bluuebunny/crossref_metadata_2025 huggingface dataset:
The in Vitro Synthesis of Hemoglobin by Human Bone Marrow in Thalassemia
Authors: NECHELES THOMAS F. , STEINER MANFRED , BALDINI MARIO
Published: October 2019

1. A technic has been described for the in vitro measurement of hemoglobin synthesis by human bone marrow. The rate of synthesis of individual hemoglobins may be investigated in this system.

2. This technic has been used to measure the rate of synthesis of hemoglobin from patients with both thalassemia trait and thalassemia major. Hemoglobin A synthesis was found to be reduced in both, and to a greater extent in thalassemia major. An apparent increase in the rate of synthesis of hemoglobin F was also noted.
Studies of Plasma Fe59 Disappearance—A Manifestation of Ineffective Erythropoiesis and of Hemolysis
Authors: GEVIRTZ NORMAN R. , WASSERMAN LOUIS R. , SHARNEY LENA , TENDLER DINA
Published: October 2019

1. Studies of the plasma radioiron disappearance data have revealed a relative "elevation" of plasma radioactivity after the second day in normal subjects, and after the first day in patients with hemolytic anemia, megaloblastic anemia and thalassemia. This elevation in plasma radioactivity in normal subjects may be interpreted as due to the return to plasma of radioiron from those cells that are "ineffectively" produced and are hemolyzed in the marrow. Other interpretations are also presented.

2. Dyspoieses involving ineffective red cell economy, but not detectably affecting iron economy are contrasted with disorders involving ineffective utilization of iron and of pigment alone.

3. After the first day plasma radioiron activity shows a diurnal variation similar to the diurnal variation in plasma iron concentration.
Studies on Schmauch Bodies. I. The Incidence in Normal Cats (Felis Domestica) and the Morphologic Relationship to Heinz Bodies
Authors: Sirec Anica , Sondić Marija , BERITIĆ TIHOMIL
Published: October 2019

Inclusions in the erythrocytes of normal cats, called Schmauch bodies, have been demonstrated by means of phase contrast microscopy and supravital staining. A very wide range of their incidence, but no correlation with the age of animals has been noted. By their identical staining reactions and common morphologic characteristics Schmauch and Heinz bodies are quite similar, although they might be produced by quite different mechanisms.
Diurnal Variation of Proliferative Activity in the Human Bone Marrow
Authors: MAUER ALVIN M. , Fisher Virginia , Scheib Ruth
Published: October 2019

A study was made of the possible diurnal variation of proliferative activity of human bone marrow cells. A distinct diurnal variation of mitotic indices was present in 5 of 6 normal subjects. The average number of mitotic figures per 1000 nucleated cells in the 6 subjects was 7.6 at 6:00 a.m., 9.5 at noon, 10.5 at 6:00 p.m., and 13.1 at midnight. An assessment of diurnal variation in the per cent of cells synthesizing deoxyribonucleic acid was made in 4 additional subjects by means of incubation of aspirated marrow samples with tritiated thymidine in vitro. By this method, no consistent variation of synthesis could be found in erythroid precursor cells, but the per cent of myeloid precursor cells incorporating the label was lowest at midnight in each subject.
The Removal of in Vitro Damaged Erythrocytes from the Circulation of Normal and Splenectomized Rats
Authors: ULTMANN JOHN E. , GORDON CLARA S.
Published: October 2019

The in vitro alterations and in vivo fate of erythrocytes treated with N-ethylmaleimide or subjected to prolonged incubation were studied in normal and splenectomized rats. Minimal injury (20 µM NEM/ml. RBC) resulted in red cells with decreased osmotic fragility and increased plasticity; however, mechanical fragility was significantly increased. These cells were removed with a half-time of 78 minutes, mainly by splenic sequestration, and splenectomy prolonged their life span. Incubation at 37 C. for 21 hours produced erythrocytes with increased osmotic and mechanical fragility and decreased plasticity. Erythrocyte clearance was more rapid (T½ = 59 minutes), with spleen and liver removing approximately an equal number of cells and splenectomy having little effect on red cell life span. With severe injury (40 µM NEM/ml. RBC), all three in vitro measurements showed marked alterations, red cell removal was rapid (T½ = 35 minutes), mainly by hepatic sequestration, and clearance was unaffected by splenectomy.

