Search PubMed⌕ Search

Biomedical subjects

C Wong

Publications and source records attributed to C Wong.

At least 37 records · Page 2Linked to original sources
PubMed2004

A randomized trial of amifostine as a cytoprotectant for patients receiving myeloablative therapy for allogeneic hematopoietic stem cell transplantation.

We initiated a randomized study of amifostine (the organic thiophosphate formerly known as WR-2721) given to patients during myeloablative conditioning therapy for allogeneic bone marrow transplantation. Amifostine was given at a dose of 1000 mg/day of conditioning and was well tolerated if attention was given to serum calcium levels, blood pressure and antiemetics. Since August 1998, 60 patients (30 on each arm) have completed the study. There was no significant difference in the days to neutrophil or platelet engraftment in either arm of the study. Significantly, the duration of grade I-IV mucositis was decreased in the group that received amifostine (P=0.02). Also grade III or IV infections (P=0.008), duration of antibiotic therapy (P=0.03) and duration of fever (P=0.04) were significantly reduced with amifostine. However, there were no differences in the incidence of grade III or IV mucositis, liver toxicity or renal toxicity. There were also no differences in early mortality, relapse and long-term survival. We conclude that amifostine, while reducing the duration of mucositis and infections (possibly through some preservation of gut mucosal integrity), has a modest effect in allogeneic bone marrow transplants given the multiplicity of factors influencing organ toxicity and survival in this setting.

Adolescent↗
PubMed2004

Susceptibility to basal cell carcinoma: associations with PTCH polymorphisms.

Loss of function of the human patched gene (PTCH) is common and critical in basal cell carcinoma (BCC) development. Indirect evidence suggests polymorphism in PTCH mediates BCC risk. We studied 659 BCC cases and 300 controls to determine if exon 2(318), 3(429), 11(1552), 12(1665), 12(1686), 14(2199) and 23(3944) and intron 9(1336-135) and 15(2560+9)PTCH variants were sufficiently common for use in case-control studies, and if selected markers were associated with risk. Intron 15(2560+9) and exon 23(3944) variants were studied further. Their genotype frequencies were not significantly different in controls and cases, though frequency of the G(2560+9)-C(3944) haplotype was lower in all cases (odds ratio=0.44, p=0.009) and those stratified by BCC site and rate of development of further tumours. This association was not mediated by the extent of UVR exposure. We confirmed the robustness of these findings by showing these associations demonstrated similar odds ratios in two groups of randomly selected cases and controls, and using the false positive report probability (FPRP) approach described by Wacholder et al. (2004). The FPRP value (0.168) was in the noteworthy category. These data, showing for the first time that PTCH polymorphism mediates susceptibility, are compatible with reports showing that PTCH haploinsufficiency influences development of BCC precursor lesions.

Aged↗
PubMed2004

The value of a CT-guided fine needle aspirate in infants with lung abscess.

OBJECTIVE: To describe the range of pathogens isolated from a lung abscess in infants less than one year of age. To assess the role of direct culture from the abscess. METHODS: The two index cases were managed in 2002. An institution-based review was conducted of all infants up to one year of age diagnosed with a lung abscess between 1989 and 2002. Data sources were hospital's disease index and Neonatal Intensive Care Unit Audit database using ICD9 and ICD10 diagnostic codes for 'lung abscess'. RESULTS: Five infants, under the age of one year, were treated for a lung abscess. In the one case where the abscess was left-sided it was associated with a congenital cystic adenomatoid malformation of the lung. Pathogens were isolated following direct culture of the abscess in four cases. In three cases a single pathogen was isolated: pseudomonas aeruginosa, staphylococcus aureus and haemophilus influenzae. In one case a mixture of escherichia coli, streptococcus milleri and an anaerobe, propionibacteria, were cultured. Antibiotic therapy was directed at the identified pathogen(s) in all four cases. There was no mortality or recurrence. CONCLUSION: Predisposing factors for a lung abscess in infancy include prematurity, assisted ventilation, congenital lung anomaly and aspiration. Given the range of potential pathogens, direct culture by CT-guided fine needle aspiration is recommended to direct appropriate intravenous medical therapy provided the abscess is located peripherally.

Anti-Bacterial Agents↗
PubMed2003

Obesity as an independent predictor of posttransplant diabetes mellitus.

