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Biomedical subjects

Gang Chen

Publications and source records attributed to Gang Chen.

At least 127 records · Page 7Linked to original sources
PubMed2005

Defective B cell responses in the absence of SH2D1A.

More than half of patients with X-linked lympho-proliferative disease, which is caused by a defect in the intracellular adapter protein SH2D1A, suffer from an extreme susceptibility to Epstein-Barr virus. One-third of these patients, however, develop dysgammaglobulenemia without an episode of severe mononucleosis. Here we show that in SH2D1A(-/-) mice, both primary and secondary responses of all Ig subclasses are severely impaired in response to specific antigens. Because germinal centers were absent in SH2D1A(-/-) mice upon primary immunization, and because SH2D1A was detectable in wt germinal center B cells, we examined whether SH2D1A(-/-) B cell functions were impaired. Using the adoptive cotransfer of B lymphocytes from hapten-primed SH2D1A(-/-) mice with CD4(+) T cells from primed wt mice into irradiated wt mice provided evidence that signal transduction events controlled by SH2D1A are essential for B cell activities resulting in antigen specific IgG production. Defects in naive SH2D1A(-/-) B cells became evident upon cotransfer with non-primed wt CD4(+) cells into Rag2(-/-) recipients. Thus, both defective T and B cells exist in the absence of SH2D1A, which may explain the progressive dysgammaglobulinemia in a subset of X-linked lympho-proliferative disease patients without involvement of Epstein-Barr virus.

Adoptive Transfer↗
PubMed2005

lux-marked Pseudomonas aeruginosa lipopolysaccharide production in the presence of rhamnolipid.

Rhamnolipid produced by Pseudomonas aeruginosa during the late logarithmic growth phase has been reported to be an effective biosurfactant. In the presence of rhamnolipid, P. aeruginosa had a higher specific lipopolysaccharide production, which was attributed to the increase of carbon to nitrogen ratios owing to the increase of the solubility of hydrophobic hydrocarbons, favoring the synthesis of lipopolysaccharides. P. aeruginosa also had a higher ratio of lipopolysaccharides in the growth medium to those on cell surfaces than in the absence of rhamnolipid because the presence of rhamnolipid stimulated the release of lipopolysaccharides from P. aeruginosa cell outer membranes. The release of lipopolysaccharides from cell surfaces made P. aeruginosa exhibit a more hydrophobic surface, enhancing the accumulation of hydrophobic hydrocarbons on P. aeruginosa cell surfaces and consequently resulting in a higher growth rate.

Bacterial Outer Membrane Proteins↗
PubMed2005

Ca2+-dependent regulation of rho GTPases triggers turning of nerve growth cones.

Cytoplasmic Ca2+ elevation and changes in Rho GTPase activity are both known to mediate axon guidance by extracellular factors, but the causal relationship between these two events has been unclear. Here we show that direct elevation of cytoplasmic Ca2+ by extracellular application of a low concentration of ryanodine, which activated Ca2+ release from intracellular stores, upregulated Cdc42/Rac, but downregulated RhoA, in cultured cerebellar granule cells and human embryonic kidney 293T cells. Chemoattractive turning of the growth cone triggered by a gradient of ryanodine was blocked by overexpression of mutant forms of Cdc42 but not of RhoA in Xenopus spinal cord neurons. Furthermore, Ca2+-induced GTPase activity correlated with activation of protein kinase C and required a basal activity of Ca2+/calmodulin-dependent protein kinase II. Thus, Rho GTPases may mediate axon guidance by linking upstream Ca2+ signals triggered by guidance factors to downstream cytoskeletal rearrangements.

Animals↗
PubMed2005

Solution structure of an RNA internal loop with three consecutive sheared GA pairs.

Internal loops in RNA are important for folding and function. Many folding motifs are internal loops containing GA base pairs, which are usually thermodynamically stabilizing, i.e., contribute favorable free energy to folding. Understanding the sequence dependence of folding stability and structure in terms of molecular interactions, such as hydrogen bonding and base stacking, will provide a foundation for predicting stability and structure. Here, we report the NMR structure of the oligonucleotide duplex, 5'GGUGGAGGCU3'/3'PCCGAAGCCG5' (P = purine), containing an unusually stable and relatively abundant internal loop, 5'GGA3'/3'AAG5'. This loop contains three consecutive sheared GA pairs (trans Hoogsteen/Sugar edge AG) with separate stacks of three G's and three A's in a row. The thermodynamic consequences of various nucleotide substitutions are also reported. Significant destabilization of approximately 2 kcal/mol at 37 degrees C is found for substitution of the middle GA with AA to form 5'GAA3'/3'AAG5'. This destabilization correlates with a unique base stacking and hydrogen-bonding network within the 5'GGA3'/3'AAG5' loop. Interestingly, the motifs, 5'UG3'/3'GA5' and 5'UG3'/3'AA5', have stability similar to 5'CG3'/3'GA5' even though UG and UA pairs are usually less stable than CG pairs. Consecutive sheared GA pairs in the 5'GGA3'/3'AAG5' loop are preorganized for potential tertiary interactions and ligand binding.