The present studies have shown that chemical injury or prolonged incubation lead to profound changes in in vitro tests of red cell integrity, the mechanical fragility predicting most closely the subsequent in vivo events. Although the entire reticuloendothelial system appears to participate in red cell removal, the spleen and liver are the major sites of sequestration in the rat. The splenic removal predominates with minimally injured cells, hepatic removal with moderately and severely altered cells. The type of injury appears to be of less significance than the degree of injury of the red cells.
Experimental Production of Cold Agglutinins in Rabbits
Authors: COSTEA NICOLAS , YAKULIS VINCENT , HELLER PAUL
Published: October 2019

The kinetics, serologic and immunochemical characteristics of cold agglutinins (CA) produced in rabbits by the intravenous injection of HKLM serotype 4b have been studied.

The cold agglutinin was a γM-immunoglobulin. It agglutinated autologous, allogeneic and human erythrocytes at 4 C. In the presence of complement the CA was hemolytic in vitro and in vivo. The relevance of these observations to concepts of autoimmunity is discussed.
Brief Report: Observations on Conjugated and Unconjugated Blood Folate Levels in Megaloblastic Anemia and the Effects of Vitamin B12
Authors: JEEJEEBHOY K. N. , PATHARE S. M. , NORONHA J. M.
Published: October 2019

Vitamin B12 deficiency was associated with a rise in unconjugated folates and marked depletion of intracellular conjugated folates. The changes could be reversed by giving vitamin B12. These results probably indicate a way by which vitamin B12 and folic acid are interrelated at the cellular level.
Alkaline Phosphatase in Neutrophil Leukocytes of Patients with Infectious Mononucleosis and the Effect of Corticosteroid Therapy
Authors: ŠRÁMKOVÁ LUDMILA , KOUBA KAREL , BENDOVÁ NADĚŽDA
Published: October 2019

A marked increase in the activity of the neutrophil alkaline phosphate enzyme (NLAPA) was observed in bacterial tonsillitis whereas in infectious mononucleosis the amount of enzyme in the leucocytes was either decreased or normal. NLAPA of patients with tonsillitis decreased in proportion to the receding disease; in infectious mononucleosis the enzyme increased during convalescence. In 16 of 20 patients with infectious mononucleosis, NLAPA increased after corticotherapy. The value of the enzyme in patients with infectious mononucleosis was much higher after superinfections caused by a different infective agent than after corticotherapy. The studies demonstrate the value of NLAPA examinations in the early diagnosis of infectious mononucleosis, carried out during the acute febrile state and especially during the first days of the illness when all other laboratory examinations may still give negative results.
The Mitotic Activity of Circulating Atypical Mononuclear Cells in Infectious Mononucleosis
Authors: CARTER R. L.
Published: October 2019

An investigation has been made into the mitotic and premitotic activity of the circulating atypical mononuclear cells which occur in infectious mononucleosis. Dividing and binucleate cells were found in 2.4 per cent of blood films and in 63.9 per cent of white cell concentrates. The number of cells in mitosis was small and they were most commonly encountered during the first three weeks of the disease; cells in prophase and metaphase predominated. The incidence of dividing cells in white cell concentrates was increased by a preliminary period of incubation with colchicine. The uptake of 3H-thymidine was shown to be increased during the first four weeks of the disease, with peak labeling in the second and third weeks; in one autoradiograph, 5.4 per cent labeling was observed. The label was confined to the nuclei of certain atypical mononuclear cells, most of which showed rather marked cytoplasmic basophilia. Karyotype analyses were consistently normal. The occurrence of similar large mononuclear cells, capable of taking up 3H-thymidine, in other pathological conditions and in normal subjects is stressed. Their origin, function and potentialities are ill-understood at the present time.

