Biomedical subjects

Wei Zhang

Publications and source records attributed to Wei Zhang.

At least 145 records · Page 8Linked to original sources

PubMed2006

Coexistence of triplet superconductivity and spin density waves.

We discuss the possibility of the coexistence of spin density waves (antiferromagnetism) and triplet superconductivity as a particular example of a broad class of systems where the interplay of magnetism and superconductivity is important. We focus on the case of quasi-one-dimensional metals, where it is known that antiferromagnetism is in close proximity to triplet superconductivity in the pressure versus temperature phase diagram. Over a range of pressures, we propose an intermediate nonuniform phase consisting of antiferromagnetic and triplet superconducting orders. In the coexistence region, we propose a flop transition in the spin density wave order parameter vector, which affects the nature of the superconducting state and leads to the appearance of several new phases.

Journal Article↗

PubMed2006

The neuroprotective role of attractin in neurodegeneration.

Loss-of-function mutations of attractin (Atrn) in animals result in age-dependent progressive neurodegeneration including neuronal cell death, hypomyelination and vacuolation. The mechanisms of how age-dependent neurodegeneration occurs in these animals are not clear. In this study, we found that reducing the endogenous expression level of Atrn exacerbated, whereas overexpressing Atrn protected against, the neuronal cell death caused by the neurotoxins, 1-methyl-4-phenylpyridinium (MPP+) and lactacystin. In addition, both MPP+ and lactacystin-induced cytochrome c and apoptosis inducing factor (AIF) release, which was inhibited by overexpressing Atrn and enhanced by knocking down Atrn, indicating that Atrn may be involved in regulating the mitochondrial function. Furthermore, we found that vast majority of the dopaminergic neurons in mice express Atrn and its expression decreases with age. Our findings demonstrated that Atrn may play a protective role against environmental toxins, and implied a potential therapeutic effect of Atrn for neurodegenerative diseases.

1-Methyl-4-phenylpyridinium↗

PubMed2006

Independent motile microplast formation correlates with glioma cell invasiveness.

Diffuse brain invasion contributes to the poor prognosis for patients with gliomas. Analyzing glioma cell migration in vitro, we have demonstrated the spontaneous shedding of anucleate cell fragments that separate from glioma cell bodies and maintain viability from hours to days. Unlike previously described cell fragments that are released from cells as diffusible vectors, glioma cell fragments are independently motile. We used computerized time-lapse microscopy to characterize the formation of these independent motile microplasts (IMMPs) in human cell cultures derived from the most highly invasive glial tumor, glioblastoma. IMMPs were larger than previously described cell fragments, ranging in size from approximately 2% to nearly half of the area of their parent cells. Complex cell-like behaviors-including establishment of polarity, extension of lamellipodia and filopodia, and change in direction of movement-remained intact in IMMPs. The average direction and velocity of the IMMPs were indistinguishable from those of their parent cells. IMMPs formed at a significantly higher rate in glioma cell lines rendered more invasive by overexpression of invasion-related genes than in vector-transfected controls. The correlation with cell invasiveness indicates that IMMP formation may be related to the cell-invasive phenotype. Further investigation will determine whether IMMPs represent a novel addition to the growing list of viable cell fragments with biological relevance.

Astrocytoma↗

PubMed2006

Regulation of intracellular free calcium concentration during heterocyst differentiation by HetR and NtcA in Anabaena sp. PCC 7120.

