bluuebunny/crossref_metadata_2025 huggingface dataset:
Hereditary Methemoglobinemia in Alaskan Eskimos and Indians
Authors: SCOTT E. M. , HOSKINS DALE D.
Published: October 2019

Methemoglobinemia is unusually frequent in Alaskan Eskimos and Indians in whom 15 confirmed cases in a population of about 20,000 are known. It appears to be due to the absence of a factor in red cells which mediates the reduction of methemoglobin by reduced pyridine nucleotides. This anomaly is probably inherited as a recessive trait.

The amount of methemoglobin present at any one time in these persons is variable, depending on some environmental influence. The evidence suggests that this environmental influence is the dietary intake of ascorbic acid.
The Response of Eosinophils to Total-Body X-Radiation of the Monkey
Authors: ELDRED EARL
Published: October 2019

1. Circulating levels of eosinophils in the monkey have been followed before and after total-body exposure to a near median-lethal dose of x-radiation.

2. Eosinophils are moderately decreased during the first three days and strongly depressed in the second and third weeks. During the fourth week these cells rapidly reappear, and an absolute and relative eosinophilia ensues which is maximal at the fifth to seventh week.
Refractory Megaloblastic Anemia Associated with Excretion of Orotic Acid
Authors: HUGULEY CHARLES M. , BAIN JAMES A. , RIVERS SHIRLEY L. , SCOGGINS ROBERT B.
Published: October 2019

A case is presented of a child who had a megaloblastic anemia which was not responsive to vitamin B12 nor to folic acid. The erythrocytes were hypochromic and microcytic, but there was no response to iron or to pyridoxine. Neither parent and no siblings had evidence of thallassemia. The autopsy did not reveal evidence of Di Guglielmo’s disease.

A striking feature was the excretion of large amounts of orotic acid in the urine.

Improvement followed administration of adrenal steroid hormones without reversal of the megaloblastic marrow nor striking reduction in orotic acid excretion.

A seemingly complete hematologic remission and a remarkable reduction in orotic acid excretion followed the administration of a crude mixture containing uridylic acid and cytidylic acid while steroid hormones were continued. Before further studies could be made the child died of severe varicella.
Life Span of Thrombocytes and Erythrocytes in Normal and Thrombocytopenic Calves
Authors: MIZUNO N. S. , PERMAN V. , BATES F. W. , SAUTTER J. H. , SCHULTZE M. O.
Published: October 2019

1. Bovine thrombocytes and erythrocytes became labeled with P32 following an intramuscular injection of DFP.32

2. The life span of bovine thrombocytes calculated from survival curves of DFP32-labeled thrombocytes was about 10 days.

3. The life span of bovine erythrocytes calculated from the linear portion of the survival curve was about 110 to 120 days.

4. There was no significant difference between the life span of the thrombocytes and erythrocytes from normal calves and those from calves with thrombocytopenia induced by the feeding of trichloroethylene-extracted soybean oil meal.
The Comparison of 6-Mercaptopurine with the Combination of 6-Mercaptopurine and Azaserine in the Treatment of Acute Leukemia in Children: Results of a Cooperative Study
Authors: HEYN R. M. , BRUBAKER C. A. , BURCHENAL J. H. , CRAMBLETT H. G. , WOLFF J. A.
Published: October 2019

The results of the first study of the Leukemia Chemotherapy Cooperative Study Group A for the evaluation of two treatment programs in acute leukemia are reported. The cases were accumulated in a period of 15 months. One hundred and twenty-five of the 168 patients started on the study were considered adequately treated and suitable for analysis. The 43 cases excluded from evaluation consisted of patients whose therapy was changed to steroids, those expiring while on treatment, and those lost for follow-up or drug errors. In 125 cases of previously untreated acute leukemia in children, no significant difference was seen in the percentage of complete remissions obtained when 6-mercaptopurine was used alone or when 6-mercaptopurine and azaserine were used in combination.

The duration of the remissions obtained with the combined therapy was not significantly longer than when 6-mercaptopurine was used alone.
Brief Note: A Variety of Human Hemoglobin with 4 Distinct Electrophoretic Components
Authors: ATWATER JEAN , SCHWARTZ I. ROBERT , TOCANTINS L. M.
Published: October 2019

A human hemoglobin with four distinct electrophoretic components was observed in an individual with leptocytosis and reticulocytosis. Three of the components were the previously reported hemoglobins A, C and G. The fourth (Porter) with a mobility of zero on conventional paper electrophoresis in alkaline buffer of pH 8.6, appears to be a new component arising as a result of the random association of the other two abnormal components.
Brief Note: Essential Hypocomplementemia: Report of a Case
Authors: SILVERSTEIN ARTHUR M.
Published: October 2019

A case of essential hypocomplementemia is reported in an individual who for at least 7 years has shown a striking deficiency in serum complement activity, due to a depression in the level of second component of complement. There is no clinical evidence to suggest that the phenomenon has occurred secondary to any recognizable disease process. The significance of complement action and complement deficiency is discussed.
Modification of Irradiation Injury in the Monkey by Bone Marrow Transplantation
Authors: CROUCH B. G. , OVERMAN RICHARD R.
Published: October 2019

Thirty-two adult monkeys were given a single dose of total-body x-irradiation of 650, 700, or 800 r. An attempt was made in 24 of the animals to alter the acute phase of the radiation injury to hematopoietic tissues sulfficiently to prolong the life of the animals by post-irradiation administration of homologous bone marrow. The other 8 animals served as irradiated non-treated controls. Of the 24 bone marrow treated monkeys, 5 survived for more than 30 days post-irradiation. However, a total of 16 animals showed some recovery of the peripheral blood elements toward normal, which seems to indicate that the bone marrow graft may have been functional in these animals. The causes of death in the face of a recovering bone marrow are discussed with regard to immunological reactions, including the "foreign bone marrow reaction," and other contributing factors.
The Segmental Nature of the Spleen
Authors: VAN R. DREYER B. J.
Published: October 2019

1. Radio-opaque material injected into the spleen of dogs and man leaves the organ quickly and in large amounts, thereby providing indirect evidence of an open circulation through the pulp.

