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Biomedical subjects

M Leung

Publications and source records attributed to M Leung.

At least 19 recordsLinked to original sources
PubMed2001

Neurologic complications due to catheterization.

In our university cardiac center, the incidence of a cohort of children with acute neurologic complications resulting from cardiac catheterization performed for acyanotic or cyanotic congenital heart disease is 0.38% (14 children of a total of 3,648 catheterization procedures). Neurologic complications consisted of convulsion (n = 10), stroke (n = 6), intracranial hemorrhage (n = 2), extrapyramidal features (n = 1), paraplegia (n = 1), visual impairment (n = 1), hearing impairment (n = 1), and brachial plexus injury (n = 1). The main risk factors included prolonged duration of catheterization procedure and interventional manipulation in addition to cardiac catheterization. The possible mechanisms causing brain injury included cerebral embolism from local clots and hypoxia resulting from complications during the procedure. Other complications included intracranial hemorrhage secondary to anticoagulation and peripheral plexopathy because of prolonged fixed posture during anesthesia. The prognosis for the majority of patients with stroke is good. Neurologic sequelae, such as global developmental delay or epilepsy, occurred in those with hypoxic-ischemic encephalopathy.

Acute Disease↗
PubMed2001

Membrane cofactor protein (MCP; CD46) expression in transgenic mice.

Human membrane cofactor protein (MCP; CD46) is a widely distributed complement regulator. In the mouse, expression of MCP is largely restricted to the testis while a related, widely expressed protein (Crry) appears to perform MCP's (CD46) regulatory activity. We have developed two mouse strains transgenic for human MCP (CD46) utilizing an approximately 400 kb YAC clone carrying the complete gene. A third mouse strain was generated using an overlapping YAC clone isolated from a second library. The expression of human MCP (CD46) in these mouse strains was characterized by immunohistochemistry, FACS, Western blotting and RT-PCR. No differences were detected in the isoform pattern or distribution among the three strains, although the expression level varied according to how many copies of the gene were integrated. The expression profile closely mimicked that observed in humans, including the same pattern of isoform expression as the donor. In addition, tissue-specific isoform expression in the kidney, salivary gland and brain paralleled that observed in man. The transgenic mice expressed low levels of MCP (CD46) on their E, in contrast to humans but in line with most other primates. These mice should be a useful tool to analyse tissue-specific expression, to establish animal models of infections and to characterize the role of MCP (CD46) in reproduction.

Animals↗
PubMed2000

Dissecting sites important for complement regulatory activity in membrane cofactor protein (MCP; CD46).

Membrane cofactor protein (MCP; CD46), a widely distributed regulator of complement activation, is a cofactor for the factor I-mediated degradation of C3b and C4b deposited on host cells. MCP possesses four extracellular, contiguous complement control protein modules (CCPs) important for this inhibitory activity. The goal of the present study was to delineate functional sites within these modules. We employed multiple approaches including mutagenesis, epitope mapping, and comparisons to primate MCP to make the following observations. First, functional sites were located to each of the four CCPs. Second, some residues were important for both C3b and C4b interactions while others were specific for one or the other. Third, while a reduction in ligand binding was invariably accompanied by a parallel reduction in cofactor activity (CA), other mutants lost or had reduced CA but retained ligand binding. Fourth, two C4b-regulatory domains overlapped measles virus interactive regions, indicating that the hemagglutinin docks to a site important for complement inhibition. Fifth, several MCP regulatory areas corresponded to functionally critical, homologous positions in other CCP-bearing C3b/C4b-binding proteins. Based on these data and the recently derived crystal structure of repeats one and two, computer modeling was employed to predict MCP structure and examine active sites.

Amino Acid Sequence↗
PubMed2000

Estimating the components of the gap effect.

