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Jian-Jun Chen

Publications and source records attributed to Jian-Jun Chen.

At least 19 recordsLinked to original sources
PubMed2006

Follow-up analysis of PSORS9 in 151 Chinese families confirmed the linkage to 4q31-32 and refined the evidence to the families of early-onset psoriasis.

Psoriasis linkage to 4q28-32 (PSORS9) was initially identified by our genome-wide scan in 61 Chinese families and subsequently supported by a meta-analysis of five genome-wide linkage scans of European populations. In this study, we performed a follow-up analysis of PSORS9 using an additional 90 families and improved marker coverage. Joint analysis of all 151 families obtained significant linkage evidence (HLOD=4.53, nonparametric linkage (NPL)=4.03 (P=0.000003)) at the marker interval D4S2997-D4S3033, and the same was obtained for the analysis of the independent new families (HLOD=4.33, NPL=3.15 (P=0.00004)). The linkage evidences from the whole families and the new families exceeded the genome-wide criteria for significant linkage. Furthermore, by performing an ordered subset analysis using mean age at onset as a covariate, we demonstrated that evidence for linkage to PSORS9 is concentrated in the early-onset families and suggested that further study of PSORS9 should focus on early-onset patients. This finding is contradictory to what was found in the Icelandic population and, together with other linkage results, suggests that Chinese and European populations are genetically different for linkage to PSORS9, which may partially explain the influence of ethnic factors on the varying prevalence of psoriasis.

Age of Onset↗
PubMed2006

The gene for a rare autosomal dominant form of pompholyx maps to chromosome 18q22.1-18q22.3.

Pompholyx is a rather common disorder characterized by recurrent crops of vesicles or bullae on the lateral aspects of the fingers, as well as the palms and soles with non-erythematous skin. Until now, very few large families have been reported, so no gene or locus has been identified. Here, we performed a genome-wide search in a large Chinese family to map the chromosome location of the responsible gene. We identified a locus at chromosome 18q22.1-18q22.3 with a maximum two-point LOD score of 3.61 at marker D18S1131 (theta = 0.00). Haplotype analyses indicated that the disease gene is located within 12.07 cM region between markers D18S465 and D18S1362, which corresponds to 8.0 Mb. This is the first locus identified for pompholyx. It will aid future identification of the responsible gene, which will be useful for the understanding of the molecular mechanism of pompholyx.

Adolescent↗
PubMed2006

A novel MGST2 non-synonymous mutation in a Chinese pedigree with psoriasis vulgaris.

A balanced translocation was recently identified in a German psoriasis patient. One of the breakpoints was mapped immediately upstream of the microsomal glutathione S-transferase 2 (MGST2) gene, suggesting it as a candidate gene. Here, we report the identification of a novel non-synonymous mutation in MGST2 by a comprehensive sequence analysis of MGST2's coding region in Chinese psoriasis samples. We demonstrate that this mutation co-segregated with the disease phenotype within a Chinese family affected with psoriasis vulgaris and is predicted to have an impact on the normal function of MGST2 protein. However, the mutation was absent in 551 additional cases and 384 healthy Chinese controls. While requiring independent confirmation, our results suggest that this rare mutation could play a causal role in a small subset of psoriasis individuals.

Adult↗
PubMed2005

Aberrant T helper cell response in tumor-bearing mice limits the efficacy of dendritic cell vaccine.

Dendritic cell (DC) vaccine is a promising immunotherapy for malignancies, but its clinical efficacy has been questioned. Here we examined the mechanisms of treatment failure with DC vaccine in a murine colon cancer model. DC vaccination of naive mice prevents tumor implantation, but it is ineffective in tumor-bearing hosts despite the induction of tumor-specific CTL activity. Analyses of tumor-specific T helper cell type 1 (Th1)/T helper cell type 2 (Th2) responses showed that DC vaccine induced a mixed Th1/Th2 response in naive mice. Interestingly, CD4+ T cells from tumor-bearing mice showed a Th1-predominant response before DC vaccination but Th2 after DC vaccination. Furthermore, interleukin-10 production was higher in CD4+ T cells from vaccinated tumor-bearing mice than in CD4+ T cells from unvaccinated tumor-bearing mice. CD4+ T cells from mice treated with lipopolysaccharide (LPS)-matured DC fusion vaccine had lower production of interleukin-10 than CD4+ T cells from mice treated with non-LPS-treated DC vaccine. However, similar to the non-LPS-treated DC vaccine, the LPS-matured DC vaccine failed to suppress tumor growth and induced a Th2 predominant tumor-specific response in tumor-bearing mice. These results suggest that the presence of tumor in the host induces an aberrant CD4+ T cell response to DC vaccine, which may contribute to the failure of the vaccine to eradicate established tumors.