2. The injected material does not diffuse through the pulp of the spleen but remains localized to the segments that have been injected. It is then drained by one or more veins. This is confirmatory evidence that the spleen consists of segments that are anatomically and physiologically separate. The behavior of contrast medium in the spleen of dog and man has been exactly similar. There is enough anatomical and experimental proof that the spleen of the dog has a segmental nature and the suggestion is made that this is also true of the human spleen.

3. A small quantity of contrast medium, retained apparently in the connective tissue framework of the spleen, disappears within 24 hours of injection.
The Relationship of Total Red Cell Volume to Total Body Water in Octogenarian Males
Authors: PIOMELLI SERGIO , NATHAN DAVID G. , CUMMINS JAMES F. , GARDNER FRANK H. , Limauro Alvera L.
Published: October 2019

1. Studies of red cell volume, total body water and extracellular water have been carried out in a group of octogenarians and in a group of young men.

2. Differences in total red cell volume, blood volume and the distribution of body water were detected.

3. The implications and interpretations of these findings are discussed.
Erythrocyte Fe59 Uptake as a Function of Bone Marrow Dose Injected in Lethally Irradiated Mice
Authors: HODGSON GEORGE S.
Published: October 2019

The relation between bone marrow cell dose and 24-hour erythrocyte Fe59 uptake has been established in lethally irradiated mice. Erythrocyte Fe59 uptake is a function of the dose of bone marrow cells and of the time after irradiation at which Fe59 is injected. By choosing appropriate bone marrow doses and times of Fe59 injection, the range of cell doses between 5 x 105 and 2 x 107 has been explored. The relation between cell dose and Fe59 uptake is linear for Fe59 uptakes between 0 to 30 per cent. The steepest line relating Fe59 uptake to cell dose is that obtained when Fe59 was injected at day 9 and covers the range of 5 X 104 to 5 X 105 cells. The curve obtained when iron is injected on day 5 is much flatter and covers the range of 1 x 106 to 2 x 107 cells. Erythropoiesis stimulating factor (ESF) in doses that stimulate erythrocyte Fe59 uptake in normal mice has no effect in irradiated, bone marrow-treated mice. Homologous marrow is slightly less effective, and rat bone marrow markedly (∼ 100 times) less effective in promoting recovery of erythropoieis. The erythrocyte Fe59 uptake of mice preimmunized with homologous or rat marrow before irradiation is much lower than that of nonpreimmunized animals.
Evidence for Stem Cells in the Peripheral Blood of Mice
Authors: GOODMAN JOAN WRIGHT , HODGSON GEORGE S.
Published: October 2019

Leukocytes from the peripheral blood of normal F1 hybrid mice have been successfully used to promote survival of lethally irradiated parent and closely related homologous animals. Identification of donor-type red cells and leukocytes has been established on samples of blood taken from several long-term survivors. Histologic data and serologic typing of cells from lymph nodes, bone marrow, and spleens of chimeras killed early after irradiation and treatment established that injected peripheral leukocytes had transplanted and were proliferating into lymphocytes, granulocytes, and erythrocytes. Fe59 was taken up by red cells and spleens of leukocyte-injected mice but not by tissues of radiation control animals. The newly formed, Fe59-labeled erythrocytes were hemolyzed by immune serum specific for donor-type antigens.
Acquired Factor X Deficiency Associated with Systematized Amyloidosis—A Report of a Case
Authors: HOWELL MARGARET
Published: October 2019

A case is described of acquired factor X deficiency in a patient with diffuse amyloidosis and myelomatosis. Rapid transfusion with fresh plasma failed to shorten the Quick single stage prothrombin time. Inhibition of factor X could not be demonstrated in the Patient's plasma in vitro.
Radiation-induced Hemorrhagic Diathesis in Dogs Unassociated with Thrombocytopenia: Association with an Intravascular Protein-Polysaccharide Particle
Authors: WINCHELL H. S. , ANDERSON A. C. , POLLYCOVE MYRON
Published: October 2019

1. Significant thrombocytopenia is not present preterminally in dogs given appropriate doses of Y90-DTPA irradiation. Nevertheless, these animals have a severe hemorrhagic diathesis at postmortem examination.