Adenine↗
PubMed2005

Stimulation of non-classical receptive field enhances orientation selectivity in the cat.

We have investigated how the nonclassical receptive field (nCRF) affects dynamic orientation selectivity of cells in the primary visual cortex (V1) in anaesthetized and paralysed cats using the reverse correlation method. We found that tuning to the orientation of the test stimulus depends on the size of the stimulation area. A significant sharpening of orientation tuning was induced by nCRF stimulation, with the magnitude of the effect increasing with the size of stimulation. The effect of the nCRF on the temporal dynamics of orientation tuning was also investigated by examining the tuning over a range of delays from stimulus onset. We found small but detectable changes in both the preferred orientation and the bandwidth of tuning over time when the classical receptive field (CRF) was stimulated alone. Stimulation in nCRF significantly increased the magnitude of these temporal changes. Thus, nCRF stimulation not only enhances the overall orientation selectivity, but also enriches the temporal dynamics of cortical neurones, which may increase the computational power of the visual cortex in information processing.

Action Potentials↗
PubMed2005

Chronic hepatitis B virus infection and mortality from non-liver causes: results from the Haimen City cohort study.

BACKGROUND: Studies of chronic hepatitis B virus (HBV) infection in endemic populations have rarely documented causes of mortality other than liver disease and hepatocellular carcinoma (HCC). METHODS: We analysed all-cause mortality related to HBV infection, focusing on the deaths not related to liver disease in a prospective cohort of adults living in Haimen City, China, who were followed from 1992 to 2002. Death certificate data from 4590 deaths among 83 794 individuals were analysed. At cohort entry, 15.0% of the 58 454 male subjects and 10.7% of 25 340 female subjects were hepatitis B surface antigen positive [HbsAg(+)]. HCC and chronic liver disease were the major causes of death in both men and women in this population. The analysis focused on non-liver causes of death. RESULTS: When liver-related causes of death were excluded, there was still a significantly higher age-adjusted death rate among HBsAg(+) individuals. The relative risks (RRs) and 95% confidence intervals (CIs) for all non-liver deaths among HBsAg(+) subjects were 1.2 (1.1-1.3) in men and 1.4 (1.1-1.7) in women. Non-liver causes were further subdivided into cancer and non-cancer groups. For all non-liver cancers, the RR was 1.2 (1.0-1.4) for males and 1.7 (1.2-2.3) for females. Non-liver, non-cancer deaths had RRs of 1.2 (1.1-1.4) and 1.2 (0.9-1.6) in males and females, respectively. CONCLUSIONS: HBV-infected individuals may be at increased mortality risk from non-liver causes. Possible reasons include a direct effect of HBV infection, changes in the host immune system as a cause or effect of chronic infection, and behavioural factors associated with HBV infection. Further studies are needed to confirm this finding.

Adult↗
PubMed2005

QSAR analyses on ginkgolides and their analogues using CoMFA, CoMSIA, and HQSAR.

Ginkgolides, isolated from ginkgo balba leaves, were found to be powerful as natural antagonists of human platelet activating factor (PAF) in treatment of some diseases such as acute inflammation, tissue rejection, asthma, and ischemic injury. Ginkgolides have a cage skeleton consisting of six five-membered rings, therefore, are very tough to be synthesized. For finding new powerful substitutes of the natural ginkgolides for treating those diseases, three methods, viz. CoMFA, CoMSIA, and HQSAR, were used to investigate the relationship between 117 ginkgolide analogues with great structural diversity and their bioactivities against PAF receptor. The high q2 released from the different QSAR methods, ranging from 0.583 to 0.684, suggests that three rational and predictive QSAR models were successfully built. These models also show clearly how steric, electrostatic, hydrophobicity, and individual atom affect molecular bioactivity as antagonists of PAF. These results could also be used to account for the unusually higher bioactivity of ginkgolide B than other ginkgolides. The possible binding mechanism between ginkgolides and human PAF receptor was also deduced based on the QSAR models. Therefore, this study should be very helpful in discovering new drugs as PAF antagonists in fighting against various diseases related to PAF and PAF receptor.