The gap effect refers to the finding that saccadic latencies are typically reduced when a fixation point is removed prior to the appearance of a peripheral target. This reduction in saccadic reaction time (SacRT) is thought to be due to a general warning effect and an oculomotor specific fixation offset that occur when the fixation point is removed. In order to estimate the contribution of each of these effects to the overall gap effect, this paper introduces a new manipulation, the partial-gap trial, where the fixation point undergoes a change in size prior to the presentation of the target. The partial-gap trial is presumed to provide the visual warning effect of the fixation offset (i.e. similar to that in a gap trial) but does not provide the fixation offset effect (FOE). When the fixation point was abruptly reduced in size before the presentation of the target, the estimated decrease in SacRT due to the visual warning effect was 5-7% and did not differ in the presence or absence of an auditory warning signal. It was found that auditory warning effect and the FOE interacted in reducing SacRTs. Additionally, when the fixation point was abruptly increased in size before the presentation of the target, SacRTs were slower than when the fixation point did not change in size and remained present for the entire trial (i.e. an overlap trial). We conclude that this new partial-gap paradigm is a useful method for researchers wishing to separately examine FOE and visual warning effects.

Adult↗
PubMed2000

Nerve growth factor potentiated the sodium butyrate- and PMA-induced megakaryocytic differentiation of K562 leukemia cells.

We have recently reported that retinoic acid (RA) induced the expression of trkA, the high affinity receptor for nerve growth factor (NGF), in human chronic myelogenous leukemia K562 cells. In this paper, we examined the ability of several other differentiation inducers to regulate the expression of trkA and NGF in K562 cells. We found that the expression of trkA was dramatically induced by the two megakaryocyte lineage inducers sodium butyrate (NaBut) and phorbol 12-myristate 13-acetate (PMA), but not by the two erythrocyte lineage inducers hemin or 1-beta-D-arabinofuranosyl cytosine (Ara-C). Furthermore, activation of the up-regulated trkA receptor by exogenous NGF potentiated the megakaryocytic differentiation of K562 cells induced by NaBut and PMA. Our results demonstrated that trkA is one of the essential genes that are up-regulated and involved in the megakaryocytic differentiation of K562 leukemia cells triggered by these differentiation inducers. Our findings suggest that NGF, in addition to its pivotal roles in the nervous system, may also play important roles in hematopoietic differentiation.

Butyric Acid↗
PubMed2000

Maximising the clinical use of exercise gaseous exchange testing in children with repaired cyanotic congenital heart defects: the development of an appropriate test strategy.

Implicit in deciding upon an exercise test strategy to elucidate cardiopulmonary function in children with congenital heart disease are appropriate application of gas exchange techniques and the significance of the data collected to the specific congenital heart disorder. Post-operative cardiopulmonary responses to exercise in cyanotic disorders are complex and, despite a large body of extant literature in paediatric patients, there has been much difficulty in achieving quality and consistency of data. Maximal oxygen uptake is widely recognised as the best single indicator of cardiopulmonary function and has therefore been the focus of most clinical exercise tests in children. Many children with various heart anomalies are able to exercise to maximum without adverse symptoms, and it is essential that test termination is based on the same criteria for these children. Choosing appropriate, valid indicators of maximum in children with congenital heart disease is beset by difficulties. Such maximal intensity exercise testing procedures have been challenged on the grounds that they do not give a good indication of cardiopulmonary function that is relevant to real life situations. Furthermore, they are prone to much interindividual variability and error in the definition of maximal exertion. Alternative strategies have been proposed which focus upon dynamic submaximal and kinetic cardiopulmonary responses, which are thought to be less dependent on maximal voluntary effort and more suited to the daily activity patterns of children. These methods are also not without problems. Variability in anaerobic threshold measurements and controversy regarding its physiological meaning have been debated. It is recommended that an appropriate cardiopulmonary exercise gas exchange test strategy, which provides clinically useful information for children with cyanotic congenital heart disease, should include both maximal and submaximal data. The inclusion of oxygen uptake kinetics and ventilatory data are encouraged, since they may allow the distinction between a pulmonary, cardiovascular or inactivity related exercise limitation.

