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Biomedical subjects

S Wong

Publications and source records attributed to S Wong.

At least 19 recordsLinked to original sources
PubMed2007

Characterization of Anaplasma phagocytophilum major surface protein 5 and the extent of its cross-reactivity with A. marginale.

Major surface protein 5 (Msp5) of Anaplasma marginale is highly conserved in the genus Anaplasma and the antigen used in a commercially available competitive enzyme-linked immunosorbent assay (cELISA) for serologic identification of cattle with anaplasmosis. This study analyzes the degrees of conservation of Msp5 among various isolates of Anaplasma phagocytophilum and the extent of serologic cross-reactivity between recombinant Msp5 (rMsp5) of Anaplasma marginale and A. phagocytophilum. The msp5 genes from various isolates of A. phagocytophilum were sequenced and compared. rMsp5 proteins of A. phagocytophilum and A. marginale were used separately in an indirect ELISA to detect cross-reactivity in serum samples from humans and dogs infected with A. phagocytophilum and cattle infected with A. marginale. Serum samples were also tested with a commercially available competitive ELISA that uses monoclonal antibody ANAF16C1. There were 100% sequence identities in the msp5 genes among all of the A. phagocytophilum isolates from the United States and a horse isolate from Sweden. Sheep isolates from Norway and dog isolates from Sweden were 99% identical to one another but differed in 17 base pairs from the United States isolates and the horse isolate. Serologic cross-reactivity was identified when serum samples from cattle infected with A. marginale were reacted with rMsp5 of A. phagocytophilum and when serum samples from humans and dogs infected with A. phagocytophilum were reacted with rMsp5 of A. marginale in an indirect-ELISA format. Serum samples from dogs or humans infected with A. phagocytophilum did not cross-react with rMsp5 of A. marginale when tested with the commercially available cELISA. These results suggest that rMsp5 of A. phagocytophilum is highly conserved among United States and European isolates and that serologic distinction between A. phagocytophilum and A. marginale infections cannot be accomplished if rMsp5 from either organism is used in an indirect ELISA.

Anaplasma marginale↗
PubMed2006

Investigation and management of severe hyponatraemia in a hospital setting.

AIMS: To evaluate the assessment and management of severe hyponatraemia in a large teaching hospital. METHODS: Inpatients with serum sodium <125 mmol/l were identified prospectively from a laboratory database over a six month period. Notes were examined and data extracted. Case notes were carefully reviewed retrospectively by a consultant endocrinologist with regard to accuracy of the diagnosis and the appropriateness of investigations and management. RESULTS: 104 patients with a serum sodium <125 mmol/l were identified. Mean (SD) age was 69 (14), 52% were female, mean hospital stay was 16 (12) days, and overall mortality 27%. Adequate investigations were rarely performed. Only 28 (26%) had plasma osmolality measured, 29 (27%) urine osmolality, 11 (10%) urinary sodium, 8 (8%) plasma cortisol, and 2 (2%) a short Synacthen test. Comparing the "ward" and "specialist review" diagnoses, there were significant discrepancies for "no cause found" (49% v 27%, p<0.001), alcohol (6% v 11% p<0.01), and syndrome of inappropriate antidiuresis (20% v 32%, p = 0.001). Treatment was often illogical with significant management errors in 33%. These included fluid restriction and intravenous saline given together (4%) and fluid restriction in diuretic induced hyponatraemia (6%). Mortality was higher in the group with management errors (41% v 20% p = 0.002). CONCLUSION: Severe hyponatraemia is a serious condition, but its investigation and evaluation is often inadequate. Some treatment patterns seem to be arbitrary and illogical, and are associated with higher mortality.

Adult↗
PubMed2006

Non-smokers seeking help for smokers: a preliminary study.

