Biomedical subjects

C Dong

Publications and source records attributed to C Dong.

At least 19 recordsLinked to original sources

PubMed2006

Identification of genetic diversity of hepatitis E virus (HEV) and determination of the seroprevalence of HEV in eastern China.

Hepatitis E, caused by the hepatitis E virus (HEV), is endemic in China. However, the molecular characteristics of HEV circulating in eastern China and the seroprevalence of HEV infection in eastern China are relatively unknown. In this study, 25 HEV strains, isolated from sporadic hepatitis E cases in eastern China, were sequenced in the RNA-dependent RNA polymerase region and subjected to phylogenetic analysis. These HEV strains were 74.6-98.7% identical in nucleotides and were all clustered into HEV genotype 4. Most of them formed new sub-genotypes and revealed a high degree of genetic variance. In addition, 12,052 serum samples were collected from people of different ages, living in urban or rural areas in eastern China. Anti-HEV IgG activity was detected in 2073 (17.20%). The prevalence of anti-HEV IgG significantly increased with age (P<0.0001), ranging from 7.92% in children (<10 years old) to 21.48% among older persons (>or=60 years old). Moreover, statistical analysis showed that there was a significant difference between rural and urban areas, with higher prevalence for people living in rural neighborhoods (P<0.001).

Adolescent↗

PubMed2006

Experimental study on genistein prevention and treatment of transplant arteriosclerosis in aortic transplants of rat.

OBJECTIVE: Our objective was to study the effects of genistein, a soy isoflavone, on transplant arteriosclerosis, in addition to its immunosuppressive and antioxidant properties. MATERIALS AND METHODS: We performed male Brown-Norway to male Lewis aortic transplantation. The recipients were randomly assigned to 3 groups: no treatment controls, dimethyl sulfoxide (DMSO; 5 mL/kg) solvent controls, and experimental group that received genistein (20 mg/kg/d) by daily intraperitoneal injection. On postoperative day 60, the graft was harvested and blood obtained. The transplanted aorta was analyzed by histology and immunohistochemistry. The serum was analyzed by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the 2 controls, leukocyte recruitment to the graft was significantly inhibited by genistein, with a profound reduction in the number of CD69 macrophages infiltrating the adventitia of the transplanted aortas. Moreover, genistein significantly inhibited the expression of VEGF and IFN-gamma production (P < .01). CONCLUSION: These results suggested that the protein tyrosine kinase inhibitor genistein inhibited graft arteriosclerosis.

Animals↗

PubMed2006

Antisense ERK1/2 oligodeoxynucleotide gene therapy attenuates graft arteriosclerosis of aortic transplant in a rat model.

UNLABELLED: Chronic rejection is a major cause of transplant loss that is effected by the extracellular signal-regulated kinases (ERK) pathway. This study investigated the effects of antisense ERK1/2 oligodeoxynucleotide(ODN) gene therapy on chronic rejection. METHODS: Lewis (RT1(1)) rats served as recipients of Brown-Norway (BN, RT1n) grafts. The BN rat abdominal aortas were harvested and orthotopically grafted into Lewis rats. The recipients were divided into three groups: (1) control group (n = 9), (2) random ODN transfer group (n = 10), and (3) antisense ODN transfer group (n = 10). At day 60 after transplantation, the recipients were sacrificed; the grafted aortas were evaluated histologically and immunohistochemically. ERK1/2 protein expression in the grafts was determined using Western Blot assays. Serum levels of slCAM-1 were detected by ELISA. RESULTS: In the control group and random ODN transfer group, we observed a remarkable degree of intimal hyperplasia and inflammatory cell infiltration, including macrophages and T cells. Compared with the control group, antisense ERK1/2 ODN gene therapy resulted in a significant reduction in neointimal proliferation (P < .01), inhibition of ERK1/2 protein expression (P < .01), decreased graft infiltration with CD4+ T lymphocytes (P < .01), CD8+ T lymphocytes(P < .05), and ED-1 macrophages (P < .01) with decreased serum levels of sICAM-1 (P < .05). We obtained a negative correlation between ERK1/2 expression and immune cell infiltration or ICAM-1 level. CONCLUSIONS: Antisense ERK1/2 gene therapy can attenuate graft arteriosclerosis so as to protect aortic allografts. The protection seemed to correlate with inhibition of inflammatory infiltration, implying that the ERK1/2 signal transduction pathway plays an important role in the process of chronic vascular rejection.

