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Biomedical subjects

C Zhang

Publications and source records attributed to C Zhang.

At least 73 records · Page 4Linked to original sources
PubMed2004

Fluorescence-enhanced optical imaging of large phantoms using single and simultaneous dual point illumination geometries.

Fluorescence-enhanced optical tomography is typically performed using single point illumination and multiple point collection measurement geometry. Single point illumination is often insufficient to illuminate greater volumes of large phantoms and results in an inadequate fluorescent signal to noise ratio (SNR) for the majority of measurements. In this work, the use of simultaneous multiple point illumination geometry is proposed for acquiring a large number of fluorescent measurements with a sufficiently high SNR. As a feasibility study, dual point excitation sources, which are in-phase, were used in order to acquire surface measurements and perform three-dimensional reconstructions on phantoms of large volume and/or significant penetration depth. Measurements were acquired in the frequency-domain using a modulated intensified CCD imaging system under different experimental conditions of target depth (1.4-2.8 cm deep) with a perfect uptake optical contrast. Three-dimensional reconstructions of the fluorescence absorption from the dual point illumination geometry compare well with the reconstructions from the single point illumination geometry. Targets located up to 2 cm deep were located successfully, establishing the feasibility of reconstructions from simultaneous multiple point excitation sources. With improved excitation light rejection, multiple point illumination geometry may prove useful in reconstructing more challenging domains containing deeply embedded targets. Image quality assessment tools are required to determine the optimal measurement geometry for the largest set off imaging tasks.

Breast↗
PubMed2003

Relationship between cardiac protein tyrosine phosphorylation and myofibrillogenesis during axolotl heart development.

The axolotl, Ambystoma mexicanum, is a useful system for studying embryogenesis and cardiogenesis. To understand the role of protein tyrosine phosphorylation during heart development in normal and cardiac mutant axolotl embryonic hearts, we have investigated the state of protein tyrosine residues (phosphotyrosine, P-Tyr) and the relationship between P-Tyr and the development of organized sarcomeric myofibrils by using confocal microscopy, two-dimensional isoelectric focusing (IEF)/SDS-polyacrylamide gel electrophoresis (PAGE) and immunoblotting analyses. Western blot analyses of normal embryonic hearts indicate that several proteins were significantly tyrosine phosphorylated after the initial heartbeat stage (stage 35). Mutant hearts at stages 40-41 showed less tyrosine phosphorylated staining as compared to the normal group. Two-dimensional gel electrophoresis revealed that most of the proteins from mutant hearts had a lower content of phosphorylated amino acids. Confocal microscopy of stage 35 normal hearts using phosphotyrosine monoclonal antibodies demonstrated that P-Tyr staining gradually increased being localized primarily at cell-cell boundaries and cell-extracellular matrix boundaries. In contrast, mutant embryonic hearts showed a marked decrease in the level of P-Tyr staining, especially at sites of cell-cell and cell-matrix junctions. We also delivered an anti-phosphotyrosine antibody (PY 20) into normal hearts by using a liposome-mediated delivery method, which resulted in a disruption of the existing cardiac myofibrils and reduced heartbeat rates. Our results suggest that protein tyrosine phosphorylation is critical during myofibrillogenesis and embryonic heart development in axolotls.

Ambystoma mexicanum↗
PubMed2003

A novel assay for discovery and characterization of pro-apoptotic drugs and for monitoring apoptosis in patient sera.

