bluuebunny/crossref_metadata_2025 huggingface dataset:
CLINICAL PROFILES
Authors: WALLERSTEIN RALPH O.
Published: October 2019

Experience by many observers in the last few years has shown that intravenously administered iron dextran is a useful and safe agent in the management of iron-deficiency anemia. The conscientious physician, who has diagnosed iron deficiency by the absence of hemosiderin in marrow or by the characteristic serum values for iron and total iron-binding capacity, may well prefer to inject the calculated correct amount of iron rather than depend on the capriciousness of the patient’s gastrointestinal tract or pill-taking habits. In clinical situations in which the doctor-patient contacts are severely limited in number, intravenous injection may be the only reliable way to administer the proper amount of iron. Treatment by intravenous injection, only after employing firm diagnostic criteria, may restore iron to its proper place in the physician’s armamentarium and elevate it from buckshot to bullet.
Brief Report: Plasma Concentrations of Hemopexin, Haptoglobin and Heme in Patients with Various Hemolytic Diseases
Authors: MULLER-EBERHARD U. , JAVID J. , LIEM H. H. , HANSTEIN A. , HANNA M.
Published: October 2019

Plasma concentrations of hemopexin, haptoglobin and heme were determined in patients with various hemolytic diseases. Diminished concentrations of hemopexin were found only when the concentrations of haptoglobin were decreased; the former were not in all instances lowered to the same extent as the haptoglobin levels. Invariably, high concentrations of heme were associated with low concentrations of hemopexin.
Brief Report: Fetal Hematopoiesis—Case Report
Authors: ROSENBERG MIRIAM
Published: October 2019

An unusually well-preserved eleven-week, 4.7 cm. human fetus exhibited active erythropoiesis in liver, and myelopoiesis in femur and humerus; the spleen was the site for sequestration and destruction of primitive erythrocytes, and the yolk sac was fibrotic. High proportions of adult type hemoglobin (A) were found in liver homogenate, and an electrophoretically distinctive fetal form of G6PD was observed.
Splenic Macrophages in Thrombocytopenia
Authors: FIRKIN B. G. , WRIGHT R. , MILLER S. , STOKES E.
Published: October 2019

Electron microscopic examination of splenic tissue obtained from patients with a variety of hematologic disorders has shown ultrastructural evidence for platelet breakdown within splenic histiocytes in seven out of eight patients with idiopathic thrombocytopenic purpura (I. T. P.). The morphologic characteristics of this intracellular digestion have been described.
Acute Monocytic Leukemia as an Explanation for "Hiatus Leukemicus" and "Myelo-Monocytic Leukemia"
Authors: OSGOOD EDWIN E.
Published: October 2019

The term "hiatus leukemicus" suggests a jump in cell development from an early stage to a late stage with nothing in between, analogous to changing from the appearance of a 10 year old to that of a 60 year old without any intermediate stages. The term "myelo-monocytic leukemia" suggests leukemia involving 2 distinct cell series. Better methods for identification of promonocytes indicate that both of these pictures are usually due to cases of acute monocytic leukemia misdiagnosed as chronic granulocytic leukemia. Monocytic leukemias have a greater tendency than other myelophthisic processes to chase normal immature cells of the granulocytic and erythrocytic series into the blood stream. The result is that blast and pro cells actually belonging to the monocytic series are frequently misinterpreted as myeloblasts and progranulocytes because of the association with normal progranulocytes and myelocytes. These misdiagnoses result in reports of too low a proportion of acute monocytic leukemias among the total leukemic population, account for a belief that leukemia is due to maturation arrest rather than early cell death or shortening of the n-cell life span, and for naming leukemias for cells more mature than the alpha-cell. Only the alpha-cell can maintain the necessary somatic genetic continuity.
Blast-Like Transformation Induced in Peripheral Blood Lymphocytes by Cellular Injury: A Comparison of Sonication and Phytohemagglutinin
Authors: TURK ARTHUR , GLADE PHILIP R. , CHESSIN LAWRENCE N.
Published: October 2019

The effects of sublethal sonication on short-term lymphocyte cultures were determined and compared to effects of phytohemagglutinin on similar cultures. Cells stimulated by sonication or PHA showed similar blastoid alteration, similar subtleties of trypan blue staining during the first three days of culture, and similar lysosomal patterns in the altered cells. However, cells from sonicated cultures did not display DNA or RNA synthesis rates above those seen in control cultures. In addition, trypan blue staining characteristics indicated a temporarily reversible injury in PHA stimulated cells, but not in sonicated cells.

These studies support the concept that blast-like transformation of lymphocytes is related to cell damage and possibly to subsequent increase in size and activity of lysosomes.
The Cytochemistry of Acute Leukemia: Observations on Glycogen and Neutral Fat in Bone Marrow Aspirates
Authors: BENNETT JOHN M. , DUTCHER THOMAS F.
Published: October 2019

A cytochemical study of 54 cases of acute leukemia utilizing the periodic acid-Schiff reaction for glycogen and Oil Red O for neutral fat was performed on air dried bone marrow smears. The majority of leukemic lymphoblasts revealed significant amounts of glycogen and neutral fat. "Blast" cells in granulocytic leukemia were devoid of glycogen and of neutral fat. The recommendation is made that both of these histochemical stains be employed to attempt to resolve the problem of specific cellular identification in acute leukemia.
Brief Report: Stimulation of Bone Marrow Colony Growth In Vitro by Human Urine
Authors: ROBINSON W. A. , STANLEY E. R. , METCALF D.
Published: October 2019

