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Biomedical subjects

X Zhang

Publications and source records attributed to X Zhang.

At least 397 records · Page 22Linked to original sources
PubMed2001

Projections from the marginal zone and deep dorsal horn to the ventrobasal nuclei of the primate thalamus.

It has been concluded recently that if a projection from the marginal zone to the ventral posterior lateral (VPL) nucleus exists, it is sparse. Given the importance of the marginal zone in nociception, this conclusion has raised doubts about the significance of the role of the ventrobasal complex in nociception. We have reexamined this projection using injections of the retrograde tracer, cholera toxin subunit B, into one side of the lateral thalamus in macaque monkeys. The injections were confined to the ventrobasal complex (with minimal spread to adjacent nuclei that do not receive spinal projections) in two animals. Many retrogradely labeled neurons were found in lamina I (as well as in lamina V) of the contralateral spinal and medullary dorsal horn. The results are consistent with the view that neurons in the marginal zone contribute prominently to the spinothalamic and trigeminothalamic projections to the VPL and ventral posterior medial (VPM) nuclei. This pathway is likely to be important for the sensory-discriminative processing of nociceptive information with respect to the location and intensity of painful stimuli.

Animals↗
PubMed2001

Elimination of k-space spikes in fMRI data.

The subtle signal changes in functional magnetic resonance imaging (fMRI) can be easily overwhelmed by noise of various origins. Spikes in the collected fMRI raw data often arise from high-duty usage of the scanner hardware and can introduce significant noise in the image and thereby in the image time series. Consequently, the spikes will corrupt the functional data and degrade the result of functional mapping. In this work, a simple method based on processing the time course of the k-space data are introduced and implemented to remove the spikes in the acquired data. Application of the method to experimental data shows that the methods are robust and effective for eliminating of spike-related noise in fMRI time series.

Algorithms↗
PubMed2001

Differential vulnerability to oxidative stress in rat cardiac myocytes versus fibroblasts.

OBJECTIVES: This study was designed to test the hypothesis that cardiac myocytes have greater vulnerability to oxidative stress compared with cardiac fibroblasts. BACKGROUND: The function of cardiac myocytes differs from that of fibroblasts in the heart, but differences in their response to oxidative stress have not been extensively studied. METHODS: Cardiomyocytes and fibroblasts from F344 neonatal rat hearts were cultured and exposed to different concentrations of hydrogen peroxide (H(2)O(2)) and menadione (superoxide generator). The mitogen-activated protein kinase (MAPK) proteins were assayed after oxidative stress; cell death was determined by trypan blue staining and deoxyribonucleic acid (DNA) ladder electrophoresis. RESULTS: The cardiac myocytes were significantly more vulnerable than the fibroblasts to oxidative damage, showing substantial DNA fragmentation and consistently poor cell survival after exposure to H(2)O(2) (100 to 800 microM), while the cardiac fibroblasts demonstrated little or no DNA fragmentation, and superior cell survival rates both over time (from 1 to 72 h after 100 microM) and across increasing doses of H(2)O(2) (100 to 800 microM). The p42/44 extracellular signal-regulated kinases were phosphorylated in both cell types after exposure to H(2)O(2), but significantly more in cardiac fibroblasts. However, p38 MAPK and c-jun NH(2)-terminal kinase were phosphorylated more in the cardiac myocytes compared to cardiac fibroblasts. This was also the case after exposure to menadione. CONCLUSION: Taken together, these results suggest that oxidative stress causes greater injury and cell death in cardiac myocytes compared with cardiac fibroblasts. It is possible that the signaling differences via the MAPK family may partly mediate the observed differences in vulnerability and functional outcomes of the respective cell types.

Animals↗
PubMed2001

Laminar distribution of nicotinic receptor subtypes in cortical regions in schizophrenia.

