bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnesium Metabolism of Human and Rabbit Erythrocytes
Authors: GINSBURG STANLEY , SMITH JAMES G. , GINSBURG FREEMAN M. , REARDON JACQUELINE Z. , AIKAWA JERRY K.
Published: October 2019

A modification of the magnesium ammonium phosphate precipitation method for the determination of serum magnesium was devised to determine the magnesium content of erythrocytes.

The concentration of magnesium in the red cells of healthy hospital personnel was 4.67 ± 0.92 mEq./L.

An increase in erythrocyte magnesium concentration was observed in patients with reticulocytosis. Experimental production of reticulocytosis by the administration of phenylhydrazine to rabbits confirmed these clinical observations.

No significant in vitro uptake of Mg28 from the suspending medium occurred in mature human erythrocytes or in mature or immature erythrocytes from rabbits.

The relative tissue uptake of Mg28 in the bone marrow was significantly increased in animals in whom anemia and marked reticulocytosis were produced by phenylhydrazine. Relative activity was decreased in the hearts, spleens, and kidneys of these animals.

Since there is no evidence for significant exchange of magnesium in immature or mature erythrocytes in the peripheral circulation, it is concluded that the magnesium content of erythrocytes is increased in the bone marrow prior to their release into the peripheral circulation.
Recovery of Lethally Irradiated Dogs Following Infusion of Autologous Marrow Stored at Low Temperature in Dimethyl-Sulphoxide
Authors: CAVINS JOHN A. , KASAKURA SHINPEI , THOMAS E. DONNALL , FERREBEE JOSEPH W.
Published: October 2019

Sixteen normal young dogs were exposed to 1200 r of Co60 radiation over their entire bodies continuously at 5 to 6 r per minute. They were then given intravenous infusions of 1 to 5 billion of their own nucleated marrow cells that had been previously aspirated and stored frozen at -80 C. in dimethyl-sulphoxide.

Nine received samples stored in 10 per cent dimethyl-sulphoxide. All made prompt clinical and hematologic recoveries. Three dogs received samples stored in 5 per cent dimethyl-sulphoxide. One died. Three received samples stored in 15 per cent dimethyl-sulphoxide. Two died.

No toxicity of dimethyl-sulphoxide was recognized in these experiments. A disagreeable odor emanated from the injected animals and persisted for a number of hours.

Dimethyl-sulphoxide in 10 per cent concentration is suitable for the preservation of dog marrow at low temperature. Because the specimens preserved in it can be administered intravenously without prior dilution, this additive has an advantage over glycerol.
Studies on the Antimitotic Activity of Leurocristine (Vincristine)
Authors: CARDINALI GIUSEPPE , CARDINALI GIULIANA , ENEIN MOSTAFA ABOUL
Published: October 2019

The effect of leurocristine (vincristine) on cell division was studied in normal bone marrow and leukemic cells (L1210 leukemia) of DBA/2 mice. It was found that vincristine possesses the ability to arrest mitosis at the metaphase stage. The accumulation of arrested metaphases in the normal bone marrow and in leukemic cells of the animals treated with vincristine followed a pattern similar to the one observed after treatment with colchicine or vincaleukoblastine (vinblastine).
Inclusions of Hemoglobin in Erythroblasts and Erythrocytes of Thalassemia
Authors: FESSAS PHAEDON
Published: October 2019

Large, usually single inclusions, having the staining properties of Heinz-bodies and occurring spontaneously in thalassemic cells, are described. Their frequency is greatest in the normoblasts, either circulating ones or those found in the bone marrow, and decreases sharply in more mature red cells. Splenectomy unmasks this inclusion phenomenon to a large extent. Some staining and other properties of these inclusion bodies are described.

It is concluded that these inclusions represent precipitated hemoglobin, very likely uncombined α-chains. The findings are discussed and related to present-day knowledge on hemoglobin synthesis and erythrocyte turnover in thalassemia.
Comparison of 6-Mercaptopurine and Busulfan in Chronic Granulocytic Leukemia
Authors:   SOUTHEASTERN CANCER CHEMOTHERAPY COOPERATIVE STUDY GROUP, HUGULEY CHARLES M. , GRIZZLE JAMES , RUNDLES R. WAYNE , BELL WARREN N. , CORLEY CHARLES C. , FROMMEYER W. B. , GREENBERG B. G. , HAMMACK WILLIAM , HERION JOHN C. , JAMES G. WATSON , LARSEN WILLIAM E. , LOEB VIRGIL , LEONE LOUIS A. , PALMER JEFFRESS G. , WILSON SLOAN J.
Published: October 2019

The relative effectiveness of 6-MP and busulfan for the achievement and maintenance of control of chronic granulocytic leukemia over a period of 12 weeks has been studied. In a randomized study, 15 patients received 6-MP and 9 busulfan. In addition, results of a similar study in which 31 patients were treated with busulfan were combined with the current study. Sequential studies in which patients received more than one course of study were made in 11 patients so that altogether 62 studies were completed in 49 patients.

6-MP produced "good" or "excellent" responses in only 5 (33 per cent) of 15 trials, whereas, 42 (89 per cent) of 47 trials using busulfan responded to this degree.

Busulfan is superior to 6-MP for the over-all control of chronic granulocytic leukemia during a 12-week course of study. Not only are the results obtainable with 6-MP inferior to those with busulfan, but 6-MP is also more difficult to use.

Busulfan in the dosage used reduces the granulocyte count somewhat more slowly than does 6-MP, but the effect is more prolonged. The escape of the granulocytes from depression by 6-MP is very rapid.

