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Biomedical subjects

C M Chan

Publications and source records attributed to C M Chan.

At least 37 records · Page 2Linked to original sources

Monitoring the toxicity of phenolic chemicals to activated sludge using a novel optical scanning respirometer.

This paper reports the development of optical scanning respirometer for determining the toxicity of chemicals to activated sludge. The respirometer is used to measure the dissolved oxygen concentration by monitoring the luminescence intensity of ruthenium dye immobilized in a polymer film in contact with the wastewater sample. The intensity is related to the extent of oxygen quenching of luminescence. The toxicity of chemicals can be evaluated by measuring the inhibition on respiration rate of microorganism using the scanning respirometer. The IC50 values (concentration of a chemical that exhibits 50% respiration inhibition) of various phenolic chemicals in activated sludge were determined. The performance of this method is compared with other toxicity methods. The experimental results indicate that the reproducibility and sensitivity of this respirometer are reasonably good.

Environmental Pollutants↗

Ophthalmologic outcome of transvenous embolization of spontaneous carotid-cavernous fistulas: a preliminary report.

We give a preliminary report of the ophthalmologic outcome of four patients with transvenous embolization studied for their spontaneous carotid-cavernous fistulas. One of them is a direct type while three of them are indirect dural shunts. In indirect dural shunts, traditional transarterial embolization rarely achieves a complete clinical cure in a short period of time. All cases had an ophthalmologic disturbance justified for endovascular intervention. We performed catheterization, and subsequently embolization with Guglielmi Detachable coils, to the cavernous sinus via the femoral vein and inferior petrosal sinus/superior ophthalmic vein. All four patients achieved clinical and angiographic improvement with a follow-up period range from two to sixteen months except for one patient who had residual bilateral sixth nerve palsy. The transvenous approach offers an effective and safe alternative for the management of spontaneous carotid-cavernous fistula.

Abducens Nerve Diseases↗

Beliefs about elderly people among social workers and the general public in Hong Kong.

Social learning theory expects the social worker to hold more favorable beliefs about elderly people and scapegoat theory expects one having higher self-esteem to be so. The role of social work and self-esteem may be factors explaining ageism at the individual level. Because ageism seems to emerge in Hong Kong as well as other industrialized societies, the study surveyed the general public, social workers, students, elderly center members to (1) determine the relative extent of ageism in terms of beliefs about physical, social, and psychological dimensions of elderly people, and (2) test hypotheses deriving from social learning and scapegoat theories. Analysis of data from 902 respondents showed that people younger than 60 years were more favorable regarding the social dimension and less favorable regarding the psychological dimension of beliefs about elderly people. One with higher self-esteem tended to be more favorable in beliefs about social and psychological dimensions of elderly people but less favorable in the belief about the physical dimension. Although the gerontological social worker was more favorable in the belief regarding the social dimension of elderly people than others, this difference might be attributable to his or her higher self-esteem. Hence the role of social work did not necessarily improve one's image of elderly people in Hong Kong.

Journal Article↗

Functional brain imaging during anesthesia in humans: effects of halothane on global and regional cerebral glucose metabolism.

BACKGROUND: Propofol and isoflurane anesthesia were studied previously with functional brain imaging in humans to begin identifying key brain areas involved with mediating anesthetic-induced unconsciousness. The authors describe an additional positron emission tomography study of halothane's in vivo cerebral metabolic effects. METHODS: Five male volunteers each underwent two positron emission tomography scans. One scan assessed awake-baseline metabolism, and the other scan assessed metabolism during halothane anesthesia titrated to the point of unresponsiveness (mean +/- SD, expired = 0.7+/-0.2%). Scans were obtained using a GE2048 scanner and the F-18 fluorodeoxyglucose technique. Regions of interest were analyzed for changes in both absolute and relative glucose metabolism. In addition, relative changes in metabolism were evaluated using statistical parametric mapping. RESULTS: Awake whole-brain metabolism averaged 6.3+/-1.2 mg x 100 g(-1) x min(-1) (mean +/- SD). Halothane reduced metabolism 40+/-9% to 3.7+/-0.6 mg x 100 g(-1) x min(-1) (P< or =0.005). Regional metabolism did not increase in any brain areas for any volunteer. The statistical parametric mapping analysis revealed significantly less relative metabolism in the basal forebrain, thalamus, limbic system, cerebellum, and occiput during halothane anesthesia. CONCLUSIONS: Halothane caused a global whole-brain metabolic reduction with significant shifts in regional metabolism. Comparisons with previous studies reveal similar absolute and relative metabolic effects for halothane and isoflurane. Propofol, however, was associated with larger absolute metabolic reductions, suppression of relative cortical metabolism more than either inhalational agent, and significantly less suppression of relative basal ganglia and midbrain metabolism.

