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Biomedical subjects

M Zhan

Publications and source records attributed to M Zhan.

At least 19 recordsLinked to original sources
PubMed2006

Transcriptional profiling suggests that Barrett's metaplasia is an early intermediate stage in esophageal adenocarcinogenesis.

To investigate the relationship between Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), we determined gene expression profiles of discrete pathological stages of esophageal neoplasia using a sequence-verified human cDNA microarray. Fifty one RNAs, comprising 24 normal esophagi (NE), 18 BEs, and nine EACs were hybridized to cDNA microarrays. Five statistical analyses were used for the data analysis. Genes showing significantly different expression levels among the three sample groups were identified. Genes were grouped into functional categories based on the Gene Ontology Consortium. Surprisingly, the expression pattern of BE was significantly more similar to EAC than to NE, notwithstanding the known histopathologic differences between BE and EAC. The pattern of NE was clearly distinct from that of EAC. Thirty-six genes were the most differentially modulated, according to these microarray data, in BE-associated neoplastic progression. Twelve genes were significantly differentially expressed in cancer-associated BE's plus EAC (as a single combined tissue group) vs noncancer-associated BE's. These genes represent potential biomarkers to diagnose EAC at its early stages. Our results demonstrate that molecular events at the transcriptional level in BE are remarkably similar to BE's-associated adenocarcinoma of the esophagus. This finding alarmingly implies that BE is biologically closer to cancer than to normal esophagus, and that the cancer risk of BE is perhaps higher than we had imagined. These findings suggest that changes modulated at the molecular biologic level supervene earlier than histologic changes, and that BE is an early intermediate stage in the process of EAC.

Adenocarcinoma↗
PubMed2005

Interferon-beta-1a induces increases in vascular cell adhesion molecule: implications for its mode of action in multiple sclerosis.

We investigated soluble vascular cell adhesion molecule-1 (sVCAM) levels and MRI lesions over 24 weeks in 15 Relapsing Remitting MS (RRMS) patients randomized prospectively to receive once-weekly (qw) IFN-beta-1a 30 mug intramuscularly (IM) (Group I, 8 patients) or three-times-weekly (tiw) IFN-beta-1a 44 mug subcutaneously (SC) (Group II, 7 patients). Both groups demonstrated a significant increase in sVCAM during treatment when compared to pre-treatment levels. Patients on IFN-beta-1a 44 mug SC tiw had a significant (p<0.0001) mean increase in sVCAM of 321.9 ng/ml which was significantly greater (p<0.0001) than with IFN-beta-1a 30 mug IM qw (68.6 ng/ml). There was a negative correlation between combined unique (CU) MRI lesions and sVCAM levels within the IFN-beta-1a 44 mug SC tiw group (slope=-0.00106, p=0.009). We postulate that the mode of action of IFN-beta therapy in MS may involve the induction of an increase in sVCAM. sVCAM could bind VLA-4 on T-cells and intercept their adhesion to the blood brain barrier (BBB). This mechanism is consistent with the observed clinical effect of IFN-beta in reducing MRI contrast enhancing lesions.

Analysis of Variance↗
PubMed2005

Epidemiology of capsular and surface polysaccharide in Staphylococcus aureus infections complicated by bacteraemia.

Staphylococcus aureus is a leading cause of serious hospital- and community-acquired infections. The discovery of serologically distinct capsular polysaccharides on the surface of clinical isolates has allowed the development of vaccines and passive protective immunity. We have studied patient characteristics, infection characteristics and the surface and capsular polysaccharide serotype distribution in patients with S. aureus infections complicated by bacteraemia admitted to VA hospitals in Maryland between 1995 and 2000. Nine hundred and ninety-three blood cultures from 331 patients were positive for S. aureus. Thirty-eight percent of patients had diabetes, 11% had end-stage renal failure, and 23% were injection drug users. Forty-two percent of infections were caused by methicillin-resistant strains (MRSA), and 60% were acquired during hospitalization. Serotyping of the first available isolate per patient (N=234 isolates) using polyclonal antibodies showed three major phenotypes--42%, type 8 (T8) capsule; 50%, type 5 (T5) capsule; and 8%, 336 polysaccharide. MRSA isolates were significantly more likely to be T5 than methicillin-susceptible isolates (66% vs. 39%, P<0.001). The proportion of T5 MRSA increased significantly (years 1-2: 41%; years 3-4: 65%; years 5-6: 90%, P<0.001). This large sample of patients with serious S. aureus infection confirms that capsular polysaccharides T5 and T8 cause most human infections, and together with serotype 336, account for nearly all those with bacteraemia.

