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Biomedical subjects

G Cheng

Publications and source records attributed to G Cheng.

At least 19 recordsLinked to original sources
PubMed2003

The art of war: Innate and adaptive immune responses.

Research over the last several years has greatly advanced our understanding of the mechanisms by which the immune system functions. There exist two main branches of immunity, termed innate and adaptive immunity. Innate immunity uses the genetic memory of germline-encoded receptors to recognize the molecular patterns of common pathogens. Adaptive immunity, akin to somatic memory, is a complex system by which the body learns to recognize a pathogen's unique antigens and builds an antigen specific response to destroy it. The effective development of the overall immune response depends on careful interplay and regulation between innate and adaptive immunity. Here we review our current understanding of how these integrated systems distinguish targets against which a response is appropriate and neutralize potentially pathogenic challenges.

Animals↗
PubMed2003

Gene therapy to target dendritic cells from blood to lymph nodes.

Peripheral lymph nodes (PLN) are strategic microenvironments where antigen-presenting dendritic cells (DC), loaded with environmental antigens, and naive lymphocytes meet to initiate immune responses. The unique capacity of DC to induce primary immune responses has led to their use in clinical medicine; however, delivering DC to lymph nodes is problematic. Intravenously injected DC cannot access to PLN, while DC injected into tissue migrate inefficiently through lymphatics to PLN. We achieved DC targeting to T-cell areas of PLN by endowing DC with a novel receptor for peripheral node addressin (PNAd), an adhesion molecule present on the lymph node venular endothelium. This novel receptor is a chimeric E/L-selectin (ELS) that, we have previously shown, binds to PNAd. DC were genetically modified by retroviral transduction to express ELS. ELS expression was targeted to tips of microvilli, and mediated rolling of DC on PNAd both in vivo and in vitro. Such genetically engineered DC could extravasate directly from blood through the lymph node endothelium as opposed to nontransduced DC. This study provides evidence that the trafficking of DC can be modified using gene transfer technologies. More efficient delivery of DC to PLN should assist the development of improved vaccination strategies.

Adoptive Transfer↗
PubMed2002

Renormalization group theory for perturbed evolution equations.

We show that proto-RG (renormaliation group) theory can be used to give a systematic description of the evolution of soltion of perturbed equations. The equations describing the deformation of its shape as the effect of perturbation are proto-RG equations. The RG approach may be simpler than inverse scattering theory (IST) and another approaches, because it dose not rely on any knowledge of IST. It is very concise and easy to understand.

Journal Article↗
PubMed2002

Iterative renormalization group for anomalous dimension in a nonlinear diffusion process.

We construct a classical successive method, the Picard method in integral equation theory, to make an iterative algorithm with the renormalization group (RG) approach to calculate the anomalous dimension in a nonlinear diffusion equation. We find our result improves than the original RG work because we begin with the var epsilonth RG solution, not the trivial fixed-point solution.

Journal Article↗
PubMed2002

Independent effect of vitamin B12 deficiency on hematological status in older Chinese vegetarian women.

We have examined the independent effect of vitamin B(12) deficiency on hematological indices in older Chinese vegetarian women using a cross-sectional study design: 119 women older than 55 years who had been vegetarian for more than 3 years were studied. Fasting blood samples were taken for complete blood count, serum iron, total serum iron binding capacity, serum iron saturation, serum vitamin B(12), serum folate, serum methylmalonic acid levels (MMA), and renal function test. Subjects with iron deficiency (iron saturation <15%) and those with serum creatinine >150 mmol/L were excluded. The prevalence of definite vitamin B(12) deficiency (vitamin B(12) level < 150 pmol/L and MMA >or= 0.4 micromol/L) was 42%. Another 32.8% had possible vitamin B(12) deficiency (either criterion). The prevalence of iron deficiency was 10%. After exclusions, 96 subjects were further analyzed. Vitamin B(12) deficiency defined by serum vitamin B(12) and MMA was associated with a decrease in hemoglobin concentrations by up to 0.9 g/dL, but it was not associated with an increase in mean corpuscular volume (MCV). Serum MMA but not vitamin B(12) levels correlated inversely with hemoglobin and platelet counts and positively with MCV, after adjustment of confounding factors. However, the percentage of subjects with anemia did not increase significantly until serum MMA became >1.0 micromol/L. In conclusion, vitamin B(12) deficiency was associated with a significant decrease in hemoglobin concentration. However, anemia associated with vitamin B(12) deficiency was seldom macrocytic. We recommend that older vegetarians should be given vitamin B(12) supplements routinely.

