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M R Kohonen-Corish

Publications and source records attributed to M R Kohonen-Corish.

14 recordsLinked to original sources
PubMed2001

A polymorphic marker for the human cathepsin B gene.

Human cathepsin B (CTSB) is a proteolytic enzyme implicated in tumor invasion and metastasis. We describe a PCR-based polymorphic marker for this gene comprising two amplimers differing in length by 19 consecutive nucleotides in intron 7, near the exon 8 splice acceptor site, identifying two gene alleles (A and B). Allele frequencies were 0.614 for A and 0.386 for the B allele, with an observed heterozygosity of 0.457 in a cohort of 70 non-related Australian blood donors. One additional nucleotide difference was also revealed through sequencing. The human CTSB gene is located on chromosome 8 and the alleles described here can potentially be used as markers in linkage and association studies of cancers and other diseases.

Alleles↗
PubMed1996

A highly polymorphic CA/GT repeat in intron 3 of the human urokinase receptor gene (PLAUR).

We describe the first highly polymorphic microsatellite marker for the human urokinase plasminogen activator receptor gene (PLAUR). The urokinase receptor (uPAR) has a central role in cancer invasion and metastasis, which may enable the development of new anti-metastatic therapies. Analysis of the marker genotypes in colorectal cancer cell lines revealed three alleles that were not detected in a series of healthy control individuals, which encourages further genetic study of the role of uPAR in cancer.

Alleles↗
PubMed1992

Antibodies to glutamic acid decarboxylase are associated with HLA-DR genotypes in both Australians and Asians with type 1 (insulin-dependent) diabetes mellitus.

Antibodies to glutamic acid decarboxylase, previously known as the 64 kD antigen, appear to be more predictive of Type 1 (insulin-dependent) diabetes mellitus in Caucasoids than other autoantibodies to islet cell antigens. However, seropositivity to glutamic acid decarboxylase is not universal at the onset of Type 1 diabetes and the prevalence in Asians is low compared to Caucasoid patients. This suggests the involvement of multiple pancreatic autoantigens in the Type 1 diabetes autoimmune process or, genetic differences within and between ethnic groups that contribute to the heterogeneous autoimmune response to glutamic acid decarboxylase or both. Alternatively some cases of Type 1 diabetes could have an aetiology unrelated to autoimmunity. This study examined the differential response to glutamic acid decarboxylase according to HLA-DR and -DQ genotypes, as determined by RFLP, in 49 white Australian and 44 Asian patients with Type 1 diabetes. Among Australians heterozygous for HLA-DR3, DR4, 85% were positive for antibodies to glutamic acid decarboxylase, significantly different (p = 0.039) from the prevalence of 48% in patients with at least one HLA-DR antigen other than DR3 or DR4. Also, among Australians, the presence of "low risk" HLA-DQ antigens, namely DQw5, DQw6 or DQw7, reduced the prevalence of antibodies to glutamic acid decarboxylase by 40% (p = 0.064). Among Asians with Type 1 diabetes and with antibodies to glutamic acid decarboxylase, HLA-DR9 was significantly (p = 0.037) increased in frequency, at 63% compared with 22% in those without glutamic acid decarboxylase antibodies, and the presence of a "low risk" HLA-DQ allele reduced the antibody rates by 87% (p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Local production of tumor necrosis factor encoded by recombinant vaccinia virus is effective in controlling viral replication in vivo.

Tumor necrosis factor (TNF) has pleiotropic effects on a wide variety of cell types. In vitro studies have demonstrated that TNF has antiviral properties and is induced in response to viral infections. However, a role for TNF in the antiviral immune response of the host has yet to be demonstrated. Here we describe the construction of and studies using a recombinant vaccinia virus that encodes the gene for murine TNF-alpha. By comparing the replication of and immune responses elicited by the TNF-encoding virus to a similarly constructed control virus, we hoped to observe immunobiological effects of TNF in the host. The in vivo experiments with this recombinant virus demonstrate that the localized production of TNF-alpha during a viral infection leads to the rapid and efficient clearance of the virus in normal mice and attenuates the otherwise lethal pathogenicity of the virus in immunodeficient animals. This attenuation occurs early in the infection (by postinfection hour 24) and is not due to the enhancement of cellular or antibody responses by the vaccinia virus-encoded TNF. This evidence suggests that attenuation of the recombinant virus is due to a direct antiviral effect of TNF on cells at the site of infection. Therefore, these results support the suggestion that TNF produced by immune cells may be an important effector mechanism of viral clearance in vivo.

Animals↗
PubMed1990

Immunodeficient mice recover from infection with vaccinia virus expressing interferon-gamma.

