bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Radiation on The Capacity of The Stem Cell Compartment to Differentiate into Granulocytic and Erythrocytic Progeny
Authors: HELLMAN SAMUEL , GRATE HELEN E. , CHAFFEY JOHN T.
Published: October 2019

Different methods have been used to measure the survival following radiation of the hematopoietic stem cell pool. Two of these systems measure the stem cell pool by its ability to proliferate and differentiate into mature progeny. In both methods, irradiated recipient mice receive syngeneic bone marrow. A period of time is allowed for the transplanted progenitor cells to divide and differentiate, and then the progeny produced are assayed. Ability to form red blood cells is assessed by the amount of radioactive iron incorporated into newly-formed erythrocytes. Capacity for granulocyte formation is measured by peripheral white blood cell counts following endotoxin stimulation. This latter is a granulocyte response and has been shown to be a measure of the marrow granulocyte reserve. The pool as measured by its ability to produce erythrocytic progeny appears to be more sensitive initially than as measured by its ability to produce granulocytic progeny. Erythropoietic repopulating ability begins recovery more promptly than the granulopoietic. These effects appear to be due to the host milieu rather than any direct effect of radiation on the stem cells, resulting in initial conservation of granulopoiesis relative to erythropoiesis with subsequent compensatory recovery of erythropoiesis. Because of recent evidence suggesting a common stem cell, these results are interpreted as consistent with the notion that radiation affects not only stem cell proliferation, but also the direction and extent of differentiation.
The Standardized Normal Ivy Bleeding Time and Its Prolongation by Aspirin
Authors: MIELKE C. H. , KANESHIRO M. M. , MAHER I. A. , WEINER J. M. , RAPAPORT S. I.
Published: October 2019

A standardized, reproducible Ivy bleeding time technic has been described which permits one to obtain accurate bleeding time data in man. The technic was used to standardize an aspirin tolerance test in which 60 normal males had a control bleeding time; were given, on a double blind basis, either placebo or 1 Gm. of aspirin, and had a second bleeding time 2 hours later. The control values were: mean, 5 min.; mean ± 2 st. dev., 2 min., 30 sec. to 10 min. The values after placebo were: mean, 5 min., 30 sec.; mean ± 2 st. dev., 2 min., 30 sec. to 11 min. The values after aspirin were: mean, 9 min., 30 sec.; mean ± 2 st. dev., 4 min. to 21 min. The difference between the mean bleeding time after placebo and after aspirin was highly significant (p < 0.001). The distribution of the bleeding times after aspirin suggested that normal subjects do not respond to aspirin as a single population. The degree of prolongation of the bleeding time and the large size of the drops of blood observed in some subjects suggested to us that small amounts of aspirin may exert a significant effect upon hemostasis in normal individuals.
Impaired Pentose Phosphate Shunt and Decreased Glycolytic Activity in Lymphocytes of Chronic Lymphocytic Leukemia. Metabolic Pathway . . . ?
Authors: BRODY JEROME I. , OSKI FRANK A. , SINGER DANIEL E.
Published: October 2019

The purpose of this study was to determine whether proportional alterations in the hexose monophosphate shunt or Embden-Meyerhof pathways of leukemic lymphocyte glycolysis might provide a biochemical explanation for excess glycogen stored in these neoplastic cells in addition to delineating a possible cause for the decreased glucose tolerance shown by a large number of patients with chronic lymphocytic leukemia (CLL). The experimental technic consisted of incubating leukemic lymphocytes separately in Krebs-bicarbonate buffer, and autologous and paired homologous normal plasma, along with glucose-1-14C. Normal, control lymphocytes were similarly handled except that corresponding leukemic plasma became the homologous substitute. Evolved 14CO2, trapped by sodium hydroxide, and collective glycolytic intermediates, isolated by anion exchange chromatography, were assayed by scintillation spectrometry. Compared to normal lymphocytes, the leukemic cells not only consumed less total sugar but also metabolized proportionately less carbohydrate via the hexose monophosphate shunt pathway as indicated by the diminished quantity of generated 14CO2. Although autologous normal plasma significantly increased all facets of normal lymphocyte glycolysis, autologous leukemic plasma failed to stimulate leukemic lymphocytes in a similar manner. In certain instances, this plasma further depressed neoplastic lymphocyte glucose utilization. These observations are consistent with the hypothesis that leukemic lymphocyte glycogenosis may be a consequence of an augmented pool of one or several glycolytic intermediates ultimately available for glycogen synthesis, and with the idea that leukemic plasma restricts in vivo glucose utilization leading to clinically detected abnormal carbohydrate metabolism in many patients with CLL.
Studies in Iron Absorption V. Effect of Gastrointestinal Factors on Iron Absorption
Authors: HÖGLUND S. , REIZENSTEIN P.
Published: October 2019

1. Since previous studies could not demonstrate that any of several general plasma factors played a major role in intestinal iron absorption, local intestinal factors were examined in 240 iron absorption studies on 150 healthy subjects.

2. When the iron dose was increased 40 times, from 0.25 to 10 mg. the percentage absorption was halved.

3. Trebling the quantity of food (bread) in the intestine did not significantly decrease absorption.

4. Ascorbic acid in the intestinal lumen trebled the absorption even of ferrous iron. A stable pharmaceutical combination of iron and ascorbic acid was tested.

5. Sifted flour did not seem to inhibit the absorption of ferrous iron, but coarse ground flour did. When fat was added, no further decrease in absorption was found although iron soaps may be formed.

