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Biomedical subjects

M Yeung

Publications and source records attributed to M Yeung.

At least 19 recordsLinked to original sources
PubMed2005

Select Listeria monocytogenes subtypes commonly found in foods carry distinct nonsense mutations in inlA, leading to expression of truncated and secreted internalin A, and are associated with a reduced invasion phenotype for human intestinal epithelial cells.

The surface protein internalin A (InlA) contributes to the invasion of human intestinal epithelial cells by Listeria monocytogenes. Screening of L. monocytogenes strains isolated from human clinical cases (n=46), foods (n=118), and healthy animals (n=58) in the United States revealed mutations in inlA leading to premature stop codons (PMSCs) in L. monocytogenes ribotypes DUP-1052A and DUP-16635A (PMSC mutation type 1), DUP-1025A and DUP-1031A (PMSC mutation type 2), and DUP-1046B and DUP-1062A (PMSC mutation type 3). While all DUP-1046B, DUP-1062A, DUP-16635A, and DUP-1031A isolates (n=76) contained inlA PMSCs, ribotypes DUP-1052A and DUP-1025A (n=72) contained isolates with and without inlA PMSCs. Western immunoblotting showed that all three inlA PMSCs result in the production of truncated and secreted InlA. Searches of the Pathogen Tracker database, which contains subtype and source information for more than 5,000 L. monocytogenes isolates, revealed that the six ribotypes shown to contain isolates with inlA PMSCs were overall more commonly isolated from foods than from human listeriosis cases. L. monocytogenes strains carrying inlA PMSCs also showed significantly (P=0.0004) reduced invasion of Caco-2 cells compared to isolates with homologous 3' inlA sequences without PMSCs. Invasion assays with an isogenic PMSC mutant further supported the observation that inlA PMSCs lead to reduced invasion of Caco-2 cells. Our data show that specific L. monocytogenes subtypes which are common among U.S. food isolates but rare among human listeriosis isolates carry inlA mutations that are associated with, and possibly at least partially responsible for, an attenuated invasion phenotype.

Bacterial Proteins↗
PubMed2004

The effect of immunomodulatory treatment on multiple sclerosis fatigue.

OBJECTIVE: To assess the effects of glatiramer acetate and beta interferon on fatigue in multiple sclerosis. METHODS: Fatigue was measured at baseline and six months using the fatigue impact scale (FIS). Groups (glatiramer acetate and beta interferon) were evaluated for the proportion improved, using Fisher's exact test. Logistic regression analysis assessed the relation between treatment group and improvement and controlled for confounding variables. RESULTS: Six month paired FIS assessments were available for 218 patients (76% female). Ages ranged between 19 and 61 years, with 86% having relapsing-remitting disease. Glatiramer acetate was used by 61% and beta interferon by 39%. At baseline, total FIS and subscale scores were comparable in the two groups. More patients improved on glatiramer acetate than on beta interferon on total FIS (24.8% v 12.9%, p = 0.033; adjusted odds ratio = 2.36, 95% confidence interval 1.03 to 5.42), and on physical (28.6% v 14.1%, p = 0.013) and cognitive subscales (21.1% v 10.6%, p = 0.045). Logistic regression analysis confirmed the association between glatiramer acetate use and improved fatigue, after accounting for baseline group differences. CONCLUSIONS: The odds of reduced multiple sclerosis fatigue were around twice as great with glatiramer acetate treatment as with beta interferon. Confirmation of this result is required.

Adjuvants, Immunologic↗
PubMed1999

Expression, purification, crystallization and preliminary X-ray analysis of Escherichia coli argininosuccinate synthetase.

A recombinant form of Escherichia coli argininosuccinate synthetase with a C-terminal polyhistidine affinity tag has been expressed, purified and subsequently crystallized using the hanging-drop vapour-diffusion technique. The crystals grow as large rectangular chunks with unit-cell dimensions a = 79.70, b = 105.84, c = 127.33 A, alpha = beta = gamma = 90 degrees. The crystals exhibit the symmetry of space group I222 and diffract to a minimum d-spacing of 1.6 A at station X8C of the National Synchrotron Light Source, Brookhaven National Laboratory. On the basis of density calculations, one monomer of this homotetrameric protein is predicted per asymmetric unit (Matthews coefficient V(m) = 2.69 A(3) Da(-1)).

