Biomedical subjects

D Chan

Publications and source records attributed to D Chan.

At least 55 records · Page 3Linked to original sources

PubMed2001

VIP receptor antagonists and chemotherapeutic drugs inhibit the growth of breast cancer cells.

The effects of vasoactive intestinal peptide (VIP) antagonists on breast cancer cells were investigated. (N-stearyl, norleucine17)VIP hybrid ((SN)VIPhyb) inhibited specific 125I-VIP binding to MCF7, SKBR3, T47D ZR75-1 and MDA-MB231 cells with high affinity (IC50 values of 0.03-0.06 microM). (SN)VIPhyb, 1 microM, inhibited the ability of 10 nM VIP to cause elevation of cAMP and to increase c-fos mRNA. Micromolar concentrations of (SN)VIPhyb inhibited the proliferation of MDA-MB231 or MCF7 cells using a MTT and clonogenic assay. Using a MTT assay, (SN)VIPhyb enhanced the ability of taxol and doxorubicin to inhibit breast cancer growth. Using nude mice bearing MDA-MB231 xenografts, VIPhyb potentiated the ability of taxol to inhibit proliferation. The results indicate that VIP receptor antagonists increase the ability of chemotherapeutic drugs to kill breast cancer cells.

Amino Acid Sequence↗

PubMed2001

Worldwide overview of critical care nursing organizations and their activities.

While critical care has been a specialty within nursing for almost 50 years, with many countries having professional organizations representing these nurses, it is only recently that the formation of an international society has been considered. A three-phased study was planned: the aim of the first phase was to identify critical care organizations worldwide; the aim of the second was to describe the characteristics of these organizations, including their issues and activities; and the aim of the third was to plan for an international society, if international support was evident. In the first phase, contacts in 44 countries were identified using a number of strategies. In the second phase, 24 (55%) countries responded to a survey about their organizations. Common issues for critical care nurses were identified, including concerns over staffing levels, working conditions, educational programme standards and wages. Critical care nursing organizations were generally favourable towards the notion of establishing a World Federation of their respective societies. Some of the important issues that will need to be addressed in the lead up to the formation of such a federation are now being considered.

Critical Care↗

PubMed2001

Novel erythropoiesis stimulating protein (NESP) for the treatment of anaemia of chronic disease associated with cancer.

Anaemia is a common haematologic disorder in patients with cancer and has a multifactorial aetiology, including the effects of the malignancy itself and residual effects from previous therapy. Novel erythropoiesis stimulating protein (NESP, darbepoetin alfa), a protein with additional sialic acid compared with erythropoietin (EPO), stimulates erythropoiesis by the same mechanism as recombinant human erythropoietin (rHuEPO) but it is biochemically distinct. NESP, with its approximately 3-fold greater serum half-life, can maintain haemoglobin levels as effectively as rHuEPO in anaemic patients with chronic renal failure and do so with less frequent dosing. We investigated the ability of NESP to safely increase haemoglobin levels of anaemic patients with non-myeloid malignancies not receiving chemotherapy. NESP was administered under the supervision of a physician at doses of 0.5, 1.0, 2.25 or 4.5 mcg kg(-1)wk(-1)for a maximum of 12 weeks. This report includes 89 patients completing the study by November 2000. NESP was well tolerated, with no reported dose-limiting toxicities or treatment-related severe adverse events. Increasing doses of NESP corresponded with increased efficacy. The percentage (95% confidence interval) of patients responding ranged from 61% (42%, 77%) in the 1.0 mcg kg(-1)wk(-1)group to 83% (65%, 94%) in the 4.5 mcg kg(-1)wk(-1)group.

Adult↗

PubMed2001

Development of an innovative tool to assess hospital learning environments.

