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Biomedical subjects

S Ng

Publications and source records attributed to S Ng.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cellular transport processes of aminoguanidine, a nitric oxide synthase inhibitor, in the opossum kidney cell culture line.

Aminoguanidine has potential pharmacologic utility for diabetes and nitric oxide - mediated inflammation. Because aminoguanidine is positively charged at physiologic pH (pK(a) approximately 10), it is unlikely that simple diffusion is a predominant mechanism for cellular penetration. This study sought to determine the transport processes by which aminoguanidine, a cationic compound, traverses across cellular membranes. In cultured opossum kidney (OK) cell monolayers, aminoguanidine transport involved both saturable and non-saturable diffusion processes. At passage numbers below 67, the observed V(max) and K(m) for saturable influx were significantly lower than that observed at passages greater than 79 (V(max): low passage, 21.2+/-7.8 pmol/(min*mg protein), n=3; versus high passage, 129.7+/-24.3 pmol/(min*mg protein), n=3, P<0.05; K(m): low passage, 23.7+/-10.8 microM, n=3; versus high passage, 101.7+/-5.6 microM, n=3, P<0.05; mean+/-S.E.M.). Nonsaturable processes were not statistically different (k(ns): low passage, 1.6+/-0.1 pmol/(min*mg protein*microM), n=3; high passage, 1.1+/-0.2 pmol/(min*mg protein*microM) n=3). Saturable influx was temperature dependent, and independent of ATP energy, sodium gradients or changes in membrane potential. Other organic cations competitively inhibited and trans-stimulated saturable influx. Aminoguanidine influx was increased in the presence of an outwardly-directed proton gradient and was inhibited in the presence of an inwardly-directed proton gradient. Correspondingly, aminoguanidine efflux was trans79) express a saturable, bi-directional carrier-mediated process to transport aminoguanidine across cellular membranes.

Animals↗
PubMed2000

Multi-centre assessment of the Spiegelberg compliance monitor: preliminary results.

Acute brain injury states (e.g. head injury, subarachnoid haemorrhage) show clear inverse relationships of ICP vs compliance, with ICP instability at times of lower compliance states. Variance in compliance values is large in hydrocephalus where ICP is relatively lower and compliance higher. Nonetheless, early experience shows that compliance data influence decisions on CSF diversion treatments. Future work will focus on the ability of intracranial compliance to predict ensuing ICP instability and methodological refinement for monitoring patients who have higher compliance states.

Brain↗
PubMed2000

A cost and performance evaluation of disposable and reusable biopsy forceps in GI endoscopy.

BACKGROUND: Biopsy forceps are widely used in gastrointestinal endoscopy, and yet few data exist on the usage and costs associated with disposable versus reusable forceps. METHODS: We prospectively measured the costs and operational performance of disposable and reusable forceps in 200 biopsy sessions; 100 sessions were performed using disposable forceps and 100 sessions were performed using reusable forceps. Total cost per use of the reusable forceps, including acquisition costs plus the costs of reprocessing per established guidelines, was determined. At the end of the study, the reusable forceps were disassembled to determine the cause of mechanical failures. RESULTS: The total cost per use of the disposable forceps was $38. For the reusable forceps, the acquisition cost per forceps was $415 and the total reprocessing cost was $16.56 +/- 0.07 per forceps. For 10, 15 and 20 uses, reusable forceps costs were $58.06, $44.23, and $37.31, respectively. Reusable forceps malfunction at 11 to 15 uses was 5%; at 16 to 20 uses was 25%; and at 21 to 25 uses reached 80% (p < 0.001). Dismantling of the reusable forceps at the end of the study demonstrated coiled sheath kinking, rust in the forceps closure mechanism, bent spikes, and biomaterial contamination. CONCLUSIONS: Up to 15 to 20 uses, disposable and reusable forceps costs were similar. If reusable forceps are used more than 20 times, then they are less expensive. However, in this range of uses, reusable biopsy forceps performance diminishes. With disposable biopsy forceps costing less than $40, cost differences between reusable and disposable forceps are minimal.

