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Biomedical subjects

R Hoffman

Publications and source records attributed to R Hoffman.

At least 397 records · Page 22Linked to original sources

Association of 5q- and refractory anemia.

The association of refractory anemia with partial deletion of the long arm of one No. 5 chromosome (5q-) has been reported in six patients within the last two years. We wish to report an additional patient with refractory anemia and an acquired chromosomal deletion, del(5)(q15), in a direct bone-moarrow preparation. The specificity of this deletion for refractory anemia is discussed. It remains to be seen whether patients with refractory anemia and 5q- tend to develop acute leukemia, as has been recently suggested.

Acute Disease↗

Autoimmune hemolytic anemia and periodic pure red cell aplasia in systemic lupus erythematosus.

A patient with systemic lupus erythematosus and autoimmune hemolytic anemia complicated by periodic episodes of red cell hypoplasia is described. Using a plasma clot culture system a serum inhibitor of erythropoiesis was detected. In addition, heat eluates of the red cells of this patient were capable of impairing erythroid colony formation. The possibility that the autoantibodies of acquired autoimmune hemolytic anemia might influence the proliferation and/or maturation of erythroid progenitor cells is raised by these findings.

Anemia, Aplastic↗

Erythropoietin dependent erythropoiesis during the erythroblastic phase of juvenile chronic granulocytic leukaemia.

A child aged 3 1/2 years with typical juvenile chronic granulocytic leukaemia whose course terminated in an erythroblastic phase is described. Both in-vivo transfusion studies and in-vitro bone marrow culture studies indicate that red cell production remains erythropoietin dependent in this situation. The relationship of erythropoietin to the reversion to fetal haematopoiesis which characterizes juvenile chronic granulocytic leukaemia is discussed.

Child, Preschool↗

T cell chronic lymphocytic leukemia: presence in bone marrow and peripheral blood of cells that suppress erythropoiesis in vitro.

The pathogenesis of the anemia associated with malignancy was investigated in a patient with T cell chronic lymphocytic leukemia. The plasma clot culture system was used as a measure in vitro of erythropoiesis. The patient's peripheral blood and marrow T lymphocytes obtained both before and after transfusion therapy suppressed erythroid colony formation by normal human bone marrow cells. Pretreatment of the patient's bone marrow T cells by antithymocyte globulin (ATG) and complement reversed this suppression. In addition, pretreatment of the patient's marrow cells with ATG and complement markedly augmented erythropoiesis in vitro. The expression of erythroid activity caused by the selective destruction of the suppressor T lymphocytes in the patient's bone marrow with ATG and the suppression of normal erythropoiesis by the patient's bone marrow and peripheral blood lymphocytes suggest that interaction between the malignant T cell and the erythropoietin-responsive stem cell is important in production of anemia in this patient.

Aged↗

Evaluation of the mechanism of zymosan-induced resistance to experimental peritonitis.

Three injections of intraperiotoneal (IP) zymosan-induced profound resistance to E. coli peritonitis in Sprague-Dawley rats. IP zymosan had minimal effects on organ weights and systemic phagocytic clearance ability, suggesting that this mode of administration had few systemic reticuloendothelial system (RES) effects. Hemoglobin (a known inhibitor of local phagocytosis) reduced the protection induced by zymosan, giving further evidence that IP zymosan acts locally. IP zymosan stimulation results in an initial marked influx of polymorphonuclear cells followed by a greater percentage replacement of mononuclear cells by the third day. Examination of these cells via chemiluminescence studies demonstrated that the phagocytic capacity of zymosan-stimulated peritoneal cells was markedly greater than the control group on a cell-for-cell basis. IP zymosan also gave some protection against intravenous (IV) E. coli, but IV zymosan did not significanly protect against IP E. coli. Possible mechanisms of action are discussed. These findings suggest that a technique of local RES stimulation could have a place in preparation of certain high-risk patients for elective abdominal surgery where peritoneal contamination is likely.

Animals↗

Suppression of erythroid-colony formation by lymphocytes from patients with aplastic anemia.

To explore the possible role of cell-mediated suppression of erythropoiesis in acquired aplastic anemia, we studied the effect of peripheral blood lymphocytes from seven patients with aplastic anemia on erythroid-colony formation by normal human bone marrow in an in vitro plasma clot-culture system. Varying numbers of peripheral blood lymphocytes (0.5 to 6 X 10(5) cells) were cocultured with 6 X 10(5) normal bone-marrow cells in the presence of 2 IU of erythropoietin for seven days. Peripheral blood lymphocytes from five of the seven patients with aplastic anemia caused a 79 to 94 per cent reduction of erythroid-colony formation. Thus, at a peripheral blood lymphocyte concentration of 2 X 10(5) cells, the numbers of erythroid colonies formed (control vs. experimental) were 374 +/- 16 (S.E.M.) vs. 22 +/- 6, 48 +/- 4, 50 +/- 16, 80 +/- 4 and 27 +/- 3. These results suggest that some patients with aplastic anemia possess a population of lymphocytes capable of suppressing in vitro erythropoiesis.

