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Biomedical subjects

K Zuckerman

Publications and source records attributed to K Zuckerman.

15 recordsLinked to original sources

The effect of diazepam on neonatal seizure: in vivo 31P and 1H NMR study.

It is assumed that when anticonvulsants arrest seizure, there is rapid return of brain high energy phosphates and brain lactate to control values. To test this hypothesis, diazepam was administered to neonatal dogs during flurothyl-induced seizure. In vivo 31P nuclear magnetic resonance spectroscopy disclosed that diazepam quickly arrested electrographic seizure and restored brain phosphocreatine and inorganic phosphate to baseline values. In contrast, in vivo 1H nuclear magnetic resonance spectroscopic measurements showed that arrest of seizure with diazepam did not return brain lactate to control values. The sustained increase in cerebral blood flow and prolonged elevation of brain lactate, acetate, valine, and succinate in the postictal period indicate that metabolic recovery of the brain occurs over an extended period of time after the normalization of EEG, phosphocreatine, and brain pH.

Acetates↗

Large granular lymphocytes from patients with expanded LGL populations acquire cytotoxic functions and release lymphokines upon in vitro activation.

The phenotypic and functional features of purified large granular lymphocytes (LGL) from ten patients with LGL population expansions and cytopenias are described. The predominant LGL phenotypes were T3+, T8+, Leu-11+/-; however, in two patients, LGL expressed a T3-, Leu-11+ phenotype. Variable combinations of other LGL markers (OKM1, Leu-7), and HLA-DR were detected in individual cases. In nine of ten cases, freshly isolated LGL did not exert cytolytic activity for K562 target cells, but purified LGL cultured in the presence of recombinant interleukin 2 (rIL2) acquired potent cytotoxic activity in all cases tested. LGL did not proliferate in response to phytohemagglutinin (PHA). However, LGL released variable amounts of IL2 and gamma-interferon (gamma-IFN) after PHA stimulation. In some cases, stimulation of fresh LGL with recombinant IL2 induced production of gamma-IFN. No correlation was found between the functional capabilities and the original phenotype of the expanded LGL populations.

Antibodies, Monoclonal↗

Stem cell migration induced by erythropoietin or haemolytic anaemia: the effects of actinomycin and endotoxin contamination of erythropoietin preparations.

The injection of erythropoietin or the induction of anaemia with phenylhydrazine leads to changes in murine pluripotent and granulocyte-macrophage stem cells indicating migration from marrow to spleen. In order to evaluate the interrelationship between erythroid differentiation and stem cell migration we have selectively suppressed erythroid differentiation with actinomycin D. Anaemia or EP injection resulted in stem cell changes consistent with migration; actinomycin blocked these changes in anaemic but not EP injected mice while blocking erythropoiesis in both groups. The erythropoietin contained from 0.01 to 1000 microgram/ml of endotoxin as defined by the limulus test; it decreased marrow erythropoiesis and stimulated marrow granulopoiesis. Adsorption of the erythropoietin preparation with limulus lysate removed endotoxin without decreasing erythropoietin activity. Adsorbed erythropoietin stimulated erythropoiesis and not granulopoiesis, and stem cell changes induced by its administration were largely blocked by actinomycin, suggesting that endotoxin in the non-adsorbed erythropoietin caused the actinomycin resistant stem cell changes. The observation that actinomycin blocks both erythroid differentiation and stem cell migration suggests that these two physiologic events are closely linked. The effects of injected erythropoietin on murine haemopoietic stem cells may, to a significant extent, be secondary to the presence of endotoxin in the erythropoietin preparations.

Anemia, Hemolytic↗

The use of stem cell assays to monitor the proliferative potential of bone marrow cells.

