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Biomedical subjects

S W Chan

Publications and source records attributed to S W Chan.

At least 37 records · Page 2Linked to original sources

Comparison of a commercial enzyme-linked immunosorbent assay with immunofluorescence and complement fixation tests for detection of Coxiella burnetii (Q fever) immunoglobulin M.

A commercially available enzyme-linked immunosorbent assay (ELISA) for the diagnosis of Q fever (PanBio Coxiella burnetii immunoglobulin M [IgM] ELISA, QFM-200) was compared to the indirect fluorescent antibody test (IFAT) for C. burnetii IgM and the complement fixation test (CFT). The ELISA demonstrated 92% agreement with the reference method (IFAT), and gave a sensitivity of 99% (69 of 70 samples) and a specificity of 88% (106 of 121). Specificity can be increased with confirmation by IFAT. CFT was found to have a specificity of 90% (107 of 119), although it was lacking in sensitivity (73%; 51 of 70). No cross-reactivity was observed in the ELISA with serum samples from patients with mycoplasma (n = 6), chlamydia (n = 5), or legionella (n = 4) infections, although 2 of 5 patients with leptospirosis and 1 of 4 samples containing rheumatoid factor (RF) demonstrated positive results in the ELISA. Results indicate that the performance of the PanBio C. burnetii (Q fever) IgM ELISA (F = 187) is superior to that of CFT (F = 163), and consequently the ELISA should be a useful aid in the diagnosis of acute Q fever.

Antibodies, Bacterial↗

Pre-column derivatization and gas chromatographic determination of alkaloids in bulbs of Fritillaria.

A method of precolumn derivatization GC with FID detection was developed for a simultaneous analysis of five major steroidal alkaloids of Fritillaria species, namely ebeiedine, ebeiedinone, verticine, verticinone and imperialine. Derivatization was carried out by trimethylsilylation of the hydroxyl-containing Fritillaria alkaloids to the corresponding trimethylsilylates with trimethylsilylimidazole. Reaction conditions were optimised and the alkaloids derivatives were characterised by on-line GC-MS. The validated GC method demonstrated a good linearity at the sampling ranges used. This analytical method is simple, convenient and reproducible. The developed assay was successfully applied to the determination of the major pharmacologically active alkaloids in three commonly used antitussive Fritillaria species: F. cirrhosa, F. thunbergii and F. pallidiflora.

Alkaloids↗

The continuum-of-addiction: cigarette smoking in relation to price among Americans aged 15-29.

We studied the relationship between current cigarette smoking and price among 34145 respondents, aged 15-29 years, to the 1992-1993 Tobacco Use Supplements to the Current Population Survey. The price elasticity of current smoking varied inversely with age: -0.831 (S.E. 0.402) for ages 15-17; -0.524 (S.E. 0.256) for ages 18-20; -0.370 (S.E. 0.188) for ages 21-23; -0.202 (S.E. 0.175) for ages 24-26; and -0.095 (S.E. 0.157) for ages 27-29. In response to higher prices, older youth were more likely to reduce the number of cigarettes smoked per day than to quit entirely. Among 15-17-year-olds, smoking cigarettes 'some days' was more sensitive to price than smoking 'every day'. Cigarette smoking was inversely related to the prices of premium brands, but not discount brands.

Adolescent↗

The use of critical pathways in caring for schizophrenic patients in a mental hospital.

To provide quality health care and at the same time, to control cost, literature suggests that using critical pathways as a tool can enhance resource management, increase collaborative practice, and benefit patient care. This study describes the processes of developing a critical pathway in caring for schizophrenic patients in a mental hospital in Hong Kong. The perceived benefits and difficulties in using the critical pathway are discussed from a nursing perspective. Nurses believed that the use of critical pathways could improve the coordination and effectiveness of care. Also, nurses' autonomy and professional status improved. However, inadequate knowledge and resistance from other disciplines were barriers to the implementation. Recommendations are given to overcome the barriers.

Cost Control↗

Human recombinant single-chain antibody fragments, specific for the hypervariable region 1 of hepatitis C virus, from immune phage-display libraries.