Biopsy↗
PubMed2000

Modulation of drug resistance by alpha-tubulin in paclitaxel-resistant human lung cancer cell lines.

Beta(beta)-tubulin isotype variation has recently been implicated in the modulation of resistance to paclitaxel in human lung cancer cells and in primary human ovarian tumour samples. Whether alpha-tubulin is involved in drug resistance has not been reported. We have generated a paclitaxel-resistant cell line (H460/T800) from the sensitive human lung carcinoma parental cell line NCI-H460. The resistant cells are more than 1000-fold resistant to taxol and overexpress P-glycoprotein. Interestingly, H460/T800 cells also overexpress alpha- and beta-tubulin as detected by Western blot analysis. From Northern blot analysis, the mechanism of tubulin overexpression appears to be post-transcriptional. To understand whether alpha-tubulin plays a role in drug resistance, we transfected antisense human kalpha1 cDNA construct into the H460/T800 paclitaxel-resistant cells. The antisense clones displayed a reduced alpha-tubulin expression, and the cells were 45-51% more sensitive to paclitaxel and other known antimitotic drugs, compared with vector transfected controls. Complementary experiments of transfecting the sense kalpha1 cDNA into H460 cells conferred a 1.8- to 3.3-fold increase in the IC(50) of several antimitotic agents. Our study suggests that alpha-tubulin is one of the factors that contributes to drug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

High-dose methotrexate for primary CNS lymphoma in the elderly.

Primary central nervous system lymphoma (PCNSL) in the immunocompetent patient reaches a peak incidence in the sixth and seventh decades of life. This retrospective study reviewed the efficacy and tolerability of high-dose methotrexate (HDMTX) in an elderly patient population. Between May 1995 and September 1998, ten consecutive elderly patients with histologically proven PCNSL were treated with HDMTX. The median age was 72.5 years and eight patients (80%) were older than 70 years. HDMTX was well tolerated with no episodes of grade 4 toxicity nor febrile neutropenia. Toxicity included grade 3 nausea (1), grade 2 mucositis (2), and grade 2 asymptomatic elevation of liver transaminases (2). Grade 1 toxicity occurred in three patients with nausea, diarrhea, and mild reversible elevation in serum creatinine in one patient each. Six patients had a complete response and three patients achieved a partial response, giving an overall response rate of 90% (95% confidence interval, 56%-100%). The median overall survival for the cohort was 36 months (range 4-43 months). In summary, HDMTX is well tolerated in this elderly population with PCNSL and achieves response rates and median survival comparable with other chemotherapy or radiotherapy regimens.

Aged↗
PubMed2000

Testosterone inhibits estrogen-induced mammary epithelial proliferation and suppresses estrogen receptor expression.

This study investigated the effect of sex steroids and tamoxifen on primate mammary epithelial proliferation and steroid receptor gene expression. Ovariectomized rhesus monkeys were treated with placebo, 17beta estradiol (E2) alone or in combination with progesterone (E2/P) or testosterone (E2/T), or tamoxifen for 3 days. E2 alone increased mammary epithelial proliferation by approximately sixfold (P:<0.0001) and increased mammary epithelial estrogen receptor (ERalpha) mRNA expression by approximately 50% (P:<0.0001; ERbeta mRNA was not detected in the primate mammary gland). Progesterone did not alter E2's proliferative effects, but testosterone reduced E2-induced proliferation by approximately 40% (P:<0.002) and entirely abolished E2-induced augmentation of ERalpha expression. Tamoxifen had a significant agonist effect in the ovariectomized monkey, producing a approximately threefold increase in mammary epithelial proliferation (P:<0.01), but tamoxifen also reduced ERalpha expression below placebo level. Androgen receptor (AR) mRNA was detected in mammary epithelium by in situ hybridization. AR mRNA levels were not altered by E2 alone but were significantly reduced by E2/T and tamoxifen treatment. Because combined E2/T and tamoxifen had similar effects on mammary epithelium, we investigated the regulation of known sex steroid-responsive mRNAs in the primate mammary epithelium. E2 alone had no effect on apolipoprotein D (ApoD) or IGF binding protein 5 (IGFBP5) expression, but E2/T and tamoxifen treatment groups both demonstrated identical alterations in these mRNAs (ApoD was decreased and IGFBP5 was increased). These observations showing androgen-induced down-regulation of mammary epithelial proliferation and ER expression suggest that combined estrogen/androgen hormone replacement therapy might reduce the risk of breast cancer associated with estrogen replacement. In addition, these novel findings on tamoxifen's androgen-like effects on primate mammary epithelial sex steroid receptor expression suggest that tamoxifen's protective action on mammary gland may involve androgenic effects.