A number of assays exist for hematopoietic stem cells in both humans and mice, but the appropriate stem cell assay for the repopulating potential of human marrow is not clear. Two murine models suggest that these assays may not always predict marrow proliferative potential. In vivo diffusion chamber culture growth of CD1 marrow depleted of pluripotent stem cells (CFU-S) by exposure to mouse-brain antisera plus complement was equivalent to or greater than that of normal serum treated control marrow. Furthermore, CF1 mice repeatedly injected with endotoxin had markedly stimulated granulopoiesis with increases in the number of marrow CFU-S and the % in S phase but no changes in the number or proliferative status of marrow CFU-C. However, inbred BDF1 mice chronically injected with endotoxin although also showing striking increases in granulopoiesis had no significant alteration in their marrow CFU-S or CFU-C number or cell cycle status relative to saline injected controls. Both models present examples where conventional stem cell assays do not provide insight into marrow cell production and suggest that in vitro clonal assays of human marrow cells may not always predict for the potential of marrow to repopulate a human transplant recipient.

Animals↗

Inhibition of normal murine hematopoiesis by leukemic cells.

Inhibition of normal mouse hemopoietic stem cells by leukemic cells (C1498) was observed with use of in vitro agar and in vivo diffusion-chamber cultures. The C1498 cells were unresponsive to colony-stimulating activity, and, above a critical threshold, they inhibited normal granulocyte progenitors in agar culture. C1498 cells added to normal marrow in diffusion chambers progressively reduced granulocyte progenitors. The larger, more rapidly growing, C1498 cells showed the most inhibitory effect. Transmembrane culture of C1498 cells adjacent to normal marrow in double diffusion chambers for five to 14 days led to reduction of recovery of granulocyte progenitors (72 +/- 7 per cent of control) and pluripotent stem cells (45 +/- 7 per cent of control) from the normal marrow chambers. These results indicate that leukemic mouse cells inhibit normal mouse-marrow stem cells by releasing a diffusible substance, and this inhibition occurs primarily at the level of the pluripotent stem cell.

Animals↗

Edwardsiella tarda bacteremia.

Presented are two case reports of patients with Edwardsiella bacteremia who survived after chloramphenicol and gentamicin therapy in one case and cephalothin and kanamycin therapy in the other case. Of four previously reported patients, only one survived. One of our two patients presented with subarachnoid hemorrhage associated with bacterial endocarditis and, to our knowledge, this is the first reported case of E tarda endocarditis. The clinical and laboratory features of disease due to this unusual pathogen are reviewed.

Adult↗

Inhibition of intestinal iron absorption by laundry starch.

The pathogenesis of iron deficiency anemia associated with amylophagia is usually attributed to dietary iron lack. However, large quantities of starch may inhibit intestinal iron absorption. Accordingly, studies were carried out to determine the effect of laundry starch on the intestinal absorption of inorganic and hemoglobin iron. In vitro, laundry starch bound 19 to 80% of the available 59FeSO4 and 34 to 68% of the available 59Fe-hemoglobin. Binding of both forms of iron was pH-dependent, with maximal binding at pH 7.0. In vivo, laundry starch significantly inhibited mucosal uptake of 59FeSO4 from isolated duodenal loops. In nonanemic rats, administration of laundry starch (100 mg) 1 hr before a 100-mug dose of 59FeSO4 significantly decreased the absorption of 59FeSO4, as compared to saline or low iron chow controls (6.2 +/- 2.0 versus 14.9 +/- 2.1 and -1.8 +/- 1.7, respectively, P less than 0.001). In anemic rats the absorption of either a 100-mug dose of 59FeSO4 or a 500-mug dose of 59Fe-hemoglobin was also significantly decreased by prior administration of laundry starch. The data obtained indicated that laundry starch (1) binds appreciable quantities of inorganic and hemoglobin iron in vitro; (2) inhibits the mucosal uptake or inorganic iron by isolated intestinal loops; (3) inhibits the intestinal absorption of inorganic iron in normal nonanemic rats, and (4) blunts the compensatory increase in inorganic and organic iron absorption in anemic rats.

Anemia, Hypochromic↗