The hypervariable region 1 (HVR1) of hepatitis C virus (HCV) may contain a potential neutralization site and the generation of human single-chain antibody fragments (scFv) to HVR1 may therefore provide a useful tool for the study of HCV. In this report, we have isolated and characterized three anti-HVR1 scFv clones from two patient-derived phage-displayed libraries and HCV HVR1 peptides. scFv S52/20 and S53/6 were selected with serologically cross-reactive HVR1 peptides. scFv p3f10 was obtained by screening the library from patient MH with an autologous HVR1 peptide. Nucleotide sequencing showed that the VH chains and Vkappa chains of all three scFv antibodies were derived from VH3 and Vkappa1 family germline V-genes, respectively. The specificity and affinity of the recombinant scFv antibodies were examined by enzyme-linked immunosorbent assay (ELISA) and an affinity biosensor, using HVR1 peptides. S52/20 scFv binding to S52 HVR1 peptide was blocked by preincubation with soluble peptide S52 and was partially competed by one of three HCV-infected patient sera. In addition, scFv S52/20 blocked the binding of HCV-susceptible Molt-4 cells to immobilized S52 peptide. This study demonstrates that recombinant human scFv antibodies to HCV HVR1 can be produced in vitro and directly confirms that HVR1 of HCV elicits highly specific antibodies. The very high specificity of these antibodies to HVR1 may limit their potential use in passive immunization therapy against HCV, and further engineering of the scFvs needs to be performed to generate broad-spectrum blocking scFvs.

Amino Acid Sequence↗

The complement system of the duck.

Antibody (Ab)-dependent and-independent activation of the duck complement (C') system were studied. Ab-independent C' activity exhibited characteristics similar to those of the mammalian alternative C' pathway (ACP), including the selective lysis of rabbit erythrocytes (RRBC), a requirement for Mg2+, but not Ca2+, depletion of activity by zymosan, and lack of sensitivity to the mammalian C1 inhibitor carrageenan. Measurement of C' activity using antisera against sheep erythrocytes (SRBC) revealed that duck Abs activate C' by a pathway resembling the mammalian classical pathway (CCP) requiring both Ca2+ and Mg2+. Ab-dependent and-independent activities were further distinguishable by their kinetics of lysis and sensitivities to heat. Duck Abs were also found to activate C' in normal and carrageenan-treated serum by a mechanism that requires only Mg2+, and thus resembles the ACP. However, this Ab-dependent ACP-like activity exhibits patterns of ionic strength dependence and ontogeny which are clearly different from those of the conventional ACP and CCP. These findings indicate that duck C' can be activated by three mechanisms: Ab-mediated activation of the CCP, and Ab-mediated and Ab-independent activation of the ACP. Duck Ab responses to SRBC and RRBC were followed by direct agglutination, antiglobulin agglutination, and activation of the CCP and ACP. While the C'-activating abilities of duck anti-SRBC Abs persisted through a 3-month programme of inoculation, the anti-RRBC response lost its ability to activate C' after 2 weeks.

Journal Article↗

Political participation in Hong Kong: a study.

AIMS: The aim of this study was to investigate nurses' level of political participation and their perception of political efficacy. METHODOLOGY: This is a descriptive study. A self-completed questionnaire survey was conducted. Some items in the adopted questionnaire were modified to suit the Hong Kong situation. SAMPLES: A convenience sample was used. Three hundred and fifty registered nurses that were studying nursing degree programmes in the three universities in Hong Kong were invited to participate in the study. FINDINGS: Three hundred and eleven registered nurses completed the questionnaire. The findings showed that there were some positive signs of both political awareness and participation in nurses. However, political activities were mainly confined to voting in general elections. Attempts to influence politicians were not evident. Subjects generally have low political efficacy, and they did not feel that nurses had the power to influence the government's policy. The results of this study are discussed in terms of the barriers to nurses' political participation and the recommendations for nursing professional development.

