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Biomedical subjects

J Zhang

Publications and source records attributed to J Zhang.

At least 433 records · Page 24Linked to original sources

Detecting bladder cancer in the Chinese by microsatellite analysis: ethnic and etiologic considerations.

BACKGROUND: Microsatellite analysis of urine sediments has shown promise as a highly sensitive and specific technique for the detection of bladder cancer. However, most studies have been conducted in Western countries with Caucasian subjects. We explored the potential of microsatellite analysis for detecting bladder cancer in Chinese people. METHODS: We performed microsatellite analysis of surgical specimens and urine sediment cells collected from Chinese patients with bladder tumors. Those microsatellite markers giving clearly readable patterns and showing susceptibility to alterations were used as a panel to detect primary tumors. A blinded study of additional patients with bladder cancer was performed to investigate the practical value of this panel for detecting bladder cancer. All statistical tests were two-sided. RESULTS: Thirty-eight bladder tumors and corresponding urine sediment specimens were initially screened for 60 microsatellite markers from 18 chromosomes. Nine markers, most of which were different from those that had been used for Western patients, with frequent alterations in the initial patients were selected for further analysis. In the subsequent blinded experiment, microsatellite alterations were observed in urine sediments from 22 (96%) of 23 patients with bladder cancer and from all three patients with inverted papilloma. None of the urine sediments from the one patient with bladder lipoma, from the one patient with neurofibroma, or from the 12 individuals without evidence of bladder tumor showed any microsatellite alterations. CONCLUSIONS: Microsatellite analysis of urine sediments could be a practical method for detecting bladder cancer in the Chinese. Our identification of different microsatellite markers highlights possible ethnic and etiologic disparities between the Chinese and Western bladder cancer patients.

Adult↗

Downregulation of Hedgehog signaling is required for organogenesis of the small intestine in Xenopus.

Hedgehog ligands interact with receptor complexes containing Patched (PTC) and Smoothened (SMO) proteins to regulate many aspects of development. The mutation W535L (SmoM2) in human Smo is associated with basal cell skin cancers, causes constitutive, ligand-independent signaling through the Hedgehog pathway, and provides a powerful means to test effects of unregulated Hedgehog signaling. Expression of SmoM2 in Xenopus embryos leads to developmental anomalies that are consistent with known requirements for regulated Hedgehog signaling in the eye and pancreas. Additionally, it results in failure of midgut epithelial cytodifferentiation and of the intestine to lengthen and coil. The midgut mesenchyme shows increased cell numbers and attenuated expression of the differentiation marker smooth muscle actin. With the exception of the pancreas, differentiation of foregut and hindgut derivatives is unaffected. The intestinal epithelial abnormalities are reproduced in embryos or organ explants treated directly with active recombinant hedgehog protein. Ptc mRNA, a principal target of Hedgehog signaling, is maximally expressed at stages corresponding to the onset of the intestinal defects. In advanced embryos expressing SmoM2, Ptc expression is remarkably confined to the intestinal wall. Considered together, these findings suggest that the splanchnic mesoderm responds to endodermal Hedgehog signals by inhibiting the transition of midgut endoderm into intestinal epithelium and that attenuation of this feedback is required for normal development of the vertebrate intestine.

Amino Acid Sequence↗

Cutting edge: a role for B lymphocyte stimulator in systemic lupus erythematosus.

Increased levels of B lymphocyte stimulator (BLyS) are associated with systemic autoimmunity in animal models of spontaneous autoimmune disease, and transgenic animals expressing BLyS develop typical autoimmune disease. Here, we demonstrate significant elevations of BLyS in the patients with systemic lupus erythematosus (SLE). The BLyS isolated from the sera of SLE patients had the same m.w. as the natural soluble form and was able to stimulate B cell activation in vitro. Increased BLyS in SLE patients was partially associated with higher levels of anti-dsDNA Ab of the IgG, IgM, and IgA classes, but not associated with the disease activity. Our results suggest that BLyS may be a useful marker for early activation of an autoimmune diathesis and likely plays a critical role in triggering activation of self-Ag-driven autoimmune B cells in human SLE. BLyS may provide an effective therapeutic target in systemic autoimmunity.

Animals↗

Variations in susceptibility to proteoglycan-induced arthritis and spondylitis among C3H substrains of mice: evidence of genetically acquired resistance to autoimmune disease.

