Biomedical subjects

M Wong

Publications and source records attributed to M Wong.

At least 109 records · Page 6Linked to original sources

PubMed1999

Poliomyelitis-like syndrome associated with Epstein-Barr virus infection.

A 20-month-old male presented with an acute clinical syndrome resembling poliomyelitis, characterized by a flaccid monoplegia, areflexia of the involved limb, and preserved sensation. Electrophysiologic studies supported a neuronopathic localization involving the anterior horn cells. Although laboratory evidence for a poliovirus infection was absent, serologic and polymerase chain reaction studies documented an active central nervous system infection with Epstein-Barr virus, indicating that a poliomyelitis-like syndrome may be produced by infectious agents other than enteroviruses.

Diagnosis, Differential↗

PubMed1999

Cyclic compression of articular cartilage explants is associated with progressive consolidation and altered expression pattern of extracellular matrix proteins.

In this study, we investigated the biosynthetic response of full thickness, adult bovine articular cartilage explants to 45 h of static and cyclic unconfined compression. The cyclic compression of articular cartilage resulted in a progressive consolidation of the cartilage matrix. The oscillatory loading increased protein synthesis ([35S]methionine incorporation) by as much as 50% above free swelling control values, but had an inhibitory influence on proteoglycan synthesis ([35SO4] incorporation). As expected, static compression was associated with a dose-dependent decrease in biosynthetic activity. ECM oligomeric proteins which were most affected by mechanical loading were fibronectin and cartilage oligomeric matrix protein (COMP). Static compression at all amplitudes caused a significant increase in fibronectin synthesis over free swelling control levels. Cyclic compression of articular cartilage at 0.1 Hz and higher was consistently associated with a dramatic increase in the synthesis of COMP as well as fibronectin. The biosynthetic activity of chondrocytes appears to be sensitive to both the frequency and amplitude of the applied load. The results of this study support the hypothesis that cartilage tissue can remodel its extracellular matrix in response to alterations in functional demand.

Animals↗

PubMed1999

Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis.

Papillon-Lefèvre syndrome, or keratosis palmoplantaris with periodontopathia (PLS, MIM 245000), is an autosomal recessive disorder that is mainly ascertained by dentists because of the severe periodontitis that afflicts patients. Both the deciduous and permanent dentitions are affected, resulting in premature tooth loss. Palmoplantar keratosis, varying from mild psoriasiform scaly skin to overt hyperkeratosis, typically develops within the first three years of life. Keratosis also affects other sites such as elbows and knees. Most PLS patients display both periodontitis and hyperkeratosis. Some patients have only palmoplantar keratosis or periodontitis, and in rare individuals the periodontitis is mild and of late onset. The PLS locus has been mapped to chromosome 11q14-q21 (refs 7, 8, 9). Using homozygosity mapping in eight small consanguineous families, we have narrowed the candidate region to a 1.2-cM interval between D11S4082 and D11S931. The gene (CTSC) encoding the lysosomal protease cathepsin C (or dipeptidyl aminopeptidase I) lies within this interval. We defined the genomic structure of CTSC and found mutations in all eight families. In two of these families we used a functional assay to demonstrate an almost total loss of cathepsin C activity in PLS patients and reduced activity in obligate carriers.

Aggressive Periodontitis↗

PubMed1999

Patterns of self-reported health care use in injured and uninjured older adults.

METHOD: Using cross-sectional data obtained from the 1994 National Population Health Survey, we have compared self-reported health-care use between injured and non-injured older adults. RESULTS: Over 12 months, 9% of non-institutionalized people over 65 reported an injury. The commonest injuries were sprains or strains and fractures and half of these were caused by a fall. Older people sustaining injuries are more likely to spend a night in hospital and receive physiotherapy.

Accidental Falls↗

PubMed1999

Polyethylene particle morphology in synovial fluid of failed knee arthroplasty.

Synovial fluid from the knees of 16 patients undergoing revision knee arthroplasty for aseptic failure was subjected to base digestion and ultrafiltration. Filtered particles were scanned using scanning electron microscopy and analyzed with an image program. Polyethylene particles were identified visually and confirmed with the use of electron diffraction spectroscopy. Averaging more than 1500 particles per patient sample, 25,148 particles were analyzed. This corresponded to a concentration of 3000 polyethylene particles per milliliter of synovial fluid. Three populations of wear debris were identified in the fluid. Small globular particles with a mean area of 75 mu 2 represented 94% of all particles observed. The particles averaged 10 mu in diameter and often were seen in clumps. Long fibrous particles with a mean area of 1164 mu 2 made up 4% of the particle population. Large rhomboidal particles with an area of 557 mu 2 were observed least commonly and comprised the remainder of the particles visualized. All three particle types were observed in each fluid sample regardless of the wear pattern of the retrieved polyethylene liner. There were no differences in absolute particle counts, particle morphologic characteristics, or particle size between patients with and without gross polyethylene wear.