Animals↗
PubMed2000

Can 16-18-year-old elite ballet dancers improve their hip and ankle range of motion over a 12-month period?

OBJECTIVE: To determine the effect of a 12-month intensive ballet training regimen on hip and ankle range of motion in male and female, first- and second-year professional dancers. DESIGN: 12-month longitudinal follow-up. SETTING: National classical ballet school in Australia. PARTICIPANTS: 28 female and 20 male full-time ballet students with a mean +/- 1 SD, ages 16.8 +/- 0.8 and 17.7 +/- 1.2 years, respectively. MAIN OUTCOME MEASURES: Degrees of range of motion of left and right sides for the following movements: standing plié in parallel-passive ankle dorsiflexion (DF); standing turnout in the balletic first position--lower leg external rotation (LLER); supine hip external rotation (ER); supine hip internal rotation (IR). An additional range of motion was calculated: external rotation below the hip joint (BHER) derived by subtracting hip ER from LLER. MAIN RESULTS: In all subjects combined, hip and ankle ranges increased statistically on the right. However, the amount was generally minimal and most at the borderline of the amount of error associated with the measurement tool. While there was no change in LLER, there was a decrease in BHER. There were no overall gender differences, and year differences existed only for left hip ER and total hip ER with first-year dancers showing significant improvements in these ranges. For DF and sum of hip IR, first-year males and second-year females had increases in range. There was a negative relationship between baseline range and the amount of change over the 12 months. CONCLUSIONS: Dancers ages 16-18 years who enter full-time ballet training did not augment their ankle dorsiflexion to any appreciable degree. Some, but certainly not all, increased their hip active external rotation over 12 months without increasing their total lower limb turnout. Hip ER was more likely to improve in the first-year rather than second-year student in this elite full-time training school.

Adolescent↗
PubMed2000

Discovery, purification, and characterization of a temperate transducing bacteriophage for Bordetella avium.

We discovered and characterized a temperate transducing bacteriophage (Ba1) for the avian respiratory pathogen Bordetella avium. Ba1 was initially identified along with one other phage (Ba2) following screening of four strains of B. avium for lysogeny. Of the two phage, only Ba1 showed the ability to transduce via an allelic replacement mechanism and was studied further. With regard to host range, Ba1 grew on six of nine clinical isolates of B. avium but failed to grow on any tested strains of Bordetella bronchiseptica, Bordetella hinzii, Bordetella pertussis, or Bordetella parapertussis. Ba1 was purified by CsCl gradient centrifugation and was found to have an icosahedral head that contained a linear genome of approximately 46.5 kb (contour length) of double-stranded DNA and a contractile, sheathed tail. Ba1 readily lysogenized our laboratory B. avium strain (197N), and the prophage state was stable for at least 25 generations in the absence of external infection. DNA hybridization studies indicated the prophage was integrated at a preferred site on both the host and phage replicons. Ba1 transduced five distinctly different insertion mutations, suggesting that transduction was generalized. Transduction frequencies ranged from approximately 2 x 10(-7) to 1 x 10(-8) transductants/PFU depending upon the marker being transduced. UV irradiation of transducing lysates markedly improved transduction frequency and reduced the number of transductants that were lysogenized during the transduction process. Ba1 may prove to be a useful genetic tool for studying B. avium virulence factors.