Two further autoradiographic studies21,22 dealing with the mitotic activity of atypical mononuclear cells in infectious mononucleosis have recently appeared, both of which record increased DNA synthesis. Epstein and Brecher21 observed peak labeling during the first two weeks of the disease; most of the labeled cells showed enhanced cytoplasmic basophilia. No variation in labeling at different phases of the disease was found by Schmid et al.,22 who, unlike previous workers, characterize the labeled cells in some detail as plasmacytoid, monocytoid and lymphocytoid elements.
Chromosomal Aberrations in Acute Leukemia
Authors: KIOSSOGLOU KOSMAS A. , MITUS W. J. , DAMESHEK WILLIAM
Published: October 2019

Chromosome studies in acute leukemia were performed in 53 adults and 12 children (two with Down’s syndrome). Abnormalities were encountered in 36 (55.4 per cent) of the cases studied. Normal patterns were found in 29 cases (44.6 per cent). The chromosomal changes varied from patient to patient and consisted of both numerical and structural aberrations. The series involved were, in decreasing order, C, G, D and E, although all chromosomes (autosome and sex) were affected. No correlations of the chromosomal abnormalities with any clinical or hematologic features could be made. In the "blast crisis" of chronic granulocytic leukemia, in addition in Ph 1 chromosome which was present in all cases, other chromosomal anomalies were found in some of these patients.

The presence of normal as well as abnormal chromosomal patterns in acute leukemia, with the great diversity of anomalies in the latter group, suggests that acute leukemia may not be a single entity but comprise instead a variety of morphologic responses to various kinds of etiologic agents.
The Effect of Orally Administered Bovine Spleen Preparations on Platelet and Leukocyte Counts of Rats
Authors: PLUNKET DANIEL C. , CROSBY WILLIAM H. , RUIZ FERDINAND , HUSER HANS-JÜRG
Published: October 2019

Several orally administered beef spleen preparations were evaluated for their effect on platelet and leukocyte counts of rats. In some studies, cow spleen exerted a definite though variable count lowering activity. Further studies yielded less dramatic or negative results. Pooled beef spleen, whole or crudely fractionated, had no demonstrable effect on the blood counts.

Other variables, including temperature, feeding methods, seasonal factors, and animal housing did not appear significant.

No consistent, predictable effect of beef spleen feedings could be demonstrated under the various conditions tested.
Lipid Storage Disease
Authors: THOMPSON IAN L. , MOLONEY WILLIAM C.
Published: October 2019

In this report a sixth case of a storage disorder of unknown etiology is described and other reported cases are discussed. No hereditary or significant etiologic factors were noted in these patients. The disease is characterized by a benign course, splenomegaly and in some cases thrombocytopenia. A lipid containing histiocyte with unique blue staining granular cytoplasm is present in bone marrow and splenic smears, and biochemically the storage material consists largely of sphingomyelin.
Brief Report: Use of Phytohemagglutinin to Stimulate Hematopoiesis in Humans
Authors: HAYES DONALD M. , SPURR CHARLES L.
Published: October 2019

PHA therapy was administered to three patients with bone marrow suppression, two with "idiopathic aplastic anemia" and one with myelofibrosis. One patient with aplastic anemia showed increased marrow erythroid activity; the others had no response. Review of the available data on PHA therapy suggests that states of marrow depression related to known etiologies may respond more readily than idiopathic states. Further studies are needed before definitive conclusions can be drawn as to the true efficacy of this agent.
Lactic Dehydrogenase of Human Chronic Lymphocytic Leukemic Leukocytes
Authors: BOTTOMLEY RICHARD H. , LOCKE S. J. , INGRAM H. C.
Published: October 2019

Lactic dehydrogenase was quantitated and its isozyme pattern studied in the leukocytes of 10 patients with chronic lymphocytic leukemia. There was a wide range of LDH activity, although all isozyme patterns by starch-gel electrophoresis showed greatest activity in the No. III isozyme band. Comparison of the rate of migration of the leukemic leukocyte LDH with LDH from normal leukocytes and erythrocytes showed no difference in migration rate, suggesting that the LDH of chronic lymphocytic leukemic leukocytes does not differ in electrical charge from LDH of normal leukocytes.
Further Studies on a "New" Human Isoprecipitin System (Australia Antigen)
Authors: ALTER H. J. , BLUMBERG B. S.
Published: October 2019

Additional information on a new human isoprecipitin system, directed against Australia antigen, has been given. The antibody defining this system is an IgG(7S) gamma globulin. Staining and ultracentrifugation suggest that Australia antigen contains small amounts of lipid, but is not identical with typical low or high density lipoprotein.
Experience with an Extended Methemoglobin Reduction Test
Authors: ROBIN HELEN , HARLEY J. D.
Published: October 2019

Experiments have been designed to elucidate the varying degrees of destruction of intact hemoglobin (methemoglobin plus oxyhemoglobin) observed on application of the methemoglobin reduction test to normal and abnormal subjects. Surprisingly, the degree of intact hemoglobin destruction was found to vary directly with the rates of methemoglobin reduction, particularly via the pentose phosphate pathway in the presence of methylene blue, and inversely with cell age. In addition, confirmation was obtained of increased susceptibility to destruction of intact hemoglobin in subjects with such congenital or acquired defects of hemoglobin stability as might result from hemoglobin H, acute lead poisoning, or prior exposure to aromatic drugs.

