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C K Chan

Publications and source records attributed to C K Chan.

At least 127 records · Page 7Linked to original sources
PubMed1997

Neuropsychological correlates of sustained attention in schizophrenia.

We employed a simple and relatively undemanding task of monotone counting for the assessment of sustained attention in schizophrenic patients. The monotone counting task has been validated neuropsychologically and is particularly sensitive to right prefrontal lesions. We compared the performance of schizophrenic patients with age- and education-matched controls. We then explored the extent to which a range of commonly employed neuropsychological tasks in schizophrenia research are related to attentional impairment as measured in this way. Monotone counting performance was found to be correlated with digit span (WAIS-R-HK), information (WAIS-R-HK), comprehension (WAIS-R-HK), logical memory (immediate recall) (Weschler Memory Scale, WMS), and visual reproduction (WMS). Multiple regression analysis also identified visual reproduction, digit span and comprehension as significant predictors of attention performance. In contrast, logical memory (delay recall) (WMS), similarity (WAIS-R-HK), semantic fluency, and Wisconsin Card Sorting Test (perseverative errors) were not correlated with attention. In addition, no significant correlation between sustained attention and symptoms was found. These findings are discussed in the context of a weakly modular cognitive system where attentional impairment may contribute selectively to a range of other cognitive deficits.

Adolescent↗
PubMed1997

Submillisecond protein folding kinetics studied by ultrarapid mixing.

An ultrarapid-mixing continuous-flow method has been developed to study submillisecond folding of chemically denatured proteins. Turbulent flow created by pumping solutions through a small gap dilutes the denaturant in tens of microseconds. We have used this method to study cytochrome c folding kinetics in the previously inaccessible time range 80 micros to 3 ms. To eliminate the heme-ligand exchange chemistry that complicates and slows the folding kinetics by trapping misfolded structures, measurements were made with the imidazole complex. Fluorescence quenching due to excitation energy transfer from the tryptophan to the heme was used to monitor the distance between these groups. The fluorescence decrease is biphasic. There is an unresolved process with tau < 50 micros, followed by a slower, exponential process with tau = 600 micros at the lowest denaturant concentration (0.2 M guanidine hydrochloride). These kinetics are interpreted as a barrier-free, partial collapse to the new equilibrium unfolded state at the lower denaturant concentration, followed by slower crossing of a free energy barrier separating the unfolded and folded states. The results raise several fundamental issues concerning the dynamics of collapse and barrier crossings in protein folding.

Animals↗
PubMed1997

Regulation of Src homology 2-containing tyrosine phosphatase 1 during activation of human neutrophils. Role of protein kinase C.

The tyrosine phosphorylation of several proteins induced in neutrophils by soluble and particulate stimuli is thought to be crucial for initiating antimicrobial responses. Although activation of tyrosine kinases is thought to mediate this event, the role of tyrosine phosphatases in the initiation and modulation of neutrophil responses remains largely undefined. We investigated the role of Src homology 2-containing tyrosine phosphatase 1 (SHP-1; also known as protein tyrosine phosphatase 1C (PTP1C), hematopoetic cell phosphatase, PTP-N6, and SHPTP-1), a phosphatase expressed primarily in hemopoietic cells, in the activation of human neutrophils. SHP-1 mRNA and protein were detected in these cells, and the enzyme was found to be predominantly localized to the cytosol in unstimulated cells. Following stimulation with neutrophil agonists such as phorbol ester, chemotactic peptide, or opsonized zymosan, a fraction of the phosphatase redistributed to the cytoskeleton. Agonist treatment also induced significant decreases (30-60%) in SHP-1 activity, which correlated temporally with increases in the cellular phosphotyrosine content. Phosphorylation of SHP-1 on serine residues was associated with the inhibition of its enzymatic activity, suggesting a causal relationship. Accordingly, both the agonist-evoked phosphorylation of SHP-1 and the inhibition of its catalytic activity were blocked by treatment with bisindolylmaleimide I, a potent and specific inhibitor of protein kinase C (PKC) activity. Immunoprecipitated SHP-1 was found to be phosphorylated efficiently by purified PKC in vitro. Such phosphorylation also caused a decrease in the phosphatase activity of SHP-1. Together, these data suggest that inhibition of SHP-1 by PKC-mediated serine phosphorylation plays a role in facilitating the accumulation of tyrosine-phosphorylated proteins following neutrophil stimulation. These findings provide a new link between the PKC and tyrosine phosphorylation branches of the signaling cascade that triggers antimicrobial responses in human neutrophils.

