bluuebunny/crossref_metadata_2025 huggingface dataset:
IgE Myeloma: Total Body Tumor Cell Number and Synthesis of IgE and DNA
Authors: SALMON SYDNEY E. , MCINTYRE O. ROSS , OGAWA MAKIO
Published: October 2019

Studies of myeloma cell DNA and immunoglobulin synthesis and total body tumor cell number were performed on a patient with IgE multiple myeloma and plasma cell leukemia; results were contrasted to similar observations in patients with IgG myeloma. Autoradiographic studies demonstrated significantly greater DNA labeling in the IgE patient’s bone marrow plasma cells than in cells from IgG myeloma patients who did not have leukemic manifestations; an additional patient with plasma cell leukemia also had a high labeling index of the myeloma cells in the blood. The IgE myeloma patient’s molecular synthesis rate for immunoglobulin averaged 26,000 molecules of IgE per minute per myeloma cell, a synthetic rate similar to that found in IgG myeloma. These observations have relevance to the normal immune response, as they can be used to approximate the number of normal IgE- and IgG-producing cells in the body. In the patient with IgE myeloma, the total body myeloma cell number was 2.7 x 1012 cells at the time of study and was of the same order of magnitude as in IgG myeloma; however, the distribution of tumor cells was strikingly different. Serial estimates of tumor cell number were made; such estimates may prove useful in evaluation and treatment of patients with multiple myeloma.
Metabolic Abnormalities of Erythrocytes in Severe Iron Deficiency
Authors: CARD ROBERT T. , WEINTRAUB LEWIS R.
Published: October 2019

Severe iron deficiency was induced in rabbits by repeated phlebotomy and maintenance on an iron-deficient diet. Erythrocytes from these animals were studied at periods of 2-10 wk following the cessation of bloodletting and were found to have a shortened survival in vivo by the 51Cr technique. These cells were found to be more susceptible than normal cells to lysis during sterile 24-hr incubation in glucose-free balanced salt solution. The severely iron deficient erythrocyte also demonstrated an increased susceptibility to sulfhydryl inhibitors in vitro. Iron-deficient erythrocytes, despite their smaller volume, were found to have an impaired ability to filter through 5-µ Millipore filters. These studies suggest the following pathogenesis for the hemolysis seen in severe iron deficiency. The abnormal plasticity may lead to excessive trapping of these cells by the spleen and reticuloendothelial cells. Within this environment these metabolically abnormal cells are exposed to hostile conditions of stasis and glucose deprivation, which may then enhance their lysis.
Studies on Lymphocytes. XVIII. Mechanism of Lymphocytosis Induced by Supernatant Fluids of Bordetella pertussis Cultures
Authors: RAI KANTI R. , CHANANA ARJUN D. , CRONKITE EUGENE P. , JOEL DARREL D. , STEVENS JERRY B.
Published: October 2019

Supernatant fluid from liquid medium cultures of phase I Bordetella pertussis organisms (pertussis supernatant) when given to calves and sheep by intravenous injection produces a marked lymphocytosis. Thoracic duct and splenic vein cannulation was performed in some animals to study the mechanism of production of this lymphocytosis. There was a transient increased mobilization of lymphocytes from the lymphoid organs as seen by the increase in output of lymphocytes from thoracic duct and splenic vein within a few minutes following administration of pertussis supernatant. This was followed by a decrease in the thoracic duct cell output as long as the blood lymphocyte count remained elevated, indicating an inhibition of recirculation of lymphocytes from blood to lymph. There was no evidence of increased new cell production.
Microscopy of Living Bone Marrow In Situ
Authors: MCCUSKEY ROBERT S. , MCCLUGAGE SAMUEL G. , YOUNKER WALDO J.
Published: October 2019

A chamber has been designed to permit chronic microscopic examination of living bone marrow in situ. The amount of metal adjacent to the tissue within the gap of the chamber appears to be critical if normal hemopoiesis is to occur, since excessive metal resulted in the regeneration of a hypocellular, gelatinous marrow. When the amount of metal was reduced, relatively normal marrow regenerated into the chamber. Most frequently this histologically resembled yellow marrow but on occasion highly active marrow was observed. Preliminary examination of the microvascular system confirmed previous reports that sinusoids generally were arranged in interconnecting polygonal networks surrounding individual or clusters of fat and hemopoietic cells. The sinusoids were lined by a definite endothelium. No "intersinusoidal capillaries" were observed.
Cell Cycle Characteristics, Maturation, and Phagocytosis In Vitro of Blast Cells From Patients With Chronic Myelocytic Leukemia
Authors: WHANG-PENG J. , PERRY S. , KNUTSEN T. A. , GART J. J.
Published: October 2019

Cell cycle characteristics, phagocytosis and maturation of immature white blood cells from seven patients with Ph1-positive chronic myelocytic leukemia were studied in vitro. In five patients whose cells contained only one Ph1 chromosome there were two in early stable phase, one in transitional phase, and two in blastic crisis. The other two patients had cell lines with more than one Ph1 chromosome in addition to cells containing one Ph1 chromosome. Cell cycle times in the seven patients as determined with tritiated thymidine ranged from 48 to 59 hr regardless of stage of the disease with one exception (32 hr in a patient who died within 1 wk). A small percentage of myeloblasts was arrested in early S or G2 for the duration of the study of up to 1 wk. Maturation in vitro was observed with appearance of the first labeled metamyelocytes at 2 hr and first labeled mature segmented and nonsegmented neutrophils at 10 hr (with the median time of 22 hr of in vitro culture). Results of this study suggest that cell precursors in blastic transformation have a diminished capability to mature despite the early presence of mature neutrophils in vitro. Early appearance of labeled mature neutrophils and irregularity of the time sequence are characteristic of cells from patients in blastic transformation. Immature granulocytic precursors were shown capable of phagocytosis in vitro, suggesting that although nuclear maturation was delayed, membrane and cytoplasmic function was intact. This dissociation may be characteristic of leukocytes from patients with chronic myelocytic leukemia.
A New Variant of Hereditary Hemolytic Anemia With Stomatocytosis and Erythrocyte Cation Abnormality
Authors: MILLER DENIS R. , RICKLES FREDERICK R. , LICHTMAN MARSHALL A. , LA CELLE PAUL L. , BATES JONATHAN , WEED ROBERT I.
Published: October 2019

