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Biomedical subjects

E C Ren

Publications and source records attributed to E C Ren.

At least 37 records · Page 2Linked to original sources
PubMed1997

Association between microsatellites within the human MHC and nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) has been known to be associated with specific HLA haplotypes, in particular HLA A2, B46 and A33, B58 haplotypes. A linkage study based on this observation suggested that HLA antigens are not the cause of NPC but that there exists a gene that lies close to if not within the major histocompatibility complex locus and confers a greatly increased relative risk of NPC. Since then, no further work has elucidated the presence of this gene. One of the difficulties faced by researchers has been the size of the region of chromosome implicated. The MHC locus alone is almost 4 Mb in length, and the number of genes encoded within it is numerous. The purpose of our study was thus to reduce the region of DNA in which the NPC susceptibility gene is likely to be. We report that the NPC susceptibility gene may be within the centromeric end of the class-1 and the telomeric end of the class-III regions of the MHC, near the D6S1624 microsatellite locus, where the presence of allele 4 of the microsatellite conferred a 3 1/2-fold increase in the risk of NPC, the highest reported for a single locus, and the presence of allele 1 of the same microsatellite conferred a highly significant protective effect against NPC.

Centromere↗
PubMed1997

Possible protective role of HLA-B*2706 for ankylosing spondylitis.

HLA-B27 is strongly associated with ankylosing spondylitis (AS) but the role of the HLA molecule itself is still unclear. In this study on Singapore Chinese, we have subtyped 50 B27 positive AS patients and 45 B27 positive normals and found that the B*2706 allele has a significant negative association with disease (p = 0.047). Together with recent data indicating the existence of AS "protective" B27 alleles, our data shows that the HLA molecule itself plays a crucial role in disease development.

Alleles↗
PubMed1996

Hepatitis B virus and hepatocellular carcinoma.

Hepatitis B virus (HBV) has been implicated as a causative factor for the development of hepatocellular carcinoma (HCC). However, no oncogenes have been identified within the HBV genome and furthermore, the virus is frequently fragmented after it integrates into the hepatocyte genome. Therefore it has been difficult to understand how HBV brings about genetic damage to result in HCC. Recent data from our laboratory show that despite fragmentation, the HBx gene is consistently retained in a functional form and therefore suggest that this gene is important to HCC development. In 4 out of 6 HCC cell lines studied, the DR2 integration sequence was destroyed during integration and points to a possible preferred target integration site. The growing importance of HBx in HCC development is supported by data from other laboratories showing that transgenic mice carrying the HBx gene alone frequently develop HCC. This review discusses the role of HBV and other factors involved in liver carcinogenesis.

Animals↗
PubMed1995

HLA-A2 allelic microvariants in nasopharyngeal carcinoma.

HLA-A2-positive nasopharyngeal carcinoma (NPC; n = 38) and normal control (n = 51) populations were analysed by high-resolution oligotyping to identify A2 allelic microvariants. Within the control group, A*0207 was found to be the most common allele, accounting for 50% of the A2 frequency in normals. In contrast, this allele was found to be present in only 23% of NPC cases, suggesting a protective effect. Of these 9 NPC patients with A*0207, all were associated with B46, unlike in the control group, where it can be found associated with non-B46 antigens. Another allele, A*0201, which was thought to be protective against NPC was in fact present in 39.5% of NPC patients, more than twice the frequency in controls. These data confirm that A*0201 is not a protective allele for NPC, and other factors such as the A*0207, non-B46 haplotype are of greater importance.

Alleles↗
PubMed1995

Inhibition of staphylococcal enterotoxin-driven lymphocyte proliferation by anti-MHC class II monoclonal antibody.

Staphylococcal enterotoxins (SE) bind to major histocompatibility complex (MHC) class II molecules and the V beta region of T cell receptors (TCR) and subsequently induces T cell proliferation. This mitogenicity is the basis of pathological effects seen in food poisoning and toxic shock syndrome. Toxin-specific monoclonal antibodies have previously been shown to be effective in blocking toxin stimulated T cell responses. In this study, a monoclonal antibody, 52BL1, was found to be a potent inhibitor of SEA-, SEB-, SEC1-, SED-, and SEE-induced lymphocyte proliferation assays, which indicates that a single anti-HLA (human leukocyte antigen) class II antibody is effective in blocking the biological effects of these toxins. These results demonstrate the possibility of using anti-HLA class II antibodies in a clinical setting as an antagonist to staphylococcal enterotoxinmediated pathogenesis.

