Identification of two novel HLA-C alleles, HLA-Cw*1217 and HLA-Cw*030404, in Singapore Chinese.
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Alleles↗
Biomedical subjects
E C Ren
Publications and source records attributed to E C Ren.
Identification of a new HLA-A*2464 variant in the Singapore Chinese population.
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Alleles↗
Hcc-1 is a novel component of the nuclear matrix with growth inhibitory function.
Hcc-1 is a novel nuclear protein containing the SAF-box DNA-binding domain. It binds to both double-stranded and single-stranded DNA with higher affinity for the single-stranded form. In addition, it also binds specifically to scaffold/matrix attachment region DNA. These nucleic acid-binding characteristics suggest a potential function for Hcc-1 as a component of the heterogeneous ribonucleoprotein complex. Using a yeast two-hybrid screen, two DEAD-box RNA helicases, BAT1 and DDX39, were identified as proteins that interact with Hcc-1. Interactions with these RNA helicases suggested a role for Hcc-1 in nucleic acid biogenesis. Expression of Hcc-1 in the HEK293 cell line resulted in a slower growth rate compared to controls (p = 0.0173) and an accumulation of cells at the G2/M phase (p = 0.0276 compared to control HEK293 cells). Taken together, these results suggest a role for Hcc-1 in growth regulation and nucleic acids metabolism.
ATP-Binding Cassette Transporters↗
Associations of HLA microsatellites with rheumatoid arthritis in Singaporean Chinese.
Rheumatoid arthritis in Singaporean Chinese has previously been shown to be associated with the DRB1*0405, DRB1*1001 haplotypes and to the DRB1*0901 haplotype when the former two were removed. The present paper focused on eight HLA associated microsatellite markers (TNFa, TNFd, D6S273, TAP1CA, DQCAR, DQCARII, D6S2222, D6S2223) and their allelic associations with Chinese RA. 60 RA patients and 75 healthy controls were studied. It appeared that DQCARII*194/DRB1*0405/TNFa*117 was part of the extended haplotype predisposed to RA, whereas DRB1*0901/D6S273*128 contributed to susceptibility to RA to a lesser degree in Singaporean Chinese. Additionally, a negative association with DQCAR*186/DRB1*0301/D6S273*122/TNFd*124 was observed. No association with disease development was observed in this study.
Arthritis, Rheumatoid↗
Antibody response to Epstein-Barr virus Rta protein in patients with nasopharyngeal carcinoma: a new serologic parameter for diagnosis.
BACKGROUND: Nasopharyngeal carcinoma (NPC) is associated closely with Epstein-Barr virus (EBV). The authors previously reported that an EBV immediate-early gene, BRLF1, was expressed frequently in NPC tumors, and a significant elevation in immunoglobulin G (IgG) antibodies directed against BRLF1 gene product Rta was detected in NPC sera by a radioactive immunoprecipitation assay. To simplify and to make the detection more quantitative, an enzyme-linked immnunosorbent assay (ELISA) was developed in this study. METHODS: Antigen domains of Rta were identified further using an immunoprecipitation assay. Two glutathione-S-transferase (GST) recombinant Rta fragments (R150-GST and R185-GST) were prepared subsequently and were used as antigens in the ELISA. Serum samples derived from 51 patients with NPC patients, 115 non-NPC ENT patients, and 47 healthy volunteers were examined for the presence of antibodies directed against Rta. RESULTS: Among the patients with NPC, 74.5% showed a positive IgG response to R150-GST, and 62.7% showed a positive IgG response to R185-GST, with 80.4% positive for either fragment. In contrast, the reactions were positive in only 8.5% of healthy volunteers and 13.0% of control patients. When using a mixture of the two recombinant Rta proteins as coating antigens, the IgG positive responses were 82.3%, 10.6%, and 14.8%, respectively, in patients with NPC, healthy volunteers, and control patients. It is noteworthy that 51.0% of the NPC sera showed a positive immunoglobulin A (IgA) response, with none of the control patients showing obvious reactivity. Both the IgG response and the IgA response to Rta protein in patients with NPC were correlated with the IgA response to EBV early antigens and virus capsid antigens, the classic serologic markers used to diagnose NPC. CONCLUSIONS: The ELISA method described for the detection of IgG antibodies directed against recombinant Rta proteins is simple and reliable and may be useful as a serologic parameter for the screening and diagnosis of patients with NPC.