Anesthesia, General↗

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

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

Antibodies, Fungal↗

Expression of nuclear receptor interacting proteins TIF-1, SUG-1, receptor interacting protein 140, and corepressor SMRT in tamoxifen-resistant breast cancer.

Regulation of gene transcription as a consequence of steroid receptor-DNA interaction is mediated via nuclear receptor interacting proteins (RIPs), including coactivator or corepressor proteins, which interact with both the receptor and components of the basic transcriptional unit and vary between cell types. The aim of this study was to test the hypothesis that resistance of some breast carcinomas to tamoxifen was associated with inappropriate expression of some of these RIPs. Using Northern analysis, we observed no significant difference between the amount of either TIF-1 or SUG-1 mRNA expressed in parental MCF-7 and MCF-7 tamoxifen-resistant cell lines. However, the expression of RIP140 mRNA was lower in the resistant cell line and in the presence of estradiol, the level of RIP140 mRNA was higher in the resistant cells but not in the parental cells. In a cohort of 19 tamoxifen-resistant breast tumor samples, there was no significant difference in the level of the RIP140 and TIF-1 and corepressor SMRT mRNA compared with tamoxifen-treated tumors (n = 6) or untreated tumors (n = 21). However, SUG-1 mRNA was lower in resistant breast tumors. These data provide no support for increased expression of these RIPs or decreased expression of corepressor SMRT for being a mechanism for resistance of breast tumors to tamoxifen.

ATPases Associated with Diverse Cellular Activitie↗

Surgical management of upper lid epiblepharon.

BACKGROUND: Upper lid epiblepharon refers to a developmental anomaly characterised by the presence of an exaggerated skin fold running horizontally across the upper lid below the lid margin, which in severe cases is associated with lash-cornea touch or even corneal punctate epithelial erosions. METHOD: This retrospective study looked at 14 patients who underwent bilateral upper lid pretarsal orbicularis debulking and skin excision to correct lash-globe contact from the upper lid. RESULTS: Surgery was successful in 25 of 28 lids, with one recurrence being successfully re-operated. The remaining 2 recurrences did not undergo further surgery as the patients were asymptomatic. CONCLUSION: This surgical procedure appears to be an effective treatment of lash inversion in upper lid epiblepharon with good aesthetic results.

Adolescent↗

The potential impact of breast cancer screening in Hong Kong.

BACKGROUND: Breast cancer is the second most common cancer and cause of death in women from Hong Kong. The Well Women Clinic at Kwong Wah Hospital offers breast cancer screening (physical examination and mammography) for women over 40 years of age. METHODS: Results of screening over a 2-year period revealed an overall malignancy detection rate of 2.6 per 1000 screens with a strong selection bias for symptomatic women. RESULTS: Screening only slightly increased the proportion of stage I cancers detected; of the malignancies detected, a significant percentage were in situ cancers with doubtful effects on breast cancer mortality. Teamwork and communication were useful in keeping a low referral rate to the surgical clinic of 6.1%, as well as a low biopsy rate for mammographic abnormalities. CONCLUSIONS: A re-evaluation of the real risk of breast cancer in young women together with the lack of proven value from screening has suggested a need for reconsideration of offering screening to women 40 years and over in Hong Kong.

Adult↗

MP1 encodes an abundant and highly antigenic cell wall mannoprotein in the pathogenic fungus Penicillium marneffei.

We cloned the MP1 gene, which encodes an abundant antigenic cell wall mannoprotein from the dimorphic pathogenic fungus Penicillium marneffei. MP1 is a unique gene without homologs in sequence databases. It codes for a protein, Mp1p, of 462 amino acid residues, with a few sequence features that are present in several cell wall proteins of Saccharomyces cerevisiae and Candida albicans. It contains two putative N glycosylation sites, a serine- and threonine-rich region for O glycosylation, a signal peptide, and a putative glycosylphosphatidylinositol attachment signal sequence. Specific anti-Mp1p antibody was generated with recombinant Mp1p protein purified from Escherichia coli to allow further characterization of Mp1p. Western blot analysis with anti-Mp1p antibody revealed that Mp1p has predominant bands with molecular masses of 58 and 90 kDa and that it belongs to a group of cell wall proteins that can be readily removed from yeast cell surfaces by glucanase digestion. In addition, Mp1p is an abundant yeast glycoprotein and has high affinity for concanavalin A, a characteristic indicative of a mannoprotein. Furthermore, ultrastructural analysis with immunogold staining indicated that Mp1p is present in the cell walls of the yeast, hyphae, and conidia of P. marneffei. Finally, it was observed that infected patients develop a specific antibody response against Mp1p, suggesting that this protein represents a good cell surface target for host humoral immunity.

