John W. Rebuck

Basophilic granulocytes in inflammatory tissues of man.

The individuality of blood basophilic granulocytes and tissue mast cells and their separate origins have been recognized since their description by E h r l i ~ h l ~ and their definitive delineation by Michels.* Nor has this distinction been effaced by the acquisition of knowledge of the similarity in the functional capacities of the two cell lines as bearers of heparin, histamine, and chymotrypsin.5-17 For 80 years prior to the observation of basophilic leukocytic migrations in man with the application of modern hematologic techniques to the study of the inflammatory tissues, detection of basophilic leukocytes in exudates even in experimental animals was reported only in the isolated investigations of Ringoenls and P1impt0n.l~ RingoeP described a pronounced basophilic granulocytic exudation in the subcutaneous connective tissues of the guinea pig four to eight days after the injection of egg white. The basophilic leukocytes were phagocytic for degenerating heterophilic leukocytes. Loss of metachromatic staining ability was rapidly followed by breakdown of the basophils and scattering of their granulation through the tissues. Plimpton19 produced a similar but biphasic migration of basophilic granulocytes into the subcutaneous tissues of both guinea pigs and rabbits at 45 minutes and again at seven to 10 days after the local injection of Ventriculin, a defatted hog gastric tissue preparation. The preliminary reports of Priest, Rebuck, and their associate^^^-^^ that investigative inflammatory lesions in the skin of patients afflicted with ulcerative colitis were marked by intensive migrations of basophilic granulocytes, have led to further explorations of the inflammatory leukocytic model in patients with ulcerative colitis and additional diversified disease processes but with basophilic leukocytic migrations as their hallmark. The results will be outlined below. Such aberrations of leukocytic defensive parameters in man in his diseased state have taken on added interest with the demonstrations by Shelley and J ~ h l i n ~ ~ ~ ~ of human basophilic leukocytic degranulation as a test for detecting anaphylactic sensitivity to cold, penicillin, bee sting, and prochlorperazine. Nor will the possible parallel behavior of the tissue mast cell in the disruption of the inflammatory processes to be studied be lost sight of.

THROMBOCYTOPENIA AND ABNORMAL BLEEDING IN MULTIPLE MYELOMA

Excerpt During the course of multiple myeloma most patients exhibit a tendency to bleed. Although it may be an early manifestation, the incidence of abnormal bleeding is greater in the more advance...

Periodic neutropenia treated by adrenocorticotrophic hormone and splenectomy; report of a case.

NEUTROPENIA associated with oral ulcers, periodic fever, benign paroxysmal peritonitis and intermittent arthralgia has been observed to occur with cyclic regularity. In 1949 Reimann and de Berardin...

Hyperreactivity to cow's milk in an infant with LE and tart cell phenomenon

LE and tart cells were demonstrated in a black male infant whose serum contained milk-percipitating antibodies and who had pulmonary infiltrates. Immunoblasts, plasmocytoid lymphocytes, and an LE cell were found in a milk-stimulated skin window. The presence of LE cells corresponded to the presence of ENA antibody. Tart cells varied with oral milk challenge. A large Arthus type of skin reaction to injected milk was demonstrated. An oral feeding of milk resulted in a decrease in plasma C3. Lymphocyte transformation resulted from in vitro milk stimulation. ENA (extractable nuclear antigen) antibody and resulting LE cell formation possibly represented the combination of nuclear protein with milk antigen. The pulmonary infiltrates may represent a hypersensitivity pneumonitis characterized by both Arthus and cell-mediated reaction to milk.

A STRUCTURAL STUDY OF RETICULUM CELL AND MONOCYTE PRODUCTION WITH QUANTITATION OF LYMPHOCYTIC MODULATION OF NONMULTIPLICATIVE TYPE TO HISTIOCYTES