Animals↗

PubMed2006

Adenovirus-mediated antisense-ERK2 gene therapy attenuates chronic allograft nephropathy.

BACKGROUND: The aim of this study was to investigate the effects of adenovirus-mediated antisense ERK2 (Adanti-ERK2) gene therapy on chronic allograft nephropathy. METHODS: We employed a rat kidney transplantation mode (F344-->Lewis) and studied four groups: (1) controls (n = 6); (2) vector controls (n = 6); (3) an Adanti-ERK2 group (n = 10); and (4) an isograft group (n = 4). The animals were monitored for proteinuria, graft histology, infiltrating cells, and immune-related gene (interleukin-2 [IL-2] and intracellular adhesion molecule-1 [ICAM-1]) expression for 20 weeks after transplantation. RESULTS: The control group had increasing proteinuria during the 20-week follow-up. All rats showed advanced chronic renal failure associated with strong immune cell infiltration and immune gene expression. Chronic graft injury was accelerated in the vector-control group, but no significant difference was observed compared with the control group. In contrast, the Adanti-ERK2 group showed less inflammation and improved graft histology/function compared with controls. Moreover, ERK2 protein expression in the Adanti-ERK2 group was lower than in the control group (P < .05) and vector-control group (P < .05). Furthermore, serial estimates of genes (IL-2, ICAM-1) related to chronic rejection showed significant downregulation in the Adanti-ERK2 group (P < .01). CONCLUSIONS: Adenovirus-mediated antisense ERK2 gene therapy attenuated chronic allograft nephropathy. The protective effects of antisense ERK2 gene therapy may have derived from a blocked ERK signal transduction pathway, which reduced ERK expression as well as those of immune-related genes.

Adenoviridae↗

PubMed2006

Extreme obesity is associated with attempted suicides: results from a family study.

This study was conducted to explore the association between attempted suicides and body mass index (BMI, kg/m2) in a family sample of 2547 individuals. As a comparison, a national NESARC (the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions) sample of 41 589 individuals was included to validate the observed association. Compared to average weight, extreme obesity showed significantly increased odds for attempted suicides both in family sample (odds ratio (OR) = 3.37 and 95% confidence interval (CI) = 1.59-7.13 for BMI = 40- < 50 kg/m2; OR = 3.85 and 95% CI = 1.71-8.66 for BMI > or = 50 kg/m2) and in NESARC sample (OR = 2.11 and 95% CI = 1.59-2.81 for BMI = 40- < 50 kg/m2; OR = 2.56 and 95% CI = 1.34-4.92 for BMI> or = 50 kg/m2) after adjustment for sociodemographic factors. Compared to general population, the risk for attempted suicide was 87 and 122% higher for those with BMI=40- < 50 and > or = 50 kg/m2, respectively. The pattern of results in the family and population studies indicates that extreme obesity is strongly associated with attempted suicide.

Black or African American↗

PubMed2005

Regression of NMU-induced mammary tumors with the combination of melatonin and 9-cis-retinoic acid.

A significant increase in tumor regression was induced in N-nitroso-N-methylurea-induced mammary tumors in rats treated with the combination of melatonin and 9-cis-retinoic acid (9cRA). Treatment groups included: control (ethanolic saline), 9cRA (30 mg/kg chow/day), melatonin 500 microg/day, melatonin 1000 microg/day, melatonin 500 microg/day+9cRA and melatonin 1000 microg/day+9cRA. Rats treated with the lower dose of melatonin 500 microg+9cRA show the greatest degree of tumor regression (78%), with 54% undergoing complete regression and a significant increase in apoptotic cells observed by TUNEL Assay. Furthermore, tumor multiplicity and burden were significantly decreased by the combination of melatonin and 9cRA.

Alitretinoin↗

PubMed2004

Relationship of obesity to depression: a family-based study.

