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Biomedical subjects

K M Chan

Publications and source records attributed to K M Chan.

At least 109 records · Page 6Linked to original sources

Detection of cell wall mannoprotein Mp1p in culture supernatants of Penicillium marneffei and in sera of penicilliosis patients.

Mannoproteins are important and abundant structural components of fungal cell walls. The MP1 gene encodes a cell wall mannoprotein of the pathogenic fungus Penicillium marneffei. In the present study, we show that Mp1p is secreted into the cell culture supernatant at a level that can be detected by Western blotting. A sensitive enzyme-linked immunosorbent assay (ELISA) developed with antibodies against Mp1p was capable of detecting this protein from the cell culture supernatant of P. marneffei at 10(4) cells/ml. The anti-Mp1p antibody is specific since it fails to react with any protein-form lysates of Candida albicans, Histoplasma capsulatum, or Cryptococcus neoformans by Western blotting. In addition, this Mp1p antigen-based ELISA is also specific for P. marneffei since the cell culture supernatants of the other three fungi gave negative results. Finally, a clinical evaluation of sera from penicilliosis patients indicates that 17 of 26 (65%) patients are Mp1p antigen test positive. Furthermore, a Mp1p antibody test was performed with these serum specimens. The combined antibody and antigen tests for P. marneffei carry a sensitive of 88% (23 of 26), with a positive predictive value of 100% and a negative predictive value of 96%. The specificities of the tests are high since none of the 85 control sera was positive by either test.

Antibodies, Fungal↗

Mature T lymphocyte apoptosis--immune regulation in a dynamic and unpredictable antigenic environment.

Apoptosis of mature T lymphocytes preserves peripheral homeostasis and tolerance by countering the profound changes in the number and types of T cells stimulated by diverse antigens. T cell apoptosis occurs in at least two major forms: antigen-driven and lymphokine withdrawal. These forms of death are controlled in response to local levels of IL-2 and antigen in a feedback mechanism termed propriocidal regulation. Active antigen-driven death is mediated by the expression of death cytokines such as FasL and TNF. These death cytokines engage specific receptors that assemble caspase-activating protein complexes. These signaling complexes tightly regulate cell death but are vulnerable to inherited defects. Passive lymphokine withdrawal death may result from the cytoplasmic activation of caspases that is regulated by mitochondria and the Bcl-2 protein. The human disease, Autoimmune Lymphoproliferative Syndrome (ALPS) is due to dominant-interfering mutations in the Fas/APO-1/CD95 receptor and other components of the death pathway. The study of ALPS patients reveals the necessity of apoptosis for preventing autoimmunity and allows the genetic investigation of apoptosis in humans. Immunological, cellular, and molecular evidence indicates that throughout the life of a T cell, apoptosis may be evoked in excessive, harmful, or useless clonotypes to preserve a healthy and balanced immune system.

Animals↗

Effect of verbascoside on decreasing concentration of oxygen free radicals and lipid peroxidation in skeletal muscle.

AIM: To detect the effects of verbascoside on decreasing the concentration of oxygen free radicals (OFR) and lipid peroxidation in skeletal muscle resulting from exhaustive exercise. METHODS: Electron spin resonance (ESR) technique and thiobarbituric acid reaction (TBAR) method were used to detect the concentration of OFR in intact gastrocnemius muscle and the contents of milondialdehyde (MDA) in muscle homogenate. RESULTS: Verbascoside decreased the concentration of OFR (P < 0.05) and the level of lipid peroxidation (P < 0.05) in muscle caused by exercise. CONCLUSION: Verbascoside has the effects of reducing oxidative stress in muscle caused by exhaustive exercise by decreasing the concentration of free radicals and the level of lipid peroxidation.

Animals↗

Posterior cerebral artery territory infarct presenting as acute psychosis.