BACKGROUND: In the general population, there is a clear association between obesity and type 2 diabetes mellitus. However, the evidence of relationship between body mass index (BMI: weight/height(2)) and the risk of posttransplant diabetes mellitus (PTDM) is inconsistent when studied at a level of single center. The aim of our study was to determine if pretransplant BMI is an independent risk factor for PTDM at our center and to demonstrate the pattern of weight gain in patients who develop PTDM. METHODS: This is a retrospective analysis of renal allograft recipients at University of Colorado Hospital. The medical records of patients who received a kidney transplant from January 1998 to March 2001 were screened to identify the cases of PTDM. Controls were matched for immunosuppressive regimen, gender, and type of donor. A total of 18 cases and 36 controls were identified. RESULTS: The incidence of PTDM in our transplant population was 10%. Of these cases, 72% developed PTDM in the first 2 months after transplant, and 38% of them required insulin. On multivariate analysis, BMI was significantly associated with PTDM (adjusted odds ratio 1.22, 95% confidence interval 1.04-1.42) while controlling for number of rejections, age, and other factors. We also noticed that weight gain was significantly lower in patients who developed PTDM after transplantation. CONCLUSIONS: We conclude that obesity is an independent predictor of PTDM. The weight gain was significantly poor among patients who developed PTDM. Among all the risk factors for PTDM, obesity is the only modifiable risk factor before transplantation. Obese patients should be treated with a less diabetogenic immunosuppressive regimen and be counseled to lose weight before transplant.

Adult↗
PubMed2003

Alpha-asarone inhibits HMG-CoA reductase, lowers serum LDL-cholesterol levels and reduces biliary CSI in hypercholesterolemic rats.

Our results showed that alpha-asarone was an inhibitor of hepatic HMG-CoA reductase and that the administration of alpha-asarone at 80 mg/kg body wt. for 8 days decreased serum cholesterol by 38% (p < 0.001) in hypercholesterolemic rats. This alpha-asarone treatment affected mainly the serum LDL-cholesterol levels, leaving serum HDL-cholesterol lipoproteins unaffected, with a consequent decrease of 74% in the LDL/HDL ratio. In addition, alpha-asarone especially stimulated bile flow in hypercholesterolemic rats (60%), increasing the secretion of bile salts, phospholipids and bile cholesterol. The drug also reduced the cholesterol levels of gallbladder bile, whereas the concentration of phospholipids and bile salts increased only slightly, leading to a decrease in the cholesterol saturation index (CSI) of bile in the hypercholesterolemic rats. This CSI decrease and the increase in bile flow induced by alpha-asarone may account for the cholelitholytic effect of alpha-asarone. It seems that alpha-asarone induced clearance of cholesterol from the bloodstream and that the excess of hepatic cholesterol provided by LDL-cholesterol is diverted to bile sterol secretion via a bile choleresis process. The inhibition of HMG-CoA reductase and the increase in bile flow induced by alpha-asarone, as well as the decrease in the CSI, could then explain the hypocholesterolemic and cholelitholytic effects of alpha-asarone.

Allylbenzene Derivatives↗
PubMed2003

Detection of antibodies to polyomavirus SV40 in two central European countries.

Simian virus 40 (SV40) is significantly associated with some human cancers. However, the frequency of tumor-associated virus detection differs by geographic regions, so it is important to understand the status of SV40 infections in different populations. Poliovaccines potentially containing live SV40 were used in well-documented nationwide vaccination programs in Hungary and the Czech Republic that are reported here. We analyzed serum samples from periodic surveillance programs in those two countries for antibodies to SV40 using a specific plaque reduction neutralization assay. The prevalence of antibodies was between 1.3 and 8.7% in Hungary and from 1.0 to 4.0% in the Czech Republic. Females had a higher rate of antibodies than males, reaching in certain age groups 15.6% in Hungary and 8.3% in the Czech Republic. Antibodies to SV40 were found in similar proportions in both countries among persons not directly exposed to poliovaccines and subjects vaccinated in the era of SV40-free vaccines. Complexities and limitations of current serological approaches to epidemiological studies of SV40 in humans are discussed. These data suggest that SV40 may be present in these populations and emphasize the importance of follow-up studies to determine the pathogenesis of infections by this emerging human agent.

Adolescent↗
PubMed2003

Primary and secondary prevention of cardiac disease: bridging the two solitudes.

Clinical cardiovascular medicine uses two models for atherosclerosis: primary and secondary prevention. The essential goal of both strategies is risk factor modification, but intervention strategies and funding mechanisms to achieve these goals have traditionally differed, leading to professional and clinical segregation. The current system defies biological reality, patients and families are not well served, and important opportunities for improved care are lost. Developing a more inclusive paradigm of primary and secondary prevention remains a significant challenge. Such a paradigm could transform a longstanding trend of two solitudes where efforts in one area rarely benefit from new developments in the other. New models need to be developed that balance and integrate diagnostic, curative and preventive care, and that coordinate public health and personal health services. Working on 'bridging strategies' will help create synergies that will lead the way to further integration and will help improve the heart health of the population.