OBJECTIVE: To identify and screen the level of arthritis susceptibility in C3H murine strains known to be resistant to proteoglycan (aggrecan)-induced arthritis, and to measure and correlate various immunologic and inflammatory parameters with susceptibility to either arthritis or spondylitis in various C3H substrains. METHODS: Mice of 10 C3H substrains (subcolonies) were immunized with cartilage proteoglycan (aggrecan) for induction of arthritis. Animals were assessed for clinical symptoms, and the peripheral joints and spine were studied by histologic methods. Proteoglycan-specific T cell responses (T cell proliferation and production of interleukin-2 [IL-2], interferon-y, and IL-4) and the B cell response to lipopolysaccharide (LPS) were measured in spleen cell cultures. Serum levels of heteroantibodies and autoantibodies as well as various cytokines (IL-6, IL-10, IL-12, and tumor necrosis factor alpha) and soluble CD44 were determined by enzyme-linked immunosorbent assay. RESULTS: Immunization with cartilage proteoglycan induced severe arthritis in the C3H/HeJCr substrain (95-100% incidence), whereas the original parent mice of the C3H/HeJ colony were resistant to proteoglycan (aggrecan)-induced arthritis. Furthermore, the progressive polyarthritis that is characteristic in susceptible C3H/HeJCr mice was accompanied by progressive inflammation around the spine. In subsequent experiments, 10 different C3H colonies with largely identical genetic backgrounds (all originating from the National Institutes of Health or Jackson Laboratory) exhibited extreme differences in susceptibility. Although none of the laboratory findings, including LPS hyporesponsiveness, immunologic parameters, and inflammatory markers, showed a correlation with susceptibility or resistance in the C3H/HeJCr and C3H/HeJ substrains, respectively, significant differences were found when all arthritic C3H mice were compared with all nonarthritic animals, regardless of their substrain origin. CONCLUSION: Because many of the C3H substrains lost arthritis susceptibility or acquired resistance, our results suggest that a preferred site for a mutation(s) in a gene(s) in a relatively upstream position of the inflammatory cascade is present. This is the first autoimmune model that exhibits extreme differences in arthritis susceptibility in the same murine strain, and is therefore a valuable tool for identification of arthritis-susceptible (or arthritis-suppressive) genes.

Animals↗

Water vapor absorption into amorphous sucrose-poly(vinyl pyrrolidone) and trehalose-poly(vinyl pyrrolidone) mixtures.

Previous studies from this laboratory suggested that a solution model (Flory-Huggins equation) modified by a free volume model (Vrentas equation) could satisfactorily describe water absorption into an amorphous solid composed of a sugar or a polymer. This paper has extended the studies of single solutes to binary mixtures of trehalose-and sucrose-poly(vinyl pyrrolidone) (trehalose-PVP and sucrose-PVP, respectively) either co-lyophilized or individually lyophilized and then physically mixed. Water vapor absorption isotherms of the binary mixtures were determined at 30 degrees C. Co-lyophilized PVP-sugar mixtures take up essentially the same amount of water as predicted by the weight average of individual isotherms, whereas sugar crystallization is significant retarded in the molecular dispersions. The sugar-PVP interaction, as reflected in the Flory-Huggins chi interaction parameter, was estimated by fitting the high relative pressure (p/p(0)) region of the isotherm, at which the system is in a liquid state, with a three-component Flory-Huggins-type model. The estimated sugar-water PVP-water, and sugar-PVP interaction parameters suggest that the solute-water interactions are not significantly affected by the sugar-PVP interaction; that is, the solute-water interaction parameters in a binary solute system are similar to those in the corresponding single solute systems. Based on these interaction parameters, the sucrose-PVP interaction appears to be stronger than that of trehalose-PVP. Manipulation of the interaction parameters suggest that the water vapor absorption isotherm is not a sensitive indicator of possible sugar-PVP interactions. Density, glass transition temperature, T(g), and the heat capacity change, DeltaC(p), at T(g) were determined to estimate the excess water absorption energy due to the plasticizing effect of water using the structural relaxation model, as described by Vrentas. Results suggest that PVP is a better antiplasticizer for sucrose than for trehalose. Consequently, the excess free energy arising from structural relaxation was disproportionally reduced by the presence of PVP in these molecular dispersions. Finally, the entire isotherms of co-lyophilized sugar-PVP mixtures are reasonably described with an extended three-component Flory-Huggins model and Vrentas glass structural relaxation model.