Argininosuccinate Synthase↗
PubMed1998

Distal hereditary upper limb muscular atrophy.

OBJECTIVES: To identify the clinical, electrophysiological, and genetic characteristics of a family with an unusual form of hereditary motor neuron disease. METHODS: Surviving members of a pedigree in which affected members presented with weakness and atrophy of distal musculature in the upper limbs were examined clinically and electrophysiologically, and had genetic testing. RESULTS: The disease was autosomal dominantly inherited and manifested as weakness and atrophy of distal musculature in the upper limbs, with minimal involvement of lower limbs, brisk reflexes, minimal sensory findings, and considerable variability in severity among the affected persons. Nerve conduction studies disclosed near normal motor conduction velocity, reduced motor compound action potential amplitude, prolonged distal motor latency, prolonged sensory latency, and normal sensory compound action potential amplitude. Needle electrode examination showed reduced number and increased size of motor unit potentials, but no fibrillations or fasciculations. CONCLUSION: Distal upper limb muscular atrophy is a distinct clinical entity.

Arm↗
PubMed1997

Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss.

BACKGROUND: Recurrent fetal loss has been well described in women with antiphospholipid antibodies. Such women also often have other autoantibodies commonly found in patients with systemic lupus erythematosus. Treating them with prednisone and aspirin may reduce the risk of fetal loss. METHODS: We screened 773 nonpregnant women who had the unexplained loss of at least two fetuses for antinuclear, anti-DNA, antilymphocyte, and anticardiolipin antibodies and for the lupus anticoagulant. Of 385 women with at least one autoantibody, 202 who later became pregnant were randomly assigned in equal numbers to receive either prednisone (0.5 to 0.8 mg per kilogram of body weight per day) and aspirin (100 mg per day) or placebo for the duration of the pregnancy. The women were stratified according to age (18 to 34 years or 35 to 39 years) and the week of gestation at which the previous fetal losses had occurred (< or = 12 or > 12 weeks). The primary outcome measure was a successful pregnancy. RESULTS: Live infants were born to 66 women in the treatment group (65 percent) and 57 women in the placebo group (56 percent, P=0.19). More infants were born prematurely in the treatment group than in the placebo group (62 percent vs. 12 percent, P<0.001). The major side effects of therapy in the mothers were hypertension (treatment group, 13 percent; placebo group, 5 percent; P=0.05) and diabetes mellitus (15 percent and 5 percent, P=0.02). CONCLUSIONS: Treating women who have autoantibodies and recurrent fetal loss with prednisone and aspirin is not effective in promoting live birth, and it increases the risk of prematurity.

Abortion, Habitual↗
PubMed1997

Quantitation of change in the medullary compartment in renal allograft by ultrasound.

Twenty-three renal allograft recipients with uncomplicated post-transplant courses were sonographically evaluated on the 3rd, 10th, 30th, and 90th post-operative day. The cortical thickness (CT), pyramidal length (PL), pyramidal width (PW), corticomedullary ratio (CMR), and medullary pyramidal index (MPI) were determined at each examination. The measurements obtained from the donor before implantation were used as the baseline. PW increased significantly in the absence of rejection and obstruction in renal allograft during the early post-transplant period. Although the MPI, and to a lesser extent the CMR, detected changes in dimensions of the medullary compartment, there was considerable intra- and inter-individual variation in their values during the post-operative period.

Adult↗
PubMed1997

Written patient information about triple-marker screening: a randomized, controlled trial.