OBJECTIVES: To examine the phenomenon of non-smokers spontaneously taking action to seek help for smokers; to provide profiles of non-smoking helpers by language and ethnic groups. SETTING: A large, statewide tobacco quitline (California Smokers' Helpline) in operation since 1992 in California, providing free cessation services in English, Spanish, Mandarin, Cantonese, Korean, and Vietnamese. SUBJECTS: Callers between August 1992 and September 2005 who identified themselves as either white, black, Hispanic, American Indian, or Asian (n = 349,110). A subset of these were "proxies": callers seeking help for someone else. For more detailed analysis, n = 2143 non-smoking proxies calling from October 2004 through September 2005. MAIN OUTCOME MEASURES: Proportions of proxies among all callers in each of seven language/ethnic groups; demographics of proxies; and proxies' relationships to smokers on whose behalf they called. RESULTS: Over 22 000 non-smoking proxies called. Proportions differed dramatically across language/ethnic groups, from mean (+/-95% confidence interval) 2.7 (0.3)% among English-speaking American Indians through 9.3 (0.3)% among English-speaking Hispanics to 35.3 (0.7)% among Asian-speaking Asians. Beyond the differences in proportion, however, remarkable similarities emerged across all groups. Proxies were primarily women (79.2 (1.7)%), living in the same household as the smokers (65.0 (2.1)%), and having either explicit or implicit understandings with the smokers that calling on their behalf was acceptable (90.0 (1.3)%). CONCLUSIONS: The willingness of non-smokers to seek help for smokers holds promise for tobacco cessation and may help address ethnic and language disparities. Non-smoking women in smokers' households may be the first group to target.

Adolescent↗
PubMed2006

Creutzfeldt-jakob disease involvement of rolandic cortex: a quantitative apparent diffusion coefficient evaluation.

BACKGROUND: Previous reports have suggested that abnormally reduced water diffusivity and T2 prolongation involving cerebral gray matter in patients with early sporadic Creutzfeldt-Jakob disease (sCJD) involves all areas of neocortex with similar frequency, except for primary sensorimotor cortex (Rolandic cortex) and visual cortex. Rolandic cortex often appears to be spared even in the presence of extensive surrounding neocortical signal intensity abnormality in adjacent frontal and parietal gray matter. A quantitative apparent diffusion coefficient (ADC) analysis was designed to investigate whether this unusual pattern results from pathophysiologic sparing of Rolandic cortex or from reduced conspicuity of signal intensity abnormality on MR imaging echo-planar diffusion-weighted images (epiDWI) related to unknown underlying features of Rolandic cortex. METHODS: ADC maps were derived from epiDWI of 6 patients with sCJD and 8 control patients. Bilateral regions of interest were manually selected in precentral gyri, superior frontal gyri, postcentral gyri, supramarginal gyri, thalamus, putamen, and caudate nuclei. ADC and relative ADC (rADC) values were calculated for each region of interest. RESULTS: Patients with CJD had significantly lower ADC values than control patients in all areas (P < or = 0.05). The trend toward decreased ADC values in the deep nuclei correlates well with previously published reports. rADC were not significantly different between CJD and control groups in any area (P > 0.25 in all cases). CONCLUSION: Quantitative ADC measurements in patients with early sCJD demonstrate a similar degree of reduced water diffusivity in the primary somatosensory cortex as in other neocortical areas, despite the normal appearance of these areas on visual inspection of epiDWI.

Aged↗
PubMed2005

Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist.

Drugs that antagonize D2-like receptors are effective antipsychotics, but the debilitating movement disorder side effects associated with these drugs cannot be dissociated from dopamine receptor blockade. The "atypical" antipsychotics have a lower propensity to cause extrapyramidal symptoms (EPS), but the molecular basis for this is not fully understood nor is the impact of inverse agonism upon their clinical properties. Using a cell-based functional assay, we demonstrate that overexpression of Galphao induces constitutive activity in the human D2-like receptors (D2, D3, and D4). A large collection of typical and atypical antipsychotics was profiled for activity at these receptors. Virtually all were D2 and D3 inverse agonists, whereas none was D4 inverse agonist, although many were potent D4 antagonists. The inverse agonist activity of haloperidol at D2 and D3 receptors could be reversed by mesoridazine demonstrating that there were significant differences in the degrees of inverse agonism among the compounds tested. Aripiprazole and the principle active metabolite of clozapine NDMC [8-chloro-11-(1-piperazinyl)-5H-dibenzo [b,e] [1,4] diazepine] were identified as partial agonists at D2 and D3 receptors, although clozapine itself was an inverse agonist at these receptors. NDMC-induced functional responses could be reversed by clozapine. It is proposed that the low incidence of EPS associated with clozapine and aripiprazole used may be due, in part, to these partial agonist properties of NDMC and aripiprazole and that bypassing clozapine blockade through direct administration of NDMC to patients may provide superior antipsychotic efficacy.

