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Biomedical subjects

C S Chan

Publications and source records attributed to C S Chan.

At least 37 records · Page 2Linked to original sources
PubMed1999

Early diagnosis of major cardiac defects in chromosomally normal fetuses with increased nuchal translucency.

OBJECTIVE: To determine the value of early ultrasound examination for prenatal diagnosis of cardiac defects in chromosomally normal fetuses with increased nuchal translucency thickness at 10-14 weeks of gestation. DESIGN: Prospective audit. SETTING: Fetal Medicine Centre. METHODS: Specialist fetal echocardiography was carried out in 398 chromosomally normal fetuses with a nuchal translucency measurement above the 99th centile (> or = 3.5 mm). In the first 75 pregnancies the cardiac scan was carried out at 17-22 weeks and the next 323 cases had one scan at 13-17 weeks and another at 20-22 weeks. Pregnancy outcome was obtained in all of the cases. RESULTS: Major cardiac defects were present in 29 (7.3% of 398) cases and in 28 of these the diagnosis was made by antenatal echocardiography. In 27 of the 29 fetuses with major cardiac defects echocardiography was carried out at 13-17 weeks and an abnormality was suspected in 24 of the cases (88%). CONCLUSIONS: Increased nuchal translucency in chromosomally normal fetuses is associated with an increased prevalence of major cardiac defects and, as such, is an indication for specialist fetal echocardiography. Most of the cardiac abnormalities are detectable on antenatal fetal echocardiography and many can be excluded by early scanning.

Echocardiography↗
PubMed1999

Hyperuricaemia in Type 2 diabetes mellitus.

This study was undertaken to find the significant parameters associated with hyperuricaemia in patients with Type 2 diabetes, and hence to determine if hyperuricaemia is associated with poor control of diabetes or increased coronary heart disease. All the diabetic patients seen at a Family Medicine Teaching Clinic within the period January to September 1997 were recruited into the study. In 273 Type 2 diabetics, serum uric acid was analysed against basic demographic data (age, sex, smoking and alcohol habits, body mass index, number of years since the diagnosis of diabetes), present medications, control of diabetic state (attending physician's estimation of the patient's diet compliance, fasting serum sugar, HbA1c), and complications (serum creatinine, total cholesterol, triglyceride, urine proteinuria, retinopathy, last blood pressure readings, history of hypertension, coronary heart disease, stroke). Serum uric acid was significantly associated with body mass index, history of hypertension, serum triglyceride and serum creatinine, but was not related to coronary heart disease, stroke or control of the diabetic state. Female diabetics were more likely to have elevated uric acid. There is not enough evidence for monitoring serum uric acid or for intervention to lower asymptomatic hyperuricaemia in Type 2 diabetic patients.

Aged↗
PubMed1998

A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers.

Genetic and biochemical studies in lower eukaryotes have identified several proteins that ensure accurate segregation of chromosomes. These include the Drosophila aurora and yeast Ipl1 kinases that are required for centrosome maturation and chromosome segregation. We have identified two human homologues of these genes, termed aurora1 and aurora2, that encode cell-cycle-regulated serine/threonine kinases. Here we demonstrate that the aurora2 gene maps to chromosome 20q13, a region amplified in a variety of human cancers, including a significant number of colorectal malignancies. We propose that aurora2 may be a target of this amplicon since its DNA is amplified and its RNA overexpressed, in more than 50% of primary colorectal cancers. Furthermore, overexpression of aurora2 transforms rodent fibroblasts. These observations implicate aurora2 as a potential oncogene in many colon, breast and other solid tumors, and identify centrosome-associated proteins as novel targets for cancer therapy.

3T3 Cells↗
PubMed1998

Multiple symmetric lipomatosis in the Chinese: ultrasound, CT and MR imaging.

We report four cases of multiple symmetric lipomatosis in the Chinese population. We believe that multiple symmetric lipomatosis in the Chinese is not uncommon and may be related to the increasing incidence of alcoholism. The ultrasound appearances of these lipomatous masses are presented for the first time. Heterogeneous echogenic masses with fine fibrous strands that insinuate around fascial planes, lymph nodes and vascular tissues are typical findings. Unlike diseases affecting the Western population, multiple symmetric lipomatosis in the Chinese appears to be limited to the head and neck.