OBJECTIVE: To investigate to what extent a newly revised educational pamphlet on triple-marker screening improves patient knowledge and to identify subgroups of women who may not benefit from these materials. METHODS: Women in six geographically and demographically diverse Ontario sites were allocated randomly to receive the pamphlet on triple-marker screening or a similar-appearing educational pamphlet on daily activities during pregnancy. The primary outcome measure was the Maternal Serum Screening Knowledge Questionnaire, a previously validated 14-item scale. RESULTS: Baseline demographic, obstetric, and medical factors were comparable in the intervention and control groups, as were measures of previous exposure to triple-marker screening. Knowledge scores were significantly higher among the 133 women receiving the intervention pamphlet than among 64 women who received the control pamphlet (0.89 versus 0.52 on a scale from -2 to +2, P < .001). Subgroups not benefiting from the pamphlet on triple-marker screening were women age 25 and younger and those not speaking English at home. Those who had completed university or postgraduate education had high levels of knowledge with and without the pamphlet. CONCLUSION: Written patient information can contribute in an important way to patient knowledge about triple-marker screening. Providers of antenatal care should be made aware of the value of written patient information as well as the limitations for some subgroups of women. These subgroups are likely to require additional educational materials and resources. It would be appropriate to make these materials available to the general public and pregnant women in their physicians' offices.

Adult↗
PubMed1997

Adverse effects of screening for gestational diabetes: a prospective cohort study in Toronto, Canada.

OBJECTIVE: To investigate the adverse effects associated with a false positive 50 g glucose challenge test for gestational diabetes mellitus (GDM). SETTING: Consecutive women attending a prenatal registration clinic at a large community hospital in suburban Toronto, Canada. METHODS: Prospective cohort study of women between 12 and 24 weeks' gestation with no previous history of diabetes mellitus or GDM. Main outcome measures included anxiety (Spielberger's State-Trait Anxiety Inventory), depression (Centers for Epidemiologic Studies Depression Scale), perceived maternal health, and concern about health of the newborn. RESULTS: Among 2564 eligible subjects, there were 897 subjects with complete data at enrollment and at 32 weeks' gestation, including 88 who had false positive glucose challenge test results. At 32 weeks, only 20% (95% confidence limits 11%, 28%) of women with false positive glucose challenge test results rated their health as excellent, compared with 38% (35%, 42%) of those having negative results and those not tested (P = 0.001). These results were sustained at 36 weeks. There was no association between glucose challenge test result and the change in anxiety (P = 0.57), depression (P = 0.09) or concern about health of the newborn (P = 0.91) between baseline and 32 weeks' gestation, nor were these associations found at 36 weeks. CONCLUSIONS: False positive glucose challenge test results are about six times more likely than true positive results in the general population. Pregnant women with false positive GDM screening results experience a significant decline in their perception of their own health. These adverse effects should be taken into account when deciding about a policy of screening all pregnant women for gestational diabetes.

Canada↗
PubMed1997

Effects of [norleucine27]growth hormone-releasing hormone (GHRH) (1-29)-NH2 administration on the immune system of aging men and women.