Calcium ions are important to some prokaryotic cellular processes, such as heterocyst differentiation of cyanobacteria. Intracellular free Ca(2+)concentration, [Ca(2+)](i), increases several fold in heterocysts and is regulated by CcbP, a Ca(2+)-binding protein found in heterocyst-forming cyanobacteria. We demonstrate here that CcbP is degraded by HetR, a serine-type protease that controls heterocyst differentiation. The degradation depends on Ca(2+) and appears to be specific because HetR did not digest other tested proteins. CcbP was found to bind two Ca(2+) per molecule with K(D) values of 200 nM and 12.8 microM. Degradation of CcbP releases bound Ca(2+) that contributes significantly to the increase of [Ca(2+)](i) during the process of heterocyst differentiation in Anabaena sp. strain PCC 7120. We suggest that degradation of CcbP is a mechanism of positive autoregulation of HetR. The down-regulation of ccbP in differentiating cells and mature heterocysts, which also is critical to the regulation of [Ca(2+)](i), depends on NtcA. Coexpression of ntcA and a ccbP promoter-controlled gfp in Escherichia coli diminished production of GFP, and the decrease is enhanced by alpha-ketoglutarate. It was also found that NtcA could bind a fragment of the ccbP promoter containing an NtcA-binding sequence in a alpha-ketoglutarate-dependent fashion. Therefore, [Ca(2+)](i) is regulated by a collaboration of HetR and NtcA in heterocyst differentiation in Anabaena sp. strain PCC 7120.

Anabaena↗

PubMed2006

[Immunopathological changes of micro-vessels in dermatomyositis].

OBJECTIVE: To investigate the immunopathological changes of micro-vessels in dermatomyositis. METHODS: Twelve patients with dermatomyositis, 5 males and 7 females, aged 40.8 (6 - 72), underwent muscle biopsy of biceps muscle of arm (n = 11) or deltoid muscle (n = 1). The specimens underwent routine histological, enzyme histochemical, and immunohistochemical staining and microscopy. Ten biopsy specimens from patients with other diseases were used as controls. RESULTS: Perifascicular atrophy of muscular fibers and inflammatory infiltration in perimysium were seen in all patients with dermatomyositis. Non-specific esterase staining showed deep staining of capillaries and micro vascular endothelium among the muscular fibers. Immunohistochemistry showed remarkable reduction of capillaries positive in von Willebrand factor (vWF), thrombomodulin (TM), and endothelial cell nitric oxide synthase (eNOS) in the perifascicular region, and low expression of .eNOS and TM in the microvascular endothelium in the perimysium. CONCLUSION: The vascular lesions of dermatomyositis are located not only in capillaries, but also in other microvessels. Lower expression of TM and eNOS in vascular endothelium suggests the reduction of anticoagulation and vasodilation functions of vascular endothelium. Dermatomyositis is an inflammatory vascular endothelial disease.

Adolescent↗

PubMed2006

Comparison of dye degradation efficiency using ZnO powders with various size scales.

ZnO powders with various size scales (mean diameter size: 10, 50, 200 and 1000nm) have been prepared by two different preparation methods, thermal evaporation method and chemical deposition method, and examined as photocatalysts for the UV-induced degradation of methyl orange in water solution. ZnO nanoparticle with diameter size 50nm prepared by thermal evaporation method showed the highest photocatalytic activity. In addition, the tetrapod ZnO nanopowders had the higher efficiency than irregular ZnO particles. However, the smallest 10nm ZnO nanoparticle prepared by chemical deposition method indicated the lower efficiency contrast to 200nm ZnO powders prepared by thermal evaporation method. The results indicated preparation method was the decisive factor rather than size and morphology. Moreover, the effect of catalyst loading, pH value and the initial dye concentration on the final degradation efficiency were discussed through the photocatalytic experiments using 50nm ZnO nanoparticle as photocatalyst.

Azo Compounds↗

PubMed2006

Biomarker analysis on breast ductal lavage cells in women with and without breast cancer.

