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Biomedical subjects

S B Krantz

Publications and source records attributed to S B Krantz.

At least 109 records · Page 6Linked to original sources
PubMed1984

Acquired immune hemolytic anemia associated with IgA erythrocyte coating: investigation of hemolytic mechanisms.

We have investigated the hemolytic mechanisms in a patient with acquired immune hemolytic anemia whose red cells appeared to be coated with IgA alone. The clinical course was similar to that of patients with hemolytic anemia mediated by warm-reacting IgG antibody. Splenic sequestration of red cells was demonstrated, and marked reduction of hemolysis occurred after corticosteroid therapy. Antibody was eluted from the patient's red cells and used to sensitize normal red cells in vitro. These sensitized red cells were not lysed by fresh autologous serum, nor did they fix detectable amounts of C3. However, red cells sensitized by eluted antibody were lysed by normal human peripheral blood monocytes in a system designed to demonstrate antibody-dependent cell-mediated cytotoxicity. Monocyte-mediated hemolysis of sensitized red cells was inhibited by the addition of low concentrations of normal serum IgA to the system, but not by IgG. The ability of the eluate to induce monocyte-mediated hemolysis was abolished by its adsorption on Sepharose-bound anti-IgA, but not by preincubation with Sepharose-bound anti-IgG. In addition, normal human monocytes were demonstrated to ingest eluate-sensitized red cells. These data demonstrate an in vitro interaction of IgA-sensitized red cells with leukocytes and suggest a possible mechanism for the patient's hemolysis.

Aged↗
PubMed1984

Studies on pure red cell aplasia. XI. Results of immunosuppressive treatment of 37 patients.

Thirty-seven patients with pure red cell aplasia (PRCA) were seen between 1966 and 1982. Ten patients had accompanying diseases described in association with PRCA, while the remainder had primary PRCA. All but two patients were treated with some form of immune manipulation, including corticosteroids, cytotoxic drugs, antithymocyte globulin, splenectomy, thymectomy, and plasmapheresis. Twenty-three patients (66%) had a remission induced by immunosuppression. In addition, there were 5 spontaneous remissions (14%). Cytotoxic drugs administered in combination with corticosteroids were the most effective form of treatment, producing 18/32 remissions (56%). Twelve of these remissions were in patients resistant to corticosteroids or in patients who had relapsed while taking them. Thirteen of the 23 patients in whom remissions were induced and one-fifth of the patients with spontaneous remissions have relapsed to date. However, with additional treatment, a second remission was induced in 10/13. Fifty-four percent of the patients with induced remissions remained transfusion-free during most of the follow-up period. Median survival in patients with primary PRCA was greater than 10 yr, whereas in patients with secondary PRCA, it was 4 yr. Infection was a major cause of morbidity and mortality. This study demonstrates the value of a variety of immunosuppressive treatments of patients with PRCA.

Adolescent↗
PubMed1983

Increased sensitivity to complement of erythroid and myeloid progenitors in paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria is an acquired hemolytic anemia characterized by a membrane defect leading to increased sensitivity of erythrocytes, granulocytes, platelets, and bone-marrow erythroid and myeloid cells to complement-mediated lysis. To determine whether the phenotype of paroxysmal nocturnal hemoglobinuria is also expressed on erythroid and myeloid progenitors, marrow cells from five patients with the disease were exposed to a sucrose hemolytic system and then assayed for colony-forming units-erythroid (CFU-E), burst-forming units-erythroid (BFU-E), and colony-forming units-granulocyte/macrophage (CFU-GM). A 50 percent or greater decrease in the numbers of erythroid and myeloid colonies was noted when marrow cells from the patients with paroxysmal nocturnal hemoglobinuria were exposed to a sucrose solution of low ionic strength in the presence of complement but not in its absence. Such a decrease was not noted in similarly treated normal marrow cells or in marrow cells from a patient with the disease in remission. These results suggest that in paroxysmal nocturnal hemoglobinuria, CFU-E, BFU-E, and CFU-GM express a membrane abnormality similar to that on erythrocytes, and that the disease is the result of a change occurring at the level of the pluripotent hematopoietic stem cell.