The reduction of platelet counts from abnormally high levels to normal is more effectively achieved with busulfan than with 6-MP since, in doses sufficient to reduce the granulocyte count, the latter drug is less likely to affect the level of platelet counts than is busulfan.

It may be possible to exploit these differences occasionally. If a patient becomes difficult to control with busulfan because of thrombocytopenia, 6-MP may offer control with greater safety. In patients whose marrow function is especially susceptible to depression with busulfan, 6-MP may offer the safety valve of a more rapid escape from overtreatment.

In general, 6-MP is not recommended for the routine management of chronic granulocytic leukemia prior to the development of the blast stage.
The Occurrence of Lymphoma in Patients with Long-standing Hyperthyroidism
Authors: ULTMANN JOHN E. , HYMAN GEORGE A. , CALDER BURTON
Published: October 2019

1) Six patients have been presented who, subsequent to long-standing hyperthyroidism, developed a lymphoma (one lymphoblastic lymphosarcoma, one Hodgkin’s disease, one giant follicular lymphoma, and three lymphocytic lymphosarcoma or leukemia).

2) Experimental evidence suggests that hyperthyroidism stimulates and hypothyroidism inhibits lymphoid structures, and hyperthyroidism promotes tumor growth in animals. The mechanism of this action is not clear.

3) Three additional cases of hyperthyroidism followed by the development of a lymphoma were found in the literature.

4) It is suggested that prolonged hyperthyroidism may be a contributory factor in the development of lymphomas or allied disorders in man.
Megaloblastosis Produced by a Cytosine Antagonist
Authors: TALLEY R. W. , VAITKEVICIUS V. K.
Published: October 2019

1. Cytosine arabinoside induced objective, but temporary, decrease of tumor masses in three patients with lymphosarcoma and slight decrease in some lesions in two out of ten treated patients with disseminated carcinomatosis.

2. In doses of 3 to 50 mg./Kg. given at varying intervals, cytosine arabinoside induced definite megaloblastic changes in the marrow of all patients studied. Mitotic abnormalities similar to those found in other megaloblastic anemias also occurred.

3. Associated with bone marrow changes, depressions of hemoglobin, white blood cells and platelets in the peripheral blood were observed.

4. The exact mechanism of action of cytosine arabinoside has not been elucidated. It is speculated that because of the close structural similarity between cytidylic acid, cytosine arabinoside could interfere with DNA synthesis.
The Influence of Race and Phenotype on the Erythrocyte D Antigen Studied by I131—labeled Anti—D
Authors: BARNES ARTHUR E. , FARR RICHARD S.
Published: October 2019

A method for the preparation of I131-labeled anti-D eluates (I[unknown] anti-D) specific for the D antigen by adsorption and elution from intact D positive red cells is presented. A standard D antigen reference system for the quantitative comparison of the red cell D antigen from various donors was developed on the basis of kinetic studies of the effect of pH, temperature and antigen concentration on the I[unknown] anti-D reaction with the D antigen. The red cell D antigen determinations of the blood from 33 Negro and 102 Caucasian donors showed wide monomodal frequency distributions which indicate a heterogeneity of quantitative D antigen reactivity consistent with previous serologic and I131-labeled anti-D studies. The average red cell D antigen reactivity of the 20 probable D homozygote and 14 established D hemizygote Caucasian donors was similar to the D antigen reactivity of the 102 random Caucasian donors. The red cell D antigen reactivity was strongly depressed by the C antigen (or C gene) in Caucasian bloods and enhanced by the E antigen (or E gene) in Negro bloods. The E antigen (or E gene) may also have enhanced the D antigen reactivity in red cells from Caucasian donors, but the difference in D zygosity provides an alternative explanation for the results. The marked influence on red cell D antigen reactivity in the presence of the C and E antigen may well have obscured any lesser influence of D zygosity.
Studies of in Vivo Phagocytosis. I. Inhibition of Phagocytosis by Intact Neoplastic Body Fluids
Authors: KIMBALL SANFORD G. , BRODY JEROME I.
Published: October 2019

1. By means of a modified skin window technic, the phagocytic response of rabbit leukocytes to external stimuli has been observed.

2. Suspensions of particulate antigens, such as rice starch and Candida albicans, made in serums or urines from patients with leukemias and lymphoproliferative disorders, were not phagocytized normally when compared to similar suspensions in normal media.

3. These results suggest that exogenous or endogenous factors, individually or in combination, interfere with normal phagocytic activity in the rabbit and, by analogy, may exercise a similar function in the human.
Virus-like Particles in the Lymphocytes of a Patient with Chronic Lymphocytic Leukemia
Authors: ZUCKER-FRANKLIN DOROTHEA
Published: October 2019

Lymphocytes from the peripheral blood of a patient with chronic lymphocytic leukemia were isolated and subjected to electron microscopy. Aggregates of virus-like particles measuring 80 to 120 Å in diameter were observed as organized structures in the cytoplasm of the cells. The true nature of the particles remains to be established.
Fetal Hemoglobin-containing Erythrocytes I. Counts of Cells Stained by the Acid Elution Method Compared with Alkali Denaturation Measurements
Authors: KIOSSOGLOU KOSMAS A. , WOLMAN IRVING J. , GARRISON MORTIMER
Published: October 2019