Enzyme Activation↗
PubMed1997

Aerosol delivery to non-ventilated infants by metered dose inhaler: should a valved spacer be used?

In a randomized double-blind cross-over study on 20 spontaneously breathing, oxygen-dependent preterm infants who had received positive pressure ventilation for respiratory distress syndrome, we tested the hypothesis that the one-way non-rebreathing valves of aerosol spacer devices might impair rather than enhance the delivery of aerosols to small infants by metered dose inhalers (MDI). Ten infants were given 2 doses (200 micrograms/dose) of MDI albuterol through a neonatal Aerochamber 4 h apart. At random sequence, one dose was delivered with the non-rebreathing valve of the Aerochamber in place; for the other dose, the valve had been removed. The experiment was repeated on another ten infants using a different spacer device (Babyhaler) with or without its one-way inspiratory valve removed. During the first hour following aerosol administration, use of the non-valved spacers was associated with a significantly greater degree of tachycardia in both groups, and also lower transcutaneous carbon dioxide tension in the Aerochamber group. All infants showed a reduction in respiratory system resistance and an improvement in functional residual capacity following albuterol treatment. In both groups, maximum reduction in respiratory system resistance, recorded 30 min after aerosol delivery, was significantly greater following the use of the non-valved spacers (Aerochamber: 51.2 +/- 3.1% vs. 35.0 +/- 2.8%, P < 0.0001; Babyhaler: 38.8 +/- 2.3% vs. 19.2 +/- 1.4%, P < 0.0001) than following the use of the spacers with a valve. The findings provide indirect evidence supporting our hypothesis and suggest that when the MDI is used to deliver therapeutic aerosols to non-ventilated newborns or small infants, a spacer device without a non-rebreathing valve should be used.

Aerosols↗
PubMed1997

Central cardiovascular actions of agmatine, a putative clonidine-displacing substance, in conscious rabbits.

Agmatine, an endogenous clonidine-displacing substance, has been shown to have an affinity for both alpha 2-adrenoceptors and imidazoline receptors (IR). In conscious rabbits, we have examined the cardiovascular effects of agmatine and its interaction with clonidine, a presumed agonist and 2-methoxyidazoxan, an antagonist at alpha 2-adrenoceptors. We have also examined the effect of agmatine on agents having high affinity for I1-imidazoline receptors namely moxonidine (agonist) and efaroxan (antagonist). Initial dose-response studies showed that agmatine administered in low doses (0.01-10 micrograms/kg) into the fourth ventricle did not change mean arterial pressure but did produce a dose-dependent bradycardia (maximum -16 +/- 3 beats/min). A higher dose of 100 micrograms/kg produced an adverse reaction in the conscious animals accompanied by a marked increase in mean arterial pressure and a reversal of the bradycardia. This is in contrast to the effects of fourth ventricular clonidine and moxonidine, which caused a dose-dependent fall in both mean arterial pressure and heart rate. Agmatine when administered at the highest well-tolerated dose of 10 micrograms/kg did not further alter the clonidine-induced hypotension but produced a greater bradycardia (-12 +/- 4 beats/min clonidine; -29 +/- 4 beats/min clonidine plus agmatine; p < 0.05). Similarly, the hypotension induced by moxonidine was not altered by agmatine but heart rate was reduced after the addition of agmatine (p < 0.01). Efaroxan and 2-methoxy-idazoxan, at doses which produced no effects when given alone, similarly reversed the fall in heart rate elicited by agmatine and caused a small but significant rise in mean arterial pressure. We have previously shown that the doses of these antagonists used in this study produce an equal reversal of the bradycardia induced by fourth ventricular alpha-methyldopa (alpha 2-adrenoceptor agonist) and clonidine and hence have similar alpha 2-adrenoceptor blocking effects. Our results show that agmatine produces bradycardia as does moxonidine and clonidine but does not mimic or block the hypotensive responses to these agents. These findings do not support the hypothesis that agmatine is an endogenous ligand for IR. However, the bradycardia induced by agmatine may be mediated via alpha 2-adrenoceptors since it was equally blocked by efaroxan and 2-methoxy-idazoxan. Thus while alpha 2-adrenoceptor actions of agmatine on heart rate are evident at relatively low doses, the reason for the lack of alpha 2-adrenoceptor mediated hypotension is not known.