Recent studies show that morphology based analysis of ductal lavage specimens failed to detect many cancers in women with breast cancer. Such an observation raises doubts about the potential role of ductal lavage in an individual's risk assessment and early detection of breast cancer. We hypothesize that biomarker-based analysis using markers of malignancy field defects including DNA 5c exceeding rate (DNA 5cER) and G-actin might provide a more reliable test for breast cancer risk. The study was performed in 2 phases, the training and validation phase. For the training phase, 36 Chinese women were recruited (13 with breast cancer, 8 with intraductal papilloma and 15 with benign breast diseases). The validation phase included 10 women with cancer and 7 women without cancer. Ductal lavage samples were processed by the ThinPrep technique and evaluated by morphology followed by biomarker analysis using laser scan cytometry (LSC) for G-actin and DNA5cER. In the training phase, biomarker analysis was performed on the 67% (24 of 36) of samples that had over 100 epithelial cells. The sensitivity of DNA5cER was 90% with a specificity of 100%, and G-actin was 100% and 93%, respectively. By contrast, the sensitivity and specificity obtained by cytology alone were 67% and 93%, respectively. Similar results were obtained from the small validation study. Quantitative analysis of biomarkers for G-actin and DNA5cER is feasible and useful in distinguishing benign from malignant breast disease on archived ductal lavage slides. Further studies are warranted to determine the value of these biomarkers in prospective trials.

Actins↗

PubMed2006

Efficient screening method of the thiopurine methyltransferase polymorphisms for patients considering taking thiopurine drugs in a Chinese Han population in Henan Province (central China).

BACKGROUND: Thiopurine S-methyltransferase (TPMT) is an enzyme that catalyzed the S-methylation of thiopurine drugs. TPMT activity exhibits an interindividual variability, mainly as a result of genetic polymorphism. Patients with intermediate or deficient TPMT activity are at risk for toxicity after receiving standard doses of thiopurine drugs. We determined a cut-off concentration of the TPMT activity assay less than which genotyping of the TPMT gene should be performed. In addition, the influence of hemodialysis on TPMT activity in uremic patients was examined. METHODS: In 248 healthy subjects and 30 uremic patients, PCR-based methods were used to analyze the most common functional mutations TPMT2, 3A, 3B and 3C. A HPLC assay was used to measure erythrocyte TPMT activity in the whole population. RESULTS: Seven TPMT3C heterozygotes were identified, while TPMT2, 3A and 3B alleles were not detected in 248 healthy subjects. The frequency of TPMT3C allele was 1.4% (7/496). The TPMT activity in healthy subjects was normally distributed, ranged from 6.09 to 28.65 nmol/h/ml pRBC with a mean of 16.03 +/- 4.16 nmol/h/ml pRBC. The cut-off for high TPMT activity and intermediate TPMT activity was 10.07 nmol/h/ml pRBC. There were 19 intermediate activity healthy subjects (7.7%) and 229 high activity healthy subjects (92.3%), and no TPMT deficiency subject was found. All of the 229 healthy subjects with high activity had no mutant alleles, while 7 of the 19 subjects with intermediate activity had a mutant allele. Phenotypes were in good agreement with genotypes for 95% of subjects. The uremic patients were all homozygous for the wild-type allele whose TPMT activity was activated significantly before hemodialysis compared with TPMT activity after hemodialysis. CONCLUSIONS: We defined the cut-off values for the TPMT phenotyping assay at 10.07 nmol/h/ml pRBC, less than which additional genotyping elucidates the individual risk for drug therapy. In uremic patients, TPMT activity is increased by some uremic factors, and dialysis shifted their TPMT activity close to that of a healthy control group.

Adult↗

PubMed2006

Hepatitis B virus infections in families in which the mothers are negative but the fathers are positive for HBsAg.

We studied a total of 37 families, in which HBsAg was positive in either or both of father and mother, to assess intra-familial transmission of hepatitis B virus (HBV). The HBsAg positive rate for children with HBsAg-negative mothers was significantly lower than that with positive mothers (4 of 31, 12.9% versus 18 of 32, 56.3%, p<0.01) of course. However, there were three families in which the infection source for children was thought to be fathers, not mothers, i.e., of eight children in these three families with HBsAg +/- father/mother pairs, 4 (50%) were positive for both HBsAg and HBV DNA of genotypes identical to those of their fathers, and another child was positive for HBcAb despite being negative for HBsAg. Interestingly, moreover, all the mothers in these three families were HBcAb-positive even though HBsAg-negative, suggesting that not only father-to-child but also inter-spouse HBV transmission might have occurred. With these findings we would suggest that all the family members with HBsAg-positive fathers should receive HBV vaccine, let alone for those with HBsAg-positive mothers.

