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Biomedical subjects

Z Ben-Ishay

Publications and source records attributed to Z Ben-Ishay.

At least 37 records · Page 2Linked to original sources
PubMed1982

A comparison of spontaneous and CSF added CFU-MG colony formation in healthy, sick and hypotrophic pre-term infants.

Myelopoietic progenitor cells (CFU-MG) have been studied from peripheral blood of healthy, sick, and hypotrophic pre-term infants. Methylcellulose cultures were prepared simultaneously with and without exogenous colony stimulating factor. It was found that large numbers of circulating CFU-M are present at birth in healthy infants, smaller numbers in sick infants, and very few in hypotrophic infants. Exogenous CSF increases the number of colonies in cultures of healthy infants at birth. A limiting factor in spontaneous colony formation is the production of CSF by the cells in culture. This is particularly evident in sick infants. During the postnatal course similar levels of circulating CFUc, higher than in adult blood, are found in all three groups of pre-term infants.

Colony-Stimulating Factors↗
PubMed1982

Differential characterization of colony-forming units in diffusion chambers from pluripotent stem cells and progenitors of granulocytes/macrophages.

Colony-forming units in diffusion chambers (CFU-D), pluripotent stem cells (CFU-S) and colony-forming units in agar cultures (CFU-C) were studied in the bone marrow of weanling mice injected twice with hydroxyurea (HU). CFU-D, CFU-S and CFU-C were assayed 2 h, 2 days and 4 days after HU administration. After 2 h the total number of CFU-D/femur marrow cells did not change, while CFU-S and CFU-C decreased to 16.6 and 13.5% of control levels, respectively. On Day 2, CFU-D and CFU-S increased to 25 and 16.6%, respectively, above control levels and CFU-C was only 52% of the normal level. Four days after HU administration, CFU-S decreased steeply to 7.6%, CFU-D 80% and CFU-C to 32% of their pretreatment levels. Bone marrow of HU-treated weanling mice was also incubated in liquid medium where CFU-S decreased more rapidly than did CFU-D. It is concluded that CFU-D in weanling mice represent a noncycling and more primitive stem cell pool than CFU-S and probably constitute a reserve pool, the mobilization of which is secondary to that of CFU-S.

Animals↗
PubMed1982

Changes of bone marrow stromal cells (MSC) in mice after drug induced eradication of hematopoietic cells: in vitro effects on normal bone marrow.

This study deals with murine marrow stromal cells (MSC) during hematopoietic regeneration. Regenerative marrow was induced in infant mice by two consecutive i. p. injections of hydroxyurea (HU) (2 X 1,000 mg/kg) which kill most cells in DNA synthesis. Two days later the marrow becomes enriched in pluripotent stem cells (CFU-S) and committed progenitors. It was found that fibroblastoid colony-forming-units (CFU-F) become concentrated approximately four fold above controls and give rise to significantly larger fibroblastoid colonies than CFU-F in control marrow. In split-phase semisolid agar cultures, i. e. adherent cells of HU-treated marrow (in under layers) and normal bone marrow cells (in upper layers), inhibition of G/M colonies in the upper layer in observed. In control split-phase cultures of both under layers and upper layers of normal bone marrow, CFU-C inhibition is by far less pronounced. In liquid cultures, pre-established adherent layers of HU-treated marrow have a stimulatory effect on normal marrow CFU-C. It is concluded that during increased demand for pluripotent stem cells and progenitors, such as after HU administration, marrow stromal cells and possibly other adherent cells produce inhibitory factor(s) of CFU-C differentiation. The inhibitory activity possibly is an effective mechanism for stem cell pool preservation. The differing effect of adherent cells of HU-treated marrow on CFU-C in liquid and in semi-solid medium suggests production of two different factors with opposing influences on CFU-C, depending upon the culture conditions.

Animals↗
PubMed1981

Effect of hydroxyurea on two different types of hematopoietic stem cells (CFU-S and DCPC) of newborn mice.

Pluripotent hematopoietic stem cells from the bone marrow of newborn mice (9--13 days of age) have been studied following the administration of hydroxyurea (HU, 1,000 mg/kg). Following a single injection as well as a regimen of eight injections complete bone marrow reconstitution was achieved after 7 days. During the recovery phase diffusion chamber progenitor cells (DCPC) from pretreated newborn mouse bone marrow proliferated strongly to give significantly higher cell yields than DCPC from control animals. By contrast (colony-forming units-spleen [CFU-S]) levels were reduced at the same time to between 15 and 40% of controls suggesting a small-sized reserve pool of resting CFU-S in newborn mice. Assuming that DCPC are less differentiated than CFU-S and are non-cycling stem cells they may possibly pass through the CFU-S stage rapidly in newborn mice under the stress of hematopoietic reconstitution and proceed directly to myelopoiesis.