Bacteremia↗
PubMed2004

Phosphatidylinositide 3-kinase/AKT in radiation responses.

Ionizing or ultraviolet radiation-induced cellular survival signaling pathways induce development of cancer and insensitivity of tumor cells to radiation therapy. Accumulating evidence suggests that the phosphatidylinositide 3-kinase (PI3K)/AKT signal pathway is a major contributor to radioresistance. In many cell types PI3K/AKT signaling is a key cytoprotective response downstream of the EGFR family receptors and mediated carcinogenesis. Cytokines, such as HGF, IGF-I, and IL-6 also protects cells against apoptosis induced by radiation through PI3K/AKT pathway. The mechanics by which PI3K/AKT signaling functions in radiation responses may include its regulation of mitochondrial proteins, transcription factors, translation machinery, and cell-cycle progression. In addition, cross-talk between the PI3K/AKT pathway and mitogen-activated protein kinases, protein kinase A, and protein kinase C signal pathway may also play an important role.

Animals↗
PubMed2004

Signalling mechanisms of anoikis.

Apoptosis following loss of cell anchorage ('anoikis') is of relevance for development, tissue homeostasis and disease. Integrins regulate cell viability through their interaction with the extracellular matrix and they can sense mechanical forces arising from the matrix and convert these stimuli to chemical signals capable of modulating intracellular signal transduction. Recently it has been shown that protein kinase signalling pathways and apoptosis-related molecular control anoikis both positively and negatively. Focal adhesion kinase, when activated by integrins, can suppress anoikis. Phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase may mediate the anoikis-suppressing effects of cells. Conversely, the stress-activated protein kinase/Jun amino-terminal kinase pathway promotes anoikis. In addition, certain bcl-2 and bcl-2-related proteins may also participate in the regulating of anoikis. In this review, molecular mechanisms of signal pathway inducing and perpetuating detachment-induced apoptosis will be discussed with special emphasis on the role of integrins, focal adhesion kinase, phosphatidylinositol 3-kinase/Akt, mitogen-activated protein kinase and bcl-2 family members.

Animals↗
PubMed2001

Phase locking in on-off intermittency.

Dynamical behavior of on-off intermittency around chaos synchronization-desynchronization bifurcation parameter line is investigated in coupled identical chaotic oscillators. Along this parameter line, we find that on-off intermittency can transit from phase-unlocking status to phase-locking one in the phase space of variable differences, which can be regarded as a codimension-two bifurcation, i.e., combinative bifurcations of desynchronization and phase locking. In the phase-locking case, the motions of all oscillators are chaotic and they show on-off intermittency with respect to the synchronous manifold, however, spatial phase order of variable differences is clearly established.

Journal Article↗
PubMed2001

Wild type p53 sensitizes soft tissue sarcoma cells to doxorubicin by down-regulating multidrug resistance-1 expression.

BACKGROUND: p53 mutations occur in almost half of all soft tissue sarcomas (STS) and may contribute to multidrug resistance (MDR) in patients with STS. Doxorubicin (Dox) is one of the most active single agents in STS but is less effective in STS with p53 mutations. The effect of reintroducing wild type (wt) p53 into STS cells harboring p53 mutations on the cytotoxicity of DOX in vitro and in vivo was studied. METHODS: The following cell lines were used in this study: SKLMS-1 STS cells, which do not express wt p53; two wt p53 stable transfectant cells derived from SKLMS-1 cells; and SKLMS-1 transfectant cells from a p53 temperature-sensitive mutant that expresses wt p53 at 32 degrees C and mutant p53 at 38 degrees C. The cytotoxicity of Dox was examined by [3-(4,5-dimethylthiazzol-2-yl)-2,5-diphenltetrazolium] (MTT) and clonogenetic assay, and the effect of reintroducing wt p53 on tumor suppression by Dox was evaluated with a tumorigenicity assay. DNA fragmentation was used to detect apoptosis. MDR-1 P-glycoprotein (P-gp) expression was detected by Western blot and immunohistochemical analyses of protein levels and by Northern blot analysis of mRNA levels, respectively. The intracellular accumulation of Dox was detected by flow cytometric analysis. RESULTS: The 50% inhibitory concentration (IC(50)) of Dox for the SKLMS-1 wt p53 transfectants decreased 16-fold compared with SKLMS-1 parental cells expressing mutant p53. Colony formation of SKLMS-1 cells after Dox treatment also was inhibited by wt p53 reintroduction. The tumorigenicity of SKLMS-1 cells was inhibited by wt p53 reintroduction alone or by Dox treatment alone and was inhibited further when p53 introduction was combined with Dox treatment in severe combined immunodeficient mice. Although no difference in DNA fragmentation, Bax expression, or Bcl-2 expression was detected among wt p53 transfectants and parental SKLMS-1 cells after Dox treatment, MDR-1 P-gp expression was decreased in wt p53 transfectants compared with parental SKLMS-1 cells. Furthermore, higher intracellular accumulations of Dox were found in wt p53 transfectants than that in SKLMS-1 cells. CONCLUSIONS: Reintroduction of wt p53 into STS cells harboring p53 mutations can enhance their chemosensitivity to Dox through the inhibition of MDR-1 P-gp expression. Thus, the combination of p53 gene therapy and chemotherapy may increase the therapeutic efficacy in the treatment of patients with STS.