Using a new technic of bone marrow culture in agar, urine samples from 50 humans have been tested for their ability to stimulate the formation of granulocyte—mononuclear cell growth in vitro. Significant colony stimulating activity has been found with 25 out of 50 unconcentrated urine samples from both normal humans and patients with a variety of disease states.
The Measurement of Iron Absorption
Authors: COOK J. D. , LAYRISSE M. , FINCH C. A.
Published: October 2019

Sources of variation in iron absorption measurements and methods of controlling them have been reviewed. There are marked differences in the mean level of absorption in different individuals and appreciable day-to-day variation in absorption in the same individual. Intersubject variations can be reduced by the selection of individuals with a more uniform iron requirement, but large variations remain which can be dealt with only by applying appropriate statistical methods to the skewed data obtained and by studying sufficient subjects to provide statistical validity to the results. Comparative studies of the availability of food iron are best carried out against a reference standard in the same subject, and intrasubject variations can be reduced by multiple dose administration.
Cytogenetic Findings in Erythroleukemia
Authors: HEATH CLARK W. , BENNETT JOHN M. , WHANG-PENG JACQUELINE , BERRY ELIZABETH W. , WIERNICK PETER H.
Published: October 2019

Cytogenetic studies of marrow cell lines were done in 10 cases of erythroleukemia and in 6 cases of potentially preleukemic refractory megaloblastic anemia. Abnormalities consisting of aneuploidy, increased polyploidy and chromosome breakage were found in 9 cases, 6 in the erythroleukemia group and 3 in the refractory anemia group. Observations in these cases support the concept that erythroleukemia is a clinical variant of acute granulocytic leukemia. They also indicate that marrow chromosome analysis can assist in the diagnosis of cases where leukemia is suspected but not clinically proven.
Immuno-Electronmicroscopic Studies of Surface Antigens of Blood Elements
Authors: Tonietti Giorgio , Andres Giuseppe A. , Accinni Lidia , Purpura Maria , Hsu Konrad C.
Published: October 2019

PART I

Immuno-Electronmicroscopic Studies of Surface Antigens of Blood Elements. I. Autoantibody on Erythrocytes in Acute Hemolytic Anemia, by Tonietti et al.

Page 179—Methods and Material: The top 6 lines on page 180 should be transposed to page 179 starting as the 3rd line under Source of Erythrocytes, and the section properly reading as follows:

Source of Erythrocytes

The patient (L.S.), a seven year old male, was studied at the Centro Nazionale Transfusione Sangue, C.R.I., in March 1967. His history of anemia dated back to May 1964. Physical examination showed a deeply jaundiced boy. On palpation of the abdomen, the liver was felt 2 cm. below the right costal margin and the spleen 3 cm. below the left costal margin. The superficial lymph nodes were minimally but definitely enlarged. Examination of the blood revealed a red cell count of 1.8 million, a total white count of 3,600 and a platelet count of 180,000 per cu. mm. Bilirubin was 4.9 mg./100 ml. and the osmotic fragility of the red blood cells was normal. The blood group was O CCDee. Etc.

Antiglobulin Tests

Direct agglutination tests performed with the patient’s erythrocytes and antiserum to human globulin and antiserum to human IgG were positive. Absorption of the antihuman globulin with pure IgG rendered the serum incapable of agglutinating the erythrocytes of the patient,6 thus showing that the antibody coating the erythrocytes was of the IgG class.
Reversible and Irreversible Sickling: a Distinction by Electron Microscopy
Authors: BERTLES JOHN F. , DÖBLER JOHANNA
Published: October 2019

Fixatives having either oxidizing or reducing properties were tested in a technic designed to preserve morphologic characteristics of circulating Hb SS erythrocytes. Red cells with cytoplasmic filaments presumably composed of deoxygenated Hb S were found at random by electron microscopy in all preparations. Glutaraldehyde provided the best preservation and was used in subsequent experiments.

Venous blood from Hb SS patients was separated by ultracentrifugation into fractions rich in ISC and rich in non-ISC. The two types of erythrocytes, either oxygenated or deoxygenated, were morphologically distinct; and the aberrant appearance of ISC membranes suggested structural damage. Deoxygenation of non-ISC was associated with loose arrangements of filaments demonstrating a tendency to lie parallel within cell protuberances and in cells’ long axes. Cytoplasm of ISC, devoid of detail when oxygenated, acquired a characteristic filamentous fine structure when deoxygenated: the filament pattern implied either i) a molecular organization of hemoglobin within oxygenated ISC invisible in the electron microscope, or ii) filament formation along paths of least resistance in these irreversibly deformed cells. Behavior of ISC in a magnetic field favored the latter explanation.

These observations are consistent with at least two sequences possibly associated with reversible sickling: filament formation leads to cell distortion, or cell distortion dictates filament arrangement. Both sequences may operate, each augmenting the other. In contrast, permanent deformation of cell shape known as irreversible sickling appears to be the morphologic contribution of membranes presumably damaged during periods of prolonged sequestration.
Increased Formation of Early-Labeled Bilirubin in Rats with Iron Deficiency Anemia: Evidence for Ineffective Erythropoiesis
Authors: ROBINSON STEPHEN H.
Published: October 2019

The production of early-labeled bilirubin and erythrocyte hemoglobin heme was measured in rats with iron deficiency anemia, using glycine-2-14C as precursor. The erythropoietic component of the early pigment fraction was significantly augmented and the formation of labeled hemoglobin depressed in the anemic animals, findings characteristic of ineffective erythropoiesis. By contrast, the hepatic component of early-labeled bilirubin was substantially enlarged during the acute response to iron therapy. These experiments illustrate that overproduction of bilirubin may originate from both erythropoietic and hepatic sources of the early-labeled fraction of bile pigment, as well as from hemolysis of circulating red blood cells.
Enzyme Changes and Polyribosome Profiles in Phytohemagglutinin Stimulated Lymphocytes
Authors: NADLER HENRY L. , DOWBEN ROBERT M. , HSIA DAVID Y. Y.
Published: October 2019