6. A further decrease in absorption was found after a complete meal.

7. When fine grain reduced iron was used to enrich flour—this is done in all Swedish flour—absorption was 50 per cent lower, and when a coarser grain reduced iron was used 85 per cent lower, than when ferrous sulfate was used for enrichment.

8. When oral iron treatment was given to persons with high iron absorption, absorption was decreased to normal.
Studies on Platelet Proteins. IV. Some Physical and Chemical Properties of Thrombosthenin
Authors: GANGULY P.
Published: October 2019

The contractile platelet protein thrombosthenin has been isolated with butanol and purified further by repeated precipitation and gel filtration. Thrombosthenin thus isolated shows all the typical properties of this protein as reported in the literature. 1 M NaCl-tris, pH 7.2 has been found to be a better solvent than 0.6 M KCl as far as stability, resolution and aggregation of the protein are concerned. In the ultracentrifuge, 0.7 per cent thrombosthenir in 0.6 M KCl shows three hypersharp boundaries with sedimentation coefficients of 36 S, 56 S and 83 S. However, at low protein concentration only the 36 S boundary is observed. In 1 M NaCl, all these components break down producing a single kinetic unit of 18 S which dissociates further to 7 S. The 7 S component retains the ATP-sensitivity typical of thrombosthenin, suggesting it to be the monomeric unit of this protein. A similar hypersharp boundary with similar sedimentation coefficient to purified thrombosthenin has been noted in platelet ghosts solubilized in presence of detergent. A combination of sedimentation and viscosity data leads to an approximate molecular weight 8.9 x 105 for thrombosthenin.
Intravascular Granulocyte Kinetics in Acute Leukemia
Authors: SPIVAK JERRY L. , BRUBAKER LEONARD H. , PERRY SEYMOUR
Published: October 2019

Intravascular granulocyte kinetics in 11 patients with acute leukemia and 8 hematologically normal individuals were studied following the infusion of autologous leukocytes labeled in vitro with diisopropylfluorophosphate (DF32P). The kinetics of the labeled granulocytes in the control subjects was similar to that reported in previous studies. Ten of eleven leukemic subjects, however, had abnormal granulocyte disappearance curves and prolonged granulocyte disappearance rates. This was true for patients in remission as well as for untreated patients. The abnormal granulocyte kinetic patterns demonstrated here are in keeping with the disorderly and diminished granulocytopoiesis and defective granulocyte mobilization found in acute leukemia.
A Study of the Sickling Phenomenon and Oxygen Dissociation Curve in Patients with Hemoglobins SS, SD, SF and SC
Authors: CAWEIN M. J. , O’NEILL R. P. , DANZER L. A. , LAPPAT E. J. , ROACH THOMAS
Published: October 2019

1. Data on pO2, T50, n values and per cent of sickle cells were obtained in patients with hemoglobins SS, SD, SF (S-thalassemia) and SC. In general the per cent of sickle cells was proportional to the per cent of hemoglobin S. The number of sickle cells was, however, influenced by the other type of hemoglobin present and by the pO2. Values for T50 were greater than normal, and values for n were less than normal.

2. The effect of therapy with O2, CO2, NaHCO3 and MgSO4 on the per cent of sickle cells in arterial and venous blood was determined. Only inhalation of O2 reduced the per cent of sickle cells.

3. The rate of sickle cell formation and its reversal were determined under conditions of deoxygenation and oxygenation. These were found to be a function of the type of hemoglobin combinations present.

4. The oxygen dissociation curves were found to be shifted to the right of the normal curve indicating a decreased affinity for oxygen. In two patients the Bohr effect was determined and found to be normal.
Preparation and Purification of Tritiated Phytohemagglutinin and Studies of Cellular Localization in Human Leukocyte Cultures
Authors: CONARD ROBERT A. , DEMOISE CHARLES F.
Published: October 2019

A tritiated bean extract was obtained from bean plants (Phaseolus vulgaris) grown hydroponically in nutrient media containing various concentrations of tritium water. Purification was accomplished by ammonium sulfate precipitation and column chromatography using DEAE, CM-52 cellulose columns, and finally by Sephadex G-100 gel filtration. The purified product showed greatly increased mitogenic activity and electrophoretically showed a single labeled protein band on electrophoresis. Radioactivity of the purified PHA varied between 0.1-0.5 µCi/mg. which, though not as high as desirable, was sufficient for autoradiographic and subcellular fractionation studies in human leukocyte cultures. Within a few hours cytoplasmic localization of the label was noted in most of the cells in culture, including neutrophils and larger mononuclear cells. Breakdown of many of these cells during the first 24 hr. resulted in labeled amorphous basophilic staining masses of cell particles.

Though agglutination of cells was commonly seen, the lack of label in red cells or surface label of leukocytes was notable. Blast forms which appeared by the second day showed prominent labeling which appeared to be largely cytoplasmic as evidenced by grain distribution. Several reasons were discussed which made it seem likely that the mitogenic molecule was represented in the cell label. Assay of subcellular fractions showed the major portion of radioactivity in the mitochondrial fraction. Specific activity, however, was too low to permit electron microscopic localization of label in individual organelles. Lack of label of RNA and DNA proteins was demonstrated by cellular distribution of the label and chemical extraction of RNA and DNA. Interesting speculation arises as to whether the PHA may stimulate mitochondrial activity and induce RNA synthesis and blastogenesis. Further experiments are in progress to obtain a purer PHA with higher specific radioactivity in order to more precisely define the site and mechanism of action of the mitogen.
Acute Leukemia Occurring During Chronic Lymphocytic Leukemia
Authors: McPHEDRAN PETER , HEATH CLARK W.
Published: October 2019