Further evidence was presented that accumulation of methemoglobin militates against intact hemoglobin destruction. It was suggested that the methemoglobin content of samples of blood after application of the methemoglobin reduction test should be assessed in relation to the simultaneous changes in the intact hemoglobin concentrations of the incubation mixtures.
Autoimmune Disease in NZB/Bl Mice
Authors: MELLORS ROBERT C. , Landy Dolores A. , Bardell David
Published: October 2019

Malignant lymphoma was found in 4 of 20 NZB/Bl mice (of the 61st generation) selected for laboratory examinations and autopsy at 9 to 11 months of age. The malignant lymphomas were of two histologic types, reticulum cell sarcoma and pleomorphic malignant lymphoma, the latter term being used to designate malignant neoplasms arising in lymphatic tissue, composed of mesenchymal cells of diverse appearance—mainly plasma cells of blast, immature, mature and Russell-body types but also large primitive (stem) cells, reticulum cells, and lymphocytes of large and small size—and frequently associated with gammopathies. One of the reticulum cell sarcomas was transplantable to, and produced lethal disseminated growth in, other NZB/Bl mice.

In each example of malignant lymphoma, warm hemagglutinins (to papain-treated mouse red cells) were demonstrable in serum. Autoimmune hemolytic disease and chronic membranous glomerulonephritis, both of common occurrence in NZB/Bl mice of comparable age, were also present. In one instance of pleomorphic malignant lymphoma, hypergammaglobulinemia of unusual quantity and quality drew attention to the possibility of lymphomatous disease.

Some evidence was brought forth indicating that in the majority of instances the autoimmune diseases preceded the malignant lymphomas. While the coexistence of autoimmunity and lymphoid neoplasia conceivably reflects nothing more than chance occurrence, other interpretations were considered: the proliferative advantage engendered in immunologically competent cells in autoimmune disease may be a step in the direction of lymphoid neoplasia; or, in some instances autoantibodies may be produced by, or in response to, the neoplastic lymphoid cells.
The Effect of Erythropoietin on Hematopoietic Organs of the Polycythemic Mouse
Authors: NAKAO K. , TAKAKU F. , FUJIOKA S. , SASSA S.
Published: October 2019

Increased RNA-P32/DNA-P32 ratio, iron incorporation and heme synthesis in spleens of polycythemic mice was demonstrated following an injection of erythropoietin. These changes were correlated with the appearance of erythroblasts. These findings suggest an intimate relation between RNA synthesis and stem cell differentiation.
Family Study in Addisonian Pernicious Anemia
Authors: ARDEMAN S. , CHANARIN I. , JACOBS A. , GRIFFITHS LORRAINE
Published: October 2019

Addisonian pernicious anemia was present in 6 of 9 siblings (Generation II). All 9 siblings had evidence of gastric pathology as judged by the presence of antibodies against parietal cells, abnormalities in the gastric biopsy, and diminution of secretion of acid and intrinsic factor.

Parietal cell antibodies were present in 10 of 17 offspring of these 9 siblings who were available for study. Gastric biopsy in the older members of this generation (III) showed atrophic gastritis; some of the younger members showed superficial gastritis.