Attitude of Health Personnel↗

Cell surface trafficking of Fas: a rapid mechanism of p53-mediated apoptosis.

p53 acts as a tumor suppressor by inducing both growth arrest and apoptosis. p53-induced apoptosis can occur without new RNA synthesis through an unknown mechanism. In human vascular smooth muscle cells, p53 activation transiently increased surface Fas (CD95) expression by transport from the Golgi complex. Golgi disruption blocked both p53-induced surface Fas expression and apoptosis. p53 also induced Fas-FADD binding and transiently sensitized cells to Fas-induced apoptosis. In contrast, lpr and gld fibroblasts were resistant to p53-induced apoptosis. Thus, p53 can mediate apoptosis through Fas transport from cytoplasmic stores.

Adaptor Proteins, Signal Transducing↗

Cooperative interactions between RB and p53 regulate cell proliferation, cell senescence, and apoptosis in human vascular smooth muscle cells from atherosclerotic plaques.

Compared with vascular smooth muscle cells (VSMCs) from normal vessels, VSMCs from human atherosclerotic plaques proliferate more slowly, undergo earlier senescence, and demonstrate higher levels of apoptosis in culture. The tumor suppressor genes p105RB (retinoblastoma, acting through the E2F transcription factor family) and p53 regulate cell proliferation, cell senescence, and apoptosis in many cell types. We have therefore determined whether these stable growth properties of plaque VSMCs reflect altered activity of RB and/or p53. VSMCs were derived from coronary atherectomies or from normal coronary arteries from transplant recipients. Compared with normal VSMCs, plaque VSMCs showed a higher ratio of the active (hypophosphorylated) to the inactive (phosphorylated) form of RB and a lower level of E2F transcriptional activity. Cells were stably transfected with retrovirus constructs that inhibited RB or p53 alone or in combination. Suppression of RB alone increased rates of cell proliferation and apoptosis and inhibited cell senescence in normal VSMCs. Suppression of p53 and RB together had similar effects but, additionally, resulted in immortalization of normal VSMC cultures. In contrast, inhibition of RB binding to E2F or ectopic expression of E2F-1 in plaque VSMCs induced massive apoptosis, which required suppression of p53 to rescue cells. Suppression of RB and p53 together increased cell proliferation and delayed senescence but failed to immortalize plaque VSMCs. Inhibition of p53 alone had minimal effects on plaque VSMCs but increased the lifespan of normal VSMCs. We conclude that human plaque VSMCs have slower rates of cell proliferation and earlier senescence than do cells from normal vessels because of a defect in phosphorylation of RB. Furthermore, both disruption of RB/E2F and inhibition of p53 are required for plaque VSMCs to proliferate without apoptosis. This observation may explain the relatively low level of cell proliferation and high level of apoptosis seen in VSMCs in human atherosclerotic plaques.

Apoptosis↗

Renal tuberculosis presenting as lateralizing hematuria diagnosis by ureteronephroscopy and selective upper tract urine culture.

A 48-year-old man presented with painless left lateralizing macroscopic hematuria. Ureteroscopy revealed flocculent material in the left kidney and white linear streaks on some upper pole papillae; urine culture from the left renal pelvis was positive for tuberculosis, whereas voided urine cultures were negative. Renal tuberculosis should be included in the differential diagnosis of lateralizing hematuria, especially in the absence of an obvious cause for the bleeding. Direct culture of urine from the renal pelvis may have more sensitivity than culture of voided urine in this circumstance.

Antitubercular Agents↗

The role of ascorbic acid in oral cancer and carcinogenesis.

L-ascorbic acid is an essential dietary vitamin in humans, primates and certain mammals and is endogenously synthesised in some species. Epidemiological and ecological studies have shown that L-ascorbic acid has a protective effect against cancer, in particular non-hormone-dependent malignancies, such as oropharyngeal neoplasms. Experimental in vivo and in vitro studies, however, have yielded more controversial results, suggesting that the effects of L-ascorbic acid are dose- and perhaps, time-dependent with different effects depending on the species or organ studied. An update of the epidemiological and experimental evidence linking L-ascorbic acid to oral cancer and carcinogenesis is discussed together with a brief review of the possible mechanisms of action of L-ascorbic acid.