Ginkgolides↗
PubMed2005

Serological identification of immunogenic antigens in acute monocytic leukemia.

In order to improve disease-free survival and potentially a cure, it is necessary to identify more potent leukemia antigen. Here, we defined the acute monocytic leukemia-associated antigen (LAA) recognized by the humoral immune system for the first time. We have applied the method of serologic analysis of recombinant cDNA expression library (SEREX) on acute monocytic leukemia (FAB M5), followed by DNA sequencing and analyzing of positive clones. Then, the reactivity of normal and other leukemia sera with positive clones were performed. Thirty-five distinct novel antigens reactive with autologous IgG were identified by SEREX analysis on an acute monocytic leukemia patient and were characterized according to cDNA sequence and the reactivity with allogeneic sera. Twenty of the 35 antigens identified in this study were recognized by IgG antibodies in normal sera, and the remaining 15 were recognized exclusively by sera from allogeneic leukemia patients but not by normal donor sera, suggested that the immune response to these 15 antigens are leukemia related. The 15 immunogenic antigens detected by immune responses in the autologous host facilitate the identification of epitopes recognized by antigen-specific cytotoxic T lymphocytes (CTL) and are potential candidates for diagnosis and immunotherapy in acute myeloid leukemia (AML).

Antibodies, Neoplasm↗
PubMed2005

Fabrication and performance of a three-dimensionally adjustable device for the amperometric detection of microchip capillary electrophoresis.

A microchip CE-amperometric detection (AD) system has been fabricated by integrating a two-dimensionally adjustable CE microchip and an AD cell containing a one-dimensionally adjustable disk detection electrode in a Plexiglas holder. It facilitates the precise 3-D alignment between the channel outlet and the detection electrode without a complicated 3-D manipulator. The performance of this unique system was demonstrated by separating five aromatic amines (1,4-phenyldiamine, aniline, 2-methylaniline, 4-chloroaniline, and 1-naphthylamine) of environmental concern. Factors influencing their separation and detection processes were examined and optimized. The five analytes have been well separated within 140 s in a 74 cm long separation channel at a separation voltage of +2500 V using a 10 mM phosphate buffer (pH 3.5). Highly linear response is obtained for the five analytes over the range 20-200 microM with the detection limits ranging from 0.46 to 1.44 microM, respectively. The present system demonstrated long-term stability and reproducibility with RSDs of less than 5% for the peak current (n = 9). The new approach for the microchannel-electrode alignment should find a wide range of applications in CE, flowing injection analysis, and other microfluidic analysis systems.

1-Naphthylamine↗
PubMed2005

Value and feasibility of HPV DNA test in cervical scraping smears.

To investigate the reliability and feasibility of human papillomavirus (HPV) DNA test in cervical scraping smears with polymerase chain reaction (PCR), 131 cases of cervical scraping specimens were collected, and the positive rates and accuracy of HPV infection were determined in normal subjects and cervical cancer patients. GP5+/GP6+ and E7 primer pairs designed for detecting HPV L1 and HPV type 16 E7 were tested in this study. Our results showed that positive rates of HPV DNA in normal population and cervical cancer patients were 32.99% and 73.53% respectively and there was significant difference between them (P < 0.001). In normal subjects, detection rates of HPV DNA with GP5+/GP6+ and E7 primer pairs were 27.84% and 16.49% respectively, with statistically significant difference between them (P > 0.05). However the detection rates in cervical cancer patients were 38.24% and 67.65% for the two markers, with a significant difference found between them (P < 0.05). It is concluded that HPV DNA test with PCR for cervical scraping smears was feasible. GP5+/GP6+ primer pairs may be a useful probe to screen HPV infection in normal population, but they are not sensitive enough in cervical cancer patients. It is suggested that high risk type HPV DNA test was very useful in population with high risk of cervical cancer.

Capsid Proteins↗
PubMed2005

Inhibitory effect of coxsackie adenovirus receptor on invasion and metastasis phenotype of ovarian cancer cell line SKOV3.