Acute leukemia occurred in two of 340 persons with chronic lymphocytic leukemia listed in a registry of leukemia cases among residents of Georgia. One case was acute myeloblastic leukemia; the cell type of the other was disputed. Before onset of acute leukemia, one patient had had numerous diagnostic x-rays, while the other had received therapeutic radiation. These data and previous case series indicate that acute leukemia in patients with chronic lymphocytic leukemia is rare, has no consistent cell type, and often follows exposure to therapeutic radiation. It seems possible that such cases of acute leukemia often represents a second malignancy than a true blast phase of chronic lymphocytic leukemia.
Hypofibrinogenemia Due to L-Asparaginase: Studies of Fibrinogen Survival Using Autologous 131I-Fibrinogen
Authors: BETTIGOLE R. E. , HIMELSTEIN E. S. , OETTGEN H. F. , CLIFFORD G. O.
Published: October 2019

Plasma fibrinogen levels fall, often dramatically, in patients receiving L-asparaginase. Studies of six patients using autologous 131I-fibrinogen showed that at a dose of 1000 I.U./kg./day L-asparaginase had no effect on their rates of fibrinogen disappearance. The fall in their plasma fibrinogen levels, therefore, must have been a result of decreased synthesis since it could not be ascribed to increased utilization or destruction of fibrinogen.
Paraproteinemia in a Child with Leukemia
Authors: LINDQVIST KAARE J. , RAGAB ABDELSALAM H. , OSTERLAND C. KIRK
Published: October 2019

A four-year-old boy was diagnosed as having lymphoblastic leukemia in January 1967. On immunosuppressive therapy he had several clinical remissions and relapses. In mid-1968 he entered a period of sustained clinical remission. At that time a monoclonal gammaglobulin peak appeared in the electrophoresis pattern of his serum. The paraprotein which was present in concentrations above 44 mg. per ml., was characterized as γG with K-chain specificity. There was no evidence of multiple myeloma, and no urinary Bence-Jones protein was detected. The patient was investigated for cellular and humoral type immunologic responsiveness during the sustained remission period with normal results. The possible relationship between the paraprotein and the favorable clinical course in this patient is discussed.
Fibrillar Bundles in the Nucleus of Blood Lymphocytes from Leukemic and Nonleukemic Patients
Authors: STEFANI STEFANO S. , TONAKI HIROSHI
Published: October 2019

Fibrillar bundles were found in the nuclei of blood lymphocytes from 15 of 30 normal individuals. Similar fibrils were found in three of 16 cases of chronic lymphocytic leukemia, and in one of eight cases of Hodgkin’s disease. Nuclear bundles when observed in a sample were found only in small numbers. No points of continuity between the nuclear and the cytoplasmic fibrils could be found.
Evaluation of a Standard Dosage Schedule with Streptokinase
Authors: HIRSH J. , O’SULLIVAN E. F. , MARTIN M.
Published: October 2019

The safety and effectiveness of a standard dosage schedule of streptokinase was evaluated in 50 patients with thromboembolic disease. A streptokinase resistance test was performed, and each patient was then treated with 250,000 units of streptokinase infused over 30 minutes followed by 100,000 units per hour. The results of serial tests of fibrinolytic activity were then correlated with the streptokinase resistance in each patient. Forty six of the fifty patients had a resistance of 250,000 units or lower and all these developed an active thrombolytic state with rapid plasminogen depletion. The four patients with a streptokinase resistance in excess of 250,000 units showed a delayed fibrinolytic response; however, once obtained, the fibrinolytic effects were similar to those found in the other 46 patients.

It is concluded that an active thrombolytic state would be obtained most consistently if the inducing dose of streptokinase is individualized for each patient. The thrombolytic effects of a standard dose schedule are less predictable, but its routine use may be an acceptable alternative in a particular community if the range and distribution of the streptokinase resistance have been determined and have been shown to be relatively low in a large percentage of the community.
Brief Report: Bone Marrow Lymphocytosis in Acute Leukemia: A Second Look
Authors: SKEEL ROLAND T. , BENNETT JOHN M. , HENDERSON EDWARD S.
Published: October 2019

A review of 54 patients with acute leukemia in remission confirms the impression that bone marrow lymphocytosis (BML) of 20 per cent or more is not a manifestation of incomplete remission, but may be an indicator of good prognosis. This concept is particularly manifest in patients with acute lymphocytic leukemia. Eight such patients without BML have had median remissions and survivals of five and 10 months, respectively, while 30 patients with BML have had remissions and survivals of nine and 35 months.
The Use of Heparin in Autoimmune Hemolytic Disease
Authors: BARDANA EMIL J. , BAYRAKCI CEMIL , PIROFSKY BERNARD , HENJYOJI HOWARD
Published: October 2019

Seven patients with various forms of autoimmune hemolytic anemia were treated with parenteral heparin. A therapeutic failure resulted in all instances. Heparin therapy did not induce a clinical response or reduce the magnitude of hemolysis. There was no demonstrable in vivo or in vitro effect of this drug on direct and indirect antiglobulin and bromelin tests. Serum complement levels and the degree of erythrocyte mobility were unaffected by heparin during the therapeutic trial.
Diagnostic Specificity of Sucrose Hemolysis Test for Paroxysmal Nocturnal Hemoglobinuria
Authors: HARTMANN ROBERT C. , JENKINS DAVID E. , ARNOLD ANITA B.
Published: October 2019