Animals↗
PubMed1978

Migration of lymphoid cells to the bone marrow of rat following eradication of cells in DNA synthesis and in mitosis.

Eradication of replicating bone marrow cells of rat by means of combined administration of single doses of hydroxyurea and vinblastin is followed within 9--10 h by an inflow of lymphoid cells of extramedullary origin in the range of 13,200,000/femur. The rat bone marrow with a high content of lymphoid cells was previously shown to be concentrated in stem cells. The factor(s) which convey the 'information' of decrease of replicating marrow cells to extramedullary sites is at present unknown.

Animals↗
PubMed1978

Growth of diffusion chamber hematopoietic colonies derived from spleen cells of rats administered hydroxyurea.

Donor rats of the Hebrew University strain were administered a single intraperitoneal injection of hydroxyurea (400 mg/kg body weight). 1--3 h following the administration of the drug, a suspension of spleen cells, the majority of which consisted of lymphocytes, was prepared. Spleen cells were placed in diffusion chambers and these were implanted in the peritoneal cavity of preirradiated mice. 5--8 days following implantation, erythroid and granulocytic colonies developed in 30.3% of the diffusion chambers studied. However, in most chambers, macrophages were observed. In control experiments with implantation of spleen cells of normal rats, granulocytic colonies did not grow and in only 3.1% of the chambers erythroid colonies were noted. Macrophage colonies, however, developed in all 32 control cultures. Our previous studies showed that administration of a single dose of hydroxyurea strips the rat bone marrow of approximately 50% of replicating cells within 9--10 h. The results of the present study indicate that such a severe depletion of rat marrow cells results in early committment of spleen stem cells to various blood cell lines.

Animals↗
PubMed1978

Erythroid "bursts" in semi-solid agar diffusion chambers: effect of cyclophosphamide administration to host and of hydroxyurea to donor animals.

Growth of erythroid bursts was induced in peritoneal diffusion chambers in a semi-solid agar medium. Mice of the "Sabra" strain received single i.p. injections of cyclophosphamide (45 mg/kg) 24 h prior to implantation of chambers. Rats of the Hebrew University strain, used as donors, received single i.p. injections of hydroxyurea (400 mg/kg), 9 h prior to being killed. Ten to fourteen days after chamber implantation, several erythroid colonies of ten to several hundred cells developed in the semi-solid agar medium. The erythroid cells in the colonies were benzidine-positive and at various stages of maturation. We suggest that growth of erythroid "bursts" in diffusion chambers, in hosts which had not received any specific erythropoietic stimuli, was made possible by a high concentration of BFU-E in the door marrow. The BFU-E enriched rat bone marrow resulted from administration of hydroxyurea which, after preferentially killing erythroblasts in cycle, stimulated mobilization of stem cells for the replenishment of the depleted compartment.

Agar↗
PubMed1977

Effects of hydroxyurea pretreatment of donor rats on growth of haematopoietic diffusion chamber colonies in mice.

A single dose of hydroxyurea (HU) (400 mg/kg body weight) was injected i.p. into rats. Hydroxyurea, a potent DNA synthesis inhibitor, killed bone marrow cells in the S-phase of the cell cycle. 9-10 h after HU administration, the rat bone marrow contained large numbers of necrotic cells and appeared predominantly lymphoid. Within 24-48 h of HU injection, resumption of normal haematopoiesis was observed. Rat bone marrow, 9-10 h following HU administration, was implanted in peritoneal diffusion chambers (DC) in irradiated mice. The results obtained suggest that pretreatment of donor rats with HU increases the bone marrow content of progenitor cells. The stem cell-enriched marrow was conductive to enhanced growth of DC colonies in irradiated mice.

Animals↗
PubMed1977

Macrophages and/or fibroblasts in hematopoietic diffusion chamber cultures.

An ultrastructural study of diffusion chamber (DC) hematopoietic colonies derived from rat bone marrow is reported. The emphasis is placed on the structural features of macrophages and fibroblasts in cultures. The observations indicate that the two cell types are normal components of DC cultures. In older cultures both macrophages and fibroblasts contain large lipid droplets, sometimes causing difficulty in the precise characterization of the cell type. The possible origin of fibroblasts from adventitial cells if sinuses or of larger blood vessels of the bone marrow implanted in diffusion chambers is discussed. It is suggested that fibroblasts exert an enhancing influence on the growth of blood cells in DC cultures, comparable to feeder layers in in vitro cultures.

