Biomedical subjects

T Krontiris

Publications and source records attributed to T Krontiris.

5 recordsLinked to original sources

PubMed1993

Population genetics of the HRAS1 minisatellite locus.

Several years ago it was reported that rare HRAS1 VNTR alleles occurred more frequently in U.S. Caucasian cancer patients than in unaffected controls. Such an association, in theory, could be caused by undetected population heterogeneity. Also, in a study clearly relevant to this issue, it was recently reported that significant deviations from Hardy-Weinberg equilibrium exist at this locus in a sample of U.S. Caucasians. These considerations motivate our population genetic analysis of the HRAS1 locus. From published studies of the HRAS1 VNTR locus, which classified alleles into types, we found only small differences in the allele frequency distributions of samples from various European nations, although there were larger differences among ethnic groups (African American, Caucasian, and Oriental). In an analysis of variation of rare-allele frequencies among samples from four European nations, most of the variance was attributable to molecular methodology, and very samples from four European nations, most of the variance was attributable to molecular methodology, and very little of the variance was accounted for by nationality. In addition, we showed that mixture of European subpopulations should result in only minor deviations from expected genotype proportions in a Caucasian database and demonstrated that there was no significant deviation from Hardy-Weinberg equilibrium in our HRAS1 data.

Alleles↗

PubMed1992

Crossreacting human lymphoma idiotypes.

We have examined an unselected series of 72 lymphomas of diverse histologies with a panel of mouse monoclonal antibodies specific for human B-lymphoma-derived Ig idiotypes (anti-ids) to determine the nature and extent of id/anti-id crossreactivity. The anti-id antibodies were prepared from Ig isolated from seven follicular center cell lymphomas by heterohybridoma technique. Thirty-six of 75 individual anti-ids obtained in this manner were further selected based on their reactivity with highly restricted or private idiotypic determinants. Twelve of the 72 (17%) lymphoma biopsies reacted with one or more of the 36 anti-ids that detect private determinants. A pool consisting of five individual antibodies would have detected 11 of the 12 crossreacting tumors. Staining of tumor cell populations was homogeneous in the positive cases, suggesting uniform idiotype expression. If there was a segregated staining pattern, it was generally related to the presence of CD3+ T cells in the section. These follicular center cell-derived anti-ids cross-reacted with follicular center cell tumors of all histologic grades with frequencies ranging from 13% to 50%. The structural basis for the crossreactivity of our lymphoma-derived private anti-ids is as yet not known. However, the reactivity of certain anti-ids with both kappa- and lambda-expressing tumors suggests a biased use of V gene segments in these crossreactive clones that is probably related to the VH gene. These data suggest the possibility that lymphoma may develop in a highly restricted pool of normal differentiated B cells or in B-cell subsets that express a limited repertoire of unmutated VH gene segments.

Animals↗

PubMed1990

Clonal diversity in human B cell lymphoma. I. Idiotypic and genetic analysis of lymphoma heterohybrids.

Secretory heterohybrid clones from seven pristine human B cell lymphomas of diverse histologic types were established to investigate the question of tumor clonal diversity. We found that in six tumors, heterohybrid-derived Ig showed similar band patterns in IEF; families of anti-Id prepared from tumor Ig reacted uniformly with individual heterohybrids and original tumor; and the V gene loci displayed little variation on Southern analysis. In one patient who was followed with serial multiple site biopsies over a 14-mo period, clonal Id was preserved until the final stage of his disease, in spite of cytotoxic treatment. In a single follicular tumor (J.M.), each of the anti-Id reacted uniformly with the parent tumor and the individual heterohybrids, except that three of six clones failed to react with a single anti-Id family member. A Southern analysis of the VH gene locus revealed an identical gene rearrangement that was shared by the parent tumor and each heterohybrid. However, there was considerable heterogeneity of J.M. heterohybrid Ig in IEF gels, and we demonstrated the production of variant lambda L chains by the heterohybrid clones. One type of lambda L chain had a normal mobility in SDS-PAGE gels but larger lambda variants were produced by four of six heterohybrids. A Southern analysis of the VL gene displayed considerable variation in the type of lambda rearrangement present in the various heterohybrids, suggesting extensive diversity at the VL gene locus. In a second tumor (S.C.) that exhibited uniform anti-Id tumor reactivity we were also able to demonstrate the presence of a second minor tumor cell population (a biclonal tumor). Our data suggest that intraclonal VH variation may vary considerably with lymphoma subtype and mutagenic exposure and that an additional mechanism for generating spontaneous intraclonal heterogeneity is genetic variation at the VL locus.

Antibodies, Anti-Idiotypic↗

PubMed1988

DNA restriction fragment length polymorphism analysis of human bronchogenic carcinoma.

DNA restriction fragment length polymorphism (RFLP) analysis has been successfully applied both to evaluate possible human susceptibility factors as well as to identify genes involved in malignant transformation of human cells. In this report we review previous applications of RFLP analysis to evaluation of human malignancies and discuss our RFLP studies of human bronchogenic carcinoma, which are in progress. Preliminary results of our analysis of the RFLP associated with the cHa ras variable tandem repeat (VTR) indicate that rare alleles of this VTR are more frequent in patients with bronchogenic carcinoma than in controls.

Carcinoma, Bronchogenic↗

PubMed1980

Transformation of NIH-3T3 mouse cells by avian retroviral DNAs.

NIH-3T3 cells were found to be transformable by RSV DNA in the absence of progeny virus production. Cells transformed by intact RSV DNAs contained rescuable RSV genomes that were integrated into cellular DNA and were colinear with unintegrated RSV DNA. NIH-3T3 cells were also transformable by subgenomic fragments of RSV DNA, synthesized in vitro or generated by restriction endonuclease digestion of intracellular RSV DNA. These cells did not contain rescuable RSV genomes but did contain RSV DNA fragments that efficiently induced transformation of NIH-3T3 cells in secondary transfection assays. Further analysis of the RSV DNA sequences present in these cells and transformation assays of defined fragments of RSV DNA may contribute to the elucidation of the sequences required for expression of the src gene of RSV. DNAs of the avian acute leukemia viruses MC29 and AEV also induced transformation of NIH-3T3 cells. The use of these cells as recipients may thus provide a system suitable for functional analysis of the transforming genes of avian leukemia viruses as well as sarcoma viruses.

Animals↗