John C. Herion

Distribution and Clearance of Circulating Endotoxin.

To elucidate the mechanisms of endotoxin action the distribution and clearance of injected endotoxin were studied in New Zealand white rabbits; some animals were rendered tolerant through successive (5 days) doses of endotoxin (E. coli lipopolysaccharide) and the remainder were nontolerant. Blood and plasma clearance of small doses of chromium-labeled endotoxin was more rapid in tolerant than in nontolerant rabbits. In both groups clearance was nearly complete within 10 minutes after injection. Circulating endotoxin was distributed between plasma and platelets in both non- and tolerant animals. A minimal amount of endotoxin was found in leukocytes by this was believed the result of contaminating platelets.

The Anticoagulant Activity of Lysosomal Cationic Proteins from Polymorphonuclear Leukocytes

A cationic protein fraction from rabbit polymorphonuclear leukocyte lysosomes has been shown to exert a potent anticoagulant effect on human blood in vitro. The anticoagulant activity is detectable in the whole blood clotting time, the recalcification time of platelet-rich plasma, the prothrombin time, the partial thromboplastin time, and the thromboplastin generation test. The lysosomal cationic proteins do not inhibit any of the known specific procoagulants. They appear to inhibit clotting by blocking the formation of intrinsic thromboplastin possibly by interfering with the role of phospholipids in the reaction involving Factors V and X and calcium.

The Procoagulant Activity of Granulocytes

Summary Rabbit granulocytes and human-blood leukocytes (mostly granulocytes) shortened the recalcification time of normal rabbit and human plasmas and human plasmas deficient in Factors VIII, IX, XI and XII but not those deficient in Factors VII and X. While these cells shortened the recalcification time of Factor V deficient plasma they failed to shorten the prothrombin time. Neither did granulocytes shorten the prothrombin time of plasmas deficient in Factors VII and X. Rabbit granulocyte lysosomes resembled the intact parent cells in their effect on normal and deficient plasmas. Rabbit lymphocytes had no detectable procoagulant activity. The minimal procoagulant activity observed with the human lymphocyte suspension may have resulted in part from contaminating granulocytes.

Effect of lysosomal cationic proteins from polymorphonuclear leukocytes upon the fibrinogen and fibrinolysis system

Heterogeneous lysosomal cationic proteins from PMN leukocytes contain substances exhibiting in vitro (1) Anticoagulant activity; (2) Fibrinogen precipitating activity; (3) Fibrin polymerizing-precipitating activity; (4) Plasminogen activator activity; and (5) Direct fibrinogenolytic and fibrinolytic activity. The anticoagulant activity is not blocked by serum or SBTI. The plasminogen activator, stable at acid pH, is blocked by EACA. An acid-labile direct fibrinogenolytic and fibrinolytic activity, stable at neutral pH, is incompletely blocked by the plasmin inhibitor, SBTI.

A method for the study of the incorporation of inorganic radiophosphorus into leukocyte deoxyribonucleic acid

Abstract A modification of the Schmidt-Thannhauser procedure for isolating DNA coupled with a new method for DNA digestion and an adaptation of the Berenblum and Chain method for phosphorus determination have been shown to be suitable for use in studying the incorporation of inorganic P 32 into leukocyte DNA. With these techniques tracer doses as small as 2 μc/kg are permitted. Peak tagging of rabbit leukocytes was found to occur on the fourth day following injection. Disappearance of the label through the tenth day was virtually exponential.

Malignant histiocytosis. A cytochemical and electron microscopic study of an unusual case

A 25‐year‐old black female presented with lymphadenopathy, fever and anemia of two months duration. The diagnosis of malignant histiocytosis was made on the basis of histiocytic infiltrations in the sinuses of spleen, liver and lymph nodes and by the demonstration of erythrophagocytosis in bone marrow. Following splenectomy, the patient developed a leukemic phase with as many as 50 × 109 abnormal histiocytes/1 and bone marrow necrosis. This patient was also atypical because of multiple granulomas in liver, spleen and lymph nodes. Cytochemical and immunofluorescent stains confirmed that the abnormal cells were derived from the monocyte‐macrophage series. Electron microscopy was used to further characterize this abnormal cell population. The electron microscopic and cytochemical evidence confirms that the malignant cells in malignant histiocytosis are derived from monocytes.

Cellular activation of factor IX (christmas factor)

Abstract We have demonstrated Factor IX activation by sonicated polymorphonuclear leukocytes (PMNs). This activation reaction required the disrupted leukocytes, calcium chloride, and a small amount of normal human plasma. The requirement for normal plasma was met by plasma deficient in all of the known coagulation factors, and thus the substance present in normal plasma which facilitates this reaction was not identified. The fact that factor XI deficient plasma supported the reaction as well as normal plasma implied that factor XIa was not involved in this activation. Strontium ions could not substitute for calcium ions in the activation reaction, also implying that factor XIa was not involved. This factor IX activating principle in leukocytes could provide a mechanism for by-passing the contact factors of blood coagulation, thus providing an explanation for the discrepancy in clinical severity between deficiencies of the contact factors on the one hand and hemophilias A and B on the other.

Effect of Phosphate Loading on Leukocyte Labelling with Inorganic P32.

Summary The effect of an intravenous load of non-isotopic inorganic phosphate following P32 on plasma clearance and on leukocyte labelling has been studied. Such a load produces immediate dilution of plasma phosphate activity, decreases rate of clearance of plasma radioactivity during the period of loading, diminishes the level of labelling of circulating leukocyte acid soluble and DNA phosphorus, and prevents development of a peak in DNA-P specific activity. The findings suggest that marrow labelling during the first 2 hours after P32 injection is responsible for development of the peak in DNA-P specific activity found in peripheral blood leukocytes.