Nursing as a profession has evolved in response to societal needs for well-prepared practitioners who provide quality care to the needed in episodes of illness, and promote health among all age groups. Clinical practice enables the student to develop competencies in the application of knowledge, skills, and attitudes to clinical field situations. The clinical learning environment is a multidimensional entity with a complex social context. Previous research on clinical learning environment was examined, yet minimal studies have been conducted on hospital learning environments from the psychosocial educational perspective. With the mission to maximize nursing students' clinical learning experiences, the author developed and validated the Clinical Learning Environment Inventory (CLEI) based on the theoretical framework in psychosocial education. It is envisaged that this tool will assist the nurse professional to facilitate nursing students to achieve a productive clinical practice. This paper highlights the need and details the conceptual framework in the development of the CLEI. Although it is not presented as a research based paper, some statistical data are included to verify the reliability and validity of the newly-developed instrument.

Education, Nursing↗

PubMed2001

A disorder of colour perception associated with abnormal colour after-images: a defect of the primary visual cortex.

A 64 year old woman with posterior cortical atrophy secondary to probable Alzheimer's disease is described. Her presenting symptom was of seeing objects as abnormally coloured after prior exposure to a coloured stimulus. Formal testing disclosed that the patient experienced colour after-images of abnormal latency, duration, and amplitude.The demonstration of prolonged colour after-images in a patient with a cortical disease process provides strong evidence that the generation of colour after-images is mediated at least in part by the visual cortex. A mechanism for the generation of colour after-images is proposed in which abnormal prolongation of the images results from excessive rebound inhibition of previously excited wavelength selective neurons in V1. This may occur as a consequence of the relative sparing of inhibitory interneurons in V1 in the context of the degeneration of excitatory neurons that occurs in Alzheimer's disease.

Afterimage↗

PubMed2001

Effect of initial tumor stage on patient follow-up after potentially curative surgery for cutaneous melanoma.

The optimal follow-up strategy after completion of therapy for melanoma is not known. We evaluated the effect of TNM stage on the self-reported surveillance strategies employed by practicing plastic surgeons caring for otherwise healthy patients subjected to potentially curative treatment for cutaneous melanoma. Hypothetical patient profiles and a detailed questionnaire based on these profiles were mailed to a random sample (N=3,032) of the 4,320 members of the American Society of Plastic and Reconstructive Surgeons. The effect of TNM stage on the surveillance strategies chosen was analyzed by repeated-measures ANOVA. There were 1,142 responses to the 3,032 surveys; 395 were evaluable. Plastic surgeons often do not provide postoperative follow-up themselves; this was the most frequent reason for non-evaluability. Surveillance of patients after resection of melanoma relies most heavily on office visits, chest X-ray, CBC, and liver function tests. All other surveillance modalities are used infrequently. Most respondents modify their surveillance practices slightly according to the patient's initial TNM stage. Most commonly used modalities are employed significantly more frequently with increasing TNM stage. This effect persists through ten years of follow-up, but the differences across stages are tiny. We conclude that most plastic surgeons performing surveillance after potentially curative surgery in otherwise healthy patients with melanoma use similar follow-up strategies for patients of all TNM stages. These data permit the rational design of a controlled clinical trial of high-intensity vs. low-intensity follow-up.

Adult↗

PubMed2001

Patterns of temporal lobe atrophy in semantic dementia and Alzheimer's disease.

Volumetric magnetic resonance imaging analyses of 30 subjects were undertaken to quantify the global and temporal lobe atrophy in semantic dementia and Alzheimer's disease. Three groups of 10 subjects were studied: semantic dementia patients, Alzheimer's disease patients, and control subjects. The temporal lobe structures measured were the amygdala, hippocampus, entorhinal cortex, parahippocampal gyrus, fusiform gyrus, and superior, middle, and inferior temporal gyri. Semantic dementia and Alzheimer's disease groups did not differ significantly on global atrophy measures. In semantic dementia, there was asymmetrical temporal lobe atrophy, with greater left-sided damage. There was an anteroposterior gradient in the distribution of temporal lobe atrophy, with more marked atrophy anteriorly. All left anterior temporal lobe structures were affected in semantic dementia, with the entorhinal cortex, amygdala, middle and inferior temporal gyri, and fusiform gyrus the most severely damaged. Asymmetrical, predominantly anterior hippocampal atrophy was also present. In Alzheimer's disease, there was symmetrical atrophy of the entorhinal cortex, hippocampus, and amygdala, with no evidence of an anteroposterior gradient in the distribution of temporal lobe or hippocampal atrophy. These data demonstrate that there is a marked difference in the distribution of temporal lobe atrophy in semantic dementia and Alzheimer's disease. In addition, the pattern of atrophy in semantic dementia suggests that semantic memory is subserved by anterior temporal lobe structures, within which the middle and inferior temporal gyri may play a key role.

