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Biomedical subjects

J Chu

Publications and source records attributed to J Chu.

At least 19 recordsLinked to original sources
PubMed2007

Characterization of the expression and activation of the epidermal growth factor receptor in squamous cell carcinoma of the skin.

BACKGROUND: Locally advanced skin cancers including squamous cell carcinoma (SCC) of the skin are increasing in incidence. Patients are often elderly with significant comorbidities and therapy can be difficult. New targeted therapies, such as treatment directed at the epidermal growth factor receptor (EGFR), may be effective and less toxic in these patients. However, before designing appropriate clinical trials it is necessary to characterize the expression and activation of targets such as the EGFR to evaluate the rationale of using EGFR inhibitors (EGFRIs) in the treatment of this type of cancer. OBJECTIVES: To characterize the expression and activation by phosphorylation of EGFR in SCC of the skin by quantitative Western blotting using the LiCor immunofluorescence detection system with validation by immunohistochemistry. Secondary objectives were to evaluate downstream targets of EGFR expression and activation in SCC of the skin and to examine the associations between EGFR, pathological features and clinical behaviour of these tumours. METHODS: Twenty-one mainly locally advanced skin SCCs collected in our institution and stored in our tissue bank over a 4-year period were used for the study. RESULTS: Nine of 21 (43%) tumours expressed EGFR above background. Of those nine, five expressed phosphorylated EGFR. There was no correlation with downstream activation of canonical signalling pathways, pathological features or clinical behaviour. CONCLUSIONS: EGFR is expressed in a minority of tumours and then is not always activated. These results show that, before designing a trial with a targeted agent such as an EGFRI in SCC of the skin, it is important to verify the presence of the appropriate target to maximize the best outcome.

Adolescent↗
PubMed2006

Chronic gestational exposure to ethanol causes insulin and IGF resistance and impairs acetylcholine homeostasis in the brain.

In fetal alcohol syndrome (FAS), cerebellar hypoplasia is associated with impaired insulin-stimulated survival signaling. This study characterizes ethanol dose-effects on cerebellar development, expression of genes required for insulin and insulin-like growth factor (IGF) signaling, and the upstream mechanisms and downstream consequences of impaired signaling in relation to acetylcholine (ACh) homeostasis. Pregnant Long Evans rats were fed isocaloric liquid diets containing 0%, 2%, 4.5%, 6.5%, or 9.25% ethanol from gestation day 6. Ethanol caused dose-dependent increases in severity of cerebellar hypoplasia, neuronal loss, proliferation of astrocytes and microglia, and DNA damage. Ethanol also reduced insulin, IGF-I, and IGF-II receptor binding, insulin and IGF-I receptor tyrosine kinase activities, ATP, membrane cholesterol, and choline acetyltransferase (ChAT) expression. In vitro studies linked membrane cholesterol depletion to impaired insulin receptor binding and insulin-stimulated ChAT. In conclusion, cerebellar hypoplasia in FAS is mediated by insulin/IGF resistance with attendant impairments in energy production and ACh homeostasis.

Acetylcholine↗
PubMed2006

Assessment of the use of spent copper slag for land reclamation.

The shortage of waste landfill space for waste disposal and the high demand for fill materials for land reclamation projects in Singapore have prompted a study on the feasibility of using spent copper slag as fill material in land reclamation. The physical and geotechnical properties of the spent copper slag were first assessed by laboratory tests, including hydraulic conductivity and shear strength tests. The physical and geotechnical properties were compared with those of conventional fill materials such as sands. The potential environmental impacts associated with the use of the spent copper slag for land reclamation were also evaluated by conducting laboratory tests including pH and Eh measurements, batch-leaching tests, acid neutralization capacity determination, and monitoring of long-term dissolution of the material. The spent copper slag was slightly alkaline, with pH 8.4 at a solid : water ratio of 1 : 1. The batch-leaching test results show that the concentrations of the regulated heavy metals leached from the material at pH 5.0 were significantly lower than the maximum concentrations for their toxicity limits referred by US EPA's Toxicity Characteristic Leaching Procedure (TCLP). It was also found that the material is unlikely to cause significant change in the redox condition of the subsurface environment over a long-term period. In terms of physical and geotechnical properties, the spent copper slag is a good fill material. In general, the spent copper slag is suitable to be used as a fill material for land reclamation.