Aged↗
PubMed1998

Technical hints for high dose rate interstitial tongue brachytherapy.

High dose rate (HDR) interstitial tongue brachytherapy is a new treatment modality. This study describes important technical details required for its successful use. Thirteen patients with carcinoma of the oral tongue were treated solely with interstitial brachytherapy using HDR remote afterloading techniques during the years 1994-1997. The afterloading catheters were positioned by the submandibular approach with the assistance of a template set. Custom-made mandibular lead shields were inserted prior to treatment. Special reusable Tuen Mun Hospital (TMH) lead buttons were made for improved radiation protection. The median dose given was 55 Gy in ten fractions over 6 days. The interfraction interval was 7 hours for the first seven patients treated and was extended to 8 hours for the other six. Shrinking field techniques were employed and the treatment length of the last fraction was reduced by 5 mm. Commencing with the second patient treated with double planar implants, the medial plane was treated with eight fractions while the lateral plane received ten fractions. To reduce further the potential risk of tract seeding, additional coverage to the implantation tracts was given for the last four patients, with the resultant isodose curves resembling a 'comb rake/brush'. The mean and median measured doses on the inner face of the mandibular shields were 113% and 93% of the reference dose respectively (range 77-247). The dose to the corresponding sites on the gingival surface can be reduced by 75% if the 3 mm thick lead shield is placed successfully. With the use of the TMH button, the transmitted dose to the tissue in direct contact can be reduced by one-third. With the 'comb rake/brush' dose distribution, the high dose volume of the single planar implants could be reduced by 44%, compared with the low dose rate technique, if loading to just 5 mm short of the submandibular skin was required. The mean doses for the combination of eight double planar plus two single planar implants, and ten double planar implants, are on average 29% and 37% greater than the reference dose respectively. An 8% reduction in absolute dose in the region between the planes of the catheters would lead to an even greater magnitude of reduction in morbidity to late responding tissue. The prerequisite for the success of HDR interstitial implants is to develop a good technique in positioning the afterloading catheters and protection of the normal tissue. Its importance merits special attention if HDR remote afterloading interstitial tongue brachytherapy is to realize its full potential.

Brachytherapy↗
PubMed1998

Torsion of the wandering spleen.

A case of torsion of the wandering spleen with splenic infarction is reported. The medical imaging studies performed with typical findings are described. Case reports have been reviewed. Although rare, torsion of the spleen remains an important differential diagnosis in patients presenting with acute abdominal pain. Early intervention is necessary to reduce the risk of splenic infarction and other complications, and an increased awareness of the condition together with the use of appropriate medical imaging can lead to the correct diagnosis more readily.

Abdominal Pain↗
PubMed1997

The Cdc42 GTPase-associated proteins Gic1 and Gic2 are required for polarized cell growth in Saccharomyces cerevisiae.

BEM2 of Saccharomyces cerevisiae encodes a Rho-type GTPase-activating protein that is required for proper bud site selection at 26 degrees C and for bud emergence at elevated temperatures. We show here that the temperature-sensitive growth phenotype of bem2 mutant cells can be suppressed by increased dosage of the GIC1 gene. The Gic1 protein, together with its structural homolog Gic2, are required for cell size and shape control, bud site selection, bud emergence, actin cytoskeletal organization, mitotic spindle orientation/positioning, and mating projection formation in response to mating pheromone. Each protein contains a CRIB (Cdc42/Rac-interactive binding) motif and each interacts in the two-hybrid assay with the GTP-bound form of the Rho-type Cdc42 GTPase, a key regulator of polarized growth in yeast. The CRIB motif of Gic1 and the effector domain of Cdc42 are required for this association. Genetic experiments indicate that Gic1 and Gic2 play positive roles in the Cdc42 signal transduction pathway, probably as effectors of Cdc42. Subcellular localization studies with a functional green fluorescent protein-Gic1 fusion protein indicate that this protein is concentrated at the incipient bud site of unbudded cells, at the bud tip and mother-bud neck of budded cells, and at cortical sites on large-budded cells that may delimit future bud sites in the two progeny cells. The ability of Gic1 to associate with Cdc42 is important for its function but is apparently not essential for its subcellular localization.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers.