Journal Article↗

PubMed2006

Regulation of Arabidopsis tapetum development and function by DYSFUNCTIONAL TAPETUM1 (DYT1) encoding a putative bHLH transcription factor.

In flowering plants, male fertility depends on proper cell differentiation in the anther. However, relatively little is known about the genes that regulate anther cell differentiation and function. Here, we report the analysis of a new Arabidopsis male sterile mutant, dysfunctional tapetum1 (dyt1). The dyt1 mutant exhibits abnormal anther morphology beginning at anther stage 4, with tapetal cells that have excess and/or enlarged vacuoles and lack the densely stained cytoplasm typical of normal tapetal cells. The mutant meiocytes are able to complete meiosis I, but they do not have a thick callose wall; they often fail to complete meiotic cytokinesis and eventually collapse. DYT1 encodes a putative bHLH transcription factor and is strongly expressed in the tapetum from late anther stage 5 to early stage 6, and at a lower level in meiocytes. In addition, the level of DYT1 mRNA is reduced in the sporocyteless/nozzle (spl/nzz) and excess microsporocytes1/extra sporogenous cell (ems1/exs) mutants; together with the mutant phenotypes, this suggests that DYT1 acts downstream of SPL/NZZ and EMS1/EXS. RT-PCR results showed that the expression levels of many tapetum-preferential genes are reduced significantly in the dyt1 mutant, indicating that DYT1 is important for the expression of tapetum genes. Our results support the hypothesis that DYT1 is a crucial component of a genetic network that controls anther development and function.

Amino Acid Sequence↗

PubMed2006

Changes in connexin 43, metalloproteinase and tissue inhibitor of metalloproteinase during tachycardia-induced cardiomyopathy in dogs.

OBJECTIVE: To study changes in connexin, metalloproteinase and tissue inhibitor of metalloproteinase levels during tachycardia-induced cardiomyopathy (TIC). METHODS: Canine models of TIC were established by rapid right atrial pacing at 350-400 beats per min for 8 weeks in 11 dogs, six dogs acted as a sham operation group. Echocardiography, left ventricular pressure and its first derivation with time (positive and negative maximum, dp/dtmax, -dp/dtmax), and intracardiac electrograms were recorded before and after rapid pacing at 1, 4 and 8 weeks. Data were acquired in sinus rhythm. Ultrastructural changes in left ventricular tissue were observed by transmission electron microscope. Connexin 43 (Cx43) levels in the left ventricular myocardium were measured by confocal laser microscopy. The relative abundance of matrix metalloproteinase (MMP-2) and tissue inhibitor of metalloproteinase (TIMP-2) were studied by immunoblotting. RESULT AND CONCLUSIONS: (1) Ventricular dilatation and systolic dysfunction occurred after 1 week of rapid right atrial pacing. (2) There was structural damage to the myofibrils, mitochondria, and the sarcoplasmic reticulum with intercalated disk discontinuity. (3) Levels of Cx43 decreased significantly and gap junction remodelling occurred during TIC. (4) TIC may result from several mechanisms, such as ultrastructural changes or gap junction and matrix remodelling.

Animals↗

PubMed2006

Alternative splicing variants of IRF-1 lacking exons 7, 8, and 9 in cervical cancer.