Animals↗
PubMed2005

A randomized controlled trial of surgery vs steroid injection for carpal tunnel syndrome.

BACKGROUND: Decompressive surgery and steroid injection are widely used forms of treatment for carpal tunnel syndrome (CTS) but there is no consensus on their effectiveness in comparison to each other. The authors evaluated the efficacy of surgery vs steroid injection in relieving symptoms in patients with CTS. METHODS: The authors conducted a randomized, single blind, controlled trial. Fifty patients with electrophysiologically confirmed idiopathic CTS were randomized and assigned to open carpal tunnel release (25 patients) or to a single injection of steroid (25 patients). Patients were followed up at 6 and 20 weeks. The primary outcome was symptom relief in terms of the Global Symptom Score (GSS), which rates symptoms on a scale of 0 (no symptoms) to 50 (most severe). Nerve conduction studies and grip strength measurements were used as secondary outcome assessments. RESULTS: At 20 weeks after randomization, patients who underwent surgery had greater symptomatic improvement than those who were injected. The mean improvement in GSS after 20 weeks was 24.2 (SD 11.0) in the surgery group vs 8.7 (SD 13.0) in the injection group (p < 0.001); surgical decompression also resulted in greater improvement in median nerve distal motor latencies and sensory nerve conduction velocity. Mean grip strength in the surgical group was reduced by 1.7 kg (SD 5.1) compared with a gain of 2.4 kg (SD 5.5) in the injection group. CONCLUSION: Compared with steroid injection, open carpal tunnel release resulted in better symptomatic and neurophysiologic outcome but not grip strength in patients with idiopathic carpal tunnel syndrome over a 20-week period.

Adult↗
PubMed2005

Resveratrol, an extract of red wine, inhibits lipopolysaccharide induced airway neutrophilia and inflammatory mediators through an NF-kappaB-independent mechanism.

Consumption of a naturally occurring polyphenol, resveratrol, in particular through drinking moderate amounts of red wine, has been suggested to be beneficial to health. A plethora of in vitro studies published demonstrate various anti-inflammatory actions of resveratrol. The aim of this research was to determine whether any of these anti-inflammatory effects translate in vivo in a rodent model of LPS induced airway inflammation. Resveratrol reduced lung tissue neutrophilia to a similar magnitude as that achieved by treatment with budesonide. This was associated with a reduction in pro-inflammatory cytokines and prostanoid levels. Interestingly, the reduction did not appear to be due to an impact on NF-kappaB activation or the expression of the respective genes as suggested by various in vitro publications. These results suggest that resveratrol may possess anti-inflammatory properties via a novel mechanism. Elucidation of this mechanism may lead to potential new therapies for the treatment of chronic inflammation.

Animals↗
PubMed2005

The Biomolecular Interaction Network Database and related tools 2005 update.

The Biomolecular Interaction Network Database (BIND) (http://bind.ca) archives biomolecular interaction, reaction, complex and pathway information. Our aim is to curate the details about molecular interactions that arise from published experimental research and to provide this information, as well as tools to enable data analysis, freely to researchers worldwide. BIND data are curated into a comprehensive machine-readable archive of computable information and provides users with methods to discover interactions and molecular mechanisms. BIND has worked to develop new methods for visualization that amplify the underlying annotation of genes and proteins to facilitate the study of molecular interaction networks. BIND has maintained an open database policy since its inception in 1999. Data growth has proceeded at a tremendous rate, approaching over 100 000 records. New services provided include a new BIND Query and Submission interface, a Standard Object Access Protocol service and the Small Molecule Interaction Database (http://smid.blueprint.org) that allows users to determine probable small molecule binding sites of new sequences and examine conserved binding residues.