Aging in humans is associated with the decline of functional activities of the GH-insulin-like growth factor I (IGF-I) axis and the immune system. Because lymphocytes express GH-IGF-I, as well as GHRH and their respective receptors, restoration of this axis in age-advanced individuals, by the administration of GHRH, may enhance immune cell function. This hypothesis was tested by a single blind randomized placebo-controlled trial of 5 months duration, in which healthy elderly subjects (10 women, 9 men) self-administered sc nightly placebo for 4 weeks, followed by 16 weeks of [norleucine27]GHRH (1-29)-NH2 at a dose of 10 micrograms/kg. Fasting (0800 h-0900 h) blood samples were obtained for immune studies and for measurements of serum concentrations of IGF-I and soluble interleukin (IL)-2 receptor. GH pulsatility was determined in blood samples obtained at 10-min intervals for 12 h (2000 h-0800 h). Freshly isolated peripheral lymphocytes were analyzed by flow cytometric analysis for determination of lymphocyte subsets and monocytes. Mitogen stimulation responses, natural killer cell number and cytotoxicity, basal and stimulated IL-2 secretion from cultured lymphocytes, and IL-2 and IL-2R messenger RNA expression were measured. These studies were conducted at baseline, after placebo, and during GHRH analog administration at 4 and 16 weeks. Treatment with GHRH analog resulted in a significant increase (107 and 70% in men and women, respectively) in the 12-h integrated GH secretion (P < .05) and serum IGF-I levels (28%) (P < .001) in both men and women by 4 weeks and lasted 12 weeks for IGF-I and 16 weeks for GH. Activation of the immune system occurred in both sexes within 4 weeks. A 30% increase (P < .001) in lymphocytes expressing the transferrin receptor (CD71) and in monocytes (CD14) (P < .05) occurred within 4 weeks. By 16 weeks, there was a significant increase (30%) in B cells (CD20) (P < .01), in cells expressing the T cell receptor alpha/beta (20%) (P < .01), and T cell receptor gamma/delta (40%) (P < .0001). There were no changes in the number of T cells (CD3), T cell subsets (CD4, CD8), or natural killer cell (CD57) over the treatment period. The increase in B cell number was associated with enhanced responsiveness (50%) to the B cell mitogens: pokeweed mitogen (P < .01 or better) and Staphylococus aureus cells (P < .001), and a transient increase at 4 weeks in circulating IgG (P < .0001), IgM, and IgA (P < .001). T cells were functionally activated, as evidenced by a 50% increase in responsiveness to phytohemagglutinin (P < .01 or better), 70% increase in the number of lymphocytes expressing the IL-2 receptor (IL-2R) (CD25) (P < .001), and enhanced IL-2R messenger RNA expression and basal IL-2 secretion (50%) (P < .05) at 16 weeks of treatment. Furthermore, circulating soluble IL-2 receptor rose significantly (15%) (P < .05) within 4 weeks of treatment and remained elevated for the duration of the study. There were no sex differences in the immune response to GHRH analog and no adverse effects. These results indicate that GHRH analog administration has profound immune-enhancing effects and may be of therapeutic benefit in states of compromised immune function.

Aged↗
PubMed1997

Comparative study of 18 gauge and 20 gauge intravenous catheters during transcranial Doppler ultrasonography with saline solution contrast.

A formal technical protocol has not been established for transcranial Doppler ultrasonography in the detection of venous to arterial shunts; techniques have been adapted from contrast echocardiography. We evaluated the effect of different diameter indwelling intravenous catheters on the detection of right-to-left shunts by transcranial Doppler ultrasonography. Fifteen patients underwent transcranial Doppler sonographic evaluation with saline solution contrast using both 18 gauge and 20 gauge indwelling intravenous catheters. The larger bore intravenous catheter delivered a greater number of signals in a shorter time to the insonated middle cerebral artery. We recommend that a standardized method for transcranial Doppler sonographic contrast studies include an 18 gauge intravenous catheter.

Adult↗
PubMed1996

Genetic elevation of monoamine oxidase levels in dopaminergic PC12 cells results in increased free radical damage and sensitivity to MPTP.

Production of hydrogen peroxide as a by-product of the breakdown of catecholamines by the enzyme monoamine oxidase (MAO) has been hypothesized to contribute to the increased proclivity of dopaminergic neurons for oxidative injury. We established clonal dopaminergic PC12 cell lines which have elevated MAO activity levels resulting from transgenic expression of the B isoform of the enzyme. Both MAO-A and MAO-B have relatively equivalent affinities for dopamine, and since PC12 primarily express the A and not the B form of the enzyme, this allowed us to distinguish the transgenic MAO activity in these cells from endogenous using the MAO-B specific substrate PEA. Elevation of MAO activity levels in the MAO-B+ cells resulted in higher levels of both free radicals and free radical damage compared with controls. In addition, increased MAO-B levels within PC12 cells caused a dose-dependent increase in sensitivity to the toxin MPTP. Our data suggests that oxidation of catecholamines by MAO can contribute to free radical damage in catecholaminergic neurons and that the low MAO-B activity levels found endogenously in these cells likely accounts for their relative resistance to MPTP toxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1996

Transcranial Doppler ultrasonography in the detection of venous to arterial shunting in acute stroke and transient ischaemic attacks.

