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Biomedical subjects

L Wong

Publications and source records attributed to L Wong.

At least 19 recordsLinked to original sources

Unravelling the complexities of the NF-kappaB signalling pathway using mouse knockout and transgenic models.

The nuclear factor-kappaB (NF-kappaB) signalling pathway serves a crucial role in regulating the transcriptional responses of physiological processes that include cell division, cell survival, differentiation, immunity and inflammation. Here we outline studies using mouse models in which the core components of the NF-kappaB pathway, namely the IkappaB kinase subunits (IKKalpha, IKKbeta and NEMO), the IkappaB proteins (IkappaBalpha, IkappaBbeta, IkappaBvarepsilon and Bcl-3) and the five NF-kappaB transcription factors (NF-kappaB1, NF-kappaB2, c-Rel, RelA and RelB), have been genetically manipulated using transgenic and knockout technology.

Animals↗

Knowledge and attitudes about deceased donor organ donation in Filipinos: a qualitative assessment.

Fewer ethnic minorities, especially Asian-Americans, become organ donors. There are cultural, religious, and personal barriers to becoming a designated organ donor. Factors that promote or inhibit organ donation in Asians, especially Filipinos, are not well understood. We conducted a series of focus groups to identify barriers and facilitators to organ donation (deceased donor) among Filipinos. Six focus groups were conducted with church members, adolescents, nurses, physicians, organ recipients, and organ donor families. The mean age of adult participants (n = 57) was 52.3 +/- 15 years, 83% were Catholic, and 72% were female. A qualitative theme analysis methodology identified dominant themes related to organ donation in the participants. The major themes were: awareness of organ donation (38%), family beliefs (25%), religion/spirituality (10%), attitude/emotions (10%), personal experience with organ donation (8%), health profession (6%), and cultural issues (3%). Seventy-five percent of the comments about awareness reflected a positive awareness of cultural issues regarding organ donation, and the rest reflected a lack of awareness or misconceptions. Almost every theme was mentioned in all six focus groups. Understanding a specific ethnic group's knowledge, attitudes, and cultural beliefs regarding organ donation is important in the development of educational campaigns to encourage organ donation in ethnic minority populations.

Adolescent↗

Survey of aflatoxins in beer sold in Canada.

Between March 1998 and March 2002, 304 samples of domestic (Canadian) and imported beers from 36 countries were picked up for the determination of aflatoxins B1, B2, G1 and G2. Twelve samples were positive with aflatoxins greater than the limit of quantitation (LOQ) (aflatoxin B1, 4.4 ng l(-1); aflatoxin B2, 3.4 ng l(-1); aflatoxin G1, 11.2 ng l(-1); and aflatoxin G2, 6.2 ng l(-1)). Five samples from Mexico, two samples from Spain and one from Portugal contained aflatoxin B1. Four samples from India contained aflatoxins B1 and B2. The remaining samples contained less than the LOQ for aflatoxins B1, B2, G1 and G2. The analytical method for this survey was based on that of Scott and Lawrence (Scott PM, Lawrence GA. 1997. Determination of aflatoxins in beer. Journal of AOAC International 80:1229-1234.). Aflatoxins B1, B2, G1 and G2 were determined at parts per trillion (ng l(-1)) levels in beer by immunoaffinity column cleanup followed by derivatization with trifluoroacetic acid and reversed-phase liquid chromatography with fluorescence detection.

Aflatoxin B1↗

Single vs. two steroid injections for carpal tunnel syndrome: a randomised clinical trial.

We investigated the efficacy of a single vs. double steroid injections in the treatment of carpal tunnel syndrome (CTS) in a randomised double-blind controlled trial. Patients with idiopathic CTS were randomised into (i) one group receiving a baseline methylprednisolone acetate injection plus a saline injection 8 weeks later and (ii) a second group receiving methylprednisolone acetate injection at baseline and at 8 weeks. The primary outcome was the Global Symptom Score (GSS). Forty patients were recruited. By 40 weeks, the mean GSS improved from 25.6 to 14.1 in the single-injection group whereas from 26.7 to 12.6 in the reinjection group, but there was no significant difference in GSS between the two groups (p = 0.26). There were also no significant differences in terms of electrophysiological and functional outcomes. The results suggest that an additional steroid injection confers no added benefit to a single injection in terms of symptom relief.

Analgesia↗

Epidemiology of venous thromboembolism in Asian patients undergoing major orthopedic surgery without thromboprophylaxis. The SMART study.

