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Biomedical subjects

C K Chan

Publications and source records attributed to C K Chan.

At least 163 records · Page 9Linked to original sources
PubMed1995

Treatment of idiopathic macular holes by induced posterior vitreous detachment.

PURPOSE: To determine if an expansile gas bubble can relieve vitreofoveal traction without vitrectomy by inducing a posterior vitreous detachment (PVD) in eyes with an idiopathic impending or full-thickness macular hole (stages 1-3). The status of the impending and full-thickness macular holes after gas injection and tamponade also was studied secondarily. METHODS: Eighteen patients participated in this pilot study. Eleven patients with an impending macular hole (stages 1A and 1B) and seven patients (8 eyes) with a full-thickness macular hole (stages 2 and 3) received gas injections and prospectively were followed for an average of 15.6 months (range, 3-42 months). RESULTS: A complete PVD was achieved in 18 of 19 eyes without a prior PVD within 2 to 9 weeks after gas injection. Ten of the 11 impending holes (all 7 had stage 1A holes; 3 of 4 had stage 1B holes) resolved after gas injection. After gas tamponade, three of six early full-thickness (stage 2) macular holes closed. None of the stage 3 macular holes closed after gas injection. The mean best-corrected visual acuity of the successful eyes was 20/32. There were no major complications. CONCLUSION: An expansile gas bubble consistently can induce a PVD in aging eyes. The ability of an expansile gas bubble to induce a PVD with minimal morbidity and expense may have clinical applications for macular hole therapy. Impending macular holes may resolve and some early full-thickness (stage 2) macular holes may close after gas injection and tamponade without vitrectomy. The efficacy and safety of this procedure may be evaluated further in the context of a carefully designed prospective and randomized study for selected patients with an idiopathic impending or early macular hole.

Aged↗
PubMed1994

Activation of the mitogen-activated protein kinase signaling pathway in neutrophils. Role of oxidants.

In addition to their role in bacterial killing, reactive oxygen intermediates (ROI) produced by the NADPH oxidase may participate in the regulation of intracellular pathways. We have recently demonstrated that ROI produced by the oxidase regulate tyrosine phosphorylation in neutrophils, possibly by alterations in the cellular redox state. The purpose of the present study was to characterize the identities of certain of the redox-sensitive tyrosine-phosphorylated substrates and the significance of the increased phosphorylation. As a prominent 42-44-kDa phosphorylated band was noted in oxidant-treated cells, we investigated the possible phosphorylation and activation of mitogen-activated protein (MAP) kinase under these conditions. Immunoprecipitation of MAP kinase followed by immunoblotting with anti-phosphotyrosine antibodies indicated that a 42-44-kDa polypeptide was tyrosine-phosphorylated in response to treatment of cells, either with the oxidizing agent diamide or with H2O2 in cells where catalase was inhibited. Using an in vitro renaturation assay with myelin basic protein as the substrate, oxidant-induced stimulation of kinase activity of a 42-44-kDa band was observed in both whole cell extracts and in MAP kinase immunoprecipitates. The mechanism of redox-sensitive activation of MAP kinase was examined. First, exposure of cells to oxidants caused a significant increase in the activity of MEK (the putative activator of MAP kinase), as determined by an in vitro kinase assay using recombinant catalytically inactive glutathione S-transferase-MAP kinase as the substrate. Additionally, oxidant treatment of cells resulted in inhibition of the activity of CD45, a protein tyrosine phosphatase known to dephosphorylate and inactivate MAP kinase. We conclude that oxidant treatment of neutrophils can activate MAP kinase by stimulating its tyrosine and (presumably) threonine phosphorylation via MEK activation, a response that may be potentiated by inhibition of MAP kinase dephosphorylation by phosphatases such as CD45.

Cells, Cultured↗
PubMed1994

Cord compression due to extramedullary hemopoiesis in a patient with thalassemia.

STUDY DESIGN: This is a case report of a patient with thalassemia who had acute spinal cord compression at the T3 to T8 level and presented for treatment. METHODS: Magnetic resonance imaging and surgical decompression and transfusion therapy was chosen as the preferred treatment modality. RESULTS: Neurologic recovery was satisfactory from the immediate postoperative period, and full recovery was observed 2 months after surgery. CONCLUSION: Clinical awareness is important for early diagnosis. Documentation with an imaging technique, such as magnetic resonance imaging, is mandatory. Optimal treatment is tailor-made and depends on the clinical situation and the expertise available.

Adult↗
PubMed1994

Potentiation of the oxidative burst of human neutrophils. A signaling role for L-selectin.