Animals↗
PubMed2005

Superior efficacy of dendritic cell-tumor fusion vaccine compared with tumor lysate-pulsed dendritic cell vaccine in colon cancer.

Dendritic cell (DC)-based tumor vaccine is a promising therapy for malignancies. Recent studies showed greater potency with DC/tumor fusion vaccines against acute myeloid leukemia and melanoma compared with lysate-pulsed DC vaccines. We compared these two vaccine strategies against murine colon cancer and investigated whether DC/tumor fusion cells continue to produce tumor antigens following fusion as a possible explanation for their increased potency. Using a mouse colon cancer model, CT26, we first showed that the DC/CT26 fusion vaccine is more effective in preventing tumor implantation than CT26 lysate-pulsed DC vaccine. Next, CT26 made to constitutively produce bioactive TGF-beta, a surrogate of tumor-derived products, was fused to DCs and found to produce bioactive TGF-beta 72 h after fusion. Our results suggest the DC/tumor fusion vaccine is more potent against colon cancer than the lysate-pulsed DC vaccine. These fusion cells have the distinct advantage of prolonged interaction with tumor antigens in vivo.

Animals↗
PubMed2005

Association of HLA class I alleles with aloplecia areata in Chinese Hans.

BACKGROUND: Some studies suggested that human HLA status may potentiate development of the AA phenotype and exists ethic differences. No report has been published about HLA class I alleles associated with AA in Chinese Hans. OBJECTIVE: To study the distribution of HLA class I alleles and haplotypes in Chinese Hans AA patients and the relation of HLA class I profile with age of onset, severity, duration of current attack, past history and family history. METHODS: The polymerase chain reaction-sequence-specific primer (PCR-SSP) method was used to analyze the distribution of HLA class I alleles in 192 patients with AA and 252 healthy controls in Chinese Hans. RESULTS: The frequencies of HLA-A*02, -A*03, -B*18, -B*27, -B*52 and -Cw*0704 were significantly higher in patients than in controls. The A*2-B*18, A*2-B*27, A*2-B*52, A*2-Cw*0704, B*18-Cw*0704, B*27-Cw*0704, B*52-Cw*0704 were found as high-risk haplotypes in developing AA in this study. The HLA-A*02 and -A*03 were observed increased frequencies in patients less than 50% hair loss, and HLA-B*27 equally in patients of 50-99% hair loss, alopecia totalis and alopecia universalis. The frequencies of HLA-A*02 and -B*27 were significantly raised in recurrent patients, and ones of HLA-A*02, -A*03 and -B*27 similarly in patients without a positive family history. CONCLUSION: This study demonstrated the positive association of HLA class I alleles and haplotypes with AA. There may be differences in genetic background in patients with different age of onset, grade of scalp hair loss, duration of current attack, a past history and a family history.

Adolescent↗
PubMed2005

Knockdown of Pu.1 by small interfering RNA in CD34+ embryoid body cells derived from mouse ES cells turns cell fate determination to pro-B cells.

The factors that regulate murine ES cell-derived hematopoietic progenitor cell (HPC) commitment to the B lymphocyte lineage remain unclear. Pu.1 plays an essential role in the development of all lymphoid lineages; however, it also regulates commitment to other blood cell lineages. In this study, we found evidence for early B cell lineage commitment as determined by coexpression of CD19 and CD45R (B220) when Pu.1 expression was knocked down in HPC by specific small interfering RNA (siRNA); moreover, the expression of early B cell factor (Ebf) and paired box protein 5 (Pax-5) transcription factors was induced when cells were treated by Pu.1 siRNA, but not by control siRNA. We also found that siRNA-mediated knockdown of Pu.1 expression was more efficient in generating progenitor B cells (pro-B cells) compared with the more common in vitro method of B lymphoid development by means of coculture of CD34+ embryoid body (EB) cells with OP9 stromal cells. To investigate whether this phenomenon also exists in HPC from other sources, we then knocked down Pu.1 gene expression in CD34+ murine bone marrow cells and found a similar effect of increased production of CD19+CD43+CD45R+ progenitor B cells upon the siRNA-mediated decrease in Pu.1 expression. We conclude that, in early B cell development from ES cell-derived HPC, constitutive Pu.1 expression inhibits the earliest B cell development through repressing early B cell factor and paired box protein 5 expression, although lower levels of Pu.1 expression in HPC play a key role in promoting B cell fate determination.

Animals↗
PubMed2005

A sensitive and specific HPLC-MS method for the determination of sophoridine, sophocarpine and matrine in rabbit plasma.

