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Biomedical subjects

R Ng

Publications and source records attributed to R Ng.

At least 19 recordsLinked to original sources

Age differences in social preferences among Taiwanese and Mainland Chinese: the role of perceived time.

Socioemotional selectivity theory holds that as people recognize the inevitable constraint of time imposed by mortality, their social goals change, motivating them to limit social contacts to those with whom they are emotionally close. This theory was tested among Taiwanese and Mainland Chinese. As predicted, results showed that older adults (aged 60-90 years) in both cultures were more likely than younger adults (aged 18-30 years) to prefer familiar social partners who were most likely to provide emotionally close social interactions. Mainland Chinese, who as a group have shorter actuarial life expectancy, were more likely to prefer familiar social partners than were Taiwanese. These age and cultural differences were eliminated when differences in perceived time were statistically controlled for.

Adult↗

Preferential expression of antioxidant response element mediated gene expression in astrocytes.

Transcriptional control of target genes by antioxidant/electrophile response elements has been well described in peripheral tissues. Genes that are regulated by this mechanism include the antioxidant enzymes NAD(P)H:quinone oxidoreductase, gamma-glutamyl cystine synthetase and glutathione-S-transferase. Antioxidant/electrophile response elements within a gene's promoter confer induction by low-molecular-weight electrophilic compounds such as tert-butylhydroquinone and dimethyl fumarate. We have now examined the ability of antioxidant/electrophile response elements to elicit gene expression in neurons and astrocytes in both brain slices and primary cultures using transient transfection of promoter reporter constructs. Our results using a heat-stable human placental alkaline phosphatase reporter indicate that antioxidant/electrophile response element mediated gene expression is largely restricted to astrocyte cell populations. Placental alkaline phosphatase expression was significantly elevated in astrocytes treated with the antioxidant/electrophile response element inducer dimethyl fumarate. Mutant constructs lacking a functional antioxidant/electrophile response element abolished all placental alkaline phosphatase expression in astrocytes. We suggest that astrocytic metabolic processes that normally aid and/or protect neurons may be controlled via this inducible system.

Animals↗

Suppression of the accumulation of triosephosphates and increased formation of methylglyoxal in human red blood cells during hyperglycaemia by thiamine in vitro.

The accumulation of triosephosphates and the increased formation of the potent glycating agent methylglyoxal in intracellular hyperglycaemia are implicated in the development of diabetic complications. A strategy to counter this is to stimulate the anaerobic pentosephosphate pathway of glycolysis by maximizing transketolase activity by thiamine supplementation, with the consequent consumption of glyceraldehyde-3-phosphate and increased formation of ribose-5-phosphate. To assess the effect of thiamine supplementation on the accumulation of triosephosphates and methylglyoxal formation in cellular hyperglycaemia, we incubated human red blood cell suspensions (50% v/v) in short-term culture with 5 mM glucose and 50 mM glucose in Krebs-Ringer phosphate buffer at 37 degrees C as models of cellular metabolism under normoglycaemic and hyperglycaemic conditions. In hyperglycaemia, there is a characteristic increase in the concentration of the triosephosphate pool of glycolytic intermediates and a consequent increase in the concentration and metabolic flux of the formation of methylglyoxal. The addition of thiamine (50-500 microM) increased the activity of transketolase, decreased the concentration of the triosephosphate pool, decreased the concentration and metabolic flux of the formation of methylglyoxal, and increased the concentration of total sedoheptulose-7-phosphate and ribose-5-phosphate. Biochemical changes implicated in the development of diabetic complications were thereby prevented. This provides a biochemical basis for high dose thiamine therapy for the prevention of diabetic complications.

Deoxyglucose↗

Internet use amongst New Zealand general practitioners.

AIMS: To assess how extensively New Zealand doctors are using medical information on the Internet, and to examine how the new technology is affecting their practice of medicine. METHODS: All general practitioners (GPs) known to be working in Otago and Southland were asked to complete a postal questionnaire regarding their use of the Internet and their impressions of patient use of online medical resources. RESULTS: Of 259 questionnaires mailed out, 168 (65%) were returned by GPs currently in practice. Of those, 114 (68%) said they used the Internet at least monthly. A total of 71% of GPs had patients who indicated they had sought medical information from the Internet. Nearly half of respondents expressed concerns that the Internet could have unwelcome effects on the doctor-patient relationship. CONCLUSIONS: Internet use among New Zealand doctors and patients is widespread, and is likely to have significant impact on medical practice now and in the future. While the potential benefits of the new technology are numerous, the Internet may become a source of conflict between doctors and patients.

Data Collection↗

Eradication of human non-Hodgkin's lymphoma in SCID mice by BCL-2 antisense oligonucleotides combined with low-dose cyclophosphamide.