Animals↗

P1,P4-dithio-P2,P3-monochloromethylene diadenosine 5',5'''-P1,P4-tetraphosphate: a novel antiplatelet agent.

We have previously demonstrated in a series of searches for antithrombotic agents that diadenosine 5',5"'-P1,P4-tetraphosphate (AppppA) and its analogues are competitive inhibitors of ADP-induced platelet aggregation. Among various analogues, the P2,P3-monochloromethylene analog of AppppA (AppCHClppA) is superior to unmodified AppppA in its antiplatelet and antithrombotic effects. In this communication, we compare the antiplatelet potency of five newly synthesized agents with that of AppCHClppA. The five new agents include four diadenosine polyphosphate analogues [Ap(s)pCHClpp(s)A (p(s) indicates a thiophosphate), dAppCHClppdA, dAp,pCHClpp(s)dA, and AppCHClpCHClppA], and an adenosine tetraphosphate analogue (AppCHClpCHClp). When tested for their inhibitory effects on platelet aggregation by ADP, the most promising agent among them was Ap(s)pCHClpp(s)A. Both molecular and functional integrity of this compound proved to be stable in blood at 37 degrees C for at least 3 h. It also showed an excellent heat stability. This agent inhibits a number of aspects of ADP-induced platelet activation-e.g., release reaction, cytoplasmic calcium mobilization, thromboxane production, fibrinogen binding sites, and platelet factor 3 activity. Moreover, platelet aggregation induced by agonists other than ADP-e.g., arachidonic acid, collagen, and epinephrine-was inhibited partially by Ap(s)pCHClpp(s)A. It is concluded that (i) Ap(s)pCHClpp(s)A is a promising antiplatelet agent; (ii) it is resistant to blood phosphodiesterases and stable to heat treatment; (iii) platelet aggregation induced by collagen, epinephrine, or arachidonic acid is also inhibited in part by this agent; and (iv) specificity of the inhibitory effects is presented by unmodified adenosine moieties of the agent. Resistance to phosphodiesterases raises the possibility of oral administration.

Blood Platelets↗

Unusual amino acid determinants of host range in the Mtx2 family of mosquitocidal toxins.

Five different mosquitocidal toxin (mtx2) gene homologs have been cloned from eight Bacillus sphaericus strains. Pairwise comparisons of the predicted amino acid sequences show between four and eight substitutions compared with the prototype Mtx2 from B. sphaericus strain SSII-1. Mtx2 from strain SSII-1 was approximately 7-fold more toxic to Culex mosquito larvae than the Mtx2 homolog from B. sphaericus strain 31-2. Conversely, Mtx2 from strain 31-2 was approximately 100-fold more toxic to Aedes mosquito larvae than Mtx2 from strain SSII-1. Lys224 in Mtx2 was found to be the most important amino acid for toxicity to Culex larvae, and substitution of Lys224 with threonine abolished the toxicity of Mtx2 from strain SSII-1 to these larvae. In complete contrast, Thr224 was found to be crucial for the toxicity of Mtx2 from strain 31-2 to Aedes larvae, and substitution of Thr224 with lysine caused a approximately 100-fold drop in toxicity to these larvae. Thus, amino acid 224 in the Mtx2 family of mosquitocidal toxins is an unusual and important determinant of mosquito larvicidal activity and host range.

Aedes↗

An expert system for the detection of cervical cancer cells using knowledge-based image analyzer.

Analyzing for abnormalities of cell images in the cervix uteri provides a basis for reducing deaths and morbidity from cervical cancer through detection of potentially cancerous cells, provision of prompt advice and opportunities for follow-up and treatments. However, cytopathology is usually based on subjective interpretation of morphological features. Arbitrary criteria have to be devised for their classifications. Subjective interpretations of such criteria are likely to result in diagnostic shifts and consequently disagreement occurs between different interpreters. This article presents a novel approach to the composition of segmentation and diagnosis processes for biomedical image analysis. A prototype expert system has been developed to provide an objective and reliable tool to gynaecologists. Special image analyzing techniques are used and a set of knowledge sources is designed. The expert system employs a robust control strategy which minimizes the amount of domain-specific control knowledge. It has been proved to work effectively in the detection of cervical cancer.