Absorption↗

Diffusion tensor imaging of the developing mouse brain.

It is shown that diffusion tensor MR imaging (DTI) can discretely delineate the microstructure of white matter and gray matter in embryonic and early postnatal mouse brains based on the existence and orientation of ordered structures. This order was found not only in white matter but also in the cortical plate and the periventricular zone, which are precursors of the cerebral cortex. This DTI-based information could be used to accomplish the automated spatial definition of the cortical plate and various axonal tracts. The DTI studies also revealed a characteristic evolution of diffusion anisotropy in the cortex of the developing brain. This ability to detect changes in the organization of the brain during development will greatly enhance morphological studies of transgenic and knockout models of cortical dysfunction. Magn Reson Med 46:18-23, 2001.

Animals↗

Increased sensitivity of mitochondrial respiration to inhibition by nitric oxide in cardiac hypertrophy.

Cardiac hypertrophy is a significant risk factor for the development of congestive heart failure (CHF). Mitochondrial defects are reported in CHF, but no consistent mitochondrial alterations have yet been identified in hypertrophy. In this study selective metabolic inhibitors were used to determine thresholds for respiratory inhibition and to reveal novel mitochondrial defects in hypertrophy. Cardiac hypertrophy was produced in rats by aortic banding. Mitochondria were isolated from left ventricular tissue and the effects of inhibiting respiratory complexes I and IV on mitochondrial oxygen consumption were measured. At 8 weeks post-surgery, 65+/-2% complex IV inhibition was required to inhibit respiration half maximally in control mitochondria. In contrast, only 52+/-6% complex IV inhibition was required to inhibit respiration half maximally in mitochondria from hypertrophied hearts (P=0.046). This effect persisted at 22 weeks post-surgery and was accompanied by a significant upregulation of inducible nitric oxide synthase (iNOS, 3.0+/-0.7-fold, P=0.006). We conclude that respiration is more sensitive to complex IV inhibition in hypertrophy. Nitric oxide is a well documented inhibitor of complex IV, and thus the combination of increased NO(.)from iNOS and an increased sensitivity to inhibition of one of its targets could result in a bioenergetic defect in hypertrophy that may be a harbinger of CHF.

Animals↗

Renin expression at sites of repair in the infarcted rat heart.

Y. Sun, J. Zhang, J. Q. Zhang and K. T. Weber. Renin Expression at Sites of Repair in the Infarcted Rat Heart. Journal of Molecular and Cellular Cardiology (2001) 33, 995-1003. Angiotensin (Ang) II has autocrine and paracrine functions that contribute to structural cardiac remodeling by fibrous tissue following myocardial infarction (MI). The recruitment of angiotensin converting enzyme (ACE) and AngII receptors by inflammatory and fibroblast-like cells involved in tissue repair of the infarcted heart is now well established. On the other hand, the temporal and spatial response and cellular source of renin in infarcted hearts have not been fully elucidated. The relationship between renin synthesis and circulating renin activity have likewise not been addressed. The present study sought to assess the cellular source, spatial distribution and temporal response of renin expression and synthesis in the rat heart following anterior transmural MI, and to determine its relationship to circulating renin activity. At day 3 and weeks 1, 2, 3 and 4 following left coronary artery ligation, the localization and optical density of cardiac renin mRNA was detected by quantitative in situ hybridization; cardiac and circulating renin activity was measured by radioimmunoassay; cells expressing cardiac renin were detected by immunohistochemistry; and injury/repair was assessed by hematoxylin/eosin and collagen-specific picrosirius red staining. Unoperated rats served as normal controls. The authors found: (1) renin mRNA and activity were not detected in either normal control or non-infarcted myocardium, but were expressed at the site of infarction and other sites of repair involving visceral pericardium and endocardium of interventricular septum at all time points; (2) cells expressing renin at day 3 and weeks 1 and 2 were predominantly macrophages, while at weeks 3 and 4, they were primarily myofibroblasts; (3) renin activity in the infarcted myocardium rose progressively over the course of 4 weeks; and (4) circulating renin activity was significantly increased at day 3 and week 1, reached a peak at week 2, declined at week 3 and returned to normal levels at week 4. Thus, renin expression and activity appear at sites of repair in the infarcted rat heart on day 3 and rise progressively thereafter over 4 weeks, independent of circulating renin. Several types of cells are responsible for renin synthesis at these sites; primarily macrophages during the inflammatory phase of repair, and myofibroblasts during the subsequent fibrogenic phase. Cardiac renin production following MI contributes to local AngII generation that regulates tissue repair and structural remodeling following MI.