Adrenergic alpha-Agonists↗
PubMed1997

Submillisecond kinetics of protein folding.

New experimental methods permit observation of protein folding and unfolding on the previously inaccessible nanosecond-microsecond timescale. These studies are beginning to establish times for the elementary motions in protein folding - secondary structure and loop formation, local hydrophobic collapse, and global collapse to the compact denatured state. They permit an estimate of about one microsecond for the shortest time in which a protein can possibly fold.

Humans↗
PubMed1997

Screening for dementia: a preliminary study on the validity of the Chinese version of the Blessed-Roth Dementia Scale.

Blessed-Roth Dementia Scale has been one of the most widely used rating scales in dementia. Previous studies indicated that this behavioral assessment scale is a useful tool for differentiating elderly subjects with no or minimal intellectual decline from those with cognitive deterioration. In the present study, the authors examined the validity of the Chinese version of the Blessed-Roth Dementia Scale (CDS) in Hong Kong. A total of 106 Chinese subjects were recruited from a social center, an old-age home, and psychogeriatric outpatient clinics. At a cutoff score of 3 of 4, the CDS achieved a sensitivity of 90.5% and specificity of 98.1% in differentiating demented from healthy control subjects. In the Chinese population studied, the scale was readily acceptable and considered to be an useful adjunct in screening of dementia.

Aged↗
PubMed1997

Study of hygroscopic properties of aqueous mixtures of disodium fluorescein and sodium chloride using an electrodynamic balance.

PURPOSE: The purposes of this study are: a) to demonstrate the use of an Electrodynamic Balance (EDB) to investigate the hygroscopic properties of pharmaceutical aerosols; and b) to evaluate the applicability of the Zdanovskii-Stokes-Robinson model (ZSR) in the associated data analysis with multicomponent pharmaceutical aerosols. METHODS: The compositional dependence of the water activity of two model materials commonly employed in the study of pharmaceutical aerosols, namely, NaCl and Disodium Fluorescein (DF), was investigated using an EDB. The water contents of single levitated droplets of NaCl and DF and their mixtures at mass ratios of 1:3, 1:1, 3:1, and 6:1 from dilute concentration to high supersaturation were determined as a function of relative humidity (RH). RESULTS: At decreasing ambient RH, supersaturated aqueous NaCl droplets lose water and crystallize to form dry solid particles at an RH of approximately 50%. Aqueous DF droplet continues to lose water until it reaches a final state containing about 20% by mass of residual water. Mixed solutions of DF and NaCl crystallize at an RH of approximately 50% and then continue to lose water at lower RHs. The resulting "dried" particle still contains water whose amount depends on the mass ratios of DF and NaCl in the mixture. Good prediction of water activity of the DF-NaCl mixture can be achieved with the ZSR model. Collection of a full set of water activity-composition data at each mass ratio of DF-NaCl requires only a few hours. CONCLUSIONS: The EDB, together with the application of the ZSR model in data treatment, appears to be a valuable tool for studying the hygroscopic properties of pharmaceutical aerosols.

Aerosols↗
PubMed1997

Folding of cytochrome c initiated by submillisecond mixing.

Cytochrome c folding was initiated using a new solution mixer that provides a time window which covers over 90% of the burst phase unresolved by conventional stop-flow measurements. Folding was followed by resonance Raman scattering. Kinetic analysis of the high frequency Raman data indicates that a nascent phase occurs within the mixing dead time of 100 microseconds. A significant fraction of the protein was found to be trapped in a misfolded bis-histidine form during the nascent phase at pH 4.5, thereby preventing the protein from folding rapidly and homogeneously. The nascent phase was followed by a haem-ligand exchange phase that populates the native histidine-methionine coordinated form through a thermodynamically controlled equilibrium.

