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Biomedical subjects

M R Klemperer

Publications and source records attributed to M R Klemperer.

14 recordsLinked to original sources
PubMed1977

In vivo leukemic transformation: cytogenetic evidence of in vivo leukemic transformation of engrafted marrow cells.

A 4-year-old girl with acute myeloblastic leukemia was treated with 50 mg/kg cyclophosphamide daily for 4 days before being given 1.7 X 10(8) bone marrow cells/kg from her HL-A identical, MLC nonreactive, cytogenetically normal brother. The patient died 92 weeks after the marrow graft. Postmortem examination showed increased myeloblasts and promyelocytes. Cytogenetic studies before transplantation showed that all sex determination metaphases had an XX pattern, and 41% of the hyperdiploid metaphases had an additional 19-20(F) chromosome. At autopsy all hyperdiploid metaphases with XY pattern and 43% of the hyperdiploid metaphases with an XX pattern had an additional F chromosome. Occasional metaphases with 47, XX, + F or 47, XY, + F were seen during the follow-up studies. These findings indicated that an acute leukemia had developed in the XY cell line of this artifically induced sex chimeric child. This suggests that a leukemic stimulus other than that proposed to be induced by total-body irradiation existed in this patient and transformed the engrafted cells.

Bone Marrow↗
PubMed1977

The effects of splenectomy and glucocorticoids on survival and hepatic uptake of damaged red cells in the mouse.

We have studied the effects of splenectomy and glucocorticoids on the survival and sequestration of Heinz body-containing red blood cells (RBC-HZB). Mice were injected with phenylhydrazine damaged 51Cr labeled isologous red blood cells (RBCs). The spleen removed 36% and the liver 19% of the injected dose after 120 hrs. Red cell survival (T 1/2) fell from 180 hrs for undamaged red cells to 16 hrs for RBC-HZB. Splenectomy resulted in an increase in hepatic uptake of damaged RBCs (36% of the injected dose) and a modest improvement in red cell survival (T 1/2 54 hrs). Treatment of non-splenectomized mice with glucocorticoids reduced the splenic uptake to 16% and the hepatic uptake to 14% of the injected dose. The reduction of splenic upatke was associated with a decrease in splenic mass rather than a decrease in uptake per unit weight of splenic tissue, while reduction in hepatic uptake was associated with both a decrease in hepatic mass and uptake per unit weight. A marked decrease was observed in hepatic uptake and in phagocytosis by Kupffer cells in glucocorticoid-treated splenectomized mice. These data suggest that increased hepatic uptake may decrease the effectiveness of splenectomy in RBC-HZB hemolytic anemia and that glucocorticoids may decrease the hepatic uptake by reducing phagocytosis by Kupffer cells.

Animals↗
PubMed1976

Exodus of 42K+ and 86Rb+ from rat thymic and human blood lymphocytes exposed to phytohemagglutinin.

We have found that PHA produces an alteration in the lymphocyte membrane which allows 86Rb+ or 42K+ in prelabeled lymphocytes to exchange for cations present in washing solutions. These observations suggested that PHA might induce an increase in the exodus of intracellular potassium during incubation in physiologic media. We, therefore, examined 86Rb+ and 42K+ efflux from rat and human lymphocytes during incubation in tissue culture medium. The rate constant for efflux, Ke, was significantly increased by PHA. 86Rb+ efflux was increased by 27% in rat thymic lymphocytes and by 78% in human blood lymphocytes following PHA treatment.

Animals↗
PubMed1976

Human lymphocyte potassium content during the initiation of phytohemagglutinin-induced mitogenesis.

The K+ content of human lymphocytes has been examined during the initial 24 hours after exposure of cells to phytohemagglutinin (PHA). We have reconfirmed that lymphocyte K+ exchanges rapidly for extracellular counterions during preparative washing if cells are exposed to PHA. By using a technique to measure cation content which does not require removal of cells from their culture medium, we have shown that K+ does not change for 24 hours following PHA treatment. Previous reports have demonstrated that an enhanced uptake of K+ occurs in lymphocytes treated with PHA. This increased uptake may be a compensatory change for an increased exodus, explaining the failure of K+ to change following lectin treatment.

Biological Transport↗
PubMed1975

A rapid phytohemagglutinin induced alteration in lymphocyte potassium permeability.

The exposure of rat and human lymphoid cells to mitogenic concentrations of phytohemagglutinin resulted in an apparent decrease in cellular K+ without a significant change in cellular Na+ when the cells were washed with isotonic Hepes buffered choline chloride prior to cation determination. The apparent reduction in total cellular Na+ plus K+ concentration, however, was not accompanied by a change in cell volume. We inferred that the constant cell volume could occur only if the lost intracellular K+ was exchanged for an external cation during the washing procedure used to prepare cells for Na+ and K+ measurement. This inference was supported by the quantitative recovery of lost cellular K+ in the choline chloride washing solution and the demonstration that a comparable proportion of 86Rb+ (K+ analogue) 42K+ was lost from prelabelled cells during choline chloride washing. Use of medium 199 with Hanks salts, 150 mM NaCl, or 100 mM MgCl2 as the washing solution did not prevent K+ exchange although exchange was less in the presence of MgCl2. These findings indicate that phytohemagglutinin produces a rapid alteration in lymphocyte plasma membranes so as to allow abnormal K+ exchange. This observation is of importance because investigators who measure intracellular solutes in phytohemagglutinin-treated lymphocytes must consider the possibility of lossduring preparative washes. Also, changes in membrane permeability following phytohemagglutinin treatment may modulate mitogenesis and/or permit the transmission of chemical messages between cells.