Actins↗

Clinical study on the treatment of 325 cases of atrioventricular node reentrant tachycardia by radiofrequency catheter ablation.

In order to improve the efficacy of modified inferior method or middle method of radiofrequency catheter ablation (RFCA) in the treatment of atrioventricular node reentrant tachycardia (AVNRT), the clinical data of 325 cases of AVNRT from March 1992 to Feb. 2000 being subjected to the treatment of RFCA were retrospectively analyzed. The results showed that the successful rate was increased and recurrence was decreased year by year. In the recent 4 years the effective rate was up to 100%. The complication of three grade of AVB occurred in 3% and recurrent rate in 9.1% before March 1996, but both of them were zero in the last 3 years. The time of RFCA procedure and X-ray exposure was significantly reduced. It was concluded that ablating more than 3 targets by modified inferior method or middle method with energy titrating and strict endpoint was the crux of obtaining satisfactory therapeutic effects and preventing recurrence.

Adolescent↗

Accuracy and consistency of respiratory inductive plethysmography for overnight tidal volume measurement.

To validate the accuracy and consistency of respiratory inductive plethysmography (RIP) in measuring tidal volume after an overnight sleep, tidal volumes of 18 patients with suspected sleep-disordered breathing and 8 normal volunteers were measured simultaneously with RIP (VTRIP) and with an ultrasonic airflow meter (VTUFM) before and after an unstrained overnight sleep on supine and lateral decubitus. The bias of the VTRIP was expressed as (VTRIP-VTUFM)/ VTUFM.100%, limits of agreement between VTRIP and VTUFM was measured by averaged bias +/- 2 s. Results showed that in normal subjects, the bias of RIP before and after overnight sleep was precise and consistent in both supine (0.7% and -1.6%) and lateral decubitus (3.7% and -0.56%). In these patients, the bias of RIP before and after sleep in supine also remained small (1.9% and 1.7%), but it became larger in lateral decubitus (24.5% and 20.4%) and 11.5% exceeded the limits of agreement observed in the evening. The patients' body mass indices (BMI) were higher than those of normal subjects (median 34.2 vs. 27.8 kg/m2). Pooled data showed that the bias of VTRIP in the morning on lateral decubitus but not on supine was correlated to BMI (Spearman R = 0.32, n = 52, P = 0.02). Thus, we were led to conclude that the accuracy of VTRIP overnight was precise and consistent in normal subjects, but the deviation of VTRIP measured on lateral decubitus in patients especially in those with excessive obesity was greater, thus, the method should not be used for quantitative determination.

Adult↗

Direct gene transfer into rabbit peripheral nerve in vivo.

Exogenous gene suture was used to achieve peripheral nerve anastomoses to probe into the feasibility that the sites of anastomoses of nerves directly transfer gene and thus enable gene to be expressed at the sites of anastomoses under the condition that perfect nerve anastomoses are ensured. PCMV beta plasmid containing cytomegalovirus promoter (CMV promoter) and Escherichia coli (E. coli) beta-Galactosidase (beta-Gal) structural gene (lacZ gene) was conducted. A soaked medical 8-0nylon suture was used to perform epineurial repair of rabbit sciatic nerve. In the control group a suture soaked in sucrose PBS was used, while in the experimental group a suture soaked in PCMV beta plasmid solution was applied. The sites of anastomoses of nerves by stages were taken out, and beta-Gal histochemical staining was performed and beta-Gal enzyme activity was assayed with 5-bromo-4-chloro-3-indolyl-beta-D-galactoside. Results showed that the sites of anastomoses of nerves were taken out 2 days, 7 days, 14 days and 30 days respectively after the operation. The beta-Gal histochemical stains at the sites of anastomoses showed no indigo positive cells at different stages in the control group, whereas displayed indigo positive cells in the experimental group. In the control group, no beta-Gal enzyme activity was detected at different stages after operation, but in the experimental group, beta-Gal enzyme activity could be detected from the 3rd day to the 30th day after operation. It was concluded that by using exogenous gene suture, exogenous gene could be transferred to the sites of peripheral nerve and expressed the exogenous gene expression products with bioactivity, which provided the feasibility of using gene therapy to accelerate the recovery of nerve function.