Artificial Intelligence↗

Induction by 4-nitroquinoline-1-oxide of oral epithelial dysplasia and neoplasia in scurvy-prone osteogenic disorder Shionogi (ODS) rats.

Carcinogenesis by 4-nitroquinoline-1-oxide (NQO) in the oral mucosa is a reliable method of obtaining oral mucosal squamous cell carcinoma (OMSCC) and allows examination of various stages of oral cancer development. In vivo and in vitro studies have indicated that L-ascorbic acid (AA) may have a role in cancer prevention. The Wistar "scurvy-prone" osteogenic disorder Shionogi (ODS) rat of the od/od substrain is unable to synthesize AA and requires supplementation for its survival. This study examined the effects of NQO on the oral mucosa of ODS and outbred Wistar rats. NQO (0.5%) was applied topically to the palatal mucosa of 72 male ODS and 36 outbred Wistar rats three times weekly for 4, 8, 12, 16, 20, and 24 wks. The ODS rats were divided so that 36 rats were given 2.5 g/l AA in the drinking water and 36 rats were given 0.33 g/l AA. Vehicle-treated and untreated control animals were included. The rats were killed two weeks after the final NQO application, and the tissues were examined. Epithelial dysplasia was assessed using a modified Smith and Pindborg (1969) index. The ordered categorical scores were analyzed appropriately. Plasma AA levels were checked in ODS and outbred rats at the start and end of the experiment. The results indicated that the oral mucosa of the ODS and outbred rats were susceptible to NQO but that the rate of dysplasia and OMSCC development differed between them, with more rapid changes being found in the ODS rats (p < or = 0.05). No significant difference was found in the dysplasia scores and in the rate of OMSCC development between ODS rats given 2.5 g/l of AA and ODS rats given 0.33 g/l of AA (p > 0.05). No epithelial changes were observed in the palatal mucosa of vehicle-treated and untreated controls. The plasma AA level mean (+/- SEM) was 56 +/- 6 microM for the outbred rats, 8 +/- 1 microM for the ODS rats given 0.33 g/l AA supplementation, and 29 +/- 2 microM for the ODS rats given 2.5 g/l AA. It was concluded that the chronic AA-deficient state in ODS rats played an insignificant role in oral carcinogenesis and that other factors, for example, genetic differences in susceptibility to NQO, contributed to the present findings.

4-Nitroquinoline-1-oxide↗

Human recombinant antibodies specific for hepatitis C virus core and envelope E2 peptides from an immune phage display library.

Hepatitis C virus (HCV) is the aetiological agent responsible for most cases of non-A non-B hepatitis. Hepatitis C is a disease of clinical importance because of its high infection rate in blood donors and its persistence as chronic infections which may lead to cirrhosis and hepatocellular carcinoma in the long term. The variability of the HCV genome has posed difficulties in serological detection and vaccine design. The recent advance in phage technology offers a means of cloning human anti-HCV antibodies of a defined specificity that may have potential therapeutic use. We now report the generation of a phage display library using the V(H) genes of a HCV-infected patient and the V(L) genes of two non-immune individuals. From this library we were able to obtain specific IgG single-chain Fvs (scFvs) that recognize viral core and envelope proteins by selection on synthetic peptides derived from the core sequence PKARRPEGRTWAQPG and the envelope E2 sequence RPIDDFDQGWGPITY. The specificity of the scFvs was demonstrated by their specific reactions with homologous peptides in ELISA and the specific blocking of scFv binding by homologous peptides, in a dose-dependent manner, in inhibition ELISA. The binding of the anticore 4c2 to homologous peptide was blocked by HCV-positive human sera in an antibody-concentration-dependent manner, suggesting that the scFv recognizes a similar if not identical epitope to those of one or more of the polyclonal antibodies present in the sera.

Amino Acid Sequence↗