OBJECTIVES: To prospectively evaluate the prevalence of venous to arterial shunting in patients with acute stroke and transient ischaemic attacks (TIAs) using transcranial Doppler ultrasonography (TCD) with saline contrast. METHODS: A consecutive series of patients with stroke or TIA underwent contrast TCD. Patients were subsequently divided into groups according to causative factors for stroke or TIA. The prevalence of right to left shunt was assessed within these groups. RESULTS: A total of 210 patients underwent contrast TCD. A right to left shunt was detected in 28.6% of patients (60 of 210). Among the patients with cryptogenic stroke or TIA, 37.1% (43 of 116) had a positive contrast TCD whereas only 18% (17 of 94) with another identifiable cause had a positive test (P = 0.0024). When age was used to further classify those patients with cryptogenic stroke, TCD was positive in 59.3% patients (16 of 27) of < or = 50 years of age versus 30.3% of patients (27 of 89) > 50 years of age (P = 0.0058). CONCLUSIONS: There was a significantly higher prevalence of venous to arterial shunting in patients with stroke or TIA of undetermined cause than in stroke patients with identifiable aetiologies, as detected by contrast TCD. The prevalence of a venous to arterial shunt was significantly higher in the younger group with cryptogenic stroke. Saline contrast TCD is a relatively non-invasive bedside procedure useful in the detection of venous to arterial shunting.

Acute Disease↗
PubMed1995

Which outcome measures should be used in rheumatoid arthritis clinical trials? Clinical and quality-of-life measures' responsiveness to treatment in a randomized controlled trial.

OBJECTIVE: To determine the discriminant validity of the core set of outcome measures proposed by the American College of Rheumatology (ACR) and the Outcome Measures in Clinical Trials (OMERACT) conference committee to be used in clinical trials of rheumatoid arthritis (RA). METHODS: Utilizing data from a multicenter randomized double-blind clinical trial of low-dose cyclosporine and placebo in RA, we estimated the relative efficiency (RE) of measures to detect a treatment effect (relative to tender joint count, which was assigned a value of 1). Four pain measures (10-cm visual analog scale [VAS], 5-point categorical scale, Health Assessment Questionnaire [HAQ] pain index, Arthritis Impact Measurement Scales [AIMS] pain score) and 3 quality-of-life measures (Problem Elicitation Technique [PET], HAQ, AIMS) were compared. RESULTS: Physician and patient global measures were the most responsive instruments, although neither was statistically superior to tender joint count. Swollen joint count, grip strength, pain measured on a 10-cm VAS, and functional status as measured by the PET and HAQ were all of intermediate responsiveness. Morning stiffness, 5-point pain scale, and erythrocyte sedimentation rate were the least responsive instruments. CONCLUSION: This study provides further evidence to support the core set of outcome measures proposed by the ACR and OMERACT:

Adolescent↗
PubMed1995

Transcranial Doppler ultrasonography and transesophageal echocardiography in the investigation of pulmonary arteriovenous malformation in a patient with hereditary hemorrhagic telangiectasia presenting with stroke.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is associated with a high incidence of pulmonary arteriovenous malformations (PAVMs), which can be the underlying cause for cerebral ischemia or brain abscess. The diagnosis of these malformations may be difficult, as clinical or radiological findings may be absent. Transcranial Doppler ultrasound (TCD) with saline contrast and transesophageal echocardiography (TEE) with saline contrast are useful in identifying patients with right-to-left shunts and may help identify PAVMs. CASE DESCRIPTION: A 68-year-old woman with HHT presented with two strokes over a 1-year period. After the first stroke, a transthoracic echocardiogram with saline contrast demonstrated significant right-to-left shunt that was interpreted as a patent foramen ovale. After the second stroke, a TCD contrast study confirmed this right-to-left shunt; however, a TEE contrast study discovered an extracardiac shunt. Pulmonary angiography revealed a left lower lobe PAVM and three telangiectasias involving the right lung. The PAVM was subsequently embolized. Postembolization radiographic imaging showed complete occlusion of the feeding vessel to the PAVM. However, repeated contrast TCD and TEE demonstrated persistent right-to-left shunting. CONCLUSIONS: In our patient, stroke may have resulted from peripheral venous emboli passing through the PAVM or from endogenous thromboemboli originating within the PAVM. TCD and TEE contrast studies were helpful in judging the efficacy of catheter embolization therapy of PAVM. TCD and TEE with saline contrast may be clinically useful follow-up examinations for recurrence or development of new PAVMs.

