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Biomedical subjects

J Chan

Publications and source records attributed to J Chan.

At least 19 recordsLinked to original sources
PubMed2006

Methylenetetrahydrofolate reductase C677T and A1298C variants do not affect ongoing pregnancy rates following IVF.

BACKGROUND: There is concern that IVF could compromise normal imprinting and methylation of DNA. Methylenetetrahydrofolate reductase (MTHFR) regulates the flow of folic acid-derived, one-carbon moieties for methylation and is critical to early embryonic development. Therefore, we hypothesized that common polymorphisms in MTHFR could associate with IVF outcome. METHODS: MTHFR C677T and A1298C polymorphism genotyping was performed on 374 subjects for this study, representing 197 couples undergoing IVF in a university setting from July 2005 to January 2006. Analysis of variance (ANOVA), chi-square and/or multivariate analyses were used to assess whether these polymorphisms are associated with embryo quality or with ongoing pregnancy or spontaneous abortion rates. RESULTS: Allele frequencies for C677T ( p=0.67, q=0.33) and A1298C ( p=0.71, q=0.29) were in Hardy-Weinberg equilibrium. The C677T and A1298C variants, either alone or in combination, did not associate with embryo quality or short-term pregnancy outcome. CONCLUSIONS: The common polymorphisms in MTHFR are not associated with embryo quality, as defined by cell number or fragmentation score, or with short-term pregnancy outcomes. Therefore, in our population in which women receive adequate folic acid, MTHFR genotypes are not informative in explaining IVF failure. Further studies, however, examining birth outcomes and the other enzymes in the folic acid pathway are warranted.

Adult↗
PubMed2006

Size exclusion chromatography of microliter volumes for on-line use in low-pressure microfluidic systems.

We have developed a new cartridge format for on-line size exclusion processing in low-pressure, portable microfluidic devices. The described system allows size exclusion chromatography of microliter volumes (termed muL-SEC) to be performed with ready integration in complex protocols for continuous-flow sample processing and analysis. The refillable cartridge format was employed for the preparation of Bacillus subtilus spores lysed in the presence of a strong reducing agent. While the reducing agent is known to interfere with subsequent fluorescent labeling of the solubilized proteins, the described continuous-flow size exclusion processing allowed complete isolation of interferences from a 10-muL sample in 70 s. Following efficient labeling, the protein sample was injected and separated on-chip using gel electrophoresis. To increase the resolution, speed, and sample capacity of buffer exchange under low-pressure operation (40 psi), parameters such as the size exclusion resin, load volumes, flow rates, buffer composition, and cartridge geometry were optimized and are presented here. The muL-SEC analysis is compatible with automated sample preparation for microfluidic systems and has resulted in significantly increased analysis speed and throughput over benchtop methods. The presented technique has the potential to improve capabilities such as buffer exchange, size fractionation, and high-abundance protein removal-steps that are frequently required prior to on-chip, point-of-care, and mass spectrometric analyses.

Bacillus subtilis↗
PubMed2006

Photonic bus with loop signal routing and multichannel wavelength selection on a single silicon-on-insulator platform.

We have demonstrated a silicon-on-insulator-based photonic bus with integrated splitters, a demultiplexer, attenuators, and a multiplexer for loop signal routing and multichannel optical wavelength selection. The integrated photonic bus has demonstrated a 33+ dB optical cross talk, a 32+ dB extinction ratio, and a rise time of 7.6 micros with two-stage Mach-Zehnder attenuators.

Journal Article↗
PubMed2006

Renal risk and renoprotection among ethnic groups with type 2 diabetic nephropathy: a post hoc analysis of RENAAL.

Type 2 diabetes is becoming the leading cause of end-stage renal disease (ESRD) worldwide. Prevalence of ESRD and the antihypertensive response to renin-angiotensin system intervention are suggested to vary among different ethnicities. The Reduction in Endpoints in Non-insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan (RENAAL) study, which included different ethnic groups, demonstrated a renoprotective effect of losartan. A post hoc analysis from RENAAL was performed where we examined in each ethnic group the ESRD risk, identified independent predictors for ESRD, effect of degree of baseline albuminuria, effect of 6-month antiproteinuric response to therapy on ESRD, and renoprotective effect of losartan assessed by albuminuria reduction and ESRD. Baseline albuminuria was the strongest predictor for ESRD in every ethnic group. Albuminuria reduction was associated with reduced risk of ESRD while losartan reduced albuminuria in every ethnic group. When accounting for independent predictors of ESRD, losartan exhibited renoprotection in all ethnic groups. In this type 2 diabetic population with nephropathy, baseline albuminuria is the predominant risk parameter for ESRD; early antiproteinuric effect of losartan predicts long-term renoprotection; and losartan appears to be renoprotective in all ethnic groups. Since the RENAAL study was not powered to determine ethnic responses, these results underline the need for prospective trials where the aim is renal protection among different ethnic groups.