We have developed an apoptosis assay based on measurement of a neoepitope of cytokeratin-18 (CK18-Asp396) exposed after caspase-cleavage and detected by the monoclonal antibody M30. The total amount of caspase-cleaved CK18 which has accumulated in cells and tissue culture media during apoptosis is measured by ELISA. The sensitivity is sufficient for use in the 96-well format to allow high-through-put screening of drug libraries. We here describe strategies allowing classification of pro-apoptotic compounds according to their profiles of induction of apoptosis in the presence of pharmacological inhibitors. The time course of induction of CK18 cleavage can furthermore be used to distinguish structurally similar compounds. We propose that compounds that induce rapid CK18 cleavage have mechanisms of actions distinct from conventional genotoxic and microtubuli-targeting agents, and we present one example of an agent that induces almost immediate mitochondrial depolarization and cytochrome c release. Finally, CK18-Asp396 cleavage products are released from cells in tissue culture, and presumably from tumor cells in vivo. These products can be measured in sera from cancer patients. We present evidence suggesting that it will be possible to use the M30-ELISA assay for measuring chemotherapy-induced apoptosis in patient sera, opening possibilities for monitoring therapy.

Antibodies, Monoclonal↗
PubMed2003

Hyperparathyroidism-jaw tumour syndrome.

Amongst hyperparathyroidism-related syndromes, hyperparathyroidism-jaw tumour syndrome is one of the least common and relatively unknown but its clinical and genetic aspects are not less interesting or important. With the recent identification of its genes, we can now better characterize the disease, both clinically and genetically, which will certainly impact the field of endocrinology and oncology. In this article, we review the clinico-pathological features and genetic basis of this syndrome with the hope that it will create awareness and interest in this disease amongst clinicians and basic scientists.

Genes, Tumor Suppressor↗
PubMed2003

The influence of maternal triglyceride levels on infant birth weight in Peruvian women with pre-eclampsia.

OBJECTIVE: Hypertriglyceridemia is an important pathophysiological feature of pre-eclampsia, a complication associated with retarded fetal growth. We studied the relation between third-trimester maternal triglyceride levels and infant birth weight in 113 pre-eclamptic and 150 normotensive women. METHODS: Plasma triglyceride concentrations were determined using enzymatic methods. The relative risk of infant low birth weight (LBW, < 2500 g) was determined using logistic regression to calculate the odds ratio (OR) and 95% confidence interval (CI). RESULTS: Approximately 12% of normotensive and 32% of pre-eclamptic mothers delivered LBW infants. After adjusting for maternal age, parity, pre-pregnancy adiposity and gestational age at delivery, pre-eclamptics were 2.3 times more likely to deliver a LBW infant as compared with normotensive mothers (95% CI 1.1-5.0). There was no association between plasma triglyceride level and infant birth weight. Pearson correlation coefficients for birth weight and triglyceride were r = 0.10 (p = 0.24) and r = 0.06 (p = 0.49) for normotensive and pre-eclamptic women, respectively. The OR for LBW associated with high triglyceride level (> or = 233 mg/dl) was 0.8 (95% CI 0.2-3.1) and 0.9 (95% CI 0.4-2.0) for the two groups. Triglyceride levels did not modify the pre-eclampsia and LBW association. Compared to normotensive women with low triglyceride level (< 233 mg/dl), the ORs for LBW were 1.2 (95% CI 0.4-4.0), 3.6 (95% CI 1.0-12.5) and 2.8 (95% CI 1.0-8.0) for normotensive and high triglyceride, pre-eclamptic and low triglyceride, and pre-eclamptic and high triglyceride mothers, respectively. CONCLUSIONS: Hypertriglyceridemia in late pregnancy, considered a maternal adaptation to maintain stable fuel distribution to the fetus, was not related to birth weight.

Adult↗
PubMed2003

A comparison of exact and approximate adjoint sensitivities in fluorescence tomography.

Many approaches to fluorescence tomography utilize some form of regularized nonlinear least-squares algorithm for data inversion, thus requiring repeated computation of the Jacobian sensitivity matrix relating changes in observable quantities, such as emission fluence, to changes in underlying optical parameters, such as fluorescence absorption. An exact adjoint formulation of these sensitivities comprises three terms, reflecting the individual contributions of 1) sensitivities of diffusion and decay coefficients at the emission wavelength, 2) sensitivities of diffusion and decay coefficients at the excitation wavelength, and 3) sensitivity of the emission source term. Simplifying linearity assumptions are computationally attractive in that they cause the first and second terms to drop out of the formulation. The relative importance of the three terms is thus explored in order to determine the extent to which these approximations introduce error. Computational experiments show that, while the third term of the sensitivity matrix has the largest magnitude, the second term becomes increasingly significant as target fluorophore concentration or volume increases. Image reconstructions from experimental data confirm that neglecting the second term results in overestimation of sensitivities and consequently overestimation of the value and volume of the fluorescent target, whereas contributions of the first term are so low that they are probably not worth the additional computational costs.

