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Biomedical subjects

Z X Zhou

Publications and source records attributed to Z X Zhou.

At least 19 recordsLinked to original sources
PubMed2005

Colossal magnetoresistance by avoiding a ferromagnetic state in the Mott system Ca3Ru2O7.

Transport and magnetic studies of Ca3Ru2O7 for temperatures ranging from 0.4 to 56 K and magnetic fields B up to 45 T lead to strikingly different behavior when the field is applied along the different crystal axes. A ferromagnetic (FM) state with full spin polarization is achieved for the B//a axis, but colossal magnetoresistance is realized only for the B//b axis. For the B//c axis, Shubnikov-de Haas oscillations are observed and followed by a less resistive state than that for B//a. Hence, in contrast with standard colossal magnetoresistive materials, the FM phase is the least favorable for electron hopping. These properties together with highly unusual spin-charge-lattice coupling near the Mott transition (48 K) are driven by the orbital degrees of freedom.

Journal Article↗
PubMed2000

Suppression by metallothionein of doxorubicin-induced cardiomyocyte apoptosis through inhibition of p38 mitogen-activated protein kinases.

Cardiomyopathy induced by doxorubicin (DOX) has long been a major impediment of clinical applications of this effective anticancer agent. Previous studies have shown that cardiac-specific metallothionein (MT)-overexpressing transgenic mice are highly resistant to DOX-induced cardiotoxicity. To investigate cellular and molecular mechanisms by which MT participates in this cytoprotection, transgenic mice containing high levels of cardiac MT and non-transgenic controls were treated intraperitoneally with DOX at a single dose of 15 mg/kg and sacrificed on the 4th day after treatment. Myocardial apoptosis was detected by a terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assay and confirmed by electron microscopy of immunogold staining of apoptotic nuclei. Dual staining of cardiac alpha-sarcomeric actin using an immunohistochemical method further identified apoptotic myocytes. Apoptosis was significantly inhibited in the transgenic myocardium. The anti-apoptotic effect of MT was further revealed in primary cultures of neonatal mouse cardiomyocytes. Furthermore, DOX activated p38 mitogen-activated protein kinase (MAPK), which was critically involved in the apoptotic process, as demonstrated by inhibition of DOX-induced apoptosis by a p38-specific inhibitor, SB203580. Both DOX-induced p38 MAPK activation and apoptosis were dramatically inhibited in the transgenic cardiomyocytes. The results thus demonstrate that DOX induces apoptosis in cardiomyocytes both in vivo and in vitro and MT suppresses this effect through at least in part inhibition of p38 MAPK activation.

Animals↗
PubMed2000

Metallothionein inhibits myocardial apoptosis in copper-deficient mice: role of atrial natriuretic peptide.

Dietary copper restriction causes heart hypertrophy in animal models. Several studies have indicated that this cardiomyopathy is mediated by oxidative stress. Metallothionein (MT), a low molecular weight and cysteine-rich protein, functions in protecting the heart from oxidative injury. We therefore used a cardiac-specific MT-overexpressing transgenic mouse model to test the hypothesis that MT inhibits copper deficiency-induced heart hypertrophy. Dams of both transgenic pups and non-transgenic littermates were fed a copper-adequate or copper-deficient diet, starting on the fourth day post-delivery, and the weanling mice were continued on the dams' diets until they were killed. Heart hypertrophy developed in copper-deficient pups by the fourth week of the combined pre- and post-weaning feeding and aggressively progressed until the end of the experiment (6 weeks). MT overexpression did not prevent the occurrence of heart hypertrophy, but inhibited the progression of this cardiomyopathy, which correlated with its suppression of cardiac lipid peroxidation. Corresponding to the progression of heart hypertrophy, myocardial apoptosis and atrial natriuretic peptide (ANP) production in the left ventricle were detected in non-transgenic copper-deficient mice; these effects were significantly suppressed in transgenic copper-deficient mice. Measurement of apoptosis by TUNEL assay and Annexin V-FITC confocal microscopy in primary cultures of cardiomyocytes revealed that ANP was largely responsible for the myocyte apoptosis and that MT inhibited ANP-induced apoptosis. The data clearly demonstrate that elevation of MT in the heart inhibits oxidative injury and suppresses the progression of heart hypertrophy in copper deficiency, although it does not block its initiation. The results suggest that MT inhibits the transition from heart hypertrophy to failure by suppressing apoptosis through inhibition of both cardiac ANP production and its apoptotic effect.