Conservation of Natural Resources↗
PubMed2005

Effects of cement on redistribution of trace metals and dissolution of organics in sewage sludge and its inorganic waste-amended products.

The suitability of using cement-stabilized sludge products as artificial soils in earth works was evaluated. The sludge products investigated were cemented sludge, cement-treated clay-amended sludge (SS+MC), and cement-treated copper slag-amended sludge (SS+CS). The leachability of lead (Pb), zinc (Zn), copper (Cu), and chromium (Cr) were assessed using the sequential extraction technique, toxicity characteristic leaching procedure (TCLP), NEN 7341 availability test, and column leaching test. The results indicated that Zn leachability was reduced in all the cement-stabilized sludge products. In contrast, Cu was transferred from the organic fraction to the readily leachable phases in the cement-stabilized sludge products and therefore exhibited increased leachability. The increased Cu leachability could be attributed to dissolution of humic substances in the sludge as a result of elevated pH. Good correlation between dissolved organic carbon (DOC) and heavy metal leaching from the cement-stabilized sludge products was observed in the column leaching experiment. Even with a cement percentage as small as 12.5%, calcium silicate hydrate (C-S-H) was formed in the SS+MC and SS+CS products. Inclusion of the marine clay in the SS+MC products could reduce the leaching potentials of Zn, and this was the great advantage of the marine clay over the copper slag for sludge amendment.

Metals, Heavy↗
PubMed2005

Direct comparison of 18F-fluorodeoxyglucose coincidence gamma camera tomography with gallium scanning for the staging of lymphoma.

BACKGROUND: The present study compared the performance of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) using a coincidence dual-head gamma camera (FDG Co-PET) with 67gallium scinti graphy (GS) in pretreatment staging of lymphoma. METHODS: A total of 46 patients underwent FDG Co-PET, computed tomography (CT) scanning and GS for pretreatment staging of lymphoma (40 newly diagnosed and recurrence) between November 1997 and December 1999. RESULTS: Histological subgroups comprised low grade (8 patients), intermediate grade (25) high-grade (3) non-Hodgkin's lymphoma and Hodgkin's disease (10). Based on clinical assessment, CT scan findings and biopsy, 100 nodal sites and 15 extra-nodal sites were deemed positive. FDG Co-PET was superior to GS in nodal site positivity rate (97%vs 79%, P < 0.0001). Compared with GS, FDG Co-PET detected 39 more abnormal sites in 22 patients (48%), of which 28 sites were validated by biopsy, CT and/or progress FDG Co-PET scanning. There was only one proven false negative FDG site in the spleen. CT + FDG Co-PET led to upstaging in 2 patients (4%), compared to CT + GS. CONCLUSION: FDG Co-PET shows potential for providing an accurate means for pretreatment staging of lymphoma and can detect extra sites of disease activity compared to GS.

Adult↗
PubMed2005

Determination of penumbral widths from ion chamber measurements.

We have investigated methods of reconstructing beam profiles in the penumbral region using a set of axially symmetric chambers, differing only in the detector radius. In principal, the transfer functions, or kernels, of such chambers should be functions of radius only. Three chambers of radii 0.297, 0.556, and 0.714 cm have been used. The transfer functions of the chambers can be determined by deconvolving the profiles measured with each detector with the PPMC profile. The results indicate that the transfer functions can be parametrized accurately as a Gaussian cutoff at 1.75(r), with (r) the average radius of the chamber. Deconvolution of the measured profiles with the transfer functions yields a profile that agrees with the PPMC profile to +/- 0.5 mm over the 20-80% penumbra.