An 82-year-old man with a past medical history of hypertension was admitted to a psychiatric hospital for sudden onset of acute psychosis. He was then transferred to an acute geriatric unit for further evaluation. During the admission the patient was noted to be very restless, agitated and noisy and was shouting and screaming incessantly. This was interspersed with occasional short periods of calm and quiet. Clinically, no obvious focal neurological deficits were detected. A CT scan of the brain was performed and it revealed an acute infarct involving the area supplied by the left posterior cerebral artery. This was a rather atypical presentation for an infarct involving this area.

Aged↗

Functional status of the elderly in Singapore.

BACKGROUND: This study was done to look at prevalence and factors affecting functional dependence. The data in this paper were part of the 'Community Study on State of Health, Function, Cognitive and Social State of Elderly People in Singapore' conducted in Singapore between September 1992 and December 1993. PATIENTS: Four hundred and one elderly, aged 60 years and above were studied. Sixty-eight subjects (17%) were dependent in at least one function of Activities of Daily Living (ADL) as measured by the Barthel's Index (BI). RESULTS: The most common problem identified using this index was urinary incontinence. Forty subjects (10.4%) were dependent in at least one Instrumental Activities of Daily Living (IADL) function. The most common mode of transportation was by public transport, of which travelling by bus was the most common (59.9%) and mass rapid transit (MRT) was the least common (4%). Female gender and age > or = 75 were significant factors associated with dependence measured on Barthel's index but not on IADL. CONCLUSION: Results of this study were also compared with two previous surveys done in Singapore. Discrepancies in results noted could be attributed to different definitions in which the functions were assessed. We should aim to standardise the definition and measures of function in the local context in order to measure changes in the elderly population.

Activities of Daily Living↗

Longitudinal study of the contractile and electrical properties of single human thenar motor units.

Serial motor unit number estimates have shed important light on the extent and rates of motoneuron losses in aging and amyotrophic lateral sclerosis. However, the estimates alone provide few clues to the health and functional status of surviving motor units. A reliable means for assessing the functional status of the surviving motor units would therefore by a welcome addition to our present tools for studying motor units. Examining the physiological properties of samples of motor units drawn at intervals during the course of a motoneuronal disease suffers from the important limitation that the samples may not be representative of one another. The latter problem could be circumvented by serially studying the same motor units. This study describes a noninvasive technique capable of longitudinally tracking the contractile and electrical properties of specific single thenar motor units in healthy subjects, in some instances over several years. The technique proved to be reasonably reliable and provided information on a wide range of contractile and electrical properties of motor units. Such an approach could serve as a potentially powerful and sensitive means of studying the life histories of single motor units in aging, diseases of the motoneuron, and in the latter instances, the responses of the motoneurons to treatment.

Action Potentials↗

The usefulness of central motor conduction studies in the localization of cord involvement in cervical spondylytic myelopathy.

Cervical spondylytic myelopathy (CSM) is common. Magnetic resonance imaging (MRI), although sensitive, often reveals extensive and sometimes clinically irrelevant findings. The purpose of this study was to investigate the usefulness of central motor conduction studies in localizing the rostral level of cord involvement in 6 patients with CSM. Central motor conduction was assessed using high-voltage stimulation for the spinal roots and magnetoelectrical stimulation for the motor cortex, recording from "marker muscles" innervated by successively higher cervical cord segments. Abnormal central motor conduction affected all subjects at C8-T1, 5 subjects at C7, but none at the C5-C6 levels. The MRI showed abnormalities at multiple levels as high as C4. Our results suggest that central motor conduction studies are helpful in localizing the clinically relevant levels of spinal cord compression in CSM and correlate well with motor abnormalities on clinical examination.

Adult↗

A longitudinal study of the pathophysiological changes in single human thenar motor units in amyotrophic lateral sclerosis.

The sequence of pathophysiological changes in amyotrophic lateral sclerosis (ALS) at the single motor unit (MU) level is not well understood. Using a recently described technique, a comprehensive range of physiological properties in two thenar MUs in ALS were intensively studied. In the first MU, despite a marked decline in the ability of the subject to voluntarily recruit the MU, the physiological properties of this MU remained remarkably stable over a 2-year period. In contrast, the physiological properties of the other MU declined rapidly over 5 months despite the fact that this MU could be recruited with ease throughout the study period. These differences between the progressively dysfunctional changes in these two MUs illustrates the value of such longitudinal studies of specific MUs in improving our understanding of the evolution of changes in single motoneurons in ALS. The broader application of longitudinally tracking the pathophysiological changes of the surviving MUs may prove to be a sensitive measure of disease progression and in evaluating the effectiveness of treatments.