Aged↗
PubMed2002

Antiproliferative activity of the extract of Gleditsia sinensis fruit on human solid tumour cell lines.

BACKGROUND: The fruit extract of Gleditsia sinensis Lam. (GSE) is a traditional herbal medicine that is saponin-rich. However, its activity on solid tumour cell lines has never been demonstrated. METHODS: The activity of GSE was demonstrated in four cancer cell lines (breast cancer MCF-7, MDA-MB231, hepatoblastoma HepG2 and oesophageal squamous carcinoma cell line SLMT-1) using MTT assay, anchorage-independent clonogenicity assay, DNA laddering and in situ cell death detection. RESULTS: The mean MTT(50) (the mean concentration of GSE to reduce MTT activity by 50%) ranged from 16 to 20 microg/ml of GSE. An anchorage-independent clonogenicity assay showed that all of the four solid tumour cell lines gradually lost their regeneration potential after treatment with GSE, DNA fragmentation and TUNEL analysis demonstrated that the action of GSE is both dose- and time course-dependent. CONCLUSIONS: Our results suggest that GSE has a cytotoxic activity and can induce apoptosis in human solid tumour cell lines.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Estrogen receptors and proliferation markers in primary and recurrent breast cancer.

To elucidate the clinical importance of estrogen receptor (ER) beta in breast cancer, 29 archival primary breast cancer specimens, six locally recurrent cancers, and five benign mammary tumors were examined histochemically for ERalpha, ERbeta and the proliferation markers Ki67 and cyclin A. In benign tumors, most epithelial cells contained ERbeta, but ERalpha was rare. In primary cancers, both ERalpha and ERbeta occurred in epithelial cells, the presence of ERbeta being associated with elevated expression of Ki67 and cyclin A, and ERalpha with decreased levels. Thus, the highest content of proliferation markers was seen in primary cancers that were ERalpha(-) ERbeta(+). Most Ki67-containing cells coexpressed ERbeta, but few showed ERalpha. In locally recurring cancers, ERalpha, ERbeta, and Ki67 were more highly expressed than in the corresponding primary tumors, and many cells containing ERbeta, but few with ERalpha, expressed Ki67. Surprisingly, ERbeta, but not ERalpha, was seen in the stromal cells of both primary and recurrent cancers. Because the response of breast cancers to tamoxifen therapy is correlated with the presence of ERalpha, cancer cells that lack ERalpha but contain ERbeta and proliferation markers represent a novel population of apparently proliferating cells that probably are not targeted by the current antiestrogens. Thus, appropriate ERbeta-specific ligands, perhaps in combination with tamoxifen, may be useful in improving the treatment of breast cancers.

Biomarkers, Tumor↗
PubMed2001

Val193 and Phe195 of the gamma 1 34.5 protein of herpes simplex virus 1 are required for viral resistance to interferon-alpha/beta.

Herpes simplex viruses (HSV) are resistant to the antiviral action of interferon. However, the underlying mechanisms are not well understood. In this report, we show that unlike that of wild-type HSV-1, replication of the gamma 1 34.5 null mutants was significantly inhibited by exogenous interferon-alpha in cells devoid of interferon-alpha/beta genes. Using a series of gamma 1 34.5 deletion mutants, the domain required for interferon resistance was mapped to the region containing amino acids 146 to 263 in the gamma 1 34.5 protein. Interestingly, Val193 Glu and Phe195 Leu substitutions in the protein phosphatase 1 interacting motif of the gamma 1 34.5 protein rendered HSV-1 sensitive to interferon-alpha. Furthermore, gamma 1 34.5 null mutants were sensitive to interferon-alpha/beta in PKR+/+ but not in PKR-/- mouse embryo fibroblasts. These findings provide evidence that the gamma 1 34.5 protein contributes to HSV-1 resistance to interferon-alpha/beta by inhibiting PKR function.