A new variant of congenital hemolytic anemia associated with stomatocytosis, reticulocytosis, decreased osmotic fragility, type I autohemolysis and shortened erythrocyte survival without specific splenic sequestration was discovered in three siblings of Swiss-German ancestry. Increased intracellular sodium (two to three times normal) and slightly decreased intracellular potassium were detected. Total sodium efflux was eight-fold greater than normal but total potassium influx was normal and ouabain-sensitive potassium influx was decreased. The ouabain-sensitive sodium efflux: potassium influx ratio was 26:1 rather than the 3:2 ratio noted in normal cells. The consanguineous parents, four other siblings, and 44 other family members had mild stomatocytosis, reticulocytosis, and, when studied, decreased osmotic fragility, increased autohemolysis, intermediate abnormalities of cation content, cation flux, and moderate shortening of erythrocyte survival. Autosomal dominant inheritance was suggested. No abnormalities of RBC enzymes, hemoglobin or lipids were observed. No abnormalities of membrane protein were detected on acrylamide gel. Substrate depletion of these hypermetabolic cells resulted in intracellular dehydration with potassium loss in excess of sodium gain and decreased deformability. Although the exact nature of the defect responsible for hemolysis is unknown, this syndrome differs from other hereditary hemolytic anemias associated with stomatocytosis.
Aminoacyl Transfer RNA Profiles in Human Myeloma Cells
Authors: FUJIOKA SEITOKU , GALLO ROBERT C.
Published: October 2019

Comparative studies of aspartyl-, leucyl-, seryl- and tyrosyl-tRNA by a reverse phase column co-chromatography have been performed between a human normal lymphoblast cell line (RPMI 1788) and a human myeloma cell line (RPMI 8226). The cell lines were derived from normal peripheral blood and peripheral blood of a patient with multiple myeloma and produce IgM and lambda-type light chain (Bence Jones protein), respectively. Similar chromatographic patterns were obtained for leucyl- and seryl-tRNA. Minor differences in aspartyl-tRNA and larger differences in tyrosyl-tRNA were observed.
The Separation and 51Chromium Labeling of Human Lymphocytes With In Vivo Studies of Survival and Migration
Authors: HERSEY PETER
Published: October 2019

This study looks at the application of 51Cr labeling of lymphocytes as a method of obtaining in vivo information about the lymphocyte in human beings. Lymphocytes were separated from whole blood by methods based on isopycnic and rate zonal centrifugation techniques and the conditions for 51Cr uptake by the separated lymphocytes standardized to enable a known amount of radioactivity to be injected into the subjects under study. The uptake of the label into various sites in the body was studied by the means of surface probes linked synchronously to a digital printout device and the survival in the circulation estimated by scintillation counting of blood samples taken at various times after injection of the label. The in vivo studies of survival and migration in 10 normal subjects show an initial rapid clearance of cells from the circulation associated with an uptake of cells into spleen and liver sites, and to a lesser extent, into sites over bone marrow and the abdomen. Survival of the circulating lymphocytes after this period appears to be relatively short, with a half-life of 1.7 days. As the available evidence suggests, this short life may be due to the differential trapping of short-lived lymphocytes in the circulation at the expense of the long-lived lymphocytes. Kinetic interpretations of the data indicate an inverse exponential uptake of cells into the sites studied, and the decline over the organs appears to follow the death rate of the cells in the body as a whole. Comparisons with studies in patients having chronic lymphatic leukemia show a relative inability of leukemic lymphocytes to leave the circulation and enter some sites in the body. These preliminary studies indicate the potential of 51Cr labeling as a useful clinical research tool in the study of lymphocytes in human beings.
Interrelationship of Rheumatoid Arthritis, Folic Acid, and Aspirin
Authors: ALTER HARVEY J. , ZVAIFLER NATHAN J. , RATH CHARLES E.
Published: October 2019

Decreased serum folate (FA) levels were detected in 71% of 51 patients with rheumatoid arthritis (RA). Of 11 patients studied more intensively, only one fulfilled the usual hematologic criteria for FA deficiency. All, however, demonstrated an abnormally rapid plasma clearance of tritium-labeled pteroylglutamic acid (3HPGA). "Binding" of 3HPGA was evaluated by dialysis to apparent equilibrium and found to be significantly reduced in the sera of patients with RA. Common to all these patients was the ingestion of aspirin (ASA). Four RA patients not taking ASA had normal 3HPGA "binding". The 3HPGA "binding" of RA sera decreased as these patients were given increased ASA dosage and vice versa. The in vitro addition of ASA to normal sera reduced "binding" to the level detected in RA sera. Progressive increases in ASA resulted in progressive decreases in "binding". Aspirin given to three normal subjects reduced 3HPGA "binding" in all and serum FA in two. Precedents for ASA-induced structural change in binding proteins and for the relation between decreased binding and lowered serum levels are discussed. It is suggested that the low serum FA concentration and rapid plasma clearance of 3HPGA in RA might reflect ASA-induced alterations of FA binding, resulting in a redistribution rather than deficiency of this vitamin.
Colony Growth of Human Leukemic Peripheral Blood Cells In Vitro
Authors: ROBINSON WILLIAM A. , KURNICK JOHN E. , PIKE BEVERLEY L.
Published: October 2019