Loss of intrinsic factor was always accompanied by loss of gastric secreting cells and there was no evidence that decline of intrinsic factor secretion occurred independently of hydrochloric acid.
Measurement of the Amounts of the Individual Vitamin B12, Binding Proteins in Plasma
Authors: HALL CHARLES A. , FINKLER ALEXANDER E.
Published: October 2019

The vitamin B12 binding capacities of transcobalamin I and II were evaluated in plasma from patients with diseases known to affect the plasma binding. In CML in relapse, the capacity of TC II was very much diminished or absent. The capacity of TC I was very much increased. There was a lesser degree of both abnormalities during remission and in AML. There was either diminished or absent binding to TC II in PA but the capacity of TC I was not altered.
The Erythropoietic Effect of Hematocrit Variations in Normovolemic Rabbits
Authors: ERSLEV ALLAN J.
Published: October 2019

Measurements of erythropoietin titer and serum iron turnover were carried out in rabbits 48 hours after the induction of normovolemic anemias and polycythemias. Although viscosity studies of blood at various hematocrits indicate that the oxygen flow to the tissues is impaired both in anemia and polycythemia, only anemias were found to be associated with production of erythropoietin and with accelerated serum iron turnover. It was concluded that if polycythemia with its associated high viscosity leads to tissue hypoxia, this tissue hypoxia will not cause production of erythropoietin.
Actinomycin and Erythropoiesis and the Production of Erythropoietin in Mice
Authors: KEIGHLEY GEOFFREY , LOWY PETER H.
Published: October 2019

In B6D2F1 female mice a single dose of 10 µg. of actinomycin will suppress normal erythropoiesis. In polycythemic mice 2 µg. is enough to prevent the stimulatory effect of 0.25 A units of erythropoietin. The curves of suppression and recovery versus time support the hypothesis that erythropoietin acts for a short time in an early stage of erythropoiesis; after this early stage developing cells are no longer so sensitive to actinomycin. Recovery, even from repeated doses, is rapid and adequate. Amounts of actinomycin which are adequate to abolish erythropoiesis do not prevent the new appearance of erythropoietin in the plasma of hypoxic mice.
Platelet Amino Acid Levels in Essential Thrombocytosis
Authors: NACHMAN RALPH L. , HOROWITZ HERBERT I. , SILVER RICHARD T.
Published: October 2019

Studies on the platelets from three patients with essential thrombocytosis were presented. The intraplatelet free amino acid levels were elevated and the pseudo-hyperkalemic phenomenon was present. In one subject the pseudohyperkalemic phenomenon was reversed after a therapeutic remission, but the elevation of amino acids persisted. The data suggest that a qualitative abnormality may exist in the platelets of patients with essential thrombocytosis.
Progressive Antithrombin: A Three-Phase System
Authors: HENSTELL HENRY H. , KLIGERMAN MIRIAM
Published: October 2019

1. Data are presented which demonstrate that progressive antithrombin activity results from the interaction of three factors: antithrombin, an antithrombin inhibitor, and a platelet factor. In plasma, the antithrombin is held inactive by combination with inhibitor so that no free antithrombic activity is present. When platelets are disrupted—namely, in clotting—the platelet factor made available binds the inhibitor, releasing antithrombin to react with thrombin.

2. Antithrombin was isolated from plasma in the 70-75 per cent ammonium sulfate fraction. It was relatively heat stable at 56-57 C. for 5 minutes and was not soluble in perchloric acid.

3. Inhibitor was isolated from plasma in the 30-50 per cent ammonium sulfate fraction. It was inactivated at 56-57 C. for 5 minutes. It was soluble in perchloric acid in which it was purified by a factor of 300.

4. Platelet factor was present in the sedimentable fragments of platelets.
Factor 13 Deficiency with Severe Hemorrhagic Diathesis
Authors: FISHER SHARON , RIKOVER MOSHE , NAOR SHIMON
Published: October 2019

This report presents the first case of Factor 13 deficiency in an adult female. Her hemorrhagic manifestations were repeated and severe: umbilical vein bleeding at birth, hematomas on various sites, late bleeding after cuts and, most important, severe uterine bleedings during 12 pregnancies, which were all interrupted by spontaneous abortions.

Plasma infusions, assuring a Factor 13 concentration of less than 10 per cent of its normal level, normalized the hemostatic functions of the patient’s plasma clots and rendered them insoluble in concentrated urea solutions.