Animals↗
PubMed2000

[A study of a mutant of thermostable alkaline phosphatase].

To reveal the mechanism of protein thermostability, we used in vivo random mutagenesis to generate variants of pTAP503F which contained thermostable alkaline phosphatase (FD-TAP). After screening about 5,000 clones, we obtained 4 temperature-sensitive mutants. The study of enzymatic properties of one mutant (TAPM3) showed that the thermostability of the mutant enzyme descended a lot, compared to the wild type, while the thermoactivity remained stable. DNA sequencing showed that the G-A transition in position 1,239 resulted in the substitution from glysine to serine in position 427. This mutation conspicuously affected thermostability, Michaelis constant and energy of activation. This suggests that only one substitution of amino acid will make great changes in thermostability and other properties, meanwhile, side-chain size, charge of residues and so on, which loosen the structure of protein, will result in the descent of thermostability.

Alkaline Phosphatase↗
PubMed1999

[Correlation analysis of (G + C)% of coding sequence and thermostability of xylose isomerase of thermophiles].

Statistical analysis about amino acids and coding sequence of xylose isomerase were performed in a number of thermophiles and mesophiles. It was found that there are correlations between the (G + C)% of the coding sequence and that of 1st, 2nd and 3rd position of the code of amino acids. There were also positive (for hydrophobic amino acids) and negative (for hydrophilic amino acids) correlation between the content of individual amino acids in the enzyme protein and the (G + C)% of their respective coding sequence. It speaks for the notion that high content of (G + C) in the coding sequence tends to increase the thermostability of the corresponding protein. The results in the statistical analysis of amino acid substitutions leading to change in thermostability of the protein may also be interpreted in the same way. An increase in the (G + C)% of DNA of a bacterium can therefore not only increase the thermostability of DNA itself but its proteins as well. Evolutionary consequence concerning thermophily and coding system are discussed.

Aldose-Ketose Isomerases↗
PubMed1998

Computer analysis system of blood oxygen saturation in an animal hypoxia model.

An experimental animal hypoxia model has been developed. It consists of two sensors (an in vitro and in vivo model), an experimental device and a computer signal processing system. This method can easily be applied to determine and analyse blood oxygen saturation at various hypoxia levels. It can also be used to evaluate the accuracy of pulse oximetry over a wide range of oxyhemoglobin desaturation levels. The DC and AC components of recorded red and infra-red signals, the dual-wavelength ratio R12 and the reading of a pulse oximeter (SpO2) can be automatically calculated and displayed on a computer screen. Preliminary results of the animal hypoxia test indicate that the measurements made by the instrument correlate well with the oxygen saturation readings of the automatic blood gas analyser AVL945. The computer analysis system is suitable for repeated estimations in the animal model.

Animals↗
PubMed1996

Reduced androgen receptor gene expression with first exon CAG repeat expansion.

The molecular basis for partial androgen insensitivity associated with adult onset spinal/bulbar muscular atrophy was investigated by transient transfection of human androgen receptor (AR) expression vectors containing increasing CAG repeat lengths in the first exon. An inverse relationship was observed between CAG repeat length and AR mRNA and protein levels. Trinucleotide repeat lengths of 43 and 65 associated with spinal/bulbar muscular atrophy decreased AR mRNA and protein levels but did not alter equilibrium binding affinity for [3H]R1881 or inherent transcriptional activity of AR, expressed as androgen-dependent fold induction of a mouse mammary tumor virus promoter-luciferase reporter vector. The findings indicate that glutamine expansion up to 66 residues in the NH2-terminal domain of AR does not alter AR functional activity. Rather, CAG repeat expansion in the region of the first exon reduces AR mRNA and protein expression. The study reveals a previously unrecognized effect of CAG repeat length on AR mRNA expression and a novel molecular mechanism for androgen resistance.

Androgens↗
PubMed1995

Evidence for an anti-parallel orientation of the ligand-activated human androgen receptor dimer.

