/AIDS status in healthcare settings.

PURPOSE: This paper aims to examine the management strategies adopted by older people living with HIV/AIDS (PHAs) to conceal their positive status in healthcare settings, and their responses taken and means used to cope with the stigmatizing and exclusionary effects as a result of the disclosure of their status by/to healthcare workers. DESIGN/METHODOLOGY/APPROACH: Under the auspices of a local NGO in Hong Kong, a total of seven male older PHAs aged 55 or above from pre-existing HIV/AIDS self-help groups were recruited for two separate focus groups. A thematic approach was adopted for data analysis and specific themes identification. FINDINGS: An analysis of the data revealed that older PHAs did exercise their own agency in preventing against and managing stigma in their access to and use of health care services. Two more specific themes around "sign of disapproval" and "discriminatory practice" as barriers to access were also identified. RESEARCH LIMITATIONS/IMPLICATIONS: Because of the small sample size, the pattern of stigmatization experiences and coping strategies cannot claim to be representative of the complete picture of the stigma associated with HIV/AIDS. ORIGINALITY/VALUE: This is the first exploratory study of the stigmatization and devaluation suffered by older PHAs in healthcare settings in the context of Hong Kong. It also explored in details the pros and cons of the stigma management strategies employed by this vulnerable group of patients. The implications for practice both on the side of healthcare workers and policy makers and that of PHAs were discussed.

Adaptation, Psychological↗

PubMed2006

Enhancement of muscle glucose uptake by the vasopeptidase inhibitor, omapatrilat, is independent of insulin signaling and the AMP kinase pathway.

Omapatrilat (OMA), a vasopeptidase inhibitor (VPI), presently being tested in clinical trials for its antihypertensive properties, inhibits both angiotensin-converting enzyme and neutral endopeptidase, and raises tissue bradykinin levels. Recent studies from our laboratory and those of others have demonstrated that VPIs enhance muscle glucose uptake in animal models, and this effect is mediated by the bradykinin-nitric oxide pathway. The mechanism of the effect of OMA on muscle glucose uptake, however, is presently unknown. To investigate the effect of OMA on insulin signaling, soleus muscle was isolated 2 or 5 min after an i.v. bolus of insulin or saline from male Zucker fatty rats (8-10 weeks of age), following a 5-day treatment period of oral OMA (15 mg/kg per day) or drug vehicle (placebo). OMA resulted in significantly lower systolic blood pressure compared with the placebo-treated group (84.4+/- 7.52 mmHg in OMA vs 112+/-2.18 mmHg in controls, P<0.01). Immunoprecipitation and Western blot analysis of insulin receptor substrate 1 (IRS-1) revealed no changes in protein mass with OMA treatment. OMA did not enhance basal or insulin-stimulated IRS-1 tyrosine phosphorylation or its subsequent association with the p85 regulatory subunit of phosphatidylinositol 3-kinase. Under basal and insulin-stimulated conditions, OMA treatment did not alter the protein mass or the phosphorylation of Akt/protein kinase B, p42/44 extracellular signal-regulated kinase or adenosine monophosphate-activated protein kinase, or GLUT4 protein expression. We conclude that the ability of OMA to enhance whole body and specifically muscle glucose uptake in Zucker fatty rats is not mediated by enhancing insulin or AMPK signaling. Future studies should examine whether hemodynamic effects of the drug, independent of insulin signaling, enhance glucose uptake in insulin-resistant skeletal muscle.

Adenylate Kinase↗

PubMed2005

Degeneration of respiratory motor neurons in the SOD1 G93A transgenic rat model of ALS.

The transgenic mutant superoxide dismutase (SOD1) mice and rats have been important tools in attempting to understand motor neuron pathology and degeneration but the mechanism behind death in this model has not been studied. We studied the electrophysiologic and pathologic properties of the cervical motor neurons and phrenic nerves in mutant SOD1 rats and demonstrated motor neuron loss, progressive reduction of phrenic nerve compound muscle action potential amplitudes, phrenic nerve fiber loss, and diaphragm atrophy suggesting respiratory insufficiency as a significant contributing factor leading to SOD1 rat death. Unlike previous observations suggesting that a dying-back process may be occurring in the mouse model of the disease, we did not observe differences between proximal and distal axon loss in phrenic nerves of SOD1 rats. This may reflect a unique feature of respiratory motor neuron biology or may be related to the relatively rapid course of decline in the rat model when compared with the mouse SOD1 model. Significant motor neuron loss was also noted in the lumbosacral spinal cord with relative sparing of motor neurons in the cranial nuclei. Taken together, these data suggest that respiratory motor neuron loss results in significant electrophysiologic changes and diaphragmatic atrophy. These changes may play a significant role resulting in death of these animals.