Aged↗

PubMed2001

Validity of the US Behavioral Risk Factor Surveillance System's health related quality of life survey tool in a group of older Canadians.

Investigators at the Centers for Disease Control and Prevention in the US have developed a brief survey tool to measure health-related quality of life (HRQOL-4). In order to support use of such tools in surveillance, it is important to assess their validity in different groups. Subjects were 926 non-institutionalized men and women (age > or = 65 years) who completed a health exam and questionnaire. Results indicated that physical and mental health and physical activity limitation were each related to self-perceived health. Compared with subjects who reported excellent health, those with poor self-rated health reported a more than 17-fold increase in the number of unhealthy days in the previous 30. While responses to questions addressing psychosocial factors were most consistently associated with the HRQOL item relating to mental health, responses to health and health behaviour questions were more consistently associated with items related to physical health. This study demonstrated that the HRQOL-4 is not only accepted by older adults in a self-administered format, but also stands up to tests of its validity.

Age Factors↗

PubMed2000

Aberrant signal peptide cleavage of collagen X in Schmid metaphyseal chondrodysplasia. Implications for the molecular basis of the disease.

Schmid metaphyseal chondrodysplasia results from mutations in the collagen X (COL10A1) gene. With the exception of two cases, the known mutations are clustered in the C-terminal nonhelical (NC1) domain of the collagen X. In vitro and cell culture studies have shown that the NC1 mutations result in impaired collagen X trimer assembly and secretion. In the two other cases, missense mutations that alter Gly(18) at the -1 position of the putative signal peptide cleavage site were identified (Ikegawa, S., Nakamura, K., Nagano, A., Haga, N., and Nakamura, Y. (1997) Hum. Mutat. 9, 131-135). To study their impact on collagen X biosynthesis using in vitro cell-free translation in the presence of microsomes, and cell transfection assays, these two mutations were created in COL10A1 by site-directed mutagenesis. The data suggest that translocation of the mutant pre-alpha1(X) chains into the microsomes is not affected, but cleavage of the signal peptide is inhibited, and the mutant chains remain anchored to the membrane of microsomes. Cell-free translation and transfection studies in cells showed that the mutant chains associate into trimers but cannot form a triple helix. The combined effect of both the lack of signal peptide cleavage and helical configuration is impaired secretion. Thus, despite the different nature of the NC1 and signal peptide mutations in collagen X, both result in impaired collagen X secretion, probably followed by intracellular retention and degradation of mutant chains, and causing the Schmid metaphyseal chondrodysplasia phenotype.

Animals↗

PubMed2000

CD95 (Fas) ligand-expressing vesicles display antibody-mediated, FcR-dependent enhancement of cytotoxicity.

Bioactive Fas ligand (FasL)-expressing vesicles were generated (vesicle preparation, VP) from two cell lines overexpressing FasL. The effect of NOK-1 anti-FasL mAb (mouse IgG1) on the cytotoxicity of FasL VP against various targets was determined. At high concentrations (1-10 microg/ml), NOK-1 inhibited the cytotoxicity. By contrast, NOK-1 in the dose range of 1-100 ng/ml significantly enhanced cytotoxicity against the FcR(+) LB27.4, M59, and LF(+) targets, but not the FcR(-) Jurkat and K31H28 hybridoma T cell targets. The ability to enhance FasL VP-mediated cytotoxicity could be blocked by the FcR-specific mAb 2.4G2. Enhancement was also observed with FcR(+) A20 B lymphoma but not with the FcR(-) A20 variant. Enhancement of FasL VP cytotoxicity was observed with five IgG anti-FasL mAbs, but not with an IgM anti-FasL mAb. Inhibition was observed with high doses of all mAb except the IgG anti-FasL mAb G247-4, which is specific to a segment outside the FasL binding site. Interestingly, under identical conditions but in the presence of 2.4G2, G247-4 inhibited the cytotoxicity of FasL VP. In addition, G247-4 inhibited the FasL VP-mediated killing of FcR(-) Jurkat. The data demonstrate that FasL-expressing bioactive vesicles display a property heretofore unknown in bioactive agents that express FasL-mediated cytotoxicity. The mechanism of the Ab-mediated, FcR-dependent enhancement of cytotoxicity of bioactive vesicles and its physiological significance are discussed.