Aged↗

PubMed1999

Toward Routine Automatic Pathway Discovery from On-line Scientific Text Abstracts.

We are entering a new era of research where the latest scientific discoveries are often first reported online and are readily accessible by scientists worldwide. This rapid electronic dissemination of research breakthroughs has greatly accelerated the current pace in genomics and proteomics research. The race to the discovery of a gene or a drug has now become increasingly dependent on how quickly a scientist can scan through voluminous amount of information available online to construct the relevant picture (such as protein-protein interaction pathways) as it takes shape amongst the rapidly expanding pool of globally accessible biological data (e.g. GENBANK) and scientific literature (e.g. MEDLINE). We describe a prototype system for automatic pathway discovery from on-line text abstracts, combining technologies that (1) retrieve research abstracts from online sources, (2) extract relevant information from the free texts, and (3) present the extracted information graphically and intuitively. Our work demonstrates that this framework allows us to routinely scan online scientific literature for automatic discovery of knowledge, giving modern scientists the necessary competitive edge in managing the information explosion in this electronic age.

Journal Article↗

PubMed1998

Audit of early experience with inhaled nitric oxide in New Zealand neonatal intensive care units.

AIMS: To audit the use of inhaled nitric oxide for the treatment of persistent pulmonary hypertension of the newborn in New Zealand neonatal intensive care units. METHODS: Prospective data collection on all infants treated with inhaled nitric oxide in neonatal intensive care units in the 20-month period from first use to December 1995. Data included perinatal factors, principal diagnosis, echocardiogram results, ventilation details and response to nitric oxide, adverse reactions and outcome. RESULTS: Twenty-eight infants received nitric oxide in three centres, all bar one being 36 weeks or more gestation. Overall survival was 68%. Thirteen infants (46%) responded to nitric oxide treatment, 12 (92%) surviving. Seven (47%) of non-responders survived. Infants with primary pulmonary hypertension or meconium aspiration syndrome had 90% survival and more often responded to nitric oxide than infants with congenital diaphragmatic hernia (40% survival) or pulmonary hypoplasia (no survivors). No serious complications of treatment were recorded. CONCLUSIONS: Inhalational nitric oxide was not universally successful treatment for pulmonary hypertension of the newborn but was likely to have been life-saving in a proportion of cases. Future studies may allow better case selection. Ongoing audit of this new treatment is warranted.

Administration, Inhalation↗

PubMed1998

Post-menopausal women and osteoporosis: available choices for maintenance of skeletal health.

OBJECTIVE: To briefly summarize the therapeutic choices for osteoporosis prevention which are currently available to post-menopausal women. METHODS: Results of randomized clinical trials and epidemiological studies in postmenopausal women, and pre-clinical studies in ovariectomized rats were summarized. RESULTS: Estrogen combined with progestogen in hormone replacement therapy (HRT) is effective in relieving perimenopausal symptoms and maintaining bone mineral density. However, the increased breast cancer risk associated with long-term HRT use makes it a less desirable option for many women. Selective estrogen receptor modulators (SERMs), such as raloxifene, are also effective in maintaining bone density, without stimulating the breast or uterus. However, SERMs do not relieve perimenopausal hot flashes. CONCLUSION: HRT is effective for acute relief of perimenopausal symptoms, but for women who are unwilling or unable to take HRT long-term, SERMs such as raloxifene are a useful therapy for the prevention of osteoporosis.

Animals↗

PubMed1998

Protein kinase B (PKB/Akt) activity is elevated in glioblastoma cells due to mutation of the tumor suppressor PTEN/MMAC.

