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Biomedical subjects

S S Chan

Publications and source records attributed to S S Chan.

At least 19 recordsLinked to original sources

Separation of 100-kilobase DNA molecules in 10 seconds.

Long double-stranded DNA molecules were separated in microfabricated hexagonal arrays in less than 1 min, several orders of magnitude faster than by using conventional technology. DNA samples were first concentrated at the entrance to the array in a thin band by entropic focusing. They were then separated by pulsed field electrophoresis. T4 (168.9 kbp) and lambda (48.5 kbp) DNAs could be resolved into two clearly separated bands in approximately 10 s in these experiments. This corresponds to a mass resolution of 6% in 11 min in a 1-cm-long array.

Algorithms↗

Near-field scanner for moving molecules.

We have fabricated using electron beam nanolithography a fixed slit near-field optical scanning device which uses near-field fluorimetry to achieve 200 nm spatial resolution of objects moving over the slits. We explore the basic physics of operating narrow slits in the waveguide cutoff mode and present data from the passage of extended double-stranded DNA molecules passing over the slits as a first example of how this device can be used to do ultrahigh spatial resolution mapping of long polymers.

Algorithms↗

Alpha-tocopherol modulates tyrosine phosphorylation in human neutrophils by inhibition of protein kinase C activity and activation of tyrosine phosphatases.

Alpha-tocopherol augmentation in human neutrophils was investigated for effects on neutrophil activation and tyrosine phosphorylation of proteins, through its modulation of protein kinase C (PKC) and tyrosine phosphatase activities. Incubation of neutrophils with alpha-tocopherol succinate (TS) resulted in a dose-dependent incorporation into cell membranes, up to 2.5 nmol/2x10(6) cells. A saturating dose of TS (40 micromol/l) inhibited oxidant production by neutrophils stimulated with phorbol myristate acetate (PMA) or opsonized zymosan (OZ) by 86 and 57%, as measured by luminol-amplified chemiluminescence (CL). With PMA, TS inhibited CL generation to a similar extent to staurosporine (10 nmol/l) or genistein (100 micromol/l), and much more than Trolox (40 micromol/l). With OZ, TS inhibited CL to a similar extent to Trolox. Neutrophil PKC activity was inhibited 50% or more by TS or staurosporine. The enzyme activity was unaffected by genistein or Trolox, indicating a specific interaction of alpha-tocopherol. TS or Trolox increased protein tyrosine phosphorylation in resting neutrophils, and as with staurosporine further increased tyrosine phosphorylation in PMA-stimulated neutrophils, while the tyrosine kinase (TK) inhibitor genistein diminished phosphorylation. These effects in resting or PMA-stimulated neutrophils were unrelated to protein tyrosine phosphatase (PTP) activities, which were maintained or increased by TS or Trolox. In OZ-stimulated neutrophils, on the other hand, all four compounds inhibited the increase in tyrosine-phosphorylated proteins. In this case, the effects of pre-incubation with TS or Trolox corresponded with partial inhibition of the marked (85%) decrease in PTP activity induced by OZ. These results indicate that alpha-tocopherol inhibits PMA-activation of human neutrophils by inhibition of PKC activity, and inhibits tyrosine phosphorylation and activation of OZ-stimulated neutrophils also through inhibition of phosphatase inactivation.

Chromans↗

Community-acquired pneumonia--implementation of a prediction rule to guide selection of patients for outpatient treatment.

The aim of this study was to determine the outcomes of outpatient treatment of community-acquired pneumonia (CAP) when a prediction rule was followed by emergency physicians to guide the selection of patients. This was a prospective observational study conducted at the emergency department of a university-affiliated hospital in Hong Kong, China. A clinical prediction rule was implemented to guide the selection of patients with CAP for outpatient treatment. All subsequent hospitalizations gial presentation were recorded, and the reasons were assessed. The utilization of the observation unit was incorporated into the treatment algorithm. Of 72 patients with CAP followed up as outpatients, 60 (83.3%) were treated successfully, nine (12.5%) required subsequent hospitalization within 30 days, and three (4.2%) were lost to follow-up. None of the patients died, and none required admission to the intensive care unit. Factors associated with subsequent hospitalization include: tuberculosis, underlying malignancy, persistent fever, comorbidity (rheumatoid arthritis and severe osteoporosis), intravenous drug addiction and alcoholism. The observation ward was utilized in 10 (16.7%) patients successfully treated as outpatients. It is concluded that the prediction rule can be safely implemented as a guide for emergency physicians. The short-stay observation unit may be usefully employed for treating low-risk CAP.