BACKGROUND: In Asian patients undergoing surgery, the incidence of venous thromboembolism (VTE) is thought to be low relative to Western patients, and the routine use of thromboprophylaxis is controversial. OBJECTIVES: The aim of this work was to study the epidemiology of VTE in Asian patients undergoing orthopedic surgery without thromboprophylaxis. PATIENTS AND METHODS: We performed a prospective observational study of a cohort of consecutive Asian patients hospitalized for total hip or knee replacement or hip fracture surgery without thromboprophylaxis. The primary study outcome was the incidence of the composite of symptomatic VTE or sudden death at hospital discharge. This outcome was also assessed at 1 month's follow-up. RESULTS: Between April 2001 and July 2002, 2420 patients were enrolled. Median age was 68 years and the median duration of hospital stay was 13 days. The rate of symptomatic VTE or sudden death as notified by investigators was 2.3%[55 patients, 99% confidence interval (CI) 1.6, 3.2] and 1.2% (28 patients, 99% CI 0.7, 1.8) after adjudication by an independent committee. Chronic heart failure, varicose veins and a history of VTE were independent risk factors (P < 0.05) for the occurrence of the primary endpoint. At 1 month's follow-up, the incidence of adjudicated symptomatic VTE or sudden death was 1.5% (35/2264 patients). CONCLUSION: In Asian patients, the incidence of symptomatic VTE after major orthopedic surgery is not low, consistent with the rates observed in Western countries. The use of thromboprophylaxis should be considered in Asian patients undergoing such high-risk surgical procedures.

Aged↗

Nutrient removal from farm effluents.

The objectives of the study were: (i) to examine the efficiency of nutrient removal during the treatment of dairy farm effluent in a two-pond system, and (ii) to produce an inexpensive but effective nutrient trap which could be recycled as a nutrient source or soil mulch. The concentration of chemical oxygen demand (COD), biological oxygen demand (BOD), nitrogen (N), phosphorus (P) and potassium (K) in a two-pond system used to treat dairy farm effluent was monitored over a period of 7 months. The retention of nutrients by two porous materials was examined both in the laboratory batch (zeolite and bark) and pilot-scale field (bark) experiments. The results indicated that biological treatment of farm effluents using the two-pond system was not effective in the removal of nutrients, which are likely to become pollutant when discharged to waterways. Both the bark and zeolite materials were effective in the removal of N, P and K from effluent. These materials can be placed in the second (i.e., aerobic) pond to treat effluents, which can then be discharged to streams with minimum impact on water quality. The nutrient-enriched porous materials can be recycled as a source of nutrients and soil conditioner.

Adsorption↗

Clinical and electrophysiological features in Chinese patients with Kennedy's disease.

Kennedy's disease is a X-linked neuromuscular disorder caused by an expanded trinucleotide repeat in the androgen receptor gene. To ascertain the clinical diagnosis of Kennedy's disease in a Chinese population, we used a rapid, accurate PCR-based sizing method for the CAG repeat allelotype. The clinical and electrophysiological features of affected patients are described. The CAG repeats ranged from 43 to 53 and were inversely correlated with the age of onset (r = -0.63; P < 0.005).

Action Potentials↗

Educational outreach in diabetes to encourage practice nurses to use primary care hypertension and hyperlipidaemia guidelines (EDEN): a randomized controlled trial.

OBJECTIVE: To determine the effectiveness of specialist nurse delivered education in primary care to improve control of hypertension and hyperlipidaemia in patients with diabetes. DESIGN AND SETTING: Practice-level randomized controlled trial, Salford, England. SUBJECTS: From 44 practices, 10 303 subjects presenting in general practice with raised blood pressure (= 140/80 mmHg), raised total cholesterol (= 5.0 mmol/l) or both. INTERVENTIONS: Practices were randomized to receive either the intervention for hyperlipidaemia or for hypertension; practices acted as control for the intervention not received. Specialist nurses arranged a schedule of visits with general practitioners and general practice nurses, reminding them of diabetes protocols and clinical targets. They provided educational materials and protocols used in secondary care for nurse and doctor interventions including stepping up pharmacotherapy when necessary. Practices received a list of patients in their practice who were poorly controlled at their last annual review; new and recalled patients were targeted. OUTCOME MEASURES: At subsequent annual review, blood pressure and total cholesterol values were obtained from the Salford electronic diabetes register for patients from participating practices. RESULTS: Overall, specialist nurse-led educational outreach to primary care was associated with no improvement in patients achieving target after 1 year-odds ratio (OR): 1.03 (95% CI 0.95-1.11; P = 0.52). Similar results were achieved with hyperlipidaemia OR: 1.04 (95% CI 0.88-1.23; P = 0.62) and hypertension OR: 1.01 (95% CI 0.80-1.27; P = 0.93). CONCLUSION: This study provides evidence that the use of specialist nurses to perform educational outreach to improve target adherence to patients with diabetes in primary care is not effective.