Biophysical Phenomena↗
PubMed2004

Electrical twitch obtaining intramuscular stimulation (ETOIMS) for myofascial pain syndrome in a football player.

BACKGROUND: Flare up of acute lower back pain associated with myofascial pain syndrome (MPS) may require various forms of treatment including activity restriction and bracing. Electrical twitch obtaining intramuscular stimulation (ETOIMS) is a promising new treatment. It involves the use of a strong monopolar electromyographic needle electrode for electrical stimulation of deep motor end plate zones in multiple muscles in order to elicit twitches. CASE REPORT: An elite American football player with MPS symptoms failed to respond to standard treatments. He then received ETOIMS which completely alleviated the pain. After establishing pain control, the athlete continued with a further series of treatments to control symptoms of muscle tightness. CONCLUSIONS: ETOIMS has a promising role in pain alleviation, increasing and maintaining range of motion, and in providing satisfactory athletic performance during long term follow up.

Adult↗
PubMed2001

PKCbeta modulates antigen receptor signaling via regulation of Btk membrane localization.

Mutations in Bruton's tyrosine kinase (Btk) result in X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. While targeted disruption of the protein kinase C-beta (PKCbeta) gene in mice results in an immunodeficiency similar to xid, the overall tyrosine phosphorylation of Btk is significantly enhanced in PKCbeta-deficient B cells. We provide direct evidence that PKCbeta acts as a feedback loop inhibitor of Btk activation. Inhibition of PKCbeta results in a dramatic increase in B-cell receptor (BCR)-mediated Ca2+ signaling. We identified a highly conserved PKCbeta serine phosphorylation site in a short linker within the Tec homology domain of Btk. Mutation of this phosphorylation site led to enhanced tyrosine phosphorylation and membrane association of Btk, and augmented BCR and FcepsilonRI-mediated signaling in B and mast cells, respectively. These findings provide a novel mechanism whereby reversible translocation of Btk/Tec kinases regulates the threshold for immunoreceptor signaling and thereby modulates lymphocyte activation.

3T3 Cells↗
PubMed2001

Separation of six uremic middle molecular compounds by high performance liquid chromatography and analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

BACKGROUND: Since the postulation of uremic middle molecule (UMM) hypothesis made by Babb et al. [Trans-Am Soc Artif Intern Organs 18 (1972) 98], there has been great interest in the separation and identification of the role of UMM. However, few of the compounds isolated from UMM fractions were demonstrated to play an important role in humans. Thus, the separation and identification of the real UMM is essential for UMM research. METHODS: Urine and serum samples from uremic patients and healthy subjects were separated by gel permeation chromatography. Two presumed UMM fractions, A and B, were obtained from uremic sera and urine, normal urine, but not normal sera. Fraction A was further isolated by anion exchange chromatography and a series of sub-peaks were obtained. The sub-fraction A-3 obtained in the second step was desalted on a Sephadex G-15 column, and characterized by IR, UV and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Further separation of sub-fraction A-3 was performed by high performance liquid chromatography (HPLC). RESULTS: By gel permeation chromatography, two UMM peaks (A and B) were detected at 206 nm in normal urine, uremic sera, but they were barely noticed in the profile of normal sera. In contrast, the absorption at 206 nm of fractions A and B from uremic serum and urine were smaller than that of fractions A and B from normal urine. Fractions A from different origins were resolved into eight to nine sub-peaks at 230 nm by anion exchange chromatography. One of these sub-peaks, A-3, was detected in uremic serum and normal urine, but is undetectable in uremic urine. After desalting, sub-fraction A-3 was separated into two parts designated as A-3-I and A-3-II. MALDI-TOF-MS revealed that fraction A-3-I and A-3-II from two origins were identical, respectively-fraction A-3-I contained three components with MW 839.69, 1007.94 and 2015.16 and fraction A-3-II consisted of another three components with MW 873.69, 1106.67 and 1680.28. Six middle molecular compounds in sub-fraction A-3 were thoroughly resolved by HPLC. CONCLUSION: Our results demonstrated that the UMM sub-fraction A-3 contains the real UMM in the MW range of 800-2015 Da. By multi-step chromatographic isolation, six real middle molecular compounds were purified and characterized with MALDI-TOF-MS. It is likely that three of these UMM compounds are important, as they readily accumulated in sera of uremic patients, but are normally excreted in healthy subjects.

