scholarly journals Humoral factors in aplastic anemia: relationship of liver dysfunction to lack of serum stimulation of bone marrow growth in vitro

Blood ◽  
1978 ◽  
Vol 51 (3) ◽  
pp. 397-414 ◽  
Author(s):  
JE Karp ◽  
LP Schacter ◽  
PJ Burke
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Liver Dysfunction ◽  
Humoral Factors ◽  
Serum Stimulation ◽  
Relationship Of ◽  
Stimulation Of

scholarly journals Aplastic anemia: lack of inhibitory effect of bone marrow lymphocytes on in vitro granulopoiesis

Blood ◽  
1980 ◽  
Vol 56 (4) ◽  
pp. 625-632 ◽  
Author(s):  
R Sullivan ◽  
PJ Quesenberry ◽  
R Parkman ◽  
KS Zuckerman ◽  
RH Levey ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Aplastic Anemia ◽  
Marrow Cell ◽  
Inhibitory Effect ◽  
Soft Agar ◽  
Control Subjects ◽  
B And T Lymphocytes ◽  
Stimulation Of

Abstract Prompted by previous reports that in certain patients with aplastic anemia, cell-mediated autoimmune suppression of myeloid stem cell proliferation may be demonstrable in vitro, we studied the effects of bone marrow lymphocytes from 18 patients with myeloid aplasia on the proliferation of committed granulocytic-monocytic progenitor cells (CFU- C). When assayed in soft agar cultures, marrow suspensions from 10 patients with aplastic anemia contained significantly fewer viable CFU- C than similar cell preparations from control subjects. To deplete marrow cell suspensions of lymphocytes, we employed rabbit anti-human thymocyte serum (ATS), which after multiple adsorptions exhibited marked cytotoxicity for human B and T lymphocytes but had negligible effect on normal CFU-C proliferation. Preincubation of marrow samples from 12 patients with ATS and complement resulted in no inhibition or enhancement of CFU-C growth. In further experiments, marrow cells from 8 patients were incubated with marrow from control subjects prior to CFU-C culture. No suppression of donor CFU-C proliferation was observed in any of these studies, and in 4 cocultures, mixture of the 2 marrow suspensions resulted in stimulation of CFU-C growth. Using these assays, we detected no evidence of cell-mediated inhibition of CFU-C proliferation in any of the 18 patients that we evaluated. Our data support the conclusion that in the majority of patients with aplastic anemia, an absolute deficiency of hemopoietic stem cells is present within the marrow that does not appear to be effected or sustained by suppressor lymphocytes. Whether the reduction of viable stem cells is the cause or the consequence of the process that leads to marrow failure remains unknown.

scholarly journals Aplastic anemia: lack of inhibitory effect of bone marrow lymphocytes on in vitro granulopoiesis

Blood ◽  
1980 ◽  
Vol 56 (4) ◽  
pp. 625-632
Author(s):  
R Sullivan ◽  
PJ Quesenberry ◽  
R Parkman ◽  
KS Zuckerman ◽  
RH Levey ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Aplastic Anemia ◽  
Marrow Cell ◽  
Inhibitory Effect ◽  
Soft Agar ◽  
Control Subjects ◽  
B And T Lymphocytes ◽  
Stimulation Of

Prompted by previous reports that in certain patients with aplastic anemia, cell-mediated autoimmune suppression of myeloid stem cell proliferation may be demonstrable in vitro, we studied the effects of bone marrow lymphocytes from 18 patients with myeloid aplasia on the proliferation of committed granulocytic-monocytic progenitor cells (CFU- C). When assayed in soft agar cultures, marrow suspensions from 10 patients with aplastic anemia contained significantly fewer viable CFU- C than similar cell preparations from control subjects. To deplete marrow cell suspensions of lymphocytes, we employed rabbit anti-human thymocyte serum (ATS), which after multiple adsorptions exhibited marked cytotoxicity for human B and T lymphocytes but had negligible effect on normal CFU-C proliferation. Preincubation of marrow samples from 12 patients with ATS and complement resulted in no inhibition or enhancement of CFU-C growth. In further experiments, marrow cells from 8 patients were incubated with marrow from control subjects prior to CFU-C culture. No suppression of donor CFU-C proliferation was observed in any of these studies, and in 4 cocultures, mixture of the 2 marrow suspensions resulted in stimulation of CFU-C growth. Using these assays, we detected no evidence of cell-mediated inhibition of CFU-C proliferation in any of the 18 patients that we evaluated. Our data support the conclusion that in the majority of patients with aplastic anemia, an absolute deficiency of hemopoietic stem cells is present within the marrow that does not appear to be effected or sustained by suppressor lymphocytes. Whether the reduction of viable stem cells is the cause or the consequence of the process that leads to marrow failure remains unknown.