Action Potentials↗

PubMed2005

Viscous fingering induced flow instability in multidimensional liquid chromatography.

Viscous fingering is a flow instability phenomenon that results in the destabilisation of the interface between two fluids of differing viscosities. The destabilised interface results in a complex mixing of the two fluids in a pattern that resembles fingers. The conditions that enhance this type of flow instability can be found in coupled chromatographic separation systems, even when the solvents used in each of the separation stages have seemingly similar chemical and physical properties (other than viscosity). For example, the viscosities of acetonitrile and methanol are sufficiently different that instability at the interface between these two solvents can be established and viscous fingering results. In coupled chromatographic systems, the volume of solvent transported from one separation dimension to the second often exceeds the injection volume by two or more orders of magnitude. As a consequence, viscous fingering may occur, when otherwise following the injection of normal analytical size injection plugs viscous fingering would not occur. The findings in this study illustrate the onset of viscous fingering in emulated coupled chromatographic systems and show the importance of correct solvent selection for optimum separation performance.

Acetonitriles↗

PubMed2005

Atorvastatin induces insulin sensitization in Zucker lean and fatty rats.

BACKGROUND: The 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors ('statins') have been implicated in preventing new onset type 2 diabetes, whereas the mechanism of this effect is not known. We investigated the effects of an HMG-CoA reductase inhibitor, atorvastatin, on insulin sensitization in Zucker lean and fatty rats. METHODS AND RESULTS: In vivo studies of insulin sensitization were performed in chow fed Zucker lean and fatty rats treated with atorvastatin 50mg/kg/day (ATORVA_50) and results were compared to Zucker lean and fatty rats treated with drug vehicle only (CONT). Additional Zucker lean rats were treated with an intermediate dose of atorvastatin 25mg/kg/day (ATORVA_25). Treatment with atorvastatin resulted in a dose-dependent improvement in whole body insulin sensitivity in both lean and fatty rats, with an approximately two-fold increase in glucose infusion rate and glucose disposal (Rd) in ATORVA_50 versus CONT (p<0.01). Atorvastatin 50mg/kg/day resulted in an increase in 2-deoxyglucose (2-DOG) uptake by skeletal muscles (approximately two-fold increase in 2-DOG uptake in quadriceps (p=0.06) and gastrocnemius (p<0.01)) in lean Zucker rats. Insulin-stimulated phosphorylation of Akt/PKB was significantly increased in skeletal muscle of ATORVA_50 versus CONT in both lean and fatty rats. CONCLUSION: Atorvastatin induces insulin sensitization in Zucker lean and fatty rats. This may be a clinically important pleiotropic effect if confirmed in insulin resistant humans.

Adipose Tissue↗

PubMed2005

Glial restricted precursors protect against chronic glutamate neurotoxicity of motor neurons in vitro.

We have examined the expression of glutamate transporters in primary and immortalized glial precursors (GRIPs). We subsequently transduced these cells with the GLT1 glutamate transporter and examined the ability of these cells to protect motor neurons in an organotypic spinal cord culture. We show that glial restricted precursors and GRIP-derived astrocytes predominantly express glutamate transporters GLAST and GLT1. Oligodendrocyte differentiation of GRIPs results in downregulation of all glutamate transporter subtypes. Having identified these precursor cells as potential vectors for delivering glutamate transporters to regions of interest, we engineered a line of GRIPS that overexpress the glutamate transporter GLT1. These cells (G3 cells) have a nearly fourfold increase in glutamate transporter expression and at least a twofold increase in the V(max) for glutamate transport. To assess whether G3 seeding can protect motor neurons from chronic glutamate neurotoxicity, G3s were seeded onto rat organotypic spinal cord cultures. These cultures have previously been used extensively to understand pathways involved in chronic glutamate neurotoxicity of motor neurons. After G3 seeding, cells integrated into the culture slice and resulted in levels of glutamate transport sufficient to enhance total glutamate uptake. To test whether neuroprotection was related to glutamate transporter overexpression, we isolated GRIPS from the GLT1 null mouse to serve as controls. The seeding of G3s resulted in a reduction of motor neuron cell death. Hence, we believe that these cells may potentially play a role in cell-based neuroprotection from glutamate excitotoxicity.

Amino Acid Transport System X-AG↗

PubMed2004

Isolation of the active constituents in natural materials by 'heart-cutting' isocratic reversed-phase two-dimensional liquid chromatography.