Albuminuria↗
PubMed2006

Concomitant developmental dental anomalies in Chinese children with dens evaginatus.

AIM: To determine the prevalence of concomitant developmental dental anomalies in a group of Chinese children with dens evaginatus. METHODS: The dental records and orthopantomograms of 10-15 year old children and adolescents who had been diagnosed with dens evaginatus in a school dental clinic were reviewed retrospectively. RESULTS: Four hundred and forty-eight of 7102 (6.3%) children were found to have dens evaginatus. Concomitant developmental dental anomalies were found in 77 children (17.2%). The most commonly seen dental anomalies in the study population were hypodontia, hyperdontia, microdontic maxillary lateral incisor, and dental impaction. The prevalence of these anomalies did not differ significantly to that found in the general Chinese population. When analysed separately, however, the prevalence of supernumerary premolars was found to be higher in children with dens evaginatus than in the general population, and the difference was statistically significant (P < 0.01). CONCLUSION: Supernumerary premolars appeared to be more prevalent in Chinese children with dens evaginatus than in the general population. There may be an association of supernumerary premolars with dens evaginatus in this study population.

Adolescent↗
PubMed2005

Delays in the administration of antibiotics are associated with mortality from adult acute bacterial meningitis.

BACKGROUND: Bacterial meningitis continues to cause high mortality. Few studies address the possible association between this mortality and antibiotic administration delays. AIM: To determine whether delays in antibiotic administration are associated with mortality from bacterial meningitis, and to identify inappropriate diagnostic-treatment sequences leading to such delays. DESIGN: Retrospective case record study. METHODS: We reviewed 123 cases of adult acute bacterial meningitis in 119 patients aged >/=16 years admitted to hospital from January 1990 to March 2002, using multivariate regression analysis to assess the association between meningitis mortality and door-to-antibiotic time (the time elapsed between emergency room presentation and antibiotics administration). RESULTS: The case fatality rate was 13% (16/123). Adjusted odds ratios (OR) for mortality were: 8.4 (95%CI 1.7-40.9) for door-to-antibiotic time >6 h; 39.4 (95%CI 4.3-358.1) for afebrility at presentation; and 12.6 (95%CI 2.2-72.0) for severely impaired mental status at presentation. Factors associated with a door-to-antibiotic time of >6 h were: (i) failure to administer antibiotics prior to transfer from another institution (OR 21.8); (ii) the diagnostic-treatment sequence: head CT then lumbar puncture, then antibiotics (OR 5.6); and (iii) the absence of the classic meningitis triad (OR 4.9). DISCUSSION: There is an independent incremental association between delays in administrating antibiotics and mortality from adult acute bacterial meningitis. Inappropriate diagnostic-treatment sequences were significant predictors of such treatment delays.

Acute Disease↗
PubMed2005

Acquired factor VIII inhibitor presenting as macular haemorrhage.

We report a rare case of idiopathic acquired factor VIII inhibitor in an 80-year old Chinese man presented as sudden onset of monocular blindness because of macular haemorrhage. This was complicated by painful glaucoma that did not respond to medical treatment. The patient died of cerebral haemorrhage shortly afterwards. Most cases of reported intraocular bleeding in acquired haemophiliacs are iatrogenic because of intraocular operations in undiagnosed cases, and spontaneous intraocular haemorrhage has never been reported. The literature reports of intraocular bleeding in hereditary and acquired haemophilia cases are summarized.

Aged↗
PubMed2005

An interinstitutional comparative study and validation of computer aided drusen quantification.

AIMS: To assess the portability and clinical applicability of a software program based on Photoshop (Adobe Systems Inc, San Jose, CA, USA) for digital drusen quantification. METHODS: Independent graders from the Digital Fundus Photo Reading Center of Columbia University and King's College Hospital used macular background levelling software to quantify the percentage of drusen in the central and middle Wisconsin subfields. 100 images of consecutive patients with choroidal neovascularisation in one eye and significant drusen in the other eye were analysed to determine suitability, and 10 were chosen for assessment by this software. RESULTS: Of the 10 images used in the interinstitutional validation, the random effects ANOVA for the central and middle subfields showed a high degree of interobserver agreement. The ICC for interobserver reliability was 0.83 (95% CI: 67 to 95) for the central subfield and 0.84 (95% CI: 69 to 99) for the middle subfield. Overall agreement with the manual grading results was good and the within patient coefficient of variation was about 20% for all the pairwise comparisons between observers and the manual stereo gradings. Of the 100 images used to assess practical applicability of the software, 79 were suitable for semiautomated analysis. 13 had extensive mixed retinal pigment epithelial (RPE) changes limiting drusen identification, five had a significant number of reticular drusen, which are poorly identified by the software, and three had multiple small areas of RPE atrophy, which are difficult to distinguish from drusen. CONCLUSIONS: The software was successfully used by two institutions demonstrating portability, with good correlation between graders and to the manual stereo grading. Digital drusen quantification was possible in 79% of the images analysed.