The laminar cortical distribution of the [125I]alpha-bungarotoxin, [3H]cytisine and [3H]epibatidine nicotinic acetylcholine receptor ligands was investigated by quantitative autoradiography in autopsy tissue from the cingulate, orbitofrontal and temporal cortices of control and schizophrenia subjects matched for age and smoking history. Different laminar binding patterns were observed for the various nicotinic ligands both in schizophrenic and control brains. [125I]alpha-Bungarotoxin binding was distributed homogeneously across all cortical layers in all three brain regions, with highest binding densities in the cingulate cortex. [3H]Cytisine and [3H]epibatidine binding varied across the cortical ribbon, with high binding in layers I, III, V and VI, within the three cortical regions. A significantly reduced [125I] alpha-bungarotoxin binding (-54%) was observed in the cingulate cortex of schizophrenia subjects, in comparison with normal individuals who smoked tobacco. In the same brain region also a significantly higher [3H]cytisine binding (48-77%) was observed in nearly all layers, except for layer I of the schizophrenia subjects, when compared to normal individuals with a history of tobacco use. No significant changes in [3H]epibatidine binding was observed within the individual cortical layers between control subjects and patients with schizophrenia, but when calculated as a whole region (i.e. measurements performed across the whole cortical ribbon), the temporal cortex showed a significant increase in [3H]epibatidine binding in schizophrenia subjects compared to control subjects. The results suggest opposite changes of the alpha4beta2 and alpha7 nicotinic receptor subtypes in the cingulate cortex of patients with schizophrenia which might reflect involvement of two different nicotinic receptor mechanisms in schizophrenia brain.

Acetylcholine↗
PubMed2001

The neuronal Rho-GEF Kalirin-7 interacts with PDZ domain-containing proteins and regulates dendritic morphogenesis.

Spine function requires precise control of the actin cytoskeleton. Kalirin-7, a GDP/GTP exchange factor for Rac1, interacts with PDZ proteins such as PSD-95, colocalizing with PSD-95 at synapses of cultured hippocampal neurons. PSD-95 and Kalirin-7 interact in vivo and in heterologous expression systems. In primary cortical neurons, transfected Kalirin-7 is targeted to spines and increases the number and size of spine-like structures. A Kalirin-7 mutant unable to interact with PDZ proteins remains in the cell soma, inducing local formation of aberrant filopodial neurites. Kalirin-7 with an inactivated GEF domain reduces the number of spines below control levels. These results provide evidence that PDZ proteins target Kalirin-7 to the PSD, where it regulates dendritic morphogenesis through Rac1 signaling to the actin cytoskeleton.

Actins↗
PubMed2001

Evaluation of the optimum cut-off point in immunochemical occult blood testing in screening for colorectal cancer.

This study was carried out to assess, from the aspects of cost-effectiveness and diagnostic validity, the optimum cut-off point for immunochemical occult blood testing using a 2-day method as a means of screening for colorectal cancer. Four thousand, two hundred and sixty asymptomatic individuals were subjects of this study. They gave samples for an immunochemical fecal occult blood test, and colonoscopy was carried out during a medical check-up. For evaluation of the optimum cut-off point, three cut-off levels of fecal haemoglobin, 50, 150 and 300 ng/ml, were used. A total of 27 patients with colorectal cancer were diagnosed. The average costs to detect one patient with colorectal cancer and the sensitivity and specificity of these three cut-off points of fecal haemoglobin were evaluated. The average costs for the detection of one cancer case were calculated as $2870.45 for cut-off level of 50 ng/ml, $2492.98 for that of 150 ng/ml and $3329.09 for that of 300 ng/ml, respectively. The sensitivity and specificity were calculated as 89 and 94% for the 50 ng/ml cut-off level, 81% and 96% for the 150 ng/ml cut-off level and 56 and 97% for the 300 ng/ml cut-off level, respectively, indicating a significant difference in the sensitivity between the 50 and 300 ng/ml levels (P<0.05), as well as between the 150 and 300 ng/ml levels (P<0.05), and a significant difference in the specificity between the 50 and 300 ng/ml levels (P<0.05). However, no significant difference was observed in the specificity between the 50 and 150 ng/ml levels. The findings show that 150 ng/ml of fecal haemoglobin is the optimal cut-off point when carrying out the OC-Hemodia test as a means of screening for colorectal cancer.

Adult↗
PubMed2001

Arylisothiocyanate-containing esters of caffeic acid designed as affinity ligands for HIV-1 integrase.

