bluuebunny/crossref_metadata_2025 huggingface dataset:
Responsiveness of Human Granulocytic Leukemic Cells to Colony-stimulating Factor
Authors: Metcalf D. , Moore M. A. S. , Sheridan J. W. , Spitzer G.
Published: October 2019

The proliferative response of normal and leukemic human granulocytic cells to stimulation by varying concentrations of the normal regulator, colony-stimulating factor (CSF), was determined by cluster counts in agar cultures of 150 blood or marrow specimens stimulated by monkey lung conditioned medium. Acute myeloid leukemic cells were slightly more responsive than normal at low concentrations of conditioned medium, but chronic myeloid leukemic cells were slightly, less responsive at all concentrations. Marrow cells from acute leukemic patients in remission exhibited a normal pattern of responsiveness. Average plasma CSF levels in leukemic patients were two to three times higher than the concentration of CSF in cultures maximally stimulated by monkey lung conditioned medium. The observed responsiveness of leukemic cells to stimulation by CSF-containing material is further evidence in support of the conclusion that most myeloid leukemias in man are conditioned, rather than autonomous, neoplasms.
Sodium and Potassium Concentration and Transmembrane Fluxes in Leukocytes
Authors: Cividalli Gabriel , Nathan David G.
Published: October 2019

Reported values for the potassium to sodium ratio in white blood cells range from less than 1 to about 4. This marked variability might be explained by in vitro cation shifts induced by extraordinarily high cation permeability. To test this hypothesis, human leukocytes from 5 ml of blood were maintained in plasma at 37°C and separated by differential centrifugation in specially devised microtubes, within less than 30 min after sampling. Intracellular water content was determined with tritiated water, and trapped plasma with 14C-sucrose. Under these conditions the intracellular concentration of potassium in human leukocytes was 120 SD ± 7 meq/liter cell water and of sodium 16 SD ± 5 meq/liter cell water, and the resultant ratio was higher than 7. Values in the same range were obtained in rabbit leukocytes and in polymorphonuclear granulocytes isolated from peritoneal exudate in guinea pigs. To determine the cation permeability of these white cells, unidirectional fluxes of potassium and sodium were measured with 42K and 22Na. All of these fluxes were in a range from 1.2 to 2.7 meq/liter/min, values more than 50 times faster than those observed in erythrocytes. When active fluxes were inhibited by ouabain, potassium loss and sodium gain occurred at an initial rate of about 0.7 meq/liter/ min. Marked changes also occurred upon incubation at low temperature. These very rapid fluxes demand rigid control of environmental conditions for accurate measurement of intracellular cations in leukocytes.
Interaction Between Rabbit Erythroblast Ferritin and Normal Plasma Proteins
Authors: Yamada Hideo , Gabuzda Thomas G. , Berenfeld Marion
Published: October 2019

Erythroblast ferritin (EF), isolated from phenylhydrazine-anemic rabbit marrow, interacts with components of normal plasma and forms a complex separable by starch granule electrophoresis and by dialysis techniques. The binding is facilitated at low ionic strength. The plasma factors responsible for binding EF are present in autologous, as well as homologous, plasma of normal nonimmune rabbits, although binding activities are quite variable in different plasmas. The binding activity for rabbit EF is also present in heterologous plasma of mouse, guinea pig, and man. The active principles in plasma were identified as two heat-stable components which fractionate as immunoglobulins, one as IgG and the other as IgM. The results support the hypothesis that natural antiferritin antibodies of low titer are present in normal plasma.
Analysis of Interacting Cell Populations in Cultures of Marrow From Patients With Neutropenia
Authors: Senn J. S. , Messner H. A. , Stanley E. R.
Published: October 2019

Utilizing an adherence separation procedure, marrow cells from six neutropenic patients were studied in cell culture for colony-forming ability (CFU-C), and for colony-stimulating function of the adherent cell (A-C) population. Assays on two patients showed reduced CFU-C and A-C function, while assays on three patients yielded normal CFU-C and A-C function; studies on the remaining patient exhibited reduced CFU-C in the presence of normal A-C function. The demonstration of these various abnormalities in marrow cell culture from neutropenic patients suggests that the in vitro techniques have relevance to the study of granulopoiesis in vivo.
Blood Viscosity in Waldenström’s Macroglobulinemia
Authors: Mannik Mart
Published: October 2019

Erythrocytes and plasma proteins contribute to viscosity of blood. Therefore, blood viscosity was measured in 16 persons with macroglobulinemia with a cone-plate viscometer at defined shear rates. In each person a significant correlation (p < 0.001) was found between hematocrit and the logarithm of blood viscosity. The regression equation of this relationship in each patient was used to calculate the blood viscosity at several hematocrits. The blood viscosity at a given shear rate and constant hematocrit was significantly correlated (p < 0.001) with the plasma macroglobulin concentration in g/100 ml. The plasma of patients with macroglobulinemia is a non-Newtonian fluid, but at a given shear rate the plasma viscosity is a function of the macroglobulin concentration. These observations allowed the construction of an equation for calculation of blood viscosity in patients with macroglobulinemia when the hematocrit and plasma macroglobulin concentrations are known.
Transient Monoclonal Gammopathy Associated With Cytomegalovirus Infection
Authors: Vodopick Helen , Chaskes Stuart J. , Solomon Alan , Stewart John A.
Published: October 2019