Adolescent↗

Using conjoint analysis to assess patients' preferences when visiting emergency departments in Hong Kong.

OBJECTIVES: To explore factors related to emergency department (ED) attendances in Hong Kong, the authors piloted the application of conjoint analysis in eliciting patient preferences regarding ED visits. METHODS: The study recruited 390 semi-urgent or non-urgent patients from a targeted convenience sample of three large EDs. Respondents were asked to rank eight scenarios structured to explore the relative importance of three key attributes-self-perceived illness severity, waiting time, and consultation fee-that may result in an ED visit. RESULTS: Seventy-eight percent of the respondents would consider visiting a parallel clinic instead of the ED for semi-urgent and non-urgent conditions. The relative importance attached to illness severity, waiting time, and consultation fee were 47.8%, 33.6%, and 18.7%, respectively. CONCLUSIONS: This study demonstrated that Hong Kong patients are receptive to the concept of parallel clinics, and illustrated that conjoint analysis is a rigorous survey technique for eliciting the views of patients on health care services in the ED setting.

Adult↗

Sorting biomolecules with microdevices.

Micro- and nanofabrication techniques have provided an unprecedented opportunity to create a designed world in which separation and fractionation technologies which normally occur on the macroscopic scale can be optimized by designing structures which utilize the basic physics of the process, or new processes can be realized by building structures which normally do not exist without external design. Since microfabrication is exceedingly sophisticated in its development, it is possible to design and construct highly creative microdevices which allow one to probe specific aspects of biological objects. We give examples of uses of micro- and nanofabrication which, as opposed to simply shrinking the size of the vessels or tubes used in macroscopic lab environments, utilize our understanding of the physics of the process to take advantage of fabrication technologies.

Animals↗

Current opinions and practices in the treatment of spontaneous pneumothorax.

The approach to the initial management of spontaneous pneumothorax differs markedly from centre to centre, and it is difficult in practice to establish a standard protocol. This article reviews the concepts behind the British Thoracic Society guidelines, and reports the varying opinions and alternative practices existing currently. There is a need for more evidence-based studies to identify what is the best approach. Based on a review of relevant recent reports, the author attempts to work out an unbiased practical approach that can be used safely and that can possibly give the best overall cost effective results.

Emergency Treatment↗

Epidemiology of health changes in older women in Hong Kong.

This paper aims to present the baseline social, mental and functional characteristics, the changes of these characteristics over a 36-month follow-up period, and the issues and implications related to these changes, particularly in older women. The cohort comprising 2030 subjects aged 70 and above has been assembled by stratified disproportional random sampling. Registrants with the Old Age Allowance Scheme, which has over 90 percent coverage of the Hong Kong elderly population, was used to define the accessible population. Face-to-face interviews were conducted at the respondents' place of residence. A number of social and health variables were collected at baseline. The surviving subjects had been followed up at 36 months and repeated measurements of the baseline variables were obtained. Older women were over-represented by low level education, financial dependency, as well as residence in institutions. Women had higher prevalence as well as incidence of musculoskeletal problems. While there was a general decline in health and social support in the elderly cohort, we observed a preponderance of older female subjects with mental and functional decline over the follow-up period. An overrepresentation of female subjects with depressive symptoms at baseline and follow-up was also noted. The descriptive data have revealed a host of social and health changes over a three-year follow-up period. Women aged 80 years and above formed a particularly disadvantaged group. The results will have direct implications for the shaping of social and health policy for strategic planning of priorities in social and health care services.

Activities of Daily Living↗

Sorting by diffusion: an asymmetric obstacle course for continuous molecular separation.