Purified human lymphocytes stimulated with PHA were shown to have increased levels of both lysosomal and "supernatant" enzymes. A redistribution of lysosomal enzymes between bound and free enzymes was shown to occur in PHA stimulated lymphocytes within the first two hours. Polyribosome profiles and a working system of polyribosomes were obtained utilizing nitrogen cavitation for disruption of the cell’s membranes.
Brief Report: Renal Erythropoietic Factor. Lack of Effect on Hypertransfused Mice
Authors: ERSLEV A. J. , KAZAL L. A.
Published: October 2019

In twelve separate studies employing hypertransfused mice, attempts were made to demonstrate the generation of erythropoietin from normal serum incubated with the "Renal Erythropoietic Factor." Despite the use in some studies of preparations found effective in another laboratory, these attempts were all unsuccessful. It is concluded that the hypothesis that erythropoietin is produced by the enzymatic activation of an inactive circulating protein needs much further study before it can be accepted.
The Quantitative Distribution of the Erythron and the RE Cell in the Bone Marrow Organ of Man
Authors: NELP WIL B. , BOWER RAE ELLEN
Published: October 2019

Studies of the quantitative distribution of the RES and the erythron in the bone marrow of the pelvis and lower extremities were performed in a 52 year old male undergoing hemicorpectomy. 198Au colloid and transferrin bound 59Fe were injected 24 hours prior to disarticulation of the lower skeleton. Thirty-three per cent of the injected 59Fe and 3.2 per cent of the injected 198Au-colloid was recovered in the excised skeleton. By calculation approximately 84 per cent of the injected 59Fe and 8 per cent of the 198Au was deposited in the total body marrow. The spatial distribution of 198Au and 59Fe activity was essentially the same in each bone and in multiple small sections of them. The results support the concept that in normal situations the quantitative distribution of the RES and the erythron in the bone marrow organ of man is essentially identical and that radioisotope photoscanning of the marrow using radiocolloids does depict the quantitative distribution of the erythropoietic marrow.
Durable Normal Erythropoiesis in Organotypic Cultures of Guinea Pig Foetal Liver
Authors: SALVATORELLI GERMANO , GULINATI ANNA MARIA , DEL GRANDE PAOLO
Published: October 2019

It is demonstrated that anemic guinea pig serum maintains erythropoiesis in organotypic cultures of fetal guinea pig liver for at least 14 days.

The action of the anemic serum seems be due to the stimulation of the differentiation of stem-cells into erythroblasts. If fetal guinea pig liver is cultured on normal serum the cytodifferentiation stops during the first days of culture whereas the maturation of normoblasts can continue for a few days. The number of stem-cells diminishes considerably and after 4 days they all disappear.

On the contrary in culture on anemic serum, their number is unaltered even after two weeks in culture and this seems to indicate that the anemic serum displays a favorable action in the maintenance of the pool of undifferentiated cells in the explants.
The Effect of Leukocyte Transfusions on Experimental Bacteremia in the Dog
Authors: EPSTEIN ROBERT B. , CLIFT REGINALD A. , THOMAS E. DONNALL
Published: October 2019

A system was developed in the irradiated dog for evaluating the effectiveness of fresh or irradiated homologous leukocyte infusions during the course of induced bacterial sepsis. Dogs with white cell counts below 1000/mm3 4 or 5 days following 1200 r. whole body irradiation were challenged with an intravenous inoculum of E. coli. Untreated animals showed an initial period of bacterial clearance followed within 24 hours by the reappearance of bacteremia. Dogs given a single transfusion of homologous leukocytes following bacterial challenge had a significantly longer period of blood sterility and subsequent survival. Leukocytes irradiated with 1000 r. were effective in extending the period of blood sterility and in prolonging life. It was concluded that the irradiated leukopenic dog challenged with a bacterial inoculum provides a model for demonstrating the usefulness of homologous leukocyte infusions.
Brief Report: Lack of Effect of L-Methionine Ingestion on 14CO2 Excretion from L-Histidine (Imidazole-2-14C) in Folic Acid and Vitamin B12 Deficient Humans
Authors: STAHELIN HANNES B. , WINCHELL H. S. , KUSUBOV N.
Published: October 2019

Three human subjects with folic acid and one with vitamin B12 deficiency failed to show any effect of ingestion of L-methionine (400-800 µg./kg. body weight) on the production of 14CO2 from parenterally administered high specific activity L-histidine (imidazole-2-14C). It is suggested that the inhibitory effect of methionine on intestinal absorption and cell membrane transport of histidine can explain previously published effects of methionine on the oxidation of the imidazole-2 carbon atom of L-histidine and that a direct effect of methionine on histidine metabolism need not be invoked.
A Family with Three βδ-Thalassemia Homozygotes
Authors: RAMOT BRACHA , BEN-BASSAT ISAAC , GAFNI DOROTHEA , ZAANOON REYAD
Published: October 2019

An Arab family with three homozygotes for βδ-thalassemia is described. The single hemoglobin present in their red cells is fetal hemoglobin. A mild hemolytic condition was seen in the propositus, while the two other siblings are completely normal. The main differential diagnosis of this condition is homozygosity for persistent fetal hemoglobin gene.
Reduction of Oxidized Glutathione in Normal and Glucose-6-Phosphate Dehydrogenase Deficient Erythrocytes and Their Hemolysates
Authors: RIEBER EGMOND E. , JAFFÉ ERNST R.
Published: October 2019