A transient monoclonal gammopathy, IgA-lambda light chain, associated with a cytomegalovirus (CMV) infection occurred in a patient with acute leukemia in remission. Evidence of CMV infection was confirmed by indirect hemagglutination titers, initially being 1:4096 and gradually falling to 1:64. During the infection, serum and salivary IgA levels rose to 2450 mg/100 ml and 72 mg/100 ml, respectively. Bence Jones proteinuria, lambda type, (0.1 g/24 hr) occurred during the period of excessive immunoglobulin synthesis. Antibody activity against CMV was detected in serum IgA and IgG. Also unusual were the histologic changes indistinguishable from malignant lymphoma seen in a cervical lymph node. After withholding for 1 wk the immunosuppressive drug (methotrexate) she had been receiving, symptoms and signs of the CMV infection and of the monoclonal gammopathy disappeared without recurrence after maintenance methotrexate was resumed.
Evidence for a Physiologic Role of Erythropoietin in Fetal Erythropoiesis
Authors: Zanjani Esmail D. , Mann Leon I. , Burlington Harold , Gordon Albert S. , Wasserman Louis R.
Published: October 2019

Administration of antibody prepared in rabbits against human urinary Ep to fetal sheep during the last third of the gestation period resulted in a suppression of erythropoiesis in the fetus. This was evidenced by a sharp decrease in the numbers of circulating reticulocytes and a reduced rate of 59Fe incorporation into RBC, spleen, and bone marrow, effects ascribable to a neutralization of endogenous Ep. In addition, there was a significant decrease in the numbers of nucleated erythroid cells in the bone marrows of these fetuses. These results point to a physiologic role for Ep in fetal erythropoiesis.
Mechanism of Erythropoietin Production by Cobaltous Chloride
Authors: Miller Marilyn E. , Howard Donald , Stohlman Frederick , Flanagan Patricia
Published: October 2019

Normal and nephrectomized Sprague-Dawley rats were treated with CoCl2 at three dose levels, 10, 20, and 25 µm/ 100 g body weight. The effects of this drug on acid-base balance were related to the production of erythropoietin. Within 6 hr after the administration of CoCl2 to normal rats, a dose-related respiratory alkalosis occurred associated with an increase in the affinity of hemoglobin for oxygen. This was followed by an increase in the production of erythropoietin. Nephrectomy altered the acid-base balance of the animal such that a profound acidosis occurred after the administration of CoCl2 with an associated decrease in the affinity of hemoglobin for oxygen. Erythropoietin could not be detected in these nephrectomized rats given CoCl2. These findings demonstrate that the production of erythropoietin after the administration of CoCl2 is related in significant measure to changes in acid-base balance with its subsequent effect on the affinity of hemoglobin for oxygen.
Platelet Retention in Glass Bead Columns: Further Evidence for the Importance of ADP
Authors: McPherson V. J. , Zucker M. B. , Friedberg N. M. , Rifkin P. L.
Published: October 2019

Plasma of normal heparinized blood contained 0.284 µM ± SD 0.097 (ADP + ATP) with an ATP:ADP ratio of 2.5:1. Plasma from thrombocytopenic blood contained only 0.106 µM ± 0.073 (ADP + ATP). Blood with normal platelet retention released 0.234 µM ± 0.187 (ADP + ATP) during passage through a glass bead column, with an ATP:ADP ratio of 1.6:1. Significantly less was released in blood with low retention, i.e., samples from patients with von Willebrand’s disease, thrombasthenia, or thrombocytopenia, and some samples from normal individuals. Thus, nucleotides in the plasma of pre- and postcolumn blood appear to be derived from platelets; their release within glass bead columns is closely associated with normal platelet retention. Since release occurred at room temperature and was not prevented by acetylsalicylic acid or accompanied by measurable release of 14C-serotonin, the classic release reaction may not have been responsible. The low retention in platelet-rich plasma was variably increased by adding 0.5 µM ADP, an increase at least partly due to trapping of preformed aggregates. Retention in undisturbed blood was markedly inhibited by creatine phosphokinase with creatine phosphate (CPK-CP) and moderately inhibited by apyrase I (ATPase:ADPase 0.8:1) at an ADP-removing activity between 1 and 5 U/ml, indicating that ADP is essential for retention. At less than 1 U/ml, both apyrase I and II (ATPase: ADPase 2.8:1) enhanced retention in undisturbed blood, but CPK-CP was still inhibitory. These results suggest that enhancement is due to conversion of released ATP to ADP, as shown to occur in studies of platelet aggregation with ATP and ADP. At less than 1 U/ml, all three enzymes protected against the inhibitory effect of disturbance; this protection was marked with apyrase II, moderate with apyrase I and slight with CPK-CP. These observations provide additional evidence that ADP is responsible for the low retention caused by disturbance of the blood.
Uptake and Subcellular Distribution of Vitamin B12 in Mouse L1210 Leukemic Lymphoblasts
Authors: Ryel Elaine M. , Meyer Leo M. , Gams Richard A.
Published: October 2019

Protein-mediated B12 uptake by L1210 lymphoblasts was shown to be calcium dependent and enhanced by TCII but not by TCI in vitro. Subcellular fractionation resulted in the majority of B12 localized in the soluble phase with significant amounts in the mitochondria. All vitamin B12 found in the soluble phase was bound to a protein similar in molecular weight to TCII. This protein was capable of delivering B12 to fresh L1210 cells.
Human Leukocyte Reactivity to Penicilloylated Erythrocytes
Authors: Griswold D. E. , Calabresi P.
Published: October 2019