Age Factors↗
PubMed1999

Ring avulsion injuries.

BACKGROUND: Ring avulsion injuries can vary in severity from mere breach of the skin through to complete amputation or degloving. Management of the more severe injuries remains controversial in deciding whether to salvage or amputate. METHOD: Six cases managed between 1991 and 1997 are presented. RESULTS: Results were comparable to the larger series published. CONCLUSION: Referral to a microsurgical unit and attempted repair where possible are recommended.

Female↗
PubMed1999

Free toe pulp transfer for digital reconstruction after high-pressure injection injury.

We report two cases of high-pressure injection injuries to the fingertip in which free toe pulp flaps were used to resurface the palmar surface of the finger following extensive wound debridement. There was good return of sensibility and, because of the high durability of the donor skin, both patients regained good functional use of the injured digits and returned to heavy manual work. There was minimal associated morbidity of the donor sites. The free toe pulp flap represents an excellent alternative for resurfacing the digit with a large residual skin defect after high-pressure injection injury.

Accidents, Occupational↗
PubMed1999

Survey of vitamin and mineral supplementation after gastric bypass and biliopancreatic diversion for morbid obesity.

BACKGROUND: The authors investigated whether practice patterns of bariatric surgeons correlate with published data regarding metabolic deficiencies after Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD). METHODS: 109 surgeons completed a questionnaire to determine use of supplements and frequency of lab tests. RESULTS: Regarding supplements routinely prescribed after RYGB, 96% of surgeons gave multivitamins, 63% gave iron, and 49% gave vitamin B12. After BPD, 96% of surgeons gave multivitamins, 67% gave iron, 42% gave vitamin B12, 97% gave calcium, 63% gave fat-soluble vitamins, and 21% gave protein supplements. Regarding laboratory tests obtained routinely after RYGB, 95% of surgeons do complete blood counts, 56% do iron determinations, 66% do vitamin B12 determinations, 58% do folate determinations, 76% do electrolyte determinations, and 8% test for proteins. After BPD, 96% of surgeons do complete blood counts, 80% do iron determinations, 67% do vitamin B12 determinations, 71% do folate determinations, 88% do electrolyte determinations, 84% do protein determinations, and 46% test for fat-soluble vitamins. Regarding frequency of blood tests, after RYGB, 22% of surgeons obtain them after 3 months, 33% after 6 months, and 41% after 12 months; 4% do not routinely obtain postoperative laboratory tests. After BPD, 46% of surgeons obtain them after 3 months, 33% after 6 months, and 16% after 12 months; one does not obtain laboratory tests. Surgeons estimated these deficiencies after RYGB: 16% iron, 12% vitamin B12, 14% anemia, 5% protein, and 3% calcium. They estimated these deficiencies after BPD: 26% iron, 11% vitamin B12, 21% anemia, 18% protein, 16% calcium, and 6% fat-soluble vitamins. The estimated incidence of deficiencies after RYGB was considerably lower than the published incidence. Unnecessary tests were commonly performed (electrolytes after RYGB). CONCLUSION: Despite wide variations in the performance of laboratory tests and the use of supplements, the practice patterns of most surgeons protect patients from developing severe metabolic deficiencies after RYGB and BPD.

Biliopancreatic Diversion↗
PubMed1997

The combined differentiating effect of retinoic acid and vincristine on acute promyelocytic leukemia.