The colony-forming potential of peripheral white blood cells from patients with acute leukemia on normal human peripheral WBC feeder layers has been studied. White blood cells from 12 of 20 patients with acute granulocytic leukemia gave rise to large numbers of colonies, while WBC from eight patients with AGL, four patients with acute lymphocytic leukemia and three patients with acute stem cell leukemia gave rise to no colonies or only small numbers. Colonies formed from WBC of patients with AGL appear to go through a process of morphologic maturation to segmented granulocyte forms. Leukemic WBC will not serve as feeder layers in this system, but are not inhibitory in this respect. The significance of these findings is discussed.
The Adsorption of Intrinsic Factor Concentrate to Glass: Occurrence and Prevention With Reference to Radioisotope Dilution Assays of Vitamin B12
Authors: NEWMARK PETER , PATEL NANU
Published: October 2019

Adsorption of IFC-B12 onto glass surfaces has been demonstrated at pH 4.0, 0.02 I, and has also been indicated under the conditions commonly occurring during the radioisotope dilution assay of vitamin B12 levels by methods that use IFC. The addition of albumin prevents adsorption of IFC onto glass and it is suggested that this explains the reported necessity for adding albumin or other proteins to "IF control tubes" in such assays.
Changes in Blood Lymphocyte Cytoplasmic Refractive Index Following Skin Grafting in Rabbits
Authors: Laaveg S. , Metcalf W. K.
Published: October 2019

A technique for measuring the refractive index of the cytoplasm of the circulating blood lymphocytes of rabbits is described. This parameter is remarkably constant in normal animals but shows a significant rise following the application of skin homografts, but not of skin autographs, in rabbits. The rise in refractive index reaches or exceeds the extreme normal range between the third and fifth day after application of the graft, with rejection coming on the tenth day. It is suggested that this technique is worth further investigation as a possible early predictor of graft rejection.
δ-Aminolevulinic Acid Synthetase Activity in Human Plasma: Relation to Erythropoiesis and Evidence of Induction in Erythropoietic Porphyria
Authors: MIYAGI KEN , WATSON C. J.
Published: October 2019

Measurement of δ-aminolevulinic acid synthetase (ALA-S) activity in human plasma has been carried out with samples from normal individuals, cases of erythropoietic porphyria (EP) and erythropoietic protoporphyria (EPP), and of the three principal forms of hepatic porphyria—acute intermittent porphyria, variegate porphyria, and porphyria cutanea tarda. The method of measurement depends on formation of 14C-ALA when the plasma is incubated with 14C-succinic acid, succinyl-Co A synthetase, glycine, and other essential substances. The normal samples, as well as those from the hepatic porphyria cases, had small but significant activity of the same extent; those from the erythropoietic group showed consistently higher values, especially in the two cases of congenital type. A remarkably high value in one of these cases in which there was outspoken erythropoiesis was believed to be related to the presence of many fluorescing normoblasts in the peripheral blood. Following multiple transfusions these disappeared concomitantly with striking reduction of the porphyria. The plasma ALA-S activity declined to 1.4% of the pretransfusion value. These results are considered in respect to the question of induction of ALA-S in the developing red cells of the disease, special attention being given to the minor increase of ALA-S activity in the plasma of a nonporphyric individual whose peripheral blood contained large numbers of circulating normoblasts.
Variability of Proliferative Patterns in Acute Lymphoid Leukemia of Children
Authors: Wagner Hans P. , Cottier Hans , Cronkite Eugene P.
Published: October 2019

Proliferative patterns of neoplastic bone marrow in five children with untreated acute lymphoid leukemia (ALL) were studied radioautographically using a combined analysis of labeling indices and median grain counts of blast cells in mitosis and in interphase as a function of time after a single intravenous injection of 3H-thymidine. The results are interpreted as follows: (1) In at least two cases, a considerable fraction of initially labeled large blasts immediately reentered another cell cycle on completion of mitosis, as evidenced from periodicities of mitotic labeling curves. The relative number of immediately recycling cells varied from patient to patient. In all cases a certain percentage of cells following division passed through a nonproliferative phase of variable duration characterized by a small nuclear size. (2) The time parameters of the mitotic cycle of leukemic blasts differed from patient to patient, although the generation times of immediately recycling cells were close to 50 hr (47-55 hr) in at least three cases. The duration of S phase varied between approximately 20 and 40 hr. Best estimates for the duration of G2 + ½ M ranged from 3 to 7 hr, and for mitotic time from 0.5 to 1.6 hr. (3) Leukemic bone marrow cells in all five cases of ALL had longer generation times than any nonneoplastic lymphopoietic or hemopoietic cell line of man investigated so far. (4) A continuous reentry of small leukemic blast cells into a proliferative phase and a concomitant increase in nuclear size occurred in all cases studied, thus confirming previous results obtained by other authors. Possible reutilization of label and its implications with regard to interpreting cytokinetic data in ALL are discussed.
Origin and Recovery of Colony-forming Units in Locally Curetted Bone Marrow of Mice
Authors: Knospe William H. , Gregory Stephanie A. , Husseini Salah G. , Fried Walter , Trobaugh Frank E.
Published: October 2019