When assayed by the ability to reduce oxidized glutathione to reduced glutathione, glucose-6-phosphate dehydrogenase deficiency of either the Negro or Caucasian mutant variety could be demonstrated in hemolysates only with hemoglobin concentrations below 2.0 Gm. per 100 ml. In intact erythrocytes, the inability to regenerate reduced glutathione was apparent regardless of the concentration of red cells. The process of hemolysis, therefore, appeared to permit the demonstration of higher levels of activity in G-6-PD deficient human erythrocytes than was possible in intact cells. A markedly deficient capacity to regenerate endogenous reduced glutathione or to reduce exogenous oxidized glutathione, however, could be demonstrated with the hemolysate of erythrocytes from a patient with hereditary nonspherocytic hemolytic anemia associated with a deficiency of glucose-6-phosphate dehydrogenase activity. These studies have emphasized the hazards involved in extrapolating the results of studies performed with hemolysates to metabolic processes within intact erythrocytes.
Megakaryocytopoiesis in Experimentally Induced Immune Thrombocytopenia
Authors: ROLOVIC ZORAN , BALDINI MARIO , DAMESHEK WILLIAM
Published: October 2019

The hypothesis that in immune thrombocytopenia, platelet antibody may not only cause destruction of the circulating platelets but also depress platelet production by injuring the megakaryocytes of the bone marrow, was tested experimentally.

Sustained thrombocytopenia was produced in rats by titrated injections of a potent heteroimmune antiplatelet serum and megakaryocytopoiesis was then studied by the use of tritiated thymidine and bone marrow autoradiography. Rats in which the platelet count was maintained at a lower than normal level by repeated thrombocytophereses, and other rats injected with platelet antiserum previously absorbed with rat platelets, served as controls.

Profoundly altered patterns of megakaryocytopoiesis were found in the rats in which thrombocytopenia was produced by the antiplatelet serum. The data indicated a severely impaired and depressed megakaryocyte maturation and, possibly, destruction of some of the megakaryocytes during their maturation process. In the rats in which the platelet level was maintained low by repeated thrombocytophereses, the pattern of megakaryocytopoiesis indicated accelerated maturation and there was also an increased megakaryocyte mass. No difference from normal was found in the rats receiving the platelet-adsorbed antiserum. It was concluded that the platelet antibody produced an injurious effect on the megakaryocytes in the bone marrow, thereby depressing platelet production, and that the immune thrombocytopenia was the result of both increased platelet destruction and defective platelet production.
Chromosomes in the Spinal Fluid: Evidence for Metastatic Origin of Meningeal Leukemia
Authors: MASTRANGELO RENATO , ZUELZER WOLF W. , ECKLUND PETER S. , THOMPSON RUBY I.
Published: October 2019

The cytogenetic findings in the spinal fluid of nine children with acute leukemia are presented. Identity or similarity of the chromosomal constitution of the leukemic populations in the spinal fluid and in the bone marrow was observed. The findings are presented as direct evidence for the metastatic nature of meningeal leukemia.
Testosterone-Induced Depletion of Thymus and Marrow Lymphocytes as Related to Lymphopoiesis and Hematopoiesis
Authors: FREY-WETTSTEIN M. , CRADDOCK CHARLES G.
Published: October 2019

Testosterone administration to normal male and female rats causes increased erythropoiesis and granulocytosis at the same time that bone marrow and thymus lymphocytic cellularity is being diminished. The volume of peripheral lymphatic tissue is maintained. Germinal center and plasma cell formation is increased and immunological responsiveness and cellular exudation following nonspecific inflammatory stimulus are retained. These various effects of androgen treatment are discussed in light of different theories of marrow lymphocyte function as stem cells.
Granulocytic Sarcoma (Chloroma)
Authors: WIERNIK PETER H. , SERPICK ARTHUR A.
Published: October 2019

Four patients with granulocytic sarcoma are described. Granulocytic sarcoma of the cheek occurred in one patient 10 months before the diagnosis of acute myelocytic leukemia could be made. Another patient had multiple bone and dural granulocytic sarcomas 17 months before she developed acute myelocytic leukemia. One patient had a breast granulocytic sarcoma and acute myelocytic leukemia diagnosis simultaneously, and a fourth patient developed a chest wall granulocytic sarcoma 11-½ months after the diagnosis of acute monocytic leukemia. The cheek and chest wall granulocytic sarcomas responded completely to antileukemic chemotherapy but subsequently recurred. Radiotherapy effected a permanent complete remission of the chest wall sarcoma, and partial regression of the bone granulocytic sarcomas in another case.

The possibility that acute myelocytic leukemic, granulocytic sarcoma and reticulum cell sarcoma are variations of the same disease is suggested and discussed.
Brief Note: Effects of Prostaglandins, Epinephrine and NaF on Human Leukocyte, Platelet and Liver Adenyl Cyclase
Authors: SCOTT ROBERT E.
Published: October 2019

Despite the limited scope of this study, the data show that homogenates of human leukocytes, platelets and liver are capable of synthesizing cyclic AMP, and that such preparations are responsive to hormonal stimulation. Epinephrine stimulates cyclic AMP production in liver and leukocyte homogenates, and NaF shows a stimulatory effect in each tissue.1,8 The data confirm the previous reports10,11 that prostaglandin E1 stimulates platelet adenyl cyclase, but further shows a lack of stimulation by prostaglandin F/1β. Incubation of leukocytes with the prostaglandins showed a similar effect.