Animals↗
PubMed2005

Post-operative radiochemotherapy for gastric cancer: adoption and adaptation.

AIMS: Intergroup study 0116 (INT-0116) showed an 11% absolute improvement in 3-year survival with post-operative radiochemotherapy for gastric cancer, but reported 33% severe acute GI toxicity using conventional simulation with large fields. We adapted the treatment using conformal radiotherapy techniques and assessed toxicity and outcome in 20 consecutive patients. METHODS: A conformal radiotherapy technique previously developed for gastric lymphoma was adapted to treat the target volume defined in INT-0116. The five-field plan used a large anterior field, plus asymmetrically matched upper AP:PA fields and lower lateral fields. Consecutive patients with ECOG PS 0-2 and stage IB-IV non-metastatic gastric cancer were treated with 5-FU (425 mg/m2 daily x 5 days) and leucovorin (20 mg/m2 daily x 5 days) for one cycle prior to and two cycles following concurrent radiation (45 Gy/25 fractions) with identical drug dosages on the first 4 and last 3 days of radiation. Acute toxicity was prospectively recorded weekly using RTOG and NCI common toxicity criteria. Patient charts were reviewed in November 2003 and late toxicity and outcome were recorded. RESULTS: Nineteen of 20 patients completed radiotherapy and 14 completed all chemotherapy cycles. One patient died of neutropenic sepsis. Maximum acute toxicity [grade (number)] was: 5(1), 4(0), 3(4), 2(10), 1(4), 0(1). There were two grade 1 late toxicities. Two-year overall survival is 70% (95% confidence interval: 50-90). CONCLUSIONS: Conformal radiotherapy may improve acute toxicity (25% grade 3 or greater toxicity as compared with 41% reported in INT-0116). Survival is comparable to that achieved in the INT-0116 treatment arm (approximately 60% at 2 years). INT-0116 results can be achieved outside a study setting; however, further efforts to improve treatment efficacy and minimize toxicity are warranted.

Adult↗
PubMed2005

Pharmacogenomics education: International Society of Pharmacogenomics recommendations for medical, pharmaceutical, and health schools deans of education.

Pharmacogenomics would be instrumental for the realization of personalized medicine in coming decades. Efforts are evident to clarify the potential bioethical, societal, and legal implications of key pharmacogenomics-based technologies projected to be soon introduced into the core practice of medicine. In sharp contrast, a lack of sufficient attention to educational aspects of pharmacogenomics, both for professionals and for society at large, is evident. In order to contribute to this discussion, a 'Pharmacogenomics Education Forum' was held on October 2, 2004 during the 3rd Annual Meeting of the International Society of Pharmacogenomics (ISP) at Santorini, Greece. The participants, members of the ISP Pharmacogenomics Education Forum, after deliberate discussions, proposed a document of 'Background Statement' and 'Recommendations and Call for Action' addressed to Deans of Education at Medical, Pharmaceutical, and Health Schools globally. This document has been considered by the education committee of the International Society of Pharmacogenomics and the result is presented here. We hope that this call would be listened to, and soon followed by beneficial action, ultimately leading to enhanced implementation of personalized medicine into core medical education and practice.

Curriculum↗
PubMed2005

Does pulmonary rehabilitation give additional benefit over tiotropium therapy in primary care management of chronic obstructive pulmonary disease? Randomized controlled clinical trial in Hong Kong Chinese.