OBJECTIVE: To examine the relationship between obesity and depression in a sample of extremely obese individuals and their siblings and parents. SUBJECTS: A total of 1730 European Americans (558 men, 1172 women, aged 49.29+/-15.42 y, body mass index (BMI) of 35.57+/-11.53 kg/m(2)) and 373 African Americans (103 men, 270 women, aged 44.85+/-15.08 years, BMI of 36.83+/-11.31 kg/m(2)) in a sample of 482 nuclear families segregating extreme obesity and normal weight. MEASUREMENTS: Individual BMI, history of depression treatment and covariates (age, sex, race, education, marital status, socioeconomic status, chronic medical conditions and exercise program). RESULTS: Greater odds for depression were found for the obese, European American, women, the unmarried, the more educated, those with chronic physical disorder(s) and the offspring of depressed parents. A trend test found that the odds ratios for depression increased with BMI and number of chronic medical conditions (P<0.0001). Multivariate logistic regression analyses indicated that BMI, race, marital status, chronic medical conditions and family history were the predicators of depression for both the genders. Hierarchical analyses revealed that BMI significantly increased the risk above that predicated by the combined effects of all other variables. CONCLUSIONS: Extreme obesity was associated with the increased risk for depression across gender and racial groups, even after controlling for chronic physical disease, familial depression and demographic risk factors. More detailed research is needed to determine the underlying mechanisms.

Adolescent↗

PubMed2004

Sox genes and cancer.

Sox genes encode transcription factors belonging to the HMG (High Mobility Group) superfamily. They are conserved across species and involved in a number of developmental processes. In vitro studies have shown at least one Sox gene to be capable of inducing oncogenic transformation of fibroblast cells. In addition, overexpression and/or amplification of Sox genes are associated with a large number of tumour types in vivo. We review here the available evidence linking Sox gene expression and cancer, and show that this link is supported by extensive EST database analysis. This work provides a basis for further studies aimed at investigating the possible role of Sox genes in the oncogenic process.

Animals↗

PubMed2003

A structural perspective on the enzymes that convert dTDP-d-glucose into dTDP-l-rhamnose.

Bacteria have a rich collection of biochemical pathways for the synthesis of complex metabolites. These conversions often involve chemical reactions that are hard to reproduce in the laboratory. An area of considerable interest is in the manipulation and synthesis of carbohydrates. In contrast with amino acids, carbohydrates are densely functionalized (each carbon atom is attached to at least one heteroatom) and this holds out the prospect of discovering novel enzyme mechanisms. The results from the study of the biosynthetic dTDP-L-rhamnose pathway are discussed. dTDP-L-rhamnose is a key intermediate in many pathogenic bacteria, as it is the donor for L-rhamnose, which is found in the cell wall of important human pathogens, such as Mycobacteria tuberculosis and Salmonella typhimurium. All four enzymes have been structurally characterized; in particular, the acquisition of structural data on substrate complexes was extremely useful. The structural data have guided site-directed-mutagenesis studies that have been used to test mechanistic hypotheses. The results shed light on three classes of enzyme mechanism: nucleotide condensation, short-chain dehydrogenase activity and epimerization.

Glucose↗

PubMed2003

Identification of a novel human sand family protein in human fibroblasts induced by herpes simplex virus 1 binding.

Studies on interaction between Herpes simplex virus 1 (HSV-1) and human fibroblasts KMB-17 have demonstrated that HSV-1 binding to the cell surface could induce a specific gene response. In this study, the HSV-1 stimulation-related gene 1 (HSRG1), a new so far unknown gene function of cellular response induced by a specific stimulation with HSV-1, was cloned from the cDNA library established from mRNA of early gene response of KMB-17 cells. The gene product consisted of 547 amino acids and had a significant homology, in six eukaryotic species. On the basis of its structure it was identified as a member of the SAND protein family. The HSRG1 protein was fused with glutathione S-transferase (GST) and expressed in Escherichia coli DHPalpha strain under the control of T7 promoter. An antibody to HSRG1 raised in mice was used to detect expression of the HSRG1 protein in KMB-17 cells stimulated by HSV-1 by an immunoprecipitation assay. It was found that the HSRG1 protein was induced in these cells by HSV-1 at high level.

Amino Acid Sequence↗

PubMed2002

Involvement of the mt1 melatonin receptor in human breast cancer.

