bluuebunny/crossref_metadata_2025 huggingface dataset:
Isoimmunity to Blood Platelets in the Rabbit
Authors: BOREL YVES , BALDINI MARIO , EBBE SHIRLEY
Published: October 2019

The occurrence of platelet isoimmunity was studied in rabbits sensitized by 3 to 12 transfusions of homologous blood. Platelet isoimmunity in the transfused animals was detected and measured by two different technics: (1) determination of the survival of homologous platelets labeled in vivo with P32 and infused in the sensitized recipient rabbits; and (2) study of platelet agglutinins in the serum of the multitransfused animals.

It was found that:

1. After 3 to 12 blood transfusions, platelet sensitization, as determined by reduction in survival of homologous platelets in the transfused rabbits, occurred in most animals.

2. Survival of homologous specific platelets, i.e., platelets collected from the sensitizing donor and infused in the respective recipient, usually had lower values than the survival of homologous non-specific platelets.

3. Higher degrees of depression in survival of homologous platelets were found in the rabbits which had received larger numbers of blood transfusions.

4. Platelet isoagglutinins could be found only in three of the five rabbits which had been sensitized with 12 blood transfusions and the test was strongly positive in only one rabbit.

5. Repeat studies performed 2½ months after the transfusions demonstrated persistence of platelet isosensitization, while after 15 months isosensitization had greatly decreased; although in one rabbit a good degree of depression in homologous platelet survival wa still present after this time interval.

These studies mainly demonstrate the high frequency of platelet isoimmunity in multitransfused rabbits and the inadequacy of the agglutinin test in the detection of even relatively severe degrees of platelet isosensitization.
The Effect of 6-Mercaptopurine on the Duration of Steroid-induced Remissions in Acute Leukemia: A Model for Evaluation of Other Potentially Useful Therapy
Authors:   ACUTE LEUKEMIA GROUP B, FREIREICH EMIL J , GEHAN EDMUND , FREI EMIL , SCHROEDER LESLIE R. , WOLMAN IRVING J. , ANBARI RACHAD , BURGERT E. OMAR , MILLS STEPHEN D. , PINKEL DONALD , SELAWRY OLEG S. , MOON JOHN H. , GENDEL B. R. , SPURR CHARLES L. , STORRS ROBERT , HAURANI FARID , HOOGSTRATEN BARTH , LEE STANLEY
Published: October 2019

The effect of 6-MP therapy on the duration of remissions induced by adrenal corticosteroids has been studied as a model for testing of new agents. Ninetytwo patients under age 20 entered the study and were accepted for analysis. Sixty-two (67 per cent) had complete or partial remissions induced by corticosteroids. Patients in remission were randomly assigned to maintenance therapy with either 6-MP or placebo. The median duration of 6-MP-maintained complete remissions was 33 weeks and for placebo, 9 weeks. A sequential experimental design was used to analyze remission times while the study was in progress. This resulted in the study being stopped after analysis of the remission times of 21 pairs of patients (42 patients). Overall survival was not significantly different for the two treatment programs, since patients maintained on placebo were treated with 6-MP when relapse occurred.

The activity of the known active antileukemic compound 6-MP was readily detected by this experimental design without compromise of optimal survival. Such a design should prove useful for the evaluation of new agents and also permit study of the remission maintenance activity of a compound separately from its remission inducing activity.
Observations on Serum B12 and Folate Activity in Normal and Leukemic Rats
Authors: LYNCH THOMAS J. , MOLONEY WILLIAM C.
Published: October 2019

In normal rats serum B12 activity was found to be similar to man but serum folate activity was a good deal higher, in the range of 129 mµg./ml. Total body radiation and administration of 3MCA did not significantly alter B12 or folate activity. Osborne-Mendel rats maintained on a vitamin A-deficient diet were found to have markedly lowered serum B12 activity; the folate levels were only slightly decreased.

Studies on leukemic rats showed that eight animals with myelogenous leukemia had no elevation of the serum B12 activity, and in these animals folate levels were slightly reduced. In two rats with radiation-induced acute lymphatic leukemia, serum B12 activity was significantly elevated due to hepatic necrosis, and folate values were somewhat below normal levels.
Blood Platelet Economy during Moderate and Intensive Heparin Therapy
Authors: MUSTARD J. F. , MURPHY EDMOND A.
Published: October 2019

A study was made of the effects of heparin on platelet survival. The same subjects were studied during control periods and during heparin treatment at two levels of dosage. In most subjects, platelet survival was considerably prolonged and platelet turnover correspondingly diminished when 8000 units of heparin were given 8-hourly, but not with smaller dosage. The evidence in no way implies that such a dosage is optimal—several patients showed little or no response to it. Comparable results were obtained with various in vitro measures of blood coagulability. There was some evidence suggesting that platelet adhesiveness was paradoxically increased when the effect of heparin was wearing off.

These findings raise questions of clinical importance. Moreover, they provide yet further evidence that the survival of the blood platelet is considerably influenced by factors in its external environment.
Megakaryocytes in the Pulmonary Circulation
Authors: SCHEININ T. M. , KOIVUNIEMI A. P.
Published: October 2019

The streptolysin 0 hemolysis method for isolation of cancer cells in the blood was employed for direct observations of the incidence and some characteristics of circulating megakaryocytes.