Recombinant vaccinia viruses (VV)-encoding murine interferon-gamma (IFN-gamma) were constructed and the effect of virus-encoded IFN-gamma on the immune response towards VV in vivo investigated. In athymic nude mice and sublethally irradiated euthymic mice, IFN-gamma expression by VV enabled the mice to recover from the infection, whereas mice infected with the control virus died. In normal CBA/H mice also, the growth of VV was greatly reduced and it was cleared faster from mouse organs than the control virus. Natural killer (NK) cell responses in these mice were not enhanced suggesting that this recovery is not NK cell mediated. Other possible mechanisms and implications of this observation are discussed.

Animals↗
PubMed1990

HLA-DP variation as additional risk factor in IDDM.

A significant increase in the frequency of DPw3/6 alleles defined by restriction-fragment-length polymorphism is observed in insulin-dependent diabetes mellitus (IDDM) patients relative to healthy control subjects (34.6 vs. 10.5%, P less than 0.009). Log-linear modeling demonstrates that this association is independent of HLA-DR3 and -DR4 and IDDM association and cannot be attributed to linkage disequilibrium between HLA-DP and -DR. The analysis also demonstrates an absence of interactive effects among the antigens in conferring IDDM susceptibility. The strength of the DPw3/6 association is not significantly less than that of either DR3 or DR4.

Diabetes Mellitus, Type 1↗
PubMed1989

Induction of cell surface expression of HLA antigens by human IFN-gamma encoded by recombinant vaccinia virus.

A recombinant vaccinia virus (VV) encoding human IFN-gamma (VV-huIFN-gamma) was constructed and its effects on MHC Ag expression in human and murine cells in vitro analyzed by flow cytometry. At high multiplicities of infection (5 pfu/cell) the IFN-gamma expressed by vaccinia was not able to overcome the profound decrease of MHC concentration, normally associated with VV infection, in any of the cells tested. However, at successively decreasing multiplicities of infection, a gradual increase in MHC class I concentration above control levels was observed in human 143B cells but not in murine L929 cells, thus indicating that the species specificity of IFN-gamma is preserved in VV-huIFN-gamma-infected cells. We infer from these data that the IFN-gamma secreted by infected 143B cells is able to exert an MHC upregulating effect on uninfected cells in the vicinity. Antiviral activity of the IFN-gamma expressed by the virus was also assessed. Pretreatment for 24 to 48 h of human 143B cells with IFN-gamma containing supernatants had a significant antiviral effect comparable to rhuIFN-gamma. However, when added 1 h after virus infection, antiviral activity was much less evident. Also, the IFN-gamma secreted by infected 143B cells in monolayers infected at low multiplicity did not efficiently inhibit spread of infection to other cells in the vicinity.

Animals↗
PubMed1988

HLA-DR and -DQ DNA genotyping in seven populations of Asia-Oceania and Australia.

Haplotype patterns of HLA-DR and -DQ restriction fragment length polymorphisms (RFLPs) were compared in seven populations in the region of Asia-Oceania: Australian Caucasoids, Melanesians, micronesians, Polynesians, Chinese, Koreans, and Japanese. Several DR beta RFLP patterns, including those correlating with DR2, 4,5, w6, 7 and w8 in Caucasoids, were associated with multiple DQ alpha/DQ beta RFLP haplotypes, of which only two occurred universally - one associated with DR4 and one with DR5. RFLPs revealed new population or group specific characteristics, which had not been previously discovered using serological or cellular HLA typing techniques. The populations of Asia-Oceania have some features of the class II RFLPs in common, which are distinctly different from Caucasoids. On the other hand, a number of characteristics distinguish between the various Asian and Pacific groups. This study demonstrates the power of RFLP analysis of closely linked genes in population genetics, and shows the value of ethnic comparisons in further characterizing the polymorphisms of the HLA class II genes.

Asia↗
PubMed1987

HLA-DR and -DQ DNA genotyping in insulin-dependent diabetes patients in South India.

Restriction fragment length polymorphisms (RFLPs) of the HLA-DR beta, -DQ alpha, -DQ beta, and -DX alpha genes have been examined in South Indian diabetic patients and controls. The DR. DQ linkage arrangements in South Indians were shown to be different for DR2, DR4, and DRw6 from those commonly seen in Europeans, so that localization of the primary disease-promoting gene in IDDM could be attempted. This study clearly implicates at least one DQ beta allele in the pathogenesis of IDDM.

DNA Probes, HLA↗
PubMed1987

Insulin-dependent diabetes mellitus: HLA-DR and -DQ genotyping in three ethnic groups.