Adult↗
PubMed2001

Pharmacodynamic-mediated reduction of temozolomide tumor concentrations by the angiogenesis inhibitor TNP-470.

The angiogenic phenotype is associated with increased tumor neovascularization and a state of vascular hyperpermeability to macromolecules. Angiogenesis inhibitors could reverse these processes, resulting in tumor capillaries that have normal membrane permeability. It was proposed that the switch from a hyperpermeable to a normal permeable state could have the untoward effect of decreasing tumor concentrations of anticancer drugs coadministered with angiogenesis inhibitors. The current investigation evaluated a potential drug interaction between the angiogenesis inhibitor O-(N-chloroacetyl-carbamoyl)-fumagillol (TNP-470) and the alkylating agent temozolomide (TMZ), in xenograft models that differentially expressed vascular endothelial growth factor (VEGF), a driving force for angiogenesis. Nude rats bearing either s.c. low VEGF (V-) or high VEGF (V+) or intracerebral V+ gliomas were administered either a multiple-dose regimen of TNP-470 or vehicle control. One day after the last dose of vehicle or TNP-470, a steady-state dosing regimen of TMZ was administered with subsequent collection and high-performance liquid chromatography analysis of plasma and either tumor homogenate or tumor microdialysis steady-state TMZ concentrations, and in some cases [5-(3-methyltriazen-1-yl)imidazole-4-carboximide] MTIC, its active metabolite. Microvessel density (MVD) was quantitated by image analysis using an anti-CD31 method. Statistical analyses of pharmacokinetic and pharmacodynamic end points in the control and TNP-470 treatment groups were completed by nonparametric tests. In both the s.c. and intracerebral V+ models, TNP-470 treatment produced significant reductions in TMZ tumor concentrations and tumor:plasma concentration ratios compared with control, being reduced an average of 25% and 50% in the s.c. and intracerebral tumors, respectively. MTIC concentrations in V+ s.c. tumors also were reduced by 50% in the presence of TNP-470. Consistent with the lower extent of neovascularization in the V- tumors, TMZ and MTIC tumor concentrations were not different in TNP-470 and control treatment groups in s.c. tumors. MVD was reduced by TNP-470 compared with vehicle control in the V+ tumors, but was unaltered in V- tumors, attesting to the use of MVD as a pharmacodynamic end point and the effectiveness of TNP-470 as an angiogenesis inhibitor. Angiogenesis inhibitor's pharmacodynamic actions on tumor angiogenesis can produce a reduction in tumor concentrations of coadministered anticancer agents. It is increasingly important to understand the pharmacokinetic and pharmacodynamic behavior of each class of drug so that optimal dosing regimens can be designed.

Angiogenesis Inhibitors↗
PubMed2001

The secondary amine/nitric oxide complex ion R(2)N[N(O)NO](-) as nucleophile and leaving group in S9N)Ar reactions.