The diagnostic specificity of the various modifications of the sucrose hemolysis test for PNH was examined in detail. In whole blood screening tests the greatest specificity was achieved using citrated or oxalated blood and room temperature incubation (23°). Defibrinated whole blood should not be used since "false positive" hemolysis may occur in blood disorders other than PNH. Mechanisms were suggested for this phenomenon. The validity of the confirmatory sucrose hemolysis test employing normal serum was further reported. Because of the clear, colorless character of serum-sucrose mixtures, an insignificant degree of hemolysis (i.e., less than 5%) is more readily visible than in other PNH hemolytic tests employing undiluted serum. Definitive instructions and criteria for interpretation were given for both the whole blood screening test and the confirmatory sucrose hemolysis test.
Ferrioxamine Iron in Rabbit Reticulocyte Heme Synthesis
Authors: GERLANC M. D. , ZAPOLSKI E. J. , RUBIN M. , PRINCIOTTO J. V.
Published: October 2019

Ferrioxamine B, a naturally occurring sideramine, serves as an iron transport agent and iron donor for heme synthesis in micro organisms. It is unable to effectively replace transferrin in iron delivery for rabbit reticulocyte hemoglobin formation.
Enlargement of Mitochondrial Compartment in Iron and Copper Deficiency
Authors: DALLMAN PETER R. , GOODMAN JOSEPH R.
Published: October 2019

Marked enlargement of the mitochondrial compartment is present in heart muscle, liver, and erythroblasts of iron- and copper-deficient rats. Mitochondria are increased in size, and may also be increased in number, particularly in heart muscle and erythroid cells. The enlarged mitochondria are more electron-lucent and in the hepatocyte may have sparser packing of cristae than in animals on a complete diet. Morphologic changes in the erythroid percursors of three iron-deficient patients are similar to those observed in the experimental animal. The morphologic response is not attributable to anemia or inanition but appears more specifically related to the lack of trace metals or cofactors required for the synthesis of certain mitochondrial enzymes.
DFP Labeling of Platelets During Recovery from Thrombocytopenia
Authors: EBBE SHIRLEY , SAPIENZA PETER , DUFFY PETER , STOHLMAN FREDERICK
Published: October 2019

Rat platelets were labeled with tritiated diisopropylfluorophosphate (3H-DFP) during recovery from acute thrombocytopenia. The results indicated that there was significant labeling of megakaryocytes by 3H-DFP which, in the presence of an increased rate of platelet production, resulted in maintenance of relatively constant values for platelet-bound radioactivity during the period of maximum platelet production and reactive thrombocytosis. Significant random loss of platelets was apparent, and, when a cohort of young platelets was transfused to normal recipients, they were destroyed at a normal rate.
Autoradiography of Diffusible Compounds in Human Nonnucleated Erythrocytes: Studies with Tritiated Glucose and Adenine
Authors: GREENWALT TIBOR J. , PAIGE JOSEPH C. , ETOH NOBUKOH , STEANE EDWIN A.
Published: October 2019

A simple method for autoradiography of diffusible substances in erythrocytes is described. It is based on retarding diffusion from the red corpuscles during fixation and processing by using the bifunctional aldehyde, glutaraldehyde; rapid drying; and applying the nuclear emulsion as a dried, preformed film.

The technique was used for studying the changes during storage in the ability of red blood cells to utilize glucose. The incorporation of glucose-6-3H by samples of blood stored for different periods of time was followed by the number of silver grains present in the red corpuscles. It was observed that the percentage of erythrocytes with fewer than four grains increased progressively during the storage of ACD blood. The incorporation of glucose as observed by the silver grain pattern was reversible toward that of freshly collected red corpuscles following incubation of the stored samples with adenosine.

Similar studies were performed using adenine-8-3H as the label in blood stored for six weeks in ACD adenine solution. Incubation of the blood samples containing 0.5 mM. adenine for one hour at 37°C resulted in autoradiographic patterns equivalent in grain counts to those given by red blood cells stored with the radiolabeled adenine for five weeks. The incubation of fresh samples with inosine was found to inhibit the incorporation of adenine, whereas inosine enhanced the number of grains in red blood cells which had "run down" during storage.

The autoradiographic technique presented should be of value for the in vitro evaluation of methods of blood preservation and for studying the metabolic heterogeneity of normal red corpuscles and other tissue cells. It should be useful for investigating hereditary and acquired abnormalities of metabolism.
In Vitro Effect of Chloramphenicol on Chromosomes
Authors: MITUS W. J. , COLEMAN NANCI
Published: October 2019

Leukocytes from normal individuals were cultured in media containing various concentrations of chloramphenicol. Chromosomes obtained from these cultures were studied for intrachromosomal vacuolation and various other structural changes such as breaks, gaps, fragmentations, etc.

Chromosomes from chloramphenicol containing cultures showed significant increase in abnormalities when compared with control preparations. Changes observed were very similar to those seen in patients receiving large doses of chloramphenicol.
Characterization and Genetic Studies of Microcytic Anemia in House Mouse
Authors: RUSSELL ELIZABETH S. , NASH DONALD J. , BERNSTEIN SELDON E. , KENT EDITH L. , MCFARLAND ELEANOR C. , MATTHEWS SUSAN M. , NORWOOD MARY S.
Published: October 2019

Microcytic anemia, inherited as a unit autosomal recessive, is the first of the twelve known single-gene induced hereditary anemias of the mouse which results entirely from alteration of individual erythrocytes rather than from reduction in number of red cells. At all ages where mk/mk individuals could be recognized, from the fifteenth day of gestation to adulthood, the erythrocyte count of mk/mk individuals was at least as high as that of normal counterparts. At all ages, the hemoglobin concentration in these small erythrocytes was also reduced, so that the total available hemoglobin was markedly reduced at all ages. The higher than normal numbers of erythrocytes in adult microcytic mice demonstrate that the cell-producing mechanisms operate efficiently. Genetic tests have shown that the mk single-gene defect has no relation to structure of either the α-chain or the β-chain of the hemoglobin molecule. The mk microcytosis and hypochromia must then result from a metabolic or structural defect independent both of the factors responsible for regulating red cell number and of those controlling hemoglobin structure.