Newer concepts of small lymphocyte peripheralization from thymus to the lymphocytic tissues40 and recirculation of small lymphocytes through the lymphocyte-forming t i s s ~ e s ~ ~ ~ ~ support our re-evaluation of the role played by the reticulum cells (histiocytes, reticuloendothelial cells) in lymphocyte formation. That the largest free stem-cell of the lymphocytic tissues (blood-forming reticulum cell, hemohistioblast) divides and gives rise to immature lymphocytes (lymphoblasts and prolymphocytes) which also undergo multiplicative divisions leading finally to large, medium, and small mature-appearing lymphocytes, has been established by classical structural d e r i v a t i ~ n , ’ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ and mitotic computation,“2 and reaffirmed by recent autoradiographic studies (cf. Yoffey,” and the careful studies by the Brookhaven group cited therein). The reticuloendothelial system (histiocytes), as defined by Aschoff and Kiy o r ~ o , * . ~ . ~ ~ included all cells capable of taking up the vital dyes (tyrpan blue and red, lithium carmine, and pyrrol blue). Although the functions of the reticuloendotheiial cells (reticulum cells, histiocytes) are diverse, it is their cytopoietic function, particularly their lymphocytopoietic and monocytopoietic functions, with which this report is concerned. Before studying the structural changes which reticulum cells undergo while transforming to lymphocytes or monocytes (described in RESULTS) it is important to reaffirm that two broad types of structural cellular transformation may occur, not just one. The first, defined by Conklin12 in 1924 and appropriately termed “cellular differentiation,” is that transformation of potential cellular function and general cell structure into specialized functions and structures. In differentiation then, the cell acquires a repertory of responses, reactions, or characteristics different from those of the cell from which it developed, concurrently suffering, however, an irretrievable loss of some of its original potentialities. Examples of such differentiation, or at least its manifestations, are: Hemoglobinization of some of the transformation products of the marrow stem-cell while others, in contrast, elaborate profibrinolysin-containing eosinophilic gran~la t ion .~ The second and newer concept of transformation, introduced by Weissag in 1949, termed “modulation,” defines that type of cellular transformation in which the cells appear to have undergone striking changes in microscopic structural criteria and yet have retained the identity of the original cellular reactions and characteristics. In this connection, Bessis6 cites as an example of modulation the resemblance, after several transplants, of epithelial cells to histiocytes, regardless of the organ from which they have come; yet upon reimplantation to the organism, they revert to the specific properties of the original epithelium. It is interesting that one of the original examples of modulation given by Weiss was the “modulation” of fixed histiocytes into free macrophages, in contradistinction to true differentiation, which implies an irreversible change in constitution. After outlining the multiplicative lymphocytopoiesis from reticulum cell to lymphocyte, it is the purpose of this paper to quantitate lymphocytic modulation

Experimental Production of the L. E. Phenomenon in the Skin of Man.

Summary and conclusions The L.E. cell phenomenon has been produced experimentally in the skin of two normal human volunteers following inoculation of windows with the plasma of a patient with acute disseminated lupus erythematosus. In vivo, under the conditions of our experiments, the neutrophilic L.E. cell usually developed as the result of ingestion of other neutrophilic nuclear lobes or nuclei which had undergone a previous partial peculiar lysis. Less commonly the L.E. cell may represent the originally affected neutrophilic leukocyte in which lobar lysis is out of step in the individual nuclear lobes. The experiments described should provide a means of testing the proposed identity of the L.E. cells and the “hematoxylin staining bodies” of the diseased tissues in acute disseminated lupus erythematosus, an identity recently suggested by several workers (11,12).

Electron Microscopy of Sickle Cells

Summary A modification of the Beck-Hertz technic permits direct mounting of sickle cells for electron microscopy studies. Electron micrographs of sickle cells essentially confirm the findings of Diggs and Bibb and substantiate pertinent optical studies as to structural detail. In addition, both corpuscular hemoglobin-membrane relationships and polar filament structure are further visualized.

Observations on the Gastrointestinal Administration of Bovine Splenic Homogenate on Hematopoiesis in Man.

Excerpt Thirty-two patients with a variety of refractory hematologic cytopenic disorders received bovine splenic (27), renal (2), muscle (1), thymus homogenate (1), and blood (1) by continuous intr...

Inflammatory Cell Dynamics in Man

Inflammation in man is the local response of the human host to any kind of damage whether it be due to trauma, chemical agents, or microorganisms or their products. Its purposes are to eliminate the degenerated portions of the injured cells and tissues, to eliminate the injurious or infective agents, and to repair the damaged site.