Blood Pressure↗

Oral lichenoid lesions (OLL) and mercury in amalgam fillings.

84 patients with oral lichenoid lesions (OLL) were seen in the contact dermatitis clinic. All these patients had reticulate, lacy, plaque-like or erosive lichenoid changes adjacent to amalgam fillings. Patch testing to metallic mercury, 0.1% thimerosal, 1% ammoniated mercury, 0.1% mercuric chloride, and in some cases 0.05% phenylmercuric nitrate and amalgam discs was undertaken. 33 (39%) patients had positive patch test findings. 30/33 patch test positive patients had replacement of their amalgam fillings, with 28 (87%) patients experiencing improvement of symptoms and signs within 3 months. This confirms that mercury allergy is a factor in the pathogenesis of OLL in some cases. In cases where patch test negative patients improve with amalgam replacement, mercury may be acting as an irritant in the pathogenesis of OLL.

Adult↗

Mutation analysis of the RET gene in total intestinal aganglionosis by wave DNA fragment analysis system.

BACKGROUND/PURPOSE: Total intestinal aganglionosis (TIA) extending from the duodenum to the rectum is the most rare form of Hirschprung's disease (HSCR) and usually is fatal. RET is the major gene associated with HSCR, and germline mutations of this gene account for up 50% of familial and up to 15 to 20% of sporadic cases in HSCR. The aim of this study was to investigate DNA variants in the RET gene in TIA patients using the WAVE DNA Fragment Analysis System. METHODS: Genomic DNA was extracted from whole blood samples from 6 patients with TIA. Polymerase chain reaction (PCR) amplification of the 21 exons of RET was performed using published oligonucleotide primers. Heteroduplexes were followed by the WAVE DNA Fragment Analysis System with the DNASep cartridge. RESULTS: WAVE system technology detected 16 variants in the RET gene in the 6 patients with TIA. Three patients had a significant mutation in exon 8, 11, and 15, respectively. Thirteen RET polymorphic variants also were detected in the 6 patients, with L746L variant in exon 13 occurring in 4 patients. CONCLUSIONS: WAVE system technology is an efficient method for the detection of DNA sequence variants. Our findings suggest that not only RET mutations but also RET polymorphic variants may contribute to the occurrence of TIA.

Amino Acid Substitution↗

Calcium phosphate deposition in human dental plaque microcosm biofilms induced by a ureolytic pH-rise procedure.

The objectives were to develop and characterize a procedure based on a ureolytic pH rise to deposit calcium phosphate into microcosm dental plaque biofilms and to test the importance of the plaque pH range. Plaque biofilms were cultured in a multiplaque culture system ('artificial mouth') with a continuous supply of a simulated oral fluid (basal medium mucin; BMM) with 146 mmol/l (5% w/v) sucrose periodically applied over 6 min every 8h. After initial plaque growth, the biofilms were periodically exposed for up to 16 days to 6-min applications of calcium phosphate monofluorophosphate urea (CPMU) solution containing 20 mmol/l CaCl(2), 12 mmol/l NaH(2)PO(4), 5 mmol/l monofluorophosphate and 500 mmol/l urea (pH 5.0). Three application regimes were examined, one included a sucrose-induced acidic pH fluctuation. Plaque hydrolysis of the urea in CPMU caused the pH to rise to between 8.2 and 8.8, depositing fluoridated and carbonated calcium phosphates, and possibly some calcium carbonate, into the plaque. Calcium, phosphate and fluoride deposition was rapid for about 4 days and then slowed. After 10 days' treatment under standard conditions (BMM containing 1 mmol/l urea and 1 mmol/l arginine), plaque calcium and phosphate concentrations had increased up to 50-fold and 10-fold to approximately 2-4 and 1-2 mmol/g plaque protein, respectively. The calcium, phosphate and fluoride content increased steadily. Calcium phosphate deposition was proportional to the plaque resting pH, increasing over four-fold when the BMM urea concentration was increased from 0 to 20 mmol/l, which raised the resting pH from 6.4 to 7.2 and yielded a mean plaque calcium concentration of 14.3 mmol/g protein, one subsample reaching 20.8 mmol/g protein. Supplementation of BMM with 20% human serum inhibited deposition. These results support the hypothesis that an alkaline pH in plaque is critical in promoting plaque mineralization and that mineral deposition is modulated by serum. These factors are likely to be important in regulating calculus formation.