Antibodies, Viral↗
An integrated approach in the discovery and characterization of a novel nuclear protein over-expressed in liver and pancreatic tumors.
An integrated approach in protein discovery through the use of multidisciplinary tools was reported. A novel protein, Hcc-1, was identified by analysis of the hepatocellular carcinoma (HCC)-M cell proteome. The assembled EST sequence of the 210 amino acid novel protein was subsequently confirmed by rapid amplification of cDNA ends (RACE). A total of 687 bp at the 5' untranslated region of Hcc-1 was identified. Promoter activity and several upstream open reading frames (uORFs) were demonstrated at this region. Bioinformatics prediction showed that the first 42 amino acids of the protein is a SAP domain with sequence matches to hnRNP from various vertebrate species. The Hcc-1 protein was localized to the cell nucleus while the gene was localized to chromosome 7q22.1. Hcc-1 cDNA level was increased in pancreatic adenocarcinoma. The level was also increased in well-differentiated hepatocellular carcinoma but decreases as the carcinoma progressed to a poorly differentiated stage.
5' Untranslated Regions↗
Towards the MHC-peptide combinatorics.
The exponentially increased sequence information on major histocompatibility complex (MHC) alleles points to the existence of a high degree of polymorphism within them. To understand the functional consequences of MHC alleles, 36 nonredundant MHC-peptide complexes in the protein data bank (PDB) were examined. Induced fit molecular recognition patterns such as those in MHC-peptide complexes are governed by numerous rules. The 36 complexes were clustered into 19 subgroups based on allele specificity and peptide length. The subgroups were further analyzed for identifying common features in MHC-peptide binding pattern. The four major observations made during the investigation were: (1) the positional preference of peptide residues defined by percentage burial upon complex formation is shown for all the 19 subgroups and the burial profiles within entries in a given subgroup are found to be similar; (2) in class I specific 8- and 9-mer peptides, the fourth residue is consistently solvent exposed, however this observation is not consistent in class I specific 10-mer peptides; (3) an anchor-shift in positional preference is observed towards the C terminal as the peptide length increases in class II specific peptides; and (4) peptide backbone atoms are proportionately dominant at the MHC-peptide interface.
Animals↗
Two-dimensional electrophoresis map of the human hepatocellular carcinoma cell line, HCC-M, and identification of the separated proteins by mass spectrometry.
Currently, one of the most popular applications of proteomics is in the area of cancer research. In Africa, Southeast Asia, and China, hepatocellular carcinoma is one of the most common cancers, occurring as one of the top five cancers in frequency. This project was initiated with the purpose of separating and identifying the proteins of a human hepatocellular carcinoma cell line, HCC-M. After two-dimensional gel electrophoresis separation, silver staining, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analyses, tryptic peptide masses were searched for matches in the SWISS-PROT and NCBI nonredundant databases. Approximately 400 spots were analyzed using this approach. Among the proteins identified were housekeeping proteins such as alcohol dehydrogenase, alpha-enolase, asparagine synthetase, isocitrate dehydrogenase, and glucose-6-phosphate 1-dehydrogenase. In addition, we also identified proteins with expression patterns that have been postulated to be related to the process of carcinogenesis. These include 14-3-3 protein, annexin, prohibitin, and thioredoxin peroxidase. This study of the HCC-M proteome, coupled with similar proteome analyses of normal liver tissues, tumors, and other hepatocellular carcinoma cell lines, represents the first step towards the establishment of protein databases, which are valuable resources in studies on the differential protein expressions of human hepatocellular carcinoma.
Carcinoma, Hepatocellular↗
Membranous nephropathy with anti-tubular basement membrane antibody may be X-linked.
The association of membranous nephropathy with Fanconi syndrome and anti-tubular basement antibodies appears to be a distinct subset of familial membranous nephropathy. We studied two Chinese families with four affected boys to evaluate the mode of inheritance of disease. HLA haplotype analysis of the family members in these two pedigrees did not reveal any significant linkages. However, microsatellite analysis of both pedigrees using markers on the X chromosome suggested linkage to the long arm of the X chromosome between the microsatellite markers DXS1001 and DXS1227. Identification and analysis of additional pedigrees may allow more precise mapping of the disease gene for anti-tubular basement membrane antibody-associated membranous nephropathy.
Autoantibodies↗
The role of HLA matching in unrelated donor bone marrow transplant.
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Bone Marrow Transplantation↗
Molecular modeling of the minor histocompatibility antigen HA-1 peptides binding to HLA-A alleles.