Domain interactions of the human androgen receptor (AR) dimer were investigated using a protein-protein interaction assay in which the NH2- and carboxyl-terminal regions of human AR were fused to the Saccharomyces cerevisiae GAL4 DNA-binding domain and herpes simplex virus VP16 transactivation domain to produce chimeric proteins. Transcriptional activation of a GAL4 luciferase reporter vector up to 100-fold was greater than Fos/Jun leucine zipper binding, indicating stable AR interaction between AR NH2-terminal residues 1-503 and steroid-binding domain residues 624-919 that was specific for and dependent on androgen binding to the steroid-binding domain and was inhibited by anti-androgen binding. Deletion mutagenesis within the NH2-terminal region indicated transactivation domain residues 142-337 were not required for dimerization, whereas deletions near the NH2 terminus (delta 14-150) or NH2-terminal to the DNA-binding domain (delta 339-499) reduced or eliminated the AR interaction, respectively. An NH2-/NH2-terminal interaction was also observed, but no interaction was detected between ligand-free or bound steroid-binding domains. The results indicate that high affinity androgen binding promotes interactions between the NH2-terminal and steroid-binding domains of human AR, raising the possibility of an androgen-induced anti-parallel AR dimer.

Animals↗
PubMed1995

Role of glycoconjugates in adherence of Salmonella pullorum to the intestinal epithelium of chicks.

1. The distribution of glycoconjugates on the surface of Salmonella pullorum and the ileal epithelium of chicks was demonstrated by lectin cytochemistry. The role of glycoconjugates in adherence of S. pullorum to the ileal epithelium was determined by a sugar inhibition assay using the scanning electron microscope. 2. S. pullorum exhibited binding to Concanavalin A (Con A) and wheat germ agglutinin (WGA) but not to soyabean agglutinin (SBA), Ricinus communis agglutinin (RCA) and Ulex europaeus agglutinin (UEA). 3. The ileal epithelium of chicks bound WGA, Con A and SBA. The binding sites for WGA were on the brush border and cytoplasm of columnar enterocytes as well as on goblet cells. The binding of Con A was confined to the cytoplasm of columnar enterocytes, while SBA bound, in a limited way, to the brush border of columnar enterocytes. 4. After an oral dose of S. pullorum, adherence to the ileal epithelium was inhibited by methyl alpha-D-mannopyranoside.

Animals↗
PubMed1995

Specificity of ligand-dependent androgen receptor stabilization: receptor domain interactions influence ligand dissociation and receptor stability.

The molecular basis for the different physiological effects of testosterone (T) and dihydrotestosterone (DHT) was investigated using recombinantly expressed wild-type and mutant androgen receptor (AR). Rates of androgen dissociation from nuclear and cytoplasmic AR were compared with hormone- and concentration-dependent receptor degradation rates. T dissociates from AR 3 times faster than DHT or methyltrienolone (R1881) and is less effective in stabilizing the receptor. Analysis of AR deletion mutants and AR/glucocorticoid receptor chimeras indicates that the AR NH2-terminal domain has a specific role in stabilizing the receptor by slowing the rate of ligand dissociation and AR degradation. Amino acid mutations that abolish receptor dimerization, nuclear localization, or DNA-binding activity have no significant effect on androgen dissociation or AR degradation. A naturally occurring steroid-binding domain mutation (Val889 to Met) that causes androgen insensitivity, but does not alter equilibrium androgen binding affinity, lowered the androgen-binding capacity as a result of increased rates of androgen dissociation and AR degradation. Thus, AR stabilization and function require prolonged receptor occupancy with androgen, with a similar extent of stabilization observed at higher concentrations of faster dissociating androgens and lower concentrations of slower dissociating androgens. Retention of receptor-bound androgen is enhanced by an interaction between the AR NH2-terminal and steroid-binding domains. The ligand specificity and concentration dependence of receptor stabilization provide an explanation for physiological differences in the actions of T and DHT.

Animals↗
PubMed1995

Identification of three proline-directed phosphorylation sites in the human androgen receptor.