Human genomic DNA samples from Caucasoids, Chinese, and Koreans of known serological DR antigen specificity were studied for IDDM-associated variation in HLA-DR and -DQ RFLPs (restriction fragment length polymorphisms). Genotyping allowed for accurate assignment of HLA-DR types and in Caucasoids DRw6 as well as DR2 was unequivocally decreased in IDDM. Further, the universality of certain DR2-associated DQ beta subtypes in protection against IDDM was established. HLA-DR3 was found to be increased in IDDM irrespective of whether carried on the B8. DR3 or B18. DR3 haplotype in Caucasoids or on the Bw58. DR3 haplotype in Chinese. These haplotypes have different DR alpha and DX alpha arrangements, so the region of susceptibility is confined to DQ alpha, DQ beta. For HLA-DR4, a 12kb/DQ beta/Bam HI fragment was increased in Caucasoid IDDM, but since this fragment is haplotype specific in Caucasoids and occurs in most healthy DR4- and w9-positive Asians, the 12 kb fragment may be a marker for a DR beta subtype of DR4 associated with IDDM in Caucasoids only. This study has shown the value of ethnic comparisons of HLA-associated diseases, where different linkage disequilibrium relationships have permitted identification of common susceptibility determinants and have provided evidence for some heterogeneity between Caucasoid and Asian populations, in the genetics of IDDM.

Australia↗
PubMed1986

HLA-DR beta gene DNA polymorphisms revealed by Taq I correlate with HLA-DR specificities.

Human genomic DNA digested with restriction endonuclease Taq I was hybridized with cDNA probes for DR beta and DQ beta, for correlation of restriction fragment length polymorphisms with HLA-DR specificities. DR beta Taq I RFLPs were distinctive for DR serological types 1 to w9, with the exception of DR3 and w6, and were markedly consistent within DR specificity. Some common variants in RFLPs did emerge within serological type; DR3, e.g., was associated with two different fragment patterns, one of which occurred on the A1.B8.DR3 haplotype and was linked with a DR alpha Bgl II variant, and the other on the B18.DR3 haplotype. In the Pacific specimens examined, RFLPs were, with few exceptions, similar to those seen in Caucasoids sharing the same DR specificity. This study indicates that genomic hybridization is a useful adjunct to serological and cellular class II typing and should be particularly informative in identifying new HLA-DR alleles in populations serologically less well-defined than Caucasoids.

Black People↗
PubMed1986

RFLP analysis of HLA-DR and -DQ genes and their linkage relationships in the Pacific.

Human genomic DNA samples from Melanesians, Micronesians, and Caucasoids of known HLA-DR type were examined with cDNA probes for HLA-DR alpha, -DR beta, -DQ alpha, and -DQ beta chain genes. DR beta hybridizations with TaqI-digested DNA did not detect any new DR specificities in the Pacific. However, within the DR5 specificity a common DNA subtype was found in Pacific Islanders that was not seen in Caucasoids. Altogether, four DNA subtypes of DR5 are described. With the DQ alpha and DQ beta probes, significantly more variation could be demonstrated between populations. For example, DR2 was associated with a DQ beta TaqI pattern in the Pacific that was very rare in Caucasoids and additional RFLP analysis with other enzymes showed that this pattern is probably associated with the Dw12 subtype of DR2. DRw8-positive samples showed two different DQ alpha TaqI patterns, and these correlated with DQw1 and DQw3 specificities. DR alpha hybridizations with BglII-digested DNA also revealed different linkage relationships of the HLA-class II region genes between Pacific and Caucasoid specimens. The different population linkage disequilibrium relationships have permitted tentative assignment of TaqI fragments to either the DR beta 1 or DR beta 2 genes and are highly suggestive that the DQw1 specificity is encoded by the DQ alpha chain gene. This study shows the value of population comparisons in contributing to knowledge of the genetic organization of the genome.

Bacterial Proteins↗
PubMedDate not supplied

Chromosome 2p linkage analysis in hereditary non-polyposis colon cancer.

Hereditary non-polyposis colon cancer (HNPCC) comprises 2-6% of the total colorectal cancer burden. Two families are described that show linkage between the HNPCC susceptibility gene and the markers D2S123 and D2S119 on chromosome 2p, producing multipoint lod scores of 3.62 and 3.83, respectively, in the largest pedigree. In our third family the multipoint lod scores for D2S123 and D2S119, -2.97 and -3.12, excluded localization of a susceptibility gene in this region indicating that there is at least one more gene that causes predisposition to HNPCC. The exclusion was based on at least one genotype for an individual who had multiple primary colon and extracolonic tumours and could not be considered to have had common forms of cancer. Our results therefore encourage further gene mapping to pursue the localization of additional HNPCC genes. These findings confirm the presence of the susceptibility gene for HNPCC, COCA1, on chromosome 2p. They allow the immediate identification of a subset of HNPCC families, and provide the means for presymptomatic testing of family members if sufficient number of members are available for study.

Chromosomes, Human, Pair 2↗