The incubation of penicilloylated mouse erythrocytes with normal human peripheral leukocytes gives rise to plaque formation in an agar medium. While the phenomenon appeared superficially to be like Jerne hemolysin plaque formation, several distinct differences were noted. First, the reaction was not dependent upon the addition of exogenous complement. In addition, plating of enriched lymphocyte populations did not favor plaque formation. In contrast, enrichment of granulocytes favored plaque formation. Furthermore, the addition of protein (bovine serum albumin or human serum) enhanced the plaque formation. Finally, the plaques appeared in normal individuals presumably not sensitized to either mouse or penicillin antigens. On the other hand, certain similarities existed. There was an obligatory incubation time at physiologic temperatures, both systems depended upon the presence of viable cells, and both systems seemed to have an immunologically specific component. Because of the correlation of plaque formation with in vitro erythrophagocytosis, it is postulated that this reaction represented a phagocytosis of penicilloylated mouse erythrocytes directed in some manner by an opsonin.
Increased Efficiency of Leukocyte Collection by the Addition of Hydroxyethyl Starch to the Continuous Flow Centrifuge
Authors: Mishler John Milton , Hadlock Daniel C. , Fortuny Ignacio E. , Nicora Robert W. , McCullough Jeffrey J.
Published: October 2019

A total of 67 leukaphereses were performed with the continuous-flow centrifuge (CFC) on 27 healthy donors for the purpose of obtaining increased yields of granulocytes for infusion into septic patients with acute leukemia accompanied by severe granulocytopenia. The addition of hydroxyethyl starch (HES) to the input line of the CFC significantly (p < 0.005) increased the total number of leukocytes and/or granulocytes collected per donation. A mean yield of 9.72 x 109 and 4.65 x 109 total granulocytes were collected by the HES-treated and control-group donors, respectively. The efficiency of cell collection as evidenced by the total number of leukocytes and/or granulocytes harvested per liter of processed blood was also significantly (p < 0.005) improved by the addition of HES to the continuous-flow centrifuge. Significant alterations in hematologic parameters were not experienced by HES-treated donors undergoing initial and multiple procedures. Pre- and postdonation leukocyte and platelet counts, hemoglobin, prothrombin time, partial thromboplastin time, and leukocyte differential counts were no different whether or not HES was employed for granulocyte collection. The results of the present study demonstrate that increased yields of granulocytes can be harvested by the addition of HES to the continuous-flow centrifuge and made available for supportive therapy to patients experiencing granulocytopenia induced by malignant disease or its treatment.
The Discocyte-Echinocyte Transformation: Comparison of Normal and ATP-enriched Human Erythrocytes
Authors: Féo Claude J. , Leblond Pierre F.
Published: October 2019

This work studies the relationship existing between intracellular ATP levels and the discocyte-echinocyte shape equilibrium in normal as well as ATP-enriched human red blood cells. Fresh erythrocytes metabolically depleted by incubation in a glucosefree buffer undergo echinocytic transformation (crenation) as intracellular ATP levels decline below 50% of their original value. When ATP is regenerated by further incubation of the same cells in the presence of glucose, inosine, and adenine (GIA), concentrations required for the complete recovery of the discocytic shape are lower than those which were necessary to maintain this shape in the first place. Addition of inorganic phosphate (Pi) to the GIA medium results in elevation of fresh cell ATP to supranormal levels. When such ATP-enriched cells are then depleted in the presence of the same concentration of inorganic phosphate, echinocytic transformation occurs much more rapidly than in normal fresh cells not previously incubated with Pi despite a similar rate of ATP depletion in both cases. It is suggested that the intrinsic mechanism responsible for shifting the discocyte-echinocyte equilibrium in the human erythrocyte is dependent on one or more intracellular or intramembrane factors occurring in conjunction with ATP depletion or repletion rather than to the absolute concentration of this nucleotide within the cell. This additional factor(s) appears to be temperature dependent and is influenced by the concentration of Pi in the medium.
Effects of Erythropoietin and Androgens on Erythroid Stem Cells After Their Selective Suppression by BCNU
Authors: Reissmann K. R. , Udupa K. B. , Kawada K.
Published: October 2019

A single injection of BCNU (LD-10 range) caused in mice a prolonged suppression of erythropoiesis, whereas granulopoiesis recovered within a few days. The suppression of erythropoiesis was due to a delayed restoration of erythropoietin-responsive cells (ERC), although the CFU were only moderately suppressed and ranged from 30% to 60% of normal. Daily erythropoietin injections promptly restored normal ERC populations without affecting CFU. Injections of androgens after BCNU had no effect on ERC restoration, but they markedly enhanced CFU regeneration and caused neutrophil counts up to ten times normal.
Specificity of Interacting Populations Affecting Granulopoiesis in Culture
Authors: Messner H. A. , Till J. E. , McCulloch E. A.
Published: October 2019

Human marrow contains two interacting populations that affect granulopoiesis in culture. The first population consists of committed granulopoietic progenitors, while the second contains cells that produce factors whose activity is essential for granulopoiesis in culture. The two populations can be separated by an adherence procedure and assayed independently. Both populations proved to be heterogeneous: the granulopoietic progenitor pool contains a subpopulation which fails to respond to semipurified colony-stimulating activity derived from peripheral leukocytes but responds to the unpurified material. The population of "factor-producing" cells contains two subpopulations that can be separated on the basis of size by velocity sedimentation. Both produce factors that stimulate granulopoietic colony formation. However, the more slowly sedimenting subpopulation is capable of interacting with granulopoietic progenitors in suspension culture yielding an increase in their number, while cells from the more rapidly sedimenting population failed to support such an increase. The results are interpreted as indicating specificity in the interaction between granulopoietic progenitors and factor-producing cells.
Regeneration of Reduced Glutathione in Erythrocytes: Stoichiometric and Temporal Relationship to Hexose Monophosphate Shunt Activity
Authors: Metz Earl N. , Balcerzak Stanley P. , Sagone Arthur L.
Published: October 2019