The quantitative study of peripheral smears for red cells containing fetal hemoglobin ("F-containing cells") by the acid elution method is a useful and dependable screening test. Findings with this approach were compared with fetal hemoglobin assay by alkali-denaturation in a series of 19 normal subjects and 63 subjects with an assortment of blood disturbances. The results of the two methods had a correlation of +.79, suggesting a reliable but far from perfect identity between the methods. The acid elution method tended to give higher readings, and seemed more sensitive for recognizing individuals with slight increases in red cell fetal hemoglobin as occurs in thalassemia minor.
The Urinary Excretion of Orally Administered Tritium-labeled Folic Acid as a Test of Folic Acid Absorption
Authors: KLIPSTEIN FREDERICK A.
Published: October 2019

The urinary excretion of radioactivity following an oral test dose of tritium-labeled folio acid was determined in a group of 40 subjects which included controls and patients with a variety of malabsorptive disorders. The results were compared with the occurrence of folic acid deficiency, as detected by subnormal serum L. casei folate levels, and with a variety of other tests available for the evaluation of intestinal absorption, including the determination of folio acid absorption based on the microbiological assay of peak serum Str. faecalis folate concentrations following the oral test dose.

The urinary excretion of H3FA in 15 subjects with normal intestinal absorption ranged from 26.0 to 57.8 per cent of the oral test dose, with a mean of 40.7 per cent. The H3FA excretion in 25 patients with intestinal malabsorption ranged from 1.9 to 38.7 per cent, with a mean of 15.3 per cent. Twenty patients in this group excreted less than 26 per cent. Those five patients who excreted greater than 26 per cent were considered to have normal absorption of folic acid since absorption studies of peak serum Str. faecalis folate levels were within the normal range.

The results of the H3FA urinary excretion test correlated well with other parameters of intestinal absorption, particularly in the instances of severe malabsorption, although three cases with malabsorption were observed in which H3FA excretion was subnormal and peak serum Str. faecalis folate concentrations were normal. Folic acid deficiency was observed in 12 patients and its incidence appeared to be related to the severity of impairment of folic acid absorption in the majority of cases.

It is concluded that the H3FA urinary excretion test is a simple, rapid and reliable index of folic acid absorption.
A New, Automatic, Disposable System for Blood Counts and Hemoglobin
Authors: FREUNDLICH MELVIN H. , GERARDE HORACE W.
Published: October 2019

A new system of blood dilution which uses a self-filling, disposable micro-pipette and a prefilled, disposable plastic dilution container has been described. By this means a single .013 ml. sample of blood is all that is required to do a WBC, RBC, Hb and platelet count.

Comparison of the system (Unopette-B-D) with standard pipette counts proved to have a high index of correlation as far as hemoglobin, erythrocyte counts and leukocyte counts were concerned.

Platelet counts tended to show less agreement, the test system giving consistently lower results. The reasons for this were discussed.

The advantages of the new system were discussed.
Extensive Leukemic Infiltration of the Gastrointestinal Tract during Apparent Remission in Acute Leukemia
Authors: EVERETT CHARLES R. , HAGGARD MARY ELLEN , LEVIN WILLIAM C.
Published: October 2019

A child with acute leukemia in an apparent hematologic remission who succumbed to the complications arising from extensive leukemic infiltration of the gastrointestinal tract is reported.

This cannot be explained by any unique anatomical properties of the circulation, such as have been proposed for central nervous system infiltration under similar circumstances.
Effect of Ascorbic Acid in Vivo on Labeling of Red Cells by Radioactive Sodium Chromate
Authors: POPPELL J. WILLIAM , HOOD MARGARET E. , DECOSSE JEROME J.
Published: October 2019

Fifty-two whole blood samples from 17 patients were analyzed for ascorbic acid concentration and Cr51 tagging. Physiologic concentrations of ascorbic acid in whole blood in vivo reduced radioactive sodium chromate in vitro and impaired tagging.
Editorial Review: The Control of Iron Balance by the Intestinal Mucosa
Authors: CROSBY WILLIAM H.
Published: October 2019

In this hypothetical model of intestinal function the ferritin apparatus of the absorptive epithelial cells provides the most important mechanism for day-to-day control of iron balance. Iron incorporated into epithelial ferritin cannot be released and therefore is lost when the cell is lost at the end of the life cycle. Information concerning the state of the body’s iron stores is conveyed to the intestine, perhaps by the concentration of plasma iron or iron-binding capacity. When the iron stores are replete the newly forming epithelial cells are constructed to contain a functional ferritin apparatus capable of synthesizing apoferritin and incorporating iron into ferritin, thus preventing its entering the body. However, this mechanism is not completely adequate to intercept all unneeded iron. When too much iron has bypassed the ferritin apparatus it may be intercepted by tissue macrophages in the villus and lost when these macrophages work their way into the lumen; or it may be loaded into newly forming villous epithelial cells thereby saturating a part of their ferritin capacity. Cells thus loaded would develop increased resistance to the incursion of dietary iron; they would also carry the ferritin iron away with them at the end of their life span. In iron deficiency the absorptive cells are constructed with a relative lack of ferritin apparatus so that dietary iron can pass freely into the cell and thence freely into the body.