Anastomosis, Surgical↗

Effect of the vacuolation of Helicobacter pylori.

Cytotoxic test in vitro combined with cytochemical stain, fluorescent stain, transmission electronmicrograph was used to study the vacuolated effect by helicobacter pylori (H. pylori) (Toxin+) and its pathological mechanism. 78.26% patients with peptic ulcer associated with H. pylori was infected with H. pylori (Toxin+), while 42.86% patients with gastritis was infected with H. pylori (Toxin+). It was positive in vacuole with acridine orange and acid phosphatase stain. Transmission electronmicrograph of vacuole revealed the presence of abounding membrane. There was a closed relationship between infection with H. pylori (Toxin+) and peptic ulcer disease. The vacuole induced by H. pylori (Toxin+) was autophagosome, which was pathological phenomenon induced by toxin.

Adolescent↗

The influence of phorbol ester on the effect of tamoxifen in breast cancer cells.

To investigate the correlation between the activity of kinases in the growth factor signal transduction pathway and the development of resistance of breast cancer to tamoxifen, reporter gene regulated by the regulating fragment of CCD1 was transfected into the MCF-7 cells, and the influence of tamoxifen on the reporter gene expression was examined under different conditions of TPA treatment. Our results showed that the reporter gene expression was inhibited by tamoxifen and promoted by TPA. Furthermore, tamoxifen exerts an agonist effect on the reporter gene expression when the cells was treated by TPA previously for 12 h. It is concluded that TPA could induce estrogen-like effect of tamoxifen on estrogen receptor positive breast cancer cells and it may be one of the mechanisms responsible for the development of tamoxifen resistance.

Antineoplastic Agents, Hormonal↗

GABA mechanisms in the pedunculopontine tegmental nucleus influence particular aspects of nicotine self-administration selectively in the rat.

RATIONALE: The pedunculopontine tegmental nucleus (PPTg) is part of the neuronal circuit activated by self-administered nicotine. The cholinergic neurons of the PPTg comprise a prominent projection to midbrain dopamine neurons. However, anatomical studies of Fos expression suggest that nicotine targets primarily non-cholinergic neurons in the PPTg, especially GABAergic and glutamatergic neurons. OBJECTIVE: The objective of these experiments was to examine the role of GABA manipulations in the PPTg on nicotine self-administration. METHODS AND RESULTS: Rats trained to self-administer nicotine or cocaine intravenously were prepared with brain microcannulae directed to the PPTg. Intra-PPTg microinfusions of the GABA agonists muscimol (10-50 ng) and baclofen (30-60 ng) reduced nicotine self-administration maintained on a fixed-ratio schedule of reinforcement (30 microg/kg per infusion); self-administration of cocaine (0.3 mg/kg per infusion) under an identical schedule was not affected. Muscimol and baclofen were also examined after intra-PPTg microinfusion in animals trained to self-administer nicotine on a progressive-ratio schedule (10 and 30 microg/kg per infusion). Progressive-ratio responding was sensitive to pharmacological manipulations such as a change in the nicotine dose available for self-administration, or intra-PPTg microinfusion of the nicotinic antagonist dihydro-beta-erythroidine (30 microg). However, nicotine self-administration on a progressive-ratio schedule was not altered by intra-PPTg microinfusions of GABA agonists. CONCLUSIONS: These data confirm that the PPTg is involved in nicotine self-administration, a conclusion that is independent of the schedule of reinforcement that is used. GABAergic mechanisms in the PPTg play a selective role in nicotine reinforcement compared to cocaine, and that role is restricted to the characteristics of reinforcement measured by fixed-ratio responding.

Animals↗

Rapid diversification of RNase A superfamily ribonucleases from the bullfrog, Rana catesbeiana.