Animals↗
PubMed1997

The modified Fuld Verbal Fluency Test: a validation study in Hong Kong.

Recent studies in the West have found that verbal fluency tests are useful in the detection of dementia. In this study, the Fuld Verbal Fluency Test (FVFT) was modified and tested for its usefulness as a screening instrument for differentiating demented from normal elderly Chinese in Hong Kong. Fifty-three normal and 56 demented subjects were administered the FVFT, the Cantonese version of the Mini-Mental State Examination (CMMSE), and the Chinese version of the Hamilton Depression Rating Scale. In addition to bearing significant correlation with the CMMSE, the verbal fluency scores for all semantic categories (animals, fruits, vegetables) were found to produce significant differentiation between the normal and demented groups. However, test-retest reliability for the individual verbal fluency scores was shown to be unsatisfactory, and a composite measure was recommended for use in future screening on the grounds of its enhanced reliability.

Aged↗
PubMed1997

Differential inhibition of lysophosphatidate signaling by volatile anesthetics.

BACKGROUND: Volatile anesthetics have been found to interfere with the functioning of several G protein-coupled receptors, effects that may be relevant to the mechanism of anesthetic action. Lysophosphatidate (1-acyl-2-sn-glycero-3-phosphate; LP) is the simplest natural phospholipid. It has pronounced biological effects and signals through a specific G protein-coupled receptor. Because of its lipophilicity, the LP receptor is a feasible site of anesthetic interaction. Therefore, the authors investigated the effects of halothane and isoflurane on LP signaling using Xenopus oocytes. METHODS: Mature oocytes were harvested from Xenopus frogs, isolated, and defolliculated manually. Lysophosphatidate receptors are endogenously present in these cells. Angiotensin receptors were expressed recombinantly to study anesthetic effects on intracellular signaling. Oocytes were studied individually with a two-electrode voltage clamp at room temperature. Integrated Ca(2+)-activated Cl- currents (ICl(Ca)) were used to evaluate the effects of anesthetics on changes in intracellular Ca2+ concentration in response to receptor agonists (10(-7) M LP or 10(-7) M angiotensin II) or intracellular inositoltrisphosphate (IP3) injection. RESULTS: Halothane depressed LP signaling in a concentration-dependent manner, with half-maximal inhibition at 0.23 mM and virtually complete inhibition at 0.34 mM. Responses could be recovered after an anesthetic-free wash. Oocyte injection with heparin, an IP3 receptor antagonist, completely blocked LP and angiotensin signaling, indicating similar IP3- dependent pathways. However, ICl(Ca) induced by angiotensin receptor activation or intracellular IP3 injection were not inhibited by halothane. Isoflurane, at comparable concentrations, did not depress LP responses in oocytes significantly. CONCLUSIONS: Lipid-mediator signaling can be affected profoundly by volatile anesthetics. At clinically relevant concentrations, halothane and isoflurane have different effects on LP signaling. The inhibitory effects of halothane on the LP signaling pathway occur before the IP3 receptor.

Anesthetics, Inhalation↗
PubMed1997

Inhibition of lysophosphatidate signaling by lidocaine and bupivacaine.