Full-length coxsackie adenovirus receptor (CAR) eukaryotic expression plasmid was transfected into an ovarian cell line, SKOV3, and its effect on the change of malignant metastasis phenotype was explored. CAR mRNA and protein expression levels among 4 ovarian cancer cell lines (A2780, SKOV3, SW626, CAOV3) and the positive control 293 (a transformed human embryo kidney cell line) was detected by using semi-quantitative RT-RCR and Western blot and compared. CAR-negative SKOV3 was transfected with the eukaryotic expression plasmid containing a full-length CAR cDNA and mock-vector respectively. The positive clones were screened by G418. The biological behavior changes of positive transfected cells were gauged by colony formation in soft agar assay and cell adhesion assay. Among the cell lines, there were obviously different CAR expression levels. CAR could not be detected in SKOV3. In transfected cell group, CAR expression was enhanced obviously as compared with non-transfected or mock-transfected groups. Cell adhesion in the transfected group was promoted. The number of colony formation was reduced significantly in transfected groups (25.32 +/- 8.91) as compared with that in non-transfected group (88.75 +/- 13. 98) and mock-transfected group (82.53 +/- 19.37). Among the 4 ovarian cancer cell lines, CAR expression level was variable. Exogenous CAR expression had a potential role in inhibiting the malignant metastasis phenotype of ovary cancer cells.

Cell Line, Tumor↗
PubMed2005

Surgical management of thymic epithelial tumors: a retrospective review of 204 cases.

BACKGROUND: Thymic epithelial tumors consist of a series of neoplasm that differ morphologically and biologically. Management strategy for these tumors remains controversial. METHODS: We retrospectively reviewed 204 thymic epithelial tumors surgically treated during the period of 1970 to 1995, and we reexamined the histologic specimens using the current World Health Organization classification. RESULTS: One hundred eighty patients (88.2%) underwent complete resections, 17 (8.3%) received partial resections, and 7 (3.4%) received biopsies only. The complete resection rate of stages I and II tumors was significantly higher than stages III and IV tumors (98.2% vs 76.6%; p < 0.001). Twenty-four patients (11.8%) experienced 29 events of complications postoperatively, including 11 events of myasthenia gravis crisis. Myasthenia gravis, partial resection or biopsy, and stages III and IV were independent risk factors for postoperative complications. Fifteen patients (7.4%) died during hospital stays, including 6 patients from myasthenia crisis. Partial resection or biopsy and myasthenia gravis were independent risk factors for postoperative mortality. There were significantly more stage I and stage II cases in histologic types A, AB, and B1 tumors than in B2, B3, and C tumors (87.6% vs 26.4%; p < 0.001), and their complete resection rate was significantly higher than the latter group (98.9% vs 78.3%; p < 0.001). The 5-year and 10-year survival rates were 63.2% and 50.4%, respectively. Masaoka stages III and IV, histologic types B2, B3, and C, and incomplete resection were independent risk factors for poor prognosis. CONCLUSIONS: Complete resection remains the hope of cure for thymic epithelial tumors. The treatment strategy should be based on the current World Health Organization histologic classification and the Masaoka staging system.

Adolescent↗
PubMed2005

Intravenous administration of Gd-DTPA prior to DWI does not affect the apparent diffusion constant.

MRI measurements of water diffusion and blood perfusion are increasingly used for the evaluation of organ functionality and tissue viability (e.g., in tumors). While diffusion-weighted imaging is performed without contrast agents, measurement of blood perfusion is normally performed based on the administration of paramagnetic substances such as gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). Simultaneous measurements of these two parameters are often preferred. However, it may be argued that Gd-DTPA causes constriction of small blood vessels or alters hemodynamic parameters such as blood viscosity, thereby corrupting subsequent measurements of the apparent diffusion constant (ADC). The objective of the current study was to investigate the possible changes in the ADC in tumors following intravenous administration of 0.2 and 0.4 mmol/kg of Gd-DTPA in mice. The study was conducted with C3H mouse mammary carcinomas inoculated in the right foot of the animal subjects. The results were compared with findings in a sham group, demonstrating that Gd-DTPA had no significant impact on the ADC as measured in a 7-T animal system.

Analysis of Variance↗
PubMed2005

Regulation of HtrA2/Omi by X-linked inhibitor of apoptosis protein in chemoresistance in human ovarian cancer cells.