We have previously shown that HL-60 cells exposed to all-trans retinoic acid (ATRA) after treatment with a non-cytotoxic concentration of vincristine (VCR) result in granulocytic maturation and differentiation, suggesting that VCR might exhibit a synergistic action with ATRA in the treatment of acute promyelocytic leukemia. In this report, leukemic cells obtained from a patient with acute promyelocytic leukemia were exposed to 20 nM VCR for 1 h followed by 1 microM ATRA for 6 days. An increase in the expression of mature myelocyte antigens, CD11b and CD15, was observed as determined by flow cytometric analysis. Treatment of VCR or ATRA alone, however, did not have any effect on the expression of these mature myelocyte antigens of the leukemic cells. These results suggest that combined VCR and ATRA may be more efficient in the differentiation therapy of acute promyelocytic leukemia, particularly in those cases showing a slow response to ATRA therapy.

Antigens, CD↗
PubMed1997

Short-term effects of topical levobunolol on the human retinal circulation.

PURPOSE: The effect of topical levobunolol HCl 0.5% on the retinal circulation was studied on 15 normal volunteers aged 21-54 years (32 +/- 10 years). METHODS: In a double-masked, randomised design, one eye of each subject received a drop of levobunolol HCl 0.5% (LEV) and the fellow eye received a drop of artificial tears (TEAR). Leucocyte velocity (VBFS) and density in the retinal macular microcirculation were measured by the blue-field simulation technique. Venous diameter (D), maximum erythrocyte velocity (Vmax) and volumetric blood flow rate (Q) were measured in a major temporal vein by laser Doppler velocimetry and monochromatic fundus photography. RESULTS: The following average changes from baseline were observed 2 hours after treatment: heart rate, -4.6 +/- 8.3% (p = 0.04); intraocular pressure, -31.7 +/- 10.6% (p = 0.0001); and perfusion pressure, 15.4 +/- 14.4% (p = 0.02) in LEV eyes; no statistically significant changes in IOP and perfusion pressure were seen in TEAR eyes. When each eye was compared with its own baseline, there were no significant changes in VBFS, density, D, Vmax and Q in LEV eyes. In TEAR eyes, there were no significant changes in VBFS, density, Vmax and Q, but a significant change in D (-1.8 +/- 2.6%; p = 0.02) was observed. A significant average percentage increase in Q of 10.9 +/- 19.2% (paired t-test between the change after LEV and the change after TEAR, p = 0.044) was seen in LEV eyes when compared with TEAR eyes. Twelve of the 15 subjects demonstrated a relative increase in Q in the LEV eyes in comparison with the TEAR eyes, while 3 subjects showed the opposite. CONCLUSION: A significant difference in the effect of levobunolol between the two eyes was detected, even though there was no statistically significant effect when each eye was compared with its baseline.

Administration, Topical↗
PubMed1997

Rarity of transferable beta-lactamase production by Klebsiella species.

We report a survey of beta-lactamases and their transferability in Klebsiella spp. isolated from blood during 1992-95. beta-Lactamases were characterized by determination of isoelectric point (pI), by hybridization of plasmid DNA preparations with probes for SHV and TEM sequences and by PCR with SHV- or TEM-specific primers. There were 80 isolates of Klebsiella pneumoniae and 22 isolates of Klebsiella oxytoca. Most isolates of K. pneumoniae had a chromosomally encoded SHV-1 beta-lactamase (or a closely related enzyme); K. oxytoca also produced chromosomal beta-lactamases, but these were distinct from SHV-1. Plasmid-encoded beta-lactamases were rare in Klebsiella spp., being found in six (7.5%) isolates of K. pneumoniae and in none of the K. oxytoca. beta-Lactamase activities were relatively low (< 100 nmoles nitrocefin hydrolysed per minute per mg of protein) and ampicillin MICs were < or = 128 mg/L for most isolates of both species. However, all isolates of K. pneumoniae with plasmid-encoded beta-lactamases, three other isolates of K. pneumoniae and three isolates of K. oxytoca had high beta-lactamase activities (> 100 nmoles/mg/min) and very high ampicillin MICs (> or = 1024 mg/L).

Ampicillin↗
PubMed1997

alpha 1-Proteinase inhibitor in gingival crevicular fluid of humans with adult periodontitis: serpinolytic inhibition by doxycycline.

