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B Clarkson

Publications and source records attributed to B Clarkson.

139 records · Page 8Linked to original sources
PubMed1967

Studies of cellular proliferation in human leukemia. I. Estimation of growth rates of leukemic and normal hematopoietic cells in two adults with acute leukemia given single injections of tritiated thymidine.

Two adults with rapidly progressive acute myeloblastic and myelomonoblastic leukemia were given single injections of tritiated thymidine, and measurements were made of the growth rates of their leukemic and normal hematopoietic cells by radioautographic methods. Although almost all leukemic blasts in both marrow and blood were metabolically active as shown by their ability to incorporate tritiated uridine and leucine in vitro, only 5.6% and 6.1% of the blasts in the marrow and even fewer in the blood incorporated tritiated thymidine. The mitotic indexes of the marrow blasts were 0.66% and 0.52%; no circulating blasts were dividing. The mean generation times of the actively proliferating blasts were estimated to be 49 and 83 hours. This cannot be equated with the doubling time of the total leukemic population as there is evidence that many blasts fail to continue dividing and die. The mean durations of the phases of the blasts' mitotic cycles were as follows: DNA synthesis (S) = 22 and 19 hours, premitosis (G(2)) = 3 hours, mitosis (M) = 0.47 and 0.62 hour (minimal estimates), and postmitosis (G(1)) = 24 and 61 hours. In both patients the maximal mean transit time of the blasts in the blood was 36 hours, and the minimal numbers of actively dividing blasts present were 1.6 and 2.6 x 10(9) per kg of body weight.Estimates were also made of the rates of proliferation and maturation of the residual normal erythrocytic and granulocytic cells in these two patients. Although total production was markedly diminished because of reduction in the number of normal elements, the relatively few remaining normal cells appeared to be dividing and maturing at rates that are about the same or only slightly slower than those found in normal subjects. We conclude that main reason leukemic blasts displace normal hematopoietic precursors in acute leukemia is that the blasts largely fail to differentiate. Many die but many others persist in the marrow and elsewhere as primitive cells and continue to proliferate. As the blasts accumulate, they gradually displace the normal hematopoietic cells, most of which continue their normal course of differentiation and leave the marrow as nondividing mature cells. It is not known why the over-all production of normal cells is not adequately increased to compensate for the anemia, granulocytopenia, and thrombocytopenia that develop, but apparently the leukemic cells somehow interfere with the proliferation or differentiation or both of normal stem cells.

Autoradiography↗
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Neuroblastoma.

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Adolescent↗
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Non-Hodgkin's lymphoma.

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Antineoplastic Combined Chemotherapy Protocols↗
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Suppression of the normal mouse c-myc oncogene in human lymphoma cells.

In Burkitt's lymphoma, which carries the t(8;14) chromosome translocation, the c-myc oncogene normally located on band q24 of human chromosome 8 (refs 1-3) translocates to the heavy-chain locus on chromosome 14 (refs 1, 4, 5); this results in transcriptional deregulation of the translocated c-myc oncogene, which is transcribed constitutively at elevated levels, while the normal c-myc oncogene on the uninvolved chromosome 8 is either silent or expressed at very low levels (A.ar-R. and C.M.C., unpublished results). We have now introduced the active c-myc oncogene of proliferating mouse spleen cells into human lymphoma cells carrying the t(8;14) chromosome translocation by hydridization, and have examined the hybrids for expression of the human and murine c-myc oncogene. The results of this analysis, reported here, indicate that the active mouse myc gene is shut off at the transcriptional level in the human lymphoma cells, implying that human B cells at the stage of differentiation of lymphoma cells used in this study are nonpermissive for normal c-myc transcription.

Animals↗
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Characterization of cellular proteins recognizing the HIV enhancer using a microscale DNA-affinity precipitation assay.

Numerous nucleic acid sequence motifs have been identified as transcriptional regulatory elements, and proteins involved in the control of gene replication and transcription have been successfully purified using nucleic acid affinity procedures. We have developed an assay that allows direct characterization of cellular proteins binding to the enhancer element of the human immunodeficiency virus (HIV), which is analogous to immunoprecipitation techniques. In extracts of H9 cells, a human CD4+ lymphoblast line clonally selected for its ability to support HIV replication, we find a class of proteins that interact specifically with the HIV enhancer. Reproducible high-resolution, two-dimensional gel electrophoresis has allowed us to resolve these proteins into two major sets. One set is common to H9 cells, two human B-lymphoblast lines, and a phytohaemagglutinin (PHA)-stimulated human CD4+ lymphoblast line (Jurkat). A second set of proteins is found only in H9 cells. Thus, with this assay we have identified HIV enhancer-binding proteins that are constitutive or inducible and that are cell-type specific.

Base Sequence↗