Biofilms↗

Outcome of hypospadias fistula repair.

Objectives To examine the long-term results of hypospadias fistula repair, the factors involved in recurrence and the outcome in cases where this has occurred. Patients and methods The study comprised 113 children undergoing urethrocutaneous fistula repair between 1984 and 1996. Most of the fistulae were closed in two to three layers, with or without a transpositional skin flap. Tunica vaginalis or a scrotal dartos flap was used in patients with inadequate vascularized tissue adjacent to the fistula. Success rates were calculated for each attempt at fistula repair until the patient was cured. Results The median (range) age at primary fistula repair was 40 (18-169) months and the median follow-up after the most recent repair 7.5 (2.3-17) years. The overall success rate of primary fistula repair was 71%. Fistulae which were >2 mm (11 of 21, 52%) were more likely to recur than were those < or = 2 mm (22 of 92, 24%). Recurrence did not relate to the initial form of hypospadias repair, to the means of skin closure nor, with the exception of multiple lesions, to the location of the fistula. The success rates of subsequent repairs were 70% at the second and 50% at the third, fourth and fifth repairs. One child was cured at the sixth attempt. The use of tunica vaginalis or scrotal dartos as a 'waterproofing' layer was limited to the third or subsequent repairs and was successful in five of six cases. Conclusion A simple layered closure with or with no transpositional skin flap is effective in 71% of repairs. For recurrent fistulae, tissues from an unscarred area (tunica vaginalis or scrotal dartos layer) should be used to cover the fistula.

Adolescent↗

A crucial role of macrophages in the immune responses to oral DNA vaccination against hepatitis B virus in a murine model.

In the previous study, we had shown that live oral vaccination with Salmonella typhimurium delivering plasmid DNA-HBsAg (oral DNA vaccine) evoked a vigorous T cell response and a weak antibody response with predominant subclass IgG2a in mice, suggesting a significant involvement by professional antigen presenting cells (APC). In the present study, this possibility was further studied by infecting peritoneal macrophages (MPhi) with the oral DNA vaccine. Although, the infected cells could only express low level of the viral antigen, they nevertheless stimulated a vigorous lymphocyte proliferation of splenocytes from immune mice, induced these cells to elaborate interferon-gamma and stimulated development of HBV-specific cytotoxicity against target cells expressing the viral antigen. Infusion of the infected MPhi evoked a vigorous Th 1 and cytotoxic T lymphocyte (CTL) response and a weak IgG2a antibody response in mice, which was essentially the same as response to the oral DNA vaccine. In contrast, recombinant protein vaccine evoked a vigorous IgG1 antibody response and a weak T cell response. While, given intramuscularly, the same plasmid DNA vaccine as that contained in the oral DNA vaccine evoked a vigorous IgG1 antibody response and a moderate T cell response in these animals. It was concluded that professional APC may orchestrate the immune response to live oral DNA vaccine and it was of interest to note that different vaccine formulation and routes of administration evoke distinct immune response to HBV.

Administration, Oral↗

Folic acid supplements during pregnancy and risk of miscarriage.

BACKGROUND: Although taking supplements that contain 400 microg of folic acid before and during early pregnancy reduces a woman's risk for having a baby with a neural-tube defect (NTD), the effects of such supplements on other pregnancy outcomes remain unclear. We examined whether the use of such supplements affects the occurrence of miscarriage. METHODS: Participants were women in China who had taken part in a recent folic acid campaign to prevent NTDs and who had registered in this campaign before they became pregnant for the first time. We examined the risk for miscarriage among women who had confirmed pregnancies and who had or had not taken pills containing only 400 microg of folic acid before and during early pregnancy. RESULTS: The overall rate of miscarriage was 9.1% (2155/23806). The rates of miscarriage among women who had and had not taken folic acid pills before and during the first trimester were 9.0% and 9.3%, respectively (risk ratio 0.97 [95% CI 0.84-1.12]). The distributions of gestational age at pregnancy diagnosis and at miscarriage were similar for both groups of women. INTERPRETATION: In this population-based study of a cohort of women whose use of folic acid supplements while pregnant had been previously documented and who had been pregnant for the first time, we found no evidence that daily consumption of 400 microg of folic acid before and during early pregnancy influenced their risk for miscarriage.

Abortion, Spontaneous↗

Effects of retinoic acid and sodium butyrate on gene expression, histone acetylation and inhibition of proliferation of melanoma cells.