BACKGROUND: Helicobacter pylori infection is common in patients with peptic ulcers caused by the use of non-steroidal anti-inflammatory drugs (NSAIDs). But the pathogenic role of H pylori in this disease is controversial. We studied the efficacy of eradication of H pylori in the prevention of NSAID-induced peptic ulcers. METHODS: We recruited patients with musculoskeletal pain who required NSAID treatment. None of the patients had previous exposure to NSAID therapy. Patients who had H pylori infection but no pre-existing ulcers on endoscopy were randomly allocated naproxen alone (750 mg daily) for 8 weeks or a 1-week course of triple therapy (bismuth subcitrate 120 mg, tetracycline 500 mg, metronidazole 400 mg, each given orally four times daily) before administration of naproxen (750 mg daily). Endoscopy was repeated after 8 weeks of naproxen treatment or when naproxen treatment was stopped early because of bleeding or intractable dyspepsia. All endoscopic examinations were done by one endoscopist who was unaware of treatment assignment. The primary endpoint was the cumulative rate of gastric and duodenal ulcers. FINDINGS: 202 patients underwent endoscopic screening for enrolment in the trial, and 100 eligible patients were randomly assigned treatment. 92 patients completed the trial (47 in the naproxen group, 45 in the triple-therapy group). At 8 weeks, H pylori had been eradicated from no patients in the naproxen group and 40 (89%) in the triple-therapy group (p < 0.001). 12 (26%) naproxen-group patients developed ulcers: five had ulcer pain and one developed ulcer bleeding. Only three (7%) patients on triple therapy had ulcers, and two of these patients had failure of H pylori eradication (p = 0.01). Thus, 12 (26%) patients with persistent H pylori infection but only one (3%) with successful H pylori eradication developed ulcers with naproxen (p = 0.002). INTERPRETATION: Eradication of H pylori before NSAID therapy reduces the occurrence of NSAID-induced peptic ulcers.

Anti-Bacterial Agents↗
PubMed1997

A novel mammalian, mitotic spindle-associated kinase is related to yeast and fly chromosome segregation regulators.

We describe a novel mammalian protein kinase related to two newly identified yeast and fly kinases-Ipl1 and aurora, respectively-mutations in which cause disruption of chromosome segregation. We have designated this kinase as Ipl1- and aurora-related kinase 1 (IAK1). IAK1 expression in mouse fibroblasts is tightly regulated temporally and spatially during the cell cycle. Transcripts first appear at G1/S boundary, are elevated at M-phase, and disappear rapidly after completion of mitosis. The protein levels and kinase activity of IAK1 are also cell cycle regulated with a peak at M-phase. IAK1 protein has a distinct subcellular and temporal pattern of localization. It is first identified on the centrosomes immediately after the duplicated centrosomes have separated. The protein remains on the centrosome and the centrosome-proximal part of the spindle throughout mitosis and is detected weakly on midbody microtubules at telophase and cytokinesis. In cells recovering from nocodazole treatment and in taxol-treated mitotic cells, IAK1 is associated with microtubule organizing centers. A wild-type and a mutant form of IAK1 cause mitotic spindle defects and lethality in ipl1 mutant yeast cells but not in wild-type cells, suggesting that IAK1 interferes with Ipl1p function in yeast. Taken together, these data strongly suggest that IAK1 may have an important role in centrosome and/ or spindle function during chromosome segregation in mammalian cells. We suggest that IAK1 is a new member of an emerging subfamily of the serine/threonine kinase superfamily. The members of this subfamily may be important regulators of chromosome segregation.

3T3 Cells↗
PubMed1997

Case report: Krukenberg tumours arising from a primary duodenojejunal adenocarcinoma.