2. Dogs systemically irradiated with Y90-DTPA, and having a terminal hemorrhagic diathesis, demonstrate an intravascular polysaccharide substance at postmortem examination. This polysaccharide has staining characteristics similar to those first reported by Andersen in dogs systemically irradiated with x-rays, and more recently observed in the lesions of thrombotic thrombocytopenic purpura.
Low Temperature Preservation of Mouse Lymphocytes with Dimethyl Sulfoxide
Authors: ASHWOOD-SMITH M. J.
Published: October 2019

Mouse lymphocytes have been successfully preserved for 3 months at -196 C. in the presence of 15 per cent dimethyl sulfoxide. Other concentrations of dimethyl sulfoxide or glycerol were less effective. The viability of the frozen lymphocytes was assessed by phase contrast microscopy, protein synthesizing activity and by the ability of these lymphocytes to produce splenomegaly when injected with F1 hybrids.
Leukocyte Kinetics in Hematologic Disorders Studied by DNA-Phosphorus Labeling
Authors: WALKER RICHARD I. , HERION J. C. , HERRING W. B. , PALMER J. G.
Published: October 2019

Leukocyte physiology in the normal and in hematopoietic disease states in humans has been studied by DNA-P labeling with inorganic P32. In the normal there is a post-mitotic granulocyte reservoir in marrow about 17 times the size of the intravascular compartment. Progress through this reservoir is orderly and requires about 6 days. Some 1-2 x 1011 cells daily are released from it into the blood. In polycythemia vera there is an increased production of granulocytes. DNA-P labeling in patients with chronic lymphocytic leukemia occurs at a very low level and is compatible with a very slow rate of cell renewal. In one patient with chronic lymphocytic leukemia, no disturbances in kinetics caused by a dose of 20 µc. of P32/Kg. were detected during the time of the study. Although a progressively rising concentration of label in circulating leukocyte DNA was found in patients with chronic granulocytic leukemia, without the lag suggesting a distinct marrow phase, it is concluded that the blood and extravascular leukopoietic compartments cannot be a single compartment. An essentially normal curve is obtained after induction of a complete remission with busulfan.
Studies on the Hemolytic Nature of Protein-Deficiency Anemia in the Rat
Authors: DELMONTE L. , ASCHKENASY A. , EYQUEM A.
Published: October 2019

The hemolytic nature of experimental protein deprivation (PD) anemia has been established (1) by in vitro evidence of (a) the abnormal hemolytic behavior of the PD erythrocytes and an impairment of their reactivity to the protective effect of normal serum and certain of its fractions, and (b) the defective antihemolytic potency of PD serum towards both PD and normal erythrocytes; and (2) by in vivo evidence of the PD erythrocytes’ decreased survival potential.

The hypersensitivity of the PD erythrocytes to chemical and mechanical trauma is interesting, in view of the fact that the cell population is heterogeneous and during the late stage actually includes a slightly elevated percentage of young forms which, normally, should be less sensitive to such trauma. Hence the findings of decreased chemical, alkali and mechanical resistance and increased osmotic resistance in vitro, decreased in vivo survival potential, and impaired responsiveness to in vitro protection by normal serum, lecithin and cholesterol against hemolytic factors, all point to a cellular origin, namely a structural defect, as the cause of the hemolytic nature of experimental PD anemia.

It is probable that the defective composition of PD serum which is less effective than normal serum in protecting normal erythrocytes against chemical, alkali and mechanical trauma in vitro, also contributes to the hemolytic nature of experimental PD anemia in the rat.
RNA Synthesis in Cultures of Normal Human Peripheral Blood
Authors: EPSTEIN LOIS B. , STOHLMAN FREDERICK
Published: October 2019

RNA and DNA synthesis were measured in cultures of normal human peripheral blood using tritiated cytidine and thymidine and autoradiographic technics. RNA synthesis preceded DNA synthesis by 24 hours. RNA synthesis occurred predominantly in the large and medium-sized "blast-like" cells, but did occur, to a lesser extent, in the small lymphocytes. RNA synthesis did not occur in the absence of phytohemagglutinin, nor did DNA synthesis. Mechanisms of action of phytohemagglutinin are discussed with particular reference to its possible antigenic nature.
The Effect of Erythropoietic Stimulation on Marrow Distribution in Man, Rabbit and Rat as Shown by Fe59 and Fe52
Authors: VAN DYKE DONALD , ANGER HAL , POLLYCOVE MYRON
Published: October 2019

Distribution of marrow within the skeleton has been determined in man, rabbits, and rats by in vivo labeling of the marrow compartment with radioiron and either assaying each bone separately for radioactivity or obtaining a gamma-ray image of the distribution of the marrow by whole body scanner or positron scintillation camera. In man, extension of marrow into unusual sites was demonstrated after prolonged and severe stimulation, excessive blood loss, or hemolysis for a long period. A rabbit made severely anemic by administration of phenylhydrazine for 7 days showed extension of marrow into the distal portion of the humeri and femora. In rats in which erythropoiesis was stimulated by erythropoietin administration there was no significant increase in total marrow volume and no change in distribution of marrow within the skeleton.

The positron scintillation camera provides an excellent method for qualitative evaluation of the marrow distribution. It has sufficient resolving power to give a good picture of the distribution of marrow with Fe52 in a skeleton as small as that of the rat. The distribution apparent from the positron pictures has been confirmed by complete skeletal analysis of individual bones.
Phagocytized Plasma Cells in Mouse Spleen Observed by Light and Electron Microscopy
Authors: SWARTZENDRUBER D. C.
Published: October 2019

A correlative light and electron microscopic study is reported of pyknotic, phagocytized plasma cells in the mouse spleen following a single intravenous injection of sheep erythrocytes or rat bone marrow. Phagocytized plasma cells were observed in both red and white pulp between 3 and 7 days after antigen injection. A few mature plasma cells and plasma cells with Russel bodies were found 10 days after stimulation with no evidence of recognizable phagocytized plasma cells. Phagocytosis clearly plays some role in the removal of plasma cells from the spleen under the conditions employed in this study, although the possibility that significant numbers of plasmacytes migrate out of the spleen is considered. A correlation of phagocytized plasma cells with the log phase of antibody appearance in the circulation is indicated.
The Effect of Total Body Irradiation on the Labeling of Circulating Mouse Lymphocytes with Tritiated Thymidine
Authors: WHITELAW D. M.
Published: October 2019