Animals↗
PubMed1975

Hereditary complement (C2) deficiency with dermatomyositis.

A 60 year old white man in previous good health presented with a 6 month history of progressive muscle weakness. Clinical and laboratory findings were typical of dermatomyositis. Muscle biopsy confirmed the presence of inflammatory myopathy; deposits of immunoglobulin G (IgG), immunoglobulin M (IgM) or third component of complement (C3) were not detected by immunofluorescence. No evidence was found for an associated neoplasm. An unexpected finding was the total absence of serum hemolytic complement activity. Further investigation revealed that the complement defect was attributable to a selective and total absence of the second component of complement (C2), as determined by both functional and immunoprecipitin assays. Family studies indicated that the defect was inherited in an autosomal recessive manner, as has been observed in the previously reported C2-deficient kindreds. This case demonstrates that typical muscle lesions of dermatomyositis can occur in the presence of a complement defect which would preclude activation of the classic (C1-C4-C2) complement pathway. The case is of further interest as one of a series of recently reported associations of rheumatic diseases with hereditary complement deficiencies. Study of the functional properties of the propositus' C2-deficient serum demonstrated normal generation of chemotactic activity in the presence of endotoxin or aggregated IgG, and normal or near normal bactericidal activity against Salmonella typhi O 901 and Hemophilus influenzae, type b. These findings emphasize the importance of the alternate (properdin) pathway of complement activiation in these functions.

Biopsy↗
PubMed1975

Cation transport and its altered regulations in human stomatocytic erythrocytes.

Cation transport in a population of stomatocytic red blood cells (RBC) is abnormal in the following respects. First, active transport against a gradient, defined as the nonisotopic net accumulation of Na+ or loss of K+ induced by 0.1 mM ouabain, is markedly elevated (7.3 and 6.3 mEq/liter cells/hr for Na+ and K+, respectively), but the Na+:K+ active transport ratio is normal. Apparent uncoupling of the Na+ and K+ isotope transport is due to disproportionately increased ouabain-sensitive 24Na+-23Na+ exchange (32.7 mEq/liter cells/hr), which is measured as a portion of 24Na+ isotope efflux. Second, cation transport is unresponsive to variations in internal Na+ concentration but decreases with decreasing extracellular Na+.

Anemia, Hemolytic, Congenital↗
PubMed1975

Contrasting splenic mechanisms in the blood clearance of red blood cells and colloidal particles.

We have studied the blood clearance and organ uptake of colloidal particles and of antibody-coated and chemically treated Na2 51Cr O4-labeled erythrocytes (RBC) in mice. Hepatic and splenic uptake of both colloidal particles and autologous RBC coated with rabbit antibody were reduced significantly following pretreatment of animals with cortisone acetate. Hepatic removal of RBC previously treated in vitro with N-ethyl-maleimide (NEM) or phenylhydrazine-HCl (PHZ) was similarly depressed by pretreatment with cortisone. In contrast, the splenic uptake of NEM- and PHZ-altered erythrocytes was unaffected by cortisone. Scanning and transmission electron microscopic examination of perfused spleens from PHZ-injected animals demonstrated extensive mechanical trapping of Heinz body-containing RBC in sinus wall apertures, whereas little erythrophagocytosis was observed. These studies suggested that, while clearance of inert particulate matter and of antibody-coated RBC from the blood occurred primarily by a cortisone-suppressible, presumably phagocytic process in the spleen, chemically altered RBC were removed primarily by a cortisone-insensitive filtration process in the splenic microvasculature.

Animals↗
PubMed1975

Hereditary C6 deficiency in man.

An 18-year-old black female (D.B.) in good general health was found to have no hemolytic activity in serum CH50 titrations. Functional assays yielded normal values for all C components except C6. C6 was not detectable in plasma or serum by two different functional assays nor by antigenic analysis using monospecific anti-C6 antibody. Hemolytic activity was restored by addition of functionally pure C6. By specific functional assay, both parents and 5 of 6 available sibs had approximately half-normal serum C6 levels and 1 sib was normal. Biologic properties of D.B. serum include: a) absent bactericidal activity against S. typhi 0 901 with or without added rabbit antibody; b) normal generation of chemotactic activity for human neutrophils in the presence of endotoxin or aggregated IgG; c) ability to sensitize appropriate cells for immune adherence of agglutination by anti-C3 Coombs serum; and d) inability to lyse PNH red cells in either acid hemolysis or "sugar water" tests. An extensive clotting workup by standard methods was within normal limits. These studies document for the first time a human kindred with C6 deficiency. This defect exhibits a classic mendelian autosomal inheritance, with all 3 genotypes being recognizable. Unlike the C6-deficient rabbits studied by others, the homozygous C6-deficient human exhibits chemotactic and coagulation functions within the range of normal.

Adolescent↗