Histologic study of locally curetted bone marrow showed a sequence of blood clot formation, displacement of the clot by a primitive reticular tissue, and hematopoietic regeneration. Histologic regeneration of sinusoidal vessels, and recovery was incomplete 12 wk later with increased fat, residual trabecular bone, and cystic areas. Recovery of colony-forming units (CFU) paralleled hematopoietic cellular recovery and did not exceed levels of 70% of normal by 12 wk postcurettage. Transplantation of cureted and irradiated mice with T6T6 marker chromosomes demonstrated that cells with marker chromosomes migrated readily into irradiated marrow but were excluded from the curetted marrow for 2 wk after curettage. Three weeks after, curettage marker cells gained ready access to curetted marrow. The early exclusion but later appearance of transplanted marker cells was correlated with the early absence and later regeneration of sinusoidal vessels. The histologic and cytogenetic studies support the concept of a dependence of hematopoiesis upon a sinusoidal system with an appropriate marrow microenvironment. These studies support the concept of a local origin of marrow regeneration within curetted cavities but do not indicate whether the hematopoietic tissue originates from small numbers of residual CFU surviving curettage or from multipotential reticular cells. There was no evidence of a stimulatory effect upon uncuretted marrow by the action of curettage.
Studies on Red Cell Aplasia. III. Treatment With Horse Antihuman Thymocyte Gamma Globulin
Authors: Krantz Sanford B.
Published: October 2019

A case of pure red cell aplasia, which did not respond to corticosteroids, splenectomy, or cyclophosphamide, has been described. In vitro studies performed with the patient’s marrow showed a much smaller response to erythropoietin than that observed with previous patients who did respond to cyclophosphamide. The patient’s plasma and γG-globulin fraction inhibited the rate of heme synthesis of normal marrow cells in vitro. The γM-globulins did not inhibit heme synthesis in the same system. The patient was treated with cyclophosphamide and horse antihuman thymocyte gamma globulin (HAHTGG) and had a definite increase in red cell production, but a severe febrile reaction occurred that prevented further use of the HAHTGG. This study indicates that HAHTGG may be of aid in treating severe cases of red cell aplasia when more effective means of minimizing hypersensitivity reactions are devised.
Cell Migration Inhibition in Human Lymphomas Using Lymph Node and Cell Line Antigens
Authors: Braun Marta , Sen Luisa , Bachmann Alois E. , Pavlovsky A.
Published: October 2019

In an attempt to demonstrate in vitro reactions against autologous and allogenic lymph node (LN) extracts in lymphoma patients, 15 cases were studied using as controls two normal LN extracts and leukocytes from 17 blood donors. The techniques applied were migration inhibition tests carried out directly on peripheral leukocytes and indirectly using lymphocyte culture supernatants on guinea pig peritoneal macrophages. The antigens (Ag) used were partially purified saline extracts of neoplastic LN, cultured neoplastic cells of lymphosarcoma (LS) origin, and normal LN. It was observed that autologous LN extracts elicited migration inhibition in the four cases of LS studied and in four out of six cases of Hodgkin’s disease (HD), while normal LN extracts gave negative results in these patients. Positive reactions were observed in four out of six LS cases using allogenic LS extracts, either from LN or from cell lines. No cross-reactions could be demonstrated in HD. All Ag gave negative results with leukocytes from normal blood donors. The positive autologous reaction suggests the presence of a tumor Ag in neoplastic LN, while the immunologic cross-reaction between some of the LS patients would point to a common Ag, persisting in at least one of the LS cell lines and perhaps related to a virus.
Oxygen Affinity in Hemoglobin Köln Disease
Authors: de Furia Frank G. , Miller Denis R.
Published: October 2019

Oxygen affinity studies in a splenectomized patient with sporadically occurring Hb Köln disease revealed high whole blood oxygen affinity (P50 O2 17.6 mm Hg) with increased 2, 3-diphosphoglycerate (DPG), low ATP, and normal RBC ΔpH. Isolated electrophoretically slow migrating Hb Köln had a high oxygen affinity, decreased Hill’s number, and normal DPG reactivity. Functional evidence for hybrid tetramers with normal mobility is presented. Partial deoxygenation may play a role in the denaturation of the Hb Köln molecule and thus account for a higher oxygen affinity (low P50 O2), measured by the mixing technique, than the actual values for P50 that exist in vivo. Increased oxygen affinity and decreased P50 O2 would result in increased erythropoiesis and account for a well-compensated hemolytic process in this patient with a normal red cell mass and normal values of hemoglobin.
Surface Immunoglobulins of Circulating Lymphocytes in Mouse Plasmacytoma. I. Characteristics of Lymphocyte Surface Immunoglobulins
Authors: Yakulis Vincent , Bhoopalam Nirmala , Schade Sylvia , Heller Paul
Published: October 2019