A separation technique employing a microfabricated sieve has been demonstrated by observing the motion of DNA molecules of different size. The sieve consists of a two-dimensional lattice of obstacles whose asymmetric disposition rectifies the Brownian motion of molecules driven through the device, causing them to follow paths that depend on their diffusion coefficient. A nominal 6% resolution by length of DNA molecules in the size range 15-30 kbp may be achieved in a 4-inch (10-cm) silicon wafer. The advantage of this method is that samples can be loaded and sorted continuously, in contrast to the batch mode commonly used in gel electrophoresis.

Chemical Fractionation↗

Passive smoking exposure of sick children in Hong Kong.

1. This study aims to investigate the extent of passive smoking exposure of sick children in Hong Kong; their father's smoking behaviors and their mother's action to protect the child from environmental tobacco smoke (ETS). 2. This cross-sectional survey was the first phase of a randomized controlled trial on a health education intervention provided by nurses in the general paediatric wards of four major hospitals in Hong Kong. The subjects are non-smoking mothers of sick children admitted to hospital and with a smoking husband living together in the same household with the child. Eligible subjects completed a self-administered baseline questionnaire before entering into the trial. 3. All the 848 children whose mothers completed the questionnaire during December 1997 to April 1998 had a smoking father. They constituted about 24% (95% CI: 22.6-24.9%) of all the sick children during the same period. More than half of the children's fathers (55%; 51.6-58.3%) smoked 1-14 cigarettes per day and about 68% (64.7-71.0%) of them were daily smokers for over 10 years. Over half (53%; 49.4-56.2%) of the fathers smoked 1-14 cigarettes at home every day. About 21% of the fathers smoked near the child occasionally and 31% (27.4-33.6%) smoked 1-14 cigarettes near the child per day. About 16% of the children lived with more than one smoker (2-3). About 86% (83.3-88.0%) of the children had 1-3 smokers who smoked at home and 61% (58.1 - 64.7%) of them had 1-3 smokers who smoked near them every day. However, 70% of the children were reported by their mothers as exposed to ETS at home. This percentage (70%) was less than the percentage (86%) of smokers who smoked at home daily. About 31.1% of the mothers reported symptoms of coughing and running nose (20.6%) in their children when they were exposed to ETS. To protect the child from ETS exposure, 43% of the mothers requested the father not to smoke near the child, 33.1% requested the father to smoke less cigarettes and 31.5% advised the father to quit smoking. 4. In conclusion, sick children in Hong Kong are at risk of exposure to ETS, but not all mothers are aware of the health risks and their actions were inadequate. There is a critical need to promote awareness of ETS exposure and the health risks in the family in Hong Kong so as to reduce illness and hospital admission in children.

Adolescent↗

Reevaluation of the determinants of tyrosine sulfation.

The posttranslational sulfation of tyrosine has been thought to be initiated by the recognition of specific consensus features by the sulfating enzyme tyrosylprotein sulfotransferase (TPST). However, using these recognition features to identify new tyrosine sulfation sites misses recently characterized sites that lack these features. Rigorous analysis of the amino acids surrounding the target tyrosine using the position-specific scoring matrix (PSSM) demonstrates that a consensus sequence does not contain all the information necessary to predict tyrosine sulfation. Instead, accurate prediction requires consideration of all residues within five amino acids on either side of the target tyrosine. These results support the notion that secondary structure is the major determinant of sulfation and that other residues within the sulfation site can compensate for deviations from commonly observed features. This view implies that specific consensus features are not critical for TPST substrate recognition but that TPST may instead broadly recognize any sufficiently exposed tyrosine residue.

Amino Acid Sequence↗

The effects of multiple-strand suture methods on the strength and excursion of repaired intrasynovial flexor tendons: a biomechanical study in dogs.