Tritiated thymidine was administered to C3H mice at frequent intervals by intraperitoneal injection over a 2-week period. About one-third of the circulating small lymphocytes were labeled by this procedure. The animals were then exposed to 208 rads of external irradiation which resulted in a fivefold drop in the total circulating lymphocyte count. The labeled newly formed lymphocytes and the unlabeled older lymphocytes proved to be equally sensitive to radiation. The rate of labeling of peripheral blood lymphocytes was unaffected by a single dose of radiation or by a subsequent dose delivered 4 days later. The decline in the curve of labeling, following the discontinuation of labeling with tritiated thymidine, was the same for irradiated and unirradiated mice. These experiments suggest that the output of new lymphocytes is directly related to the level of circulating small lymphocytes and may possibly depend on transformation of small lymphocytes to large proliferating cells.
The Influence of Chemotherapy on Survival in Acute Leukemia
Authors: MANGALIK A. , BOGGS D. R. , WINTROBE M. M. , CARTWRIGHT G. E.
Published: October 2019

Three-hundred and ninety-nine patients with acute leukemia examined during the period 1947-1964 were divided into three sequential series and their survival, from diagnosis to death, was compared.

A statistically significant increase in duration of survival for myeloblastic leukemia from a median of 2 to 5 months occurred between series I and series III. This is the first convincing evidence that 6-mercaptopurine therapy influences survival in myeloblastic leukemia.

A steady increase in median survival of patients with lymphoblastic leukemia from 4 to 8 to 12 months was found in the three series. The results of analysis of these series are compared to other reported series. The hypothesis —that the longer survivals reported for patients treated in hematology clinics compared to that of patients selected from population areas reflects patient selection—was examined and appeared unlikely.
Factors Controlling Erythropoiesis in Birds
Authors: ROSSE WENDELL F. , WALDMANN THOMAS A.
Published: October 2019

1. Erythropoiesis in birds is stimulated by bleeding and environmental hypoxia and is suppressed by induced polycythemia, indicating that the physiologic response is similar to that in mammals.

2. This response is mediated through a humoral factor which stimulates erythropoiesis of birds but not of mammals. Similarly, the erythropoietin of mammals does not stimulate the erythropoiesis of birds.

3. Although both the erythropoiesis stimulating factor of birds and of mammals appear to require an intact protein structure for biological activity, the erythropoietin of birds differs from that of mammals in that it is not destroyed by sialidase and does not lose its activity when reacted with antibody to human urinary erythropoietin.
Hemangioma-Thrombocytopenia Syndrome Associated with Microangiopathic Hemolytic Anemia
Authors: PROPP RICHARD P. , SCHARFMAN WILLIAM B. , Dylong Vivian M. , Scott Helen F.
Published: October 2019

An infant with hemangioma-thrombocytopenia syndrome who was successfully treated with x-irradiation over the hemangioma is described. Studies showed suggestive platelet sequestration in the tumor (as well as spleen), decreased platelet survival, and red cell changes compatible with cell trauma. Speculations concerning the mechanism of the thrombocytopenia are discussed. It is suggested that careful attention should be given to red cell morphology in cases of giant hemangioma in children, particularly those associated with thrombocytopenia.
Ultrastructural Observations on Platelet Adhesion Reactions
Authors: ERICHSON ROBERT B. , KATZ ALFRED J. , CINTRON JOSE R.
Published: October 2019

The morphology of platelet-fibrin interaction in retracting clots and following exposure of platelets to preformed fibrin particles has been studied with the electron microscope. The interaction involved close conformity of the structures at a finite distance, usually 100 to 200 angstroms, and platelet engulfment of fibrin. The morphology closely resembles other platelet adhesion reactions, and it is suggested that the interaction described here is the ultrastructural representation of platelet-fibrin adhesion.
Brief Report: Erythrocytosis Associated with Hepatocellular Carcinoma
Authors: MCFADZEAN A. J. S. , TODD D. , TSO S. C.
Published: October 2019

Employing the polycythemic mouse technic, plasma erythropoiesis-stimulating factor (ESF) was assayed in eight patients with hepatocellular carcinoma of whom four had associated erythrocytosis. An increase was demonstrated in three of the four patients with erythrocytosis. Tumor homogenates from two patients with erythrocytosis were also assayed for ESF but showed no activity.
THE PATHOGENESIS OF ANEMIA IN ACUTE GLOMERULONEPHRITIS. ESTIMATIONS OF BLOOD PRODUCTION AND BLOOD DESTRUCTION IN A CASE RECEIVING MASSIVE TRANSFUSIONS
Authors: EMERSON CHARLES P.
Published: October 2019

1. A 27 year old patient with an initial episode of acute glomerulonephritis was observed over a fifty day period, studies being directed primarily in an attempt to define the mechanisms responsible for a rapidly developing anemia. Hematologic data, including serial blood volume measurements and selective agglutination counts were obtained before and after the introduction of massive transfusion therapy.

2. The administration of group-O whole blood containing incompatible anti-A isoagglutinins in the first series of transfusions failed to improve the anemia but initiated a sustained reticulocyte response. Following this therapy there was evidence of increased blood destruction involving both the recipient’s and the normal donor erythrocytes.

3. Data obtained following a second series of transfusions employing plasma-free group-O red cells, administered during a recovery phase when renal function had improved, indicated that blood destruction had largely abated and that hemopoietic activity was normal.