The two previously identified major splice variants of interferon regulatory factor 1 (IRF-1) do not appear to affect IRF-1-mediated gene activation. We searched for additional splice variants and examined their effect on wild-type IRF-1. RT-PCR experiments using normal and malignant human cervical tissue samples revealed five variants lacking some combination of exons 7, 8, and 9; their expression levels were higher in the malignant samples. These variants had predicted deletions of the functional domain or truncated protein isoforms, had different transcriptional activities, and attenuated transcriptional activity of IRF-1. Unlike the cell cycle-dependent IRF-1 transcript, the splice variant mRNA levels remained consistent throughout the cell cycle. The variant proteins were more stable than the IRF-1 protein, which may explain the strong inhibition of IRF-1 transcription in the presence of relatively small quantities of the alternative transcripts. In conclusion, alternative splicing in exons 7, 8, and 9 is an important mechanism for negatively regulating IRF-1 in cervical cancer.

Alternative Splicing↗

PubMed2006

Shape-persistent macrocycles: structures and synthetic approaches from arylene and ethynylene building blocks.

Shape-persistent arylene ethynylene macrocycles have attracted much attention in supramolecular chemistry and materials science because of their unique structures and novel properties. In this Review we describe recent examples of macrocycle synthesis by cross-coupling (Sonogashira: aryl acetylene macrocycle or Glaser: aryl diacetylene macrocycle) and dynamic covalent chemistry. The primary disadvantage of the coupling methods is the kinetically determined product distribution, since a significant portion of oligomers grow beyond the length of the cyclic targets ("overshooting"). Better results have been obtained recently by a dynamic covalent approach involving reversible metathesis reactions that afford macrocycles in one step. Mechanistic studies demonstrate that macrocycle formation is thermodynamically controlled by this route. Remaining synthetic challenges include the efficient preparation of site-specifically functionalized structures and larger, more complex two- and three-dimensional molecules.

Journal Article↗

PubMed2006

[Mesorectal metastasis of middle and lower rectal cancer].

OBJECTIVE: To detect mesorectal metastasis of middle and lower rectal cancer and to evaluate its relationship with clinicopathologic characteristics. METHODS: Cancer specimens resected from 56 patients with middle and lower rectal cancer who received total mesorectal excision were examined by routine pathologic observation. The relationship between mesorectal metastasis and clinicopathologic characteristics of middle and lower rectal cancer was also investigated. RESULTS: Mesorectal metastasis was detected in 36 (64.3%) of 56 cancer specimens. In 18 cancer specimens with tumor diameter > or = 5 cm, 15 (83.3%) were detected mesorectal metastasis, while in 38 cancer specimens with tumor diameter < 5 cm only 21 (55.3%) were detected mesorectal metastasis (P = 0.041). Mesorectal metastasis was more frequent in T(3) cancer specimens (81.5%) and T(2) cancer specimens (56.6%), compared with T(1) cancer specimens (1/6) (P = 0.007). 85.7% poorly differentiated cancer specimens were detected mesorectal metastasis, while moderate and well-differentiated cancer specimens were only 63.2% and 1/5 respectively (P = 0.028). Mesorectal metastasis was more frequent in stage III cancer specimens (100%), compared with stage II and I cancer specimens (27.3% and 1/5 respectively, P = 0.000). No significant correlations were found between mesorectal metastasis and other variables such as age, gender and Ming classification (P > 0.05). CONCLUSION: Mesorectal metastasis of middle and lower rectal cancer has significant correlation with tumor diameter, tumor invasion, tumor differentiation and TNM stage. Total mesorectal excision or > or = 5 cm mesorectal distal to the rectal tumor should be followed in the management of middle and lower rectal cancer.

Adult↗

PubMed2006

A mixture model-based discriminate analysis for identifying ordered transcription factor binding site pairs in gene promoters directly regulated by estrogen receptor-alpha.