Adjuvants, Immunologic↗

PubMed2000

Structural studies on bioactive compounds. 30. Crystal structure and molecular modeling studies on the Pneumocystis carinii dihydrofolate reductase cofactor complex with TAB, a highly selective antifolate.

The crystal structure of the ternary complex of NADPH, the potent antifolate [2, 4-diamino-5-¿3-[3-(2-acetyloxyethyl)-3-benzyltriazen-1-yl]-4 -chloroph enyl¿-6-ethylpyrimidine] (TAB, 1) and Pneumocystis carinii dihydrofolate reductase (pcDHFR), refined to 2.1 A resolution, reveals that TAB binds similar to the antifolates trimethoprim and methotrexate. These data also reveal multiple conformations for the binding geometry of TAB with two preferred orientations of the acetyloxy and benzyl groups that results from a 180 degrees rotation about the N2-N3 triazenyl bond. The methyl of the acetyloxy and benzyl ring of TAB probes large hydrophobic regions of the p-aminobenzoyl folate binding pocket of the active site, in particular the region near Phe69, which is unique to the pcDHFR sequence. These results confirm prior molecular modeling investigations of the binding of TAB to pcDHFR that identified four low-energy binding geometries, two involving rotations about the terminal N(2)-N(3) triazenyl linkage and two involving atropisomerism about the pivotal pyrimethamine-phenyl bond. The primary differences in the molecular dynamics (MD) models and those observed in this crystal complex result from small conformational changes in active-site residues on energy minimization. However, two MD models place the acetyloxy and benzyl ring groups in a region of the active site between the cofactor-binding region and the p-aminobenzoyl folate pocket; an orientation never observed in any DHFR crystal structure to date. These conformers interact with solvent near the enzyme surface and are probably not observed due to the loss of specific hydrogen bonds with the enzyme. The high species pcDHFR selectivity of TAB could be the result of ligand flexibility that enables multiple binding orientations at the enzyme active site. Further modification of the acetyloxy region of TAB could increase its potency and selectivity for pcDHFR.

Binding Sites↗

PubMed2000

Expression and localization of rab escort protein isoforms in parotid acinar cells from rat.

Rab proteins are geranylgeranylated on their carboxyl terminal cysteine motifs by geranylgeranyltransferase II (GGTase). Rab escort protein (REP) is required to present Rab proteins to GGTase. REP may remain bound to newly isoprenylated Rab proteins and present them to their target membrane. Other studies have shown that Rab proteins cycle between the membrane and cytosolic compartments and that cytosolic Rab proteins are complexed with rab-GDI. In the present study, we examined the expression and localization of REP isoforms in parotid acinar cells. Although both REP isoforms, REP-1 and REP-2, were detected in parotid cytosol, REP-2 was the predominant isoform. Subcellular fractionation revealed that approximately 42% of cellular REP-2 is membrane-associated. REP-2 was partially removed from parotid membranes with 1 M NaCl or Na(2)CO(3), indicating that REP-2 is a peripheral membrane protein. Membrane-associated REP-2 did not colocalize with Rab3D on secretory granule membranes. However, density gradient centrifugation revealed that membrane-associated REP-2 and Rab3D colocalize on low- and high-density membrane fractions in parotid acinar cells. Isoproterenol, an agent which induces amylase release from parotid glands, caused a shift in both REP-2 and Rab3D to less dense membrane fractions. When acinar cell cytosol was fractionated by gel filtration chromatography, Rab3D eluted exclusively with REP, not rab-GDI. In contrast, Rab1B and Rab5 eluted with both REP and Rab-GDI. Colocalization of Rab3D and REP-2 on acinar cell membranes suggests that REP-2 plays a role in delivering Rab3D to parotid membranes and may regulate guanine nucleotide binding to membrane-associated Rab3D. In addition, unlike other Rab proteins, cytosolic Rab3D appears to associate exclusively with REP, not rab-GDI in parotid acinar cells.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Mannose-binding lectin and rheumatoid arthritis in southern Chinese.