BACKGROUND: Lidocaine and bupivacaine impair wound healing, but the mechanism of this side effect has not been determined. The phospholipid messenger lysophosphatidate is released from activated platelets and induces fibroblast and smooth muscle proliferation. Because it may play a role in wound healing, the authors studied the effects of local anesthetics on lysophosphatidate signaling in Xenopus oocytes. METHODS: Defolliculated Xenopus oocytes expressing endogenous G protein-coupled lysophosphatidate receptors were voltage clamped and studied in the presence or absence of lidocaine or bupivacaine. Lysophosphatidate-induced Ca(2+)-activated Cl- currents (IC1(Ca)) were measured. To determine the site of action of the local anesthetics on the signaling pathway, the authors studied 1) the effects of local anesthetics on signaling induced by intracellular injection of the second messenger inositoltrisphosphate, and 2) the effects of local anesthetics on functioning of recombinantly expressed angiotensin II receptor signaling through the same pathways as the lysophosphatidate receptor. RESULTS: Lysophosphatidate signaling was inhibited in the presence of local anesthetics. The half maximal inhibitory concentration (IC50S) for lidocaine and bupivacaine were 29.6 mM and 4.7 mM, respectively. Neither responses induced by inositoltrisphosphate injection nor angiotensin signaling were influenced by local anesthetics. CONCLUSIONS: Lysophosphatidate signaling is inhibited by the extracellular application of lidocaine or bupivacaine. In contrast, inositoltrisphosphate or angiotensin signaling was not affected by local anesthetics. Therefore local anesthetics have a specific, extracellular effect on lysophosphatidate receptor functioning. As the local anesthetic concentrations used were similar to those observed after injection around surgical wounds, LP inhibition may play a role in the observed detrimental effects of local anesthetics on wound healing.

Anesthetics, Local↗
PubMed1997

Does treatment of Helicobacter pylori with antibiotics alone heal duodenal ulcer? A randomised double blind placebo controlled study.

BACKGROUND: Treatment of Helicobacter pylori infection prevents duodenal ulcer relapse. It has not been established if treatment of the infection heals duodenal ulcer. AIM: To test the hypothesis that treatment of the infection was associated with healing of duodenal ulcer. METHODS: A randomised, double blind placebo controlled trial was performed to study the efficacy of an antibiotic only regimen consisting of 300 mg metronidazole, 500 mg amoxycillin, and 250 mg clarithromycin, each given four times daily for two weeks, in the healing of duodenal ulcer as assessed by endoscopy. Symptoms were controlled with acetaminophen and antacids. RESULTS: Of 100 consecutive patients with endoscopically established duodenal ulcer, 97 with positive rapid urease test on antral biopsy specimens were admitted into the study and 81 completed the trial. Of these, 40 were randomised to receive antibiotics and 41 to receive placebo. Treatment with antibiotics resulted in 92.5% (95% confidence interval (95% CI) 84.3-100) healing at four weeks and 100% at eight and 12 weeks; the corresponding healing rates for placebo treatment were respectively, 36.6%, 61%, and 63.4% (95% CIs 21.8-51.3, 46.0-75.9, and 48.7-78.2 respectively). The differences between the two treatment groups were significant at p < 0.001 at each time point and by life table analysis. Clearance of H pylori as assessed by urease test on antral biopsy specimens at four weeks and eradication of the organism as determined by 13C-urea breath test at eight weeks were achieved in 85% and 62.5% of patients respectively. Duodenal ulcer healed at four weeks in 87.2% and 86.2% (95% CIs 76.7-97.7 and 73.7-98.8) of patients in whom H pylori clearance or eradication, was achieved, versus 42.9% and 51.9% (95% CIs 27.9-57.8 and 38.3-65.5; p < 0.001 and < 0.003 respectively) in whom these processes failed. Stepwise discriminant analysis on 32 clinical, personal, and endoscopic characteristics as well as H pylori clearance and eradication identified H pylori clearance as the most discriminative variable for the healing of duodenal ulcer at four weeks, followed by ulcer depth and eradication of the organism. CONCLUSIONS: Treatment with an antibiotic only regimen was effective for the healing of duodenal ulcer, and clearance as well as eradication of H pylori contributed significantly to the healing. The results constituted the strongest evidence to date that H pylori infection was aetiologically related to duodenal ulceration, and support the concept of treating duodenal ulcer associated with H pylori as an infection and relieving its symptoms with acid reducing agents such as antacids.

Adult↗
PubMed1997

How are psychotic symptoms perceived? A comparison between patients, relatives and the general public.