Coronary Artery Disease↗
PubMed2002

Isolation and characterisation of a novel rabbit sulfotransferase isoform belonging to the SULT1A subfamily.

Sulfotransferases (SULTs) catalyse the sulfonation of both endogenous and exogenous compounds including hormones, catecholamines, drugs and xenobiotics. While in most occasions, sulfonation is a detoxication pathway, in the case of certain drugs and carcinogens, it leads to metabolic activation. Since, the rabbit has been extensively used for both pharmacological and toxicological studies, the purpose of this study was to further characterise the sulfotransferase system of this animal. In the present study, a novel sulfotransferase isoform (GenBank Accession no. AF360872) was isolated from a rabbit liver cDNA lambdaZAP II library. The full-length sequence of the clone was 1138 bp long and contained a coding region of 888 bp encoding a cytosolic protein of 295 amino acids (deduced molecular weight 34,193 Da). The amino acid sequence of this novel SULT isoform showed >70% identity with members of the SULT1A subfamily of sulfotransferases from other species. Upon expression of the encoded rabbit sulfotransferase in Escherchia coli (E. coli), it was shown that the enzyme was capable of sulfonating both p-nitrophenol (K(m) and Vmax values of 0.15 microM and 897.5 nmol/min/mg protein, respectively) and dopamine (K(m) and V(max) values of 175.3 microM and 151.1 nmol/min/mg protein, respectively). Based on the sequence data obtained and substrate specificity, this new rabbit sulfotransferase was named rabSULT1A1. Immunoblotting was used to demonstrate that rabSULT1A1 protein is expressed in liver, duodenum, jejunum, ileum, colon and rectum.

Amino Acid Sequence↗
PubMed2002

Reduction in nocturnal functional bladder capacity is a common factor in the pathogenesis of refractory nocturnal enuresis.

OBJECTIVE: To evaluate the diurnal and nocturnal bladder reservoir function in patients with refractory primary nocturnal enuresis (PNE). PATIENTS AND METHODS: Ninety-five children (68 boys, 27 girls, mean age 9.3 years) with significant PNE (>/=3 wet nights/week) that was refractory to treatment with desmopressin +/- an enuretic alarm were assessed using detailed recording of voiding frequency and urinary volume both day and night, natural filling cystometry during the day and continuous cystometry with simultaneous electroencephalogram monitoring during sleep at night. RESULTS: Patients could be broadly categorized into two groups. Group A comprised those with normal daytime urodynamics and functional bladder capacity (FBC) on detailed frequency-volume recording, but who developed marked detrusor instability associated with a significant reduction in nocturnal FBC and small-volume voiding only after sleep at night (33 patients, 35%); and group B, those with abnormal daytime urodynamics and with reduced FBC and small-volume voiding both day and night, but who somehow managed to mask their bladder symptoms during the day (62 patients, 65%). There was no evidence of nocturnal polyuria in either group and the ratios of day : night urinary output volumes for type A and type B patients were 1.48 and 1.99, respectively. CONCLUSION: A reduction in nocturnal FBC, either occurring only after sleep at night in association with the appearance of detrusor instability in patients with normal daytime urodynamics and FBC, or as a manifestation of occult voiding dysfunction or bladder outlet obstruction that affects the bladder reservoir function both day and night, appears to be a common factor and probably the main cause for a mismatch between nocturnal urine output and bladder storage capacity in patients with severe bed-wetting that was refractory to treatment.

Adolescent↗
PubMed2002

Evaluation on the use of a portable unit versus the laboratory for the monitoring of International Normalized Ratio (INR) in orally anticoagulated patients.

