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Biomedical subjects

B I Lord

Publications and source records attributed to B I Lord.

At least 109 records · Page 6Linked to original sources
PubMed1977

The effects of red blood cell extracts on the proliferation of erythrocyte precursor cells, in vivo.

Saline incubation extracts of mature erythrocytes were assayed in vivo by a variety of techniques in order to study their ability to modify the proliferation of maturing erythroid cells. Using comparable extracts from granulocytes and lymphocytes, the specificity of the effect of the red cell extract for erythroid cells was confirmed by measurement of autoradiographic labelling indices, radio-iron incorporation and spleen colony growth. The erythroid cells were found to be very sensitive to the effects of the extract, as little as 10 microgram per mouse producing a maximum effect on iron incorporation. It was found that the extract does not block erythroid cells proliferation completely but simply lengthens the cell cycle, mainly by increasing the GI phase of the cycle. There was no effect on the committed erythroid precursor cells. The in vivo activity, specificity and non-toxicity to the cells, together with the cells' sensitivity to red cell extract suggest, therefore, that this inhibitor may play a physiological role in the control of red cell production.

Anemia↗
PubMed1977

Regulation of CFU-S proliferation by locally produced endogenous factors.

The presence of proliferating and non-proliferating CFU-S in, respectively, the bone marrow and spleens of phenylhydrazine (PHZ) treated mice has afforded the opportunity to investigate the presence and role of local factors responsible for the control of CFU-S proliferation. When bone marrow cells from PHZ treated mice are incubated with irradiated spleen cells taken from the same mice, there is a marked fall in the proportion of femoral CFU-S in DNA synthesis. In the converse experiments rapid triggering of splenic CFU-S is achieved. Changes in CFU-S proliferation have also been demonstrated in other situations where cell populations containing proliferating and minimally proliferating CFU-S are mixed.

Animals↗
PubMed1977

A stimulator of stem cell proliferation in regenerating bone marrow.

A factor, capable of stimulating resting haemopoietic stem cells into DNA-synthesis has been extracted from regenerating bone marrow. It has a molecular weight in the range of 30.000-50.000 daltons and is not detectable in normal bone marrow. Used in combination with a stem cell proliferation inhibitor, previously described, it will restimulate proliferation in stem cells initially stopped by the inhibitor. Conversely, stimulation produced by this factor can be reversed by the addition of inhibitor. It is concluded that stem cell proliferation is controlled by an appropriate balance of endogenously produced stimulatory and inhibitory factors.

Animals↗
PubMed1977

Lack of effect of a granulocyte proliferation inhibitor or their committed precursor cells.

Using the agar culture technique, we have measured the effect of granulocyte extracts GCE (and of erythrocyte-RCE and lymph node extracts-LNE) on the growth and proliferation of the committed granulocytic precursor cells, CFU-C. In addition we have determined their effects on the proliferation of the developing colony cells and on the ultimate cell production in the colonies. The results show that GCE has no effect on the growth or proliferative activity on the CFU-C. It does, however, reduce both the autoradiographic labelling indices of the developing colony cells and the net colony cellularities, acting as a cell cycle modulator. These are effects specific to the GCE since at the dose levels used, neither RCE nor LNE affected these measurements.

Animals↗
PubMed1976

Inhibitor of stem cell proliferation in normal bone marrow.

A saline extract from normal bone marrow cells having a molecular weight in the range 50000-1000000 daltons has been found to protect rapidly proliferating haemopoietic spleen colony forming cells (CFUs) from the lethal effects of large doses of tritiated thymidine. This extract is non-toxic to the cells. It is not found in regenerating marrow where the CFUs population is rapidly proliferating. Its effect appears to be specific for the CFUs since it has no effect on the proliferation of its close descendant, the granulocytic precursor cell (CFUc), and no effect on the average cytoplasmic structuredness of the whole bone marrow cell population. The active material is probably protein since it is degraded by trypsin.

Animals↗
PubMed1975

Modification of granulocytopoietic cell proliferation by granulocyte extracts.

Saline extracts of mature granulocytes have been partially purified by an ultrafiltration technique. The fraction in the 500-2000 daltons molecular weight range was retained and tested in a variety of experimental systems. Comparable fractions of erythrocyte and lymphocyte extracts were used for control purposes. Measurement of the structuredness of the cytoplasmic matrix (SCM) of cells is shown to be a very sensitive measure of the effects of the extract. Specific and reversible increases in SCM of proliferating granulocytic cell populations indicate changes compatible with reduced proliferation and these are confirmed by autoradiographic observations following tritiated thymidine labelling. Repeated labelling experiments to obtain the rate of flow of cells through the cycle gave a mean cell cycle time of 15 hrs in the controls but in animals treated with the granulocyte extract this was increased to about 30 hrs. The duration of DNA synthesis was increased slightly but there was no effect on G2 as measured by the stathmokinetic index method. Cell production in developing spleen colonies was reduced by repeated doses of the extract over a period of 4 days. Approximately two cell doublings were lost during this period due to the prolonged cell cycle.

Animals↗
PubMed1975

The relative spatial distributions of CFUs and CFUc in the normal mouse femur.

Femoral bone marrow was divided longitudinally into two groups of cells of varying size. By assaying CFU and CFU in the two zones of the marrow, their distributions across the diameter of the femur was determined. It is shown that the concentration of CFU increases from the femoral axis (15 CFU/105 bone marrow cells) to the bone surface (44 CFU/105 cells), obeying approximately a square-law relationship. The CFU concentration, on the other hand, increases from the femoral axis (32CFU/105 cells) to a peak value (260 CFU/105 cells) at about 330 um from the axis and thence falls off against to the bone surface (77 CFU/105 cells). Selective kinning cells in DNA synthesis using the tritiated thymidine suicide technique, in vivo, showed that CFU, near the bone surface are proliferating at a faster rate than those more distant from bone, but that CFU have a fast proliferation rate irrespective of their position in the distribution. Thus, bone marrow cell populations are shown to conform to a well-defined spatial organization corresponding to the chronologic relationships between marrow cells.

Animals↗
PubMed1974

Inhibitors of haemopoietic cell proliferation? Specificity of action within the haemopoietic system.

The specificity of action of mature blood cell extracts on their own progenitor cells was investigated by measuring their effects on the structuredness of the cytoplasmic matrix (SCM) using the technique of fluorescence polarization. Changes in SCM induced by the various extracts are probably closely related to the proliferation state of the cells.Saline extracts of lymphocytes, granulocytes and erythrocytes (LNE, GCE and RCE respectively) have been partially purified by ultrafiltration into selected molecular weight ranges and each tested against proliferative populations of lymphoid, granulocytic and erythroid cells. In all cases, complete specificity of effect on SCM was found, LNEs affecting only lymphoid cell populations, GCEs affecting only the granulocytic cell populations and RCEs affecting only erythroid cells. In each case, with the possible exception of the RCEs, the active fractions reside in the molecular weight ranges reported in the literature for cell extracts possessing proliferation inhibitory properties.

Animals↗