OBJECTIVE: Development of cisplatin resistance by cancer cells is a major hurdle in successful treatment of human ovarian cancer. However, the mechanism of cisplatin resistance in ovarian cancer cells remains unclear. In this study, we have examined the possible role of X-linked inhibitor of apoptosis protein (Xiap) in the development of cisplatin resistance in ovarian cancer cells and investigate if suppressed cytosolic high temperature required protein A (HtrA2/Omi) level is an important factor in cisplatin resistance in ovarian cancer. METHODS: Cisplatin-sensitive (A2780 and COC1) and -resistant (A2780/DDP and COC1/DDP) ovarian cancer cells were cultured for different durations (0-24 h) and with different cisplatin concentrations (0-20 muM). Xiap content and cytosolic HtrA2/Omi content were analyzed by Western blot. Antisense oligonucleotides were used to downregulate Xiap content in ovarian cancer cells. RESULTS: Cisplatin decreased Xiap content and increased cytosolic HtrA2/Omi content and caspase-3 activity in cisplatin-sensitive ovarian cancer cell lines (A2780 and COC1), but not in the resistant variants (A2780/DDP and COC1/DDP). Downregulation of Xiap by antisense Xiap oligonucleotides increased caspase-3 activity and sensitized cisplatin-resistant cells to cisplatin treatment. Cytosolic HtrA2/Omi level increased while Xiap was downregulated in cisplatin-resistant ovarian cancer cells. CONCLUSION: Development of cisplatin resistance may be due to Xiap neutralizing caspase-3 activation and lower cytosolic HtrA2/Omi level in response to cisplatin in human ovarian cancer cells. Cytosolic HtrA2/Omi level is partly regulated by Xiap in ovarian cancer cells.

Adenocarcinoma↗
PubMed2005

Thermal conductivity modeling of core-shell and tubular nanowires.

The heteroepitaxial growth of crystalline core-shell nanostructures of a variety of materials has become possible in recent years, allowing the realization of various novel nanoscale electronic and optoelectronic devices. The increased surface or interface area will decrease the thermal conductivity of such nanostructures and impose challenges for the thermal management of such devices. In the meantime, the decreased thermal conductivity might benefit the thermoelectric conversion efficiency. In this paper, we present modeling results on the lattice thermal conductivity of core-shell and tubular nanowires along the wire axis direction using the phonon Boltzmann equation. We report the dependence of the thermal conductivity on the surface conditions and the core-shell geometry for silicon core-germanium shell and tubular silicon nanowires at room temperature. The results show that the effective thermal conductivity changes not only with the composition of the constituents but also with the radius of the nanowires and nanopores due to the nature of the ballistic phonon transport. The results in this work have implications for the design and operation of a variety of nanoelectronic devices, optoelectronic devices, and thermoelectric materials and devices.

Electronics↗
PubMed2005

The host type I interferon response to viral and bacterial infections.

Type I interferons (IFN) are well studied cytokines with anti-viral and immune-modulating functions. Type I IFNs are produced following viral infections, but until recently, the mechanisms of viral recognition leading to IFN production were largely unknown. Toll like receptors (TLRs) have emerged as key transducers of type I IFN during viral infections by recognizing various viral components. Furthermore, much progress has been made in defining the signaling pathways downstream of TLRs for type I IFN production. TLR7 and TLR9 have become apparent as universally important in inducing type I IFN during infection with most viruses, particularly by plasmacytoid dendritic cells. New intracellular viral pattern recognition receptors leading to type I IFN production have been identified. Many bacteria can also induce the up-regulation of these cytokines. Interestingly, recent studies have found a detrimental effect on host cells if type I IFN is produced during infection with the intracellular gram-positive bacterial pathogen, Listeria monocytogenes. This review will discuss the recent advances made in defining the signaling pathways leading to type I IFN production.

Animals↗
PubMed2005

Survey of the two polymorphisms in DAZL, an autosomal candidate for the azoospermic factor, in Japanese infertile men and implications for male infertility.

The DAZL (DAZ-like) gene is suggested to be an ancestral gene of the DAZ (deleted in azoospermia) gene on the Y chromosome, which is a strong candidate for the azoospermic factor. Recently, it has been reported that the T54A (Thr54-->Ala) polymorphism in exon 3 of the DAZL gene is associated with spermatogenic failure in the Taiwanese population. In this study, to investigate whether this polymorphism is associated with spermatogenic failure in Japanese males, we analysed genomic DNA derived from 234 patients with azoospermia or oligozoospermia and 131 fertile controls. The T54A polymorphism was completely absent in both the patients and the controls. The T12A (Thr12-->Ala) polymorphism in exon 2 of the DAZL gene was found at a similar frequency in the patients and controls, 15.4% and 13.7%, respectively (P = 0.67). However, the frequency of T12A was higher for the azoospermic (20.5%) than oligozoospermic (9.6%) individuals in infertile men without DAZ deletions, although statistical difference was not so apparent (chi2 test: P = 0.037, OR = 2.413, 95% CI = 1.035-5.629; Yate's chi2 test: P = 0.058, OR = 2.319, 95% CI = 0.973-6.166). Our results show that the T54A polymorphism in DAZL has no major role in Japanese males with azoospermia or oligozoospermia. The distribution of the T54A polymorphism may be restricted to the narrow area including Taiwan.

Adult↗