A large proportion (24-45%) of circulating lymphocytes of normal BALB/c mice was found to have surface immunoglobulins with polyclonal characteristics. Following implantation with plasmacytoma, the percentage of these normal receptor-carrying lymphocytes (RCL) was found to decrease. Concomitant with the growth of the tumors, the proportion of lymphocytes having receptors with the structural properties of the specific plasmacytoma globulin gradually increased. The antisera with which these new surface structures were demonstrated were specific for the variable portion of the Fab fragment, the idiotypic determinant of the plasmacytoma globulin. These antisera were not only raised in rabbits and rendered antiidiotypic by appropriate absorptions, but also in BALB/c mice. Evidence is presented that this alteration of receptors on the normal lymphocytes depends on the presence of tumor cells and is not caused by nonspecific absorption of the immunoglobulins to the lymphocytes.
Surface Immunoglobulins of Circulating Lymphocytes in Mouse Plasmacytoma. II. The Influence of Plasmacytoma RNA on Surface Immunoglobulins of Lymphocytes
Authors: Bhoopalam Nirmala , Yakulis Vincent , Costea Nicolas , Heller Paul
Published: October 2019

Circulating lymphocytes of plasmacytoma-carrying BALB/c mice were found to lose their normal surface immunoglobulins; in their place surface structures characteristic of the specific plasmacytoma globulin were demonstrated by the immunocytoadhesion technique. These changes were experimentally reproduced by the incubation of normal BALB/c lymphocytes with an RNA preparation obtained by hot phenol extraction from the excised plasmacytomas. RNA treated by RNAse was inactive, while DNAse or trypsin had no inactivating effect. Lymphocytes, killed with heat or KCN, underwent no alteration of surface receptors following incubation with the tumor RNA. Plasmacytoma RNA, injected intraperitoneally into normal mice, also altered the reactivity of circulating lymphocytes. These observations suggest the possibility that this effect contributes to the functional impairment of the immune system in this disease.
DNA Synthesis in Chronic Myelogenous Leukemia Cells: Comparison of Results in Cells Containing Folate Binding Factor to Replicating Cells Without Binder
Authors: daCosta Maria , Rothenberg Sheldon P. , Kamen Barton
Published: October 2019

Some chronic myelogenous leukemia (CML) cells contain a factor with binding determinants for folic acid (PGA), dihydrofolic acid (FH2) and methotrexate (MTX). To determine whether this factor may have some effect on DNA synthesis and the pharmacologic activity of the folate antagonists, the effect of deoxyuridine (dU), PGA, FH2, and MTX, on the incorporation of 3H-dU and 3H-thymidine (3H-TdR) into DNA was compared in short-term cultures of CML cells containing a high and low concentration of binder and in bone marrow cells with no binder. The following observations were made in CML cells with high binder: greater inhibition of 3H-dU incorporation into DNA by 102 pmoles of stable dU; lesser or no stimulation of 3H-dU incorporation into DNA by FH2 and PGA; inhibition rather than stimulation of 3H-TdR incorporation into DNA by FH2, PGA, and MTX; and reversal of these effects when this CML patient was given oral PGA and unsaturated binder concentration in the cells decreased. These findings suggest that the presence of a high concentration of unsaturated folate binder in replicating cells can affect the capacity for de novo DNA synthesis, probably by binding FH2. In addition, because of binding determinants for MTX, the pharmacolgic activity of this drug can also be altered.
Daunorubicin Metabolism in Acute Myelocytic Leukemia
Authors: Huffman David H. , Bachur Nicholas R.
Published: October 2019

Daunorubicin reductase is a cytoplasmic enzyme that converts daunorubicin to a principal metabolite, daunorubicinol, in the presence of NADPH. This enzyme, found in mammalian tissues and studied in rat tissue preparations and normal human blood components, is also present in human leukemic myeloblasts. The enzymes from both normal and leukemic leukocytes require NADPH for activity, have similar kinetics and substrate saturation characteristics, and have a Km, of 1.7 x 10-4M. When daunorubicin reductase levels in leukemic myeloblasts are related to the clinical response to daunorubicin therapy, we find that patients with a high enzyme level respond favorably to daunorubicin therapy with either a complete or partial remission, whereas those patients with a lower enzyme level experience either no response or die during therapy. These observations suggest that the level of daunorubicin reductase in the leukemic myeloblast may be important in determining the susceptibility of that cell to daunorubicin. Moreover, the measurement of daunorubicin reductase level may have prognostic value regarding the clinical response to daunorubicin therapy.
Effect of Heinz Bodies on Red Cell Deformability
Authors: Lubin Alan , Desforges Jane F.
Published: October 2019

Decreased deformability of acetylphenylhydrazine-treated erythrocytes, measured by in vitro filtration experiments, was found to parallel Heinz body formation. The decreased deformability seemed unrelated to methemoglobin formation, ATP depletion, red cell size, or membrane effect. Hemolysis of Heinz body erythrocytes occurred during filtration of severely damaged cells, in an all-or-none fashion. In mixtures, separation of untreated cells from Heinz body-containing erythrocytes could be accomplished by filtration. There may be a relationship of these filtration properties to intravascular, in vivo destruction of severely damaged cells in Heinz body anemias.
Correspondence
Authors: CROSBY WILLIAM H.
Published: October 2019

In Correspondence by William H. Crosby (Blood: No. 2, February, 298, 1971), "iron absorbed from bread by patients with hemochromatosis" should read "iron absorbed from the total diet of patients who have undergone treatment of hemochromatosis."
Fatalities During Remission of Childhood Leukemia
Authors: Simone Joseph V. , Holland Elizabeth , Johnson Warren
Published: October 2019