Adolescent↗

The extensive homology between mRNA sequences of normal and SV40-transformed human fibroblasts.

The poly(A)-containing messenger RNA of normal diploid fibroblast and SV40-transformed progeny cells are compared by cross-hybridizing cDNA. We find a high degree of homology between the mRNA from normal and transformed cells. Despite imperfections in the procedure, the technique permits the conclusion that, at most, 3% of the mRNA in the transformed cell has sequences not present in the normal parental cell. Furthermore, much of the difference appears to occur in low and intermediate complexity classes of mRNA molecules. Extension homology in the mRNA sequences of disparate cell lines may be a general phenomenon, and even HeLa cell mRNA is nearly identical to that of diploid human fibroblasts.

Base Sequence↗

Erythroid colony formation by polycythemia vera bone marrow in vitro. Dependence on erythropoietin.

In the plasma clot culture system both normal and polycythemia vera (PV) bone marrow cells respond to erythropoietin (Ep), giving rise to large numbers of colonies of erythroid cells. In PV, but not in normal individuals, the marrow produced endogenous erythroid colonies (EED) in the absence of exogenous Ep. The number of EEC formed varied from patient to patient comprising anywhere from 6 to 29% of the total number of colonies formed in the presence of Ep. Exposure, before use in culture, of fetal calf serum and citrated bovine plasma to the gammaglobulin fraction of rabbit anti-Ep serum followed by treatment with goat anti-rabbit gamma-globulin re sulted in a significant decrease in EEC formation. Addition of anti-Ep directly to the culture medium produced similar results. In addition, the production of EEC in response to added Ep was inhibited in the presence of anti-Ep. Addition of very small doses of highly purified Ep to anti-Ep-treated cultures resulted in the reappearance of a significantnumber of EEC formation in PV may be due to a population of erythroid-committed precursors that are abnormally sensitive to small concentrations of Ep which may be present in fetal calf serum and citrated plasma. Although the mechanism of formation of these cells is not known, it appears that the final steps in the formation of red cells derived from this clone of precursors is subject to the usual Ep control.

Adult↗

Patient progress rounds on a university hospital cardiology service.

The authors describe patient progress rounds, a weekly meeting of representatives of all disciplines associated with a university hospital cardiology service. The objective is coordination of treatment for all patients in the interest of providing comprehensive care. Each patient's clinical status is reviewed, but primary attention is given to psychosocial aspects. These rounds provide a medium for identifying and dealing with patients' needs, a cooperative teaching and learning venture for staff, a multidisciplinary team approach that increases quality of care, and an opportunity for doctors to confront the reality of their patients as psychosocial beings. Case vignettes illustrate the use and effectiveness of patient progress rounds.

Adult↗

Effect of cytochalasin B on human lymphocyte responses to mitogens: time and concentration dependence.

Human peripheral blood mononuclear cells were exposed to various concentrations of concanavalin A (Con A) and cytochalasin B (CB). Low concentrations of CB (0.5 to 2.0 microng/ml) augmented, whereas high concentrations of CB (greater than 2.0 microng/ml) inhibited the mitogenic response to Con A when Con A and CB were added at the initiation of culture. Augmented responses could also be found by adding normally inhibitory high concentrations of CB after 72 to 96 hr incubation with Con A. Preincubation of the cells with CB 5 min to 4 hr before adding Con A also resulted in potentiation of the mitogenic response. CB did not increase spontaneous transformation and worked as well in various solvents (dimethyl sulfoxide, acetone, and ethanol). The effect was totally reversible by removing CB before adding Con A. CB had no effect on 3H-Con A binding to cells. The potentiating effect of CB was still evident after removal of CB, Con A, or both from cultrues that had been simultaneously exposed to Con A and CB for at least 2 days. CB augmented the response of human lymphocytes to Con A-adsorbed, x-rayed autologous lymphocytes. In the presence of optimal concentrations of CB, x-ray-damaged cells respond better to Con A; the response to suboptimal and supraoptimal concentrations of Con A is better, and the response with delayed addition of alpha-methyl-D-mannoside is better. CB also potentiates the response of human lymphocytes to pokeweed mitogen and phytohemagglutinin. Direct observation of cells in culture demonstrated the development of huge clusters of cells during mitogenic responses to Con A in the absence of CB. Circumstances which inhibited the mitogenic response to Con A totally prevented the development of cellular aggregates (prolonged incubation with high concentrations of CB). Each of the conditions which augmented the mitogenic response to Con A was accompanied by the formation of multiple small, relatively uniform cellular aggregates. These observations suggest that CB affects cell-cell interaction possibly by affecting distribution of Con A on the cell surface, by affecting cell sruface net negative charge, or by increasing the response to chemotactic stimuli. CB may be acting in some manner to enable certain nonresponsive cells to respond to a mitogenic stimulus, although an increase in the response of individual cells cannot be ruled out.

Binding Sites↗