INTRODUCTION: Measuring the International Normalized Ratio (INR) through a laboratory requires venipuncture and takes about 1 hour for results to be available. A portable monitor (CoaguChek Plus System), which measures the INR using fingerstick samples, is evaluated in this study to determine its clinical significance in anticoagulated and non-anticoagulated individuals. The hospital's outpatient and inpatient laboratories were also compared in the study. MATERIALS AND METHODS: Paired venous and capillary blood INRs were performed on anticoagulated patients using the monitor and the Singapore General Hospital (SGH) outpatient and inpatient laboratories (OPS and IPS labs). Paired INRs of control samples were also performed using the monitor and the IPS lab. RESULTS: We plotted the difference in INR by the 2 methods (monitor and OPS lab, n = 91) against their mean, and calculated the limits of agreement (95% of the difference would lie between -0.90 to 0.70). After a logarithmic transformation on the data, we found that for 95% of the cases, the OPS lab would differ from the monitor by 13% below to 14% above. There was also a marginal difference (95% limits of agreement of -0.14 to 0.10) when we compared the INR obtained from OPS and IPS laboratories (n = 43). Our control sample (n = 19) showed that the 95% confidence interval for the bias was -0.04 to 0.10. CONCLUSION: The monitor should be used with caution in patients with INR > 3. We suggest use of the monitor in situations where the non-anticoagulated state of a patient needs to be measured. There is a difference in INR measured by laboratories within the same institution.

Anticoagulants↗
PubMed2001

Heterogeneity of endothelial junctions is reflected by differential expression and specific subcellular localization of the three JAM family members.

Endothelial cells are linked to each other through intercellular junctional complexes that regulate the barrier and fence function of the vascular wall. The nature of these intercellular contacts varies with the need for permeability: For example, in brain the impervious blood-brain barrier is maintained by "tight" contacts between endothelial cells. By contrast, in high endothelial venules (HEVs), where lymphocytes continuously exit the bloodstream, the contacts are generally leaky. The precise molecular components that define the type of junction remain to be characterized. An immunoglobulin superfamily molecule named JAM-2, specifically expressed in lymphatic endothelial cells and HEVs, was recently identified. JAM-3 was cloned and characterized in the current study, and JAM-1, -2, and -3 were shown to form a novel protein family belonging to the larger cortical thymocyte Xenopus (CTX) molecular family. Using antibodies specific for each of the 3 family members, their specific participation in different types of cell-cell contact in vivo and their specific and differential localization in lateral contacts or tight junctions were demonstrated. Furthermore, it was shown that JAM-1 and JAM-2 differentially regulate paracellular permeability, suggesting that the presence of JAM-1, -2, or -3 in vascular junctions may play a role in regulating vascular function in vivo.

Amino Acid Sequence↗
PubMed2001

Protein kinase CK2 is involved in G2 arrest and apoptosis following spindle damage in epithelial cells.

p53 undergoes phosphorylation on several residues in response to cellular stresses that include UV and ionizing radiation, however the influence of spindle damage on this parameter is relatively unclear. Consequently, the effect of nocodazole on serine 392 phosphorylation was examined in two epithelial cell lines. We show that this process is dependent upon the stepwise activation of p38 mitogen-activated protein kinase (p38 MAPK) and protein kinase casein kinase 2 (CK2). Furthermore, this activation correlated with the biochemical regulation of the maturation-promoting factor (MPF, cdc2/cyclin B), as both DRB and antisense depletion of CK2, as well as SB203580 were associated with an inhibition of its activation in response to nocodazole. Strikingly, when the cell cycle characteristics of nocodazole treated cells were examined, we observed that depletion or inhibition of the catalytic subunit of CK2, in the presence of microtubule inhibitors, resulted in a compromise of the G2 arrest (spindle checkpoint). Furthermore, CK2-depleted, nocodazole treated cells demonstrated a dramatic reduction in the apoptotic cell fraction, confirming that these cells had been endowed with oncogenic properties. These changes were observed in both HeLa cells and HCT116 cells. We also show that this effect is dependent on the presence of functional wild-type p53, as this phenomenon is not apparent in HCT116 p53(-/-) cells. Collectively, our results indicate two novel roles for CK2 in the spindle checkpoint arrest, in concert with p53. Firstly, to maintain increased cyclinB/cdc2 kinase activity, as a component of G2 arrest, and secondly, a role in p53-mediated apoptosis. These findings may have implications for an improved understanding of abnormalities of the spindle checkpoint in human cancers, which is a prerequisite for defining future therapies.

Apoptosis↗
PubMed2001

Erythrocyte ankyrin promoter mutations associated with recessive hereditary spherocytosis cause significant abnormalities in ankyrin expression.