Bacteriophages↗
PubMed2000

An outbreak of ciguatera fish poisoning in Victoria.

An outbreak of ciguatera fish poisoning in outer Melbourne in September 1997 was traced to a 16.2 kg Maori Wrasse fish imported into Victoria from Trunk Reef in Queensland. The outbreak involved 46 individuals attending a banquet at an Asian restaurant at which four different dishes prepared from the flesh and viscera of the fish were offered. In all 30 individuals consumed at least one of these dishes and all reported one or more symptoms, in the main gastrointestinal and/or in 18 cases neurological. Seventeen cases were seen in four different hospitals and nine were treated with parenteral mannitol therapy. Nine of 18 cases were still symptomatic 10 weeks after the episode. Education of Asian restaurateurs and the wider community about the risks of ciguatera fish poisoning was undertaken.

Adult↗
PubMed1999

Differential expression of NF1 type I and type II isoforms in sporadic borderline and invasive epithelial ovarian tumors.

The NF1 gene, a putative tumor suppressor gene, contains a GAP related domain (GRD) which accelerates hydrolysis of ras-bound GTP to GDP, thereby converting the ras oncogene from its active to inactive form. Two forms of the NF1 GRD transcript (Type I and Type II) are differentially expressed in neuroectodermal tumor tissue relative to differentiated neural cells, and in gastric cancer cell lines relative to normal stomach mucosa. We measured relative expression of NF1 Type II and Type I isoforms in cultured normal and malignant human ovarian surface epithelial cells(HOSE) and in invasive and borderline ovarian tumor tissue. We demonstrated an 11-fold increase in Type II:Type I ratio in 7 HOSE cultures relative to eight ovarian cancer cell lines. Our findings indicate a significant decrease in Type II isoform expression and increase in Type I expression in ovarian cancer cells and tumor tissue relative to HOSE cells. We also demonstrate an increase in Type II:Type I ratio, and a decrease in cell proliferation rate in three ovarian cancer cell lines on treatment with retinoic acid. We propose that differential expression of the NF1 Type I and Type II isoforms is related to cellular differentiation in ovarian epithelial cancer and strategies based on alteration in NF1 isoform expression may have therapeutic potential in ovarian malignancies.

Adenocarcinoma↗
PubMed1999

Is there room for managed care in Canada? A preliminary inquiry of physicians.

Managed care, which is becoming increasingly prevalent in the United States, is virtually absent in Canada. Yet managed care, if implemented judiciously, has the potential to provide comprehensive, high quality care while containing spiraling healthcare expenditures. Managed care is also the foundation of integrated health systems, which have been widely discussed during the past few years. Then why has Canada been so slow to accept managed care? Since physicians have a great deal of influence on how healthcare is ultimately delivered, a group of Ontario physicians was surveyed to determine their perceptions of managed care. It was found that physicians were knowledgeable about the cost-containment capabilities of managed care but had misperceptions about managed care with respect to quality of patient care, preventive services and necessary medical care. Education and further research are recommended so that any debate about managed care, integrated systems or alternative physician payment can be meaningful, objective, beneficial and accurate.

Attitude of Health Personnel↗
PubMed1999

Combinatorial discovery process yields antimicrobial peptoids.

N-alkylated glycine trimers are generically referred to as peptoids. The identification of antimicrobial peptoids from a statistically unbiased diverse combinatorial chemistry library led to the design of the optimization peptoid library that we describe in this manuscript. This optimization library was designed using structural information from the most active peptoids in the unbiased library. Screening of the optimization library for antimicrobial activity identified a single pool of peptoids with activity against both Staphylococcus aureus and Escherichia coli. The active peptoids from this pool were active against drug sensitive and drug resistant organisms and represent novel antibacterial compounds.