The purpose of this study is to determine the frequency, causes, and circumstances of death during remission of childhood leukemia and to delineate predisposing or contributing factors. While overall mortality has decreased, the frequency of remission fatalities at this institution has increased progressively to l6% of all children dying with acute lymphocytic leukemia. This increase coincides with more aggressive therapy, longer remissions and survival, and a larger patient population at risk. The primary causes of death were nonbacterial infections in 23 of the 26 children. Pneumocystis carinii, herpesviruses, cytomegalovirus, and fungi were the principal microorganisms. All but two patients had received intensive combination chemotherapy, and 20 of 26 had received radiotherapy. All patients had experienced hematologic and other toxicity, but severe leukopenia and granulocytopenia did not correlate with the onset of terminal illness. A frequent side effect of therapy was failure to gain weight. Most patients had potentially fatal infections prior to the terminal illness. Despite complete clinical remission for at least 1 mo before death, leukemia was found at autopsy in nine of 20 patients.
Cellular Differentiation in a Murine Myelomonocytic Leukemia
Authors: Cline M. J. , Metcalf D.
Published: October 2019

Mouse peritoneal macrophages and macrophages derived from normal bone marrow progenitors in vitro possess surface receptors whose predominant specificity is directed toward the IgG2a subclass of IgG moleclues. Myelomonocytic leukemic cells also possess such IgG receptors but in an abnormally low frequency and without demonstrable subclass specificity. Within the leukemic population, monoblasts are distinguished from myeloblasts by their greater adhesiveness to glass, higher frequency of cells with surface receptors for IgG, and by erythrophagocytosis. Leukemic monoblasts, myeloblasts, and their morphologically mature progeny demonstrate impaired phagocytic ability. A concept of the development of surface receptors for IgG in the monocyte-macrophage cell line is presented.
Similarities of the Erythrocytes in Juvenile Chronic Myelogenous Leukemia to Fetal Erythrocytes
Authors: Maurer Helen S. , Vida Loyda N. , Honig George R.
Published: October 2019

A 4-yr-old boy was studied who showed typical findings of juvenile chronic myelogenous leukemia, including massive hepatosplenomegaly, thrombocytopenia, low leukocyte alkaline phosphatase, and absence of a Philadelphia chromosome. The erythrocytes of the patient exhibited many characteristic features of erythrocytes of newborn infants: the fetal hemoglobin concentration was greatly elevated (72%); the oxygen dissociation curve of the whole blood was displaced to the left of the curve from normal adult blood; the hemoglobin A2 level and the erythrocyte I antigen titer were reduced; and a structural analysis of the γ-chain of the fetal hemoglobin showed the glycine to alanine ratio in γ-136 to be typical of the neonatal pattern. These findings support the suggestion that juvenile chronic myelogenous leukemia is accompanied by reversion to a fetal pattern of erythropoiesis.
Macroglobulinemia: An Analysis for Forty Patients
Authors: MacKenzie Malcolm R. , Fudenberg H. Hugh
Published: October 2019

Forty patients with Waldenström’s macroglobulinemia were evaluated for criteria of diagnosis, clinical presentation and course, response to therapy, and appropriateness of the classification primary or secondary. A wide spectrum of presentations, course, and complications were present. Thus, the major criteria for diagnosis was a monoclonal IgM serum protein abnormality present in concentrations greater than 1 g/100 ml. Clinical manifestations included weight loss, mucous membrane bleeding, presence of abnormal masses, lymphadenopathy, hepatosplenomegaly, peripheral neuropathy, and central nervous system abnormalities. A high incidence (60%) of associated malignancy was noted. The hyperviscosity syndrome was a frequent complication (33%). Alkylating drugs were successful in inducing remission in approximately 40% of the patients. Plasmapheresis was uniformly successful in relieving hyperviscosity. It was found that attempts to classify patients as primary or secondary frequently proved in error with long-term observation and as such should be discarded. Hypotheses of etiology are discussed and include the IgM proteins as: markers of a malignant lymphoid line, antibodies to microscopic or submicroscopic organisms related (or not related) to tumor induction, and antibodies to tumor-specific antigens. Firm evidence for any of these possibilities is not available.
RESULTS OF THERAPY OF ERYTHROBLASTOSIS WITH EXCHANGE TRANSFUSION
Authors: WIENER ALEXANDER S. , WEXLER IRVING B.
Published: October 2019

1. In the authors’ technic of exchange transfusion, citrated blood is introduced into the saphenous vein at the ankle and the infant’s blood simultaneously withdrawn from the radial artery at the wrist, coagulation being prevented by the administration of small amounts of heparin. The procedure besides being simple, is safe, there having been no operative mortality in more than 40 transfusions.

2. The results of exchange transfusion therapy in erythroblastosis in our first 28 cases are presented. Of these 28 cases, 16 were very severe and almost certainly would have been lethal if left untreated, 6 were of moderate severity, and 6 were mild. Only 7 of the infants died, and the available data indicate that the mortality would have been at least twice as high had the usual treatment with simple transfusions been given.

3. Aside from its greater efficacy in reducing mortality, exchange transfusion is more efficient, so that supplementary treatment is not required as a rule.

4. Fresh blood should be used instead of bank blood because of its greater survival time and smaller likelihood of introducing infection.

5. All infants who have survived have developed normally both physically and mentally and have shown no sequelae of liver or brain damage.

6. The most reliable index of the severity of the disease in the erythroblastotic infant is provided by antenatal titrations of the maternal univalent Rh antibodies, as well as by tests for the presence of univalent antibodies in the infant’s blood.
THE CHAIN REACTION OF THE BLOOD CLOTTING MECHANISM IN RELATION TO THE THEORY OF HEMOSTASIS AND THROMBOSIS
Authors: MILSTONE J. H.
Published: October 2019

Detailed evidence has been accumulating that at least one chain reaction occurs during the coagulation of blood. Both the metamorphosis of platelets and the development of thrombokinase appear to be involved. The autocatalytic effect may serve a function in making possible the growth of a hemostatic plug. It also offers advantages in the physiologic control of the clotting mechanism. It is likely that the chain reaction occurs in most instances where a thrombus forms, and plays some part in its propagation.