4. Two factors of undetermined origin are believed to have been implicated in the pathogenesis of anemia in this case: one, the occurrence of abnormally rapid blood destruction, and the other, impairment of blood formation. Both phenomena were associated with the presence of nitrogen retention, despite which, however, a prompt erythropoietic response followed the transfusion of whole blood with quantitative replacement of patient’s red cells with donor erythrocytes, suggesting that previous bone marrow inactivity was not attributable to "toxic suppression."
The Effect of Preceding Blood Transfusions on the Fate of Homologous Bone Marrow Grafts in Lethally Irradiated Monkeys
Authors: VAN PUTTEN L. M. , VAN BEKKUM D. W. , DE VRIES M. J. , BALNEB H.
Published: October 2019

Attempts at bone marrow transplantation after total body irradiation in Rhesus monkeys which have received multiple blood transfusions leads only rarely to acceptance of the graft, whereas in animals that were not previously transfused, a take of the graft is the rule. Immunization against subsequent bone marrow transplants was not only observed after transfusions with blood from the future donor, but also after multiple transfusions from unrelated third-party donors.

From these observations in monkeys it is concluded that many of the failures to observe a take of attempted bone marrow transplants in man may be related to the fact that the recipient had received multiple blood transfusions prior to transplantation.
Brief Report: Immune Response in Mice with Plasma-Cell Tumor (X5563) Assayed by Agar Plaque Technique
Authors: HIRANO SHINJI , IMAMURA YUKIO , TAKAKU FUMIMARO , NAKAO KIKU
Published: October 2019

The immune response to sheep erythrocytes in mice with the gamma-type plasma-cell tumor (X5563) was measured on a cellular level by agar plaque technique of Jerne et al. It was demonstrated that there was a reduction in the number of plaque-forming cells involved in the primary response but not in the secondary response in the mice which were immunized shortly before the inoculation of the tumor. These findings indicate that the lowered antibody response in mice with the tumor is due to a diminished number of antibody-forming cells.
Intraerythroblastic Instability of Hemoglobin β4 (Hgb H)
Authors: FESSAS PHAEDON , YATAGHANAS XENOPHON
Published: October 2019

The bone marrow of three cases of hemoglobin H disease was examined by vital staining with methyl violet. Intraerythroblastic precipitation of hemoglobin, presumably β-chains, was observed in varying degree in all three cases. The process has been studied in relation to erythroblastic maturation and the occurrence of precipitates during early stages of hemoglobin synthesis was demonstrated. The observations are discussed in relation to present-day knowledge concerning hemoglobin β4 and the α-thalassemias.
Physical Properties of Red Cells as Related to Effects in Vivo. I. Increased Rigidity of Erythrocytes as Measured by Viscosity of Cells Altered by Chemical Fixation, Sickling and Hypertonicity
Authors: HAM THOMAS HALE , DUNN REBECCA F. , SAYRE RICHARD W. , MURPHY JOHN R.
Published: October 2019

Changes in the physical properties of red cells were produced by chemical fixation, the sickling process, by suspension in hypertonic sodium chloride and by a combination of hypertonicity and sickling.

These resulted in a loss of deformability or increased rigidity of cells as indicated by a rise in viscosity of cell suspensions and hemolysates, more Newtonian flow, diminished filtration of cell suspensions through microfilters, resistance to packing by centrifugal force and abnormal susceptibility to mechanical trauma. The results of these studies show that in hypertonic sodium chloride all cells have an increased viscosity and are more rigid. The relationship of these physical properties to the behavior of cells in the microcirculation is discussed for normal subjects and those with sickle cell disease, including the effect on the kidney.
Physical Properties of Red Cells as Related to Effects in Vivo. III. Effect of Thermal Treatment on Survival of Red Cells in the Dog. Role of the Spleen
Authors: CARLSON DENNIS J. , HAM THOMAS HALE
Published: October 2019

Dog red cells heated at 49 C. for 15 minutes with no change in osmotic fragility, showed a decreased rate of survival in vivo, and increased sequestration by the spleen, and an increase in the osmotic fragility when recovered from the spleen. The peripheral blood showed normal osmotic fragility at all times. These changes were comparable to those seen in the spleen in homozygous sickle-cell disease and hereditary spherocytosis. There was no hemoglobinemia. Splenectomy decreased the rate of destruction of such heated red cells in vivo. In these studies the rigidity of the red cells with increased viscosity, but with normal osmotic fragility, may have resulted in the removal of the heated red cells by the spleen and subsequent conditioning of these cells in the spleen.

In contrast to the 15 minutes heating, dog cells heated at 49 C. for 60 minutes had increased osmotic fragility and were rapidly removed from the circulation. There was sequestration by the spleen or by the liver with hemoglobinemia. The red cells with the greatest increase in osmotic fragility were not preferentially removed in vivo.
Studies on Antibody-Producing Cells by Hemolytic Plaque Method and Phase Contrast Microscopy
Authors: KIYOHIRO IRIMAJIRI , HORIOCHI ATSUSHI , OKAMOTO YUJI , AMAKI ICHITA
Published: October 2019

The numbers of the PFC in the thoracic duct and lymph node of the immunized rabbit were counted by the hemolytic plaque method and the morphologic features of the PFC in the lymph node were simultaneously observed by phase contrast microscopy.

The number of the PFC in the lymph node maintained a relatively high level on the fourth to seventh days, and then rose to attain the maximum on the ninth to thirteenth days, and then decreased.

The number of the PFC in the thoracic duct reached the maximum on the fourth day after the immunization and then dropped rapidly. The mechanism was discussed.