Integrase is an enzyme found in human immunodeficiency virus, which is required for the viral life cycle, yet has no human cellular homologue. For this reason, HIV integrase (IN) has become an important target for the development of new AIDS therapeutics. Irreversible affinity ligands have proven to be valuable tools for studying a number of enzyme and protein systems, yet to date there have been no reports of such affinity ligands for the study of IN. As an initial approach toward irreversible ligand design directed against IN, we appended isothiocyanate functionality onto caffeic acid phenethyl ester (CAPE), a known HIV integrase inhibitor. The choice of isothiocyanate as the reactive functionality, was based on its demonstrated utility in the preparation of affinity ligands directed against a number of other protein targets. Several isomeric CAPE isothiocyanates were prepared to explore the enzyme topography for reactive nitrogen and sulfur nucleophiles vicinal to the enzyme-bound CAPE. The preparation of these CAPE isothiocyanates, required development of new synthetic methodology which employed phenyl thiocarbamates as latent isothiocyanates which could be unmasked near the end of the synthetic sequence. When it was observed that beta-mercaptoethanol (beta-ME), which is required to maintain the catalytic activity of soluble IN (a F185KC280S mutant), reacted with CAPE isothiocyanate functionality to form the corresponding hydroxyethylthiocarbamate, a variety of mutant IN were examined which did not require the presence of beta-ME for catalytic activity. Although in these latter enzymes, CAPE isothiocyanate functionality was presumed to be present and available for acylation by IN nucleophiles, they were equally effective against Cys to Ser mutants. One conclusion of these studies, is that upon binding of CAPE to the integrase, nitrogen or sulfur nucleophiles may not be properly situated in the vicinity of the phenethyl aryl ring to allow reaction with and covalent modification of reactive functionality, such as isothiocyanate groups. The fact that introduction of the isothiocyanate group onto various positions of the phenethyl ring or replacement of the phenyl ring with naphthyl rings, failed to significantly affect inhibitory potency, indicates a degree of insensitivity of this region of the molecule toward structural modification. These findings may be useful in future studies concerned with the development and use of HIV-1 integrase affinity ligands.

Amino Acid Substitution↗
PubMed2001

Two polymorphic forms of human histamine methyltransferase: structural, thermal, and kinetic comparisons.

BACKGROUND: Histamine plays important biological roles in cell-to-cell communication; it is a mediator in allergic responses, a regulator of gastric acid secretion, a messenger in bronchial asthma, and a neurotransmitter in the central nervous system. Histamine acts by binding to histamine receptors, and its local action is terminated primarily by methylation. Human histamine N-methyltransferase (HNMT) has a common polymorphism at residue 105 that correlates with the high- (Thr) and low- (Ile) activity phenotypes. RESULTS: Two ternary structures of human HNMT have been determined: the Thr105 variant complexed with its substrate histamine and reaction product AdoHcy and the Ile105 variant complexed with an inhibitor (quinacrine) and AdoHcy. Our steady-state kinetic data indicate that the recombinant Ile105 variant shows 1.8- and 1.3-fold increases in the apparent K(M) for AdoMet and histamine, respectively, and slightly (16%) but consistently lower specific activity as compared to that of the Thr105 variant. These differences hold over a temperature range of 25 degrees C-45 degrees C in vitro. Only at a temperature of 50 degrees C or higher is the Ile105 variant more thermolabile than the Thr105 enzyme. CONCLUSIONS: HNMT has a 2 domain structure including a consensus AdoMet binding domain, where the residue 105 is located on the surface, consistent with the kinetic data that the polymorphism does not affect overall protein stability at physiological temperatures but lowers K(M) values for AdoMet and histamine. The interactions between HNMT and quinacrine provide the first structural insights into a large group of pharmacologic HNMT inhibitors and their mechanisms of inhibition.

Amino Acid Sequence↗
PubMed2001

Production of no-carrier-added 186Re via deuteron induced reactions on isotopically enriched 186W.

Rhenium-186 was produced from the reaction induced by 16 MeV deuterons on isotopically enriched 186W metal powder target. Following its separation from 187W, 183Ta and the bulk of target materials 186W through an acid alumina column, the 186Re was converted to HNO3 solution through an anion exchange column, or to ammonia solution by extracting with N-235-dimethylbenzene, and finally the no-carrier-added 186Re saline solution was obtained. The radionuclidic purity of 186Re was >99.9% and the isotopic impurities were mainly 183Re (5.0 x 10(-3)%) and 184gRe (4.6 x 10(-2)%). The experimental thick-target yield of 186Re was determined to be approximately 529 microCi/microA h and the overall chemical recovery yield was > 80%.