Cancers overexpressing Bcl-2 protein, which prevents programmed cell death (apoptosis), are less sensitive to stresses that produce cellular damage, including chemotherapy. If the level of Bcl-2 protein can be reduced sufficiently using antisense oligonucleotides (ASOs) targeting the gene message, then cytotoxic agents may be rendered more effective in eliminating disease and increasing cure rate. Preclinical studies in SCID mice bearing Bcl-2 overexpressing systemic human B-cell lymphoma (DoHH2) were undertaken to support development of a clinical trial. These data confirm that a combination of an ASO (5 mg/kg) targeting bcl-2 and a low dose of cyclophosphamide (35 mg/kg) was an effective strategy, leading to the eradication of the DoHH2 cells in vivo and cure of the animals. When mice deficient in natural killer cell activity were treated with an ASO, similar results were observed, suggesting that ASO stimulation of the host immune system was not a significant factor in elimination of lymphoma cells. These studies indicate that therapeutic strategies involving the use of an ASO targeting bcl-2 in combination with a cytotoxic agent may improve clinical outcomes.

Animals↗

Nasopharyngeal brush biopsies and detection of nasopharyngeal cancer in a high-risk population.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is an important tumor in many countries. Ethnic and regional factors strongly influence disease risk. NPC is usually diagnosed late in disease development, and 10-year survival rates are as low as 10%. Epstein-Barr virus (EBV), a possibly causative agent, is present in all cells of essentially all undifferentiated NPCs. We wished to determine the following: 1) whether an ambulatory nasopharyngeal brush biopsy could provide sufficient tumor cell DNA for the detection of EBV and 2) whether the detection of EBV in this locale reflects the presence of tumor cells or simply EBV carrier status. METHODS: We collected nasopharyngeal tissue via ambulatory brush biopsies from 21 patients with newly diagnosed NPC and from 157 subjects with other otolaryngologic complaints. The majority of study subjects were from high-risk populations. Sample DNA was analyzed for the presence of EBV genomic sequences by use of the polymerase chain reaction (PCR). RESULTS: Ninety-six percent of samples yielded sufficient DNA for PCR amplification. Nineteen of 21 patients with NPC brushed positive for EBV DNA, while all but two (1.3%) of 149 informative control subjects were negative for EBV (two-sided P<.0001). One of the EBV-positive control subjects had an EBV-positive inverted sinonasal papilloma; the other EBV-positive control subject exhibited no overt clinical disease. CONCLUSION: Demonstration of EBV DNA in nasopharyngeal brush biopsy specimens detects NPC with a sensitivity of at least 90% (95% confidence interval = 89.63%-91.32%) and a specificity of approximately 99% (95% confidence interval = 98.64%-98.68%). This technique merits further testing as a possible ambulatory screening strategy in high-risk populations.

Adolescent↗

Close relationships and adjustment to a life crisis: the case of breast cancer.

When life crises occur, significant others are thought to help alleviate distress and resolve practical problems. Yet life crises may overwhelm significant others, eroding their ability to provide effective support. The accuracy of these contrasting accounts of relationship functioning was evaluated in a study of 102 breast cancer patients and their significant others, interviewed at 4 and 10 months after diagnosis. Results largely confirmed the negative account of relationship functioning. Although significant others provided support in response to patients' physical impairment, they withdrew support in response to patients' emotional distress. Moreover, support from significant others did not alleviate patients' distress or promote physical recovery. These results reveal limits to the effectiveness of close relationships in times of severe stress.

Activities of Daily Living↗

Neutralization of endogenous IL-6 suppresses induction of IL-1 receptor antagonist.

IL-1 is a potent cytokine that promotes host defense and inflammation. These processes may be modulated by an IL-1 receptor antagonist (IL-1Ra) that binds to and blocks IL-1 receptors. The objective of this study was to define the cellular origin and regulation of IL-1Ra production during bacterial infection. Oral infection of mice with Yersinia enterocolitica resulted in expression of IL-1Ra mRNA and synthesis of IL-1Ra in Peyer's patches (PP), the local site of infection, as well as in noninfected organs such as spleens. By immunostaining, recruited circulating neutrophils were identified to be the primary source of IL-1Ra in tissues. Only approximately 20% of the IL-1Ra-staining cells were accounted for by inflammatory macrophages. Strikingly, neutralization of IL-6 by anti-IL-6 antiserum caused a suppression of both IL-1Ra mRNA in PP and synthesis of IL-1Ra in circulating neutrophils. Confirmatory evidence that IL-6 participates in the generation of IL-1Ra was obtained when rIL-6 induced, and anti-IL-6 antiserum blocked, IL-1Ra expression in cultures of macrophage and polymorphonuclear leukocytes (PMN). These findings suggest that IL-6 induced induction of IL-1Ra may provide a negative feedback loop, facilitating resolution of the inflammatory response locally and presumably at remote sites of infection.