This mk/mk microcytic anemia shows some similarities to human thalassemias: hypochromia, microcytosis and presence of target cells, combined with splenomegaly, reticulocytosis, and higher than normal erythrocyte counts (like thalassemia minor). As in thalassemia, hemoglobin structure is normal, although the amount per cell is subnormal. Human hemolytic anemias also share some of these characteristics. The similarities of mk/mk microcytic anemia of the mouse to certain human anemias are sufficient to warrant its further investigation as an animal model for understanding of human hereditary disease.
Analytic Review: Disorders of Phagocyte Function
Authors: DOUGLAS STEVEN D.
Published: October 2019

The physiologic aspects of neutrophil and monocyte function as related to bactericidal capacity have been reviewed. Recent studies have demonstrated clinical syndromes involving defects in chemotaxis, opsonization, and a spectrum of intracellular neutrophil and monocyte defects. The present concepts of the pathophysiology of these syndromes have been considered. The elucidation of the basic defects awaits the development of new approaches to the study of phagocyte function.
Total Body Counting in the Assessment of Vitamin B12 Absorption in Patients with Pernicious Anemia, Achlorhydria Without Pernicious Anemia and in Acid Secretors
Authors: IRVINE W. J. , CULLEN D. R. , SCARTH LAURA , SIMPSON J. D. , DAVIES S. H.
Published: October 2019

The absorption of 58Co-vitamin B12 was assessed by the method of total body counting in 25 patients with frank P.A., five with latent P.A., 47 with achlorhydria but without malabsorption of vitamin B12 and 47 acid-secreting patients. A total of 192 tests was done. With or without prior stimulation of intrinsic factor secretion by pentagastrin the upper level of absorption of vitamin B12 in patients with frank or latent P.A. was 25 per cent. Taking an equivocal result to be 21-25 per cent inclusive, the total body counting method was able to distinguish P.A. patients from those with achlorhydria without P.A. with 87 per cent accuracy and one per cent error and from non-P.A. achlorhydric patients and acid secretors combined with 91 per cent accuracy and 0.5 per cent error.

Pentagastrin stimulation did not improve the separation between achlorhydric patients with and without P.A. but raised the lower limit of retention of vitamin B12 from 24 to 44 per cent in the acid secreting patients.

The method of total body counting is recommended as a method of assessing vitamin B12 absorption.
Evidence for Cyclic -3',5'-Adenosine Monophosphate as Chemotactic Agent for Polymorphonuclear Leukocytes
Authors: LEAHY DENNIS R. , McLEAN EDWARD R. , BONNER J. T.
Published: October 2019

Using the Boyden test for chemotaxis, it was possible to show that cyclic-3',5'-AMP attracts polymorphonuclear leukocytes. Although this effect is definite, casein has a more potent effect. Since cyclic AMP is synthesized by bacteria, and is a heat stable molecule of small molecular weight, it is presumed to be one of the components in bacteria capable of producing positive chemotaxis in leukocytes.
An Improved Method for Performing Neutrophil Survival Studies
Authors: DEINARD AMOS S. , PAGE ARTHUR R.
Published: October 2019

An improved method for doing DFP32 neutrophil survival studies is described that allows quantitative measurement of total circulating neutrophil-associated radioactivity. DFP32 labeled neutrophils are quantitatively trapped on a nylon fiber column and washed free of contaminating radioactivity. The neutrophil-associated radioactivity is then counted in a liquid scintillation counter. Data so obtained can then be used to construct both a true neutrophil survival curve and a curve for the fall-off of neutrophil specific activity. Leukokinetic data on hematologically normal individuals compare favorably with the values for normal persons that Athens and his collaborators have published.
Muramidase in Polycythemia Vera
Authors: BINDER RICHARD A. , GILBERT HARRIET S.
Published: October 2019

The serum muramidase levels of 45 patients with polycythemia vera were found to be significantly elevated above the values in 20 normal subjects. The patients with polycythemia vera who were studied included those with active disease, those controlled with myelosuppressive agents and those in the spent phase. A high degree of correlation was found between muramidase levels and leukocyte count, granulocyte count, serum uric acid, serum vitamin B12 content and unsaturated vitamin B12 binding capacity. No correlation was found between muramidase levels and hematocrit, monocyte count and leukocyte alkaline phosphatase activity. It is felt that this study lends support to the origin of serum muramidase from granulocytes and that elevated levels of serum muramidase in the subjects studied are a reflection of the involvement of the granulocyte in the proliferative process responsible for polycythemia vera.
Effect of Erythropoietin on Proliferation of Erythroid Stem Cells in the Absence of Transplantable Colony-forming Units
Authors: REISSMANN KURT R. , SAMORAPOOMPICHIT SOMMART
Published: October 2019