Production of reactive oxygen intermediates (ROI) by the NADPH oxidase of neutrophils is a major mechanism of bacterial killing and, in pathologic circumstances, tissue damage. Integrins and selectins participate in neutrophil adhesion but may also play a role in intracellular signaling. The role of L-selectin in ROI production and Ca2+ signaling in suspended neutrophils was examined using the DREG series of anti-L-selectin antibodies. NADPH oxidase activation was assessed in three ways: H2O2 production using either scopoletin or dihydrorhodamine and O2- production using cytochrome c. Alterations in [Ca2+]i were measured using Fura 2-AM and fluorescence spectrophotometry. Cross-linking of L-selectin with DREG and 2 degrees antibody did not trigger production of H2O2 by itself but significantly enhanced the subsequent response to two soluble activating agents; the formyl peptide formyl-Met-Leu-Phe (fMLP) and tumor necrosis factor (TNF). Potentiation of the oxidative burst was observed using F(ab')2 fragments but not with irrelevant antibodies and was observed whether 2 degrees antibody was added before or after fMLP. Cross-linking of L-selectin also triggered a rise in [Ca2+]i, due, in part, to release from intracellular stores. The intracellular Ca2+ chelator BAPTA blocked both the rise in [Ca2+]i and the potentiation of the oxidative burst in response to fMLP or TNF. We conclude that cross-linking of L-selectin induces intracellular signals, including release of Ca2+, which may contribute to potentiation of the oxidative burst.

Antibodies↗
PubMed1994

The treatment of choroidal neovascular membranes by alpha interferon. An efficacy and toxicity study.

PURPOSE: The purpose of this phase 2 study was to determine the potential efficacy and safety of systemic alpha interferon in the treatment of subfoveal choroidal neovascularization associated with age-related macular degeneration or ocular histoplasmosis. METHOD: Subcutaneous alpha interferon was administered to 24 patients (24 eyes), and they were prospectively studied. Alpha interferon was administered subcutaneously four times daily at a dose of 3 x 10(6) U/m2 (average total dose, 204 MU). The studied parameters included best-corrected visual acuity, membrane size, blood, exudates, and subretinal fluid. Toxic effects and performance status were graded according to the National Cancer Institute toxicity criteria and Karnofsky performance scale, respectively. RESULTS: Of the 24 treated eyes, 5 (21%) showed objective evidence of anatomic improvement, as defined by decrease in membrane size or improvement in fluorescein angiographic characteristics, but in only 3 of these 5 was the improvement maintained. The same three patients achieved and maintained functional success (visual improvement). Two of the five patients with initial anatomic improvement had subsequent membrane recurrence, which resulted in no visual change in one but visual loss in the other. For the majority of patients, the anatomic and visual status remained the same or became worse after treatment. All patients experienced some degree of adverse reactions involving multiple organ systems. Decreased performance status affected 80% of the patients. CONCLUSION: This study documents that regression of choroidal neovascularization that occurred with alpha interferon treatment was minimal. Toxic effects interfering with patients' performance status are associated with alpha interferon treatment. Although a randomized trial of interferon versus no therapy may be warranted, fundamental issues (i.e., the biologic properties of interferon versus other more potent agents against choroidal neovascularization, medication dosages, and routes of administration), need to be addressed before embarking on such a trial.

Aged↗
PubMed1994

Effects of cephalometric landmark validity on incisor angulation.

An experimental cephalometric study on the accuracy of independently locating eight landmarks and the subsequent effects on the maxillary (ILs/NL) and mandibular (ILi/ML) incisor angulation was carried out on 30 dry skulls. The true location of each landmark was marked with a steel ball glued onto the skulls. Two additional steel balls were used as reference markers. A purpose-designed skullholder was made to assure a firm and reproducible positioning of the skulls in the cephalostat. Six series of cephalograms were recorded. One reference series with all the steel balls, four series each with a single steel ball marker removed, one at a time, from each jaw and one series with all the steel ball markers removed, except the reference markers. The combined method error in relocating and replacing the steel ball markers, repositioning the skulls into the skull holder, and digitizing, was low. From the first series, the true position of the palatal plane (NL), the maxillary incisor line (ILs), the mandibular plane (ML) and the mandibular incisor line (ILi) were assessed. From series 2 to 5, each of the landmarks without the steel ball markers was estimated. The accuracy of each landmark was then assessed relative to the true cephalometric plane and its perpendicular. On average, the accuracy was high for all the landmarks except posterior nasal spine (PNS), which was estimated 1.2 mm too far anteriorly (p < 0.05). The standard deviations of the accuracy of the dental and skeletal landmarks were similar, being 1.4 to 2.4 mm. The maxillary incisors were proclined 1.1 degrees (p < 0.05) by the estimates of incision superior (Is).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Penang cancer cases reported to the National Cancer Registry of Malaysia, 1987-1990: an epidemiological analysis.