Ankyrin defects are the most common cause of hereditary spherocytosis (HS). In several kindreds with recessive, ankyrin-deficient HS, mutations have been identified in the ankyrin promoter that have been proposed to decrease ankyrin synthesis. We analyzed the effects of two mutations, -108T to C and -108T to C in cis with -153G to A, on ankyrin expression. No difference between wild type and mutant promoters was demonstrated in transfection or gel shift assays in vitro. Transgenic mice with a wild type ankyrin promoter linked to a human (A)gamma-globin gene expressed gamma-globin in 100% of erythrocytes in a copy number-dependent, position-independent manner. Transgenic mice with the mutant -108 promoter demonstrated variegated gamma-globin expression, but showed copy number-dependent and position-independent expression similar to wild type. Severe effects in ankyrin expression were seen in mice with the linked -108/-153 mutations. Three transgenic lines had undetectable levels of (A)gamma-globin mRNA, indicating position-dependent expression, and four lines expressed significantly lower levels of (A)gamma-globin mRNA than wild type. Two of four expressing lines showed variegated gamma-globin expression, and there was no correlation between transgene copy number and RNA level, indicating copy number-independent expression. These data are the first demonstration of functional defects caused by HS-related, ankyrin gene promoter mutations.

Animals↗
PubMed2001

Effects of olfactory bulbectomy on NMDA receptor density in the rat brain:.

Olfactory bulbectomy (OBX) transects the glutamatergic efferents from the olfactory bulbs, and the changes of glutamatergic N-methyl-D-aspartate (NMDA) receptor-mediated function are though to be involved in the behavioral deficits seen in OBX rats. In the present study, irritability scores in OBX male Wistar rats were correlated with discrete regional effects on NMDA receptor function measured using a [3H] MK-801 binding assay. Irritability scores, measured before and for 2 weeks after OBX, showed a gradual increase in irritability after OBX. A reduction of the NMDA receptor density was observed in the cerebral cortex and amygdala 16 days after OBX, but not in the striatum, olfactory tubercle, entorhinal cortex, and hippocampus. These results demonstrate that OBX causes changes in the NMDA receptor system in certain brain regions and suggest that these changes may be responsible for the behavioral deficits of OBX rats.

Animals↗
PubMed2001

Sulfated glycans and elevated temperature stimulate PrP(Sc)-dependent cell-free formation of protease-resistant prion protein.

A conformational conversion of the normal, protease- sensitive prion protein (PrP-sen or PrP(C)) to a protease-resistant form (PrP-res or PrP(Sc)) is commonly thought to be required in transmissible spongiform encephalopathies (TSEs). Endogenous sulfated glycosaminoglycans are associated with PrP-res deposits in vivo, suggesting that they may facilitate PrP-res formation. On the other hand, certain exogenous sulfated glycans can profoundly inhibit PrP-res accumulation and serve as prophylactic anti-TSE compounds in vivo. To investigate the seemingly paradoxical effects of sulfated glycans on PrP-res formation, we have assayed their direct effects on PrP conversion under physiologically compatible cell-free conditions. Heparan sulfate and pentosan polysulfate stimulated PrP-res formation. Conversion was stimulated further by increased temperature. Both elevated temperature and pentosan polysulfate promoted interspecies PrP conversion. Circular dichroism spectropolarimetry measurements showed that pentosan polysulfate induced a conformational change in PrP-sen that may potentiate its PrP-res-induced conversion. These results show that certain sulfated glycosaminoglycans can directly affect the PrP conversion reaction. Therefore, depending upon the circumstances, sulfated glycans may be either cofactors or inhibitors of this apparently pathogenic process.

Animals↗
PubMed2001

Human scFv antibody fragments specific for the epithelial tumour marker MUC-1, selected by phage display on living cells.

New anti-cancer agents are being developed that specifically recognise tumour cells. Recognition is dependent upon the enhanced expression of antigenic determinants on the surface of tumour cells. The tumour exposure and the extracellular accessibility of the mucin MUC-1 make this marker a suitable target for tumour diagnosis and therapy. We isolated and characterised six human scFv antibody fragments that bound to the MUC-1 core protein, by selecting a large naive human phage display library directly on a MUC-1-expressing breast carcinoma cell line. Their binding characteristics have been studied by ELISA, FACS and indirect immunofluorescence. The human scFv antibody fragments were specific for the tandem repeat region of MUC-1 and their binding is inhibited by soluble antigen. Four human scFv antibody fragments (M2, M3, M8, M12) recognised the hydrophilic PDTRP region of the MUC-1 core protein, which is thought to be an immunodominant region. The human scFv antibody fragments were stable in human serum at 37 degrees C and retained their binding specificity. For imaging or targeting to tumours over-expressing MUC-1, it might be feasible to use these human scFv, or multivalent derivatives, as vehicles to deliver anti-cancer agents.

Amino Acid Sequence↗