Amino Acids↗
PubMed2001

Inflammatory chemokine transport and presentation in HEV: a remote control mechanism for monocyte recruitment to lymph nodes in inflamed tissues.

Interstitial fluid is constantly drained into lymph nodes (LNs) via afferent lymph vessels. This conduit enables monocyte-derived macrophages and dendritic cells to access LNs from peripheral tissues. We show that during inflammation in the skin, a second recruitment pathway is evoked that recruits large numbers of blood-borne monocytes to LNs via high endothelial venules (HEVs). Inhibition of monocyte chemoattractant protein (MCP)-1 blocked this inflammation-induced monocyte homing to LNs. MCP-1 mRNA in inflamed skin was over 100-fold upregulated and paralleled MCP-1 protein levels, whereas in draining LNs MCP-1 mRNA induction was much weaker and occurred only after a pronounced rise in MCP-1 protein. Thus, MCP-1 in draining LNs was primarily derived from inflamed skin. In MCP-1(-/-) mice, intracutaneously injected MCP-1 accumulated rapidly in the draining LNs where it enhanced monocyte recruitment. Intravital microscopy showed that skin-derived MCP-1 was transported via the lymph to the luminal surface of HEVs where it triggered integrin-dependent arrest of rolling monocytes. These findings demonstrate that inflamed peripheral tissues project their local chemokine profile to HEVs in draining LNs and thereby exert "remote control" over the composition of leukocyte populations that home to these organs from the blood.

Adoptive Transfer↗
PubMed2001

Enhanced sensitivity to apoptosis in Ras-transformed thyroid cells.

Ras mutations occur at high frequency in thyroid cancer. In vitro, the effects of Ras in thyroid cells are pleiotropic in that expression of activated Ras has been reported to stimulate proliferation and apoptosis. An understanding of the factors that contribute to the survival versus demise of Ras-transformed cells is essential to our understanding of the contribution of Ras to thyroid neoplasia and other cancers. Constitutive expression of oncogenic H-Ras sensitized Wistar rat thyroid (WRT) cells to apoptosis stimulated by multiple insults. When deprived of matrix attachment, Ras-transformed cells perished by apoptotic cell death at a high frequency. In contrast, parental cells were more resistant to suspension-induced cell death. Ras effects on anchorage-independent cell death were reproduced by a mutant protein that signals selectively to Raf-1, but not by mutant Ras that preferentially binds to RalGDS. Expression of a Ras mutant that selectively activates PI3K resulted in substantial protection from detachment-induced cell death. MAPK activity was increased in adherent Ras12V- and Ras12V35S-expressing cells, but abolished upon detachment. Interestingly, impaired MAPK activity was sufficient to stimulate apoptosis in adherent Ras-transformed cells, but not in parental cells. Treatment with a PI3K inhibitor also stimulated apoptosis selectively in Ras-transformed cells. These results demonstrate that constitutive expression of activated Ras elicits differential effects on the survival of thyroid cells. Moreover, Ras expression results in a greater dependence of thyroid cells on MAPK and PI3K activity for their survival.

Amino Acid Substitution↗
PubMed2001

Signaling lymphocytic activation molecule is expressed on CD40 ligand-activated dendritic cells and directly augments production of inflammatory cytokines.

Dendritic cells (DC) comprise a key part of the innate immune system that, upon activation, profoundly influences the nature of the adaptive T cell response. In this study, we present evidence that signaling lymphocytic activation molecule (SLAM), a molecule first identified in activated T and B cells, is strongly up-regulated in DC activated through CD40, as well as in response to inflammatory stimuli, including polyinosinic polycytidylic acid and LPS. mRNA encoding both membrane-bound and soluble secreted isoforms of SLAM was detected in CD40 ligand-activated DC, comprising two of the four known SLAM isoforms. Expression of membrane-bound SLAM protein peaked at 12 h poststimulation with CD40 ligand, gradually returning to baseline levels after 6 days. SLAM up-regulation appears to be a direct result of the induction of DC maturation, as inflammatory cytokines released during this process do not affect SLAM expression. Functionally, engagement of SLAM enhances DC production of IL-12 and IL-8, while having no effect on production of IL-10. Because SLAM is involved in the activation of T cells, the expression of SLAM on DC may provide a bidirectional signaling mechanism in which interacting DC and T cells are simultaneously and synergistically activated to mount proinflammatory Th1 responses.