Two putative melatonin receptors have been described including the cell surface G-protein-linked receptors, mt1 and MT2, and the nuclear retinoic orphan receptor alpha (RORalpha). The mt1 receptor, but not the MT2 receptor, is expressed in human breast tumor cell lines, and melatonin-induced growth suppression can be mimicked by the mt1 and MT2 agonist, AMMTC, and blocked by the antagonist, CBPT. RORalpha receptors are also expressed in MCF-7 breast cancer cells and the putative RORalpha agonist CPG-52608 inhibits MCF-7 cell growth but with a very different dose-response than melatonin. Finally, melatonin and AMMTC, but not CPG-52608, can repress RORalpha transcriptional activity in MCF-7 cells.

Breast Neoplasms↗

PubMed2002

Signaling and cell death in lymphocytes.

After activation, CD4 helper T (Th) cells differentiate into Th1 or Th2 effector cells. These two subsets produce distinct profiles of cytokines and regulate different immune responses. Here we discuss transcription factors and signaling pathways that are selectively expressed or activated in Th1 and Th2 cells to regulate cytokine gene expression, cell proliferation and apoptosis.

Animals↗

PubMed2002

The protective effects of melatonin from oxidative damage induced by amyloid beta-peptide 25-35 in middle-aged rats.

This work investigated the ability of melatonin to prevent oxidative damage in brain tissue induced by injection of beta-amyloid peptide 25-35 (Abeta25-35) in middle-aged rats. The Morris water maze was used to evaluate the cognitive function of the rats. Thiobarbituric acid-reactive substances and antioxidative enzymes (superoxide dismutase and glutathione peroxidase) activities were measured. It was found that injection of (Abeta25-35) (20 microg) into the rat hippocampus caused an increase in the latency (the time to find the platform), the total swimming distance to the platform, and the starting angles in (Abeta25-35)-treated rats. Furthermore, a significant rise in lipid peroxidation and decrease in antioxidative enzyme activities in brain tissue were found. Melatonin (0.1, 1, and 10 mg/kg, i.g. x 10 days) improved the spatial resolution of amnesic rats in the Morris water maze test. Meanwhile, melatonin antagonized the lipid peroxidation in both the mitochondria (P < 0.01) at the doses of 0.1, 1.0, and 10 mg/kg and in the cytoplasm at the doses of 0.1 and 1.0 mg/kg. Also in the amnesic rats, melatonin (0.1, 1.0, and 10 mg/kg. i.g. x 10 days) stimulated the antioxidative enzyme activities. The results show that melatonin effectively reduced lipid peroxidation and enhanced the antioxidative enzyme activities in Abeta(25-35)-treated rats, which may contribute to the improvement of rats' learning and memory impaired by Abeta(25-35).

Age Factors↗

PubMed2001

Defective antigen processing in GILT-free mice.

Processing of proteins for major histocompatibility complex (MHC) class II-restricted presentation to CD4-positive T lymphocytes occurs after they are internalized by antigen-presenting cells (APCs). Antigenic proteins frequently contain disulfide bonds, and their reduction in the endocytic pathway facilitates processing. In humans, a gamma interferon-inducible lysosomal thiol reductase (GILT) is constitutively present in late endocytic compartments of APCs. Here, we identified the mouse homolog of GILT and generated a GILT knockout mouse. GILT facilitated the processing and presentation to antigen-specific T cells of protein antigens containing disulfide bonds. The response to hen egg lysozyme, a model antigen with a compact structure containing four disulfide bonds, was examined in detail.

Amino Acid Sequence↗

PubMed2001

Second primary neoplasms among 53 159 haematolymphoproliferative malignancy patients in Sweden, 1958-1996: a search for common mechanisms.

The Swedish Family-Cancer Database was used to analyse site-specific risk of second primary malignancies following 53 159 haematolymphoproliferative disorders (HLPD) diagnosed between 1958 and 1996. Standardized incidence ratio (SIR) of a second malignancy was calculated as the ratio of observed to expected numbers of second malignancies by applying site-, sex-, age-, period-, residence- and occupation-specific rates in the corresponding population in the Database to the appropriate person-years at risk. Among 18 960 patients with non-Hodgkin's lymphoma (NHL), there was over a 3-fold significant increase in cancer of the tongue, small intestine, nose, kidney and nervous system, squamous cell carcinoma (SCC) of the skin, NHL, Hodgkin's disease (HD) and lymphoid and myeloid leukaemia. Among 5353 patients with HD, there was over a 4-fold significant increase in cancer of the salivary glands, nasopharynx and thyroid, NHL and myeloid leukaemia, and over a 1.6-fold increase in cancer of the stomach, colon, lung, breast, skin (melanoma and SCC), nervous system and soft tissues and lymphoid leukaemia. Among 28 846 patients with myeloma and leukaemia, there was a significant increase in cancer of the skin, nervous system and non-thyroid endocrine glands and all HLPD except for myeloma. Our findings showed some clustering between first and second primaries among Epstein-Barr virus-, ultraviolet radiation- and immunosuppression-related cancers.