2,124 cases of cancer diagnosed and/or treated in Penang between 1987-1990 were reported to the National Cancer Registry of Malaysia by hospitals in Penang. 1,762 met the criteria for Penang incident cases first diagnosed between 1987-1990, and were the subjects on which all subsequent analyses were based. 85 per cent of case notifications were from Mount Miriam Hospital. Among males, all-site cancer incidence rates (age-standardised) were highest among Chinese, and lowest among Malays. Among females, the Indian female incidence rate was highest, higher than that of any other ethnic-gender sub-group. Site-specific cancer rates varied according to ethnicity and gender, but overall the four most frequent cancers reported from Penang were breast, lung, cervix and nasopharynx cancers. It needs to be emphasised that all these results are highly tentative since they are based on notified cancer occurrences and hence are very uncertain proxies for true cancer incidence. Based on incidence rates from the Singapore Cancer Registry (1978-1982), the expected number of incident cases in 1989 for Penang (Malays, Chinese and Indians combined) was 1,561. The number notified to the National Cancer Registry was 496. This underlines the tentative nature of this analysis of the returns for 1987-1990 from Penang.

Adolescent↗
PubMed1993

Fast events in protein folding initiated by nanosecond laser photolysis.

Initiation of protein folding by light can dramatically improve the time resolution of kinetic studies. Here we present an example of an optically triggered folding reaction by using nanosecond photodissociation of the heme-carbon monoxide complex of reduced cytochrome c. The optical trigger is based on the observation that under destabilizing conditions cytochrome c can be unfolded by preferential binding of carbon monoxide to the covalently attached heme group in the unfolded state. Photodissociation of the carbon monoxide thus triggers the folding reaction. We used time-resolved absorption spectroscopy to monitor binding at the heme. Before folding begins we observe transient binding of both nonnative and native ligands from the unfolded polypeptide on a microsecond time scale. Kinetic modeling suggests that the intramolecular binding of methionine-65 and -80 is faster than that of histidine-26 and -33, even though the histidines are closer to the heme. This optical trigger should provide a powerful method for studying chain collapse and secondary structure formation in cytochrome c without any limitations in time resolution.

Amino Acid Sequence↗
PubMed1993

Regulation of tyrosine phosphorylation in neutrophils by the NADPH oxidase. Role of reactive oxygen intermediates.

Neutrophils possess a multicomponent NADPH-oxidase that produces large quantities of superoxide, which can in turn generate other reactive oxygen intermediates. Superoxide and its dismutation product, hydrogen peroxide, are powerful oxidants. Because the activity of certain tyrosine kinases and phosphatases can be affected by their redox state, we considered the possibility that endogenously generated reactive oxygen intermediates (ROI) may alter phosphotyrosine formation and thereby function as intra- or intercellular messengers in neutrophils. Exposure of human neutrophils to exogenous oxidants such as diamide induced marked tyrosine phosphorylation of several cellular proteins. More importantly, activation of the NADPH oxidase in permeabilized neutrophils, by direct stimulation of GTP-binding proteins, also resulted in enhanced tyrosine phosphorylation. The latter was NADPH-dependent, paralleled by production of superoxide, and was inhibited by diphenylene iodonium, an inhibitor of the flavoprotein component of the oxidase. Neutrophils, from a patient with chronic granulomatous disease, which are deficient in the production of ROI, demonstrated no such phosphotyrosine accumulation. We conclude that ROI produced by the NADPH oxidase can regulate tyrosine phosphorylation in granulocytes, possibly by effects of oxidation-sensitive tyrosine kinases and/or phosphatases.

Animals↗
PubMed1993

Okadaic acid-induced actin assembly in neutrophils: role of protein phosphatases.