Thrombopoietin-Induced Stimulation of Megakaryocyte- Enriched Bone Marrow Cultures

1979 ◽  
Author(s):  
K. L. Kellar ◽  
B. L. Evatt ◽  
C. R. McGrath ◽  
R. B. Ramsey
Keyword(s):  
Bone Marrow ◽  
Dna Synthesis ◽  
Bone Marrow Cells ◽  
Rabbit Plasma ◽  
Bone Marrow Cultures ◽  
Plasma Fractions ◽  
Marrow Cultures ◽  
Stimulation Of

Liquid cultures of bone marrow cells enriched for megakaryocytes were assayed for incorporation of 3H-thymidine (3H-TdR) into acid-precipitable cell digests to determine the effect of thrombopoietin on DNA synthesis. As previously described, thrombopoietin was prepared by ammonium sulfate fractionation of pooled plasma obtained from thrombocytopenic rabbits. A control fraction was prepared from normal rabbit plasma. The thrombopoietic activity of these fractions was determined in vivo with normal rabbits as assay animals and the rate of incorporation of 75Se-selenomethionine into newly formed platelets as an index of thrombopoietic activity of the infused material. Guinea pig megakaryocytes were purified using bovine serum albumin gradients. Bone marrow cultures containing 1.5-3.0x104 cells and 31%-71% megakaryocytes were incubated 18 h in modified Dulbecco’s MEM containing 10% of the concentrated plasma fractions from either thrombocytopenic or normal rabbits. In other control cultures, 0.9% NaCl was substituted for the plasma fractions. 3H-TdR incorporation was measured after cells were incubated for 3 h with 1 μCi/ml. The protein fraction containing thrombopoietin-stimulating activity caused a 25%-31% increase in 3H-TdR incorporation over that in cultures which were incubated with the similar fraction from normal plasma and a 29% increase over the activity in control cultures to which 0.9% NaCl had been added. These data suggest that thrombopoietin stimulates DNA synthesis in megakaryocytes and that this tecnique may be useful in assaying thrombopoietin in vitro.

scholarly journals Effect of natural killer cells on syngeneic bone marrow: in vitro and in vivo studies demonstrating graft failure due to NK cells in an identical twin treated by bone marrow transplantation

Blood ◽  
1985 ◽  
Vol 66 (5) ◽  
pp. 1043-1046
Author(s):  
GD Goss ◽  
MA Wittwer ◽  
WR Bezwoda ◽  
J Herman ◽  
A Rabson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Aplastic Anemia ◽  
Nk Cells ◽  
Natural Killer ◽  
Marrow Transplantation ◽  
Bone Marrow Failure ◽  
Cell Activity ◽  
High Dose

Bone marrow transplantation for severe idiopathic aplastic anemia was undertaken in a patient, using his monozygotic twin brother as the donor. In spite of the use of syngeneic bone marrow, failure of engraftment occurred on two occasions. In vitro studies demonstrated that natural killer (NK) cells from the recipient markedly inhibited the growth of donor bone marrow granulocyte progenitor cells. On a third attempt, successful bone marrow engraftment was achieved following high-dose cyclophosphamide, which has previously been shown to be inhibitory to NK cells. We conclude that NK cell activity may play an important role in bone marrow failure as well as being responsible for at least some cases of aplastic anemia.

scholarly journals In vitro stimulation of primate hemoglobin synthesis by L-thyroxine

Blood ◽  
1977 ◽  
Vol 49 (3) ◽  
pp. 407-413 ◽  
Author(s):  
JE Fuhr ◽  
N Gengozian ◽  
M Overton
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Leucine Incorporation ◽  
Hemoglobin Synthesis ◽  
Globin Chains ◽  
Stimulation Of ◽  
Marrow Cells

Abstract Bone marrow cells from adult and abortus primates (marmosets) were incubated in vitro to determine their responsiveness to L-thyroxine. 3H- leucine incorporation into purified globin chains was the parameter assayed to determine responsiveness. Bone marrow from spontaneously aborted animals consistently was stimulated by the presence of physiologic levels of L-thyroxine. Bone marrow cells from adult animals were unaffected by the hormone.

Defective monocyte-to-macrophage maturation in patients with aplastic anemia

Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 2150-2156 ◽  
Author(s):  
R Andreesen ◽  
W Brugger ◽  
C Thomssen ◽  
A Rehm ◽  
B Speck ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Single Cells ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Staining Technique ◽  
Enzyme Linked Immunosorbent Assay ◽  
Immunoperoxidase Staining ◽  
Maturation In Vitro

Abstract Macrophages (MAC) are important effector cells of the immune system but also play an essential role as regulatory cells in hematopoiesis. They originate from circulating monocytes (MO) as immature precursor cells that undergo terminal differentiation upon migration from the capillary bed into the various tissues. In the presence of serum, MAC maturation from blood MO is observed in vitro and can be followed by the expression of maturation-associated antigens (MAX.1, .3, .11, and .26; transferrin receptor, 13C2, CD16). We have tested blood MO from 22 patients with aplastic anemia (AA) for their capacity to undergo terminal maturation in vitro. After isolation, blood MO in six patients expressed CD14 molecules at low density when compared to normals. On culture for 7 days, in 15 patients various abnormalities could be shown by phenotype analysis using cell-enzyme-linked immunosorbent assay (ELISA) and an immunoperoxidase staining technique of single cells. Abnormalities ranged from the distinctive failure of mature MAC to express single surface antigens (eg, gp64-MAX.1) to complete inhibition of the development of a MAC maturation-associated phenotype. In three patients the maturational defect was found to persist in complete remission after successful therapy with antileukocyte globulin (ALG). Neither in other immunosuppressed or multiple-transfused patients nor in those with bone marrow hypoplasia secondary to cancer chemotherapy and during hematologic reconstitution following autologous bone marrow transplantation (BMT), defective MO maturation in vitro was seen. Our data provide evidence for the existence of serious disorders within the MO-MAC lineage in patients with AA. This observation may either reflect the stem-cell defect or indicate a MAC involvement in the pathogenesis of the disease.

Sign in / Sign up

Export Citation Format

Share Document