A method has been developed to use the polymerase chain reaction to amplify and sequence the chain determining region 3 (CDR 3) of the human immunoglobulin heavy-chain gene, and to use the sequence as a marker for rare neoplastic B... more
A method has been developed to use the polymerase chain reaction to amplify and sequence the chain determining region 3 (CDR 3) of the human immunoglobulin heavy-chain gene, and to use the sequence as a marker for rare neoplastic B lymphocytes. Consensus primers for the Variable and Joining regions of the gene were constructed and shown to enable efficient amplification, directed cloning, and sequencing of CDR 3. Using leukaemic cell line PFMC as a test system, CDR 3 was sequenced, specific primers synthesized, and PFMC DNA was detected down to a dilution of 1:1300 in DNA from normal lymphocytes. This strategy should be useful for monitoring therapy and detecting early disease relapse in B lymphoproliferative disease.
The aim of this study was to characterize MHC mutant cell lines by studying haplospecific markers within the MHC and specifically in the 250 kilobase (kb) region between the HLA B and TNF loci. This region has been difficult to define... more
The aim of this study was to characterize MHC mutant cell lines by studying haplospecific markers within the MHC and specifically in the 250 kilobase (kb) region between the HLA B and TNF loci. This region has been difficult to define because of the lack of appropriate markers. Spontaneous MHC mutants were isolated after immunoselection with an anti-HLA A2 monoclonal antibody and complement. Ten mutants were characterized using serological or allelic and genomic DNA markers within the HLA A to HLA DQ region of the MHC. Most mutants lost at least the 3 megabases of DNA from HLA A to HLA DQ viz the whole haplotype carrying HLA A2. Variants which have lost either HlA A alone or HLA A and HLA B were also found. The results show that it is possible to map the extent of the deletion between HLA B and TNF. Haplospecific scanning patterns for the CL region appear particularly useful.
A number of cytotoxic drugs were tested in mice for their ability to produce residual damage to the bone marrow. This was assessed by the ability of the drug to produce depletion of pluripotential stem cells and granulocytic progenitor... more
A number of cytotoxic drugs were tested in mice for their ability to produce residual damage to the bone marrow. This was assessed by the ability of the drug to produce depletion of pluripotential stem cells and granulocytic progenitor cells persisting for at least two months after ...
Abstract A cell line (FMC-Hu-1-B) was established from a biopsy of an abdominal mass of a child with non-Burkitt's lymphoma. The establishment of the cell line initially required the presence of normal bone marrow stromal cells... more
Abstract A cell line (FMC-Hu-1-B) was established from a biopsy of an abdominal mass of a child with non-Burkitt's lymphoma. The establishment of the cell line initially required the presence of normal bone marrow stromal cells and phytohaemagglutinin stimulated ...
A means of measuring in vivo mutations in man would be valuable in assessing the importance of mutation in ageing and human disease and for monitoring individuals exposed to environmental mutagens and carcinogens. The hypoxanthine-guanine... more
A means of measuring in vivo mutations in man would be valuable in assessing the importance of mutation in ageing and human disease and for monitoring individuals exposed to environmental mutagens and carcinogens. The hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus has been used to study mutagenesis in cultured mammalian (and other) cells1; clones are selected by their ability to grow in
Expression of the normally cryptic blood group antigen Tn has occasionally been reported in hematologic disease, but the true frequency of this change is not known. A mouse monoclonal antibody (FBT3) and immunohistochemistry were used to... more
Expression of the normally cryptic blood group antigen Tn has occasionally been reported in hematologic disease, but the true frequency of this change is not known. A mouse monoclonal antibody (FBT3) and immunohistochemistry were used to examine expression of the Tn antigen. Expression was not detected in 35 normal bone marrow aspirates examined, but it was detected in 5 of 725 abnormal bone marrow aspirates, including 2 (3.6%) of 55 cases of de novo acute nonlymphocytic leukemia and 2 cases that terminated in acute nonlymphocytic leukemia. In two patients, one with acute myeloblastic leukemia and the other in blast transformation of chronic myeloid leukemia, the Tn antigen was expressed on 2 percent of blast cells. In one case of non-Hodgkin's lymphoma, 4 percent of normal myeloid cells expressed the antigen. In the other two cases, one of acute myelomonocytic leukemia and the other of myelodysplasia, only 2 to 8 percent of myeloid and erythroid cells initially were Tn positive. Subsequent serial immunohistochemical studies of bone marrow aspirates and peripheral blood in these two cases showed increasing numbers of Tn-positive erythroid and myeloid cells 8 to 12 months before polyagglutination was detected serologically. Tn-positive cells increased to > 90 percent in the terminal phase in both cases of both diseases. The results suggest that Tn expression in these two patients may have conferred a growth advantage to the cells and could be related to disease progression.