Analysis of Variance↗
PubMed2004

An in-vivo model to interrogate the transition from acute to chronic inflammation.

This study describes the modulation of the rodent foreign body giant cell (FBGC) response to subcutaneously implanted, biodegradable poly(lactide-co-glycolide)/calcium phosphate (PLGA/CaP) composites by application of a thin surface coat of calcium phosphate. Macroporous PLGA/CaP composite scaffolds, with interconnecting macroporosity, were half coated with a 3mm thick layer of CaP by immersion in simulated body fluid. Half-coated scaffolds were implanted subcutaneously in the dorsum of male Wistar rats for 1, 4 and 8 weeks. Specimens were embedded in paraffin and tissue sections evaluated by light microscopy with particular reference to the FBGC response. Histomorphometry revealed that FBGCs were in contact with 6% (+/- 3.5%) of the uncoated half, at 1 week, but no FBGCs were seen on the coated half. By 4 weeks, FBGCs were seen on both the uncoated and coated halves of the scaffolds with 87% (+/-10%) and 36% (+/-4%) FBGC/polymer contact respectively. By 8 weeks these FBGC contact percentages had risen to 97% (+/-0.45%) in the case of the uncoated halves of scaffolds, but decreased to 22% (+/-4%) in the case of the CaP-coated halves. Thus the CaP coating abrogated the FBGC response to the underlying polymer. Such a model may prove useful in providing an experimental system whereby both the mechanisms of biocompatibility and the transition from acute to chronic inflammation could be interrogated.

Absorbable Implants↗
PubMed2004

Compartment-specific localization of cannabinoid 1 (CB1) and mu-opioid receptors in rat nucleus accumbens.

Interactions between cannabinoid and opioid systems have been implicated in reward and drug seeking behaviors involving neuronal circuitry in the nucleus accumbens (Acb) shell and core. To determine the relevant sites, we examined the electron microscopic localization of cannabinoid type-1 (CB1) receptors and mu-opioid receptors in each Acb compartment in rat brain. CB1 receptor immunogold labeling was seen on the plasma membrane and within the cytoplasm of neuronal and glial profiles throughout the Acb. These neuronal profiles included somata and dendrites as well as axon terminals, many of which formed excitatory-type, asymmetric synapses with notable perforations that are often associated with synaptic plasticity. The number of CB1-labeled terminals within the neuropil of the Acb shell was significantly greater than in the core. Mu-opioid receptors were also detected in axonal and dendritic profiles. These dendrites were most prevalent in the Acb shell, where mu-receptors also were located in 21% of the dendritic profiles and 3% of the axon terminals containing CB1 receptors. More of the CB1-labeled terminals contacted dendrites expressing mu-opioid receptors in the shell (19%) compared with the core (13%). Conversely, of the synaptic mu-labeled terminals, 20% in the shell and 10% in the core contacted dendrites containing CB1 receptors. These findings provide ultrastructural evidence that cannabinoid-opioid interactions are mediated by activation of CB1 and mu-opioid receptors within the same or synaptically linked neurons in the Acb shell and core. They also suggest a particularly important role for presynaptic CB1 receptors in the reward circuit of the Acb shell.

Animals↗
PubMed2003

Regulation of the expression of the prostate-specific antigen by claudin-7.

Claudins are a family of proteins involved in forming tight junctions between cells. Here we describe two forms of claudin-7 (CLDN-7), a full-length form of CLDN-7 with 211 amino-acid residues and a C-terminal truncated form with 158 amino-acid residues. These two forms of CLDN-7 are able to regulate the expression of a tissue-specific protein, the prostate-specific antigen (PSA), in the LNCaP prostate cancer cell line. We also found that the expression of CLDN-7 is responsive to androgen stimulation in the LNCaP cell line, suggesting that this protein is involved in the regulatory mechanism of androgen. Both forms of claudin-7 are expressed in human prostate, kidney and lung samples, and in most samples, the full-length form of claudin-7 was predominant. However, in some prostate samples from healthy individuals, the truncated form of claudin-7 is predominantly expressed. Our results demonstrated that unlike other claudins, CLDN-7 has both structural and regulatory functions, and the two forms of CLDN-7 may be related to cell differentiation in organ development.