From morphologic observations, the PFC were classified into lymphogonia, lymphoblast, basophilic mature lymphocyte and plasma cell. The lymphogonia and lymphoblast, which belonged to immature lymphocyte series, were frequent in the early stage and the plasma cell was increased in the later stage of the immunization. The basophilic mature lymphocyte constituted more than 55 per cent through the whole process and were most frequent of the plaque forming cells.
The Ultrastructure of Phytohemagglutinin (PHA) Stimulated Lymphocytes of Chronic Lymphatic Leukemia
Authors: CLAUSEN KATHRYN P. , BOURONCLE BERTHA A.
Published: October 2019

Cultured lymphocytes of chronic lymphatic leukemia have been shown to have a delayed and diminished response to phytohemagglutinin (PHA) stimulation.

By electron microscopic examination, a morphologically distinct intermediate blastoid cell was identified in the stimulated cultures which showed minimal differences between those derived from normal and leukemic lymphocytes. It was distinguished by a large vesicular nucleus and relatively scant cytoplasm with few organelles. This intermediate blastoid cell frequently predominated in cultures with a low total percentage of blastogenesis. It is suggested that this intermediate blastoid cell represents a premitotic phase in lymphocytic transformation, though the possibility of it’s being a nonmitotic blastoid cell cannot be excluded.

No morphologic differences were noted between the large blastoid cells transformed from normal and leukemic lymphocytes.
Radioautographic Studies of the Lymphocytic Bone Marrow
Authors: GRIFFITHS DAVID A.
Published: October 2019

A method is described for producing large numbers of bone marrow lymphocytes in Lewis rats. The bone marrow of posthypoxic polycythemic rats contained larger numbers of lymphocytes than was found in mice and guinea pigs subjected to similar procedures. Autoradiographical studies on the rebound bone marrow, produced evidence that the majority of the lymphocytes were produced in situ, and that they were rapidly turning over. One hundred per cent labeling was achieved after thrice daily intraperitoneal injections of 3/4 µc, tritiated thymidine for 4 days.
Effect of Amino Acids on Iron Absorption from a Staple Vegetable Food
Authors: MARTINEZ-TORRES CARLOS , LAYRISSE MIGUEL
Published: October 2019

Black beans, a staple food consumed in large amounts in Central and South America, were used as a model for the studies of the effect of fish or amino acids present in fish on iron absorption from vegetable food.

The iron absorption rate in 137 subjects showed an asymmetric distribution. The mean iron absorption was 2.6 per cent and the limit of one standard deviation was from 0.8-8.2 per cent.

Iron absorption from black beans increased about twice when the food was administered with either fish or with amino acids in number and proportion as present in 100 Gm. of fish. Further experiments showed that the absorption is not enhanced if the black beans were mixed with either basic amino acids (Histidine, Arginine and Lysine), aromatic amino acids (phenylalanine, Tyrosine and Tryptophan) or other amino acids grouped as "aliphatics" (Glycine, Alanine, Leucine, Isoleucine, Serine, Threonine, Aspartic acid and Glutamic acid). However, either cysteine plus methionine, or cysteine alone enhances iron absorption from black beans in similar proportion as observed when this food was mixed with fish or total amino acids present in fish.
The Response of Chronic Lymphocytic Leukemia to Treatment by Extracorporeal Irradiation of the Blood, Assessed by Isotope-labeling Procedures
Authors: FIELD E. O. , DAWSON K. B. , PECKHAM M. J. , HAMMERSLEY P. A. , COOLING C. I. , MORGAN R. L. , SMITHERS D. W.
Published: October 2019

The changes in circulating and extravascular lymphocyte pools that followed treatment by extracorporeal irradiation of the blood (ECIB) have been studied by isotopic labeling methods in three patients with chronic lymphocytic leukemia (CLL), each of whom exhibited one of three characteristic patterns of response. The patterns of response, and their interpretations in terms of cell kinetics, were as follows:

A rapid, sustained reduction in circulating leukocytes which occurs when extravascular pools are small in relation to the circulating pool.

A rapid rise in peripheral count after ECIB due to a transfer of cells from the extravascular depots when extravascular pools are relatively large and cellular exchange is slow.

A continuing fall in leukocyte count after ECIB resulting from a differential depletion of proliferating cells when the circulating leukocytes consist both of nonproliferating end cells and of their precursors.

These studies have shown that in planning a treatment schedule it is important to determine the nature of the kinetic processes involved.
Normal and Variant Isoenzymes of Human Blood Cell Hexokinase and the Isoenzyme Patterns in Hemolytic Anemia
Authors: ALTAY CIGDEM , ALPER CHESTER A. , NATHAN DAVID G.
Published: October 2019

Electrophoresis of red cell hexokinase in agarose electrophoresis revealed two major (1 and 2) and two minor (3 and 4) bands. Platelet and leukocyte hexokinase patterns differed from those of red cells. There was a strong band 1, but considerably faster bands termed 5, 6 and 7 were also observed which were sensitive to changes in glucose concentration. The presence of contaminating leukocytes can significantly alter the electrophoretic pattern of "red cell" hexokinase activity. Bands 2, 3 and 4 of red cells appeared to be synthesized independently of band 1 and absence of band 1 did not effect either red cell metabolism or survival. Absence of bands 2, 3 and 4 may be associated with hemolytic anemia, decreased erythrocyte hexokinase activity and decreased erythrocyte glycolysis. Young red cells had increased activity of all bands, particularly band 2. No influence of hemoglobin type on hexokinase patterns was observed, nor was there any selective influence of cell storage, medium glucose, or 2-mercaptoethanol on individual bands. None of the various isoenzyme patterns were associated with abnormal hexokinase kinetics.
Hemoglobin Switching in Nonanemic Sheep. III. Evidence for Presumptive Identity between the A→ C Factor and Erythropoietin
Authors: THURMON THEODORE F. , BOYER SAMUEL H. , CROSBY EMILIO F. , SHEPARD MARGUERITE K. , NOYES ANDREA N. , STOHLMAN FREDERICK
Published: October 2019