Adult↗
PubMed1983

Isolation of erythropoietin-sensitive cells from Friend virus-infected marrow cultures: characteristics of the erythropoietin response.

Murine erythroid precursor cells, stimulated to proliferate in vitro in the absence of added erythropoietin (EP) by the anemia strain of Friend virus (FVA), will subsequently respond to EP by complete erythrocyte differentiation. If not exposed to EP, the erythroid cells divide for about 120 hr in culture, and they maintain the potential for full differentiation in response to EP added at any time during the period from 72 to 120 hr. Between 96 and 120 hr of culture without added EP, the EP-sensitive erythroid precursor cells that have formed discrete erythroid bursts can be isolated in relatively large numbers from such cultures by plucking with a Pasteur pipette. The addition of EP initiates the final stages of erythroid differentiation, including heme synthesis in 70%-80% of these isolated cells. With respect to homogeneity of the precursor cells, quantity of EP-responsive cells obtainable, and uniformity of EP responsiveness, this system is uniquely favorable for biochemical studies of the late differentiation effects of EP. The overall changes in gene expression accompanying EP-induced terminal differentiation were examined by two-dimensional gel electrophoresis of proteins labeled for a short time with radioactive amino acids. Several new proteins are synthesized in these erythroid cells during terminal differentiation, but the number is a very small percentage of the total number of proteins being made. Thus, in this system, the effect of EP is to initiate expression of a small group of genes, including those for globins, spectrin, and other proteins involved in the final stages of erythroid differentiation.

Animals↗
PubMed1982

Antibody-dependent cellular cytotoxicity to allogeneic but not autologous erythroblasts in vitro.

Antibody-dependent cellular cytotoxicity (ADCC) is a very sensitive mechanism for immune injury of target cells, which utilizes extremely low concentrations of antibody. We have developed a method for demonstrating this type of cytotoxicity to normal human erythroblasts. The latter were enriched 3- to 4-fold and were then labeled with 59Fe. Blood lymphocytes from the same donor were enriched to 93% and were added as effector cells at a 60:1 ratio to the target cells. After 4 hr at 37 degrees C, as 5- to 10-fold increase in the release of 59Fe occurred when the plasma or IgG from patients with pure red-cell aplasia was present. This activity was not present when the effector cells were absent. However, this activity was found in the remission plasmas of patients and was not found when autologous erythroblasts were used. These studies demonstrate a method for detecting ADCC to allogeneic normal human erythroblasts. This ADCC does not appear to be related to the disease since a similar autoimmune activity to the patients' own erythroid cells was not detected. Further studies are suggested using other effector cells in this system.

Anemia, Aplastic↗
PubMed1982

Specific differentiation events induced by erythropoietin in cells infected in vitro with the anemia strain of Friend virus.

Mouse bone marrow cells infected in vitro with the anemia strain of Friend leukemia virus from large clusters (bursts) of erythroblasts after 5 days in culture in methylcellulose medium. Two types of erythroblast populations can be isolated from bursts of infected cells by manipulation of the culture conditions. One type of erythroblast, which is obtained when erythropoietin (EP) is added to the culture, has proliferated and undergoes differentiation to become an erythrocyte. The second type of erythroblast, which is obtained when no EP is added to the culture, is the product of extensive proliferation, but it fails to undergo the terminal stages of erythroblast differentiation. Comparisons of these two types of erythroblasts demonstrate that specific EP effects include changes in the nucleus, cytoplasm, and membrane of the treated cells. Those events of erythroid differentiation shown to be directed by EP were extrusion of the nucleus from the erythroblast, induction of uroporphyrinogen I synthetase activity, increased iron incorporation into protoporphyrin, synthesis of alpha- and beta-globin polypeptides due largely to increased mRNA production, and synthesis and incorporation of spectrin into the cell membrane. In this system, EP promotes these effects without observable stimulation of progenitor proliferation in addition to that caused by the virus alone. Thus, the role of EP in terminal erythrocyte differentiation is not simply that of an erythroid-specific mitogen.