OBJECTIVE: To evaluate whether multidisciplinary pulmonary rehabilitation programme (PRP) provides additional benefit over tiotropium therapy in managing chronic obstructive pulmonary disease (COPD) in primary care. DESIGN: A randomized controlled trial to analyse the difference in outcomes of COPD patients receiving tiotropium plus PRP vs. tiotropium treatment alone. SETTING: Two primary care teaching clinics affiliated with a university which serves a population of 600,000. PARTICIPANTS: Fifty primary care COPD patients. METHODS: Fifty subjects underwent spirometry and their status of COPD was confirmed by using the Vitalograph Gold Standard. They were then assessed by the 6-min walking distance (6MWD), Peak Visual Analogue Scale (Peak VAS) and Chronic Respiratory Disease Questionnaire (CRQ). All subjects were given tiotropium to optimize their treatment. After a 6-week period, half were randomized to the intervention group (i.e. receiving PRP), whereas the rest were randomized to control group which received only medication. Spirometry, 6MWD, Peak VAS and CRQ were performed in both groups at 6 weeks, 12 weeks and 3 months. OUTCOMES: Spirometry, 6MWD, Peak VAS and CRQ. RESULTS: Significant improvement (P < 0.05) was seen in 6MWD, symptoms of dyspnoea measured by Peak VAS and CRQ. The improvement was sustained at 3-month follow-up. However, no additional significant improvement was seen in the intervention group when compared with control. CONCLUSION: Tiotropium therapy has improved health outcomes in COPD patients in primary care settings. A 6 weekly PRP did not give any additional benefits in patients already given tiotropium.

Aged↗
PubMed2004

Construction of stabilized proteins by combinatorial consensus mutagenesis.

We constructed stabilized variants of beta-lactamase (BLA) from Enterobacter cloacae by combinatorial recruitment of consensus mutations. By aligning the sequences of 38 BLA homologs, we identified 29 positions where the E.cloacae gene differs from the consensus sequence of lactamases and constructed combinatorial libraries using mixtures of mutagenic oligonucleotides encompassing all 29 positions. Screening of 90 random isolates from these libraries identified 15 variants with significantly increased thermostability. The stability of these isolates suggest that all tested mutations make additive contributions to protein stability. A statistical analysis of sequence and stability data identified 11 mutations that made stabilizing contributions and eight mutations that destabilized the protein. A second-generation library recombining these 11 stabilizing mutations led to the identification of BLA variants that showed further stabilization. The most stable variant had a mid-point of thermal denaturation (Tm) that was 9.1 degrees C higher than the starting molecule and contained eight consensus mutations. Incubation of three stabilized BLA variants with several proteases showed that all tested isolates have significantly increased resistance to proteolysis. Our data demonstrate that combinatorial consensus mutagenesis (CCM) allows the rapid generation of protein variants with improved thermal and proteolytic stability.

Amino Acid Sequence↗
PubMed2004

Sole BCR-ABL inhibition is insufficient to eliminate all myeloproliferative disorder cell populations.

Protein kinase inhibitors can be effective in treating selected cancers, but most suppress several kinases. Imatinib mesylate has been useful in the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia and B cell acute lymphoblastic leukemia through the inhibition of BCR-ABL tyrosine kinase activity. Imatinib mesylate has also been shown to inhibit KIT, ARG, and platelet-derived growth factor receptors alpha and beta, and potentially other tyrosine kinases. We have produced a mutant allele of BCR-ABL (T315A) that is uniquely inhibitable by the small molecule 4-amino-1-tert-butyl-3-(1-naphthyl)pyrazolo[3,4-d]pyrimidine and used it to demonstrate that sole suppression of BCR-ABL activity was insufficient to eliminate BCR-ABL(+) KIT(+)-expressing immature murine myeloid leukemic cells. In contrast, imatinib mesylate effectively eliminated BCR-ABL(+) KIT(+)-expressing leukemic cells. In the cellular context of mature myeloid cells and Pro/Pre B cells that do not express KIT, monospecific BCR-ABL inhibition was quantitatively as effective as imatinib mesylate in suppressing cell growth and inducing apoptosis. These results suggest that the therapeutic effectiveness of small molecule drugs such as imatinib mesylate could be due to the inhibitor's ability to suppress protein kinases in addition to the dominant target.

Apoptosis↗
PubMed2004

[Therapeutic management of intra-abdominal and retroperitoneal soft tissue sarcomas].

In this article, we review the diagnostics, therapy, follow-up, and prognosis of intra-abdominal and retroperitoneal soft tissue sarcomas. There are descriptions and discussion of the surgical techniques, advantages and disadvantages of various types and combinations of adjuvant and neoadjuvant therapies, therapy in case of nonresectability, and procedures for desmoid tumors. Further, treatment results, control methods, and studies on new therapeutic approaches are presented.

Abdominal Neoplasms↗