Anti-Bacterial Agents↗
PubMed1999

Barriers to meeting the mental health needs of the Chinese community.

BACKGROUND: This study aimed to identify the barriers encountered by Chinese people with mental health needs in England which hindered their obtaining appropriate help from the National Health Service (NHS). METHODS: Attenders at Chinese community centres in health authority districts with resident Chinese population in excess of 2000 were invited to fill in a 12-item Chinese Health Questionnaire (12-CHQ). Individuals who scored two or above, indicating a high probability of a mental health problem, were invited to undertake a semi-structured interview. RESULTS: A total of 401 completed the 12-CHQ. Eighty-six (21.4 per cent) screened positive and 71 (82.6 per cent) agreed to be interviewed. Although 70 (98.6 per cent) were registered with a general practitioner (GP), there were long delays before they made contact with health professionals, and the GP was the first port of call for help in only 27 (38.6 per cent) interviewees. Fifty-two (74.3 per cent) had encountered difficulties when they sought professional help. The main barriers were language, interviewees' perceptions of symptoms as somatic rather than psychiatric in origin, lack of knowledge about statutory services, and lack of access to bilingual health professionals. Doctors, particularly GPs, were pivotal in the management of their conditions. The majority were prescribed psychiatric medication with only a small number in contact with community psychiatric services. Unemployment and social exclusion were common. Stigma associated with mental illness and limited knowledge in the community were identified as the causes for the widespread discrimination experienced by the interviewees. CONCLUSION: The mental health needs of these Chinese people were not adequately met by statutory services, nor could they rely on family and friends for care and support. Training for health service staff and access to health advocates are essential to maximize the effectiveness of health professional-patient contacts. The promotion of better understanding of mental illness by the Chinese community is important, and greater flexibility within the NHS is required to ensure those professionals with bilingual skills are used to the best effect.

Adult↗
PubMed1999

A nursing home outbreak of Clostridium perfringens associated with pureed food.

OBJECTIVE: To investigate and ascertain the source of a nursing home outbreak of gastroenteritis in Melbourne in 1997. METHOD: A retrospective cohort study. We obtained fecal and food samples and environmental swabs, and reviewed food handling. RESULTS: There were 25 cases, and 21 of these had their meals pureed (liquidised). The relative risk for eating pureed food and becoming ill was 5.8 (95% CI 2.2-15.4). Clostridium perfringens and its enterotoxin was detected in nine fecal samples. Samples of pureed food tested positive for coliforms. CONCLUSIONS: This outbreak was caused by C. perfringens contaminating pureed food. Food liquidising provides opportunities for re-contamination of cooked food through the use of contaminated equipment and deficiencies in food handling practices. Pureed foods should be reheated to 70 degrees C after liquidising to inactivate pathogens. IMPLICATIONS: Health care facilities need to take specific precautions to manage the special hazards involved in preparing pureed food.

Aged↗
PubMed1999

Characterization of novel antimicrobial peptoids.

Peptoids differ from peptides in that peptoids are composed of N-substituted rather than alpha-carbon-substituted glycine units. In this paper we report the in vitro and in vivo antibacterial activities of several antibacterial peptoids discovered by screening combinatorial chemistry libraries for bacterial growth inhibition. In vitro, the peptoid CHIR29498 and some of its analogues were active in the range of 3 to 12 microg/ml against a panel of gram-positive and gram-negative bacteria which included isolates which were resistant to known antibiotics. Peptoid antimicrobial activity against Staphylococcus aureus was rapid, bactericidal, and independent of protein synthesis. beta-Galactosidase and propidium iodide leakage assays indicated that the membrane is the most likely target of activity. Positional isomers of an active peptoid were also active, consistent with a mode of action, such as membrane disruption, that does not require a specific fit between the molecule and its target. In vivo, CHIR29498 protected S. aureus-infected mice in a simple infection model.

Animals↗