This study was designed to determine the effects of in vivo multistrand, multigrasp suture techniques on the strength and gliding of repaired intrasynovial tendons when controlled passive motion rehabilitation was used. Twenty-four adult mongrel dogs were divided into 4 groups and their medial and lateral forepaw flexor tendons were transsected and sutured by either the Savage, the Tajima, the Kessler, or the recently developed 8-strand suture method. The tendon excursion, joint rotation, and tensile properties of the repaired tendons were evaluated biomechanically at 3 and 6 weeks after surgery. It was found that neither time nor suture method significantly effected proximal and distal interphalangeal joint rotation or tendon excursion when the 4 techniques were compared to each other. Normalized load value (experimental/control) was significantly affected by both the suture method and the amount of time after surgery, however. The Savage and 8-strand repair methods had significantly greater strength than did the Tajima method at each time interval (p < .05 for each comparison). In addition, the 8-strand method had significantly greater normalized load values than did the Savage method at each time interval (p < .05 for each comparison). Normalized stiffness (experimental/control) for the 8-strand repair method was significantly greater than that for the Tajima and Savage methods at 3 and 6 weeks after surgery (p < .05). In addition, the normalized stiffness values for the 6-week groups was significantly greater than those for the 3-week groups (p < .05). It was concluded that the method of tendon suture was a significant variable insofar as the regaining of tendon strength was concerned and that the newer low-profile 8-strand repair method significantly expands the safety zone for the application of increased in vivo load during the early stages of rehabilitation.

Animals↗

Functional activity of blood polymorphonuclear leukocytes as an oxidative stress biomarker in human subjects.

In the present work, we studied the role of polymorphonuclear leukocytes (PMN) in aged individuals and coronary heart disease (CHD)-bearing patients, two physiopathological processes associated with overproduction of reactive oxygen species (ROS). The effects of antioxidant supplementation on the functional activity of PMN from CHD patients were also determined. The function of PMNs was evaluated by measuring of phagocytosis, killing activity, and ROS production. Luminol amplified chemiluminescence (CL) was used to estimate ROS production by stimulated PMNs. Total cholesterol and the LDL-cholesterol fraction from CHD patients were found to be higher than those recommended, returning to normal levels after antioxidant therapy. PMN CL of CHD patients was found to be higher than the associated control groups. Antioxidant therapy administrated to CHD patients lead to an increase in the killing activity accompanied by a decrease in PMN CL of these subjects. The study also showed that killing activity of PMN from human subjects over 60 years was significantly lower than the activity measured in younger subjects. PMN CL produced after stimulation was found to be positively correlated with the increasing age of human subjects (r=.946, p < .01).

Adult↗

Identification and characterization of growth hormone receptors in snakehead fish (Ophiocephalus argus cantor) liver.

The specific binding of 125I-labeled fish growth hormone (GH) to hepatic membranes prepared from several freshwater fish was assessed. A high level of growth hormone receptor (GHR) was detected on the hepatic membranes of the snakehead fish (Ophiocephalus argus Cantor). Scatchard analysis of the binding data showed a single class of high affinity binding site with a binding affinity (Ka) of 1.45 +/- 0.23 x 10(9) M-1 and a binding capacity (Bmax) of 198 +/- 57 fmol/mg protein. The binding was specific for fish GH and was saturable. In addition, the specific binding was temperature- and time-dependent, reaching a steady state after 16 hr of incubation at 25 degrees . The molecular weight of GHR as measured by Sephadex G-200 column chromatography and Western blot analysis using a monoclonal antibody (Mab263) against GHR was found to be 200-400 and 90-93 kDa, respectively. Two bands at 65 and 89 kDa were identified in ligand crosslinking studies of membrane receptors. A sensitive teleost GH radioreceptor assay (RRA) was developed, using recombinant fish GH and a membrane preparation from snakehead fish liver, capable of measuring bioactive GH in fish sera or other samples.

Animals↗

Temperature-dependent ultraviolet resonance Raman spectroscopy of the premelting state of dA.dT DNA.