Apoptosis↗
PubMed2001

Generalized splay state in coupled chaotic oscillators induced by weak mutual resonant interactions.

Dynamic behavior of coupled chaotic oscillators is investigated. A transition from high-dimensional hyperchaos to a generalized periodic splay state is found for extremely weak coupling. Chaotic nature of a single oscillator and mutual resonant interactions are regarded to be responsible for this self-organized ordering. The functional phase distribution of the generalized splay state, which is essentially different from the equal-phase-separation distribution of the conventional splay states, can be well predicted by analyzing a single periodically forced oscillator.

Journal Article↗
PubMed2000

A whole-genome assembly of Drosophila.

We report on the quality of a whole-genome assembly of Drosophila melanogaster and the nature of the computer algorithms that accomplished it. Three independent external data sources essentially agree with and support the assembly's sequence and ordering of contigs across the euchromatic portion of the genome. In addition, there are isolated contigs that we believe represent nonrepetitive pockets within the heterochromatin of the centromeres. Comparison with a previously sequenced 2.9- megabase region indicates that sequencing accuracy within nonrepetitive segments is greater than 99. 99% without manual curation. As such, this initial reconstruction of the Drosophila sequence should be of substantial value to the scientific community.

Algorithms↗
PubMed2000

Optimizing human demineralized bone matrix for clinical application.

The use of human demineralized bone matrix (DBM) powder in periodontal and orthopedic applications is limited by the variability in the osteoinductive or osteoconductive properties of the material. The goal of the present study was to establish simple in vitro and in vivo assays of DBM that would allow us to screen different lots of the material prior to testing in more rigorous animal models. The results demonstrate a wide variability in the performance of individual lots of DBM powder obtained from a single tissue bank. The studies also demonstrate that relatively simple screening can be used to establish the quality of the different lots, and that performance and ease of handling can be improved by using relatively small particle sizes delivered in a fibrin sealant matrix.

Animals↗
PubMed2000

Synchronization of chaos in coupled systems

The stability of synchronous chaos of coupled oscillators with diffusive and gradient couplings is investigated. The stability boundaries of all transverse modes can be simultaneously drawn by justifying the boundary of a single mode, according to a scaling relation. Therefore, the distribution of stable and unstable regions can be explicitly shown in control parameter space. Bifurcations through different unstable modes, leading to different spatial orders, are analyzed.

Journal Article↗
PubMed2000

Nonlocal chaotic phase synchronization

A novel synchronization behavior, nonlocal chaotic phase synchronization, is investigated. For two coupled Rossler oscillators with only one forced by an injected periodic signal, the phase of the unforced oscillator can be locked to the phase of the periodic signal while the forced one is well unlocked by the signal; in a chain of coupled chaotic oscillators with nearest coupling, the phase of an oscillator (or a cluster) can be locked to another nonneighbor one. Moreover, the mechanism underlying the transition to nonlocal synchronization is discussed in detail.

Journal Article↗
PubMed2000

Intermingled basins and on-off intermittency in a multistate system

We consider a dynamical system containing infinite low-dimensional symmetric invariant subspaces, each of which has a chaotic state. Intermingled basins are found between these multiple chaotic states when they are stable in the subspaces. As a parameter of the system varies, the largest Lyapunov exponent transverse to the invariant subspace can change from negative to positive; then, the system dynamics changes from an intermingled basin state to a multistate on-off intermittency. The statistical behavior and physical transportation property for different dynamic states are investigated in detail.

Journal Article↗
PubMed2000

[Preliminary study on pathogenicity of hepatitis G virus].