Algorithms↗
PubMed2002

Dalitz plot analysis of the decay D(+)-->K(-)pi(+)pi(+) and indication of a low-mass scalar Kpi resonance.

We study the Dalitz plot of the decay D(+)-->K(-)pi(+)pi(+) with a sample of 15090 events from Fermilab experiment E791. Modeling the decay amplitude as the coherent sum of known Kpi resonances and a uniform nonresonant term, we do not obtain an acceptable fit. If we allow the mass and width of the K(*)(0)(1430) to float, we obtain values consistent with those from PDG but the chi(2) per degree of freedom of the fit is still unsatisfactory. A good fit is found when we allow for the presence of an additional scalar resonance, with mass 797+/-19+/-43 MeV/c(2) and width 410+/-43+/-87 MeV/c(2). The mass and width of the K(*)(0)(1430) become 1459+/-7+/-5 MeV/c(2) and 175+/-12+/-12 MeV/c(2), respectively. Our results provide new information on the scalar sector in hadron spectroscopy.

Journal Article↗
PubMed2002

Ca(2+)-independent but voltage-dependent secretion in mammalian dorsal root ganglion neurons.

We have investigated the Ca(2+) dependence of vesicular secretion from the soma of dorsal root ganglion (DRG) neurons, which secrete neuropeptides by exocytosis of dense-core vesicles. In patch-clamped somata of rat DRG neurons, we found a depolarization-induced membrane capacitance increase (DeltaC(m)) in the absence of extracellular Ca(2+) and in the presence of a Ca(2+) chelator (BAPTA) in the intracellular solution. Depletion of internal Ca(2+) stores by thapsigargin in the Ca(2+)-free bath also did not block the DeltaC(m), indicating that Ca(2+) release from internal Ca(2+) stores may not have been involved. Furthermore, the Ca(2+)-independent DeltaC(m) was blocked by whole-cell dialysis with tetanus toxin and was accompanied by pulsatile secretion of false transmitters, as detected by amperometric measurements. These results indicate the existence of Ca(2+)-independent but voltage-dependent vesicular secretion (CIVDS) in a mammalian sensory neuron.

Action Potentials↗
PubMed2002

Reelin gene alleles and susceptibility to autism spectrum disorders.

A polymorphic trinucleotide repeat (CGG/GCC) within the human Reelin gene (RELN) was examined as a candidate gene for autism spectrum disorders (ASDs). This gene encodes a large extracellular matrix protein that orchestrates neuronal positioning during corticogenesis. The CGG-repeat within the 5' untranslated region of RELN exon 1 was examined in 126 multiple-incidence families. The number of CGG repeats varied from three to 16 in affected individuals and controls, with no expansion or contraction observed during maternal (n = 291) or paternal (n = 287) transmissions in families with autistic probands. Although the frequencies of the RELN alleles and genotypes in affected children were not different from those in the comparison group, a family-based association test (FBAT) showed that the larger RELN alleles (> or = 11 repeats) were transmitted more often than expected to affected children (S = 43, E(S) = 34.5, P = 0.035); this was particularly the case for the 13-repeat RELN allele (S = 22, E(S) = 16, P = 0.034). Affected sib-pair (ASP) analysis found no evidence of excess sharing of RELN alleles in affected siblings. The impact of genotypes with large alleles (> or = 11 repeats) on the phenotypes in individuals with ASD was analyzed by ANOVA in a subset of the families for which results of the Autism Diagnostic Interview-Revised were available. Children with large RELN alleles did not show any difference in scores for questions related to the core symptoms of autistic disorder, but there was a tendency for children with at least one large RELN allele to have an earlier age at first phrase (chi(2) = 3.538, P = 0.06). Thus, although the case-control and affected sib-pair findings did not support a role for RELN in susceptibility to ASD, the more powerful family-based association study demonstrated that RELN alleles with larger numbers of CGG repeats may play a role in the etiology of some cases of ASD, especially in children without delayed phrase speech.