A single administration of Myleran eradicated colony-forming stem cells from marrow or spleen of mice for a period of two weeks or longer. Erythropoiesis was restored during that time, and the exclusion of cell influx from the colony-forming progenitors into the intermediary erythroid stem cell compartment permitted a study of the effects of erythropoietin on the kinetics of the latter. The results indicate that erythropoietin, in addition to its role in transforming immediate precursors into proerythroblasts, stimulated the proliferation of erythroid stem cells. The significance of this in regard to stem cell kinetics and rate regulation of erythropoiesis is discussed.
A Simple Spot Screening Test for Fast Detection of Red Cell NADH-Diaphorase Deficiency
Authors: KAPLAN JEAN-CLAUDE , NICOLAS ANNE-MARIE , HANZLICKOVA-LEROUX ALENA , BEUTLER ERNEST
Published: October 2019

A rapid spot screening test for NADH-diaphorase deficiency is described. Nitrited blood is added to a reaction mixture freshly prepared from stable stock reagents. Spots are made at intervals on filter paper and examined for defluorescence as NADH is oxidized. All of six patients with NADH diaphorase deficiency studied have been correctly identified using this technique, but it is not suitable for the detection of heterozygotes.
Eosinophil Kinetics in Two Patients with Eosinophilia
Authors: HERION J. C. , GLASSER R. M. , WALKER R. I. , PALMER J. C.
Published: October 2019

Leukocyte kinetics were studied in two individuals with marked eosinophilia. Blood leukocytes, labeled in vitro with Na251CrO4, disappeared from the circulation at different rates in the two subjects during the first eight hours after infusion. In one, label disappeared exponentially with a T/2 of 4.5-5.0 hours; in the other, the level of radioactivity remained constant. In both, however, a significant rise in radioactivity appeared during the second 24 hours, suggesting recirculation of the eosinophils. Blood leukocyte DNA-32P labeling was similar in both subjects and closely resembled neutrophil DNA-32P labeling observed in normal individuals. Hydrocortisone infusion produced an exponential decrease in circulating eosinophils in one subject and, for reasons unknown, a linear decrease in the other; the drug exhibited no effect on eosinophils in vitro.
Effect of L-Asparaginase on Mouse Bone Marrow, Assayed by In Vitro Culture
Authors: BROWN CLARENCE H. , CANELLOS GEORGE P. , CARBONE PAUL P.
Published: October 2019

L-asparaginase administered in therapeutic doses to mice was found to reduce the total number of nucleated marrow cells and colony-forming cells when assayed 4 hours after administration by a methylcellulose bone marrow culture technique. Both marrow cellularity and the fraction of surviving IVCFC/femur were normal by 24 hours after injection, except with very large doses, at a time when there were sufficient quantities of L-asparaginase free or cellularly bound within the marrow to be toxic to the culture system. The enzyme could be removed from the marrow specimens with repeated washings. It is postulated that the bone marrow of the mouse is similar to the regenerating rat liver in that both have the ability to compensate for Lasparagine depletion, even in the presence of active L-asparaginase. The rarity of clinically observed myelosuppression in human subjects could be the result of a similar mechanism.
Synthesis of Riboflavin Nucleotides by Mature Human Erythrocytes
Authors: MANDULA BARBARA , BEUTLER ERNEST
Published: October 2019

Intact human red blood cells can synthesize FAD and FMN from riboflavin. The rate of synthesis of FAD is linearly proportional to the concentration of riboflavin in the medium at levels below 0.9 µM. With 0.9 µM riboflavin, the rate of synthesis is about 0.1 mµmole FAD/ml. red blood cells/hour. Incubation of red blood cells with riboflavin can result in increased red cell glutathione reductase activity when the enzyme is measured in the absence of added FAD. This indicates that the FAD concentration in the red cells increased during the incubation. The rate of incorporation of radioactive riboflavin into red blood cells is the same whether the cells are suspended in plasma or in a phosphate-saline-glucose medium. The time it takes for half the FAD in normal human red blood cells to turn over is calculated to be about 6 days, assuming a single mixing pool of red cell FAD.
Technique for Human Marrow Grafting
Authors: THOMAS E. DONNALL , STORB RAINER
Published: October 2019

A technique is described for marrow aspiration from living human donors and for processing the marrow for intravenous infusion to marrow graft recipients.
Simplified Method for Estimation of Serum and Plasma Viscosity in Multiple Myeloma and Related Disorders
Authors: WRIGHT DORIS J. , JENKINS DAVID E.
Published: October 2019

In the present study, the red blood cell pipette was tested and found to be a suitable viscometer for detection of the hyperviscosity syndrome in multiple myeloma and macroglobulinemia. Additional studies demonstrated that in normal subjects and in most patients there was little difference in relative viscosity values whether serum or plasma was used and whether the test was performed at room temperature or 37° C. Based on these observations, a rapid screening test for the measurement of serum or plasma viscosities was described.
The Effect of Iron Therapy in Paroxysmal Nocturnal Hemoglobinuria
Authors: ROSSE WENDELL F. , GUTTERMAN LORENCE A.
Published: October 2019

Two patients with paroxysmal nocturnal hemoglobinuria who were iron deficient were treated with parenteral iron compounds. In both instances, a marked increase in hemoglobinuria followed, beginning 4 days after the first administration of the iron compound. The rise in hemolysis paralleled the rise in reticulocyte count. When erythropoiesis was suppressed with transfusion, the administration of iron did not bring about an increase in hemolysis. This indicates that the effect of iron in bringing about hemolysis in patients with paroxysmal nocturnal hemoglobinuria is due to an increase in erythropoiesis, resulting in the production of excessive numbers of complement-sensitive cells.
Central Nervous System Involvement in Burkitt’s Lymphoma
Authors: ZIEGLER JOHN L. , BLUMING AVRUM Z. , MORROW RICHARD H. , FASS LEROY , CARBONE PAUL P.
Published: October 2019