Ions of structure R(2)N[N(O)NO](-) and their alkylation products have seen increasing use as nitric oxide (NO)-generating agents for biomedical research applications. Here we show that such diazeniumdiolate anions can readily displace halide from a variety of electrophilic aza- or nitroaromatic substrates to form O(2)-arylated derivatives of structure R(2)N-N(O)=N-OAr. The site of arylation and the cis arrangement of the oxygens were confirmed by X-ray crystallography. Displacement by various nucleophiles showed R(2)N[N(O)NO](-) to be a reasonably good leaving group, with rate constants for displacement by hydroxide, methoxide, and isopropylamine that were between those of chloride and fluoride in the S(N)Ar reactions we surveyed. The Meisenheimer intermediate could be spectrally observed. These O(2)-aryl diazeniumdiolates proved capable of reacting with the nucleophilic sulfur of the HIV-1 p7 nucleocapsid protein's zinc finger assembly to eject the zinc, disrupting a structural motif critical to viral replication and suggesting possible utility in the drug discovery realm.

Amines↗
PubMed2001

Social influences on androgen levels in the southern leopard frog, Rana sphenocephala.

Social cues play an important role in modulating neuroendocrine and hormonal states in many vertebrates. Social cues in the form of conspecific advertisement calls have been demonstrated to modulate plasma androgen levels in male Rana sphenocephala, the Southern leopard frog. Male R. sphenocephala were captured and brought to the laboratory for testing. Animals were exposed to one of two acoustical environments: a recording of an active conspecific breeding chorus or a recording of the same chorus in which all the spectral frequencies had been digitally shifted 500 Hz higher. Following 12 nights of exposure to either stimulus, plasma androgen levels were assessed by radioimmunoassay and gonadal morphology was examined to compare group differences. Plasma levels of dihydrotestosterone were significantly higher in males exposed to the conspecific chorus, compared with males exposed to the altered version of the chorus. Gonadal morphology did not differ between the two groups. These results suggest that in addition to environmental cues such as rainfall and other seasonal changes, social cues may also serve as environmental synchronizers among anurans to coordinate reproductive effort.

Acoustic Stimulation↗
PubMed2001

Initial experience of vocal cord evaluation using grey-scale, real-time, B-mode ultrasound.

BACKGROUND: To evaluate whether grey-scale, real-time, B-mode ultrasound (US) is a reliable alternative to nasopharyngoscopy for assessing vocal cord function post-thyroid and post-parathyroid surgery. METHODS: A prospective validation study was undertaken comparing grey-scale, real-time, B-mode vocal cord US with the standard of nasopharyngoscopy in 100 consecutive patients undergoing thyroid and parathyroid surgery between 1 February 1999 and 31 August 1999, with seven patients with known cord palsy. The sensitivity and specificity of grey-scale, real-time vocal cord US for the detection of vocal cord palsy when compared to the standard of nasopharyngoscopy was analysed. RESULTS: In the postsurgical group, there were six nerves (3.2% of the nerves at risk) transient and no permanent vocal cord palsies. US identified four of six transient palsies and reported two false negatives and three false positives. US identified four of seven cord palsies in the non-surgical group with known cord palsy. Analysis of the 107 combined patients showed US had sensitivity of 62% (8/13), specificity of 97% (91/94), a positive predictive value of 73% (8/11) and a negative predictive value of 95% (91/96) for detecting cord paralysis compared to the standard of nasopharyngoscopy. CONCLUSION: Despite the enthusiasm of earlier reports, our initial experience with grey-scale, real-time, B-mode US suggests it is not a reliable alternative to nasopharyngoscopy for assessing vocal cord function post-thyroid and post-parathyroid surgery. Further recruitment of patients with known vocal cord palsy is required to confirm or refute these initial impressions.

Female↗
PubMed2001

Is surgical decontamination definitive treatment of "body-packers"?

The current recommendations for body-packers are based on packet content, the presence of drug toxicity, or of bowel obstruction. Asymptomatic patients are usually treated with activated charcoal and whole bowel irrigation (WBI). Surgical removal of packets is advocated in symptomatic cocaine body-packers and in those with bowel obstruction. Currently, surgery is regarded as definitive. However, we report 2 body-packers who show the limitations of this technique. These cases show the importance of confirming the absence of drug packets in the gastrointestinal (GI) tract as the definitive end-point in the treatment of body-packers.

Adult↗