We present sequences of five novel RNase A superfamily ribonuclease genes of the bullfrog, Rana catesbeiana. All five genes encode ribonucleases that are similar to Onconase, a cytotoxic ribonuclease isolated from oocytes of R. pipiens. With amino acid sequence data from 14 ribonucleases from three Rana species (R. catesbeiana, R. japonica, and R. pipiens), we have constructed bootstrap-supported phylogenetic trees that reorganize these ribonucleases into five distinct lineages--the pancreatic ribonucleases (RNases 1), the eosinophil-associated ribonucleases (RNases 2, 3, and 6), the ribonucleases 4, the angiogenins (RNases 5) and the Rana ribonucleases--with the Rana ribonucleases no more closely related to the angiogenins than they are to any of the other ribonuclease lineages shown. Further phylogenetic analysis suggests the division of the Rana ribonucleases into two subclusters (A and B), with positive (Darwinian) selection (dN/dS > 1.0) and an elevated rate of radical nonsynonymous substitution (dR) contributing to the rapid diversification of ribonucleases within each cluster. This pattern of evolution-rapid diversification via positive selection among sequences of a multigene cluster-bears striking resemblance to what we have described for the eosinophil-associated ribonuclease genes of the rodent Mus musculus, a finding that may have implications with respect the physiologic function of this unique family of proteins.

Amino Acid Sequence↗

The use of serum levels of cardiac troponin T to compare the protective activity of dexrazoxane against doxorubicin- and mitoxantrone-induced cardiotoxicity.

PURPOSE: To compare the protective effect of dexrazoxane (DRZ) against cardiotoxicity induced by doxorubicin (DXR) and mitoxantrone (MTX). METHODS: Adult male spontaneously hypertensive rats (SHR) were treated with 1 mg/kg DXR (i.v.) or 0.5 mg/kg MTX (i.v.), either alone or 30 min after 25 mg/kg DRZ (i.p.) weekly for up to 12 weeks. Animals treated with DXR alone either died (n = 2) or were killed (n = 3) at a cumulative dose of 10 mg/kg. The severity of cardiac lesions (cytoplasmic vacuolization and myofibrillar loss) were graded semiquantitatively by light microscopy on a scale of 0 to 3. RESULTS: Cardiac lesions were observed in all SHR given DXR or MTX alone, and were attenuated in those given DRZ prior to either DXR (mean lesion scores 2.7 vs 1.5; P < 0.05) or MTX (mean lesion scores 2.0 vs 1.25; P < 0.05). Cardioprotection was also demonstrated by monitoring serum levels of cardiac troponin T (cTnT), which were elevated in all animals receiving DXR or MTX alone. These elevations were attenuated in SHR given the combination of DXR and DRZ (mean values 0.79 ng/ml vs 0.24 ng/ml; P < 0.05) and MTX and DRZ (mean values 0.19 ng/ml vs 0.04 ng/ ml; P < 0.05). Biochemical studies have shown that both DXR and MTX form potentially cardiotoxic complexes with iron. ADR-925 (the hydrolysis product of DRZ) and other chelators (EDTA, diethylenetriaminepentaacetic acid and desferrioxamine) removed Fe(III) from its complex with MTX or DXR. CONCLUSIONS: The present study showed that DRZ significantly attenuates the cardiotoxicity induced by DXR and MTX, and that this protective activity can be assessed by morphological evaluation of cardiac tissues and by monitoring the concentrations of cTnT in serum.

Animals↗

Monitoring of bio-oxidation process of ferrous ion by using piezoelectric impedance analysis.

A new method of monitoring the bio-oxidation process of ferrous ion in the presence of Thiobacillus ferroxidans was proposed by piezoelectric impedance analysis. The time courses of the responses of impedance parameters for a quartz crystal in a culture system were simultaneously obtained and discussed. It was found that the frequency shift response originates mainly from the adsorption of bacterial metabolites on the surface of gold electrode. Experiments also examined the effect of culture temperature on the bio-oxidation process. Combined with the growth situation of the bacterium, an impedance response model reflecting the process was established. By fitting Delta f vs. time curves toward the proposed model, we obtained and discussed the bacterial growth parameters. The results showed that the proposed method could provide real time and multidimensional information to monitoring of the bio-oxidation process.

Acidithiobacillus thiooxidans↗