OBJECTIVE: Insufficiency of mannose-binding lectin (MBL) is associated with recurrent infections. Rheumatoid arthritis (RA) may represent an aberrant immune response to infections. This study examined the phenotypic expression and variant alleles of the MBL gene and its etiologic role in Chinese with RA. METHODS: We studied 211 RA patients and 196 healthy subjects. Serum MBL concentrations and codon-54 mutation of the MBL gene and its promoter polymorphisms were analyzed. Clinical characteristics and disease activity were also examined. RESULTS: Patients with RA had significantly lower serum MBL levels and higher frequency of codon-54 mutation of the MBL gene compared with controls. Additionally, there was a significant difference in the distribution of promoter polymorphisms, H/L, between RA patients and controls, although the frequencies of Y/X and those of nonstructural polymorphisms, P/Q, did not differ between the 2 groups. Furthermore, patients with RA had a lower incidence of the highest-producing haplotype HY and a higher incidence of the lowest-producing haplotype LX compared with controls. Serum MBL levels did not correlate with drug treatment or with disease activity. However, patients with erosive and serious extraarticular disease had significantly lower serum MBL levels than those without these disease manifestations at the time of study. Also, significantly more patients with erosive disease had a codon-54 mutation of the MBL gene compared with those with nonerosive disease. CONCLUSION: The codon-54 mutation and low-producing promoter polymorphisms of the MBL gene are associated with RA. A low serum level of MBL predisposes to the development of RA and is a risk factor for severe disease in southern Chinese.

Arthritis, Rheumatoid↗

PubMed2000

Geographic variation in patient surveillance after radical prostatectomy.

BACKGROUND: Prostate cancer is often diagnosed early enough in its clinical course to permit radical prostatectomy to be done with curative intent, yet many patients experience tumor recurrence. Most patients receive postoperative surveillance, but the intensity of testing varies appreciably. We sought to evaluate the influence of geographic location on the variability of surveillance intensity. METHODS: Questionnaires pertaining to postoperative surveillance were mailed to 4467 members of the American Urological Association (AUA). Practice pattern variation was assessed among 24 large metropolitan statistical areas, among nine United States census regions, and by health maintenance organization penetration rate. RESULTS: Of 4467 urologists surveyed, 1416 (32%) responded and 1050 (24%) responses were evaluable. Correlation analysis showed that mean follow-up intensity across modalities surveyed was highly correlated across tumor, node, metastasis (TNM) stages and years postsurgery. We found no significant main effects attributable to metropolitan statistical area, United States (US) census region, or health maintenance organization (HMO) penetration rate for commonly used surveillance modalities: serum prostate-specific antigen (PSA), office visit, and urinalysis. For infrequently used modalities, there were minimal effects on testing intensity of US census region, metropolitan statistical area, and HMO penetration rate. Few two-way and three-way interactions were significant. CONCLUSIONS: The utilization of commonly used surveillance modalities by urologists caring for patients after radical prostatectomy is not affected by metropolitan statistical area, US census region, or HMO penetration rate.

Adult↗

PubMed2000

Interindividual differences in intraindividual changes in proactivity during organizational entry: a latent growth modeling approach to understanding newcomer adaptation.

Intraindividual change over time is the essence of the change phenomenon hypothesized to occur in the individual newcomer adaptation process. Many important adaptation questions cannot be answered without an adequate conceptualization and assessment of intraindividual change. Using a latent growth modeling approach to data collected from 146 doctoral program newcomers over 4 repeated measurements spaced at 1-month intervals, the authors explicitly modeled interindividual differences in intraindividual changes in newcomer proactivities (information seeking, relationship building) and proximal adaptation outcomes (task mastery, role clarity, social integration) during organizational entry. Results indicated that changes in proactivity may be related to newcomer characteristics and adaptation outcomes in interesting ways that have not been previously examined.