Action Potentials↗

Dissociation of the electrical and contractile properties in single human motor units during fatigue.

The surface EMG area often exhibits progressive enlargement during a submaximal fatiguing contraction, but the underlying reasons still remain uncertain. Fatigue-induced changes in the surface-detected motor unit action potentials (S-MUAPs) of 10 human thenar motor units (MUs) with widely differing physiological properties were examined. After 2 min of repetitive 40-Hz stimulation, the size of the S-MUAPs of all MUs increased, the magnitude of which was negatively correlated with their tetanic tension changes. These findings suggest that during muscle fatigue, in addition to reflecting recruitment of new MUs and increases in firing rates of the active MUs, the surface EMG may also be markedly influenced by changes in the S-MUAPs, especially in fast fatigable muscles.

Adult↗

Pyridinoline in relation to ultimate stress of the patellar tendon during healing: an animal study.

The ultimate stress of the central one-third of the patellar tendon was studied in a gap wound-healing model in the rat. The specimens were also analyzed for collagen and nonreducible crosslinks, as measured by hydroxyproline and pyridinoline content, respectively. Thirty days after injury, the ultimate stress of the healing patellar tendon was restored to an average of 71% of the control value and remained constant over time. The pyridinoline content of the healing tendon was twice the control value by 30 days after injury and reached a plateau; however, the hydroxyproline content did not change significantly over time. Stepwise regression analysis demonstrated that pyridinoline was a better biochemical marker for ultimate stress than was hydroxyproline. The current study provides insights into the functional behaviour of the healing patellar tendon by establishing the relationship between the two biochemical components and the ultimate stress of the healing patellar tendon. This study also suggests the possibility of using pyridinoline content as an indirect marker of the ultimate stress because in vivo assessment is impossible.

Amino Acids↗

Articular cartilage lesions of the knee following immobilisation or destabilisation for 6 or 12 weeks in rabbits.

Eighty mature female New Zealand White rabbits were sacrificed 6 or 12 weeks after either section of the medial collateral and the anterior cruciate ligaments with removal of the anterior third of the medial meniscus of one knee, or immobilisation of one knee, using the contralateral non-treated knee as the control. The area of degenerated joint surface of the distal femur, and water and proteoglycan content were measured, and the articular cartilage stained using haematoxylin and eosin and safranin O. Destabilisation resulted in a significantly larger time-dependent degenerated joint surface area. Water content significantly increased after 6 weeks with no significant differences between immobilisation and destabilisation. Destabilisation resulted in a significantly greater decrease in proteoglycan content. At 12 weeks, the control knees of the animals undergoing destabilisation showed significant degenerative changes. There were more extensive lesions in destabilisation, while 6 weeks of immobilisation produced moderate degenerative joint disease.

Analysis of Variance↗

A prospective randomized trial of suture of the patellar tendon defect after harvesting.

In a rabbit model, we studied the long-term biomechanical and biochemical effects of leaving the patellar tendon unsutured, or closing the defect with absorbable sutures, after harvesting one third. Using a prospective randomized design, after harvest of its central third, the patellar tendon was either sutured side to side with absorbable sutures, or left unsutured in 112 skeletally mature rabbits. The rabbits were killed at 2 and 6 weeks, and 6 and 9 months postoperatively. After an initial increase in both groups (.001 < P < .019), water content decreased from 2 weeks to 9 months after the operation (.02 < P < .0045), and remained significantly greater than in the control contralateral limb at all times (.00 1 < P < .003). Collagen content showed no significant differences between the two experimental groups. The operated tendons always showed a decreased collagen content at all time periods (.012 < P < .049). Failure load, ultimate stress, stiffness, and energy absorbed before failure tended to gradually return to normal over 9 months after a significant initial drop. There were no significant differences between the two experimental groups in failure load, ultimate stress stiffness, and energy absorbed before failure. At 9 months, the operated patellar tendon was significantly thicker (.0016 < P < .03) and had a greater cross-sectional area (.01 < P < .03) than the contralateral control regardless of whether it had been sutured or left open. After removal of the central third, closing the tendon gap with absorbable sutures or leaving it open makes little difference on the biomechanical and biochemical properties of the remaining patellar tendon.