In a series of 168 patients, circulating megakaryocytes were found in 77 per cent of the blood samples. Each sample contained an average of 1.2 megakaryocytes per ml. of blood. The megakaryocytes were most frequent in pulmonary arterial blood and a number of the cells had an apparently intact abundant cytoplasm. Pulmonary venous blood contained megakaryocytes much less frequently. These were almost always without cytoplasm or with only a narrow rim of it and as a rule small naked nuclei or their fragments were found. Manipulation of lung tissue resulted in an increased amount of megakaryocytes in the pulmonary venous blood.

The megakaryocytes in pulmonary and systemic circulation were more numerous in advanced malignant disease than in early cases, and more common in inflammatory disease or severe anemia than in other nonmalignant disease.
Leukemia in Burkitt’s Lymphoma
Authors: CLIFT R. A. , WRIGHT D. H. , CLIFFORD PETER
Published: October 2019

1. Four cases of Burkitt’s tumor with terminal lymphoblastic leukemia are recorded.

2. The lymphomatous nature of the disease is thus confirmed.

3. The relationship of Burkitt’s tumor to classical lymphoblastic leukemia and its possible viral etiology are discussed.
Renoprival Hemolysis and Its Prevention by Renal Tissue
Authors: MUIRHEAD E. E. , JONES FRANCES
Published: October 2019

The life span of erythrocytes is prominently shortened following bilateral nephrectomy of the dog. This is due to an intracorpuscular defect which appears to develop rapidly. While this defect develops, the erythrocytes remain normochromic and normocytic, display a normal osmotic fragility and are not coated with globulin. Intact renal tissue, as exemplified by the ureterocaval preparation, improves significantly the life span of the erythrocyte. Autoexplanted renal cortex, liver and spleen and the acutely hydronephrotic kidney do not protect against the shortened life span of the erythrocyte. The renal function which appears to protect against in vivo hemolysis seems to be primarily of nonexcretory type and mainly of medullary origin.

The results suggest the presence of a renal principle operating either directly at renal tissue level or indirectly by a humoral factor in preventing in vivo hemolysis.
Studies on Several Genetic Hematologic Characteristics of the Mexican Population
Authors: LISKER RUBÉN , RUIZ-REYES GUILLERMO , LORIA ALVAR
Published: October 2019

The clinical, genetic and electrophoretic characteristics of what is very likely a new hemoglobin variant, hemoglobin Mexico, are presented. It is clinically silent, transmitted by an autosomal co-dominant gene, and in alkaline pH moves faster than hemoglobin A.
Intestinal Mucosal Mechanisms Controlling Iron Absorption
Authors: CONRAD MARCEL E. , CROSBY WILLIAM H. , Merrill Betty
Published: October 2019

Radioautographic studies provide evidence to support a concept of the mechanism whereby the small intestine controls absorption of iron. Three different states of the body’s iron stores have been considered in this regard: iron excess, iron deficiency and normal iron repletion. As the columnar epithelial cells of the duodenal villi are formed they incorporate a portion of intrinsic iron from the body’s iron store, the amount depending upon the body’s requirement for new iron. It is predicated that with iron excess the iron-receptor mechanism in these cells is saturated with intrinsic iron; this then prevents the cell from accepting dietary iron. In the normal state of iron repletion the receptor mechanism remains partly unsaturated, allowing small amounts of dietary iron to enter the cell. Part of this proceeds into the body to satisfy any metabolic requirement for iron. Part is retained in the mucosal epithelial cells to complete the saturation of the iron-receptor mechanism. This bound iron is subsequently lost when the epithelial cells are sloughed at the end of their life cycle. In iron deficiency it is postulated that the receptor system is inactive or diminished so that entry of dietary iron into the body is relatively uninhibited.
A New Variant of Human Fetal Hemoglobin: Hb FRoma
Authors: SILVESTRONI E. , BIANCO I.
Published: October 2019

A new type of abnormal fetal hemoglobin, identified in Rome from the cord blood hemolysate of a healthy newborn girl, is described. This abnormal hemoglobin, which the authors provisionally name Hb FRoma, has an electrophoretic mobility at alkaline pH identical to that of Hb Bart’s and a spectrum in the U. V. of the fetal type. It is, however, composed of normal alpha chains and altered gamma chains. Hb FRoma, which was present at birth in the portion of 17 per cent, disappeared completely during the 5th month of life. No abnormal hemoglobins were identified in the parents.
A Comparison of the Percentage of Fetal Hemoglobin in Human Umbilical Cord Blood as Determined by Chromatography and by Alkali Denaturation
Authors: ARMSTRONG DAVID H. , SCHROEDER W. A. , FENNINGER WILLIAM D.
Published: October 2019

A comparison has been made of the determination of fetal hemoglobin in human umbilical cord blood by column chromatography and alkali denaturation. A careful study has also been made of the variables that control the accuracy and precision of the methods. Minor modification has led to much improved control of the 1-minute alkali denaturation procedure.

The percentage of fetal hemoglobin in the umiblical cord blood of full term infants has been found to cover a far narrower range than is commonly reported. By chromatography, the average is 85.5 per cent with a range from 79 to 91 per cent that includes more than 95 per cent of normal full term infants. By alkali denaturation, the average is 74.0 per cent with a range from 63 to 87 per cent.

Possible correlations with several clinical parameters have been examined. The highest correlation by both methods of determination occurred in the group of 12 samples from infants with a duration of gestation less than 37 weeks. In this group the linear correlation with weight was greater than 0.6.