We report a case of a bilateral Krukenberg tumour of the ovaries arising from a primary adenocarcinoma of the duodenojejunal flexure. Adenocarcinoma of the small bowel is uncommon, representing 1% of all primary malignant tumours of the gastrointestinal tract [1]. Krukenberg tumours arising from a primary duodenojejunal adenocarcinoma are even more unusual. To our knowledge there are less than five reported cases in the English literature [2,3]. Mazur et al. reviewing 325 cases of metastases to the female genital tract over 31 years, found only one case of ovarian metastasis from a primary small bowel carcinoma [2]. Most small bowel adenocarcinomas tend to metastasize to regional lymph nodes and the liver.

Adult↗
PubMed1997

The trouble with family medicine.

BACKGROUND: The trouble with family medicine is that the perceptual framework it uses to view the phenomena of health and illness is at variance with the frameworks traditionally used by medicine generally. This creates difficulties in communication between those in family medicine and those in other disciplines, and sometimes leads to misunderstanding of the nature of the discipline of family medicine and its place in the health care system. Those who practise family medicine need to be 'multilingual', able to understand and speak the language and use the metaphors of family medicine, yet equally able to use the language and metaphors of other disciplines. OBJECTIVES: This paper, which begins with a clinical scenario, reviews the contemporary biomedical paradigm, proposes an alternative, and examines the conceptual frameworks which underpin the discipline of family medicine.

Adult↗
PubMed1997

Magnetic resonance imaging of tuberculous spinal infection.

The magnetic resonance imaging (MRI) characteristics of 15 cases of tuberculous (TB) spinal infection were reviewed. The commonest site was the lumbar spine (53.3%), often with three or more contiguous vertebrae involved (47%). Destruction of the vertebral body and the presence of paraspinal soft-tissue masses were noted in 73.3%. Posterior element abnormalities, which is a significant finding, were seen in 40%, a slightly lower incidence rate than in other reported series. Epidural disease (53.3%) and disc abnormalities (73%) were more frequent than was realized. The role of intravenous contrast is discussed. Intravenous gadolinium is useful because it increases diagnostic confidence by characterizing and delineating the disease process, detects reactivation in old and healed TB, helps in treatment management and may prove valuable in monitoring therapy. Magnetic resonance imaging should be considered to be the imaging modality of choice for patients with suspected tuberculous spinal infection.

Adult↗
PubMed1996

Characterization of the human cyclin-dependent kinase 2 gene. Promoter analysis and gene structure.

Cyclin-dependent kinase 2 is a serine/threonine protein kinase essential for progression of the mammalian cell cycle from G1 to S phase. CDK2 mRNA has been shown to be induced by serum in several cultured cell types. Therefore, we set out to identify elements that regulate the transcription of the human CDK2 gene and to characterize its structure. This paper describes the cloning of approximately 2.4-kilobase pair genomic DNA fragment from the upstream region of the human CDK2 gene. This fragment contains five transcription initiation sites within a 72-nucleotide stretch. A 200-base pair sub-fragment that confers 70% of maximal basal promoter activity was shown to contain two synergistically acting Sp1 sites. However, a much larger DNA fragment containing approximately 1.7 kilobase pairs of upstream sequence is required for induction of promoter activity following serum stimulation. The intron exon boundaries of seven exons in this gene were also identified, and this information will be useful for analyzing genomic abnormalities associated with CDK2.

3T3 Cells↗
PubMed1996

Functional analysis of the human cyclin D2 and cyclin D3 promoters.

The D-type cyclins promote progression through the G1 phase of the cell cycle and may provide a link between growth factors and the cell cycle machinery. We determined the nucleotide sequence of the 5'-flanking region of the human cyclin D2 and cyclin D3 genes and identified the transcription start sites. Analysis of the upstream sequences required for transcription of the cyclin D2 and cyclin D3 genes in continuously dividing cells revealed marked differences in their regulatory elements. In the cyclin D2 gene positive elements were localized between positions -306 and -114 relative to the ATG codon at +1. Additional positive elements were localized between -444 and -345, whereas sequences that reduced transcription were identified between nucleotides -1624 and -892. In the cyclin D3 gene all of the positive elements required for maximal transcription were localized between nucleotides -366 and -167, and no negative elements were found. The activities of a reporter gene linked to the upstream regulatory sequences of the cyclin D2 gene but not the cyclin D3 gene were induced when starved cells were serum stimulated. This suggests that although the abundance of both the cyclin D2 and cyclin D3 mRNAs is increased by serum stimulation, only the cyclin D2 gene is up-regulated at the transcriptional level. Sequences between nucleotides -306 and -1624 of the cyclin D2 gene were necessary for serum inducibility.