Animals↗

Quantitation in EMG.

The neuromuscular system may be affected by disorders of the central nervous system as well as other disorders affecting motoneurons, axons, neuromuscular transmission, the sarcolemmal membrane, the contractile elements and other components of the muscle fibers themselves. One or a combination of these possibilities can present in patients in the critical care unit. This paper reviews various qualitative and quantitative methods for assessing the various components of the peripheral contributions to the electrical and force output as well as the central motor drive to motoneurons. These methods all have their own strengths and weaknesses but many are complementary and together, can provide important diagnostic and prognostic information to guide management.

Brain↗

Characterization of a prostanoid EP3-receptor in guinea-pig aorta: partial agonist action of the non-prostanoid ONO-AP-324.

Contraction of guinea-pig isolated aorta induced by the prostaglandin E analogue sulprostone (1-400 nM) has a lower maximum response (40%) than that of phenylephrine or U-46619 (TP-receptor agonist). A prostanoid EP3-receptor subtype is involved based on agonist potency ranking: equi-effective molar ratios (EMR) are sulprostone (EC50 approximately equal to 23 nM) 1.0, SC-46275 0.11, misoprostol 2.2, gemeprost 3.3, PGE2 5.4, 17-phenyl PGE2 6.0, GR-63799 8.9. GR-63799, which contains a bulky ester group, is relatively more potent on neuronal EP3 preparations than on the aorta. ONO-AP-324, a relative of the non-prostanoid prostacyclin mimetic series, behaves as an EP3 partial agonist on the aorta, inhibiting sulprostone responses but acting synergistically (in a similar manner to sulprostone) with phenylephrine; it may be a useful pharmacological tool for studying EP3-receptors. Sulprostone contractions are markedly suppressed in zero-Ca2+ bathing fluid containing either 2 mM EDTA or 50 microM EGTA, and by Cd2+ (500 microM), but are usually unaffected by nifedipine (0.3 microM) and verapamil (4.44 microM). Influx of Ca2+, but not through L-type Ca2+-channels, appears to be the major contractile mechanism. The guinea-pig aorta is a valuable addition to the vascular EP3 preparations available and may increase our knowledge of the mechanisms whereby Gi-coupled receptors mediate vasoconstriction (c.f. 5-HT1B/D- and alpha2-receptors). The possibility of certain EP3 agonists distinguishing EP3-receptor isoforms is discussed.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Detection of specific antibodies to an antigenic mannoprotein for diagnosis of Penicillium marneffei penicilliosis.

The disseminated and progressive fungal disease Penicillium marneffei penicilliosis is one of the most common infectious diseases in AIDS patients in Southeast Asia. To diagnose systemic penicilliosis, we developed an enzyme-linked immunosorbent assay (ELISA)-based antibody test with Mp1p, a purified recombinant antigenic mannoprotein of P. marneffei. Evaluation of the test with guinea pig sera against P. marneffei and other pathogenic fungi indicated that this assay was specific for P. marneffei. Clinical evaluation revealed that high levels of specific antibody were detected in two immunocompetent penicilliosis patients. Furthermore, approximately 80% (14 of 17) of the documented penicilliosis patients with human immunodeficiency virus tested positive for the specific antibody. No false-positive results were found for serum samples from 90 healthy blood donors, 20 patients with typhoid fever, and 55 patients with tuberculosis, indicating a high specificity of the test. Thus, this ELISA-based test for the detection of anti-Mp1p antibody can be of significant value as a diagnostic for penicilliosis.

AIDS-Related Opportunistic Infections↗