Autistic Disorder↗
PubMed2002

Inhibition of human neuroblastoma cell proliferation and EGF receptor phosphorylation by gangliosides GM1, GM3, GD1A and GT1B.

The inhibitory action of gangliosides GT1B, GD1A, GM3 and GM1 on cell proliferation and epidermal growth factor receptor (EGFR) phosphorylation was determined in the N-myc amplified human neuroblastoma cell line NBL-W. The IC50 of each ganglioside was estimated from concentration-response regressions generated by incubating NBL-W cells with incremental concentrations (5-1000 microm) of GT1B, GD1A, GM3 or GM1 for 4 days. Cell proliferation was quantitatively determined by a colourimetric assay using tetrazolium dye and spectrophotometric analysis, and EGFR phosphorylation by densitometry of Western blots. All gangliosides assayed, with the exception of GM1, inhibited NBL-W cell proliferation in a concentration-dependent manner. The IC50s for gangliosides GT1B [molecular weight (MW) 2129], GM3 (MW 1236), and GD1A (MW 1838) were (mean +/- SEM) 117 +/- 26, 255 +/- 29, and 425 +/- 44 m, respectively. In contrast, the IC50 for GM1 (MW 1547) could not be determined. Incubation of NBL-W cells with epidermal growth factor (EGF) concentrations ranging from 0.1 to 1000 ng/ml progressively increased cell proliferation rate, but it plateaued at concentrations above 10 ng/ml. EGFR tyrosine phosphorylation, however, was incrementally stimulated by EGF concentrations from 1 to 100 ng/ml. The suppression of EGF-induced EGFR phosphorylation differed for each ganglioside, and their respective inhibitory potencies were as follows: EGFR phosphorylation [area under curve (+ EGF)/area under curve (- EGF)]: control (no ganglioside added) = 8.2; GM1 = 8.3; GD1A = 6.7; GM3 = 4.87, and GT1B = 4.09. The lower the ratio, the greater the inhibitory activity of the ganglioside. Gangliosides GD1A and GT1B, which have terminal N-acetyl neuraminic acid moieties, as well as one and two N-acetyl neuraminic acid residues linked to the internal galactose, respectively, both inhibited cell proliferation and EGFR phosphorylation. However, GD1A was a more potent suppressor of cell proliferation and GT1B most effective against EGFR phosphorylation. GM3, which only has a terminal N-acetyl neuraminic acid, inhibited cell proliferation and EGFR phosphorylation almost equivalently. These data suggest that gangliosides differ in their potency as inhibitors of NBL-W neuroblastoma cell proliferation and EGFR tyrosine phosphorylation, and that perturbations in the differential expression of membrane glycosphingolipids may play a role in modulating neuroblastoma growth.

Animals↗
PubMed2001

Multivariate outlier detection and remediation in geochemical databases.

In this study, outliers are classified into three types: (1) range outliers; (2) spatial outliers; and (3) relationship outliers, defined as observations that fall outside of the values expected from correlation within the dataset. The multivariate methods of principal component analysis (PCA), multiple regression analysis (MRA) and an autoassociation neural network (AutoNN) method are applied to a dataset comprising 203 samples of rare earth element (REE) concentrations in soils of Jamaica which shows the expected good correlations between the elements. PCA is shown to be effective in detection of high value range outliers, while AutoNN and MRA are effective in detection of relationship outliers. A backpropagation neural network was used to predict the 'expected values' of the outliers. Four obvious relationship outliers with unexpected low Sm concentrations were selected as an example for remediation. The predicted Sm values were confirmed on remeasurement. Neural network methods, with the advantages of being model-free and effective in solving non-linear relationship problems, appear to provide an automated and effective way for the quality control of environmental databases.