Animals↗
PubMed1996

Rho1p, a yeast protein at the interface between cell polarization and morphogenesis.

The enzyme that catalyzes the synthesis of the major structural component of the yeast cell wall, beta(1-->3)-D-glucan synthase (also known as 1,3-beta-glucan synthase), requires a guanosine triphosphate (GTP) binding protein for activity. The GTP binding protein was identified as Rho1p. The rho1 mutants were defective in GTP stimulation of glucan synthase, and the defect was corrected by addition of purified or recombinant Rho1p. A protein missing in purified preparations from a rho1 strain was identified as Rho1p. Rho1p also regulates protein kinase C, which controls a mitogen-activated protein kinase cascade. Experiments with a dominant positive PKC1 gene showed that the two effects of Rho1p are independent of each other. The colocalization of Rho1p with actin patches at the site of bud emergence and the role of Rho1p in cell wall synthesis emphasize the importance of Rho1p in polarized growth and morphogenesis.

Cell Polarity↗
PubMed1996

What do patients expect from consultations for upper respiratory tract infections?

BACKGROUND AND OBJECTIVE: A cross-sectional survey was conducted amongst patients who consulted for upper respiratory tract infections (URTI) at 22 private practitioners' offices. METHOD: A total of 505 adult patients and 504 guardians (parents or grandparents of child patients) completed a self-administered questionnaire. RESULTS: The majority thought that URTI would not resolve on its own, while half thought that injections would speed recovery. But 78% disagreed with the statement that "taking multiple medications means faster recovery". Although 91% consulted for medicines, only 36% went specifically for antibiotics and 20% for injections. More than half would accept it if the doctor advised no medicine. More guardians (85%) than adult patients (69%) went for reassurance and to exclude complications. Using logistic regression analysis, the more educated respondents and the working guardians had higher knowledge scores, while the working guardians and respondents who knew the viral cause were less likely to worry and to demand antibiotics and injections. CONCLUSION: Much patient education and a change in doctors' prescribing habits in the management of URTI are needed in Hong Kong.

Adolescent↗
PubMed1996

The LIM domain-containing Dbm1 GTPase-activating protein is required for normal cellular morphogenesis in Saccharomyces cerevisiae.

Normal cell growth in the yeast Saccharomyces cerevisiae involves the selection of genetically determined bud sites where most growth is localized. Previous studies have shown that BEM2, which encodes a GTPase-activating protein (GAP) that is specific for the Rho-type GTPase Rho1p in vitro, is required for proper bud site selection and bud emergence. We show here that DBM1, which encodes another putative Rho-type GAP with two tandemly arranged cysteine-rich LIM domains, also is needed for proper bud site selection, as haploid cells lacking Dbm1p bud predominantly in a bipolar, rather than the normal axial, manner. Furthermore, yeast cells lacking both Bem2p and Dbm1p are inviable. The nonaxial budding defect of dbm1 mutants can be rescued partially by overproduction of Bem3p and is exacerbated by its absence. Since Bem3p has previously been shown to function as a GAP for Cdc42p, and also less efficiently for Rho1p, our results suggest that Dbm1p, like Bem2p and Bem3p, may function in vivo as a GAP for Cdc42p and/or Rho1p. Both LIM domains of Dbm1p are essential for its normal function. Point mutations that alter single conserved cysteine residues within either LIM domain result in mutant forms of Dbm1p that can no longer function in bud site selection but instead are capable of rescuing the inviability of bem2 mutants at 35 degrees C.

Amino Acid Sequence↗