A sensitive and specific method was developed for the determination of sophoridine (SRI), sophocarpine (SC) and matrine (MT) in rabbit plasma by HPLC-MS. After an administration of Kuhuang by injection, blood samples were collected and extracted with methanol. The extract solutions were analysed by HPLC-MS method. The separation was performed on a ZORBAX Extend-C18 column using methanol/water/diethylamine (50:50:0.07, v/v/v) as mobile phase. The quinolizidine alkaloids were detected by using mass spectrometry in the SIM mode. There was a good linear relationship between peak area and concentration of analytes over the concentration range of 13.2-995.0 ng mL(-1) for SRI, 7.0-530.0 ng mL(-1) for SC and 8.8-655.0 ng mL(-1) for MT, respectively. The absolute recovery of this method was more than 57% for SRI, 87% for SC and 91% for MT. The accuracy of assay was more than 90%. The limits of detection (LODs) were 6.8 ng mL(-1) for SRI, 3.5 ng mL(-1) for SC and 4.2 ng mL(-1) for MT, respectively. The limits of quantitation (LOQs) were 13.2 ng mL(-1) for SRI, 7.0 ng mL(-1) for SC and 8.8 ng mL(-1) for MT, respectively. The intra-day and inter-day coefficients of variation (RSDs) were less than 10.1, 6.3 and 5.8% for SRI, SC and MT, respectively. The developed method was applied to determine the concentration-time profiles of SRI, SC and MT in rabbit plasma after injection of Kuhuang.

Alkaloids↗
PubMed2005

A novel linkage to generalized vitiligo on 4q13-q21 identified in a genomewide linkage analysis of Chinese families.

Generalized vitiligo is a common, autoimmune, familial-clustering depigmentary disorder of the skin and hair that results from selective destruction of melanocytes. Generalized vitiligo is likely a heterogeneous disease, with five susceptibility loci reported so far--on chromosomes 1p31, 6p21, 7q, 8p, and 17p13--in white populations. To investigate vitiligo susceptibility loci in the Chinese population, we performed a genomewide linkage analysis in 57 multiplex Chinese families, each with at least two affected siblings, and we identified interesting linkage evidence on 1p36, 4q13-q21, 6p21-p22, 6q24-q25, 14q12-q13, and 22q12. Subsequently, to extract more linkage information, we investigated our initial genomewide linkage findings in a follow-up analysis of 49 new families and additional markers. Our initial genomewide linkage analysis and our subsequent follow-up analysis have identified a novel linkage to vitiligo on 4q13-q21, with highly significant linkage evidence (a nonparametic LOD score of 4.62 [P=.000003] and a heterogeneity LOD score of 4.01, under a recessive inheritance model), suggesting that 4q13-q21 likely harbors a major susceptibility locus for vitiligo in the Chinese population. We observed a minimal overlap between the linkage results of our current genomewide analysis in the Chinese population and the results of previous analyses in white populations, and we thus hypothesize that, as a polygenic disorder, vitiligo may be associated with great genetic heterogeneity and a substantial difference in its genetic basis between ethnic populations.

China↗
PubMed2005

Identification of a novel mutation in the DSRAD gene in a Chinese pedigree with dyschromatosis symmetrica hereditaria.

Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant skin disorder characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the face and dorsal aspects of the extremities that appear in infancy or early childhood. The DSH locus has recently been mapped to chromosome 1q21 and then pathogenic mutations have been identified in the DSRAD gene. In the study reported here we examined the DSRAD gene mutations of a three-generation Chinese pedigree with DSH by direct sequencing. We identified a novel heterozygous nucleotide T-->C transition at position 3388 in exon 14 of the DSRAD gene which induces a C1130R change in the putative deaminase domain of DSRAD. Our study expands the database on the DSRAD gene mutations in DSH and enriches the knowledge about the function of the DSRAD gene.

Adenosine Deaminase↗
PubMed2005

Two frameshift mutations in the RNA-specific adenosine deaminase gene associated with dyschromatosis symmetrica hereditaria.

OBJECTIVE: To report and analyze the mutations of the double-stranded RNA-specific adenosine deaminase (DSRAD) gene in 2 Chinese pedigrees with dyschromatosis symmetrica hereditaria (DSH). DESIGN: Pedigree study. SETTING: Anhui province of China. PATIENTS: Two Chinese families, consisting of 19 individuals (family 1) and 5 individuals (family 2). INTERVENTIONS: We directly performed mutation detection of the DSRAD gene in 2 Chinese families with DSH by sequencing. The whole coding region of DSRAD was amplified by polymerase chain reaction, and products were analyzed by direct sequencing. MAIN OUTCOME MEASURES: Frameshift DSRAD gene mutations. RESULTS: The c.3513insC (Arg1171fs) mutation was found in all patients but not in the healthy individuals from family 1, and the c.3220_3224delGCATC (Gly1073fs) mutation was found in 2 patients but not in the healthy members of family 2. These 2 mutations were not found in 96 unrelated control individuals. CONCLUSION: Our data suggest that these 2 novel frameshift mutations in the DSRAD gene could cause DSH in the Chinese Han population and add new variants to the repertoire of DSRAD mutations in DSH.