The stoichiometric and temporal relationships between glutathione reduction and hexose monophosphate shunt (HMPS) activity in normal red blood cells were investigated using azoester to oxidize reduced glutathione (GSH) and an ionization chamber-electrometer apparatus to measure continuously the 14CO2 derived from 14C-glucose. Under air, azoester produced rapid oxidation of GSH followed by rapid regeneration. The HMPS response was delayed and occurred after the period of maximal GSH regeneration. Due to the generation of hydrogen peroxide by azoester, cumulative shunt activity was far in excess of that theoretically required to regenerate GSH oxidized directly by azoester. Under carbon monoxide, no hydrogen peroxide was generated by azoester, and a stoichiometric relationship existed between GSH regeneration and HMPS activity. Again, however, the response of the HMPS was temporally dissociated from GSH regeneration. These findings demonstrate that under carefully controlled conditions there is a stoichiometric relationship between the regeneration of GSH and CO2 production by the HMPS but that this stoichiometry is not the result of a "direct linkage" of the two reactions.
Surface Remodeling vs. Whole-Cell Hemolysis of Reticulocytes Produced With Erythroid Stimulation or Iron Deficiency Anemia
Authors: Come Steven E. , Shohet Stephen B. , Robinson Stephen H.
Published: October 2019

32P in membrane phosphatidylethanolamine (PE) and red cell 14C, reflecting cytoplasmic hemoglobin, were measured sequentially in rats given transfusions of doubly-labeled reticulocytes. With reticulocytes from normal rats there was a small decline in the levels of both the membrane and the cytoplasmic labels; the changes were almost parellel, although loss of membrane PE-32P exceeded that of 14C to a small extent. By contrast, with "stress reticulocytes" from bled donors, there was a markedly disproportionate loss of the membrane label; this asymmetrical loss of membrane material was diminished when recipients had been splenectomized. With transfusions of doubly-labeled reticulocytes from rats with severe iron deficiency anemia, there was a marked loss of both membrane PE-32P and red cell 14C which was only moderately asymmetrical. The asymmetrical loss of the membrane label found with stress reticulocytes supports the conclusion that these cells undergo a process of surface remodeling during their maturation in the peripheral blood. The spleen is partly responsible for this process. Normal reticulocytes also appear to undergo a minor degree of remodeling. On the other hand, the almost symmetrical loss of membrane and cytoplasmic label observed with reticulocytes from iron deficient rats indicates that many of the cells in this model of ineffective erythropoiesis are hemolyzed in their entirety. These experiments demonstrate that stress reticulocytes differ under different conditions and may lose cellular material by two, possibly interrelated, mechanisms: surface remodeling or whole-cell hemolysis.
Leukemia in Shoe-Workers Exposed Chronically to Benzene
Authors: Aksoy Muzaffer , Erdem Şakir , DinÇol Günçağ
Published: October 2019

From 1967 to September 1973, 26 patients with acute leukemia or preleukemia were seen in Istanbul among 28,500 shoeworkers exposed chronically to benzene. The incidence of leukemia among these workers was 13/100,000, which is a marked and statistically significant increase over that for leukemia in the general population and provides cogent evidence for the clinical impression of a leukemogenic effect of benzene in man.
Inhibiting Effects of Human Plasma and Serum on Neutrophil Random Migration and Chemotaxis
Authors: Keller H. U. , Hess M. W. , Cottier H.
Published: October 2019

Various authors have associated increased susceptibility to infectious diseases in certain patients to inhibitors of neutrophil chemotaxis demonstrable in serum or diluted plasma of these patients. The present experiments showed, however, that serum and diluted plasma but not undiluted plasma from normal human donors consistently inhibited chemotactic migration of autologous human neutrophil granulocytes. Therefore, the presence of such inhibitors in the circulating blood can only be assessed by the evaluation of undiluted plasma. The findings suggest that the experimental conditions which have been used in the past to demonstrate such inhibitors in the circulating blood of patients with increased susceptibility to infections are inadequate, and results need reexamination. The inhibitors affect random locomotion and chemotaxis of neutrophil granulocytes but not phagocytosis or the metabolic burst resulting in nitroblue—tetrazolium reduction. On the other hand, phagocytosis of Staphylococcus albus rendered neutrophils chemotactically unresponsive. The significance of so-called cellular defects of neutrophil chemotaxis in such patients is also considered.
PHA Responsiveness and Subpopulations of Circulating Lymphocytes in Pernicious Anemia
Authors: MacCuish A. C. , Urbaniak S. J. , Goldstone A. H. , Irvine W. J.
Published: October 2019