In iron storage disease other populations of cells are used for excretion of iron. In general these are the glandular epithelial cells and tissue macrophages. Both varieties of cells are able to accept and store relatively large amounts of nonfunctional iron. They are deciduous cells which are shed from the internal surfaces of the body, and when they go their iron goes with them. The capacity of the excretory mechanism is not great, perhaps about 5 mg. per day. When the rate of introduction of iron into the body exceeds this capacity, siderosis of parenchymal tissues develops due to accumulation of excess iron.
The Pelger-Huët Anomaly and Megaloblastic Anemia
Authors: ARDEMAN S. , CHANARIN I. , FRANKLAND A. W.
Published: October 2019

A patient is described with addisonian pernicious anemia and with the Pelger-Huët anomaly of leukocytes. Before the patient was treated with vitamin B12, her peripheral blood contained three- and four-lobed neutrophils, but with therapy almost all the neutrophils showed the characteristic bilobed form of the Pelger-Huët anomaly. Before treatment the sex chromatin appendage was present in the neutrophils in normal numbers, but these could not be identified after treatment.
Congenital Erythropoietic Protoporphyria
Authors: PORTER F. STANLEY , LOWE BETTY A.
Published: October 2019

Two cases of erythropoietic protoporphyria in brothers are presented in detail. The results of clinical studies and porphyrin analyses are presented. The pathogenesis of hepatic involvement and resulting hypersplenism exhibited by one of the cases is discussed.
Congenital Erythropoietic Protoporphyria
Authors: PORTER F. STANLEY
Published: October 2019

Investigations into the pathophysiology of erythropoietic protoporphyria suggest that the basic defect is an inborn error of metabolism resulting in the overproduction of protoporphyrin IX by the bone marrow not in response to a failure of heme synthesis. A method is described for evaluating the in vitro synthesis of protoporphyrin and heme by human bone marrow.
Phosphate Partition in the Erythrocytes of Normal Newborn Infants and Infants with Erythroblastosis Fetalis. IV. Ion Exchange Chromatography
Authors: GREENWALT T. J. , MORELL S. A. , AYERS V. E.
Published: October 2019

Ion exchange chromatography was used to study perchloric acid extracts of the erythrocytes from the cord blood of normal infants and infants with erythroblastosis fetalis due to anti-D and, for comparison, the red blood cells of adults. Adenosine triphosphate, 2,3-diphosphoglycerate and the total phosphates were found to be highest in the infants with the most severe form of erythroblastosis fetalis. Evidence is given to show that these findings are not related to the relative immaturity of the erythrocytes in hemolytic discase of the newborn. No changes could be demonstrated in the partition of the intraerythrocytic phosphates in a patient with pernicious anemia before B12 therapy and at the height of the reticulocyte response. It is suggested that the high level of 2,3-diphosphoglycerate found in the erythrocytes in hemolytic disease due to anti-D may be due to alterations in the Embden-Meyerhof glycolytic pathway. The nature of the upheaval is not clear at present.
Serology of Acquired Hemolytic Anemias
Authors: WEINER W. , VOS G. H.
Published: October 2019

The investigation of 60 "pan-agglutinating, unspecific" eluates has disclosed distinct blood group specificity within the rhesus system in at least 70 per cent. This has increased our confidence in their true antibody nature. Their investigation has also contributed to our understanding of the makeup of this complex system of Rhesus antigens and antibodies.
The "Infectious Mononucleosis Cell" A Cytochemical Study
Authors: GALBRAITH PETER , MITUS W. J. , GOLLERKERI MOHAN , DAMESHEK WILLIAM
Published: October 2019

The abnormal cells in the peripheral blood of patients with infectious mononucleosis were studied by available histochemical technics and with immunofluorescent and autoradiographic technics. The findings indicated a close relationship of these cells to lymphocytes, although the strong acid phosphatase reaction observed in the infectious mononucleosis (IM) cells was not usually seen in normal lymphocytes, but rather in monocytes and reticulum cells. There was no evidence of antibody production by the IM cells of the peripheral blood.

Studies of the lymph nodes showed two abnormal cell types: one, similar to the IM cells in the peripheral blood but more immature, and the second, a primitive cell with various indications of immunologic competence.
The Sustained Action of Erythropoietin Injected Repeatedly into Rats and Mice
Authors: KEIGHLEY GEOFFREY , HAMMOND DENMAN , LOWY PETER H.
Published: October 2019

Rats and mice were given exogenous erythropoietin for periods from 40 to over 200 days. Increased erythropoiesis was maintained as long as erythropoietin was given; when it was stopped, erythropoiesis returned to its normal level; when the dose was dimished, erythropoiesis fell accordingly.

In mice there was no long-term increase of platelets or change in the differential leukocyte counts and leukocyte counts were, during the middle period of the experiment, decreased.

One mouse developed a tumor. It is pointed out that humans with certain chronic anemias have lived for years with greatly elevated concentrations of erythropoietin in their blood and urine, yet they have normal leukocyte and platelet counts and no tumors.
The Development of Platelet Factor 3 Activity by Latex Particles—An Interaction with Plasma
Authors: HOROWITZ HERBERT I. , MARCUS AARON J.
Published: October 2019

Platelet factor 3 activity of polystyrene latex particles was found to be absent when the particles were tested without prior incubation with plasma. Following such incubation, the particles developed considerable but suboptimal activity. An interaction between the particles and some plasma component(s) during the incubation period which gives rise to a labile type of activity has been postulated.
Synthesis of AHF in von Willebrand’s Disease
Authors: LEWIS JESSICA H.
Published: October 2019

A 5 year old girl suffering from a severe hemorrhagic disorder which appears identical to von Willebrand’s disease is presented. Transfusion of either normal or hemophilic plasma resulted in brief shortening of the bleeding time and gradual and sustained elevation of the AHF (factor VIII) level. The latter observation suggested that this patient was able to synthesize her own AHF when infused with a material present in normal or hemophilic plasma.
Leukemia and Background Radiation in Northern New England
Authors: SEGALL ASCHER
Published: October 2019

A survey of background radiation and mortality from leukemia was conducted in the states of Maine, New Hampshire and Vermont. The radioactivity in bedrock underlying each of 1,178 minor civil divisions was estimated on the basis of radiogeological analysis. Values were found to range from 5 parts per million equivalent uranium in the limestone areas of Vermont to 45 parts per million equivalent uranium in the Conway granite region of New Hampshire.