Animals↗

Effect of growth hormone on bone marrow grafts in fracture healing--an experimental study in rabbits.

The lack of effectiveness of growth hormone in stimulating the healing of fresh fractures has been attributed to the presence of insufficient precursor osteogenic cells at the fracture site for the growth hormone to exert its influence. We tested the effect of growth hormone on healing in a rabbit non-union model after injection of autogenous marrow cells into the fracture gap. Two millilitres of bone marrow were injected percutaneously into 1 cm diaphyseal defects of rabbit radii. The test group was given subcutaneous human recombinant growth hormone at 0.3 IU/kg/day in divided doses for 2 weeks, while the control group received subcutaneous saline injections. Biomechanical, radiological and callus calcium content assessments were carried out at 4 and 7 weeks. There was significantly increased tensile strength and callus calcium concentration in the group given growth hormone both at 4 and 7 weeks but there was no significant difference in stiffness or in callus volume in the 2 groups. These data suggest that growth hormone can enhance the osteogenic potential of bone marrow as a graft in the treatment of fracture non-union.

Animals↗

Behaviour disorder in pre-school children in Hong Kong. A two-stage epidemiological study.

A representative sample of 855 Hong-Kong Chinese children aged 36-48 months were assessed using the BSQ and the PBCL. Good reliability for both instruments were found. For the BSQ and PBCL, 12.75% and 27.5% were above the cut-off points of 10+ and 12+ respectively and 5.9% were above both cut-off points. In the second stage, 234 subjects were recruited by stratified random sampling according to the results of the screening state. A clinician interviewed the parent, child and teacher before making a diagnosis. The prevalence of behaviour disorder was: nil, 53.7%; dubious, 23.1%; mild, 18.0%; moderate, 4.5%; and severe, 0.7%. There were significantly more boys in the categories mild, moderate and severe.

Adult↗

Mutational and in vitro protein-binding studies on centromere DNA from Saccharomyces cerevisiae.

Centromeres on chromosomes in the yeast Saccharomyces cerevisiae contain approximately 140 base pairs (bp) of DNA. The functional centromere (CEN) region contains three important sequence elements (I, PuTCACPuTG; II, 78 to 86 bp of high-AT DNA; and III, a conserved 25-bp sequence with internal bilateral symmetry). Various point mutations or deletions in the element III region have a profound effect on CEN function in vivo, indicating that this DNA region is a key protein-binding site. This has been confirmed by the use of two in vitro assays to detect binding of yeast proteins to DNA fragments containing wild-type or mutationally altered CEN3 sequences. An exonuclease III protection assay was used to demonstrate specific binding of proteins to the element III region of CEN3. In addition, a gel DNA fragment mobility shift assay was used to characterize the binding reaction parameters. Sequence element III mutations that inactivate CEN function in vivo also prevent binding of proteins in the in vitro assays. The mobility shift assay indicates that double-stranded DNAs containing sequence element III efficiently bind proteins in the absence of sequence elements I and II, although the latter sequences are essential for optimal CEN function in vivo.

Base Sequence↗

Correlation of fibrinolytic activity with invasion and metastasis of R3230 AC rat mammary carcinoma cell lines.

The parent R3230 AC rat mammary carcinoma cell line and the two variant cell lines, R3230 AC MET and R3230 AC LR, differ with respect to their abilities to invade bony matrices and to form lung colonies (experimental metastases). Both the R3230 AC and the R3230 AC MET, a cell line selected in vivo for enhanced metastatic capability, express high potentials for invasiveness and lung colony formation, while the Con A- and WGA-resistant R3230 AC LR cell line grows expansively at the periosseus implantation site and is unable to form lung colonies after intravenous inoculation. The abilities to invade bone and to metastasize to the lung are well correlated with the fibrinolytic activity and the production of urokinase-type plasminogen activators. The contribution of plasminogen activators to invasiveness and metastasis has been ascribed to its role in the fibrinolytic and collagenolytic (i.e., activation of latent collagenase) cascades.

Animals↗

Structural studies on centromeres in the yeast Saccharomyces cerevisiae.