Amino Acid Sequence↗

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

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

AIDS-Related Opportunistic Infections↗

Localization of P2X1 purinoceptors by autoradiography and immunohistochemistry in rat kidneys.

P2 receptors have been identified in rat kidney by autoradiography, using the radioligand [3H] alpha, beta-methylene ATP, and by immunohistochemistry, using a polyclonal antibody to the P2X1 purinoceptor. They have been localized to the vascular smooth muscle of intrarenal arteries, including arcuate and interlobular arteries, and afferent arterioles, but not glomeruli, postglomerular efferent arterioles, or renal tubules. We conclude that at least some of the P2 receptors present on vascular smooth muscle are of the P2X1 subtype. The functional significance of these findings in the vascular control of the kidney is discussed.

Animals↗

Identification of an exon 3 deletion splice variant androgen receptor mRNA in human breast cancer.

Androgens and androgen receptor (AR) are involved in many regulatory processes in the growth of female breast cells. Mutations in the AR gene and/or alterations of the AR protein sequence may be related to the development and progression of breast cancer. Using reverse transcription-polymerase chain reaction we have examined 31 female breast-cancer samples, 5 normal female breast tissues and 6 breast-cancer cell lines for the presence of splice variants of AR mRNA and have identified an exon 3 deletion splice variant (delta3AR). The higher expression of the variant relative to the wild-type AR (WT AR) was found in 7 breast-cancer samples (delta3/WT > 15%) and relatively lower levels of the variant were observed in 3 breast-cancer cell lines (delta3/WT < 5%). However, in normal breast tissues, expression of the variant was undetectable by Southern blot analysis. In vitro translation of the delta3AR mRNA resulted in a variant AR protein of about 105 kDa, smaller than the WT AR by about 5 kDa. We thus report an exon deletion splice variant of AR mRNA in breast cancer. The variant protein is predicted to lack the second zinc finger within the DNA-binding domain and is expected to be unable or to have reduced ability to bind to androgen-response elements and to activate transcription. The relatively high expression of this AR variant in some breast-cancer tissues may indicate its role in regulating the growth of these cancers.

Alternative Splicing↗

Monitoring the therapy of pulmonary tuberculosis by nested polymerase chain reaction assay.

Monthly clinical and microbiological parameters (by sputum smear, culture and PCR assay), of 50 patients with documented pulmonary tuberculosis and on anti-tuberculosis therapy, were monitored over a period of 18 months. PCR converters (70%) who had PCR conversion before the sixth month of treatment did not have clinical or microbiological evidence of failure or relapse, while nine of 15 PCR persisters (30%) had clinical failure (7) and relapse (2). The PCR persisters were significantly associated with more underlying medical illnesses, high mean radiographic scores on the extent of disease involvement, previous drug treatment, initial sputum smear positivity and multi-drug resistance. Of the eight PCR persisters infected by susceptible Mycobacterium tuberculosis, all had marked residual radiographic changes despite completion of drug therapy. The findings may have important implications in the application of PCR on individualization of the duration of anti-tuberculosis therapy.

Adult↗

Oestrogen receptor mutants and variants in breast cancer.

Oestrogen receptor (ER) status is the only biochemical predictive factor which is routinely measured in breast carcinomas. ER gene mutations can profoundly change the biochemical activity of the protein. If these occurred in vivo, they could be expected to affect breast cancer risk or phenotype, such as endocrine responsiveness. However, no mutations of significance have been described in breast carcinomas. In contrast, numerous variant forms of ER have been reported at the mRNA level. Most of these appear to be due to aberrant exon splicing which results in predicted protein products whose activities range from dominant positive to dominant negative. In some instances, these mRNA variants have also been demonstrated in normal tissue (breast and others). Their biological and clinical significance might be profound, but remain to be established because of a lack of evidence for their existence at the protein level. On the currently available data, routine analysis for ER mutants and variants is not justified.

Biomarkers, Tumor↗

A novel estrogen receptor variant mRNA lacking exons 4 to 6 in breast carcinoma.