Thirty-five of 77 patients (46%) with Burkitt’s lymphoma presented or developed evidence of central nervous system involvement by tumor. Neurologic abnormalities included paraplegia, cranial neuropathy, altered levels of consciousness and malignant pleocytosis. An analysis of this series disclosed the following: Paraplegia is a common presenting feature of Burkitt’s lymphoma and is responsive to systemic chemotherapy. The association of cranial neuropathy and malignant pleocytosis with facial tumors points to direct tumor extension to intracranial structures (duraarachnoid) as the pathogenesis of these lesions. Intrathecal chemotherapy temporarily reverses malignant pleocytosis but systemic chemotherapy is required to treat cranial neuropathy. A poor prognosis follows presentation or development of malignant pleocytosis. The limitations of the current forms of therapy for CNS involvement are discussed.
Chromosomal Evidence for the Secondary Role of Fibroblastic Proliferation in Acute Myelofibrosis
Authors: VAN SLYCK ELLIS J. , WEISS LESTER , DULLY MARILYN
Published: October 2019

A 22-year-old white woman with acute myelofibrosis and agnogenic myeloid metaplasia is reported. She was found to have a consistent chromosomal aberration in her myeloblasts, interpreted as a 1-3 translocation. Bone marrow fibroblasts were successfully cultured, yielding a normal karyotype. The lymphocyte karyotype in this patient was also normal. It is proposed that these findings favor a secondary role of the fibroblastic proliferation in myelofibrosis and suggest that the primary cellular disturbance resides only in the hematopoietic cell lines.
Myelofibrosis in Chronic Granulocytic Leukemia
Authors: GRALNICK HARVEY R. , HARBOR JOHN , VOGEL CHARLES
Published: October 2019

In 181 patients with chronic granulocytic leukemia (CGL) 39 patients demonstrated myelofibrosis (MF) during the course of their disease. These groups can be divided into two groups: one group initially presenting with the clinical and laboratory findings of CGL but with concomitant MF and a second group in whom MF developed late in the course of CGL. The occurrence of MF with CGL was associated with three findings: (1) elevation of the leukocyte alkaline phosphatase, (2) a very poor prognosis and (3) the frequent association of MF and blastic transformation of CGL. MF should be considered an integral part of CGL and when present should be considered part of the terminal phase of CGL and treated accordingly.
A Note on the Increased Risk of Polycythemia Vera in Jews
Authors: MODAN B. , KALLNER H. , ZEMER D. , YORAN C.
Published: October 2019

A whole community study of polycythemia vera in Israel revealed a mean annual incidence of 6.7 per million. Ratio of age adjusted rates between European and non-European-born foreign residents was 2.2 among males and 3.1 among females. A comparison with the only other community study of polycythemia shows higher incidence in Israel as compared with the city of Baltimore, but similar rates among European-born Jews in Israel and Jewish residents in Baltimore. The data indicate that the risk of developing polycythemia vera is higher among Jews of European extraction, independent of residence.
Ultrastructural and Immunofluorescence Studies of the Cells Associated With µ-Chain Disease
Authors: ZUCKER-FRANKLIN DOROTHEA , FRANKLIN EDWARD C.
Published: October 2019

Fluorescence and electron microscopy studies were carried out on the blood and bone marrow cells of the first patient observed to have µ-chain disease. Since previously reported cases of γ and α heavy-chain disease did not elaborate any light chains, it was of interest to determine whether both the µ-chain fragments and the κ chains found in the serum of this patient originated in the same cell or whether mutations had affected two different clones. The use of rhodamine-conjugated and fluorescein-conjugated antisera to heavy and light chains respectively established that both antigenic determinants were present in the same cell. On electron microscopy, the plasma cells showed large vacuoles which appeared to form in the vicinity of the Golgi zone and frequently extended to the surface of the cell. It is postulated that the structural defect in the µ chain interferes with proper assembly of the gamma-globulin molecule. This in turn may preclude transport via the normal secretory pathway. The accumulated protein fragments may be released by a process of limited cytolysis.
Interactions of Polylysine With Platelets
Authors: JENKINS C. S. P. , PACKHAM M. A. , KINLOUGH-RATHBONE R. L. , MUSTARD J. F.
Published: October 2019

Platelet aggregation induced by the cationic polypeptide, polylysine, differs in many respects from aggregation induced by ADP. Polylysine causes immediate, irreversible aggregation and the aggregates form a tight mosaic with electrondense material between the membranes and coating the surface. Inhibitors of ADP-induced aggregation or of the platelet release reaction do not inhibit polylysine, but negatively charged polymers (heparin and mucopolysaccharides) are inhibitory and also cause deaggregation. In contrast to agents such as thrombin, polylysine does not cause the release of serotonin, ATP, or ADP from the platelet granules, but it does cause a leak of adenine nucleotides and lactic dehydrogenase from the platelet cytoplasm. This leak from the cytoplasm can be inhibited by prostaglandin E1. Polylysine inhibits serotonin uptake by platelets, but ADP does not. Low concentrations of polylysine inhibit ADP or thrombin-induced aggregation and thrombin-induced release. Collagen-induced release and aggregation are potentiated by polylysine. Both ADP and polylysine cause increased C14O2 production from platelets incubated with glucose-6-14C. Prostaglandin E1 inhibits this stimulation by both these agents. Mucopolysaccharides and heparin inhibit only the polylysine-induced stimulation of metabolism. The increased aerobic metabolism observed with both ADP and polylysine may be related to changes that occur when platelets change shape and adhere to each other and it may not be a specific reaction to ADP.
Separation of Erythropoietin-sensitive Cells From Hemopoietic Spleen Colony-forming Stem Cells of Mouse Fetal Liver by Unit Gravity Sedimentation
Authors: STEPHENSON JOHN R. , AXELRAD ARTHUR A.
Published: October 2019