Adenocarcinoma↗
PubMed2003

Identification of fetal mesenchymal stem cells in maternal blood: implications for non-invasive prenatal diagnosis.

Strategies for genetic prenatal diagnosis on fetal cells in the maternal circulation have been limited by lack of a cell type present only in fetal blood. However, the recent identification of mesenchymal stem cells (MSC) in first trimester fetal blood offers the prospect of targeting MSC for non-invasive prenatal diagnosis. We developed protocols for fetal MSC enrichment from maternal blood and determined sensitivity and specificity in mixing experiments of male fetal MSC added to female blood, in dilutions from 1 in 10(5) to 10(8). We then used the optimal protocol to isolate fetal MSC from maternal blood in the first trimester, using blood taken after surgical termination of pregnancy as a model of increased feto-maternal haemorrhage. In model mixtures, we could amplify one male fetal MSC in 2.5 x 10(7) adult female nucleated cells, yielding a 100% pure population of fetal cells, but not one fetal MSC in 10(8) nucleated cells. Fetal MSC were identified in one of 20 post-termination maternal blood samples and confirmed as fetal MSC by XY fluorescence in-situ hybridization (FISH), immunophenotyping and osteogenic and adipogenic differentiation. We report the isolation of fetal MSC from maternal blood; however, their rarity in post-termination blood suggests they are unlikely to have a role in non-invasive prenatal diagnosis. Failure to locate these cells routinely may be attributed to their low frequency in maternal blood, to sensitivity limitations of enrichment technology, and/or to their engraftment in maternal tissues soon after transplacental passage. We speculate that gender microchimerism in post-reproductive maternal tissues might result from feto-maternal trafficking of MSC in early pregnancy.

Adult↗
PubMed2003

Nitric oxide in experimental joint inflammation. Benefit or detriment?

The host response to infection or injury initiates a cascade of events involving recruitment of leukocytes and the release of multiple inflammatory mediators. One of these mediators, nitric oxide (NO), not only represents an important microbicidal agent in host defense, but also functions as a biological signaling and effector molecule in inflammation and immunity. However, overproduction of NO can be autotoxic and contribute to tissue damage and has been implicated in pathogenesis of tumors, and infectious, autoimmune and chronic degenerative diseases. NO is generated via constitutive and inducible nitric oxide synthases (iNOS) which catalyze the oxidation of a guanidino nitrogen associated with L-arginine. Whereas endothelial NOS (eNOS) and neuronal NOS (nNOS) are constitutively expressed, iNOS is transcriptionally induced by bacterial constituents and inflammatory mediators, including TNF alpha and IL-1. In an experimental model of bacterial component-induced joint inflammation and tissue degradation, functionally distinct roles of the constitutive NOS and iNOS were demonstrated. Following systemic delivery of an arthritogenic dose of streptococcal cell walls (SCW), these bacterial peptidoglycan-polysaccharide complexes disseminate and target the peripheral joints, liver and spleen of the treated animals. Following deposition of the SCW in the peripheral joints, an initial innate inflammatory response to the bacterial components progresses into an adaptive immune response with the recruitment and activation of mononuclear phagocytes and T lymphocytes. With the release of cytokines and inflammatory mediators, there is an upregulation of gene expression for iNOS, but not the constitutive nNOS or eNOS. Nonetheless, the constitutive NOS isoforms, regulated by calcium fluxes and interaction with calmodulin, may also enhance NO production. Increased release of NO was detected not only in the synovium, but also in the circulation, and plasma levels of nitrate plus nitrite, the stable products of NO reactions, correlated with disease progression. Following inhibition of NO production with nonspecific NOS inhibitors, such as N(G)-monomethyl-L-arginine, which target all three isoforms, there is a striking therapeutic benefit with reduced signs and symptoms of erosive arthritis. In contrast, selective targeting of iNOS with N-iminoethyl-L-lysine resulted in exacerbation of the synovial inflammation and degradation of joint structures. Based on these data, it appears that the constitutive isoforms of NOS contribute to the pathophysiology of the arthropathy, and that induced NOS and NO may function, in part, in a protective pathway. Moreover, the suppression of NO following treatment with TNF alpha antagonists results in reduced inflammation and the associated synovial pathology. Collectively, these data implicate discrete roles for the NOS isoforms in the emergence of local tissue pathology and underscore the need to define the specific pathways that are being targeted for interventional strategies.

Animals↗