It is suggested that further study may establish a relationship between adenyl cyclase stimulation and chemotaxis or phagocytic activity of circulating leukocytes as has been reported in amebae.12 Since systemic enzyme deficiencies such as phosphorylase in Hers’ Disease13 and amylo-1.4→1.6-transglucosidase in Andersens’ Disease14 are evident in leukocytes, it is suggested that further study of circulating leukocytes may also detect an abnormal responsiveness or a deficiency of adenyl cyclase.
Storage of Platelet Concentrates at 22°C
Authors: MURPHY SCOTT , SAYAR SEYED N. , GARDNER FRANK H.
Published: October 2019

A technique has been proposed which allows easy preparation of platelet concentrates within a closed, sterile system and maximal utilization of other blood components. Lifespan studies have been performed to demonstrate the viability of platelets prepared in this manner. Such concentrates can be stored for as long as three days with adequate maintenance of viability for tranfusion purposes if certain technical requirements are met. Important among these are attention to concentrate volume and pH; agitation of the concentrate is helpful for maintenance of viability. Twelve studies in thrombocytopenic recipients suggest that stored concentrates will be safe and effective in transfusion practice.
Heavy Chain Disease of the µ (γM) Type: Report of the First Case
Authors: FORTE FRANK A. , PRELLI FRANCES , YOUNT WILLIAM J. , JERRY L. MARTIN , KOCHWA SHAUL , FRANKLIN EDWARD C. , KUNKEL HENRY G.
Published: October 2019

The serum of a patient with chronic lymphocytic leukemia, and amyloidosis, was found to contain an unusual protein with µ chain antigenic determinants. It was devoid of light chains and was present in the form of multiple disulfide linked polymers. The patient also had a kappa Bence Jones protein in the serum and urine. The possibility is raised that the heavy chain lacks a portion of the chain necessary for coupling with light chains.
Congenital Erythropoietic Porphyria. II. The Effects of Induced Polycythemia
Authors: HAINING ROBERT G. , COWGER MARILYN L. , LABBE ROBERT F. , FINCH CLEMENT A.
Published: October 2019

Polycythemia and anemia were induced in a patient with congenital erythropoietic porphyria as a possible means of altering erythropoiesis and its attendant porphyrin production. Maintenance of hematocrits at 50 per cent and 60 per cent for periods of 2 weeks decreased both erythropoiesis and porphyrin excretion to about one-half of their initial levels. Conversely with a hematocrit of 25, erythropoiesis and porphyrin production were increased to about twice the basal level. Examination of the marrow showed fluorescence in all late normoblasts and indicated that the patient has only one red cell population. During induced polycythemia, a shift in marrow erythroid population to relatively mature forms, apparently related to delayed enucleation, was accompanied by a retention of the reticulocyte pool and fluorescent cells within the marrow. During anemia, the occurrence of relatively more immature erythroid cells was accompanied by a shift of the reticulocyte pool and fluorescent cells into the circulating blood. During polycythemia, increases were observed in the relative number of nuclear vacuoles peculiar to this disease, in the retention of radioiron in the marrow and in the relative amount of stercobilin excretion. In anemia these parameters decreased towards normal.
Leukemia in Fanconi’s Anemia: Cytogenetic and Tumor Virus Susceptibility Studies
Authors: DOSIK HARVEY , HSU LILLIAN Y. , TODARO GEORGE J. , LEE STANLEY L. , HIRSCHHORN KURT , SELIRIO EVA S. , ALTER AARON A.
Published: October 2019

Fanconi’s anemia is an inherited disorder characterized by multiple congenital abnormalities, chromosome anomalies and irreversible aplastic anemia. Patients, and possibly family members, have been noted to have an increased incidence of leukemia and other tumors. A family with two affected male children, one of whom developed acute myelomonocytic leukemia, is described. Chromosome preparations in both parents showed abnormalities, a previously unreported finding. Fibroblast cultures from both parents and one brother inoculated with Simian Virus 40, a known oncogenic agent, developed increased numbers of transformed colonies, compared with normal control cultures similarly inoculated. The presence of chromosome abnormalities and cellular susceptibility to oncogenic agents appear to be related to an increased risk of malignancy.
Cytogenetic Studies in Acute Myelocytic Leukemia with Special Emphasis on the Occurrence of Ph1 Chromosome
Authors: WHANG-PENG J. , HENDERSON E. S. , KNUTSEN T. , FREIREICH E. J. , GART J. J.
Published: October 2019

Cytogenetic studies were carried out on 103 unselected patients with acute myelogenous leukemia (AML) at the Clinical Center of the National Institutes of Health. Seventy-three patients (70.9%) had a normal karyotype and 30 patients (29.1%) were aneuploid. No unique chromosomal abnormalities were found in patients with aneuploidy; however, there was a significantly higher incidence of G group involvement. Four cases had a history of radiation exposure; three of these four patients had a normal karyotype and one had one Ph1 chromosome in her bone marrow cells. Another patient with no history of radiation also had one Ph1 chromosome in his marrow cells. Reclassification of AML patients with Ph1 chromosomes as a rare entity of blast crisis in chronic myelogenous leukemia (CML) rather than as AML’s is proposed. Two patients exhibited the 45 chromosome syndrome before the diagnosis of AML was made. The normal and aneuploid groups had about the same median survival time and same median date from diagnosis to chromosome study; however, none of the patients in the aneuploid group lived longer than 26 months after the date of diagnosis, while seven patients (nearly 10%) in the normal group did so, one living over 112 months.
Acquisition of Autophagic Vacuoles by Human Erythrocytes Physiological Role of the Spleen
Authors: HOLROYDE CHRISTOPHER P. , GARDNER FRANK H.
Published: October 2019