OBJECTIVE: The aim of this study is to compare patients with schizophrenia with their relatives and the general public in their attitudes towards schizophrenic psychotic symptoms. METHOD: We used a case vignette depicting a person with typical schizophrenic psychotic symptoms and compared the attitudes of 44 inpatients and 47 outpatients with schizophrenia, 48 of their relatives and 43 members of the general public. We also compared the attitudes of patients with schizophrenia to their own symptoms and the symptoms described in the vignette. RESULTS: Subjects from the general public tended not to recognise psychotic symptoms as features of mental illness and tended not to consider drug treatment and hospitalisation as required. Sex, education level as well as previous contact with the mentally ill were found to be significant determinants of attitude. The levels of symptom awareness in patients with schizophrenia and their relatives are higher but still relatively low. In addition, we found that patients with schizophrenia who correctly appraised psychotic symptoms in another person were also aware of their own mental symptoms and need of treatment. CONCLUSIONS: The level of recognition of psychotic symptoms and awareness of a need for treatment are low in the general public, as well as in patients with schizophrenia and their relatives. These findings are discussed in relation to the assessment of insight in patients and a need for psychoeducational programs for each group.

Adolescent↗
PubMed1997

Current trends in HIV-related hospital admissions and their impact on hospital resource utilization in Ontario.

OBJECTIVE: To assess changes in patterns of hospital admissions, in frequency of admissions and in average length of stay (ALOS) at a tertiary HIV referral centre, and to investigate the overall impact of care for patients with HIV infection of AIDS on peer hospitals in Ontario. DESIGN: Descriptive study. PARTICIPANTS: Data were obtained on patients with HIV infection or AIDS treated at the Wellesley Hospital in Toronto for the fiscal years (May 1 to Apr. 31) 1990-91, 1991-92 and 1992-93, and on admissions for HIV or AIDS in 9 peer hospitals in Ontario during the same period. INTERVENTIONS: For the Wellesley Hospital, review of medical records of HIV-related admissions to determine the reasons for admission and to examine concurrent illnesses. For the Wellesley Hospital Hospital and peer hospitals, analysis of changes in ALOS and Resource Intensity Weights (RIWs). RESULTS: Between May 1, 1990, and Apr. 31, 1993, the number of admissions for treatment of Pneumocystis carinii pneumonia (PCP) fell, but admissions for respiratory infections other than PCP remained very common, although they decreased slightly. Overall, infection remained the main reason for admission. The frequency of gastrointestinal complications necessitating admission increased. The frequency of admissions remained high, although the ALOS decreased significantly. In the period between Apr. 1, 1991, and Mar. 31, 1994, the proportion of HIV-related discharges and total hospital discharges among the 9 peer hospitals remained stable. The HIV-related ALOS decreased substantially. Although the HIV-related average RIW decreased slightly, this measure and the mortality rate are still much higher for HIV-related admissions than for overall admissions. CONCLUSIONS: This contemporary survey suggests that nonrespiratory infection complications have become the main reason for admission of patients with HIV infection or AIDS, but that the HIV tertiary hospitals are coping with the load of HIV-related admissions and the high average RIW associated with these patients by reducing the ALOS.

Female↗
PubMed1996

Fast events in protein folding.

Understanding how proteins fold is one of the central problems in biochemistry. A new generation of kinetic experiments has emerged to investigate the mechanisms of protein folding on the previously inaccessible submillisecond time scale. These experiments provide the first glimpse of processes such as secondary structure formation, local hydrophobic collapse, global collapse to compact denatured states, and fast barrier crossings to the native state. Key results are summarized and discussed in terms of the statistical energy landscape theory of protein folding.

Apoproteins↗
PubMed1996

Expectancy bias in trait anxiety.

The ability of anxious and control participants to learn about signals for danger and safety was tested within an autonomic conditioned inhibition (A+/AB-) procedure. Only participants who could verbalize the differential contingencies between the stimuli and shock (aware participants) showed discrimination on electrodermal and shock expectancy measures. In Experiment 1, aware high-anxious participants showed similar responding to control participants. However unaware high-anxious participants showed heightened shock expectancy to all stimuli. Experiment 2 replicated this expectancy bias in anxious unaware participants controlling for shock intensity. In both experiments, expectancy bias was associated primarily with anxiety rather than depression. Results support the notion of an interpretive bias in anxious participants under ambiguous threat, consistent with recent findings from information-processing research on linguistic stimuli.

Adult↗