A multidimensional heart-cutting reversed-phase HPLC separation approach, where two columns were operated independently via two six-port two-position switching valves, was employed in the isolation of a major bioactive found in the ethanol-water (80:20) crude extract of Clerodendrum floribundum. In this mode of operation, the specific productivity of the multidimensional approach under overload conditions was twice that of conventional gradient methods with the same loading factor. Isolated sample purities were greater than 99% with recoveries of 95%. The independent operation of each of the two columns employed in the multidimensional approach allowed the cycle time to be less than 7 min, compared to 23 min in the gradient elution single-dimension mode of operation.

Biological Factors↗

PubMed2004

Evaluation of the uniformity of analytical-size chromatography columns prepared by the downward packing of particulate slurries.

The axial heterogeneity of downward slurry-packed chromatography columns was evaluated. A series of columns were prepared that varied in total length from 5 to 30 cm. Each column was packed in stainless steel tubing that was sectioned to allow the column to be divided into 5-cm sections after packing. Each 5-cm section of these columns was then tested for chromatographic performance. In total, 22 such column sections were tested. The results of the study show that the consolidation of the packed bed is a very complex problem, yet systematic variations of the column performance were observed, depending on the location of the section tested from within the entire column. For example, when columns longer than 20 cm were packed, the most homogeneous and best performing section of the column was the lower midsection. Whereas for columns shorter than 20 cm in length, the best sectioned region of the bed was the lower and outlet region. In all cases, the most poorly packed region of the bed was the column inlet section, irrespective of the bed length. The phenomenon associated with this axial heterogeneity undoubtedly results from a complex interplay between wall friction, particle momentum, and the pressure pulsations resulting from the packing process.

Journal Article↗

PubMed2004

Glutamate transporter expression and function in human glial progenitors.

Glutamate is the major neurotransmitter of the brain, whose extracellular levels are tightly controlled by glutamate transporters. Five glutamate transporters in the human brain (EAAT1-5) are present on both astroglia and neurons. We characterize the profile of three different human astroglial progenitors in vitro: human glial restricted precursors (HGRP), human astrocyte precursors (HAPC), and early-differentiated astrocytes. EAAT 1, EAAT3, and EAAT4 are all expressed in GRPs with a subsequent upregulation of EAAT1 following differentiation of GRPs into GRP-derived astrocytes in the presence of bone morphogenic protein (BMP-4). This corresponds to a significant increase in the glutamate transport capacity of these cells. EAAT2, the transporter responsible for the bulk of glutamate transport in the adult brain, is not expressed as a full-length protein, nor does it appear to have functional significance (as determined by the EAAT2 inhibitor dihydrokainate) in these precursors. A splice variant of EAAT2, termed EAAT2b, does appear to be present in low levels, however. EAAT3 and EAAT4 expression is reduced as glial maturation progresses both in astrocyte precursors and early-differentiated astrocytes and is consistent with their role in adult tissues as primarily neuronal glutamate transporters. These human glial precursors offer several advantages as tools for understanding glial biology because they can be passaged extensively in the presence of mitogens, afford the potential to study the temporal changes in glutamate transporter expression in a tightly controlled fashion, and are cultured in the absence of neuronal coculture, allowing for the independent study of astroglial biology.

Amino Acid Transport System X-AG↗

PubMed2004

Using analytical multidimensional isocratic HPLC methods of separation to isolate active constituents in natural products.

Multidimensional reversed-phase HPLC was employed to isolate the active constituents from a crude extract of Clerodendrum floribundum R. Br. These active constituents were known to have bioactivity against the enzyme xanthine oxidase and potentially could be employed in the treatment of gout. Using a multidimensional separation approach, rapid isolation of the active constituents was achieved from a complex sample matrix. As each separation dimension was isocratic, no equilibration time was required and consequently the technique shows promise in the scale up to preparative levels where high throughput is important.

Biological Products↗

PubMed2004

What's in store for medical students? Awareness and utilization of expert nutrition guidelines among medical school preceptors.

BACKGROUND: Instruction of physicians and other health professionals in medical nutrition sciences is among the expert recommendations to promote population health and reduce risks for cancer and other major causes of morbidity and mortality in the population. However, formal training in nutrition in United States medical schools is still lacking compared to the gains in basic and applied medical nutrition sciences. We sought to understand the awareness and current utilization of expert nutrition recommendations and practice guidelines among medical student faculty preceptors. METHODS: We surveyed the teaching faculty who precept for first-, second-, and third-year medical students in two required courses at Boston University. The instrument queried preceptor awareness and current utilization of expert nutrition recommendations, nutritional management practice guidelines, as well as faculty-student interactions regarding patient nutritional education and counseling. RESULTS: Of 187 faculty surveyed, 139 (74%) responded. Faculty reported using 2.3 expert guideline sources (N = 111; SD = 1.8; range = 0-8) but 83% had considered only one or no sources or did not remember what guidelines they had used. Eighty-four percent of preceptors expected students to routinely discuss nutritional practices with patients and/or their families; however, less than half of preceptors routinely provided feedback to students on patient nutritional education or counseling strategies. CONCLUSION: Our findings suggest gaps in faculty awareness and utilization of expert nutrition recommendations and practice guidelines relating to cancer and other chronic disease-risk reduction and population health promotion, underscoring the need for improvements in faculty and medical student training in basic and applied medical nutrition sciences.