The degree of A → C hemoglobin switching following administration of a human urine erythropoietin preparation to a non-anemic sheep was compared, in the same animal, with the switching obtained with administration of anemic sheep plasma containing known amounts of erythropoietin. A strong correlation emerges between the dosage of erythropoietin given and the degree of A → C switching observed. This correlation between erythropoietin dose and A → C response is maintained despite the use of materials that originated in different species (man and sheep), were assayed for erythropoietin in yet another species (mouse), and had grossly different specific activities (units/mg.) of erythropoietin, so that the specific activity of the human urine preparation was approximately 400 to 1600 times that of anemic sheep plasma. We believe these observations provide substantial evidence for a provisional hypothesis of identity between erythropoietin and the A → C switching factor.
Effect of Surface Digestion and Metabolic Inhibitors on Appearance of Ferritin in Guinea Pig Erythroblasts In Vitro: Evidences for the Production of Apoferritin on the Erythroblast Cell Membrane
Authors: TANAKA YASUKAZU , BRECHER GEORGE
Published: October 2019

Short-term cultures of guinea pig erythroblasts permitted observation on the micropinocytosis (rhopheocytosis) of ferritin. In the presence of enzymes that attack the cell surface (neuraminidase and trypsin) or of an inhibitor of RNA synthesis (puromycin), accumulation of ferritin in the micropinocytotic vesicle was reduced. No change was seen in presence of lead nitrate, which inhibits transport of iron into hemoglobin-synthesizing cells only slightly. In the presence of potassium cyanide, which inhibits iron transport markedly, ferritin increased two-seven times over controls. The data are compatible with the notion that apoferritin is made on or near the cell surface in response to an excess of iron which accumulates on the cell surface due to failure or overloading of the normal transport mechanism.
Gaucher’s Cells in Thalassemia
Authors: ZAINO EDWARD C. , ROSSI MARIO B. , PHAM TUAN DUC , AZAR HENRY A.
Published: October 2019

Gaucher or Gaucher-like cells are described in the spleen and bone marrow of patient with thalassemia major, by light and electron microscopy. The ultrastructure shows intracytoplasmic tubules and phagocytosis of mature and immature erythrocytes. The spleen has an increase in monohexosyl ceramide. These findings support the concept that the intracytoplasmic tubular material of the Gaucher’s cells is of extracellular origin. Erythrophagocytosis common in Gaucher’s disease, chronic myelogenous leukemia, and thalassemia suggest that impaired catabolism of erythrocytes may give rise to the increased glucocerebroside.
Bactericidal and Metabolic Properties of Human Eosinophils
Authors: MICKENBERG IRA D. , ROOT RICHARD K. , WOLFF SHELDON M.
Published: October 2019

The bactericidal and metabolic activities of peripheral leukocytes obtained by dextran sedimentation from six patients with eosinophilia (50%-90%) due to a variety of etiologies were compared to cells collected from normal donors (70%-95% polymorphonuclear leukocytes). Eosinophils exhibited less phagocytosis than granulocytes, which appeared to account for diminished bactericidal activity against S. albus, S. aureus, and E. coli. The oxidation of glucose-1-14C, glucose-6-14C, and formate-14C were all significantly greater by nonphagocytizing eosinophils than neutrophils. With phagocytosis the increase in glucose-1-14C and glucose-6-14C oxidation was greater for eosinophils than neutrophils despite less measurable particle ingestion. The oxidation of formate-14C by phagocytizing eosinophils was similar to neutrophils in two patients studied. Leukocytic pyrogen (LP) was produced by phagocytosis of heat-killed S. albus or exposure to endotoxin in four out of five cases studied. Blood cells obtained from the fifth patient who had a probable myeloproliferative disorder did not produce significant amounts of LP when similarly stimulated. The common feature of diminished phagocytic activity and elevated resting oxidative metabolism in all patients regardless of etiology of the eosinophilia suggest that this property is common to all eosinophils. The failure of the morphologically abnormal eosinophils of the last patient to release LP served as another distinguishing feature of his cells and may be common to myeloproliferative disorders of the granulocyte series in general.
"Impotent" Platelets in Albinos With Prolonged Bleeding Times
Authors: Maurer Harold M. , Wolff James A. , Buckingham Sue , Spielvogel Arthur R.
Published: October 2019

Functional, biochemical, and morphologic platelet abnormalities are reported in four children with the syndrome of albinism, mild bleeding tendency, prolonged bleeding time, and normal platelet count. In these children, primary platelet aggregation with adenosine diphosphate occurred normally, but secondary aggregation was impaired. Collagen and norepinephrine produced almost no platelet aggregation. Platelet content of serotonin (5-HT) was markedly reduced, and uptake and retention of 5-HT by the platelets in vivo and in vitro was poor. In one child who was given a tryptophan load, urinary tryptophan metabolites were normal, suggesting that there was no evidence of a block in the 5-HT synthetic pathway in the gastrointestinal tract. Electron microscopy revealed an absence of densely osmophilic granules in 5-HT poor platelets. Platelets from other albinos with no history of bleeding contained normal amounts of 5-HT and densely osmophilic granules.
Dyskeratosis Congenita: Relationship to Fanconi’s Anemia
Authors: Steier William , Van Voolen G. Arthur , Selmanowitz Victor J.
Published: October 2019