Full-length wild type and deletion mutant human androgen receptors (AR) were transiently expressed in monkey kidney COS cells to identify the phosphorylated amino acid residues. Phosphoamino acid analysis indicated serine (Ser) and threonine (Thr) residues as the major sites of phosphorylation. Both NH2- and carboxyl-terminal fragments containing the DNA-binding domain were highly phosphorylated, suggesting the presence of phosphorylation sites throughout the protein. Site-directed mutagenesis of wild type and deletion mutant AR at proline-directed consensus phosphorylation sites replaced Ser or Thr residues with Ala; wild type and mutant ARs were expressed in the presence of [32P]orthophosphate and isolated by immunoprecipitation using AR-specific antipeptide antibodies. Three proline-directed phosphorylation sites were identified: Ser 81 and 94 in the NH2-terminal region and Ser 650 in the hinge region. Expression of a series of NH2-terminal AR fragments provided evidence for additional sites in the NH2-terminal region. The effect of loss of each phosphorylation site on receptor function was determined by introducing the Ser to Ala mutations into full-length AR. Substituting Ser 81 and 94 with Ala had little effect on transcriptional activity when assayed by transient cotransfection. Substituting Ser 650 with Ala in the hinge region reduced transcriptional activity up to 30%. The results suggest at least three proline-directed phosphorylation sites in AR, one of which, serine 650, contributes to optimal gene activation by AR.

Alanine↗
PubMed1994

A ligand-dependent bipartite nuclear targeting signal in the human androgen receptor. Requirement for the DNA-binding domain and modulation by NH2-terminal and carboxyl-terminal sequences.

The amino acid sequence requirements for androgen-dependent androgen receptor nuclear import were determined by immunostaining transiently expressed full-length wild type and mutant human androgen receptors (AR) in monkey kidney COS cells and measuring transcriptional activity by cotransfection with a luciferase reporter vector in monkey kidney CV1 cells. Mutagenesis studies revealed a bipartite nuclear targeting sequence in the DNA binding and hinge regions at amino acids 617-633, consisting of two clusters of basic amino acids separated by 10 amino acids, (sequence: see text). In a series of deletion mutants, AR NH2-terminal fragments (residues 1-639 through 1-723) displayed constitutive nuclear import, and transcriptional activity was similar to that of the ligand-activated full-length wild type AR. In contrast, nuclear import and transcriptional activation were inhibited by sequence extensions into the steroid-binding domain (1-771). Constitutive nuclear import was regained in part by NH2-terminal deletions of full-length AR. Expression of AR/pyruvate kinase chimeras defined a sequence required for pre-dominant nuclear localization as residues 580-661, comprised of the second zinc finger region of the DNA-binding domain, the 17-amino-acid putative targeting sequence, and 28 residues of flanking carboxyl-terminal sequence. These studies suggest that the bipartite nuclear targeting sequence of AR includes flanking sequence and is modulated by interactions between the NH2-and carboxyl-terminal regions.

Amino Acid Sequence↗
PubMed1994

Characterization of glycoconjugates in the endometrium of the miniature pig during different reproductive periods.

Lectin-binding glycoconjugates in the endometrium of miniature pigs were determined for sexually immature, dioestrus, oestrus and early pregnancy periods, using five horseradish peroxidase-labelled lectins. Apparent changes associated with sexual maturity were increases in binding intensity of wheat germ agglutinin (WGA), Glycine max agglutinin (SBA) and Ulex europaeus agglutinin (UEA) and the appearance of Ricinus communis agglutinin (RCA) binding. The binding intensity of WGA, SBA and UEA further increased at oestrus, particularly for UEA which showed a stage-specific binding on the surface of endometrial epithelium. Pregnancy-related changes included an increase in WGA binding and a decrease in UEA and RCA binding. The results indicate that stage-specific alterations in lectin binding glycoconjugates occur in the endometrium of pigs associated with sexual maturity and the reproductive cycle.

Animals↗
PubMed1993

Steroid requirement for androgen receptor dimerization and DNA binding. Modulation by intramolecular interactions between the NH2-terminal and steroid-binding domains.