Kinetics↗
PubMed2001

Cellular accumulation and retention of the technetium-99m-labelled hypoxia markers BRU59-21 and butylene amine oxime.

BRU59-21 and 99mTc-butylene amine oxime (BnAO, HL91) are being evaluated for imaging hypoxia in tumors. Both tracers: 1) rapidly reached a plateau in aerobic Chinese hamster ovary cells in vitro but continuously accumulated in hypoxic cells; 2) ceased to accumulate when hypoxic cells were exposed to air; 3) showed approximately 40% retention upon washing the cells; 4) showed selective hypoxic accumulation only at 37 degrees C; 5) accumulation could be modulated by addition of electron-affinic compounds; and 6) exhibited higher accumulation in cells which overexpress cytochrome P450 reductase. Both BRU59-21 and 99mTc-BnAO share properties making them suitable for hypoxia imaging.

Animals↗
PubMed2001

Activation and anergy in bone marrow B cells of a novel immunoglobulin transgenic mouse that is both hapten specific and autoreactive.

Available evidence indicates that B cell tolerance is attained by receptor editing, anergy, or clonal deletion. Here, we describe a p-azophenylarsonate (Ars)-specific immunoglobulin transgenic mouse in which B cells become anergic as a consequence of cross-reaction with autoantigen in the bone marrow. Developing bone marrow B cells show no evidence of receptor editing but transiently upregulate activation markers and appear to undergo accelerated development. Mature B cells are present in normal numbers but are refractory to BCR-mediated induction of calcium mobilization, tyrosine phosphorylation, and antibody responses. Activation marker expression and acquisition of the anergic phenotype is prevented in bone marrow cultures by monovalent hapten. In this model, it appears that induction of anergy in B cells can be prevented by monovalent hapten competing with autoantigen for the binding site.

Alleles↗
PubMed2001

Shammah-induced oral leukoplakia-like lesions.

A Shammah-induced oral leukoplakia-like lesion is described in a 44-year-old Algerian patient, who used this specific chewing tobacco since 33 years. The extended white lesion was located to the right mandibular vestibule and had a homogeneous appearance. Shammah is a chewing tobacco consisting of powdered tobacco leaves with carbonate of lime and other substances. It has been associated with oral cancer in Saudi Arabia. Histologically, acanthosis, hyperortho- and parakeratosis were seen. The spinous cell layer showed large pale staining epithelial cells with pycnotic nuclei. Atypia was not observed, however, an increase in mitotic activity was apparent. The subepithelial infiltrate was mild. Electron microscopy showed changes in the basal membrane with interruptions, duplications and triplications. Follow-up of the patient for 2 years revealed that, whenever, the patient changed the location of application, the white lesion regressed or disappeared within 4-6 weeks. Due to the composition of Shammah, the lesion induced has features of a mucosal burn. In contrast to other smokeless tobacco variants, Shammah seems to cause changes which, according to the small number of reports, may transform into oral cancer. As such, Shammah-induced oral leukoplakia-like lesions may be considered precancerous.

Adult↗
PubMed2001

Impact of localized treatment in reducing risk of progression of low-grade oral dysplasia: molecular evidence of incomplete resection.