Databases, Factual↗
PubMed2001

[Dynamic change of tumor necrosis factor and endothelin during perioperative period in patients undergoing coronary artery bypass grafting].

OBJECTIVE: To observe the dynamic changes of tumor necrosis factor-alpha(TNF-alpha) and endothelin (ET-1) during perioperative period in patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) and to investigate their pathological significance so as to bring up feasible measure to increase therapeutic effect. METHODS: Blood samples of 32 patients undergoing CABG with CPB were drawn before operation, induction period of anaesthesia, after aortic crossclamping and declamping, by the end of surgery, and 2 hours, 8 hours, and 24 hours after surgery. The plasma TNF-alpha and ET-1 were measured by radioimmunoassay (RIA). RESULTS: (1) The plasma TNF-alpha level increased markedly after aortic crossclamping (18.3 ng/L +/- 3.4 ng/L vs 12.1 ng/L +/- 2.0 ng/L, P < 0.05) and went up to the peak value(22.4 ng/L +/- 3.6 ng/L) after aortic declamping, and then decreased. However, till 24 hours after operation, the TNF-alpha concentration maintained at a level higher than that before surgery (18.5 ng/L +/- 4.1 ng/L vs 12.1 ng/L +/- 2.0 ng/L, P < 0.05. After aortic declamping, during reperfusion of the lungs the TNF-alpha level was significantly higher than that after aortic crossclamping and before declamping (22.4 ng/L +/- 3.6 ng/L vs 18.3 ng/L +/- 3.4 ng/L P < 0.05). (2) The plasma ET-1 increased significantly after aortic crossclamping (146 ng/L +/- 20 ng/L vs 97 ng/L +/- 14 ng/L, P < 0.05) and went down after aortic declamping. Two hours after surgery, the plasma ET-1 increased again and reached the second height (134 ng/L +/- 19 ng/L), and then went down again and decreased to 92 ng/L +/- 18 ng/L 24 h after operation. CONCLUSION: (1) Attenuation of inflammatory reactions mediated by TNF-alpha should be considered an important strategy for myocardial and lung protection. (2) During the perioperative period of CABG the plasma ET-1 level shows two peaks, occurring respectively after aortic crossclamping and 2 h after surgery, which may result from operation itself and ischemia-reperfusion injury.

Adult↗
PubMed2001

Activation of JNK and transcriptional repressor ATF3/LRF1 through the IRE1/TRAF2 pathway is implicated in human vascular endothelial cell death by homocysteine.

Endothelial cell injury underlies an increased occurrence of thromboembolic vascular disease in hereditary hyperhomocysteinemia. We have previously shown that homocysteine causes activation of c-Jun NH(2)-terminal kinase (JNK) and activating transcription factor 3/liver regenerating factor 1 (ATF3/LRF1) and induces apoptosis in human umbilical vein endothelial cells (HUVECs). In this study, the activation of JNK and ATF3 in HUVECs was mediated by the endoplasmic reticulum (ER) resident transmembrane kinase IRE1alpha and beta, which sense and transduce signal of the accumulationj of unfolded proteins in the ER. Moreover, dominant negative mutants of tumor necrosis factor receptor-associated factor 2 and mitogen-activated kinase kinase 4 and 7, as well as antisense ATF3 cDNA, inhibited cell death by homocysteine. These results indicate that the activation of JNK and ATF3 through the ER stress of homocysteine plays a role in the homocysteine-induced cell death. The JNK-ATF3 pathway may be implicated in endothelial cell injury associated with hereditary hyperhomocysteinemia.

Activating Transcription Factor 3↗