Adolescent↗

PubMed2001

Positive signaling through CD72 induces mitogen-activated protein kinase activation and synergizes with B cell receptor signals to induce X-linked immunodeficiency B cell proliferation.

CD72 is a 45-kDa B cell transmembrane glycoprotein that has been shown to be important for B cell activation. However, whether CD72 ligation induces B cell activation by delivering positive signals or sequestering negative signals away from B cell receptor (BCR) signals remains unclear. Here, by comparing the late signaling events associated with the mitogen-activated protein kinase pathway, we identified many similarities and some differences between CD72 and BCR signaling. Thus, CD72 and BCR activated the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinase (JNK) but not p38 mitogen-activated protein kinase. Both CD72- and BCR-mediated ERK and JNK activation required protein kinase C activity, which was equally important for CD72- and BCR-induced B cell proliferation. However, CD72 induced stronger JNK activation compared with BCR. Surprisingly, the JNK activation induced by both BCR and CD72 is Btk independent. Although both CD72 and BCR induced Btk-dependent ERK activation, CD72-mediated proliferation is more resistant to blocking of ERK activity than that of BCR, as shown by the proliferation response of B cells treated with PD98059 and dibutyryl cAMP, agents that inhibit ERK activity. Most importantly, CD72 signaling compensated for defective BCR signaling in X-linked immunodeficiency B cells and partially restored the proliferation response of X-linked immunodeficiency B cells to anti-IgM ligation. These results suggest that CD72 signals B cells by inducing BCR-independent positive signaling pathways.

Agammaglobulinaemia Tyrosine Kinase↗

PubMed2001

Second primary neoplasms in 633,964 cancer patients in Sweden, 1958-1996.

The Swedish Family-Cancer Database was used to analyze concordant (same site) and discordant (different site) second primary neoplasms in 633,964 cancer patients diagnosed from 1958 to 1996. Cases of second malignant neoplasms were extracted from the Database if the diagnosis date of the first and second cancer differed by at least 1 month. The expected numbers of cancers were obtained by applying site-, sex-, age-, period-, residence- and socioeconomic level-specific rates in the corresponding population in the Database to the appropriate person-years at risk. The standardized incidence ratio (SIRs) of a second cancer was taken to be the ratio of observed to expected numbers of second cancers. Of all cancers, 8.5% were subsequent neoplasms (8.4% for males and 8.7% for females). SIRs for both concordant and discordant subsequent cancer were elevated in patients with cancer of the upper aerodigestive tract, colon, nose, breast, other female genitals, testis, kidney, urinary, bladder, skin, nervous system, endocrine, bone, connective tissue, melanoma, lymphoma and leukemia. The risks at some concordant sites, such as nose, squamous cell skin, bone and connective tissue in both sexes, breast in males and upper aerodigestive tract and leukemia in females, were very high (>10). At discordant sites, SIRs were less than 2 but significantly increased after all but gastric and prostatic cancer. Compared with the general population, cancer patients were at a modestly increased risk for new primary cancer after cancers at many sites, calling for attention in treatment, management and prevention.

Databases, Factual↗

PubMed2001

Second primary cancers after anogenital, skin, oral, esophageal and rectal cancers: etiological links?

The Swedish Family-Cancer Database was used to analyze second cancers after oral, esophageal, rectal, cervical, genital and skin (squamous cell carcinoma) cancers. A strong and consistent association of second cancers was observed at all these sites, in men and women. As a novel finding, an association of rectal cancer with the human papillomavirus (HVP)-related cancers was shown. New evidence on an excess of skin cancer with the HPV-related cancers was also provided. As an epidemiological study, the associations were strong and often supported by a number of comparisons. These could not be explained by bias or long-term treatment related effects. However, whether the findings on rectal and skin cancer are due to HPV or other infections, transient or inherited depressed immune function or other constitutional factors remains to be established.

Esophageal Neoplasms↗