Infection of Spodoptera frugiperda Sf9 insect cells with recombinant human androgen receptor (AR) baculovirus results in expression of a 118-kDa phosphoprotein that displays high affinity androgen binding and androgen-dependent targeting to the nucleus. Using the DNA mobility shift assay, specific in vitro binding of full-length AR to androgen response element DNA (ARE) requires intracellular hormone exposure. The ability of a variety of steroids to induce ARE binding paralleled their transcriptional potential. Certain antihormones, cyproterone acetate and RU486, promote ARE binding, but a pure antiandrogen, hydroxyflutamide, inhibits AR binding to ARE DNA. AR dimerization requires incubation of recombinant baculovirus-infected insect cells with androgen, but only when one or both components of the dimer contain the NH2-terminal domain. Based on the intensities of ARE binding and lack of binding to an ARE half-site, it appears that, unlike the glucocorticoid receptor, AR binds DNA primarily as a dimer. Thus, full-length baculovirus-expressed AR requires intracellular hormone exposure for dimerization and ARE binding to overcome inhibition imposed by the AR NH2-terminal domain. Antihormones with agonist activity promote dimerization and ARE binding, while a pure antiandrogen blocks AR DNA binding. It is concluded that intramolecular interactions between the NH2-terminal and steroid-binding domains are regulated by the specificity of hormone binding and modulate receptor dimerization and DNA binding.

Androgens↗
PubMed1992

[Factors influencing recurrence and metastasis after curative resection for rectal carcinoma].

This paper analyzes 737 cases of curative resection for rectal carcinoma treated from January 1958 to December 1987. Males 407 and females 330. The ages ranged from 17-84. The follow up period was 1 to 30 years. 217 patients developed recurrence or metastasis and the disease-free survival was 3 months to 15.5 years with a median of 24.2 months. Most of the recurrence occurred in 2 years and was found in the pelvis after abdominoperineal resection and the site of anastomosis after anterior resection. The chief metastatic sites were: lung, liver and inguinal nodes in order of frequency. Factors influencing recurrence and metastasis were: site of cancer, Dukes stage, pathologic type, differentiation of cancer, node involvement, and method of operation. Adjuvant irradiation could reduce local recurrence. Patients prone to developing recurrence should be closely followed and the resectable lesions be resected whenever possible.

Adenocarcinoma↗
PubMed1991

A frameshift mutation destabilizes androgen receptor messenger RNA in the Tfm mouse.

A composite mouse androgen receptor DNA sequence was obtained by amplifying genomic DNA or cDNA using the polymerase chain reaction. The open reading frame was 2,697 basepairs, encoding a polypeptide of 899 amino acids (98,204 mol wt). Amino acid sequence comparisons indicated that the mouse androgen receptor (AR) is 97% homologous with rat AR and 83% with human AR. The amino acid sequences of the three receptors are identical within the DNA- and steroid-binding domains. Northern blot analysis revealed the predominant mouse AR mRNA to be 10 kilobases (kb). A 1.7-kb mRNA species was detected in mouse kidney using a cDNA probe containing only 5' untranslated AR sequence. Lack of hybridization with AR-coding sequence probes suggested that the 1.7-kb mRNA was not a truncated form of AR mRNA. Sequencing of genomic DNA isolated from testicular feminized (Tfm) mice revealed a single base deletion in the N-terminal domain, resulting in a frameshift mutation. Cycloheximide treatment caused a dramatic increase in AR mRNA in kidneys of Tfm mice, but not wild-type mice, suggesting that the Tfm mutation results in an unstable AR mRNA.

Amino Acid Sequence↗
PubMed1990

Scanning and transmission electron microscopic observations of bacteria adhering to ileal epithelial cells in growing broiler and White Leghorn chickens.

1. Bacteria adhering to the ileal epithelial cells in broiler and White Leghorn (WL) chickens aged 1 to 60 d were observed with scanning (SEM) and transmission (TEM) electron microscopes. 2. In SEM observations, bacteria were not found on day 1 after hatching in either breed. In 10-d-old broilers many bacteria were observed around the apical area of villi. The number decreased with age and disappeared by 50 d. In WL chicks, the bacteria were first observed at 20 d. Numbers were much fewer than in broilers and none were seen after 30 d. 3. TEM investigations showed that bacteria had a cytoplasmic membrane, cell wall and nucleus but no nuclear membrane and organella, were compartmentalised and resembled Streptobacillus moniliformis. At the attachment zone to the epithelium, many mitochondria were observed in the epithelial cells; the bacterial membrane did not fuse to the epithelial cell membrane except at the apex of the attachment end where the bacterial membrane seemed to undergo lysis, suggesting a possibility that some bacterial components were transferred to the epithelial cells. 4. It is possible that the bacterial aid in the functioning of ileal epithelial cells. Possible functions are discussed in relation to the morphological features.

Animals↗