The Bleeding Time Is Inversely Related to Megakaryocyte Nuclear DNA Content and Size in Man

SummaryThe relation between the bleeding time and the megakaryocyte nuclear DNA content and size was evaluated in eleven consecutive patients with normal steady state thrombopoiesis undergoing thoracotomy. A statistically significant inverse correlation was found between the bleeding time and both megakaryocyte DNA content (r = −0.71, p <0.05), megakaryocyte total size (r = ‒0.58, p <0.05), megakaryocyte cytoplasmic size (r = −0.64, p <0.05) and megakaryocyte nuclear size (r = −0.58, p <0.05). The megakaryocyte total size and the megakaryocyte cytoplasmic size were statistically significantly larger in men than women (p <0.02 and p <0.03 respectively). Changes in the megakaryocytes in the bone marrow are associated with changes in primary haemostasis in normal individuals.

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Ex vivo zidovudine (AZT) treatment of CD34+ bone marrow progenitors causes decreased steady state mitochondrial DNA (mtDNA) and increased lactate production

Human & Experimental Toxicology ◽

10.1191/0960327104ht437oa ◽

2004 ◽

Vol 23 (4) ◽

pp. 173-185 ◽

Cited By ~ 12

Author(s):

L D Lewis ◽

S Amin ◽

C I Civin ◽

P S Lietman

Keyword(s):

Bone Marrow ◽

Mitochondrial Dna ◽

Steady State ◽

Nuclear Dna ◽

Ex Vivo ◽

Lactate Production ◽

Nuclear Dna Content ◽

Content Ratio ◽

The Mean

Haematopoietic suppression is one of the dose-limiting side effects of chronic zidovudine (AZT) therapy. We tested the hypothesis that AZT would reduce mitochondrial DNA (mtDNA) content in haematopoietic progenitors causing impaired haematopoiesis and mitochondrial dysfunction. We studied the effects of AZT 0 / 50 M in vitro, on normal human CD34 / haematopoietic progenitor cells cultured ex vivo for up to 12 days. The mean AZT IC50 for granulocyte (phenotype CD15 / /CD14 /) and erythroid (phenotype glycophorin / /CD45 /) cell proliferation was 2.5 M (SD9 / 0.7) and 0.023 M (SD9 / 0.005), respectively. In myeloid-rich cell cultures, the mean lactate content of the media, compared to untreated controls, increased by 86% (SD9 / 23) at 10 M AZT and in erythroid-rich cultures it increased by 134% (SD9 / 24) in the presence of 0.5 M AZT. In myeloid-rich cultures the AZT IC50 for the reduction in the mitochondrial/nuclear DNA content ratio was 5.6 M, whereas in erythroid rich cultures this AZT IC50 was B / 0.0005 M. AZT produced concentration-dependent inhibition of CD34 / progenitor proliferation into both myeloid and erythroid lineages; erythropoiesis was more sensitive than myelopoiesis. Concurrently, AZT reduced steady state mtDNA content, while increasing lactate production. These findings support the hypothesis that mtDNA is one of the intracellular targets involved in the pathogenesis of AZT-associated bone marrow progenitor cell toxicity.

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Inverse correlation between mean nuclear DNA content and cell number in nurse cell clusters of Drosophila

Chromosoma ◽

10.1007/bf00293528 ◽

1986 ◽

Vol 94 (1) ◽

pp. 36-44 ◽

Cited By ~ 14

Author(s):

Johannes Bohrmann ◽

G�nter Kiefer ◽

Klaus Sander

Keyword(s):

Dna Content ◽

Nurse Cell ◽

Nuclear Dna ◽

Nuclear Dna Content ◽

Inverse Correlation ◽

Cell Number ◽

Cell Clusters

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Computerized measurement of the DNA content, areas, and autoradiographic grains of the same nuclei: demonstration that lightly (3H)thymidine-labeled bone marrow cells are predominantly in G0/G1 and G2.

Journal of Histochemistry & Cytochemistry ◽

10.1177/32.11.6386975 ◽

1984 ◽

Vol 32 (11) ◽

pp. 1197-1203 ◽

Cited By ~ 10

Author(s):

D C Allison ◽

J Meyne ◽

P F Ridolpho ◽

K Bose ◽

M Chakerian ◽

...

Keyword(s):

Bone Marrow ◽

Dna Content ◽

Nuclear Dna ◽

Bone Marrow Cells ◽

Nuclear Dna Content ◽

Mouse Bone Marrow ◽

Computer File ◽

Cellular Dna ◽

Marrow Cells

A computerized "flying spot" microdensitometer and scanning stage have been combined to measure the cellular DNA content, nuclear areas, and autoradiographic grain areas of the same cells. The slide positions of the Feulgen-stained, (3H)thymidine-labeled cells are mapped with the computerized stage, and nuclear DNA content and areas are then determined by integral absorbance measurements at 588 nm. Following autoradiograph preparation, the cells are relocated and the areas of the autoradiographic grains over each nucleus are measured at a light wavelength (625 nm) and an optical density setting (greater than 0.10) that do not detect the Feulgen stain. The microcomputer calculates the portion of each nucleus covered with autoradiographic grains (grain area proportion, GAP), and it links the GAP value to the DNA content of each nucleus in the computer file for subsequent sorting and analysis. By using this system in a study of mouse bone marrow cells labeled in vivo with (3H)thymidine, we found that all S-phase cells were clearly labeled after 8 or more days of autoradiographic exposure. Prolonged exposures (up to 64 days) led to detection of lightly labeled cells (0.1 less than GAP less than 0.8) with G1/G0 and G2 DNA content.

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