The precision and accuracy of the chromatographic method recommend it in the study of such subjects as prematurity, twinning, dysmaturity, intrauterine growth retardation, and infants of diabetic mothers.
Serologic and Physicochemical Characterization of Donath-Landsteiner Antibodies from Six Patients
Authors: HINZ CARL F.
Published: October 2019

Donath-Landsteiner antibodies from six patients were studied serologically and physicochemically. All had similar serologic properties including a requirement for complement in the cold phase. Five of the antibodies were associated with the 7S γ2-globulins, while the sixth was associated with 7S γ-globulins of slightly faster electrophoretic mobility and slightly different chromatographic behavior.
Eosinophilic Leukemia Presenting with Erythrocytosis
Authors: THOMAS J. E.
Published: October 2019

Clinical and pathologic data on a young Negro male with a progressive and eventually fatal eosinophilic proliferative disease of 3 years duration has been presented. Unique features were the dual disturbance in the bone marrow and treatment with Myleran.
Rates of Proliferation and Interrelationships of Cells in the Mesenteric Lymph Node of the Rat
Authors: RIEKE WILLIAM O. , CAFFREY RUTH W. , EVERETT N. B.
Published: October 2019

Single and multiple injections of tritiated thymidine were combined with radioautography to study the rates of proliferation and interrelationships of the various cell lines in the mesenteric lymph node of the rat. The appearance and labeling patterns of the different cells are described from studies of both smears and tissue sections. Reticular cells exhibit wide variations in labeling intensity, phagocytize labeled lymphocytes, and become labeled in high percentages only when TTH is administered over a period of many days. Other slowly proliferating cell types include small lymphocytes, fat cells, endothelial cells and mast cells.

Rapidly proliferating cell lines include plasmablasts, hemohistioblasts, proplasmacytes and large lymphocytes. The generation time of plasmablasts and hemohistioblasts was determined to be approximately 9 and 12 hours respectively. Mature plasma cells constitute a non-dividing population which is renewed in lymph node in not more than 5 days.

Evidence is presented that the most primitive cells in the lymphocyte and plasma cell lines are the hemohistioblasts and plasmablasts respectively. Reticular cells most probably are not stem cells. No evidence is found to support previous reports that plasma cells derive from lymphocytes.
The Development of Large Immature Mononuclear Cells in Mixed Leukocyte Cultures
Authors: BAIN BARBARA , VAS MAGDALENE R. , LOWENSTEIN LOUIS
Published: October 2019

1. When leukocytes from two normal, unrelated subjects are mixed together and cultured, some of them transform into large basophilic cells that can synthesize DNA and undergo mitosis.

2. The stimulus for this change is the presence of two sets of leukocytes. Foreign erythrocytes, plasma or platelets have no effect.

3. Studies with mixtures of leukocytes from pairs of identical and nonidentical twins indicate that the reaction may be related to genetic differences between the two subjects.

4. It is suggested that the reaction in leukocyte mixtures may be related to homograft immunity.
Some Data on Mechanism of Leukopenia and Leukocytosis Following Irradiation
Authors: GIDÁLI JULIA , FEHÉR IMRE , Osgyáni Julia
Published: October 2019

1. In rabbits irradiated with 150 to 600 r, granulocytosis is preceded by a prompt significant granulocytopenia developing 5-15 minutes after irradiation but persisting for a short time.

2. The plasma taken at the minimum of the initial granulocytopenia produced a similar two-phase reaction when injected into normal animals: a promptly developing significant granulocytopenia persisting for a short period followed by prolonged granulocytosis. Prolonged thrombocytopenia might be induced by the very same plasma.

3. The above-mentioned reactions may he reproduced satisfactorily with the administration of dilute starch solutions.

4. On the basis of the results obtained, it seems likely that the agent demonstrable in the plasma after irradiation, and influencing the level of circulating granulocytes and thrombocytes, is not a toxin (leukotoxin) but a substance that may be formed following physiologic stimuli as well.
Autologous Bone Marrow Transplantation Studies in Dogs Irradiated by Y90-DTPA Urine-Recycling Technic
Authors: WINCHELL H. S. , POLLYCOVE MYRON , LOUGHMAN W. D. , LAWRENCE J. H.
Published: October 2019

1. Autologous bone marrow infusions are able to save the lives of dogs lethally irradiated with Y90-DTPA.

2. In certain cases the autologous marrow was able to save the life of the Y90-DTPA-irradiated dogs without any marked early elevation in circulating formed blood elements.

3. In contrast to results obtained using external irradiation technics, animals treated with Y90-DTPA and autologous marrow did not show early return of circulating lymphocytes.
Influence of Cobalt, Sheep Erythropoietin and Several Hormones on Erythropoiesis in Bone Marrows of Isolated Perfused Hind Limbs of Dogs
Authors: FISHER JAMES W. , ROH B. L. , COUCH CHARLES , NIGHTINGALE W. O.
Published: October 2019

A technic has been developed for studying the femoral bone marrow of the dog by perfusing the isolated hind limb. With the use of this method, bone marrows were perfused for 4-6 hours with donor dog blood alone and blood containing sheep erythropoietin, cobalt, growth hormone, hydrocortisone, 3,5,3'-triiodothyronine or testosterone. Significant increases were seen in nucleated erythroid cell counts within femoral marrows perfused with blood containing sheep erythropoietin and cobalt. A slight increase was also noted in the bone marrows from limbs in which growth hormone was added to the perfusion system. It may be concluded from these experiments that erythropoietin, cobalt and growth hormone are capable of stimulating erythroid hyperplasia in the bone marrow directly.
Erythrocyte and Plasma Lipids in Sickle Cell Anemia
Authors: WESTERMAN MAXWELL P. , PIERCE LAWRENCE E. , JENSEN WALLACE N.
Published: October 2019