Lymphocyte transformation responses to the mitogen phytohemagglutinin (PHA) were measured in 20 patients with proven pernicious anemia (PA) and 20 matched controls using 3H-thymidine label. The patients with PA showed significant depression of lymphocyte transformation to the three doses of PHA employed, as judged by beta counting; however, radioautographic examination of PHA-stimulated cells indicated that the results were due to a failure of intranuclear incorporation of 3H-thymidine by PA lymphocytes, rather than a failure of PHA to induce blastogenesis. The percentages and numbers of T and B lymphocytes in peripheral blood were measured in 30 patients and controls by rosette and immunofluorescence techniques, respectively. There was no significant difference in the B cell subpopulations between patients and controls; the T cell subpopulation was slightly lower in the PA patients (mean 62.4%) than in the controls (mean 65.5%), but the difference was not statistically significant. The depressed uptake of 3H-thymidine by stimulated lymphocytes in PA would seem to reflect a chemical defect rather than inherent immunologic abnormality.
Red Cells Shrink During Sickling
Authors: Masys Daniel R. , Bromberg Philip A. , Balcerzak Stanley P.
Published: October 2019

Rapid transformation of discoid hemoglobin SS erythrocytes into grossly distorted sickled forms suggests alteration of surface/volume ratio. We, therefore, examined the effect of deoxygenation on red cell volume. 131I-labeled albumin was used as a marker of plasma volume in normal (Hb AA), sickle (Hb SS), and sickle-C (Hb SC) blood. Heparinized blood was incubated for 30 min at 37°C in a tonometer under deoxy (90% N2, 10% CO2) or oxy (90% O2, 10% CO2) atmospheres. Whole blood and plasma concentrations of radioactivity were determined. The hematocrits thus obtained with 131I-albumin showed that deoxygenation caused: (1) Hb AA cells to swell (mean MCV +4.0 cu µ ± 3.0, p < 0.01), as is predicted by the Bohr effect; (2) Hb SS cells to shrink (mean MCV -9.4 cu µ ± 2.9, p < 0.001); Hb SC cells to shrink (mean MCV -4.1 cu µ ± 0.8, p < 0.02). We also measured size distributions of glutaraldehyde-fixed oxy and deoxy cells using a Coulter Model B counter. This method confirmed the results of the radioalbumin experiments. These results demonstrate loss of cell volume during sickling of intact erythrocytes. Possible mechanisms for this loss include potassium efflux with obligatory water efflux, increased intracellular hydrostatic pressure from deformation of the cell membrane, or loss of intracellular osmotic activity of hemoglobin secondary to polymerization. This dehydration enables the sickled cell to develop more extreme shape distortion without membrane disruption, may facilitate continued hemoglobin polymerization, and may play a role in the formation of "irreversibly" sickled cells.
Congenital hypoplastic anemia inhibition of erythropoiesis by sera from patients with congenital hypoplastic anemia
Authors: Ortega JA , Shore NA , Dukes PP , Hammond D
Published: October 2019

An in vitro marrow culture assay designed to measure erythropoietic capability was used to ascertain the presence of an inhibitor in the sera of patients with congenital hypoplastic anemia (CHA). Marrow cells from nine anemic CHA patients responded to the stimulatory effect of exogenous erythropoietin (EPO) by an increase in heme synthesis in the presence of normal serum. The effect on heme synthesis was less than that observed with normal marrow cells. CHA serum inhibited heme synthesis by both normal and CHA marrow cells. It is concluded that an in-inhibitor of erythropoiesis is present in serum from CHA patients. This inhibitor most likely blocks the EPO-sensitive stem cell receptor sites, causing decreased response to the hormone.
Abnormal red cell metabolism in patients with chronic uremia: Nature of the defect and its persistence despite adequate hemodialysis
Authors: Yawata Y , Jacob HS
Published: October 2019

A red cell metabolic abnormality, which diminishes the maximum activity of the pentose phosphate shunt, occurs in some uremic patients, even those adequately dialyzed with fluids prepared from distilled or charcoal-filtered water. Within individual patients the severity of this abnormality does not change even after 9 mo of consecutive hemodialyses. However, between patients it does correlate inversely with hematocrit. When erythrocytes from patients with the abnormality are stressed with oxidant compounds, such as ascorbate, erythrocyte glucose consumption and lactate formation are abnormally increased, while lactate/pyruvate ratios abnormally diminish. Concomitantly, red cell glycolytic intermediates, including fructose-1,6-diphosphate, glyceraldehyde-3-phosphate, 3-phosphoglycerate, phosphoenol pyruvate, and pyruvate, markedly accumulate. Surprisingly, no increase of 2- phosphoglycerate occurs, which suggests that inefficient phosphoglyceromutase activity underlies this perturbation of erythrocyte metabolism and its associated hemolytic process.
Multiple myeloma with intramedullary masses of M-component
Authors: Bernier GM , Duca Jr VD , Brereton R , Graham Jr RC
Published: October 2019

The bone marrow of a patient with light chain myeloma and amyloidosis was substantially infiltrated with basophilic globular particles. The globules, which were confined to the bone marrow, ranged in size from tiny intracytoplasmic inclusions to large (100 mu) extracellular particles. Both the intra- and extracellular globules stained with fluorescent antibody directed against the light chain (kappa) produced by the patient's abnormal clone, and not with other fluorescent antiserums. By electron microscopy, even the largest extracytophasmic globules were bounded at least in part by rough membranes, suggesting that their extreme size was the result of cellular synthesis rather than extracellular coalescence.
Lipid synthesis in human erythroid cells: the effect of sickling
Authors: Lane TA , Ballas SK , Burka ER
Published: October 2019