Glioblastomas are highly malignant tumors of the central nervous system that are resistant to radiation and chemotherapy [1]. We explored the role of the phosphatidylinositol (PI) 3-kinase signal transduction pathway in glioblastomas, as this pathway has been shown to inhibit apoptosis induced by cytokine withdrawal and the detachment of cells from the extracellular matrix [2]. Components of this pathway have been implicated in tumor development [3-6]. We show that glioblastoma cells, in contrast to primary human astrocytes, contain high endogenous protein kinase B (PKB/Akt) activity and high levels of PI 3,4,5-triphosphate (PI(3,4,5)P3) and PI(3,4)P2, the lipid products of PI 3-kinase. These glioblastoma cells express mutant forms of the putative 3' phospholipid phosphatase PTEN, also known as MMAC. Expression of wild-type PTEN derived from primary astrocytes, but not of mutant forms of PTEN, reduced the levels of 3' phosphoinositides and inhibited PKB/Akt activity. PTEN antagonized the activation of PKB/Akt by growth factors, by activated PI 3-kinase and by PI-dependent protein kinase-1 (PDK1), but did not antagonize the phospholipid-independent activation of PKB/Akt lacking the pleckstrin homology (PH) domain. These results suggest a role for PTEN in regulating the activity of the PI 3-kinase pathway in malignant human cells.

3-Phosphoinositide-Dependent Protein Kinases↗

PubMed1998

RANTES and MIP-1alpha activate stats in T cells.

The chemokines RANTES (regulated on activation, normal T cell expressed and secreted) and MIP (macrophage inflammatory protein)-1alpha have been implicated in regulating T cell functions. RANTES-induced T cell activation is apparently mediated via two distinct signal transduction cascades: one linked to recruitment of pertussis toxin-sensitive G proteins and the other linked to protein-tyrosine kinase activation. In this report, we identified that the transcription factors Stat1 and Stat3 (for signal transducers and activators of transcription) are rapidly activated in T cells in response to RANTES and MIP-1alpha. Nuclear extracts from MOLT-4 and Jurkat T cells treated with RANTES or MIP-1alpha contain tyrosine-phosphorylated Stat1:1 and Stat1:3 dimers that exhibit DNA-binding activity. We demonstrated that RANTES and MIP-1alpha treatment of Jurkat cells resulted in transcriptional activation of a Stat-inducible gene, c-fos, with kinetics consistent with Stat activation by these chemokines. RANTES and MIP-1alpha mediate their effects via shared chemokine receptors (CCRs): CCR1, CCR4, and CCR5. Our data revealed a concordance between chemokine-induced Stat activation and c-fos induction and CCR4 and CCR5 expression. These findings indicate that chemokine-mediated activation of G-protein-coupled receptors leads to signal transduction that invokes intracellular phosphorylation intermediates used by other cytokine receptors.

Chemokine CCL3↗

PubMed1998

Determining cerebral perfusion pressure thresholds in severe head trauma.

Laboratory studies suggest the pulsatile component of the transcranial doppler (TCD) waveform may be useful in determining lower autoregulatory threshold. This study aimed to assess the effect of increasing CPP on jugular bulb oximetry (SjO2) and middle cerebral artery (MCA) TCD flow velocities in the early management of severe head injury. 16 severely head injured patients (GCS < or = 8), had intracranial pressure (ICP), mean arterial pressure, SjO2 and MCA Doppler velocity monitored continuously. CPP was increased by intravenous fluids (right atrial pressure approximately equal to 10) and supplemented with adrenaline infusion until TCD pulsatility (Gosling pulsatility index [PI] reached a plateau. The mean CPP at which SjO2 surpassed 55% was 62 +/- 6.2 mm Hg. TCD PI did not plateau until a significantly higher mean CPP of 74 +/- 5.1 mm Hg was achieved (p < 0.01). In 8 cases, increased CPP was associated with a fall in ICP, ranging from 1 to 8 mm Hg. We conclude that a critically low level of SjO2 is a late indicator of failed autoregulation. CPP values associated with intact autoregulation identified by TCD assessment of MCA flow are significantly higher than those indicated by SjO2 monitoring. MCA Doppler flow assessment may be useful in determining the level of CPP at which therapy should be aimed in the early resuscitation of head trauma.

Adolescent↗

PubMed1998

Diffuse neuronal perikaryon amyloid precursor protein immunoreactivity in a focal head impact model.