Animals↗
PubMed1976

Macrophage killing capacity. Aspects of mechanism.

Immune macrophages have the capacity to kill in mixed macrophage cultures (MMC) allogeneic macrophages bearing the alloantigens used for immunization. The killing is expressed by a lytic mechanism as neither phagocytosis nor fusion between effector and target cells could be detected by E.M. T but not B lymphocytes isolated from immune spleen cells, are able to "arm" syngeneic nonimmune macrophages and render them cytotoxic. It is suggested that mediator(s) and/or membranal components are released from T cells and attach to macrophages. Such an "arming" factor enables the macrophage to recognize and kill target cells.

Animals↗
PubMed1975

Ultrastructural study of bone morrow-derived granulocytic colonies in diffusion chambers in rats.

An ultrastructural study of diffusion chamber granulocytic colonies is reported. The colonies were derived from normal rat bone marrow cells and the chambers were inserted into the peritoneal cavity of lethally irradiated rats. The colonies were processed en bloc for electron microscopy enabling observation of cellular relationship to be made. Ultrastructural analysis of colonies disclosed normal maturing cells at all stages of maturation, with the exception of occasional granulocytes on neutrophil type that presented narrow strips of chromatin ('nuclear blebs'). The cells in colonies generally occurred in close apposition to one another and to occasional macrophages. This organization possible enhanced transmission of factors of maturation. Advantages of diffusion chamber haematopoietic culture are discussed; among the most important are the occurrence of fibroblasts originating from implanted marrow cells and the local formation of fibrin within the chambers.

Animals↗
PubMed1975

Selective eradication of rat bone marrow erythroid cells by administration of cytosine arabinoside. Observations on resumption phase of erythropoiesis.

The in vivo effect of a single i.p. injection of cytosine arabinoside (250 mg/kg body weight) on the rat bone marrow is reported. Cytosine arabinoside (ara-C), a potent inhibitor of DNA-synthesis, was seen to produce selective necrosis of fast cycling bone marrow erythroblasts. The depleted erythroid marrow is replenished by stem cells which are members of the lymphoid-transitional cells compartment. An indirect correlation between the degree of erythroid cell depletion and the extent of marrow lymphocytosis was noted 6-12 h after the administration of ara-C. At 24-48 h, however, the marrow returned to its normal activity. The rat bone marrow 6-12 h following a single injection of ara-C is suggested as an experimental model for providing stem cells committed to the erythroid line.

Animals↗
PubMed1975

The lymphoid bone marrow. An experimental model.

An experimental model is proposed whereby rat bone marrow is converted to a lymphoid-like tissue. A single i.p. injection of hydroxyurea (250 mg/kg body weight) destroys replicating marrow cells in DNA synthesis. Bone marrow erythroblasts constitute the vast majority of cells in cycle under the steady-state of hematopoiesis. Six hours following a single injection of hydroxyurea, selective damage of erythroblasts is noted. The depleted erythroid compartment appears to be replenished by cells of a lymphoid configuration. At 24 hr after injection the erythroid compartment is restored to normal activity. It is suggested that 6 hr after administration of hydroxyurea, lymphoid cells of rat bone marrow may be a source of stem cells for the depleted erythroid compartment.

Animals↗
PubMed1975

Ultrastructural analysis of erythroid colonies in diffusion chambers in irradiated rats. Effect of cytosine arabinoside administration on donor rats.

Ultrastructural observations of erythroid colonies in diffusion chambers implanted in lethally irradiated rats are reported. The donor cells were obtained from rats treated with cytosine arabinoside (250 mg/kg body weight) 6 h prior to seeding. The marrow of donor rats contained a high proportion of stem cells committed to the erythroid line. 9 days after implantation, vast numbers of erythroid colonies developed in the diffusion chambers. The erythroid cells were observed arranged around a central macrophage resembling erythroid islands in bone marrow. Erythroid colonies most probably differentiated from committed stem cells in the inoculum. It is postulated that development of erythroid colonies in diffusion chambers is conditioned by, among other factors, the presence of a special type of macrophages. These macrophages have the same function as those of central reticular cells (CRC) in bone marrow erythroid islands.

Animals↗