Adult↗
PubMed2001

Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a multidomain oxidase/peroxidase with homology to the phagocyte oxidase subunit gp91phox.

High molecular weight homologues of gp91phox, the superoxide-generating subunit of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, have been identified in human (h) and Caenorhabditis elegans (Ce), and are termed Duox for "dual oxidase" because they have both a peroxidase homology domain and a gp91phox domain. A topology model predicts that the enzyme will utilize cytosolic NADPH to generate reactive oxygen, but the function of the ecto peroxidase domain was unknown. Ce-Duox1 is expressed in hypodermal cells underlying the cuticle of larval animals. To investigate function, RNA interference (RNAi) was carried out in C. elegans. RNAi animals showed complex phenotypes similar to those described previously in mutations in collagen biosynthesis that are known to affect the cuticle, an extracellular matrix. Electron micrographs showed gross abnormalities in the cuticle of RNAi animals. In cuticle, collagen and other proteins are cross-linked via di- and trityrosine linkages, and these linkages were absent in RNAi animals. The expressed peroxidase domains of both Ce-Duox1 and h-Duox showed peroxidase activity and catalyzed cross-linking of free tyrosine ethyl ester. Thus, Ce-Duox catalyzes the cross-linking of tyrosine residues involved in the stabilization of cuticular extracellular matrix.

Amino Acid Sequence↗
PubMed2001

Controlled nucleation and growth of surface-confined gold nanoparticles on a (3-aminopropyl)trimethoxysilane-modified glass slide: a strategy for SPR substrates.

The thickness of the gold film and its morphology, including the surface roughness, are very important for getting a good, reproducible response in the SPR technique. Here, we report a novel alternative approach for preparing SPR-active substrates that is completely solution-based. Our strategy is based on self-assembly of the gold colloid monolayer on a (3-aminopropyl)trimethoxysilane-modified glass slide, followed by electroless gold plating. Using this method, the thickness of films can be easily controlled at the nanometer scale by setting the plating time in the same conditions. Surface roughness and morphology of gold films can be modified by both tuning the size of gold nanoparticles and agitation during the plating. Surface evolution of the Au film was followed in real time by UV-vis spectroscopy and in situ SPRS. To assess the surface roughness and electrochemical stability of the Au films, atomic force microscopy and cyclic voltammetry were used. In addition, the stability of the gold adhesion is demonstrated by three methods. The as-prepared Au films on substrates are reproducible and stable, which allows them to be used as electrodes for electrochemical experiments and as platforms for studying SAMs.

Journal Article↗
PubMed2001

Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5.

gp91phox is the catalytic subunit of the respiratory burst oxidase, an NADPH-dependent, superoxide generating enzyme present in phagocytes. In phagocytes, the enzyme functions in host defense, but reactive oxygen generation has also been described in a variety of non-phagocytic cells, including cancer cells. We previously reported the cloning of Nox1 (NADPH oxidase1), a homolog of gp91phox, its expression in colon and vascular smooth muscle, and its oncogenic properties when overexpressed [Suh et al. (1999). Nature 401, 79-82]. Herein, we report the cloning and tissue expression of three additional homologs of gp91phox, termed Nox3, Nox4 and Nox5, members of a growing family of gp91phox homologs. All are predicted to encode proteins of around 65 kDa, and like gp91phox, all show 5-6 conserved predicted transmembrane alpha-helices containing putative heme binding regions as well as a flavoprotein homology domain containing predicted binding sites for both FAD and NADPH. Nox3 is expressed primarily in fetal tissues, and Nox4 is expressed in not only fetal tissues, but also kidney, placenta and glioblastoma cells. Nox5 is expressed in a variety of fetal tissues as well as in adult spleen and uterus. Nox isoforms are aberrantly expressed in several cells derived from human cancers, with Nox4 being the isoform most frequently expressed in the tumor cells investigated. Thus, expression of Nox family members is likely to account for some of the reactive oxygen generation seen in non-phagocytic cells.

Amino Acid Sequence↗
PubMed2001

Requirements for activation and RAFT localization of the T-lymphocyte kinase Rlk/Txk.