Mortality records from the tri-state study area for the period 1925-54 were examined. One thousand nine hundred and seventy deaths from leukemia were identified and tabulated by minor civil division. An expected number of deaths by decade was calculated for each minor civil division using the tristate age specific rates for standardization. Minor civil divisions were grouped into four categories according to mean equivalent uranium concentration in underlying bedrock. The difference in annual dose rate from external background sources was estimated to be 14.65 mrads per year. No significant difference in exposure to internal emitters was noted.

The observed and expected numbers of deaths were compared within each of the four radiogeological categories. No statistically significant association was observed between mortality from leukemia and radiogeological category either for the entire 30-year study period or within successive decades.

These data do not allow rejection of the hypothesis that leukemia mortality varies with background radioactivity if the dose response relationship is of the order of that estimated from studies in humans at doses of 100 rads or greater. It seems unlikely that such a hypothesis could be adequately tested in the United States where geographic variation in background radiation is relatively small.
Electron Microscope Studies on Normal Human Myeloid Elements
Authors: CAPONE ROBERT J. , WEINREB EVA LURIE , CHAPMAN GEORGE B.
Published: October 2019

The development of representative myeloid elements is traced by correlated light and electron microscopy. Cytoplasmic changes during maturation of granulocytes from the myeloblast include loss of basophilia, development of the endoplasmic reticulum complex, decrease in number of mitochondria, and granule formation. The endoplasmic reticulum vesicles increase in size and number during the promyelocyte and myelocyte stages, accompanied by the appearance of non-specific and specific granules, and decrease again during the cytosomal maturation of the metamyelocyte. A reduction in number of mitochondria is noted through the metamyelocyte stage. The apparent continuity of the limiting membranes of both the granules and mitochondria with those of the cisternae of endoplasmic reticulum suggests a direct connection among cytosomal organelles. The role of the endoplasmic reticulum in granulogenesis is discussed. Maturation of the nucleus involves a loss of nucleolar differentiation by a loosening of the compact fibrillar aggregates, and progressive chromatin condensation.
Brief Note: Long-Term Survival of Lethally Irradiated Dogs Given Homografts of Bone Marrow
Authors: THOMAS E. DONNALL , PLAIN G. L. , GRAHAM T. C. , FERREBEE JOSEPH W.
Published: October 2019

Chemical, hematologic, biochemical, immunologic and pathologic data are presented in a group of 15 dogs that survived lethal total body radiation, 1200-1800 r, and a transplant of allogeneic marrow for periods ranging from 5 months to 4 years.
Bx, A Subtype of B
Authors: ALTER AARON A. , ROSENFIELD RICHARD E.
Published: October 2019

A subtype of B, termed Bx, was found to have serologic characteristics analogous to those described for subtype Ax. The B determinants of the erythrocytes and salivary secretions of the Bx person could be detected when anti-B was absorbed by and eluted from her red cells. These particularly reactive antibody molecules were best demonstrated by using acacia to support agglutination. Other described subtypes of B have been reviewed and reclassified in accordance with analogous criteria employed for subtypes of A. Evidence was found for two other examples of Bx as well as for B3, Bm and Bg, but not for B2.
Clinical Bone Marrow Scanning with Radioisotopes
Authors: EDWARDS C. LOWELL , ANDREWS G. A. , SITTERSON B. W. , KNISELEY R. M.
Published: October 2019

Thirty-two series of bone marrow scans were performed on 29 patients. The scans were made with three colloid preparations, the most satisfactory of which has been colloidal Au198. Distinct pictures exhibiting the distribution of hematopoietic marrow have been obtained with the ORNL Research Scanner. Local lesions within the marrow organ has been demonstrated and confirmed by histologic studies. Variations in the size and distribution of the marrow organ have been shown in a graphic fashion which have hitherto been impossible. The doses of Au198 required, although rather large, do not produce any detectable early radiation effects. The possibility of harmful effects years after administration limits the present method to selected patients. Bone marrow scanning using the procedure reported here can be of considerable assistance to the investigator, and with improvements anticipated in the technic, it may find its place as a practical clinical procedure.
Rate of Sickling of Red Cells during Deoxygenation of Blood from Persons with Various Sickling Disorders
Authors: CHARACHE SAMUEL , CONLEY C. LOCKARD
Published: October 2019