Using interference-contrast microscopy, erythrocyte vacuoles can be rapidly and easily distinguished. Because of the shadowing effect inherent in this optical system they appear as surface indentations. Twenty splenectomized patients with both normal and abnormal erythropoiesis had 54.3 per cent vacuolated cells as compared to 2.1 per cent in a control group of normal adults. A splenectomized patient with pure red cell aplasia, whose erythrocyte mass was maintained with fresh normal blood, had 44 per cent vacuolated cells. Electron microscopy thin sections showed numerous erythrocyte inclusions and vacuoles which were morphologically suggestive of hemoglobin degeneration. Similar inclusions were noted in all splenectomized subjects studied, and were found in greater numbers in patients with young cell populations. They were rare in normals with intact spleens. Transfusion studies show that these inclusions can be acquired by normal mature erythrocytes when circulating in an asplenic patient. Further, they are cleared from the circulation in the presence of an intact spleen without measurable loss of red cell viability. The evidence suggests that, in the absence of a spleen, autophagic vacuoles may occur in situ in all circulating red cells. It is presumed that these inclusions would normally be removed as a physiological process by a functioning spleen.
Folic Acid Absorption in Pregnancy: Comparison of the Pteroylpolyglutamate and Pteroylmonoglutamate
Authors: MCLEAN FREDERICK W. , HEINE M. WAYNE , HELD BEREL , STREIFF RICHARD R.
Published: October 2019

The gastrointestinal absorption of naturally occurring folate (pteroylpolyglutamate) and therapeutic folate (pteroylmonoglutamate) was studied in a series of pregnant subjects. No significant difference in absorption was found. Furthermore, the elevated estrogen and progesterone levels which occur during pregnancy do not inhibit absorption of pteroylpolyglutamate.
Transplantation of HL-A Identical Allogeneic Bone Marrow to a Patient With Acute Lymphocytic Leukemia
Authors: GRAW ROBERT G. , BROWN JAMES A. , YANKEE RONALD A. , LEVENTHAL BRIGID G. , WHANG-PENG JACQUELINE , ROGENTINE G. NICHOLAS , HENDERSON EDWARD S.
Published: October 2019

An 8-year-old boy with acute lymphocytic leukemia, no longer responsive to conventional chemotherapy after 2 years, was successfully grafted with bone marrow from his HL-A genotypically identical 10-year-old sister. Prior to transplantation, he had received 141 blood component transfusions and had become sensitized to histocompatibility antigens (HL-A), as demonstrated by the presence of circulating lymphocytotoxic antibodies. Except for the occurrence of a possible mild graft-versus-host-reaction and a documented cytomegalovirus infection, the patient remained clinically well until full return of his leukemia 91 days after the transplant. This case demonstrates that bone marrow transplantation can be accomplished between HL-A identical siblings even though the recipient may have been previously sensitized to other HL-A antigens by earlier transfusion. Allogenic bone marrow transplantation offers the opportunity for remissions in patients with leukemia unresponsive to conventional drug therapy.
Treatment of Aplastic Anemia with Nandrolone Decanoate
Authors: DAIBER A. , HERVEÉ L. , CON I. , DONOSO A.
Published: October 2019

Highly satisfactory results obtained with 50 mg./week nandrolone decanoate (Deca-Durabolin) for 3-16 months are reported in 10 cases of aplastic anemia. In the series thus treated there were only two deaths, occurring after only a few months of treatment. All other cases benefited to a large degree: in six, normalization was achieved, and a distinct improvement was seen in two still under treatment. Once therapy had been commenced, there was a period of latency which fluctuated between 1 and 9 months. Except for one patient with Fanconi’s anemia, the other normalized cases have not relapsed after suspension of the drug.
Urinary Iron Excretion in Valvular Heart Disease and After Heart Valve Replacement
Authors: ROESER H. PETER , POWELL L. W.
Published: October 2019

Urinary iron excretion and other aspects of iron metabolism were studied in patients with valvular heart disease before and after valve replacement with heterografts or Starr-Edwards prostheses. Eighty-one per cent of preoperative patients had increased daily urinary iron excretion (0.14-2.2 mg./24 hours) and 61 per cent had a reduced 51Cr survival time. Serum iron levels were low in two patients but iron-deficiency anemia was not observed. Fifty-three per cent of bone marrow aspirates had reduced or absent storage iron. Patients with normally functioning heterografts had no hemolysis and urinary iron excretion decreased exponentially with time until normal values were reached in 6-10 months after surgery. Calculated iron loss over a 6-month postoperative period varied from 11 to 360 mg. Serum iron levels and results of ferrokinetic studies returned towards normal, as did marrow iron stores. Seven patients (78%) with Starr-Edwards valves had evidence of hemolysis by the 51chromium survival method and six were anemic. Urinary iron loss was abnormal in all nine patients (0.8-10.8 mg./24 hours) and iron deficiency was a significant factor in the anemia noted. Iron therapy raised hemoglobin values in the two patients to whom it was administered. Urinary iron excretion was found to be a sensitive index of intravascular hemolysis, particularly in the presence of an intermittent hemolytic process.
In Vitro Growth of Granulocytic and Mononuclear Cell Colonies From Blood of Normal Individuals
Authors: CHERVENICK PAUL A. , BOGGS DANE R.
Published: October 2019