Dyskeratosis congenita and Fanconi’s anemia share impressive features in common: primary refractory pancytopenia; bone marrow hyperplasia (curtailed phase) and megaloblastosis, eventuating in severe hypoplasia of the marrow; cutaneous melanotic dyschromia; lacrimal duct blockage and a host of other minor abnormalities, in addition to mental retardation and generalized impairment of growth. Evaluation of two brothers with dyskeratosis congenita, and review of previous reports, indicate the following to be more prominent in dyskeratosis congenita than in Fanconi’s anemia: cutaneous telangiectatic erythema and atrophy; exocrine, ungual, and dental dysplasias; mucosal leukoplakia, carcinomatosis, and stenosis; and esophageal diverticula. Prominent in Fanconi’s anemia but not dyskeratosis congenita are the renal and particular skeletal anomalies. Possible transition cases are discussed. The proband studied suffered from progressive refractory pancytopenia, fevers, abdominal pains, malabsorption syndrome, and finally subarachnoid hemorrhage. Cultured leukocytes had normal-appearing karyotypes. The proband’s brother had cutaneous alterations of dyskeratosis congenita, but a hemogram revealed only mild thrombocytopenia and macrocytosis. Both brothers had elevated levels of hemoglobin F, leukocyte alkaline phosphatase, serum IgG, and thyroglobulin antibody, and both had reduced levels of serum IgM and vitamin B12.
EXPERIMENTAL THORACIC DUCT FISTULA OBSERVATIONS ON LYMPHOCYTE OUTPUT
Authors: GLENN WILLIAM W. L. , BAUER FRANCIS X. , CRESSON SAMUEL L.
Published: October 2019

Thoracic duct fistulae in dogs created under local anesthesia and draining continuously from two to eight days have been utilized for the study of lymphocyte output. Too few observations have been made for them to be statistically significant. It is realized that after several days of fistula drainage, factors other than the simple loss of lymphocytes through the thoracic duct fistula may have influenced the lymphocyte output. The necessity for taking into consideration the many factors which may influence lymphocyte output in the evaluation of the effect of any single factor is emphasized.
THE USE OF REPLACEMENT TRANSFUSION IN DISEASES OTHER THAN HEMOLYTIC DISEASE OF THE NEWBORN
Authors: BESSIS M.
Published: October 2019

The technic of exchange transfusion in adults and children is given. It differs from that in newborns only by the use of arm or leg veins and of a motor driven pump to withdraw and inject the blood. The use of exchange transfusion in acute toxemia with anuria was tried on the theory that by withdrawing sufficient toxic products, the patient could be tided over the acute phase. Seven patients were thus treated, all with success.

The use of exchange transfusion in leukemia is based on the theory that normal persons have an antileukemic substance in their blood. Thirty-eight cases were treated with the following results: 30 clinical remissions, of which 15 also had peripheral blood remissions; and of these, 6 had complete clinical peripheral blood and marrow remissions. The author concludes by pointing out some possible applications of this technic.
A Family of Congenital Atransferrinemia
Authors: Goya Nagahide , Miyazaki Sumio , Kodate Saburo , Ushio Bunichi
Published: October 2019

An 8-yr-old boy with familial congenital atransferrinemia was studied. He had marked hypochromic anemia but did not respond to administration of iron. The patient responded favorably to parenteral "Eisen-mangel" human serum transferrin. One gram of transferrin was infused intravenously; it disappeared almost completely from the serum within a week. However, the hemoglobin and erythrocytes increased, and there was general improvement in the color and activity of the patient. After 3-6 mo, his clinical picture had returned to that seen prior to treatment. Thus, it appeared that the hemopoiesis was stimulated by transferrin and that the clinical effectiveness of transferrin was related to the resultant increased red cell production and the duration of the effect to the life-span of the erythrocyte. Neither side effects nor reduction in the effectiveness of transferrin administration was noticed during a year and a half of treatment.
Cellular Handling of Antigen Following Injection Into Neonatal Rabbits
Authors: Garvey Justine S.
Published: October 2019

Newborn rabbits were injected intraperitoneally with a tolerance-inducing dose of labeled radioactive bovine serum albumin. At varying times, 12 hr to 6 wk after injection, tissues were obtained for radioautography. Cellular uptake of antigen appeared confined to the liver, occurring as follows: (1) It became attached initially to erythrocytes in the intravascular system of the liver. (2) Within 1-2 days after injection, it adhered to the cells in extravascular sites where erythropoiesis persisted. (3) Still later. it was associated with hepatocytes. Erythrocytes with adherent antigen were also found in the peripheral blood throughout the period of investigation. The latter finding led to studies of the peripheral erythrocytes of the neonate; membrane properties of these were found unique compared with the adult. It is inferred that erythropoiesis in the liver represents a distinct stage in cellular development. Studies of nonforeign protein, i.e., rabbit serum albumin in neonates, strongly suggested that the erythrocyte-antigen-hepatocyte interaction in the neonate involved a pattern of cellular recognition of foreign protein. Both hematopoiesis and maturation of the liver are discussed as principal factors modulating antigen handling, antibody production, and/or its detection in the neonatal environment that led to the condition commonly defined as "tolerance."