Amyloid precursor protein (APP) has been shown to accumulate in traumatically injured axons as early as 1 hour after injury. This accumulation may be due to interruption of fast axoplasmic transport and/or upregulation of APP synthesis. The aim of this study was to examine the neuronal cell body response to head impact using APP immunostaining in a focal non-missile head impact model. Ten anaesthetised and ventilated 2 year old Merino ewes were subjected to graded impact in the left temporal region by captive bolt. 2 hours after impact the brain was perfused fixed with formaldehyde. The tissue was mounted in paraffin, sectioned and stained with a monoclonal antibody to APP and standard H&E stain. APP positivity was semi-quantitated using a modification of our previously described sector scoring system [1]. Widespread neuronal APP positivity was found in the cerebral hemispheres and brain stem distant from the site of focal injury in all 10 animals. The most prominent APP positivity was found in the nerve cell bodies of the impacted left cerebral hemisphere. APP positive neurons were also found within regions which were structurally normal when stained with H&E. These results demonstrate diffuse neuronal perikaryon APP immunoreactivity following a focal head impact injury. The expression of APP within the neuronal cell body may be due to upregulation of APP synthesis or alterations in the availability of epitopes of APP. Further studies are in progress to address these hypotheses.

Amyloid beta-Protein Precursor↗

PubMed1998

Extraction of incurred sulphamethazine in swine tissue by microwave assisted extraction and quantification without clean up by high performance liquid chromatography following derivatization with dimethylaminobenzaldehyde.

A rapid and reliable method using microwave energy is described for the extraction of spiked and incurred (freeze-dried and fresh) sulphamethazine residues from swine tissues/organs (muscle, liver and kidney). Incurred tissues were obtained from an abattoir and freeze-dried pig tissue reference materials were produced as part of a reference material study for the Community Bureau of References, European Communities. The extraction was achieved by irradiating the sample in methanol for 25 s in a household microwave oven, commonly referred to as microwave-assisted extraction (MAE). The extracts were analysed without clean-up by high performance liquid chromatography (HPLC) using a C18 column and detected at 450 nm after derivatization with 4-dimethylaminobenzaldehyde (DMABA) in a heated rector at 40 degrees C. The limit of quantitation was 2.5 micrograms kg-1 of wet tissues. A comparison of MAE with an homogenization technique indicated that MAE worked extremely well for freeze-dried samples, while it showed significant variation for wet tissues. No sulphamethazine was detected in retail pork meat and liver samples when analysed by the MAE technique.

Animals↗

PubMed1998

Establishment of a highly differentiated thyroid cancer cell line of Hürthle cell origin.

Hürthle cell carcinomas (HCC) of the thyroid are a variant of follicular thyroid tumors. In contrast to follicular thyroid carcinoma, HCC rarely take up radioiodine and frequently metastasize to the lymph nodes. Histologically they are indistinguishable from Hürthle cell adenomas except for evidence of invasion and metastasis. How these carcinomas develop and why they behave differently than other follicular tumors is not known. Although some differentiated thyroid cancer cell lines exist, none are from Hürthle cell tumors. We have established a well-differentiated thyroid cancer cell line from a metastasis of a HCC, designated XTC.UC1. In vitro, XTC cells display epitheloid morphology, grow with a population doubling time of 4.3 +/- 0.3 days, migrate, and invade through reconstituted basement membranes. The cells are immunoreactive for and release thyroglobulin, respond to thyrotropin (TSH) with increase of intracellular cyclic adenosine monophosphate (cAMP), proliferation, and invasion of reconstituted basement membrane, thus exhibiting characteristics of well-differentiated thyroid carcinoma. In vivo, xenografted XTC cells grow with a doubling time of 9.8 +/- 0.8 days. Tumors spontaneously metastasize to the lymph nodes and less frequently to the lungs and the liver. The cells retained their differentiated function in vivo as assessed by human thyroglobulin (hTG) secretion and immunohistochemistry. This is a first report of the establishment of a unique, highly differentiated thyroid carcinoma cell line derived from an HCC. Based on the ability to invade through reconstituted basement membrane in vitro and the potential to metastasize in vivo, this cell line may provide a unique model to study invasion and metastazation of well-differentiated thyroid cancer.

Adenocarcinoma↗

PubMed1998

Clock-face drawing, reading and setting tests in the screening of dementia in Chinese elderly adults.

Comprehensive neuropsychological batteries focus on the subtle cognitive deficits in dementia, but a brief screening instrument is also of immense practical value. As the clock-drawing test encompasses a number of cognitive domains frequently disturbed by the dementing process, it is considered to be a suitable screening instrument for the disorder. We documented the usefulness of a new scoring method of the clock-drawing test for screening of dementia in the elderly Chinese in Hong Kong. Fifty-three demented individuals and 53 healthy elderly controls were assessed. At a cutoff score of 3/4, the sensitivity and specificity of the clock-drawing test in screening of dementia was 83% and 79%. With a composite test of clock reading and clock setting, the positive predictive value of the clock face test was 98%. This new scoring method of clock-drawing proved to be a valid measure for screening of dementia. It is applicable in non-English speaking populations and should be a useful adjunct for quick screening assessment of dementia.