The chain reaction is a potentially explosive phenomenon which demands an adequate countermechanism. With materials derived from blood, reactions have long since been demonstrated which can reduce thrombokinase activity, inactivate thrombin and liquefy fibrin. These reactions may help to maintain the fluidity of the circulating blood by removing the products of smoldering clotting reactions.

Such effects could help to delimit the growth of a hemostatic plug, or to end the propagation of a thrombus.

While it is now possible to correlate in this way the data on blood coagulation with present knowledge of hemostasis and thrombosis, critical gaps in our understanding still remain.
TUBERCULOUS SPLENOMEGALY WITH THE HYPERSPLENISM SYNDROME
Authors: MEREDITH H. C. , EARLY J. Q. , BECKER WALTER
Published: October 2019

A case of tuberculous splenomegaly with leukopenia and anemia following miliary tuberculosis has been presented. Splenectomy was required after streptomycin failed to control the cytopenias, progressive emaciation, and splenic infection. However, following what appeared to be six weeks of marked improvement, the patient developed a fulminating tuberculous meningitis and died.
HEINZ BODY PHENOMENON IN ERYTHROCYTES
Authors: WEBSTER STEWART H.
Published: October 2019

Certain morphologic changes in the erythrocytes, first described accurately by Heinz in 1890, have been noted by many investigators both in experimental animals and in man. These Heinz bodies, called by various names, appear to be newly formed particles originating either from the protoplasm or the membrane of the red blood cells in the course of irreversible injury by a toxic agent. The chemical nature of these particles is uncertain but they appear to consist largely of denatured proteins. They may occur in the blood in the absence of methemoglobin or sulfhemoglobin and without anemia, these phenomena being independent of each others. Removal of these bodies from the blood stream is frequently accomplished by their destruction in the spleen, often with resulting increase in size of this organ.

From the staining characteristics of Heinz bodies it is usually possible to distinguish them from other similar particles and to measure them quantitatively. Little is known of the relationship of chemical constitution of toxic substances to Heinz body formation. The indications are that some inorganic substances are capable of inducing this action as well as many aromatic nitro and amino compounds.

The presence in the blood stream of significant amounts of Heinz bodies is evidence of some injury to the erythrocytes. If this injury is severe it may lead to marked hemolysis and anemia.

Clinical cases of Heinz body occurrence in man, due either to drugs or to industrial poisoning, are cited and the need for further work and especially for Heinz body evaluation in routine hematologic examinations is pointed out. A bibliography is included in this review of the literature covering the chief contributions to work on Heinz bodies.
AN EVALUATION OF STERNAL ASPIRATION AS AN AID IN DIAGNOSIS OF THE MALIGNANT LYMPHOMATA
Authors: COOPER TALBERT , WATKINS CHARLES H.
Published: October 2019

Neither diagnostically significant features nor consistent abnormalities of other character were demonstrated in the specimens of sternal marrow obtained in 15 cases of Hodgkin’s disease. With improvements in technic, particularly in patients presenting clinical evidence of bone or bone marrow involvement, the procedure might become more valuable.

As an aid in diagnosis in cases of obscure malignant lymphoma, sternal aspiration is likely to prove of greatest value in cases of lymphosarcoma. In 7 of 10 proved cases, abnormal lymphocytic cell types were encountered and in 3 instances bone marrow infiltrations were demonstrated in fixed section preparations. The latter were felt to be diagnostic of lymphosarcoma.

In 2 cases of follicular lymphoma the specimens of sternal marrow presented no striking abnormalities. However, because of the apparently close relationship which this disease bears to lymphosarcoma it is felt that study of a larger number of cases may prove the procedure of some diagnostic value.
MEGAKARYOCYTES IN NORMAL AND IN THROMBOCYTOPENIC INDIVIDUALS
Authors: DE LA FUENTE VICTORINO
Published: October 2019

The megakaryocytes in 5 normal and 20 thrombocytopenic individuals were studied. The stages ofdevelopment undergone by the cells were delineated and a new classification, according to maturation and function, was made.

Using this classification, the megakaryocytic reactions in the 20 cases of thrombocytopenia were grouped into three distinct types. The first is characterized by a rapid multiplication of cells and a marked inhibition of platelet-formation without change in the process of maturation. The second is similar to the first with this exception that the total number of cells is not increased. The third reaction shows a normal or low total number of cells, with inhibited platelet-formation and accelerated maturation.

From the collected facts, the following conclusions are inferred: (1) The factors of maturation and of platelet-production affecting the megakaryocytes are different. (2) Certain diseases may disturb either of the two processes or both. (3) The number of platelets in the circulating blood is directly related to the percentage of megakaryocytic "C" cells in general. (4) Lesions affecting the spleen usually check the fragmentation of platelets from the megakaryocytic cytoplasm. (5) Infection and primary blood disorders may cause changes in the megakaryocytes but the explanation for this is still to be investigated.
THE EFFECT OF THE PARENTERAL INJECTION OF EPINEPHRIN ON LEUKOCYTE COUNTS IN NORMAL SUBJECTS AND IN PATIENTS WITH ADDISON’S DISEASE
Authors: GABRILOVE JACQUES L. , VOLTERRA MARIO , JACOBS MILDRED D. , SOFFER LOUIS J.
Published: October 2019

Ten normal subjects and 11 patients with Addison’s disease were studied as to their leukocyte response following the subcutaneous administration of epinephrin. The pattern of response was found to be similar in both groups, diphasic curves being noted. In general, the patients with Addison’s disease differ from normal individuals in having: (1) a lower and less labile white count, (2) a lower and less labile neutrophile count, (3) a higher lymphocyte count, (4) a slightly lesser percentage fall in absolute number of lymphocytes, and (5) a higher lymphocyte percentage.