In the yeast Saccharomyces cerevisiae, circular or linear plasmids containing a functional centromere (CEN) and a chromosomal replicator (ARS) are mitotically stable and segregate as ordinary yeast chromosomes in the first and second meiotic divisions. A centromere in S. cerevisiae consists of a region of DNA, approximately 150 bp in length, containing three important sequence elements, which are folded with proteins into a specific conformation in the chromatin (the yeast kinetochore). Each of the functional CEN sequences contains a high (91% to 95%) AT region (element II), 78 to 86 bp in length, flanked on one side by the common sequence PuTCACPuTG (element I), and on the other by the sequence TGTTT.TG.TTTCCGAAA....AAA (element III). Deletions in the element II region partially inactivate mitotic function and cause precocious separation of the sister chromatids in meiosis I. Element III appears to be a protein binding site, as evidenced by the following observations. Various point mutations in element III inactivate centromere function, especially in the central CCG (17). One or more protein binding sites in the element III region can be demonstrated by an exonuclease III blocking assay. Wild-type CEN sequences compete strongly in this binding assay, whereas certain functionally inactive mutant CEN sequences do not. In addition, various DNA segments containing either CEN3 or the element III region strongly repress expression of the yeast GAL1 gene when inserted immediately upstream from the transcriptional start site. Helical DNA segments containing CEN3 or CEN14 are shown to be bent or distorted in shape in the high-AT element II region.

Base Sequence↗

Canine orthotopic liver transplantation--is systemic veno-venous shunting necessary?

The experience of a single operating team performing the first 30 consecutive orthotopic liver transplants in dogs is reported. In 22 experiments during the anhepatic phase and as the liver graft is inserted in the recipient animal, the portal circulation is protected by a shunt to the jugular vein. Nine dogs survived 2-17 days. In 8 other unselected animals, both the portal vein and the infrahepatic vena cava were shunted to the jugular vein. Although blood pressure was better maintained in animals with 2 shunts, only one dog survived 10 days. Mention is also made of 11 subsequent transplant operations using a single porta-jugular shunt but reducing operating time by having 2 surgeons working on the donor and recipient animal simultaneously. Nine of the 11 dogs survived 2-6 days after the liver transplantation. The survival figures are comparable to those of other centres where double shunting is routinely performed. Our experience suggests that systemic veno-venous shunt may be omitted if the transplant procedure is performed expeditiously.

Animals↗

Effect of sample dilutions on arterial blood gas determinations.

A study was undertaken to determine the blood gas effects of incompletely purging heparinized saline flush solution from an indwelling arterial catheter and pressure tubing. Hematocrit and blood gases were measured after withdrawing 0, 2, 4, 6, 8, and 10 ml of flush-blood solutions before sampling from a 20-ga radial artery catheter and 7-ft pressure tubing and stopcock. The pH and hematocrit were nearly unchanged between purging volumes of 8 and 10 ml. The PaO2 had a 2.4% error, while the PaCO2 had a 4.4% error. Because there is no standard arterial line setup, it is recommended that each ICU undertake a similar study to determine the optimal volume of aspirated flush-blood solution before blood gas sampling, in order to achieve accurate blood gas results and minimize blood waste.

Blood Gas Analysis↗

Plasminogen activator activity in human breast cancer cytosols.

Plasminogen activators are an enzyme complex which first appears in the trophoblast and may contribute to the invasive and metastatic process in neoplastic growth. In this study, 102 cytosols from human breast cancer biopsies were analyzed for PAA (with the chromogenic tripeptide S2251 KABI), steroid receptors (ER and PR), age, nodal and menopausal status. The data were submitted to log (X + 1) transformation and the raw and transformed data were analyzed for distribution. Because of the largely non-normal distribution of the data, Spearman's rank order correlation coefficients were generated to test for relationships between these differentiation markers and the clinical data. Nodal and menstrual status groups were compared for PAA and receptor levels using the Wilcoxon rank sum test. We found significant positive correlations between net PAA and ER (p = 0.0001), net PAA and PR (p = 0.0001), and net PAA and age (p less than 0.05). PAA levels for nodal status groups were found to be significantly different (negative at p less than 0.05). Nodal metastases predict poor prognosis while higher receptor levels indicate a better prognosis. As PAA levels correlate with the above biologic properties of breast tumors, they may provide additional prognostic information, especially in cases in whom auxiliary node status is unknown.

Breast Neoplasms↗

Chemical and clinical evaluation of the random access analyzer "RA-1000".

In the RA-1000, a random-access discrete analyzer, an inert fluorocarbon fluid is used to prevent interaction and carryover. Production-model instruments were evaluated in two laboratories with respect to determination of glucose, creatinine, total protein, inorganic phosphorus, cholesterol, alkaline phosphatase, lactate dehydrogenase, creatine kinase, gamma-glutamyltransferase, and aspartate and alanine aminotransferases. Within-run, among-run, and day-to-day (for 15 days) precision was assessed, and results were correlated with those obtained by the methods routinely in use in our departments. Precision was excellent, correlation acceptable.

Autoanalysis↗