Activation of neutrophils results in morphological and functional alterations including changes in cell shape and initiation of motile behavior that depend on assembly and reorganization of the actin cytoskeleton. Phosphoproteins are thought to be key intermediates in the regulation of cytoskeletal alterations and whereas much attention has been directed at the role of protein kinases, relatively little information is available on the importance of phosphatases. To elucidate the role of protein phosphatases, we studied the effects of the phosphatase inhibitors okadaic acid and calyculin A on the actin cytoskeleton of human neutrophils. Exposure of cells to okadaic acid resulted in assembly and spatial redistribution of actin, which peaked at 25 min and returned to baseline levels by 45 min, as assessed by flow cytometric analysis of NBD-phallacidin stained cells and confocal fluorescence microscopy, respectively. These effects correlated with an increase in protein phosphorylation, determined by incorporation of 32P into cellular proteins using SDS-PAGE and autoradiography. Similar but more rapid responses were observed in electropermeabilized cells treated with okadaic acid or calyculin A. The dose dependence of these effects was compatible with a role for phosphatase type 1 as the target enzyme. These findings also suggested the presence of constitutively active protein kinases capable of effecting actin polymerization. Phosphorylation of myosin light chain (MLC) has been postulated to promote actin assembly, but myosin light chain kinase (MLCK) appeared not to be involved because: (1) the effect of okadaic acid was not inhibited by the MLCK inhibitor KT5926 and (2) in permeabilized cells suspended in medium with free calcium [Ca2+] < 10 nM (conditions under which MLCK is inactive), the effect of okadaic acid persisted. The role of phosphatases in stimulus-induced actin assembly was assessed in cells preincubated with okadaic acid for 45 min, after F-actin levels had returned to baseline. Under these conditions, okadaic acid completely abrogated actin assembly induced by phorbol myristate acetate, platelet activating factor, and leukotriene B4, whereas the effects of the chemotactic peptide fMLP and opsonized zymosan (OpZ) were unaffected. We conclude that serine and threonine phosphatases exert a tonic negative influence on actin assembly and organization. Furthermore, divergent pathways seem to mediate the response to lipidic stimuli, on one hand, and fMLP and OpZ, on the other, as evidenced by the differential susceptibility to inhibition by okadaic acid.

Actins↗
PubMed1993

Treatment of community-acquired pneumonia. A multicenter, double-blind, randomized study comparing clarithromycin with erythromycin. Canada-Sweden Clarithromycin-Pneumonia Study Group.

The efficacy and safety of orally administered clarithromycin and erythromycin in the treatment of community-acquired pneumonia were assessed in a multicenter, double-blind, randomized study. Two hundred sixty-eight patients were randomized to receive either clarithromycin, 250 mg twice a day, or erythromycin stearate, 500 mg 4 times a day, for 7 to 14 days. Efficacy was evaluable in 173 patients (92 for clarithromycin, 81 for erythromycin). No statistically significant difference in clinical success rate (cure or improvement) was observed between the two groups (clarithromycin, 97 percent; erythromycin, 96 percent). Both groups had identical radiologic response (97 percent with resolution or improvement). Similarly, no statistically significant difference in bacteriologic response toward the target pathogens was observed among evaluable patients (clarithromycin, 23/26; erythromycin, 17/17; p value = 0.287). Clinical response toward Mycoplasma and Chlamydia pneumonia was comparable between the two groups (clarithromycin, 15/16; erythromycin, 10/11). However, patients receiving erythromycin had a twofold higher incidence of adverse events, mostly related to the gastrointestinal system, and were five times more likely to withdraw from therapy because of drug-related adverse events. These results show that clarithromycin is as effective as erythromycin in the outpatient treatment of community-acquired pneumonia. Furthermore, the lower incidence of adverse events associated with clarithromycin indicates that it is more acceptable to patients and, therefore, can enhance compliance.

Adolescent↗
PubMed1993

Handedness and sleep apnea.

Left-handedness is associated with shorter life span. Many of the factors contributing to this higher mortality (eg, alcohol consumption, automobile accident, smoking) are the same as in patients with sleep apnea, who also have higher mortality than nonapneic controls. The authors hypothesized that (1) there is a higher prevalence of sinistrality in patients suspected of having sleep apnea than in the general population, and (2) left-handed persons with sleep apnea have a more severe disorder than right-handed ones. These hypotheses were tested in a prospective cohort of 970 patients referred to a sleep disorders center because of suspected sleep apnea. All patients underwent nocturnal polysomnography and measurements of blood pressure. Sixty-one patients were left-handed. The distribution of handedness as a function of age in this cohort was similar to that in the general population. There were 486 patients with an apnea/hypopnea index greater than 10; of these, 34 were left-handed, and 452 were right-handed. Oxygen saturation, blood pressure, age, smoking history, and body mass index were similar in both groups. Left-handed patients with sleep apnea had a significantly higher respiratory disturbance index (RDI) than the right-handed ones (52 +/- 30 vs 38 +/- 35 [p < 0.005]). Right-handed patients were distributed equally among RDI quartiles, but 41 percent of the left-handed patients were within the highest RDI quartile, compared to 12 percent within the lowest quartile. Sinistrality appears to be associated with more severe sleep apnea, which may help to explain the higher mortality seen among the left-handed persons.

Adult↗
PubMed1993

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

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

Adolescent↗