The use of this method to demonstrate adrenal cortical destruction is not feasible with the dosage of epinephrin employed in this study.
STUDIES OF BLOOD PASSED THROUGH AN ARTIFICIAL KIDNEY
Authors: DE LEEUW NANNIE K. M. , BLAUSTEIN A.
Published: October 2019

1. In vitro blood studies using the artificial kidney are discussed in detail.

2. In vitro experiments in which samples of blood in cellophane tubing are rotated on the drum showed a diminution in the red cell volume, leukocyte and platelet counts.

Dilution, caused by the passage of the dialyzing fluid through the cellophane membrane and by the presence of some of the rinsing fluid, and rotation of the drum are factors of importance in this regard.

3. The influence of heparin and the chemotactic role of cellophane on the leukocytes are discussed.

Heparin in concentration of 1 mg./10 cc. of blood causes in vitro agglutination and disintegration of leukocytes after approximately one hour.

Photographs are shown that demonstrate coating of the cellophane by granulocytes. This is in keeping with the findings of Chambers and Grand that cellophane exerts a positive chemotactic influence on the granulocytes.

4. Hypersegmentation of the leukocytes was noted in samples of blood rotated on the drum for fifteen minutes. Exteriorization and slow speed centrifugation probably account for this phenomenon.
A METHOD FOR THE RAPID SEPARATION OF LEUKOCYTES AND NUCLEATED ERYTHROCYTES FROM BLOOD OR MARROW WITH A PHYTOHEMAGGLUTININ FROM RED BEANS (PHASEOLUS VULGARIS)
Authors: LI JONAH G. , OSGOOD EDWIN E.
Published: October 2019

A method is described for rapid and efficient separation of leukocytes and nucleated erythrocytes from blood or marrow. It is based on the rediscovery of a nontoxic hemagglutinin, isolated from common red or navy beans, which agglutinates all human erythrocytes and those of the animals which have been tested with it. The time from drawing the blood to complete separation of the cells is less than ten minutes. The cells remain in suspension in their own plasma and are countable. Negligible amounts of foreign material are introduced, a great advantage in chemical studies. The cells so isolated are living and suitable for culture studies. Any volume of blood from less than 1 ml. to over 500 ml. may be processed. In marrow nucleated erythrocytes are separated with the leukocytes and in their original porportions. The volume, motility, morphology and life span of the cells in cultures are not altered by addition of the bean extract.
A FACTOR IN SERUM WHICH ACCELERATES THE CONVERSION OF PROTHROMBIN TO THROMBIN
Authors: ALEXANDER BENJAMIN , DE VRIES ANDRE , ADDELSON EUNICE
Published: October 2019

The sera from thrombocytopenic blood show abnormally large residual prothrombin activity and small amounts of prothrombin conversion accelerator. The addition of normal platelets or thromboplastin corrects these abnormalities. In one subject the clotting defect persisted despite temporary remission of the thrombocytopenia consequent to splenectomy.
LYMPHATIC LEUKEMIA AND LYMPHATIC LEUKEMOID STATES IN CANCER OF THE STOMACH
Authors: BICHEL JØRGEN
Published: October 2019

The author reports the case of a patient with chronic lymphatic leukemia, who after some years developed dyspeptic symptoms, increasing cachexia, and eventually died. The leukemia had been subleukemic for several years. Necropsy revealed an adenocarcinoma of the pylorus and lymphatic leukemic changes in the lymph nodes, spleen and liver. In two other cases a lymphatic leukemic blood picture and clinical signs of leukemia (including lymph node enlargements and leukemic changes in the bone marrow) gradually disappeared as tumors of the stomach developed, and in both cases the leukemic blood picture was replaced by a state of lymphopenia. In one of them, the necropsy revealed an adenocarcinoma of the pylorus; in the other, necropsy could not be obtained, but the clinical picture and the radioscopic examinations strongly suggested carcinoma of the stomach in this case, too. These last two cases must be interpreted as lymphatic leukemoid states produced by the presence of the carcinomatous neoplasms, though the possibility can not be excluded that certain carcinomas of the gastrointestinal tract may be capable of primarily or secondarily exercising an inhibitory influence on the leukemic processes.

In connection with the report of these cases, the author reviews the cases from the literature, of lymphatic reactions in cancer and of the coexistence of lymphatic leukemia and cancer in the same individual.
LYMPHOCYTIC LEUKEMOID REACTION OF THE BLOOD ASSOCIATED WITH MILIARY TUBERCULOSIS
Authors: GARDNER FRANK H. , METTIER STACY R.
Published: October 2019

Two cases of miliary tuberculosis that were diagnosed clinically as lymphocytic leukemia are presented. Both cases had evidence of chronic tuberculosis which was of 43 years’ duration in Case 1 and of 28 years’ duration in Case 2. Both patients had granulocytopenia and anemia.

Autopsy findings revealed no evidence of leukemic infiltration, but a diffuse miliary tuberculosis, involving all of the hematopoietic tissues, existed in both Cases.