Animals↗
PubMed1982

Velocity sedimentation profiles of normal and regenerating primitive erythroid burst-forming units: relation to phase of cell cycle and growth in vitro.

The primitive burst-forming unit-erythroid (BFU-e) derived from normal and regenerating murine bone marrow was examined by velocity sedimentation at unit gravity. An increase in the modal sedimentation velocity and the percentage of rapidly sedimenting BFU-e was found in regenerating marrow as compared to normal marrow. Neither hypertransfusion-induced plethora nor administration of erythropoietin (Ep) during regeneration altered the changes from normal in the velocity sedimentation profile observed during regeneration. Separated marrow cells were pooled as rapidly sedimenting and slowly sedimenting and then examined for percentage of BFU-e in DNA synthesis and growth response in vitro to increasing concentrations of a partially purified Ep preparation. The percentage of BFU-e in DNA synthesis as determined by tritiated thymidine killing does not correspond to the BFU-e growth response to Ep in vitro. No difference in growth was noted between BFU-e from rapidly and slowly sedimenting normal marrow cells despite an increased percentage in DNA synthesis of normal BFU-e which sedimented rapidly. No significant difference in the percentage of BFU-e in DNA synthesis was found between the rapidly and slowly sedimenting subpopulations of regenerating BFU-e, but the latter had a reduced growth response to low concentrations of Ep.

Animals↗
PubMed1982

Mode of action of the IgG inhibitor of erythropoiesis in transient erythroblastopenia of children.

Twelve cases of transient erythroblastopenia of childhood (TEC) have been studied to evaluate their marrow cell erythropoiesis in vitro and the effect on it of their serum or IgG. The number of colony-forming units-erythroid (CFU-E) and burst-forming units-erythroid (BFU-E) in the bone marrow of nine cases was extremely variable and did not allow any conclusion regarding the pathogenesis of this anemia. An IgG inhibitor of growth of erythroid colonies or bursts was detected in 8/12 cases. This IgG inhibitor had no effect on the growth of granulocyte-macrophage colonies. Further studies on its mode of action indicated that the IgG did not have antierythropoietin antibody properties and did not affect the mature erythroblasts, as shown by a lack of inhibition of their responses to erythropoietin and by the lack of a cytotoxic effect on 59Fe-labeled erythroblasts. In four cases, preincubation studies demonstrated a direct effect of the IgG on the CFU-E, which was complement-mediated in three cases and complement-independent in one case. In two other cases, the IgG suppressed the growth of normal BFU-E only without affecting the growth of CFU-E. The IgG inhibitor was no longer present after the erythroblastopenia had remitted. These studies demonstrate that in the majority of cases of TEC, an IgG suppressor of erythropoiesis in vitro is present. Its mode of action is heterogeneous regarding its requirement for complement. Its target cells are the earlier or later erythroid progenitors, BFU-E or CFU-E, but not the differentiated erythroblasts.

Adolescent↗
PubMed1981

Red cell aplasia and chronic granulocytic leukaemia.

Two patients with chronic granulocytic leukaemia developed red cell aplasia during the course of their disease. In one of them, cell culture studies demonstrated the presence in the patient's serum of an IgG inhibitor of haemoglobin synthesis by his own mature erythroblasts and erythroblasts grown in vitro from his erythroid colony forming cells. The IgG fraction was also found to be cytotoxic for the patients' marrow erythroblasts that were present after disappearance of the red cell aplasia. Treatment with corticosteroids resulted in reappearance of the erythroblasts in the marrow and decrease in the transfusion requirement. Red cell aplasia can occur before, at the same time or after the onset of chronic granulocytic leukaemia and may have the same immune pathogenesis as chronic idiopathic pure red cell aplasia. It occurs without busulphan treatment and seems to have no direct relation to the terminal metamorphosis. Treatment of the red cell aplasia with corticosteroids would appear worthwhile as it may reduce the transfusion requirement without affecting the course of the underlying leukaemia.