Measurement of various lipid moieties of the nonsickled erythrocytes of patients with sickle cell disease demonstrate an increased concentration of all lipid fractions when compared to a normal similarly aged population of erythrocytes. Highly significant increases in sickle disease cells occurred only in the total lipid fraction. The nonsickled erythrocyte of patients with sickle cell disease appears flatter and has a larger surface area than similarly aged normal cells. Significant decreases in plasma total lipid, phospholipid and cholesterol were present.
Relatively Selective Beta Irradiation of Lymphatic Structures in the Dog Using Y90-DTPA
Authors: WINCHELL H. S. , POLLYCOVE MYRON , ANDERSEN A. C. , LAWRENCE J. H.
Published: October 2019

In an attempt to provide relatively selective irradiation of tissues responsible for the homograft rejection response and to minimize exposure of other radiosensitive tissues, we developed a technic using internally administered Yttrium-90 chelated with DTPA (diethylene triamine-pentaacetic acid). Dogs given sublethal doses of Y90-DTPA radiation had a benign clinical course, the only remarkable finding being a selective lymphopenia without depression of granulocytes, platelets, or reticulocytes. Dogs lethally irradiated with Y90-DTPA showed depression of all formed blood elements, and severe depression of lymphocytes was most prominent. As the homograft rejection response appears to be a function of lymphatic tissues, the results obtained suggest the use of this procedure to prepare large mammals for homologous tissue transplantation.
The Chromatography of Hemins from Normal and Abnormal Human Erythrocytes
Authors: LEE G. RICHARD , HAUT ARTHUR , CAINE THOMAS H. , CARTWRIGHT GEORGE E. , WINTROBE MAXWELL M.
Published: October 2019

1. Erythrocyte hemins, extracted with acid-acetone, exhibited multiple components on two chromatographic systems. However, this heterogeneity can be explained by various physicochemical properties of hemin in solution and does not imply that heme, when attached to globin in the native hemoglobin molecule, is heterogeneous.

2. The presence of a non-polar fraction may be accounted for by esterification of protohemin as a result of reaction with small amounts of methanol contaminating the acetone and/or the presence of some un-ionized protohemin molecule in solutions of low pH.

3. The presence of poorly soluble fractions is probably the result of polymerization of the hydroxyhemin molecule into so-called β- and γ-hematins.

4. The formation of mesohemin is considered unlikely, but the formation of deuterohemin or hematohemin cannot be excluded.

5. No changes in hemin chromatographic patterns were noted in disease.

6. It is necessary to evaluate reports concerning chromatographic hemin heterogeneity in the light of the artifacts described above before attributing physiologic or pathogenetic significance to the findings.
The Nature of Some Subtypes of A
Authors: ALTER AARON A. , ROSENFIELD RICHARD E.
Published: October 2019

The subtype AxB has been encountered and described, along with two new examples of the subtype Ax. Anti-A and anti-A,B that has been absorbed by and eluted from erythrocytes of subtype Ax are sensitive to at least partial inhibition by the salivary secretions of the Ax person, thereby implying that A determinants are expressed in the salivary secretions as well as on the erythrocytes. Saliva of the AxB person did not possess such inhibitory activity. However, family study disclosed that this person was likely to possess an unusual A2B genotype in which the B gene suppresses, at the phenotypic level, the expression of paired A. Furthermore, an underlying disease, myeloid metaplasia, may have further suppressed the expression of A determinants on both erythrocytes and in salivary secretions. Three other pedigrees revealed suppression of A by paired B, and in one instance, the genotype A1B was found to give rise to the phenotype A2B. Some population studies fail to demonstrate satisfactory Hardy-Weinberg equilibrium when tested in accordance with the usual four allele theory of inheritance for the A1A2BO phenotypes. An additional allele, suppressor B (B[unknown]) was assumed for five such studies, and a more satisfactory fit between expected and observed values was obtained.
Fibrin Suspension Assay for Fibrinolytic Activity
Authors: DYER A. E. , KADAR D.
Published: October 2019

A new method has been described for measuring fibrinolytic activity. The method is based on the change in turbidity resulting from the dissolution of suspended particles of fibrin under the influence of fibrinolytic agents. Because the technic exposes a vast surface area of substrate, measurable changes occur rapidly. The procedure is not complex, yet provides more accurate estimates than other methods employing fibrin as a substrate.

The method also has the advantage that conditions such as temperature, pH and length of incubation can be varied. Experiments illustrating this have been reported.

The following two fibrinolytic agents were studied.

1. Human plasmin activated with glycerin.

2. An extract of Aspergillus oryzae.
The Role of Zinc, Copper and Calcium in the Etiology of the "Meat Anemia"
Authors: GUGGENHEIM KARL
Published: October 2019

The suggestion that the "meat anemia" of mice is due to a dietary lack of copper accompanied by an excess of zinc in meat was investigated.

Muscle meat contains small amounts of copper and much more zinc whereas liver which protects against "meat anemia" contains more copper and less zinc than muscle. Supplementation of meat with copper or liver, which reduce the zinc-copper ratio of the diet, prevents anemia. Addition of zinc, which increases the zinc-copper ratio, leads to anemia.

Calcium prevents anemia even when the zinc-copper ratio is high. Treatment with vitamin D does not protect against anemia. It is concluded that calcium acts before its absorption in the intestinal tract, probably by interfering with the absorption of zinc.