Currently, there is no consensus on the appropriate treatment for low-grade oral dysplasia. This is mainly due to the difficulty in predicting outcome for this heterogeneous group of lesions. In this study, we constructed a detailed clinical history of 66 mild and moderate dysplasias in order to determine how treatment affected outcome, and to evaluate the effect of treatment on lesions with different genetic profiles, which are defined by patterns of loss of heterozygosity (LOH) associated with low, intermediate and high risk of progression [Clin. Cancer Res., 6, 357-62, 2000]. The results showed that although treatment guided by clinical removal of leukoplakia reduced cancer progression risk in all three risk groups, the amount of reduction in our study group did not reach statistical significance. To assess whether completeness of lesion removal was a major factor in recurrence, repeat biopsies at the primary sites were analyzed for persistent LOH status on chromosomes 3p, 4q, 8p, 9p, 11q, 13q and 17p. Strikingly, eight of 17 cases judged clinically removed contained the same molecular clones in the initial and subsequent biopsies, suggesting incomplete removal. When molecular information was included in the assessment of lesion removal, treatment significantly reduced the risk of progression for cases with intermediate (P=0.043) and high risk (P=0.001) genetic profiles, but not cases with low-risk profiles. A 9.1-fold decrease in progression risk was observed for those with high-risk profile. Altogether, these data suggest the use of molecular profiles to guide the treatment of low-grade dysplasia. Our data also suggest that currently an inadequate margin may in part be responsible for the high rate of recurrence, especially in high-risk lesions.

Adult↗
PubMed2001

Post-transfusion alloimmunization to granulocytes and platelets in Japanese patients as determined by the MPHA method.

The current occurrence of alloimmunization to granulocytes and platelets after blood transfusion is unclear due to the fact that antibody assays are cumbersome. Using the MPHA method with extracted granulocyte and platelet antigens, a randomized, blinded trial was conducted to investigate three types of alloantibodies in 431 Japanese patients receiving leukocyte-depleted blood transfusions prepared with or without our latest leukocyte-reduction filter. The frequency of granulocyte, platelet and HLA class I alloantibodies was 0.44%, 0.44% and 16.74%, respectively, in patients receiving non-filtered products and 0%, 0% and 0.49%, respectively, in patients receiving filtered products. The granulocyte antibody reacted with an antigen approximately of 51 KDa. The platelet-specific alloantibody was associated with GPIIb/IIIa and GPIa/IIa. The important factors affecting alloimmunization were the transfusion dose and the use of unfiltered platelet products.

Antibody Formation↗
PubMed2001

Allium chemistry: synthesis, natural occurrence, biological activity, and chemistry of Se-alk(en)ylselenocysteines and their gamma-glutamyl derivatives and oxidation products.

Syntheses are reported for gamma-glutamyl Se-methylselenocysteine (Sa), selenolanthionine (16), Se-1-propenylselenocysteine (Gd), Se-2-methyl-2-propenyl-L-selenocysteine (6e), and Se-2-propynyl-L-selenocysteine (6f). Oxidation of 8a and Se-methylselenocysteine (Ga) gives methaneseleninic acid (24), characterized by X-ray crystallography, and dimethyl diselenide (25). Oxidation of Se-2-propenyl-L-selenocysteine (6c) gives allyl alcohol and 3-seleninoalanine (22). Compound 22 is also formed on oxidation of 16 and selenocystine (4). Oxidation of 6d gives 2-[(E,Z)-1-propenylseleno]propanal (36). These oxidations occur by way of selenoxides, detected by chromatographic and spectroscopic methods. The natural occurrence of many of the Se-alk(en)ylselenocysteines and their gamma-glutamyl derivatives and oxidation products is discussed. Three homologues of the potent cancer chemoprevention agents 6a and 6c, namely 6d-f, were evaluated for effects on cell growth, induction of apoptosis, and DNA-damaging activity using two murine mammary epithelial cell lines. Although each compound displays a unique profile of activity, none of these compounds (Gd-f) is likely to exceed the chemopreventive efficacy of selenocysteine Se-conjugates Ga and 6c.

Allium↗
PubMed2001

Proteomic detection of changes in protein synthesis induced by NGX6 transfected in human nasopharyngeal carcinoma cells.

In the previous study, we cloned a new gene, named NGX6, related to nasopharyngeal carcinoma (NPC) at 9p. To study its function in the pathogenesis of NPC, we have investigated changes in protein synthesis between NPC cell line HNE1 and that transfected with the gene. Using high-resolution two-dimensional electrophoresis, we found that 22 protein spots showed variations that were significant and reproducible. Analysis of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and database searches identified seven proteins that were upregulated and seven proteins that were downregulated. These proteins included Fas, zinc-finger protein (ZNF), RAB, and Ah receptor-interacting protein (AIP). The functional implications of the identified proteins are discussed.

Down-Regulation↗