The clinical severity of various sickle hemoglobinopathies was directly related to the rate of increase of viscosity of blood during deoxygenation. The principal determinants of the rate were the concentration of hemoglobin S in the red cell and the degree of interaction between hemoglobins when more than one major type was present. There was a close correlation between the rate of change of viscosity of blood under the conditions employed and the minimum concentration of the deoxygenated hemolysate required for gelation. Hemoglobin DPunjab showed the most marked interaction with hemoglobin S and hemoglobin F the least, accounting for the striking clinical differences between S-D and S-F heterozygotes. Clinical status of the patients and rate of increase of viscosity of partially deoxygenated blood were not closely correlated with the percentage of hemoglobin S in the hemolysate, the mean corpuscular sickle hemoglobin concentration, or the solubility of the hemoglobin. The viscosity of deoxygenated blood was directly related to the proportion of sickled red cells, but filamentous forms were associated with a greater viscosity than holly leaf forms; accordingly, viscosity could not be predicted precisely from the percentage of sickled erythrocytes in a blood specimen. The viscosity of blood containing sickled erythrocytes was approximately proportional to the square of the hematocrit value, an observation of relevance in explaining the frequent occurrence of vascular occlusive manifestations in patients with certain heterozygous sickling disorders without appreciable anemia. The data of this study support the concept that all of the clinical manifestations of sickle cell disease are attributable to the consequences of intravascular sickling of erythrocytes. Clinical differences between patients whose red cells appear to be similar probably can be explained by extracorpuscular factors influencing rates of sickling.
Hereditary Persistence of Fetal Hemoglobin in Greece. A Study and a Comparison
Authors: FESSAS PHAEDON , STAMATOYANNOPOULOS GEORGE
Published: October 2019

The features of hereditary persistence of fetal hemoglobin in six Greek families are described. In eight cases this abnormality was associated with typical β-thalassemia; in all these cases Hb A was the major hemoglobin component. The clinical and hematologic picture was that of mild thalassemia. The findings are compared to relevant observations in cases of Negro origin and several differences are stressed. It is tentatively concluded that the inherited abnormality occurring in these families is responsible for an incomplete shift from the fetal to the adult type of hemoglobinopoiesis, i.e., from synthesis of γ-chains to the production of β-and δ-chains.
Autoradiographic Study on the Origin and Fate of Small Lymphoid Cells in the Dog Bone Marrow: Effect of Femoral Artery Clamping during in Vivo Availability of H3-Thymidine
Authors: KEISER G. , COTTIER H. , ODARTCHENKO N. , BOND V. P.
Published: October 2019

The origin and fate of small lymphoid cells in the dog bone marrow were studied autoradiographically by observing the effect of clamping of the femoral artery during in vivo availability of H3-thymidine. Heavily labeled small lymphoid cells appeared in the bone marrow of the clamped leg 3 hours after injection of the tracer and increased in number up to 6 days. The labeling indices of these cells, however, were significantly lower than those of control marrow. A possible interpretation is that dog bone marrow contains two populations of small lymphoid cells, one migrating into the marrow via the blood stream, the other originating from local precursor cells within the marrow. There was no evidence for a transformation of migrated small lymphoid cells into erythroblasts during the first 48 hours after injection of H3-thymidine.
Combined Hemophilia and Christmas Disease
Authors: ROBERTSON J. H. , TRUEMAN ROSEMARY G.
Published: October 2019

A case of combined hemophilia (AHG deficiency) and Christmas disease is described. Five other members of the family had either hemophilia or Christmas disease.

The manner of inheritance of the two disorders was uncertain but it was considered most probable that in the mother of the combined case, coupling of the two genes had resulted from a cross-over involving the X-chromosome. It is believed that the findings are consistent with the view that the hemophilia and Christmas disease genes have quite separate loci on the X-chromosome.
Experimental Renal Erythrocytosis. I. Effects of Pressure and Vascular Interference
Authors: MITUS W. J. , GALBRAITH PETER , GOLLERKERI MOHAN , TOYAMA K. , Dorson-Halfond Brenda
Published: October 2019

Experimental data presented in this study indicate that prolonged pressure exerted on the kidneys of rabbits may lead to true erythrocytosis. With approximately 60 per cent of rabbits developing erythrocytosis, the pressure of experimentally induced unilateral hydronephrosis appears to be most effective in this respect. It is suggested that of the role of the renal medulla in the production of erythrocytosis is an important one. Interference with renal arteries and veins did not result in erythrocytosis. The role of erythropoietin and the possible mechanisms by which "renal pressure erythrocytosis" is produced is discussed.
The Presence of Deoxyribonucleic Acid (DNA) Synthesizing Cells in Patients with Refractory Anemia
Authors: COOPER I. A. , FIRKIN B. G.
Published: October 2019

An autoradiographic technic with tritiated thymidine to label cells in the peripheral blood undergoing DNA synthesis, has been utilized to study patients with refractory anemia.

Included in this study are patients with aplastic or hypoplastic anemia and acquired hemolytic anemia. Patients with anemia and chronic renal failure and normal persons as controls have been included.

The patients with aplasia, with no history of exposure to toxic agents, showed a marked increase in labeling index, whereas the patients with a history of exposure to toxic agents showed a normal labeling index.

The patients with refractory hemolytic anemia and positive Coombs’ test revealed a marked increase in labeling.

The cells revealing the increased labeling have the morphologic characteristics of the young lymphocyte.