Antibodies, Monoclonal↗
PubMed1993

A monoclonal antibody with specificity to the HLA-DR1 and -DR51 antigens.

A monoclonal antibody 137BL7 raised against purified DR1 protein was shown to bind specifically to 5/5 DR1, 18/18 DR2 cells and 0/23 non-DR1,2 cells by cell-EIA. Further analysis by FACS using HLA-transfectants revealed that 137BL7 also bound specifically to the DRB5 transfectants in addition to the expected DR1 transfectants. However, it did not bind to the DR2 (DR15) transfectants, showing that cross-reactivity with DR2 cells lies with the DRB5 (DR51) rather than the DRB1 gene product. A comparison of the HLA-DR amino acid sequences of DR1 and DR51 antigens revealed a common glutamic acid residue at position 96, which may form the putative binding epitope of this mAb.

Alleles↗
PubMed1993

Human leucocyte antigen DNA typing in Singaporean Chinese patients with Graves' disease.

Human Leucocyte Antigen (HLA) A, B, C, DR, DQ and DP locus alleles in 35 Chinese patients with Graves' disease and 80 controls were typed for using serological and DNA polymerase chain reaction/sequence specific oligonucleotide (PCR/SSO) methods. B46 was found to be strongly associated with male patients (p = 0.0002; RR = 8.2, 95% confidence interval 2.1-32.2). In HLA class 1 alleles, besides B46, the frequencies of A2 and Cw1 were increased and A24 and B63 decreased in patients compared to controls. In HLA class 2 alleles, the frequencies of DRB1*1602, *0301, *1405, DRB5*02, DQB1*0502 were increased and DRB1*1501, DQB1*0301 decreased in patients.

Adult↗
PubMed1992

Identification and cloning of a novel heterogeneous nuclear ribonucleoprotein C-like protein that functions as a transcriptional activator of the hepatitis B virus enhancer II.

Liver specificity of hepatitis B virus (HBV) replication has been attributed to the action of its second enhancer (EII). We report here the characterization of EII and the subsequent isolation of a novel liver-specific DNA-binding protein which binds to and activates EII. The cDNA clone of the protein, designated E2BP, was isolated from a lambda gt11 expression library constructed from the hepatoma cell line HuH-6 which was screened with a binding site probe derived from EII. Sequence analysis of E2BP revealed 86.6% homology with a rat heterogeneous nuclear ribonucleoprotein C protein sequence, while conformational studies suggest a helix-loop-helix motif as a DNA-binding site. Cloned E2BP expressed in human fibroblasts by transient transfection displayed EII binding and activating characteristics similar to those of native E2BP in hepatocytes.

Amino Acid Sequence↗
PubMed1991

Cellular and molecular approaches to developing human monoclonal antibodies as drugs.

Attempts to bring murine monoclonal antibodies into clinical therapeutic use have always been thwarted by the body's reaction to foreign antigens. Although there has been some success with the use of murine monoclonal antibodies in the control of renal transplant rejection, its potential will remain limited. The solution then is to produce human mAbs, which are much less immunogenic in the patient and therefore, allow repeated administration. However, for the past decade, efforts to produce human monoclonal antibodies were focused on using the hybridoma fusion technique and Epstein-Barr virus transformation to generate lymphoblastoid cell lines. It is now certain that these two methods in their present form will yield neither the variety nor the quantity of human monoclonal antibodies sufficient for therapeutic use. A compromise approach which is to "humanise" murine antibodies by substituting up to 90-95% of their amino acids with human sequences will most likely become the method of choice in human monoclonal antibody production. These "chimeric" monoclonal antibodies have been shown to be much less immunogenic in patients and is a sign that monoclonal antibodies will soon be an important mode of immunotherapy.