Anemia also develops in mice which are maintained on a semisynthetic low-calcium diet with a higher content of zinc than of copper. Supplementation of this diet with calcium likewise alleviates the anemia.

Rats, which are resistant to "meat anemia," are less susceptible to the toxic effects of zinc than mice.

"Meat anemia" of mice seems, therefore, to result mainly from the presence in meat of insufficient amounts of copper accompanied by an excess of zinc, the effects of which are accentuated by a concomitant lack of calcium. Genetic factors determining the particular sensitivity to zinc seem to play an important role as well.
The Reservoir Function of the Spleen and Its Relation to Postsplenectomy Anemia in the Dog
Authors: ELENES NICOLAS ARIAS , EWALD ROGER A. , CROSBY WILLIAM H.
Published: October 2019

Nylon nets sutured around intact dog spleens mechanically prevented them from functioning as red cell reservoirs. Failure of the animals to develop anemia indicates that loss of the reservoir function of the spleen is not involved in the postsplenectomy anemia of the dog.
Coexistent Paroxysmal Nocturnal and Cold Hemoglobinuria Preceded by Aplastic Anemia: A Case Report and Family Study
Authors: MENGEL CHARLES E. , HYMAN BARRY N. , O’MALLEY BERT W. , HOWELL DORIS A.
Published: October 2019

This report described a patient with coexistent paroxysmal cold and nocturnal hemoglobinuria. The hemolytic processes were preceded by a period of marrow aplasia. He demonstrated two complications of prolonged hemolysis and hemoglobinuria, namely iron deficiency and probably "relative folate deficiency." Forty of his family members were investigated for evidence of PNH or PCH and none was found. The need for evaluation and follow up of patients with aplastic anemia in terms of PNH was emphasized.
Cell Antigens and Cell Specialization. II. Demonstration of Some Red Cell Antigens of Human Normoblasts
Authors: YUNIS JORGE J. , YUNIS EDMOND J.
Published: October 2019

Evidence is presented for the presence of the antigens of nine blood group systems on normoblasts. The antigen receptors are detected on all stages of normoblasts. The in vivo demonstration of gamma globulin coating the reticulocytes and the normoblasts of a patient with erythroblastosis fetalis and the normoblasts of a patient with autoimmune hemolytic anemia are discussed in relationship to the pathogenesis of the anemia in both conditions.
Iron Absorption: Effects of Sugars and Reducing Agents
Authors: POLLACK SIMEON , KAUFMAN RICHARD M. , CROSBY WILLIAM H.
Published: October 2019

The effect of the iron-chelating sugars, fructose, glucose and galactose, on iron absorption in rats has been examined. Fructose has an effect in increasing iron absorption. Glucose and galactose have no effect on iron absorption. These findings suggest that the metabolism of fructose is responsible for changing iron absorption in the rat since it is metabolized during its absorption, while glucose and galactose are not.

Pyruvate and lactate, the final products of glycolysis, also increase iron absorption in the rat. The effects of lactate and hydroquinone on iron absorption are additive, suggesting independent actions. The effects of cysteine and hydroquinone on iron absorption are additive, suggesting independent actions of these two reducing agents in increasing iron absorption. Alternative hypotheses are offered in explanation of these observations.
Macrocytosis Resulting from Early Denucleation of Erythroid Precursors
Authors: SENO SATIMARU , MIYAHARA MASANOBU , ASAKURA HIKARU , OCHI OSAMU , MATSUOKA KENICHI , TÔYAMA TAKENORI
Published: October 2019

In an attempt to elucidate the mechanism of production of macrocytosis in acute anemia, we studied changes in red cell volume and hemoglobin content, the RNA level of normoblasts and reticulocytes and RNA synthesis in reticulocytes of rabbits made anemic by blood loss or phenylhydrazine administration. The results were as follows:

(1) In severe phenylhydrazine anemia, red cell volume and hemoglobin content per cell increased to twice the normal values.

(2) The RNA level of normoblasts decreases with the maturation of the cells and reaches a minimum at the orthochromatic stage. The decrease is similar in the normal and anemic rabbits.

(3) The RNA level of reticulocytes in the bone marrow is higher in anemic than in normal rabbits. In general, the RNA level of reticulocytes of anemic rabbits is comparable to that of the polychromatic normoblasts, while in normal rabbits this value is comparable to that of orthochromatic normoblasts.

(4) Autoradiographs of reticulocytes incubated with H3-uridine indicate that the increased level of reticulocyte RNA of anemic rabbits is not due to newly synthesized RNA.

From these results, we conclude that in an "emergency" situation of erythropoietic stimulation denucleation of normoblasts occurs at the polychromatic stage of red cell maturation, with skipping of the terminal cell division to orthochromatic cells and formation of macrocytic reticulocytes and red cells.
Central Nervous System Involvement by Leukemia in Children. II. Therapy with Intrathecal Methotrexate
Authors: HYMAN CAROL B. , BOGLE JAMES M. , BRUBAKER CHARLES A. , WILLIAMS KENNETH , HAMMOND DENMAN
Published: October 2019

1. Thirty-six children with leukemic involvement of the CNS were treated with one to seven courses of methotrexate given intrathecally.

a. Complete or partial symptomatic relief occurred in 57 of 67 episodes treated.

b. Onset of improvement ranged from immediately after the initial lumbar puncture to 18 days later.

c. Duration of response, with complete relief from symptoms, ranged from eight to 751 + days, median 84 days.

d. Median values for CSF pressure, white cell count, and sugar were abnormal during therapy but were normal one week after therapy was complete. In individual episodes, abnormalities persisted longer.

e. Systemic toxicity was infrequent.

f. CNS leukemia has the same sensitivity or resistance to intrathecal methotrexate as the systemic disease had when initially treated with oral methotrexate. The response of CNS leukemia to intrathecal methotrexate may be predicted by the responsiveness of the systemic disease when initially treated with oral methotrexate.

g. Intrathecal methotrexate may still be effective therapy for CNS leukemia in patients whose systemic disease was initially sensitive but later developed resistance to oral methotrexate.