Adult↗
PubMed1981

Beneficial effect of hepatitis in leukemic reticuloendotheliosis.

A patient with leukemic reticuloendotheliosis had splenomegaly, neutropenia, and a severe underproduction anemia. During a three-year period, the hematocrit was never in the normal range, and periodic transfusions were required. However, after an episode of hepatitis that was positive for B surface antigen, the spleen became smaller, the number of neutrophils increased, the transfusion requirement disappeared, and the hematocrit rose to normal. Several mechanisms for this observation are proposed.

Hepatitis B↗
PubMed1980

Helper virus is not required for in vitro erythroid transformation of hematopoietic cells by Friend virus.

The Friend polycythemia virus complex (FVP), consisting of the replication-defective spleen focus-forming virus (SFFV) and a helper Friend murine leukemia virus (MuLV-F), produces erythroleukemia within 2-3 weeks in vivo. We have recently reported in vitro transformation of bone marrow cells by FVP, producing clusters of erythroid colonies (erythroid bursts) 4-6 days after infection. In contrast to uninfected bone marrow cells, FVP-treated cells proliferated and differentiated (synthesized hemoglobin) in the absence of added erythropoietin, the physiologic regulator of erythropoiesis. The relative roles of helper murine leukemia virus (MuLV) and SFFV in the in vitro erythroid transformation have now been examined. Pseudotype studies and the finding that cloned MuLV-F (free of SFFV) did not induce burst formation indicated that SFFV was essential for this in vitro effect of FVP. Because SFFV could not be obtained free of helper MuLV, we assessed the requirement of MuLV in the transformation by kinetic analyses of helper-deficient and helper-excess FVP preparations. Whereas helper-excess FVP gave single-hit kinetics both in vivo and in vitro, the helper-deficient FVP followed multiple-hit kinetics when titrated for spleen focus formation in vivo. Addition of MuLV-F to helper-deficient FVP prior to injection resulted in a marked enhancement of spleen focus formation and a conversion from multiple-hit to single-hit kinetics. In contrast, titration of this same preparation for erythroid burst transformation in vitro yielded single-hit kinetics, and the addition of helper MuLV-F had no effect. The time course of burst development was similar with or without added MuLV-F. Unlike burst transformation, SFFV production by these infected cultures followed multiple-hit kinetics. Addition of MuLV-F at the time of infection led to an enhancement of SFFV production and conversion of the titration curve from multiple-hit to single-hit. These data are consistent with the idea that SFFV is competent for erythroid transformation in vitro, but requires helper MuLV for its replication.

Animals↗
PubMed1980

Combined effect of friend polycythemia virus and erythropoietin on erythroid burst formation in vitro.

The infection of mouse bone marrow or spleen cells in vitro with the polycythemia strain of Friend virus (FVP) results in the formation of erythroid bursts after 4-6 days in plasma clot or methylcellulose cultures in the absence of added erythropoietin (Ep). We have now used this cell culture system to study the effect of added Ep on FVP-induced burst formation. The number of bursts that developed following infection of bone marrow cells with equilibrium density gradient purified FVP was increased by the addition of low concentrations of highly purified human urinary Ep (70,000 units/mg protein) to the infected cultures. The addition of as little as 0.001 unit per ml of Ep to infected cultures resulted in a 2-fold increase in burst formation. Increasing the concentration of Ep to 0.05 unit per ml caused a 4-fold increase in the number of bursts that developed. These concentrations of Ep were ineffective in inducing erythroid bursts when added to cultures of uninfected cells. The addition of Ep within 6 hr after FVP infection was necessary to observe increased burst formation. These experiments demonstrate that FVP-burst formation is enhanced by extremely low levels of Ep. Although a precise mechanism for the increase in FVP-induced erythroid bursts with added Ep is not apparent from these experiments, a number of possibilities are discussed.

Animals↗