Adenosine Deaminase↗
PubMed2005

The genetic concept of vitiligo.

Vitiligo is a relatively common, acquired pigmentary disorder characterized by areas of depigmented skin resulting from loss of epidermal melanocytes. The prevalence of this disease varies from 0.1 to 2% in various global populations. The genetics of vitiligo cannot be explained by simple Mendelian genetics; it is characterized by incomplete penetrance, multiple susceptibility loci and genetic heterogeneity. Unraveling the complex genetics of vitiligo is a daunting challenge but the perseverance of vitiligo gene hunters has produced commendable results in recent years. Although environmental factors are important, there is considerable evidence that genes also play a significant role in its pathogenesis. Strong evidence from twin and family studies indicates the importance of genetic factors in the development of vitiligo, although it is clear that these influences are complex. Linkage and association studies have also provided strong support for vitiligo susceptibility genes on chromosomes 4q13-q21, 1p31, 7q22, 8p12 and 17p13, while loci of interest at 6p, 6q, 14q, 9q, 13q, 19p and 22q require further follow-up. Although important obstacles to further progress will need to be overcome, the successes of the past 5 years suggest that a detailed description of the genetic basis of vitiligo is a realistic goal. In the future, dissection of the complex genetic architecture of vitiligo will provide new approaches for treatment and prevention. In this article, we will give an overview of the latest findings in the genetics of vitiligo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Reciprocal cross-talk between Nod2 and TAK1 signaling pathways.

Mutations in the leucine-rich repeat (LRR) domain of Nod2 have been implicated in the pathogenesis of Crohn's disease, yet the function of Nod2 and regulation of the Nod2 pathway remain unclear. In this study, we determined that mitogen-activated protein kinase kinase transforming growth factor (TGF)-beta-activated kinase 1 (TAK1) interacts with Nod2 and is required for Nod2-mediated NF-kappaB activation. The dominant negative form of TAK1 abolished muramyl dipeptide-induced NF-kappaB activation in Nod2-expressing cells. Nod2, acting in a reciprocal manner, inhibited TAK1-induced NF-kappaB activation in RICK-deficient embryonic fibroblasts. Nod2 appears to interact with TAK1 through its LRR region to exert its inhibitory effect on TAK1-induced NF-kappaB activation. Further, wild-type LRR more effectively suppressed NF-kappaB activation induced by TAK1 than LRR with a 3020insC mutation. Considered together, these findings demonstrate a critical role for TAK1 in Nod2-mediated innate immune responses and reveal a novel function for Nod2 in the regulation of the TAK1 signaling pathway.

Animals↗
PubMed2004

Expression of Fas ligand is not a main mechanism used by tumors to counteract antitumor immunity.

The role of Fas ligand (FasL) in tumor immune privilege is controversial. In this study, 22 human tumor cell lines reported to be FasL+ were reevaluated by Western blot analysis, ELISA, and a functional assay. None of the cells lines expressed FasL. To assess whether human tumors express FasL in vivo, susceptibility to FasL-mediated killing was evaluated. About 75% of the 22 tumors tested were sensitive to FasL-mediated apoptosis, suggesting, therefore, that only about 25% could possibly express FasL. To investigate whether "FasL+" human tumor cells could suppress the proinflammatory effects of FasL in vivo, FasL transfectants were generated from two prototype "FasL+" tumor cell lines. The transfectants expressing FasL were rejected by SCID mice. In contrast, all the mice inoculated with parental tumor cells developed large tumors. These results suggested that human tumor cells that express FasL and resist both FasL-mediated apoptosis and inflammation are rare or nonexistant. We concluded that FasL expression is not a main mechanism that tumors use to counteract antitumor immunity.

Animals↗
PubMed2004

Seven novel mutations of the ADAR gene in Chinese families and sporadic patients with dyschromatosis symmetrica hereditaria (DSH).

Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant pigmentary genodermatosis characterized by hyperpigmented and hypopigmented macules of on the extremities and caused by the mutations in the ADAR gene(also called DSRAD) encoding for RNA-specific adenosine deaminase. Here we reported clinical and molecular findings of 6 Chinese multi-generation families and 2 sporadic patients with DSH. We found that the same mutation could lead to different phenotypes even in the same family and we did not establish a clear correlation between genotypes and phenotypes. Seven novel heterozygous mutations of ADAR were identified, which were c.2433_2434delAG (p.T811fs), c.2197G>T (p.E733X), c.3286C>T (p.R1096X), c.2897G>T (p.C966F), c.2797C>T (p.Q933X), c.2375delT (p.L792fs) and c.3203-2A>G respectively. Our data add new variants to the repertoire of ADAR mutations in DSH.

Adenosine Deaminase↗