The hypotheses have been put forward that the cases of aplasia showing an increased labeling index together with the cases of refractory hemolytic anemia may be explained on an auto-immune basis or an increased number of circulating totipotential cells in response to the anemia.
A Case of Red Cell Aplasia Occurring as a Result of Antituberculous Therapy
Authors: GOODMAN STEPHEN B. , BLOCK MATTHEW H.
Published: October 2019

A case of reversible pure red cell aplasia, due to antituberculous therapy, is reported. Re-administration of isoniazid and para-aminosalicylic acid again produced erythroblastic aplasia.
Effect of Prolactin on Erythropoiesis in the Mouse
Authors: JEPSON J. H. , LOWENSTEIN L.
Published: October 2019

The effect of prolactin, growth hormone, progesterone, testosterone, lactating mouse plasma (fifth postpartum day), pregnant mouse plasma (sixteenth to nineteenth day of pregnancy) on erythropoiesis in the polycythemic mouse has been studied and compared. Prolactin was found to stimulate erythropoiesis in the intact mouse. Also, pregnant mouse plasma and lactating mouse plasma had an erythropoietic stimulating effect. Prolactin produced an increase in the red cell mass when administered over a prolonged period to normal and orchidectomized mice. This suggests that the testes are not necessary for the action of prolactin. It is suggested that prolactin could function as an erythropoietic stimulatory component in pregnant and lactating mouse plasma.
A Comparison of Some Physical and Chemical Properties of Erythropoiesis-Stimulating Factors from Different Sources
Authors: ROSSE WENDELL F. , WALDMANN THOMAS A.
Published: October 2019

In the present study we have compared some molecular characteristics of factors stimulating erythropoiesis found in the serum from patients with (a) aplastic anemia and (b) with erythremia due to anoxia, and in cyst fluid from patients with erythremia secondary to (c) a renal cyst and (d) a cerebellar hemangioblastoma. The biological activity of each of the four materials was found to migrate as an α2-globulin on zonal electrophoresis and was destroyed by treatment with sialidase and trypsin; this implies that these materials are mucoproteins with similar electrophoretic mobility. The erythropoietin activity was also completely neutralized by an antiserum made in rabbits to an extract of urine of anemic patients. This implies that these materials share common antigenic determinants. Thus, the erythropoiesisstimulating factors in human anemic and anoxic serum, cerebellar hemangioblastoma cyst fluid, and renal cyst fluid appear to be similar, if not identical. Therefore, the pathogenesis of the erythrocytosis seen in association with renal cysts and cerebellar hemangioblastomas appears to be due to the secretion of erythropoietin by these lesions.
Demonstration of Isoantigenic Receptors on Human Epidermal Cells and Established Cell Lines
Authors: YUNIS EDMOND J. , YUNIS JORGE J. , BRAND K. GERHARD
Published: October 2019

This paper describes mixed agglutination and serum absorption experiments for the demonstration of A, B, H, M, N, D, C, E, c and e isoantigens in human epidermal cells and cultured cells. It was found that only A, B and H antigens are present on human epidermal cells and that this does not appear to be related to the secretor status of the donor. The same antigens were also examined on six different established human cell strains (HeLa, EE, ERK-1, Maben, Chang conjunctiva, Chang liver), and one established mouse cell strain (L). It was found that the H antigen persists in established human cell cultures. The M antigen which is not seen in normal epithelial cells can be demonstrated on HeLa cells by mixed agglutination reaction and by absorption experiments. Guinea pig antisera against established cell lines of human origin were found to contain a small fraction of agglutinins with H specificity, but no anti-M, anti-N or anti-Rh agglutinins.
Study of Immunologic Reactivity in Hemoblastosis. Circulating Antibody Formation as a Response to Antigenic Stimulus in Leukemia, Malignant Lymphoma, Myeloma and Myelofibrosis
Authors: LIBÁNSKY J.
Published: October 2019

If we summarize our observations, we see that the capacity for antibody formation as a response to Brucella endotoxin stimulation is well preserved especially in acute leukemia, chronic myelosis, and in myelofibrosis. It is significantly decreased only in chronic lymphadenosis. A decrease, but lacking statistical significance, was further observed in reticulosarcoma and lymphosarcoma, Hodgkin’s disease, and myeloma, i.e., in affections in which the RES is mainly involved.

The very frequent infectious complications affecting patients with acute leukemia cannot in most cases be ascribed to deficient capacity to form antibodies, as often erroneously claimed, but rather to other factors which will be dealt with elsewhere. In contrast to this, in chronic lymphadenosis the frequent infectious complications are very probably due to impaired antibody formation together with relatively frequent hypogammaglobulinemia.

Chemotherapy, corticoid and x-ray treatment in the usual clinical doses doses were not found to inhibit antibody formation as a response to an antigenic stimulus.

Even changes in the leukocyte count—leukocytosis, neutropenia or lymphopenia—did not seem to inhibit the capacity for antibody formation to Brucella endotoxin.

In 2 patients with idiopathic chronic agranulocytosis, who were examined for comparison, we found a strikingly high titer of circulating antibodies to the Brucella endotoxin. It is suggested that, in chronic agranulocytosis, the capacity for circulating antibody formation may be enhanced to compensate for the decrease in the number of polymorphonuclears.
Intraerythrocytic Hemoglobin Crystals in Sickle Cell-Hemoglobin C Disease
Authors: DIGGS L. W. , BELL ANN
Published: October 2019

On 70 per cent of the blood smears from 60 cases of electrophoretically proven sickle cell-hemoglobin C disease, there is observed a misshapen erythrocyte that contains condensed hemoglobin crystals which are dark-hued, homogeneous and elongated and which have parallel sides with one end terminating in a pyramid or rounded shape. A red blood corpuscle may have multiple protuberances at varying angles to each other. The incidence of intracellular hemoglobin crystals was found to be 0-24 per 1000 red blood cells with an average of 3.2/1000. Recognition of this unusual morphology is presumptive evidence of sickle cell-hemoglobin C and warrants examination by electrophoretic procedures.
Granulocyte Reserve Following Radiation Therapy as Studied by the Response to a Bacterial Endotoxin
Authors: HELLMAN SAMUEL , FINK MARTIN E.
Published: October 2019