An assay method for erythropoietin-sensitive cells has been developed based on the fact that cells of mouse fetal liver respond to erythropoietin in vitro by increased heme synthesis. To determine whether or not hemopoietic colony-forming stem cells are identical with erythropoietin-sensitive cells, C3H/Bi 13-day fetal liver cells were separated into fractions on the basis of size by unit gravity sedimentation through a 1-2 per cent bovine serum albumin gradient. The cell fractions obtained were assayed for erythropoietin-sensitive cells by the present method and for spleen colony-forming cells by the method of Till and McCulloch. It was found that the modal sedimentation velocity of erythropoietin-sensitive cells was greater than that of the spleen colony-forming cells of mouse fetal liver, showing that these two classes of cells are distinct.
Hemoglobin Synthesis in Murine Virus-induced Leukemic Cells In Vitro. I. Partial Purification and Identification of Hemoglobins
Authors: SCHER WILLIAM , HOLLAND J. GILBERT , FRIEND CHARLOTTE
Published: October 2019

Hemoglobin synthesis in murine Friend virus-induced leukemic cells established in tissue culture has been demonstrated. These cells have exhibited a limited degree of differentiation along the erythroid line throughout their serial passage history. Cloned lines differ in the extent of differentiation as evaluated by benzidine staining and the amount of hemoglobin produced. The hemoglobin present in these cells was identified by its histochemical staining properties, peroxidatic activity, incorporation of 59Fe, absorption spectrum, and characteristic migration pattern during discontinuous electrophoresis on polyacrylamide gels. Three hemoglobin components were detected on 10.0 per cent polyacrylamide gels. The electrophoretic pattern of these three hemoglobins appeared similar to that of hemolysates of adult DBA/2J mice, the strain from which the cells originated.
The Response of Leukemic Lymphocytes to Cortisol: A Suggested Role of Transcortin
Authors: WERTHAMER SEYMOUR , AMARAL LEONARD
Published: October 2019

Lymphocytes obtained from patients with chronic lymphocytic leukemia (CLL) respond to the in vitro presence of cortisol by depressed incorporation of precursors into RNA and protein. The decreased incorporation of uridine into RNA is the sum of (1) an inhibition in the synthesis of RNA and (2) an enhanced destruction of newly synthesized RNA. Whereas cortisol was not dependent upon plasma for the manifestation of the above effects, the presence of plasma was an absolute requirement in order for cortisol to have an inhibitory effect on the synthesis of protein. A comparison of leukemic and normal lymphocytes demonstrated that the magnitude of inhibition of precursors into RNA and protein was greater in leukemic cells. Because it is believed that the plasma factor required is transcortin, determination of transcortin levels by cortisolbinding gel filtration technics were performed. These indicated that transcortin levels of CLL plasma were about 50 per cent lower than that of the normal. Consequently, further experiments involving type-specific plasma substitutions were performed. The results obtained from these experiments indicated that the magnitude of the effect of cortisol on the synthesis of lymphocyte protein was directly related to the transcortin level of the plasma employed.
Changes in Proliferative Activity of Marrow Leukemic Cells During and After Extracorporeal Irradiation of Blood
Authors: CHAN B. W. B. , HAYHOE F. G. J.
Published: October 2019

Proliferation activity of bone marrow cells was studied in six patients with acute myeloid leukemia treated by extracorporeal irradiation of the blood (ECIB). One patient with acute lymphoblastic leukemia in full remission was also studied and one patient received splenic irradiation in addition to ECIB. The observations support the hypothesis that ECIB may alter feedback mechanisms of growth control within the leukemic tissue, resulting in an increased proliferative fraction. It is suggested that the nonproliferative leukemic blast cell is not an end cell but is capable of being recalled into cell cycle by an appropriate stimulus such as ECIB.
The Effect of Cold on Platelets. I. Cold-induced Platelet Aggregation
Authors: KATTLOVE HERMAN E. , ALEXANDER BENJAMIN
Published: October 2019

Low temperatures induce platelet aggregation. This effect is greatest when chilled platelet-rich plasma (PRP) is stirred while it is warming or just after it has warmed. The stirring of chilled PRP at low temperature or after prolonged warming causes little aggregation. The extent of aggregation increases as the temperature at which the PRP is chilled is lowered, and as the time of chilling is lengthened. This phenomenon resembles ADP-induced aggregation in that the shape of the aggregation curves of both are similar and both are inhibited by the same compounds. In addition, both forms of aggregation require calcium. However, cold-induced aggregation is not mediated by ADP since this compound is not found in the supernatant of chilled PRP. Nor is the effect of cold on plasma proteins responsible for cold-induced aggregation since cold causes aggregation of platelets suspended in a nonprotein medium. The mechanism of this phenomenon may be similar to ADP-induced aggregation. Its clinical significance is that it may account for the deleterious effect of cold on the preparation and preservation of platelet concentrates.