MOTIVATION: To detect and select patterns of transcription factor binding sites (TFBSs) which distinguish genes directly regulated by estrogen receptor-alpha (ERalpha), we developed an innovative mixture model-based discriminate analysis for identifying ordered TFBS pairs. RESULTS: Biologically, our proposed new algorithm clearly suggests that TFBSs are not randomly distributed within ERalpha target promoters (P-value < 0.001). The up-regulated targets significantly (P-value < 0.01) possess TFBS pairs, (DBP, MYC), (DBP, MYC/MAX heterodimer), (DBP, USF2) and (DBP, MYOGENIN); and down-regulated ERalpha target genes significantly (P-value < 0.01) possess TFBS pairs, such as (DBP, c-ETS1-68), (DBP, USF2) and (DBP, MYOGENIN). Statistically, our proposed mixture model-based discriminate analysis can simultaneously perform TFBS pattern recognition, TFBS pattern selection, and target class prediction; such integrative power cannot be achieved by current methods. AVAILABILITY: The software is available on request from the authors. CONTACT: lali@iupui.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Algorithms↗

PubMed2006

Long-term depression at the mossy fiber-deep cerebellar nucleus synapse.

Several lines of evidence have indicated that the deep cerebellar nuclei (DCN) are a site of memory storage for certain forms of motor learning, most notably associative eyelid conditioning. In particular, these experiments, together with network models, have implicated the excitatory glutamatergic synapse between mossy fibers and DCN neurons in this memory trace. However, to date, evidence for persistent use-dependent change in the strength of this synapse has been almost entirely absent. Here, we report that high-frequency burst stimulation of mossy fibers, either alone or paired with postsynaptic depolarization, gives rise to long-term depression (LTD) of the mossy fiber-DCN synapse. This form of LTD is not associated with changes in the paired-pulse ratio and is blocked by loading with a postsynaptic Ca2+ chelator but not by bath application of an NMDA receptor antagonist. Mossy fiber-DCN LTD requires activation of a group I metabotropic glutamate receptor (mGluR) and protein translation. Unlike mGluR/translation-dependent LTD in other brain regions, this form of LTD requires mGluR1 and is mGluR5 independent.

Animals↗

PubMed2006

Effect of SLCO1B1 genetic polymorphism on the pharmacokinetics of nateglinide.

AIMS: Nateglinide is a meglitinide analogue with antidiabetic action. A recent study showed that SLCO1B1 (which codes the OATP1B1 gene, also known as OATP-C, OATP2) is a major determinant which markedly affects the pharmacokinetics of repaglinide. Our objective was to assess the association between single nucleotide polymorphisms (SNPs) of SLCO1B1 and the pharmacokinetics of nateglinide. METHODS: Seventeen healthy volunteers with different SLCO1B1 genotypes (11 with 521TT, four with 521TC and two with 521CC) were enrolled in this study. Each was given a single oral dose of 90 mg nateglinide. Plasma concentrations of nateglinide were measured up to 8 h by HPLC. RESULTS: The C(max) and AUC(0,infinity) of nateglinide were 83% (P = 0.002) and 82% (P = 0.001) higher in the SLCO1B1521TC subjects (n = 4), and 76% (P = 0.016) and 108% (P = 0.001) higher in the SLCO1B1521CC subjects (n = 2) than in the SLCO1B1521TT subjects (n = 11), respectively. The t(1/2) of nateglinide in SLCO1B1521CC subjects was 78% longer than that in 521TT subjects (P = 0.036). The difference in t(max) values among the three genotypic groups was not statistically significant. CONCLUSIONS: Our results suggest that OATP1B1-mediated hepatic uptake of nateglinide may be the prior step for its metabolism and elimination. SLCO1B1521T > C SNP might play an important role in the pharmacokinetics of nateglinide.

Adult↗

PubMed2006

Extraordinary plasticity of ductile bulk metallic glasses.

Shear bands generally initiate strain softening and result in low ductility of metallic glasses. In this Letter, we report high-resolution electron microscope observations of shear bands in a ductile metallic glass. Strain softening caused by localized shearing was found to be effectively prevented by nanocrystallization that is in situ produced by plastic flow within the shear bands, leading to large plasticity and strain hardening. These atomic-scale observations not only well explain the extraordinary plasticity that was recently observed in some bulk metallic glasses, but also reveal a novel deformation mechanism that can effectively improve the ductility of monolithic metallic glasses.

Journal Article↗