Adult↗

PubMed2004

Do maternity care provider groups have different attitudes towards birth?

OBJECTIVE: To compare family physicians', obstetricians' and midwives' self-reported practices, attitudes and beliefs about central issues in childbirth. DESIGN: Mail-out questionnaire. SETTING/POPULATION; All registered midwives in the province, and a sample of family physicians and obstetricians in a maternity care teaching hospital. Response rates: 91% (n = 50), 69% (n = 97) and 89% (n = 34), respectively. METHODS: A postal survey. MAIN OUTCOME MEASURES: Twenty-three five-point Likert scale items (strongly agree to strongly disagree) addressing attitudes toward routine electronic fetal monitoring, induction of labour, epidural analgesia, episiotomy, doulas, vaginal birth after caesarean section (VBACs), birth centres, provision educational material, birth plans and caesarean section. RESULTS: Cluster analysis identified three distinct clusters based on similar response to the questions. The 'MW' cluster consisted of 100% of midwives and 26% of the family physicians. The 'OB' cluster was composed of 79% of the obstetricians and 16% of the family physicians. The 'FP' cluster was composed of 58% the family physicians and 21% the obstetricians. Members of the 'OB' cluster more strongly believed that women had the right to request a caesarean section without maternal/fetal indications (P < 0.001), that epidurals early in labour were not associated with development of fetal malpositions (P < 0.001) and that increasing caesarean rates were a sign of improvement in obstetrics (P < 0.001). The 'OB' cluster members were more likely to say they would induce women as soon as possible after 41 3/7 weeks of gestation (P < 0.001) and were least likely to encourage the use of birth plans (P < 0.001). The 'MW' cluster's views were the opposite of the 'OBs' while the 'FP' cluster's views fell between the 'MW' and 'OB' clusters. CONCLUSIONS: In our environment, obstetricians were the most attached to technology and interventions including caesarean section and inductions, midwives the least, while family physicians fell in the middle. While generalisations can be problematic, obstetricians and midwives generally follow a defined and different approach to maternity care. Family physicians are heterogeneous, sometimes practising more like midwives and sometimes more like obstetricians.

Analgesia, Epidural↗

PubMed2002

Visualization of bed compression in an axial compression liquid chromatography column.

The consolidation of a packed bed undergoing axial compression was studied in glass columns using an on-column visualization process. In this visualization process the refractive indices of the mobile phase (carbon tetrachloride) and the stationary phase (YMC C18 silica) matched perfectly, hence the otherwise opaque stationary phase became transparent to the eye. Alumina layers, which have a different refractive index, were placed at regular intervals along the column bed. These layers were therefore visible and their movement could be tracked during the axial compression of the bed. Consequently, the Young's modulus could be measured at three radial locations and at four bed depths below the head fitting. Theresults showed that the bed was heterogeneous in packing density, both radially (with the bed density increasing from the column center toward the wall) and axially (with the density increasing from the column top toward its center). Furhermore, the bed was shown to be non-symmetrical about the column axis. This was thought to be due to the column inlet head fitting making contact with the packing material on one side of the column first, rather than making contact with the entire cross section of the packing simultaneously.

Carbon Tetrachloride↗

PubMed2002

Cognitive profile for Chinese patients with stroke.

PRIMARY OBJECTIVE: This study aimed to investigate the usefulness of the Chinese version of Cognistat for patients with stroke in a Chinese community. METHODS AND PROCEDURES: A total of 53 patients and 34 normal elderly with age, gender and literacy level matched were tested with the Chinese translated version of Cognistat. OUTCOMES AND RESULTS: The results suggest that the patients performed significantly lower than their normal counterparts on the test. The Orientation, Attention and Calculation sub-tests were the most significant contributors to its high sensitivity (0.79) and specificity (0.85), which is largely consistent with the original English version. A two-factor structure was confirmed with the 10 sub-tests clustered into the areas of fluid and crystallized abilities, which indicates that the translation of the test content did not alter the structure of the instrument. However, the low level of literacy of the local elderly population and language structure tends to slightly alter the cognitive profile of the patients. CONCLUSIONS: Further studies are recommended to further explore the cross-cultural issues and clinical implications on establishing cognitive profile for patients with stroke with Cognistat.

Aged↗