Aged↗

PubMed1998

Ambulatory urodynamics of female soldiers.

The purpose of this study was to assess the accuracy of ambulatory urodynamic monitoring compared with conventional urodynamic studies for the detection of exercise-induced urinary incontinence in the female soldier. Fifty active duty female soldiers with exercise-induced urinary incontinence and 10 asymptomatic control soldiers underwent conventional multichannel cystometry and then ambulatory monitoring during work or exercise. Ambulatory monitoring detected a greater number of abnormalities than conventional multichannel urodynamic studies in exercise-induced urinary incontinence. This greater sensitivity is valuable in formulating more effective treatment. Behavioral interventions were effective in treating exercise-induced urinary incontinence in this population. Test results normalized after behavioral intervention. It is neither cost-effective nor efficacious to require sophisticated urodynamic testing before instituting behavioral interventions.

Adult↗

PubMed1997

Cyr61, product of a growth factor-inducible immediate-early gene, regulates chondrogenesis in mouse limb bud mesenchymal cells.

Chondrogenesis during embryonic skeletal development involves the condensation of mesenchymal cells followed by their differentiation into chondrocytes. We describe herein a previously unrecognized regulator of mammalian chondrogenesis encoded by a murine growth factor-inducible immediate-early gene, cyr61. The Cyr61 protein is a secreted, heparin-binding protein (379 amino acids with 38 conserved cysteines) that promotes cell adhesion, migration, and proliferation. The expression pattern of the cyr61 gene during embryogenesis is tissue specific and temporally regulated. Most notably, cyr61 is transiently expressed in mesenchymal cells of both mesodermal and neuroectodermal origins undergoing chondrogenesis, suggesting that Cyr61 may play a role in the development of the embryonic skeleton. In this communication, we demonstrate that the Cyr61 protein promotes chondrogenesis in micromass cultures of limb bud mesenchymal cells in vitro and is likely to play a similar role in vivo based on the following observations: (1) Cyr61 is present in the embryonic limb mesenchyme during chondrogenesis in vivo and in vitro; (2) purified recombinant Cyr61 protein added exogenously to micromass cultures promotes chondrogenesis as judged by precocious expression of type II collagen, increased [35S]sulfate incorporation, and larger Alcian blue-staining cartilage nodules; (3) Cyr61 enhances cell-cell aggregation, an initial step in chondrogenesis, and promotes chondrogenic differentiation in cultures plated at subthreshold cell densities that are otherwise unable to support differentiation; and (4) neutralization of the endogenous Cyr61 with specific antibodies inhibits chondrogenesis. Taken together, these results identify Cyr61 as a novel player in chondrogenesis that contributes to the development of the mammalian embryonic skeleton.

Animals↗

PubMed1997

Prevalence of child physical and sexual abuse in the community. Results from the Ontario Health Supplement.

CONTEXT: Although child maltreatment is considered common, few community surveys have examined the prevalence of more than 1 type of maltreatment among both males and females. OBJECTIVE: To determine the prevalence of a history of physical and sexual abuse during childhood among the general population. DESIGN: General population survey. SETTING: Household dwellings in the province of Ontario, Canada. PARTICIPANTS: A random sample (N=9953) of residents aged 15 years and older participated in the Ontario Health Supplement. MAIN OUTCOME MEASURE: Self-administered questionnaire about a history of physical and sexual abuse in childhood. RESULTS: A history of child physical abuse was reported more often by males (31.2%) than females (21.1%), while sexual abuse during childhood was more commonly reported by females (12.8%) than males (4.3%). Severe physical abuse was reported by similar proportions of males (10.7%) and females (9.2%). A greater percentage of females reported a history of severe sexual abuse (11.1%) compared with males (3.9%). Age of the respondent was not significantly associated with childhood abuse within any category for males. However, for females, the reported prevalence in childhood of sexual abuse, co-occurrence of physical and sexual abuse, and both categories of severe abuse decreased with increasing age of the respondent. CONCLUSIONS: A history of childhood maltreatment among Ontario residents is common. Child abuse may be more prevalent in younger women compared with older women, or there may be a greater willingness among younger women to report abuse.

Adolescent↗