Adaptation, Psychological↗

PubMed2000

Validation of prediction equations for basal metabolic rate in chinese subjects.

OBJECTIVES: To examine the validity of existing prediction equations for basal metabolic rate (BMR) and two generated regression equations in healthy Chinese subjects and patients with chronic diseases. SUBJECTS: One-hundred and thirty-four healthy Chinese volunteers of aged 16-88 among staff working in Shatin Hospital and their relatives, and 30 elderly patients with heart disease, stroke and chronic obstructive airway disease (COAD) were recruited. INTERVENTIONS: Height, weight, biceps and triceps skinfold thickness, body fat percentage, and BMR were measured in the healthy subjects and patients. Two regression equations were derived from 70 healthy Chinese subjects. Three existing equations (WHO, Liu and Jia equations) and two derived equations were then cross-validated in 64 subjects and 30 patients. RESULTS: For the healthy Chinese subjects, as well as patients, the BMR calculated by Liu was the closest to the measured BMR among all the equations, although there was slight underestimation for patients. CONCLUSION: This study confirms that the Liu equation is the most appropriate for predicting BMR in healthy Chinese subjects, but it underestimates the BMR in those with chronic diseases. Fat-free mass is the best predictor of measured BMR. SPONSORSHIP: Unrestricted research grant in nutrition from the Bristol-Myers Squibb Foundation.

Adolescent↗

PubMed2000

Current practice of patient follow-up after potentially curative resection of cutaneous melanoma.

Follow-up care for patients who have undergone potentially curative resection of cutaneous melanoma varies widely among physicians, and the underlying rationale has not been assessed. To quantify current practice patterns and to discern motivation, a custom-designed questionnaire was mailed to U.S. and non-U.S. surgeons, all of whom were members of the American Society of Plastic and Reconstructive Surgeons (ASPRS). Surveys were mailed to 3,032 ASPRS members, chosen randomly from a total of 4,320 members. Of the 1,142 questionnaires that were returned, 395 were evaluable. Nonevaluability was usually due to lack of melanoma patients receiving follow-up in the surgeons' practices. Surveillance of patients after resection of melanoma relies most heavily on office visit, chest x-ray, complete blood count, and liver function tests. There was surprisingly little influence of elective node dissection on follow-up practices. Imaging tests such as computed tomography, magnetic resonance imaging, and position emission tomography scan were rarely employed. Surveillance is motivated by many factors, particularly early detection of recurrence of the index melanoma and second primary melanomas. This survey provides information regarding current follow-up strategies recommended by ASPRS surgeons after potentially curative resection of cutaneous melanoma. There is considerable variation in surveillance intensity and in motivation among practitioners, thus representing a lack of consensus.

Adult↗

PubMed2000

The doctor-patient relationship: a survey of attitudes and practices of doctors in Singapore.

This article reports the results of a survey, by mailed questionnaire, of the attitudes, values and practices of doctors in Singapore with respect to the doctor-patient relationship. Questionnaires were sent to a random sample of 475 doctors (261 general practitioners and 214 medical specialists), out of which 249 (52.4%) valid responses were completed and returned. The survey is the first of its kind in Singapore. Questions were framed around issues of medical paternalism, consent and patient autonomy. As the doctors were exposed to Western ethical concepts in their training, we were not surprised to find that they would mostly allow patients some say in decision-making and keep patients reasonably informed. In respecting patient autonomy, they would usually seek to influence patient choice by persuasion. However, the residual 'Asian-ness' of doctors in Singapore gives rise to some inconsistencies between values and practices. Many doctors still believe that a number of their patients are incapable of rational choice. There is some lack of openness in telling patients the whole truth. When patients choose to refuse treatment, many doctors are prepared to involve family members in making a consensus decision. Doctors were also asked how they made ethical judgements in the face of dilemmas, and how they would like disputes with patients to be resolved. By and large, the doctors prefer to make their own judgements rather than to rely on rules. They also wish to keep the law courts out of disputes with patients, preferring less public ways of settling disputes.

Attitude of Health Personnel↗