The serum protein, alpha 1-proteinase inhibitor (alpha 1-PI), defends the host against serine proteinases, e.g. PMN elastase. Using a rabbit anti-serum against human alpha 1-PI, this protein in GCF was quantified from a standard curve constructed from dot-blot analysis and characterized by Western blot. GCF was collected on filter paper strips from healthy (H), gingivitis (G) and adult periodontitis (AP) patients, then extracted with Tris/NaCl/CaCl2 buffer, pH 7.6. alpha 1-PI concentration increased with G and was highest in AP subjects. H sites only showed intact alpha 1-PI (52 kDa); no degradation fragments (48 kDa) were detected. In G and AP subjects, alpha 1-PI degradation fragments were seen in 17% and 71% of GCF samples, respectively. Both collagenase and alpha 1-PI-degrading activities in GCF increased with severity of inflammation (GCF flow). Moreover, the alpha 1-PI degrading (or serpinolytic) activity was characterized as a matrix metalloproteinase, probably collagenase, based on its in vitro response to a panel of different proteinase inhibitors including doxycycline. We propose: (1) that collagenase promotes periodontal breakdown not only by degrading collagen, but also by depleting alpha 1-PI regulation of elastase and other serine-proteinases, thereby favoring a broader attack on extracellular matrix (ECM) constituents, and (2) based on a recent longitudinal double-blind study using the techniques described above for alpha 1-PI analysis, that low-dose doxycycline administration to humans with adult periodontitis can inhibit this broad cascade of ECM degradation.

Adult↗
PubMed1996

Complementation analysis of mutants of nitric oxide synthase reveals that the active site requires two hemes.

For catalytic activity, nitric oxide synthases (NOSs) must be dimeric. Previous work revealed that the requirements for stable dimerization included binding of tetrahydrobiopterin (BH4), arginine, and heme. Here we asked what function is served by dimerization. We assessed the ability of individually inactive mutants of mouse inducible NOS (iNOS; NOS2), each deficient in binding a particular cofactor or cosubstrate, to complement each other by generating NO upon cotransfection into human epithelial cells. The ability of the mutants to homodimerize was gauged by gel filtration and/or PAGE under partially denaturing conditions, both followed by immunoblot. Their ability to heterodimerize was assessed by coimmunoprecipitation. Heterodimers that contained only one COOH-terminal hemimer and only one BH4-binding site could both form and function, even though the NADPH-, FAD-, and FMN-binding domains (in the COOH-terminal hemimer) and the BH4-binding sites (in the NH2-terminal hemimer) were contributed by opposite chains. Heterodimers that contained only one heme-binding site (Cys-194) could also form, either in cis or in trans to the nucleotide-binding domains. However, for NO production, both chains had to bind heme. Thus, NO production by iNOS requires dimerization because the active site requires two hemes.

Animals↗
PubMed1996

Occlusion of large atrial septal defects with a centering buttoned device: early clinical experience.

A feasibility clinical study was conducted for the transcatheter occlusion of large ostium secundum atrial septal defects with the centering buttoned device. The centering buttoned device is a modification of the regular buttoned device in which a centering counter-occluder is sutured at the central 40% portion of the occluder. During centering it is stretched, forming a parachute-shaped structure and pulling the occluder over the center of the defect. During buttoning, the counter-occluder forms a double figure eight, opposing the right atrial side of the atrial septum. Occlusion was performed in 12 patients aged 6 to 56 years. All had been rejected for transcatheter occlusion by the regular buttoned device, because of either their defect size or the lack of adequate septal rim. The defect size varied between 23 and 31 mm, and the device size varied between 45 and 60 mm. Nine had immediate effective occlusions of their defects and three residual shunts. One patient with unbuttoning had hemolysis at 2 weeks and underwent surgery. Early results of the transcatheter occlusion of large atrial septal defects are promising, and larger clinical trials are justified.

Adolescent↗