Human reticulocytes are capable of synthesizing membrane lipids from 14C-glycerol de novo. In both sickle and nonsickle reticulocytes the majority of 14C-glycerol was incorporated into phospholipids, primarily phosphatidylserine and phosphatidylcholine. Incorporation into sphingomyelin was minimal. The most abundant neutral lipid synthesized was triglyceride. In the absence of sickling, the rate of lipid synthesis in sickle reticulocytes was similar to that of nonsickle reticulocytes. With the induction of sickling under anoxic conditions sickle reticulocytes showed a prompt increase in the rate of lipid synthesis to an average of 69% above control values, while nonsickle reticulocytes under similar conditions decreased the rate of lipid synthesis. An increase in the rate of membrane lipid synthesis is associated in the mammalian erythroid cell with cell membrane damage. The findings further confirm that lesions of the erythroid cell membrane in sickle cell anemia are secondary to the sickling process itself.
Effect of splenectomy on tolerance to combination chemotherapy in patients with lymphoma
Authors: Ihde DC , DeVita VT , Canellos GP , Young RC
Published: October 2019

Enhanced tolerance to combination chemotherapy has been cited as an ancillary benefit of staging laparotomy and splenectomy in Hodgkin's disease. Seventeen patients with Hodgkin's disease and 15 with non- Hodgkin's lymphoma were subjected to nontherapeutic splenectomy as part of the staging procedure prior to their initial treatment with MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) or CVP (cyclophosphamide, vincristine, and prednisone) chemotherapy, respectively. Matched control patients of comparable age, pathologically proven stage, and presence or absence of bone marrow lymphoma and previous radiotherapy were selected. Although leukocyte (in non-Hodgkin's patients) and platelet counts (in both groups) were significantly higher in the patients with splenectomy during most of the first six cycles of therapy, there was no difference in the number of cycles during which a leukocyte count below 1000 (or below 2000 in Hodgkin's disease) or platelet count below 50,000 was recorded in the splenectomized and control patients. The total dose of all drugs actually delivered, time required to complete six cycles of treatment, and the portion of patients entering complete remission were not significantly different in the two groups. We have found no evidence that splenectomy per se, in lymphoma patients without findings of hypersplenism, improves the ability to administer planned amounts of drugs during initial combination chemotherapy.
A family with red cell pyrimidine 5'-nucleotidase deficiency
Authors: Ben-Bassat I , Brok-Simoni F , Kende G , Holtzmann F , Ramot B
Published: October 2019

Congenital hemolytic anemia associated with pyrimidine 5′-nucleotidase deficiency is reported in two siblings. Both have had moderate chronic hemolytic anemia, splenomegaly, and jaundice since early infancy. The peripheral blood smear is characterized by striking red cell basophilic stippling. As this feature has been found in all previously reported cases, it should be the clue to the diagnosis.
BENIGN PERICARDIAL EFFUSION IN THE COURSE OF CHRONIC MYELOGENOUS LEUKEMIA
Authors: FRIEDMAN NATHAN H. , SILVERMAN JACOB J.
Published: October 2019

1. Pericarditis with effusion is a rare complication, except terminally, during the course of leukemia.

2. A patient is presented who developed a benign pericardial effusion with recovery during the course of chronic myelogenous leukemia.
THE ELECTRICAL CONDUCTIVITY OF BLOOD
Authors: HIRSCH FREDERIC G. , TEXTER E. CLINTON , WOOD LLOYD A. , BALLARD WILLIAM C. , HORAN FRANCIS E. , WRIGHT IRVING S. , FREY CONSTANCE , STARR DOROTHY
Published: October 2019

1. The factors influencing blood conductivity have been noted.

2. An accurate apparatus has been designed to measure blood and plasma conductivity.

3. A new cell has been designed to measure conductivity of blood.

4. Through studies on normal blood before and after dilution, a correlation has been shown to exist between blood conductivity and the red cell count.

5. The form factor for normal human red cells has been determined to be 1.393.

6. A mathematical equation is presented relating red cell count with conductivity for normal blood.

See PDF for Equation

7. The factor C on the basis of 33 determinations has been calculated to be 10.80.
STUDIES IN ELECTRON MICROSCOPY OF BLOOD CELLS
Authors: BESSIS M.
Published: October 2019

The study of blood cells with the electron microscope necessitates special methods which as yet are not completely precise. The methods of smearing on Formvar, of destruction by pressing on a wet smear, and of shadow casting are those which have been used most frequently.

The author reviews the electron microscopy of thrombocytes, granulocytes and erythrocytes and discusses the ultrastructure of the hyaloplasm. Azurophilic, neutrophilic and eosinophilic granules can be very well observed with the electron microscope. Chronic and acute luekemic cells exhibit certain granules and paracrystals, the significance and specificity of which are not yet clearly established.
THE EFFECT OF DESOXYCORTICOSTERONE ACETATE AND VITAMIN C ON CHRONIC LEUKEMIA
Authors: METTIER STACY R. , ELLENHORN MATTHEW J. , GORDAN GILBERT , MCBRIDE ALICE , MILLS EDITH
Published: October 2019

1. Four patients with chronic lymphatic (lymphocytic) leukemia, and 3 patients with chronic myelocytic leukemia were given ten daily treatments of desoxycorticosterone acetate (5 milligrams) and vitamin C (1 gram) parenterally.

2. No significant immediate or post-treatment effects resulting from this treatment were observed in either group.

3. Desoxycorticosterone acetate and vitamin C in combination have no lympholytic action in patients with chronic lymphatic leukemia.
THE TREATMENT OF ERYTHROBLASTOSIS FETALIS BY TRANSFUSION WITH SEDIMENTED RED CELLS
Authors: PENNELL SAMUEL
Published: October 2019

1. A method is described for the treatment of patients with erythroblastosis fetalis by the transfusion of compatible sedimented red cells from bank blood.