The granulocyte response to an intravenous injection of Pyrexal, a highly purified bacterial endotoxin was used as an assay of the marrow granulocyte reserve in patients who had received radiation therapy for various types of neoplasms. The response to the endotoxin was correlated with the amount of marrow irradiated. Only those patients with large volumes of marrow irradiated had abnormal responses to Pyrexal. No patient receiving radiation therapy to the head and neck, or thorax, or pelvis alone, regardless of dose, developed an abnormal response to Pyrexal. Early changes in the marrow granulocyte reserve were also studied in patients before, during and after radiation therapy.
Defective Globin Synthesis in Hypochromic Hypersideremic Anemia (α-Thalassemia?)
Authors: HELLER PAUL , VAN STONE JOHN , APPLE DAVID , COLEMAN RICHARD D.
Published: October 2019

1. The clinical, hematologic and biochemical findings in a patient with hereditary hypochromic hypersideremic anemia are described. The pattern of heme and globin production, measured by glycine-2-C14 incorporation, suggests an abnormality of globin synthesis.

2. The hypothesis that this disorder might represent a variant of thalassemia, probably α-thalassemia, is discussed.

3. The partial therapeutic response to pyridoxine is considered to be due to pharmacodynamic stimulation of heme synthesis. The hemoglobin level was not restored to normal, probably because of the limited capacity for globin synthesis.

4. It is suggested that kinetic studies of hemoglobin synthesis may aid in the classification of hereditary hypochromic hypersideremic anemias.
Patterns of Granulocyte Kinetics in Health, Infection and in Carcinoma
Authors: GALBRAITH PETER R. , VALBERG LESLIE S. , BROWN MALCOLM
Published: October 2019

Leukokinetic studies were performed using granulocytes labeled in vitro with radioactive diisopropylfluorophosphate (DFP32). The half-time of the granulocytes in the circulation, blood granulocyte mass and granulocyte turnover rates were determined.

In control subjects the mean half-life was 6.44 hours with a range of 5.1 to 7.7 hours. The mean blood granulocyte mass was 38 x 109 cells with a range of 19.9 to 36.4 x 109 cells and the granulocyte turnover rate was 4.08 x 109 cells per hour with a range of 2.51 to 5.50 x 109 cells per hour. There was a direct relationship between the half-life and the blood granulocyte mass in the control subjects.

In 6 subjects with infection the blood granulocyte mass was uniformly increased. The mean half-life and mean granulocyte turnover rate were both increased above the normal range.

In 11 subjects with carcinoma several different leukokinetic patterns were found. The blood granulocyte mass was raised in 5 patients, but in only one of these was the granulocyte turnover rate increased above the normal range. In 6 subjects the blood granulocyte mass was within the normal range and deviations from the mean control value were accompanied by proportionate changes in the granulocyte turnover rate in all but 1 patient.

No relation was found between the half-life and the blood granulocyte mass in subjects with infection and/or carcinoma. The possibility that this was due to the establishment of a new steady state of blood granulocyte mass at altered levels of granulocyte production, or that steady state conditions did not exist has been considered. However the data are interpreted no evidence for suppressed granulopoiesis was found in subjects with advanced malignant disease.
The Development of a Myeloma-Like Condition in Mink with Aleutian Disease
Authors: PORTER DAVID D. , DIXON FRANK J. , LARSEN AUSTIN E.
Published: October 2019

Aleutian disease of mink, apparently of viral etiology, is characterized by an extreme diffuse proliferation of plasma cells, and a marked hypergammaglobulinemia, which is electrophoretically heterogeneous. In some mink with this disease serially followed by serum protein electrophoresis, a transition to a homogeneous myeloma-like hypergammaglobulinemia, together with the appearance of Bence Jones proteinuria, was observed late in their course. Thus, this viral disease shows plasma cell proliferation beginning as a multiclonal hyperplasia which may terminate as a monoclonal, possibly neoplastic overgrowth of the plasma cell system.
Steroid Hormone Metabolism in Chronic Myelogenous Leukemia
Authors: GALLAGHER T. F. , HELLMAN LEON , ZUMOFF BARNETT , MILLER DANIEL G.
Published: October 2019

Individual metabolites of steroid hormones were isolated and measured from the urine of patients with chronic myelogenous leukemia. The results were compared with earlier studies of patients with chronic lymphatic leukemia, men with prostatic cancer, women with breast cancer and normal men and women. The metabolites of hydrocortisone were in the normal range for the patients with chronic myelogenous leukemia but the amount of tetrahydrocortisol was generally greater than that of tetrahydrocortisone. There was no evidence for a sex difference in the production of these metabolites. The tentative conclusion was drawn that metabolites of the "adrenal androgens" were also in the normal range in chronic myelogenous leukemia. These results contrast with those in chronic lymphatic leukemia patients where a sex difference in production of hydrocortisone was evident and the metabolites of "adrenal androgens" were at low levels in both sexes.
Origin of Pulmonary Megakaryocytes
Authors: KAUFMAN RICHARD M. , AIRO ROMANO , POLLACK SIMEON , CROSBY WILLIAM H. , DOBERNECK RAYMOND
Published: October 2019

1. Evidence is presented which indicates that pulmonary megakaryocytes do not originate in the lungs but elsewhere in the body and are carried to the lungs in the venous blood.

2. Some megakaryocytes in the lungs evidently deliver platelets to the blood.

3. Surgery is a potent stimulus to megakaryocyte production; the numbers of megakaryocytes found in the lung postoperatively is significantly increased.