BACKGROUND: The Tec family kinases are implicated in signaling from lymphocyte antigen receptors and are activated following phosphorylation by Src kinases. For most Tec kinases, this activation requires an interaction between their pleckstrin homology (PH) domains and the products of phosphoinositide 3-Kinase, which localizes Tec kinases to membrane RAFTs. Rlk/Txk is a Tec related kinase expressed in T cells that lacks a pleckstrin homology domain, having instead a palmitoylated cysteine-string motif. To evaluate Rlk's function in T cell receptor signaling cascades, we examined the requirements for Rlk localization and activation by Src family kinases. RESULTS: We demonstrate that Rlk is also associated with RAFTs, despite its lack of a pleckstrin homology domain. Rlk RAFT association requires the cysteine-string motif and is independent of PI3 Kinase activity. We further demonstrate that Rlk can be phosphorylated and activated by Src kinases, leading to a decrease in its half-life. A specific tyrosine in the activation loop of Rlk, Y420, is required for phosphorylation and activation, as well as for decreased stability, but is not required for lipid RAFT association. Mutation of this tyrosine also prevents increased tyrosine phosphorylation of Rlk after stimulation of the T cell receptor, suggesting that Rlk is phosphorylated by Src family kinases in response to T cell receptor engagement. CONCLUSIONS: Like the other related Tec kinases, Rlk is associated with lipid RAFTs and can be phosphorylated and activated by Src family kinases, supporting a role for Rlk in signaling downstream of Src kinases in T cell activation.

Cell Line↗
PubMed2001

The electrochemically induced conformational transition of disulfides in bovine serum albumin studied by thin layer circular dichroism spectroelectrochemistry.

The conformational transition of disulfides in bovine serum albumin (BSA) induced by electrochemical redox reaction of disulfides were monitored by in-situ circular dichroism (CD) spectroelectrochemistry, with a long optical path thin layer cell and analyzed by a singular value decomposition least square (SVDLS) method. Electrochemical reduction of disulfides drives the left-handed conformation of disulfides changed into the right-handed. At open circuit, eight of the 17 disulfides were of left-handed conformation. Four of the 17 disulfides took part in the electrochemical reduction with an EC mechanism. Only one-fourth of the reduced disulfides returned to left-handed conformation in the re-oxidation process. Some parameters of the electrochemical reduction process, i.e. the number of electrons transferred and electron transfer coefficient, n = 8, alpha n = 0.15, apparent formal potential, E1(0') = -0.65(+/-0.01) V, standard heterogeneous electron transfer rate constant, k1(0) = (2.84 +/- 0.14) x 10(-5) cm s(-1) and chemical reaction equilibrium constant, Kc = (5.13 +/- 0.12) x 10(-2), were also obtained by double logarithmic analysis based on the near-UV absorption spectra with applied potentials.

Algorithms↗
PubMed2001

Transfusion of peripheral blood stem cells from donor homozygous for a shared HLA-haplotype: avoiding fatal transfusion-associated graft-versus-host disease while preserving anti-leukemic effect.

BACKGROUND: Fatal transfusion-associated graft-versus-host disease was observed in immunocompetent patients transfused with blood from donors homozygous for a shared haplotype with the recipient (the P-F1 barrier). We tested whether it was possible to carry out successful transplantation in a patient with relapsed acute myeloid leukemia, using peripheral blood stem cells from his HLA-homozygous brother (HLA A2, B46, DRB1 901) who shared a haplotype with the patient (HLA A2, B46,75, DRB1 901,12). METHODS: A CD34 positively selected cell fraction (5.46x 10(6) CD34 cells/kg) was infused first, followed by subsequent infusion of graded doses of donor T cells (total 7.25x10(7) T cells/kg). Nonmyeloablative chemotherapy with idarubicin and cytarabine was given during the transplantation to reduce the leukemic burden and facilitate engraftment. Polymerase chain reaction with the VNTR primers, D1S80, was used to detect engraftment. RESULTS: Complete remission (>300days) and successful donor engraftment (90%) were achieved. CONCLUSIONS: Peripheral blood stem cells transplantation from a donor with a homozygous shared haplotype is possible with a minimal preparative regimen.

Acute Disease↗