2. The case histories of 28 patients with erythroblastosis fetalis, treated by this method, have been analyzed. Three, or 10.7 per cent, of the patients died. This mortality rate compares favorably with other reports in which exchange transfusion was the therapeutic procedure.

3. The transfusion of sedimented red cells in 50-60 cc. amounts is sufficient to cause an adequate rise in the hemoglobin values with a minimum of load on the infant’s circulation.

4. This method, in contrast to that of exchange transfusion, has the advantage of reducing the administration of plasma to a minimum, thereby preventing further hemolysis of the infant’s red cells by enhancing the agglutinin titer. In addition, excessive amounts of extraneous substances such as sodium citrate are not given.
PLASMACYTOSIS IN DISEASES OTHER THAN THE PRIMARY PLASMACYTIC DISEASES
Authors: FADEM ROBERT S. , McBIRNIE JOHN E.
Published: October 2019

1. This limited study has revealed plasmacytosis of 5.4 per cent to 23.6 per cent in the bone marrow of six diseases other than the primary plasmacytic diseases.

2. The plasmacytic elements observed in these responses were predominantly mature varieties consisting of plasmacytes and degenerative plasmacytes.

3. In each of the cases described a coexisting increase of reticulum cells was observed in the bone marrow.

4. Plasmacytic elements with nuclear and cytoplasmic characteristics of reticulum cells were described and lend additional morphologic evidence to the suggested reticulum cell origin of the plasmacytic series.

5. Even though a morphologic analysis of these cells has revealed a predominance of plasmacytes and degenerative plasmacytes it has not been suggested that plasmacytic responses can be distinguished from the primary plasmacytic diseases on the morphologic appearance of the plasmacytic elements in the bone marrow. Rather, the demonstration of bone marrow plasmacytosis should be subjected to careful evaluation with consideration of other diagnostic criteria before a diagnosis of primary plasmacytic disease is made.
HEREDITARY NONSPHEROCYTIC HEMOLYTIC ANEMIA
Authors: CROSBY WILLIAM H.
Published: October 2019

1. An hereditary hemolytic anemia is described which is normocytic and normochromic, transmitted as a mendelian dominant and not cured by splenectomy. In the family studied, the anemia was associated but not genetically linked with brachyphalangia. Acute idiopathic porphyria may also have been associated. All anemic members were of blood group A.

2. Neither the degree of anemia nor the rate of hemolysis was favorably influenced by splenectomy.

3. Various studies of erythrocyte fragility and hemoglobin metabolism are presented.

4. Although the red cells in this anemia were more resistant to fragility tests in vitro than the red cells of hereditary spherocytosis, they were more rapidly destroyed in vivo.

5. The disease is differentiated from other hereditary and hemolytic anemias. Of the hereditary anemias, this disease seems most closely to resemble hereditary spherocytosis. Yet the differences of cellular survival in vivo and in vitro and the failure of splenectomy in hereditary nonspherocytic hemolytic anemia suggest a difference in the hemolytic mechanism.

6. The demonstration of porphobilinogen in this patient suggests a possible relationship of this hereditary hemolytic anemia to hereditary porphyria.
BONE MARROW FIBROSIS DEVELOPING IN ALEUKEMIC MYELOSIS
Authors: TAYLOR H. E. , SIMPSON W. W.
Published: October 2019

1. A case of aleukemic myelosis with leuko-erythroblastic anemia is presented, in which the development of extramedullary hematopoiesis in liver and spleen, and fibrosis of marrow was studied by multiple punch biopsies and eventual autopsy.

2. This case offers further support to the theory that many cases of marrow fibrosis are fundamentally leukemic in nature belonging to the group of atypical granulocytic leukemias (aleukemic myelosis).

3. The extramedullary hematopoiesis in this case was interpreted as being of leukemic nature rather than a compensatory metaplasia.

4. Since there are other definite causes of marrow fibrosis and since no adequate etiology has been found to explain some cases, it is suggested that marrow fibrosis be classified as (a) primary idiopathic or (b) marrow fibrosis secondary to aleukemic myelosis, neoplasm, chemical toxins etc.
THROMBOTIC THROMBOCYTOPENIC PURPURA
Authors: SINGER KARL , MOTULSKY ARNO G. , SHANBERGE JACOB N.
Published: October 2019

Thrombotic thrombocytopenic purpura (generalized platelet thromboses) is an acute febrile disease characterized by a diagnostic triad: thrombocytopenic purpura, hemolytic anemia, and transitory focal neurologic signs. Twenty cases with this condition have been reported so far. Another case is described in which the diagnosis was made ante mortem on the basis of the above criteria. Detailed hematologic, immunologic, and pigmentary studies revealed a hemolytic process unaccompanied by evidence of autoimmunization. The differential diagnosis, etiologic factors, and pathologic physiology of the disease are discussed together with the possibility that a hypersensitivity reaction might be present.
THROMBOCYTOPENIC PURPURA COMPLICATING INFECTIOUS MONONUCLEOSIS
Authors: ANGLE RICHARD M. , ALT HOWARD L.
Published: October 2019

A case has been presented in which thrombocytopenic purpura was a complication of infectious mononucleosis. A review of the literature revealed 6 other cases in which there was an association between these conditions. Serial platelet counts were made in 7 consecutive cases of infectious mononucleosis. There was a slight depression of the platelets early in the illness, followed by a thrombocytosis and a subsequent return to normal. Hypersplenism is considered as a possible cause for the thrombocytopenia in infectious mononucleosis.
TRANSMISSION OF ANTIANEMIC PRINCIPLE ACROSS THE PLACENTA AND ITS INFLUENCE ON EMBRYONIC ERYTHROPOIESIS
Authors: JONES OLIVER P. , SMITH ADOLPH
Published: October 2019

1. Prehepatic embryonic erythropoiesis is influenced when normal pregnant rats are injected with potent antianemic substances.

