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Biomedical subjects

R W Tindle

Publications and source records attributed to R W Tindle.

41 records · Page 3Linked to original sources

A new approach to the classification of human leukaemias: measurement of the relative abundance of a specific RNA sequence by means of molecular hybridisation.

A recombinant plasmid library representing polyadenylated RNAs in the leucocytes of a Ph1-positive chronic granulocytic leukaemia (CGL) has been constructed. One recombinant (designated pCG14) isolated from this library contains a DNA sequence complementary to a small polyadenylated RNA that is abundant in RNA from CGL leucocytes. The relative concentrations of pCG14 RNA in the RNAs from a variety of normal and leukaemic leucocytes and human haemopoietic cell lines have been measured with a molecular hybridisation assay. This has shown that pCG14 RNA is 10 to 50 times more abundant in RNA from CGL leucocytes than in the RNAs from these other cells. The data indicate that the occurrence of pCG14 RNA in high abundance is sufficiently characteristic of a CGL leucocyte population to distinguish it from other populations of leucocytes. They suggest that the measurement of the concentrations of specific RNA species in leucocyte RNA by means of molecular hybridisation with cloned complementary DNAs may provide additional markers for the objective classification of human leukaemias which could be particularly useful since the method exploits a criterion different from any currently in use.

Autoradiography↗

Resistance of mice to Krebs ascites tumour, sarcoma S180 and PC6 plasmacytoma after immunisation with Salmonella enteritidis 11RX.

Resistance to Krebs ascites tumour, sarcoma S180 (ascitic form) and PC6 plasmacytoma can be induced with prior immunisation with live Salmonella enteritidis 11RX. One thousand to ten thousand more tumour cells are needed to give an LD50 after immunisation. Resistance to PC6 could be recalled 137 days after intravenous immunisation with 11RX protein antigen intraperitoneally as measured by prolonged survival or monitoring the death of 5[131I]-iodo-2'-deoxyuridine labelled tumour cells in vivo. The range of tumours to which resistance can be produced by 11RX immunisation suggests that the mechanism of resistance does not involve antigens common to the tumours and Salmonella enteritidis 11RX.

Animals↗

Characterization of myeloid leukemias with monoclonal antibodies 3C5 and MY9.

The expression of two membrane antigens identified by the monoclonal antibodies (McAb) My9 and 3C5 has been investigated in cells from 80 acute leukemias. My9 was positive in the blasts of 33 out of the 38 (87 per cent) cases of acute myeloid leukemia (AML) tested, regardless of FAB subtype, and in 13 of 18 (72 per cent) cases of chronic granulocytic leukemia (CGL) in myeloid blast crisis. The reactivity of 3C5 was confined to myeloblastic (M1) AML, 85 per cent of cases, and to lymphoblastic leukemia (ALL) of B-lineage, 70 per cent of cases, including CGL in lymphoid transformation. My9 was negative in ALL except for an unusual case. The phenotype My9+, 3C5+ was seen exclusively in M1 (69 per cent) and M2 (14 per cent) AML. Ultrastructural analysis with the immunogold method in combination with the myeloperoxidase (MPO) reaction showed that expression of My9 increased in parallel with MPO activity whereas 3C5 was expressed mainly in myeloblasts with little MPO content. We conclude that the use of these two McAb will contribute to the diagnosis and classification of AML and may throw some light to the pathogenesis of biphenotypic acute leukemias, including TdT + AML.

Antibodies, Monoclonal↗

The molecular specificity of linear B-epitopes in the E7 open reading frame protein of human papillomavirus 16 defined by monoclonal antibodies.

Human papillomavirus (HPV) 16 is highly associated with premalignant and malignant anogenital epithelial lesions. The transforming function resides within the viral E7 open reading frame protein. We have defined three immunodominant linear B-epitopes in the E7 protein. In the present study, we determine the contribution of individual amino acid residues to antibody binding of these three epitopes using replacement set analysis. In this approach, each epitope residue is substituted in turn by each of the other 19 genetically encoded amino acids to produce analogues which are tested for specific monoclonal antibody binding. We demonstrate the specificity of the monoclonal antibodies for epitopes of HPV 16 E7 in binding studies using synthetic epitope analogues of other HPV genotypes. Comparison between HPV 16 and other HPV genotypes suggests that variability in amino acid composition at the E7 epitopic sites does not appear to be host-antibody driven.

Amino Acid Sequence↗