Colonies of eosinophils, neutrophils, monocytes, and macrophages were grown in vitro from peripheral leukocytes of normal individuals. The concentration of circulating nucleated cells capable of giving rise to such colonies is considerably less than in marrow. In blood obtained from six healthy adults, between 4.5 and 21.6 colonies were observed per 106 nucleated cells plated. Growth characteristics of these colonies were similar to those arising from marrow cells. Colony formation was observed after 6-10 days of incubation and increased to a maximum size of 200-1000 cells after 18-20 days and then began to undergo degeneration. Colonies of eosinophils were the most frequent cell type observed. Neutrophil and monocyte colonies were the next most common and occurred with about equal frequency; colonies of mixed cell type were less frequent than the above three types. These colonies were mainly observed at about 3 weeks of incubation. Colonies examined after 4 weeks of incubation consisted primarily of large histiocytes and macrophages. Studies with tritiated thymidine (3H-TDR) revealed that all colonies examined contained labeled cells, indicating that these colonies arose from cell proliferation.
The Effect of 2,3-DPG on the Sickling Phenomenon
Authors: BEUTLER E. , PANIKER N. V. , WEST C.
Published: October 2019

Red cells were depleted of 2,3-diphosphoglycerate (2,3-DPG) by storage in acid-citrate-dextrose (ACD) solution. No change in the sickling-oxygen saturation curve was observed. 2,3-DPG did not affect the viscosity of deoxygenated sickle hemoglobin solutions. It appears, then, that the interaction between 2,3-DPG and sickle hemoglobin does not produce configuration changes which influence the aggregation leading to sickling.
Iron for Erythropoiesis
Authors: JACOBS PETER , FINCH CLEMENT A.
Published: October 2019

Rabbits were rendered anemic by phlebotomy, by parenteral administration of phenylhydrazine and by phlebotomy coupled with transfusion of nonviable erythrocytes. Measurements were made of the number and iron uptake of immature erythroid cells, and the size and hemoglobin content of the circulating erythrocytes. All groups of animals showed the same degree of erythroid cellular proliferation in response to anemia. The total amount of hemoglobin synthesized was determined by the supply of iron to the marrow and was reflected in variations in hemoglobin content within the individual erythrocyte. For maximal production of hemoglobin in the animal with increased cellular proliferation, an increased plasma iron level is required.
Stimulation of DNA Synthesis In Vitro in Mouse Thymic Cells by Bone Marrow Preparation
Authors: KNYSZYNSKI AHUVA , BURGER M.
Published: October 2019

Some characteristics of a bone marrow factor were ascertained, on the basis of its ability to increase 3H-thymidine incorporation into thymic cells in vitro. It was found that the factor was not detectable in kidney or spleen preparations derived from the same mice from which active bone marrow preparations were obtained. The activity of the factor was reduced shortly after total-body irradiation of the mice, and increased again during the regeneration of the bone marrow. It is further shown here that the bone marrow factor has no effect on 3H-thymidine incorporation into mouse bone marrow cells. Leukemic mouse thymic cells show a significantly reduced response towards the bone marrow factor in comparison to normal thymic cells. The bone marrow factor has less effect on protein synthesis than on DNA synthesis in thymic cells, and its stimulatory effect on DNA synthesis is not dependent on protein synthesis. The isolated bone marrow factor is resistant towards heating at 100°C, even at a very low or very high pH. However, it is more labile to heat when in an impure state. Its activity is not affected by RNase, DNase, pronase and carboxypeptidase. It is insoluble in ether, but soluble in absolute ethanol.
Quantitative Studies of Localized Leukocyte Mobilization in Acute Leukemia
Authors: HOLLAND JAMES F. , SENN HANSJOERG , BANERJEE TARIT
Published: October 2019

Localized leukocyte mobilization into autologous serum consists almost entirely of normal appearing granulocytes in normal subjects as well as in patients with acute myelocytic (AML) and acute lymphocytic leukemia (ALL). Sharp reduction in mobilization and in clearance of granulocytes was seen in patients with untreated AML, independent of morphologic subclass, whereas this was not found in ALL. Recombination experiments with leukemic and nonleukemic sera did not reproduce or correct the defects in AML. Nearly normal mobilization and clearance occurred in the remission state. These data taken together suggest that mature granulocytes in florid AML may be mature leukemic cells.
Ceroid Histiocytosis of Spleen and Bone Marrow in Idiopathic Thrombocytopenic Purpura (ITP): A Contribution to the Understanding of the Sea-blue Histiocyte
Authors: RYWLIN ARKADI M. , HERNANDEZ JUAN A. , CHASTAIN DOYLE E. , PARDO VICTORIANO
Published: October 2019

Ceroid-containing histiocytes are described for the first time in the spleen and marrow of a patient with ITP. Ceroid results from the oxidation and polymerization of unsaturated lipids and may appear in histiocytes in a variety of diseases. With the Wright or Giemsa methods, ceroid granules are stained sea-blue, and ceroid-containing macrophages appear as "sea-blue histiocytes." This sea-blue color is not pathognomonic for ceroid. Therefore, the finding of seablue histiocytes in the bone marrow should be followed by histochemical studies to confirm the presence of ceroid. The spleen from a case of the recently described "syndrome of the sea-blue histiocyte" showed numerous ceroid-containing macrophages. In view of the lack of specificity of the sea-blue histiocyte, it is suggested that the syndrome be renamed "idiopathic ceroid histiocytosis of spleen and marrow."
Effect of Neonatal Thymectomy on Hemopoietic Tissue in Mice
Authors: RESNITZKY PERETZ , ZIPORI DOV , TRAININ NATHAN
Published: October 2019