2. Symptoms due to CNS leukemia may respond to lumbar puncture without the injection of medication. Symptomatic improvement was observed within 48 hours and lasted from 23 to 110 days in a small number of patients not given intrathecal methotrexate therapy. However, lumbar puncture per se did not significantly alter the abnormal CSF findings.
Electron Microscopy of the Red Cells in Erythropoietic Porphyria
Authors: GROSS SAMUEL , SCHOENBERG MELVIN D. , MUMAW VIRGIL R.
Published: October 2019

With the aid of electron microscopy two different red cell lines have been identified in erythropoietic porphyria. A normal red cell series has been found in association with hemoglobin containing normoblastic nuclei and ferritin laden reticulocytes. The abnormal line presumably represents the porphyrin containing cells. A possible explanation to account for the abnormality in heme synthesis has been proposed.
Canine Systemic Lupus Erythematosus
Authors: LEWIS ROBERT M. , SCHWARTZ ROBERT , HENRY WILLIAM B.
Published: October 2019

A naturally occurring immunologic disease, characterized by autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura and nephritis, is described in seven dogs. The disease primarily affected formed elements in the blood, glomeruli and blood vessels. Abnormal serum proteins, including the LE factor, rheumatoid factor and antithyroid antibody were found in affected dogs. Corticosteroids and splenectomy were effective in controlling the hematologic components of the disease, but apparently had no effect on the renal lesions. Recurrence was frequent and the prognosis was grave. Additional abnormalities, including malar eruption, intermittent lameness and alopecia were occasionally found as an integral part in the sequential involvement of several tissues during the course of the disease.
DNA and RNA Synthesis of Circulating Atypical Lymphocytes in Infectious Mononucleosis
Authors: EPSTEIN LOIS B. , BRECHER GEORGE
Published: October 2019

The percentages of mononuclear cells synthesizing DNA and RNA in serial studies of blood from 13 patients with infectious mononucleosis were determined. Early in the disease a high percentage of atypical lymphocytes were in DNA synthesis but this percentage decreased rapidly as the disease progressed. Late in the disease many atypical lymphocytes were still present but few, if any, were synthesizing DNA. Similar results were found for RNA synthesis.

Presumably active proliferation of atypical cells in the tissues is restricted to an early period of the disease, whereas release of such atypical cells may continue for a considerable period.
Thrombocytopenia Inherited as an Autosomal Dominant Trait
Authors: BITHELL T. C. , DIDISHEIM P. , CARTWRIGHT G. E. , WINTROBE M. M.
Published: October 2019

This report summarizes information obtained on four generations of a kindred afflicted with a mild hemorrhagic diathesis. Studies carried out on a family of eight members and platelet counts obtained on fifty-one additional members demonstrated only mild thrombocytopenia in eleven members of three generations. The thrombocytopenia appears to be inherited as an autosomal dominant trait.
Evaluation of a Technic for Counting Dog and Human Platelets
Authors: WEED ROBERT I. , CRUMP S. LEE , SWISHER SCOTT N. , Trabold Norma C.
Published: October 2019

1. The addition of Na2EDTA (2.5 to 5 mg./2 ml. of whole blood) to dog or human blood samples has been shown to eliminate the problem of platelet clumping and to provide satisfactory samples for use in enumeration of blood platelets. The statistical errors of platelet counts in blood samples prepared with Na2EDTA agree well with previously published results obtained with unmodified technic. In blood samples prepared without Na2EDTA, where clumping is appreciable, the field error is inflated.

2. Variation in the time during which the platelets are permitted to settle in the chamber before counting, between limits of 30 and 90 minutes, has no effect on the count.

3. The period of standing of the diluted blood in 1 per cent ammonium oxalate, from 30 minutes to four hours, appears to have no effect on the out-come of the platelet counting results when the platelets are not clumped.
The Effect of Incubation and Storage on Human Platelet Structure as Studied by Electron Microscopy
Authors: FIRKIN BARRY G. , O’NEILL BARRY J. , DUNSTAN BETH , OLDFIELD RONALD
Published: October 2019

The electron microscopic appearance of platelets incubated at 37 C. and stored at 4 C. are described, and the relationship of these changes to normal platelet structure are discussed together with the hypothesis that the observation may be due to lysosome activity of some of the platelet granules.