2. Both liver extract and PGA (folic acid) cause a reduction in mean cell diameters, but the former is slightly more effective.

3. The rate of mitosis is increased and the relative proportions of individual phases altered.

4. The distribution of light areas in the cytoplasm—negative images of organoids as seen in dry smears—is altered to a greater extent by PGA than by liver extract.

5. The in vitro and in vivo action of drugs on erythropoietic cells are discussed.
THE SIGNIFICANCE OF ABO COMPATIBILITY AND ITS RELATIONSHIP TO THE INTENSITY OF RH IMMUNIZATION
Authors: LUCIA S. P. , HUNT MARJORIE L.
Published: October 2019

1. A series of 1337 obstetric cases, of which 170 were instances of sensitized Rh negative women, were studied with regard to (a) the incidence of the ABO blood groups, and (b) the incidence of ABO compatibility between the mother and child.

2. The incidence of ABO compatibility between the mother and child was found to vary with the blood group of the mother.

3. ABO compatibility between the mother and child was found to be present in 80 per cent of an unselected obstetric population in contrast to 95 per cent in a group of sensitized Rh negative women who bore infants afflicted with hemolytic disease of the newborn.

4. ABO compatibility appears to be related to the occurrence of hemolytic disease of the newborn.

5. In 120 sensitized Rh negative women who bore afflicted infants, the incidence of group A mothers was greater than expected.
β-GLUCURONIDASE OF HUMAN WHITE BLOOD CELLS
Authors: ROSSITER R. J. , WONG ESTHER
Published: October 2019

1. The β-glucuronidase activity of suspensions of mixed white cells, obtained from human blood by the centrifuging technic or by flotation on gum acacia, has been studied.

2. The correlation between β-glucuronidase activity and total white-cell count was greater than that between the activity of the enzyme and either the polymorphonuclear leukocyte count or the lymphocyte count.

3. On the average, the ratio of the enzyme activity in the polymorphonuclear leukocyte to that of the lymphocyte was 5:4.
Activation of bovine factor VII by hageman factor fragments
Authors: Radcliffe R , Bagdasarian A , Colman R , Nemerson Y
Published: October 2019

During the early events of coagulation of human blood by the intrinsic pathway, factor XII is activated to a form which can activate factor XI, and is proteolytically fragmented to smaller species (30,000 daltons and 70,000 daltons) which have lost most of the ability to activate factor XI but which can activate prekallikrein rapidly. The effect of these fragments on factor VII was studied. It was found that these Hageman factor fragments promoted rapid proteolysis of one-chain factor VII to a more active two-chain form. The amino-terminal sequences of the chains of activated factor VII were found to be Ala- Asx-Gly- and Ile-Val-Gly-, the same as were earlier observed after activation of factor VII by activated factor X. This finding indicates that initiation of coagulation by the intrinsic pathway also primes the extrinsic pathway.
Terminal stages of erythroid differentiation: persistent production of globin messenger RNA is necessary to sustain globin synthesis
Authors: Ullu E , Farace MG , Gambari R , Orsi P , Lunadei M , Fantoni A
Published: October 2019

The kinetic relationship between the globin mRNA accumulation and the rate of synthesis of globin chains was studied during the terminal stages of differentiation in erythroid cells derived from the yolk sac of mouse fetuses. RNA derived from the whole cells and from different cell compartments were hybridized to DNA complementary to embryonic globin mRNA. The relative proportion of embryonic globin RNA molecules and their absolute number per cell were estimated on the 11th, 12th, and 13th days of mouse fetal development. During erythroid terminal differentiation globin mRNA became progressively predominant on polyribosomes along with the progressive specialization of cell functions. The number of embryonic globin RNA molecules per cell remained constant while yolk sac erythroid cells underwent two rounds of cell division. These data indicate that the transcription of globin genes is operative throughout the last stages of terminal differentiation and that there is no detectable storage of globin RNA sequences in these cells. The rates of accumulation of mRNA molecules and of globin synthesis both seem correlated to the length of the cell cycle.
The relationship of hemoglobin synthesis to erythroid colony and burst formation
Authors: Eliason JF , Van Zant G , Goldwasser E
Published: October 2019

We have demonstrated that the cyclohexanone method for the extraction of hematin can be used to measure hemoglobin synthesis induced by erythropoietin (epo) in mouse bone marrow cells cultured in medium containing methyl cellulose. The time course of hemoglobin synthesis by mouse marrow cells showed two effects due to epo: an increase in hemoglobin synthesis at day 2, which corresponded to the formation of small erythroid colonies resulting from the CFU-E (colony-forming unit, erythroid), and a very large increase in hemoglobin synthesis, which was maximal at days 7–8 and corresponded to the formation of large erythroid colonies (bursts) resulting from the BFU-E (burst-forming unit, erythroid). The epo dose-response curves for CFU-E colony counts and day-2 hemoglobin synthesis were similar, and the cell-number- response curves for these two paramaters were parallel. The epo dose- response curve for BFU-E colony counts reached a plateau at an epo concentration between 3 and 5 units/ml, whereas the dose-response curve for 6–8-day hemoglobin synthesis did not reach a plateau even at an epo dose of 10 units/ml.