The influence of neonatal thymectomy on the behavior of hemopoietic stem cells of bone marrow and spleen was investigated by studying the colony-forming capacity (CFC) of these cells. Bone marrow cells (2 x 104) from neonatally thymectomized C3H mice, injected into lethally irradiated (850 R) recipients, showed a reduced CFC in relation to that of intact control donors. This decrease, which was more evident in female than in male mice, started early in life after thymectomy, and persisted throughout all the ages investigated. In most of the experiments a concomitant decrease in the total number of nucleated bone marrow cells was observed following thymectomy. When spleen cells (105) from neonatally thymectomized mice were tested under similar experimental conditions, they manifested a CFC equivalent to that of intact controls. Neonatal thymectomy increased the number of spontaneous colonies appearing in the spleen of mice after a sublethal (650 R) total-body irradiation. In contrast, when neonatal splenectomy was tested, a moderate increase in the CFC of bone marrow and in the total number of bone marrow cells was observed. The present results suggest that the thymus plays a role in the proliferative pattern of hemopoietic stem (progenitor) cells located in the bone marrow, whereas it does not influence the behavior of more mature (precursor) hemopoietic cells populating the spleen.
Lipid Content and In Vitro Incorporation of Free Fatty Acids Into Lipids of Human Platelets: The Effect of Storage at 4°C
Authors: OKUMA MINORU , STEINER MANFRED , BALDINI MARIO
Published: October 2019

Lipid content and capacity to incorporate in vitro palmitate-1-14C and linoleate-1-14C into lipids was investigated in fresh and stored (4°C) human platelets. Cholesterol and phospholipids decreased 30% during storage for 6 days. Molar ratio of cholesterol to phospholipids and percentage distribution of individual phospholipids were similar in fresh and stored platelets. Palmitate bound to albumin was rapidly transferred by an energy-independent mechanism into a free fatty acid fraction of platelets. From there it was incorporated into glycerides and phospholipids, a process requiring energy. More palmitate than linoleate was incorporated into fatty acids and glycerides of fresh and stored platelets but linoleate exceeded palmitate in its incorporation into phosphatidylethanolamine. Storage of platelets produced the following changes: (1) Incorporation of palmitate into total lipids was significantly reduced but not that of linoleate. (2) Both palmitate and linoleate showed increased incorporation into phosphatidylethanolamine. (3) Incorporation of linoleate into free fatty acids and triglycerides and of palmitate into phosphatidylcholine was reduced.
Treatment of Meningeal Leukemia With Pyrimethamine
Authors: GEILS GEORGE F. , SCOTT CHARLIE W. , BAUGH CHARLES M. , BUTTERWORTH CHARLES E.
Published: October 2019

Pyrimethamine, a substituted pyrimidine with potent folate antagonistic properties, was given orally to treat two episodes of meningeal leukemia in a longterm survivor with acute myeloblastic leukemia. Remissions of seven and at least 6 mo duration were obtained on the two occasions. Spinal fluid concentrations of pyrimethamine were 10-25% of the simultaneous plasma concentrations. Considerations regarding lipid solubility, body distribution, and easily reversible toxicity of pyrimethamine suggest that further therapeutic trials are warranted, especially in childhood lymphoblastic leukemia.
Effect of High Concentrations of Leukocytes on Whole Blood Viscosity
Authors: STEINBERG MARTIN H. , CHARM STANLEY E.
Published: October 2019

Whole blood viscosity of patients with leukemic leukocytosis was compared to that of normals with a similar total packed cell volume (TPCV). Leukocytes in suspension were also studied and found to have a greater viscosity than erythrocytes. We found no relation between the magnitude of the leukocyte count and whole blood viscosity. The presence of anemia in the patients with leukemia prevented elevation of their TPCV. This, as well as the normal variability of blood viscosity obscured any increase that could have been produced by the greater viscosity of massed leukocytes.
A Method for Leukokinetic Study in the Nonsteady State
Authors: ROTHSTEIN G. , BISHOP C. R. , ATHENS J. W. , ASHENBRUCKER H. E.
Published: October 2019

In these studies, the DF32P leukokinetic technique has been modified so that neutrophil kinetics may be studied in the nonsteady state. In order to achieve this modification, an acid citrate solution was used in preparing leukocytes for radioactive assay. This results in a suspension free of cell agglutination so that a specific activity related only to neutrophils is obtained. This technique has been successfully employed in the study of the early phase of cortisol-induced granulocytosis, allowing measurement of cell flow rate in and out of the circulating granulocyte pool. This method is also useful in the study of subjects with pronounced neutropenia.
Nutritional Deficiency and Anemia in Latin America: A Collaborative Study
Authors: COOK J. D. , ALVARADO J. , GUTNISKY A. , JAMRA M. , LABARDINI J. , LAYRISSE M. , LINARES J. , LORíA A. , MASPES V. , RESTREPO A. , REYNAFARJE C. , SÁNCHEZ-MEDAL L. , VÉLEZ H. , VITERI F.
Published: October 2019

A collaborative study of nutritional anemia in third trimester pregnancy was performed in seven Latin American countries. Laboratory measurements included hemoglobin level, mean corpuscular hemoglobin concentration (MCHC), serum iron and iron-binding capacity, serum folate, vitamin B12 and albumin. Iron deficiency (transferrin saturation below 15%) was found in 48% of pregnant women, as compared with 21% of nonpregnant females and 3% of male controls of comparable age. The prevalence of folate deficiency (serum folate below 3 ng/ml.) was 10%, 10% and 9% in these three groups, respectively. Vitamin B12 deficiency (serum level below 80 pg/ml.) was found in 15% of pregnant women, but in less than 1% of both control groups. Anemia, as defined by current WHO criteria, was found in 38.5% of pregnant women, 17.3% of nonpregnant women and 3.9% of men. Analysis of the frequency distribution for hemoglobin levels, based on a Gaussian distribution in normal subjects, suggested that a large portion of subjects considered anemic by WHO criteria were normal and that the true incidence of anemia in pregnant and nonpregnant females was 22 and 12% respectively. Correlation analysis indicated that iron deficiency was of major importance as a cause of anemia, while folate lack was contributory only in pregnancy; no relationship could be demonstrated between vitamin B12 deficiency and anemia.