Aged↗
PubMed1995

Impact of pathologic extraprostatic disease on local and systemic progression following radical prostatectomy.

Fifty patients underwent radical prostatectomy for localized prostate cancer (Stages A2, B) between 1977 and 1982. Surgical specimens were examined for tumor grade and extraprostatic extension of the disease. Forty-one of the 50 patients had capsular involvement (82%), 26 (52%) positive margins and 14 (28%) seminal vesicular involvement. Six patients progressed locally, six systematically and three both. Eight patients progressed at five years and an additional seven at ten years. In all 15 progressors tumor involved the capsule yet four patients with capsular involvement alone progressed. Eleven of the 26 patients (42%) with positive margins progressed. Five of the 14 patients (37%) with seminal vesicle involvement progressed, all five had positive margins as well. None of the patients with disease confined within the capsule progressed. Gleason score for non-progressors ranged between three and nine with a median of six while for progressors it ranged between five and nine with a median of seven. Long rank test and Cox Proportional Hazard Model statistical analysis were employed among all the factors: capsular involvement, positive margins, positive seminal vesicles and grade of tumor. Positive margins was the only statistically significant factor affecting local progression of the disease in both univariate and multivariate analysis at a 95% confidence (p=0.04). All factors were statistically insignificant in affecting systemic progression (p>0.5).

Journal Article↗
PubMed1994

Compliance with prescribed drug therapy in asthma.

Morbidity and mortality from asthma in the Western world is increasing despite effective prophylactic drugs. Beta agonists are increasingly considered causal; while under-prescribing of inhaled steroids or other anti-inflammatories are accepted as causes for the problems, but the role of non-compliance with inhaled asthma therapy is rarely mentioned. Using a novel electromechanical counter MDI actuations have been recorded in three small (9-11 patients), short (2-3 weeks) studies. When aware compliance with prescribed inhaled steroids was under scrutiny, six patients were fully compliant, two took just 70% of the prescribed regimen, but two did not follow the prescribed regimen at all. When unaware of scrutiny, six out of 11 were compliant but five patients were estimated as taking less than 30-51% of the prescribed dose of inhaled steroid. When asked to monitor rescue bronchodilator usage patients consistently under-recorded. Under-use as well as under prescription of inhaled steroids and under-estimation (8) of beta 2-agonists use may be contributory factors to the present increase in asthma mortality and morbidity. These potential problems of poor compliance need larger scale studies to show how and if behaviour can be altered to improve compliance.

Adrenergic beta-Agonists↗
PubMed1993

Cyclosporine as possible prophylaxis for obstructive airways disease after allogeneic bone marrow transplantation.

The objective of this study was to evaluate the impact of cyclosporine (cyclosporin A; CyA) prophylaxis for graft-versus-host disease (GVHD) on the development of obstructive airways disease (OAD) after allogeneic bone marrow transplantation (BMT) in leukemic patients. Patients with normal pulmonary function tests (PFTs) prior to BMT were followed with serial PFTs for the development of OAD. Follow-up PFTs were performed at 3, 6, 9, and 12 months, and thereafter at consecutive yearly intervals. Obstructive airways disease was defined as FEV1 less than 80 percent, ratio of FEV1 over the forced vital capacity (FEV1/FVC) less than 80 percent of predicted, maximal midexpiratory flow rate at 50 percent vital capacity less than 65 percent of predicted, or residual volume greater than 120 percent of predicted. In the period prior to CyA prophylaxis for GVHD development (March 1983 to September 1986), 17 (39 percent) of the 44 patients undergoing BMT developed OAD, compared with 2 (4 percent) of 45 in the post-CyA period (September 1986 to March 1990) (chi 2 = 17; p < 0.00005). Age, sex, type of leukemia, severity of GVHD, histocompatibility status, presence of acute GVHD, and sex mismatch between donor and recipient were not associated with development of OAD. Although chronic GVHD was associated with OAD in univariate analysis, a multivariate logistic regression analysis showed that the only significant independent predictor for OAD was the use of CyA. We conclude that CyA is protective against the development of OAD after BMT in leukemic patients.

Adolescent↗