OBJECTIVE: To study the clinical, enzymatic and liver pathological changes in patients with hepatitis G virus (HGV) infection. METHODS: RT- nested PCR was applied to detect HGV RNA in 368 patients with hepatic diseases. The liver biopsy tissue from one liver cirrhosis patient with simple HGV infection was examined. RESULTS: Simple HGV RNA positive were found in 7 cases of 71 acute hepatitis jaundice, in 22 cases of 155 chronic hepatitis and in 3 cases of 51 liver cirrhosis. The immunohistochemistry of the liver biopsy tissue from a liver cirrhosis patient showed HGV NS5 antigen positive. However, HGV infection might occur simply or in combination with hepatitis B or C virus or super infected. CONCLUSIONS: HGV RNA could be detected in acute hepatitis jaundice, chronic hepatitis, hepatitis B or C carriers, liver cirrhosis and hepatocellular carcinoma. HGV is proved to be a hepatotropic virus by pathological examination and immunohistochemistry, the virus located in the cytoplasm of the liver cells. It may cause chronic hepatitis and even liver cirrhosis, so HGV is pathogenic to liver tissue.

Adolescent↗
PubMed2000

[Coexpression of the preS1(1-42) and the Core(1-144) antigen of HBV in E. coli].

OBJECTIVE: To study the therapeutic T cell vaccine for the treatment of chronic hepatitis B. METHODS: The genes of HBcAg (1-144) and preS1 Ag (1-42) were amplified and fused by PCR. This fusion gene was inserted in the prokaryotic expression vector pET-11d and expressed in E. coli. RESULTS: It was showed by SDS-PAGE that the protein molecular weight of the coexpression product was about 20,000, twenty percent of all bacteria protein. The monoclone antibody against Core and preS1 antigen could react with this fused protein by Western-blot technique respectively. The fused gene was verified by sequencing. Under the immune electron microscopy, this fused protein is a typical particle of HBcAg but in an aggregated form. CONCLUSIONS: The results may aid for studying T cell immunotherapeutic vaccine to chronic hepatitis B.

Artificial Gene Fusion↗
PubMed1999

[Expression of non-structural region 3 gene of the Chinese HGY and analysis of the antigenicity of the recombinant proteins].

OBJECTIVE: This study is to analyze the antigenicity of the NS3 proteins of Chinese HGV and their potential use in the serological diagnosis. METHODS: All three gene fragments of NS3 region of Chinese HGV were cloned into the pRSET vectors to construct recombinant plasmids. In E. coli BL21, all three recombinant plasmids achieved a high expression level with induction of IPTG. The expressed products were analyzed with Western blot and ELISA. RESULTS: The recombinant protein PA, P3 and P4 have a molecular weight of 42,000, 30,000 and 24,000, respectively. They all could react with HGV positive sera in Western blot and ELISA. Among them, the protein that covers the N terminal of NS3 region of HGV had a stronger reaction with HGV positive sera than the other two proteinsdid. CONCLUSION: The N terminal in the NS3 region of Chinese HGV includes an dominant antigenic determinant, and its gene product has relatively strong antigenicity.

Antibodies, Viral↗
PubMed1999

Sequence heterogeneity within three different regions of the hepatitis G virus genome.

Two sets of primers derived from the 5'-terminal region and the NS5 region of the hepatitis G virus (HGV) genome were used to amplify PCR fragments from serum specimens obtained from different parts of the world. All PCR fragments from the 5'-terminal region (5'-PCR, n = 56) and from the NS5 region (NS5-PCR, n = 85) were sequenced and compared to corresponding published HGV sequences. The range of nucleotide sequence similarity varied from 74 and 78% to 100% for 5'-PCR and NS5-PCR fragments, respectively. Additionally, five overlapping PCR fragments comprising an approximately 2.0-kb structural region of the HGV genome were sequenced from each of five sera obtained from three United States residents. These sequences were compared to 20 published sequences comprising the same region of the HGV genome. Nucleotide and deduced amino acid sequences obtained from different individuals were homologous from 82.9 to 93. 6% and from 90.4 to 99.0%, respectively. Sequences obtained from follow-up specimens were almost identical. Comparative analysis of deduced amino acid sequences of the HGV structural proteins and hepatitis C virus (HCV) structural proteins combined with an analysis of predicted secondary structures and hydrophobic profiles allowed prediction of processing sites within the HGV structural proteins. A phylogenetic sequence analysis performed on the 2.0-kb structural region supports the existence of three previously identified HGV genetic groups. However, phylogenetic analysis performed on only small DNA fragments yielded inconsistent genetic grouping and failed to confirm the existence of genetic groups. Thus, in contrast to HCV where almost any region can be used for genotyping, only large or carefully selected genome fragments can be used to identify consistent HGV genetic groups.

5' Untranslated Regions↗