Leukokinetic Studies V. Uptake of Tritiated Diisopropylfluorophosphate by Leukocytes.

Abstract

in doses up to 20 mg dissolved in Locke-Ringer solution and injected into the coronary inflow cannula produced only slight. transient depression of contractions and some reduction of rate.Concentrations of panganiic acid up to 6 X 10r4 M did not alter spontaneous contractions of the isolated rabbit ileum. nor did this concentration of drug modify contractions produced by acetylcholine. Our data demonstrate that pangamic acid is not without pharmacologic effect. 11-e have found the LD-50 in mice after intraperitoneal administration to be much lower than the value previously reported for this compound. It has been reported that thiamine hydrochloride possesses neuromuscular blocking activity and that this effect is antagonized by neostigmine methylsulfate(4.5. 6 ) . I t has also been demonstrated that intravenous administration of thiamine hydrochloride produced a transient but marked hypotension with concomitant bradycardia ir! anesthetized dogs. In these respects, pangamic acid produces pharmacological effects not unlike those of thiamine hydrochloride. Circulatory collapse has been reported clinically from intravenous and intramuscular injections of thiamine hydrochloride ( 10). 11-e are not aware of any clinical reports of respiratory depression or severe hypotension resul t ing from administration of pangamic acid. However, it is conceivable that pan-gamic acid could produce undesirable clinical effects under circumstances of overdosage. Sumnz~ry. Pangamic acid (Vit. B-15)possesses definite pharmacologic properties. These include neuromuscular blocking activity in the rabbit and chicken as well as production of hypotension in anesthetized dogs. Neostigmine methylsulfate is an effective antagonist to the neuromuscular blockade produced in the rabbit. These effects appear to be qualitatively similar to those reported for thiamine hydrochloride.The use of radioactive diisopropylfluoro-this laboratory( 1-3). Leukocytes have been phosphate (DFPA2) as a label for leukocytes labeled in vitro and returned to the circulahas been described in previous reports from tion of the donor(2), or they have been la-*This investigation was supported in part by a beled in vivo by administering the DFP32 inresearch grant from Nat. Inst. of Arthritis and travenously ( 1,s ) -During these studies it Metab. Dis., Nat. Inst. Health, U.S.P.H.S. and in was demonstrated that pdymorphonuclear part by U. S. Atomic Energy Commission. (PMN) neutrophils but not lymphocytes are by guest on July 27, 2015 ebm.sagepub.com Downloaded from LEUKOCYTE UPTAKE OF TRITIATED DFP 423 labeled by DFPJ2. It was not possible to determine whether eosinophils, basophils and monocytes are labeled.When leukocytes were labeled in vivo following intravenous administration of DFP32, the blood leukocyte radioactivity curve obtained was complex( 1,3). The shape of the curve suggested that granulocytes in the bone marrow as well as in the circulation were labeled, but that the circulating granulocytes, due to exposure to a higher initial concentration of D F P 2 , were ...

Diisopropylfluorophosphate Uptake by Granulocytopoietic Cells in Chronic Myeloid Leukaemia and in Normal Individuals

“…The present observations differ from those of K urth et al [8] in that promyelocytes showed heavier labelling than myelocytes in normal indi viduals as well as in CML patients. This discrepancy may be apparent rather than real.…”

“…This discrepancy may be apparent rather than real. First, in the study by K urth et al [8] the difference be tween promyelocyte and myelocyte grain counts was only 6% of the peak value. Second, in view of the fact that these authors found it difficult to observe the cytoplasmic granules through the photographic emulsion, some promyelocytes may have been interpreted as myelocytes.…”

“…A lower but rather uniform activity was observed in the more mature forms. The grain count varied considerably between individual cells within each ma turation compartment.Radioactive diisopropylfluorophosphate (DFP) has been used to label granulocytes in kinetic studies, either by intravenous infusion of DFP or in vitro followed by reinfusion of the labelled blood [1,2,[4][5][6][7], From the disappearance rates of labelled cells the intravascular granulocyte half-life has been deduced.The uptake of DFP :!H by granulocyte precursors and mature cells has been investigated in an earlier study by Kurth et al [8]. It was con cluded that myeloblasts showed very little uptake, myelocytes a high up take and the other cell types intermediate relative labelling.…”

Neutrophil Kinetics in Acute Infection*

“…Intravenously administered DF82P labels blood neutrophils, the myelocytes of the bone marrow, and marrow neutrophils more mature than myelocytes (11,12). Promyelocytes and myeloblasts, lymphocytes, eosinophils, basophils, and monocytes are not labeled detectably.…”

The Kinetic Behaviour of Transfused Donor Bone Marrow Neutrophils and their Precursors in Neutropenic Patients

“…3H-TdR labels those cells which are synthesizing DNA at the time of exposure (Cronkite et al, 1959). DF32P labels both mature and immaturc cells with neutrophilic granules (Kurth et al, 1961).…”