Mismatch of the minor histocompatibility antigen HA-1 has been shown to correlate with graft-versus-host disease in HLA-matched sibling marrow transplants. The HA-1H peptide (VLHDDLLEA) that generates this response is known to be presented by HLA-A*0201. In order to understand the interaction of HA-1 peptides with other HLA-A alleles, we have used the LOOK interface to construct molecular models of both HA-1H peptide (VLHDDLLEA) and HA-1R peptide (VLRDDLLEA) binding with 103 HLA-A alleles. The results show that in addition to A*0201, 21/103 other HLA-A alleles should be able to bind HA-1H peptide but not HA-1R peptide. Based on the modeled predictions, HLA alleles can be categorised into 4 groups with respect to their interaction with HA-1 peptides: Group 1 - bind HA-1H peptide but not HA-1R peptide; Group 2 - bind HA-1R peptide but not HA-1H peptide; Group 3 - bind both HA-1H and HA-1R peptides; Group 4 - bind neither peptide. These predicted binding patterns of HA-1 peptides will be useful as an aid for defining a wider pool of HLA-A alleles in which HA-1 disparities among donor-recipient pairs can be investigated.
Alleles↗
Variability in CD34+ cell counts in umbilical cord blood: implications for cord blood transplants.
OBJECTIVE: To determine if total nucleated cell counts alone are sufficient for predicting the efficacy of cord blood units for transplant from neonatal umbilical cord blood samples. METHODS: Umbilical cord blood samples were collected from 200 mothers at delivery and the cord blood units processed. The total nucleated cells and CD34+ cells were enumerated and compared for each sample. RESULTS: Despite an apparent linear correlation between total nucleated cell counts and CD34+ cell counts, each group of total nucleated cell counts demonstrated a high degree of variation in CD34+ cell counts and could be as low as 0.1% of total nucleated cell counts. CONCLUSIONS: Large variations in CD34+ cell counts per total nucleated cell count are present for cord blood units from neonatal umbilical cord samples. Hence a CD34+ cell count for each cord blood unit would improve selection of samples for transplant.
Antigens, CD34↗
Diversity of GB virus C/hepatitis G virus isolates in Singapore: predominance of group 2a and the Asian group 3 variant.
The occurrence of GBV-C/HGV infection was studied in 160 individuals from two high-risk groups in Singapore. RT-PCR of the 5'-UTR detected GBV-C/HGV RNA in 3/73 (4.1%) of patients undergoing maintenance hemodialysis for chronic renal failure, and in 17/87 (19.5%) of patients coinfected with HCV who tested positive for HCV RNA. Phylogenetic analysis of 5'-UTR sequences from these 20 samples showed that the Asian or group 3 variant was found in 45% of the samples sequenced, thus confirming the high frequency of this variant in the region. Group 2a variants accounted for 50% of the samples with a complete absence of group 2b. Our analysis also provided strong bootstrap support for the subdivision of group 2 into subgroups 2a and 2b. This study shows that isolates belonging to all three main groups of GBV-C/ HGV can be detected in Singapore, with the large majority belonging to groups 2a (50%) and 3 (45%). Only a single group 1-like sequence was detected within the 20 isolates. Of interest also is that all group 3 isolates were identified in Chinese patients while group 2a was found in both Chinese and Malay.
5' Untranslated Regions↗
A special report: histocompatibility testing guidelines for hematopoietic stem cell transplantation using volunteer donors. Quality Assurance and Donor Registries Working Groups of the World Marrow Donor Association.
The World Marrow Donor Association has formulated guidelines for establishing the extent and quality of histocompatibility testing for unrelated donor registries, umbilical cord blood banks, and transplant centers involved in international exchange of hematopoietic stem cells for allogeneic transplantation. Registry and cord blood bank guidelines suggest that, at a minimum, initial HLA typing should be performed for three HLA loci, HLA-A, -B, and -DR, at low resolution/split antigen level. DNA-based testing methods should be utilized for HLA-DR typing. DNA-based testing for HLA-A and -B should replace serologic testing of new volunteer donors and cord blood units as robust protocols and reagents become available to the laboratories. Transplant center guidelines for typing of patient, family and to confirm the HLA types of potential unrelated donors should include, at the minimum, typing HLA-A, B, and -DR loci using primarily DNA-based testing methods at allele level resolution for DRB1 and low resolution/split antigen level for HLA-A and -B. It is strongly recommended that the typing of a patient and the selected donor be performed using the same set of reagents, methodology, and interpretation criteria with fresh tissue samples to ensure HLA identity. Guidelines for laboratory accreditation, approaches to quality assurance and quality control for HLA testing, and suggestions for the format of the HLA database of donor types are also outlined.