Animals↗
PubMed1990

Detection of integrated hepatitis B virus DNA in hepatocellular carcinoma cell lines by nonradioactive in situ hybridization.

A sensitive and specific nonradioactive in situ hybridization method capable of detecting single-copy integrated hepatitis B virus (HBV) DNA sequences in hepatocellular carcinoma (HCC) cell lines was developed. In situ hybridization of biotinylated HBV (adr, adw) DNA probes with nine different human HCC cell lines were carried out in 96-well microtiter plates. Integration was detected in HCC cell lines HCCM, Hep3B, huH-1, huH-4, and PLC/PRF/5. Detection of single-copy HBV DNA sequences was also achieved in Hep3B and huH-4. HCC cell lines HepG2, HUH-6, HUH-7, Mahlavu, and the non-HCC control MCF-7, gave clear negative results. These results show a 100% correlation with those obtained by Southern blot hybridization assay. The results demonstrate that nonradioactive detection of single-copy integrated HBV DNA sequences in HCC cell lines is possible by the method described, which has potential application for viral genome analysis requiring in situ hybridization.

Carcinoma, Hepatocellular↗
PubMed1990

Immunotoxins: the potential in cancer treatment.

Since its development in 1975, monoclonal antibody (mAb) technology has greatly enhanced our ability to analyse complex antigenic systems as well as improve the sensitivity and speed of many diagnostic tests. In particular, the study of tumour associated antigens using mAbs have revealed that many transformed cell phenotypes have useful markers on their plasma membrane, cytoplasm, or as secreted forms which can be used in developing diagnostic assays. Therapeutic application of these anti-tumour mAbs has however, been slow relative to the research and diagnostic applications. This article will discuss how the therapeutic effectiveness of anti-tumour mAbs can be enhanced by coupling them to drugs, toxins or radionucleids; and review the current advances and problems related to the application of these mAb conjugates.

Humans↗
PubMed1988

Effect of recombinant gamma interferon on hepatocellular carcinoma cell lines.

The effects of recombinant gamma interferon (rIFN-gamma) were tested on 4 different hepatocellular carcinoma (HCC) cell lines PLC/PRF/5, HepG2, Hep3B and SK-Hep1. Exposure of these HCC cells to 100/ml of rIFN-gamma induced high levels of major histocompatibility complex (MHC) class I expression on their membrane, but not class II antigens. The enhancement of class I antigen synthesis occurs without a corresponding increase in synthesis of HBsAg by HBV genome positive PLC/PRF/5 and Hep3B cells. A 5 log dose of rIFN-gamma also did not trigger the integrated HBV genome into active replication as indicated by a lack of HBcAg and HBeAg synthesis. These results point to a possible role for the use of rIFN-gamma to enhance tumour cell recognition by the host immune system via the increased MHC class I expression.

Carcinoma, Hepatocellular↗
PubMed1988

Subtype analysis of the hepatitis B surface antigen using monoclonal antibodies.

A series of monoclonal antibodies (mAb) were produced against the hepatitis B surface antigen (HBsAg) and their specificity tested against 2 separate panels of known HBsAg subtypes. Using an enzymeimmunoassay, mAbs that specifically bind to the 'a', 'd' and 'w' epitopes were identified. There were also a number of mAbs that expressed binding patterns that do not correspond to the standard serological classification--which is not unusual since the mAbs were of murine origin. These mAbs are at present being used to replace the conventional goat or guinea-pig derived HBsAg subtyping antisera which are available in limited quantities and often vary in titer.

Animals↗
PubMed1984

Mitogenic capacity of oxidized human B cell lines.

A combination of neuraminidase and galactose oxidase alters the membrane glycoproteins to generate highly reactive aldehyde groups on galactose moieties. Human B cell lines oxidized in this way were able to induce strong proliferative responses from normal untreated peripheral blood lymphocytes. Oxidized cell lines that stimulate well were also correlated to some extent with their ability to bind responder lymphocytes. The present investigation demonstrates the usefulness of oxidized B cell lines as a novel mitogen for use in the study of lymphocyte activation.

B-Lymphocytes↗