A novel estrogen receptor mRNA splice variant which lacks the entire exon 5 and part of exon 4 and 6 was identified using reverse transcription PCR in human breast carcinomas. The variant was translated in vitro and produced a protein of approximately Mr 31000 which lacked the ligand binding domain. The binding of the variant estrogen receptor (ER) to a synthetic estrogen-responsive element (ERE) was compared with that of the wild-type ER (wtER). The variant ER bound weakly to the synthetic ERE, both in the presence and absence of estradiol, whilst the wtER bound strongly in the absence and the presence of estradiol. When wtER and variant ER were simultaneously translated in vitro, no heterodimerization was observed using band shift assay. Addition of increasing amounts of variant ER protein to the wtER in the ERE binding reaction showed that the variant protein competed with the binding of the wtER to the synthetic ERE. Furthermore, variant ER are not transcriptionally active. The variant was also expressed in 96% of the 102 breast tumours analysed, of which 62 were tamoxifen-resistant tumours. The expression of this variant was significantly higher (relative to ER) in untreated ER-positive breast tumours which were both progesterone receptor (PgR) negative and pS2 negative phenotype.

Amino Acid Sequence↗

Penetrating keratoplasty in the Singapore National Eye Centre and donor cornea acquisition in the Singapore Eye Bank.

We analyzed all penetrating keratoplasties performed in the Singapore National Eye Centre from 1 January 1991 to 31 December 1995, using records of the Singapore Eye Bank Registry, evaluating the indications, complications, causes of graft failure, visual outcome and graft survival rate. We also looked into donor cornea acquisition in the Singapore Eye Bank and its influence on the development of corneal transplantation in the Singapore National Eye Centre. A total of 327 penetrating keratoplasties were performed during the 5-year period. Bullous keratopathy was an indication in 26.3% of cases. Of these, aphakic bullous keratopathy accounted for 11.6% of all cases, while pseudophakic bullous keratopathy accounted for 11.3%. Other indications were regrafts (11.9%), corneal dystrophies (10.4%), traumatic corneal scarring (10.1%) and keratoconus (9.8%). Graft rejection was a complication in 20% of all cases. Of these, 40.9% led to graft failure. Other major complications were raised intraocular pressure (18%), epithelium-related problems (7.3%), wound dehiscence (4.3%), cataract (3.3%) and microbial keratitis (3.1%). The main causes of graft failure were graft rejection (8.2%), endothelial failure (2.4%), infection (2.4%) and glaucoma (2.1%). Of the 327 grafts, 40.3% achieved best corrected visual acuity of 6/12 or better; 70.8% achieved vision of 6/24 or better. The overall graft survival rate was 82.3% after a mean follow-up period of 2 years. Donor corneas for the penetrating keratoplasties were obtained from foreign eye banks as well as locally, with the local donation rate steadily increasing from 1991 to 1996, with the establishment of proper eye banking facilities and the Singapore Eye Bank. These results show that the indications and outcome of penetrating keratoplasty in the Singapore National Eye Centre are similar and comparable to that of other centres with established corneal grafting programmes. The establishment of the Singapore Eye Bank has ensured the proper co-ordination of acquisition of donor material which has been vital to the development of corneal transplantation in the Singapore National Eye Centre.

Adolescent↗

Immediate breast reconstruction in Chinese women using the transverse rectus abdominis myocutaneous (TRAM) flap.

BACKGROUND: Total mastectomy remains the mainstay of operative treatment for breast cancer mainly because it is preferred by surgeons. The techniques and benefits of reconstructing the amputated breast have been well documented in the medical literature but there have been very few reports on this issue in Chinese women. Immediate breast reconstruction using the transverse rectus abdominis myocutaneous (TRAM) flap in Chinese women suffering from early breast cancer who require mastectomy is summarized. METHODS: Since September 1991, the option of immediate breast reconstruction was offered to all patients less than 60 years of age suffering from early cancer (Tis, T1 or T2) who were not suitable for breast-conserving treatment or who preferred to have a mastectomy. The single-pedicled TRAM flap was used. RESULTS: From September 1991 to September 1994, 27 reconstructions were performed. Partial flap loss occurred in four patients (15%), fat necrosis in three patients (11%) and abdominal bulging in one patient (4%). Operations performed by two teams simultaneously reduced operating time by 1.5 h without increasing the risk of complications. Twenty-one patients (78%) were satisfied or very satisfied with the outcome of reconstruction. CONCLUSIONS: The TRAM flap is a satisfactory method of breast reconstruction in Chinese women. A two-team approach can be employed safely to shorten operative time. Overall patient satisfaction was high.

Adult↗