Bone Marrow Transplantation↗
Identification of a novel HLA-C allele, Cw*0406, in a Singapore Malay.
A novel allele, C*0406, has been identified and is characterised by a single nucleotide substitution at position 196 of exon 3 when compared with its closest related allele, C*0403. The latter is found in 4/69 Chinese and 7/80 Malays while Cw*0406 was found in only one Malay individual within the study populations. The data suggest that Cw*0406 may have arisen as a relatively recent genetic event either by gene conversion or as a simple point mutation variant of Cw*0403.
Alleles↗
A special report: histocompatibility testing guidelines for hematopoietic stem cell transplantation using volunteer donors.
The World Marrow Donor Association has formulated guidelines for establishing the extent and quality of histocompatibility testing for unrelated donor registries, umbilical cord blood banks, and transplant centers involved in international exchange of hematopoietic stem cells for allogeneic transplantation. Registry and cord blood bank guidelines suggest that, at a minimum, initial HLA typing should be performed for three HLA loci, HLA-A, -B, and -DR, at low resolution/split antigen level. DNA-based testing methods should be utilized for HLA-DR typing. DNA-based testing for HLA-A and -B should replace serologic testing of new volunteer donors and cord blood units as robust protocols and reagents become available to the laboratories. Transplant center guidelines for typing of patient, family and to confirm the HLA types of potential unrelated donors should include, at the minimum, typing HLA-A, B, and -DR loci using primarily DNA-based testing methods at allele level resolution for DRB1 and low resolution/ split antigen level for HLA-A and -B. It is strongly recommended that the typing of a patient and the selected donor be performed using the same set of reagents, methodology, and interpretation criteria with fresh tissue samples to ensure HLA identity. Guidelines for laboratory accreditation, approaches to quality assurance and quality control for HLA testing, and suggestions for the format of the HLA database of donor types are also outlined.
Hematopoietic Stem Cell Transplantation↗
Histocompatibility testing guidelines for hematopoietic stem cell transplantation using volunteer donors: report from The World Marrow Donor Association. Quality Assurance and Donor Registries Working Groups of the World Marrow Donor Association.
The World Marrow Donor Association has formulated guidelines for establishing the extent and quality of histocompatibility testing for unrelated donor registries, umbilical cord blood banks, and transplant centers involved in international exchange of hematopoietic stem cells for allogeneic transplantation. The ability to identify unrelated stem cell donors in one country for patients in another country requires cooperation and standardization in many areas. The adoption of guidelines for histocompatibility testing, such as those summarized in this report, will facilitate these opportunities and rapidly provide accurately typed donors for patients in need.
Adult↗
Elevated blood levels of soluble tumor necrosis factor receptors in nasopharyngeal carcinoma: correlation with humoral immune response to lytic replication of Epstein-Barr virus.
Nasopharyngeal carcinoma (NPC) is tightly associated with Epstein-Barr virus (EBV) infection and a heavy infiltration of lymphoid cells in the tumor tissue. Although various lines of evidence have shown that the immune systems of NPC patients have the potential to attack the tumor cells, it is not yet understood how this potential is blocked. In this study we determined the circulatory soluble tumor necrosis factor receptors (sTNFRI and sTNFRII), which are proven to be inhibitory to the anti-tumor effects of tumor necrosis factor-alpha (TNF-alpha), in NPC patients. The serum concentration of both sTNFRI and sTNFRII was determined with an ELISA method, and shown to be significantly higher in 28 NPC patients than in matched healthy controls. This elevation was found to be positively correlated with the serum titers of IgA against EBV early antigens and viral capsid antigens in NPC patients, suggesting that the increased serum concentration of sTNFRI and sTNFRII is possibly due to the EBV infection in NPC tumor cells. This is partly supported by FACS analysis of the circulatory T cells. Phenotypical expression of activation markers such as CD25, CD38, CD69 and CD71 in blood T cells was not significantly different between the NPC and control individuals, indicating the elevation of the sTNFRs is indeed derived from the local immune response in the tumor area. Based on these results, it seems that the increased sTNFRs may act as an inhibitor to decrease the host immune response towards tumor cells in NPC patients.
Adult↗