The platelet’s ATP level during incubation and storage was also followed and it was concluded that this relates more to the platelet’s ability to sustain clot retraction than to its viability.
A Normal Inhibitor of the Blood Coagulation Contact Reaction Product
Authors: NOSSEL H. L. , NIEMETZ J.
Published: October 2019

A method is described for studying and measuring the activity of a normally occurring inhibitor of the blood coagulation contact reaction product (activated PTA). The inhibitor, stable on storage at -20 C. was inactivated by heating plasma to 56 C. for 30 minutes. The inhibitor was stable between pH 5 and 9. Inhibitory activity was increased by aluminum hydroxide adsorption and not apparently affected by celite exhaustion of plasma. The inhibitor was present in the fraction of plasma precipitated between 55 and 65 per cent ammonium sulphate saturation and migrated with the alpha globulins electrophoretically. The action of the inhibitor was prevented by soy bean trypsin inhibitor. Inhibitory activity was present in serum and in all normal plasma samples examined as well as in plasma from patients deficient in Hageman factor, PTA factor or factors VIII or IX. The physiologic and pathologic significance of this inhibitor remains to be determined.
Effects of in Vivo Hyperoxia on Erythrocytes. II. Hemolysis in a Human after Exposure to Oxygen under High Pressure
Authors: MENGEL CHARLES E. , KANN HERBERT E. , HEYMAN ALBERT , METZ EARL
Published: October 2019

During the course of an investigation of the effects of in vivo hyperoxia on erythrocytes, one patient developed hemolytic anemia following a relatively brief exposure to oxygen under high pressure. Special studies carried out on his erythrocytes revealed them to be normal in terms of the usual oxido-reduction transformation system components. However, his cells did demonstrate an unusual in vitro sensitivity to hydrogen peroxide and formed unusually high levels of lipid peroxides during incubation with hydrogen peroxide. The similarities between his erythrocytes and those from vitamin E-deficient rodents were noted and the implications of these findings in terms of mechanisms for hyperoxic hemolysis were discussed.
Brief Report: Adherence and Separation of Leukemic Cells on Glass Bead Columns
Authors: RABINOWITZ YALE
Published: October 2019

Leukemic cells showed differences in adherence to glass bead columns which permitted their partial to complete separation. Several fractions with markedly varied differential cell counts could be obtained from the same blood. Such fractions may be utilizable for a variety of assays which, with simple, or sometimes more complex calculations (computer), would be valuable in the determination of values for individual cell types.
Tissue Culture of Cells Already in DNA Synthesis from Patients with Infectious Mononucleosis
Authors: MACKINNEY ARCHIE A.
Published: October 2019

1. Peripheral blood cultures from patients with infectious mononucleosis contained approximately 50 times more cells incorporating tritiated thymidine at time 0 than normal cultures.

2. Cultures from these patients showed active cell division within the first 24 hours. No cell division was seen during this time in cultures of normal cells.

3. Cells dividing within the first 24 hours were identified as cells which had incorporated thymidine at time 0 by observation of metaphases containing tritiated thymidine.

4. Cell division ceased after 18-24 hours in the absence of phytohemagglutinin.

5. The data suggest that a population composed of immature lymphocytic cells in the circulation of patients with infectious mononucleosis is in the process of cell division. Proliferative capacity of peripheral blood cells cannot be studied adequately by ordinary morphologic technic.
Unbound Amino Acids in the Plasma and Erythrocytes of Children with Various Anemias and with Erythroblastosis Fetalis
Authors: NICOLAIDOU MARIA , LUND CHARLES C. , MCMENAMY RAPIER H.
Published: October 2019

The unbound amino acid concentrations in the plasma and erythrocytes of 24 children with anemias of various types have been determined by the method of salt-saturated paper chromatography (iron deficiency anemia— 8 subjects; sickle cell anemia—3 subjects; hereditary spherocytosis—3 subjects; erythroblastosis fetalis—4 subjects; and 1 subject each for thalassemia minor, thalassemia major, unstable reduced glutathione, acquired hemolytic anemia, autoimmune hemolytic anemia, S & F hemoglobinopathy). Anemia per se was found to have little effect on the plasma amino acid concentrations, although a marked increase in the erythrocyte concentrations of every amino acid determined was found. In multiple regression and correlation analyses, the unbound amino acid concentrations in the erythrocytes were found to be a function of both the reticulocyte counts and the blood hemoglobin content, with a somewhat greater dependence on the latter. No recognizable distinction as to the disease category was evident in the unbound amino acid patterns of the anemia patients. The extent of the unbound amino acid elevations in the erythrocytes was largely a reflection of the severity of the anemia.

The subjects with erythroblastosis fetalis were in a category different from those with anemia. Their erythrocyte amino acid concentrations were probably the same as those of normal babies during the first few hours after birth.
Comparison of Hematologic and Febrile Response to Endotoxin in Man
Authors: WOLFF SHELDON M. , RUBENSTEIN MELVIN , MULHOLLAND JOHN H. , ALLING DAVID W.
Published: October 2019

The infusion of endotoxin in man is followed by a fall in mononuclear cell count and subsequent granulocytosis. Significant granulocytopenia was not observed, nor were changes in plasma fibrinogen levels or platelet counts noted. Although a correlation was demonstrated between dose of endotoxin administered and hematologic response, there was no correlation between the magnitude of fever and hematologic changes. Hematologic responsiveness was unchanged following the development of febrile tolerance to endotoxin.
Measurement of Serum Vitamin B12 Level Using Radioisotope Dilution and Coated Charcoal
Authors: LAU KAM-SENG , GOTTLIEB CHESTER , WASSERMAN LOUIS R. , HERBERT VICTOR
Published: October 2019

A method for measurement of serum B12 level using radioisotope dilution and charcoal coated with albumin or hemoglobin is presented. Its advantages over previously described radioisotopic methods and the classical bioassay procedure are greater simplicity, rapidity and reproducibility. The sensitivity range appears to extend from the lowest to the highest B12 values of normal and pathologic sera. The materials for the assay are readily available and the procedure can be completed within an hour. The assay can be applied to other biologic fluids and materials and also readily adopted for routine use by any clinical laboratory equipped to use radioisotopes.
Brief Report: Simplified Myeloperoxidase Stain Using Benzidine Dihydrochloride
Authors: KAPLOW LEONARD S. , Ladd Charlotte
Published: October 2019