Retinoic acid (RA) induces growth-arrest of many tumor cell lines but it is an ineffective therapeutic against melanoma. We investigated whether the histone deacetylase (HDAC)-inhibitor sodium butyrate (BUT) can restore or potentiate the RA-response of RA-resistant human A375, and RA-responsive S91 murine melanoma cells. BUT induced expression of RARbeta and p21(waf1/cip1) mRNA in A375 cells but in S91 cells only p21(waf1/cip1) was induced. RA and BUT synergistically activated transcription of an RA-dependent reporter gene in S91, but not A375 cells. BUT increased histone H4-acetylation in both cell types. RA potentiated BUT-mediated inhibition of S91 cell proliferation, whereas A375 cells remained largely resistant to both compounds. HDAC-inhibitors may enhance the activity of RA on RA-responsive melanoma cells.

Animals↗

Epidermal growth factor (EGF) receptor kinase-independent signaling by EGF.

The ErbB family of receptors, which includes the epidermal growth factor receptor (EGFR), ErbB2, ErbB3, and ErbB4, mediate signaling by EGF-like polypeptides. To better understand the role of the EGFR tyrosine kinase, we analyzed signaling by a kinase-inactive EGFR (K721M) in ErbB-devoid 32D cells. K721M alone exhibited no detectable signaling capacity, whereas coexpression of K721M with ErbB2, but not ErbB3 or ErbB4, resulted in EGF-dependent mitogen-activated protein kinase (MAPK) activation. The kinase activity, but not tyrosine phosphorylation, of ErbB2 was required for EGF-induced MAPK activation. The presence of tyrosine phosphorylation sites in K721M was not a requisite for signaling, indicating that transphosphorylation of K721M by ErbB2 was not an essential mechanism of receptor activation. Conversely, the mutated kinase domain of K721M (residues 648-973) and tyrosine phosphorylation of at least one of the receptors were necessary. EGF was found to activate the pro-survival protein kinase Akt in stable cell lines expressing K721M and ErbB2 but, unlike cells expressing wild-type EGFR, was incapable of activating signal transducers and activators of transcription (STAT) or driving cell proliferation. These results demonstrate that EGFR-ErbB2 oligomers are potent activators of MAPK and Akt, and this signaling does not require EGFR kinase activity.

Cell Line↗

The combined effect of isolation and Fasciola hepatica infection on the life history traits of Fossaria cubensis.

Life history traits of Fossaria cubensis were compared between isolated and paired snails after infection with three miracidia of Fasciola hepatica. Four experimental groups were tested: isolated-unexposed, paired-unexposed, isolated-infected, and paired-infected. A repeated-measures ANOVA showed statistically significant interactions among isolation, infection, and age effects for shell size, number of egg masses per snail, number of eggs per snail, and number of viable eggs per snail. Isolated-unexposed snails exhibited the higher values of these variables and those of survival and finite and intrinsic rates of natural increase. Infection stimulated shell growth during the prepatent period, but differences were present only in paired snails since isolation causes a similar effect. Reproduction, in terms of the number of egg masses per snail and the number of eggs per mass per snail, decreases in the presence of parasitic infection, whereas isolation stimulates it. These effects were observed from early stages of infection.

Animals↗

Pharmacodynamics induced by direct electric current for the treatment of 5-fluorouracil resistant tumor: an animal experiment.

The repeated use of chemotherapy to treat patients with colorectal carcinoma may be limited by the fact it creates resistance cells. However, we have observed a remarkable decrease in certain types of drug resistance in patients treated with direct electric current. Experimental studies were therefore performed in animals to determine the differences in pharmacodynamics between chemotherapy with and that without electric treatment. Tumors were created in BALB/c mice by intradermal injection of 0.25 ml 4 x 10(6) Colon 26 cells/ml in the abdomen. Seven days later the mice were divided into two groups: controls and those that underwent electric treatment. Direct electric current (1,000 V, 0.2-0.8 microA) was passed between a platinum electrode inserted intradermally and the earth during and for 1 h after a single intravenous injection of 5-fluorouracil (5-FU; 12.5 mg ml(-1) kg(-1)). Peripheral blood samples were collected before and 5, 10, 20, 30, 45, and 60 min after the injection of 5-FU. Concentrations of 5-FU in the sera and tissues were measured by HPLC. The intratumoral concentrations of 5-FU in the electric treatment group were higher than those in the controls (P<0.05, two-factor analysis of variance), but the serum concentrations were not statistically different between the two groups. Pharmacodynamic changes were thus observed as a result of electrostatic treatment during chemotherapy. This elevated 5-FU concentration in the tumor tissue is considered one of the reasons for the effective inhibition of 5-FU resistance in clinical cases.

Animals↗