Poly(dA).poly(dT) and DNA duplex with four or more adenine bases in a row exhibits a broad, solid-state structural premelting transition at about 35 degrees C. The low-temperature structure is correlated with the phenomena of "bent DNA." We have conducted temperature-dependent ultraviolet resonance Raman measurements of the structural transition using poly(dA).poly(dT) at physiological salt conditions, and are able to identify, between the high and low temperature limits, changes in the vibrational frequencies associated with the C4 carbonyl stretching mode in the thymine ring and the N6 scissors mode of the amine in the adenine ring of poly(dA).poly(dT). This work supports the model that the oligo-dA tracts' solid-state structural premelting transition is due to a set of cross-stand bifurcated hydrogen bonds between consecutive dA. dT pairs.

Base Composition↗

Biomechanics of knee ligament healing, repair and reconstruction.

Injuries of the anterior cruciate ligament (ACL) and the medial collateral ligament (MCL) are common, accounting for 90% of all knee ligament injuries in young and active individuals. During the last decade, our research center has focused on MCL healing and ACL reconstruction. We have found that the MCL heals without intervention after an isolated injury, and that primary repair offers no apparent advantage. After a combined injury of the ACL and MCL, the ACL requires reconstruction, whereas primary repair again contributes little or nothing toward MCL healing. Midsubstance ACL injuries have limited healing ability. Hence, the treatment of choice for a torn ACL in a young, active patient is generally reconstruction with an autograft or allograft. However, the appropriate replacement graft and reconstruction technique to use are still debated. Current research efforts have been placed on investigating the magnitude and direction of in situ forces in the human ACL. We use a six-component universal force moment sensor combined with a six-degree-of-freedom (DOF) robotic manipulator to learn as well as to reproduce the six-DOF motion of the knee before and after ACL injury. This way, the in situ force in the ACL under an anterior posterior tibial load of 110 N was obtained. This methodology should make it possible to obtain the needed data to aid in better understanding of ACL reconstruction and possible development of improved clinical management.

Animals↗

Motor power pharmacodynamics of subarachnoid hyperbaric 5% lidocaine in the sitting position.

BACKGROUND: Repetitive dynamometric measurement using a plantar flexion power device (PFPD) provides detailed data describing the onset and offset of motor block following spinal administration of lidocaine. The aim of this study was to evaluate administration of two doses of spinal lidocaine in the sitting position to determine whether our dynamometric model produces data consistent with our current understanding of the pharmacokinetics of subarachnoid, hyperbaric, 5% lidocaine. METHODS: Twenty male patients (54 to 80 yr) undergoing cystoscopy received spinal anaesthesia with either 75 mg (n = 10) or 100 mg of hyperbaric lidocaine 5%, in the sitting position, under standardised conditions. Plantar flexion muscle power was recorded during onset and offset of anaesthesia using a load cell interfaced with a computer (PFPD). RESULTS: Onset of paralysis following spinal block in the sitting position was rapid and complete with motor power declining exponentially to 5% of preoperative values by 8.5 min in all patients. There was no difference in decay or recovery of plantar flexion motor power data between dosage groups in the sitting position. Measurement using the PFPD shows that onset of motor paralysis is described by an exponential decay and that motor recovery occurs at a fixed rate. Extent of block to cold and pinprick was similar in both dosage groups in the sitting position (median T4). CONCLUSION: This study shows that in the sitting position, doses less than 75 mg of 5% hyperbaric lidocaine are required to significantly improve ambulatory times.

Aged↗

Deleted in Colorectal Cancer (DCC) encodes a netrin receptor.

The guidance of developing axons in the nervous system is mediated partly by diffusible chemoattractants secreted by axonal target cells. Netrins are chemoattractants for commissural axons in the vertebrate spinal cord, but the mechanisms through which they produce their effects are unknown. We show that Deleted in Colorectal Cancer (DCC), a transmembrane protein of the immunoglobulin superfamily, is expressed on spinal commissural axons and possesses netrin-1-binding activity. Moreover, an antibody to DCC selectively blocks the netrin-1-dependent outgrowth of commissural axons in vitro. These results indicate that DCC is a receptor or a component of a receptor that mediates the effects of netrin-1 on commissural axons, and they complement genetic evidence for interactions between DCC and netrin homologs in C. elegans and Drosophila.

Amino Acid Sequence↗