A method is described for demonstrating leukocyte peroxidase activity in which benzidine dihydrochloride is used as the indicator compound instead of the more commonly used but potentially more hazardous benzidine base. The method is highly sensitive and rapid and permits the use of fixed blood smears and organ imprints. The incubation mixture, which incorporates safranin as a counterstain, may be used over and over again, for as long as 6 months. The method is also applicable to fresh frozen tissue sections.
Polycythemia Vera: Age Relationships and Survival
Authors: OSGOOD EDWIN E.
Published: October 2019

Study of our first 201 cases of polycythemia vera and of cases reported in the literature shows a remarkable age distribution for this disease. The age at onset, age at diagnosis, age at first treatment, and age at death, as well as survival times, each fits a normal distribution.

In our cases, the median age at onset is 57 years with a standard deviation of 13 years, an entirely different distribution from that for the population of Oregon. This requires a logarithmic increase in relative age specific incidence from age 20 to 40, when there is little difference in the number of persons alive at each age, with a doubling of the proportion occurring in each 5-year interval every 7.5 years. After age 55, the proportion of new cases developing follows the slope of the number alive in the population. This means that the incidence remains almost constant after the peak age incidence is reached.

Unfortunately, no data exist to transform these figures to absolute values, but if enough of the population could be studied to give absolute values at any one point, all other points could be determined. The implication is that polycythemia vera is due to a single cause which is highly correlated with age.

The normal distribution of survival times means that polycythemia vera is not a malignant process since survival times in all malignancies studied fit a log normal distribution. The constant value of age at death means that age at first treatment is a most important prognostic factor.

The mean age at death of patients with polycythemia vera, treated with P32, is 69 years ± 1, and treated without radiation therapy is 65 years ± 1. Apparently, if a patient lives to be treated with P32 previous treatment by other modalities or no treatment prior to that, will not affect the years to be gained by P32 treatment. However, the total survival time is highly correlated with age and the sooner after onset that the patient can be treated the more likely it is he will benefit from P32 therapy.
Anemia in Experimental Protein Deficiency in the Rhesus Monkey with Special Reference to Iron Metabolism
Authors: SOOD S. K. , DEO M. G. , RAMALINGASWAMI V.
Published: October 2019

1. This investigation deals with a study of the anemia of protein deficiency in Rhesus monkeys.

2. Protein deficiency was induced in 17 rhesus monkeys. Seven animals, given a protein-rich diet, served as controls. The diets of both the groups were identical in all respects, except protein. All animals were tube-fed to ensure adequate caloric intake.

Hematocrit, hemoglobin, erythroctye count, serum iron, serum iron binding capacity, plasma iron tolerance curves, and iron absorption using the Fe59 fecal recovery method were studied before and at intervals of the experiment in both deficient and control groups.

Protein-deficient monkeys consistently developed normocytic normochromic anemia of moderate severity. A striking fall in serum iron binding capacity, total proteins and albumin with a rise in gamma globulin was observed in all deficient animals. A significant and comparable fall in serum iron was also observed. The Fe59 absorption was depressed and there was flattening of plasma iron tolerance curves. Two deficient animals, refed a high protein diet, showed reversal of all these changes. The control animals did not show any of these changes.

The mechanism of anemia and decreased iron absorption observed in the protein-deficient animals and the relevance of these findings to those in Kwashiorkor are discussed.
Heinz Body Anemia: An Ultrastructural Study. II. Red Cell Sequestration and Destruction
Authors: RIFKIND RICHARD A.
Published: October 2019

This study reports electron microscope observations on the process of red cell sequestration and destruction in the spleen and liver of the phenylhydrazine-treated rabbit. Damaged red cells are recognized by virtue of their Heinz bodies, a morphologic manifestation of the oxidative injury which they have sustained. Sequestration, in the spleen, involves the selective accumulation of damaged cells within the vascular spaces of the Billroth cords. Erythrophagocytosis and the intracellular digestion of red cells follows sequestration. More severely injured cells may undergo intravascular hemolysis within the splenic red pulp. In the liver, however, no evidence for the intravascular sequestration of injured red cells is observed. Damaged cells are removed directly from the sinusoidal blood by erythrophagocytosis. The selectivity of spleen and liver for red cells subjected to different degrees of injury is discussed in terms of the observed differences in the vascular architecture of the two organs.
Erythroid Homograft Following Leukocyte Transfusion in a Patient with Acute Leukemia
Authors: SCHMIDT PAUL J. , YOKOYAMA MITSUO , MCGINNISS MARY H. , LEVIN ROBERT H.
Published: October 2019

The establishment of a hematopoietic graft of stem cells from a donor with chronic myelogenous leukemia in a patient with acute leukemia took place in the face of ABO red cell group incompatibility. The donor was group A and the recipient who was group O gradually increased his red cell mass to become 80 per cent group A.

There was both active and passive immunity to A present at the time of induction of the graft. The graft flourished despite persistent anti-A agglutinins and an immune response in the B agglutinin and hemolysin system.

Failure of the graft coincided with a fall in antibody levels and was followed by a second immune response which included marked elevation of 7S gamma globulin levels. Red cell incompatibility was not a barrier to this graft and failure of the graft was probably due to other immune mechanisms.