By regular transfusions of plasma the patient’s last pregnancy had a normal course; a cesarian section was performed without any incident, and she gave birth to a normal child.
Brief Report: Hypocupremia and Neutropenia in Copper Deficiency
Authors: CORDANO ANGEL , PLACKO ROBERT P. , GRAHAM GEORGE G.
Published: October 2019

Copper deficiency was often found in severely malnourished infants rehabilitated on exclusive milk diets. Marked, persistent neutropenia was its earliest and most constant manifestation.
The Production of Hemoglobin C in Sheep Carrying the Gene for Hemoglobin A: Hematologic Aspects
Authors: MOORE S. L. , GODLEY W. C. , VAN VLIET G. , LEWIS J. P. , BOYD E. , HUISMAN T. H. J.
Published: October 2019

The first part of this study describes the hematologic and physiologic changes observed in sheep homozygous for the hemoglobin A during severe blood loss anemia. It was found possible thus experimentally to replace Hb A entirely with a new hemoglobin type, Hb C. The following additional observations were made: (1) Hb C could not be distinguished from Hb A by submitting the appropriate red blood cells to an "acid elution" technic. These two hemoglobin types were found to be more resistant to this treatment than a second adult hemoglobin type, Hb B, while the fetal hemoglobin of the new-born lamb was found to be highly resistant. In sheep heterozygous for Hb A and Hb B, both hemoglobin types were equally distributed among all red blood cells. (2) During stages of severe blood loss relatively small quantities of acid resistant red blood cells of larger size were demonstrable in homozygous Hb A sheep; these cells were considered to be reticulocytes. Additional observations regarding variations in red cell parameters are also presented. (3) The oxygen affinities and the Bohr effects of blood samples and red cell hemolysates containing over 90 per cent Hb C are presented and compared with those of samples containing only Hb A, Hb B or the hemoglobin of the newborn lamb.

Attempts to produce Hb C in sheep homozygous for Hb A by means other than phlebotomy are described in the second part of this report. Small amounts of Hb C were demonstrable in a sheep homozygous for Hb A after repeated injections of a urinary extract of human origin with high erythropoietic activity. Administration of cobalt and of thyroxin did not result in the formation of significant amounts of Hb C.
Hemoglobin H Disease
Authors: NECHELES THOMAS F. , CATES MARJORIE , SHEEHAN RICHARD G. , MEYER HEIDI J.
Published: October 2019

1. Three siblings with Hb H thalassemia disease have been observed in a family in which 17 members from 3 generations have been examined. Four additional family members have α-thalassemia minor.

2. A genetic examination of the family provides further evidence for the theory that Hb H thalassemia disease is due to the interaction of the α-thalassemia gene and another "silent" gene which, however, does appear to produce minor morphologic abnormalities when present alone.

3. Reevaluation of the effects of splenectomy indicate that this procedure may be of significant benefit only in the more severe cases of Hb H disease.
Platelet Function in a Patient with Thrombasthenia
Authors: ZUCKER MARJORIE B. , PERT JAMES H. , HILGARTNER MARGARET W.
Published: October 2019

The platelets of a patient with congenital thrombasthenia were not aggregated by ADP, thrombin, connective tissue particles, Polybrene, or phospholipase C, and did not adhere to glass as measured either on a glass slide or by retention in a glass-bead column. Clot retraction was markedly diminished. Raising the magnesium level partially corrected clot retraction but did not restore ADP-induced clumping. The platelets were less able to promote prothrombin consumption. Fibrinogen concentration in the supernatant of frozen and thawed platelets was low, but surface fibrinogen appeared to be normal.

The thrombasthenic platelets were normal in the following respects: concentration of ATP and glyceraldehyde-3-phosphate-dehydrogenase; adhesion to connective tissue fibers; aggregation by antiplatelet serum; microelectrophoretic mobility; isoelectric point; disc shape of platelets at 37 C.; ability of platelets to change shape with ADP or cold; decrease in ATP concentration and auramine staining of granules by thrombin; release of serotonin, ADP, and other materials absorbing at 260 mµ. by thrombin or connective tissue particles; liberation of acid phosphatase during blood clotting; and platelet Factor 5 activity.

It is concluded that responses of thrombasthenic platelets to thrombin and connective tissue particles are normal except that the liberated ADP fails to cause aggregation. The first stage of the reaction to ADP, transformation from disc to spiny sphere, is normal. Still to be determined at the molecular level is the cause(s) of failure of clot retraction and ADP-induced aggregation and the relationship of these defects to the low fibrinogen concentration of platelet extracts.
The Periodic Acid-Schiff Reaction in Neutrophil Leukocytes in Untreated and Myleran-Treated Chronic Myelocytic Leukemia
Authors: GAHRTON GÖSTA
Published: October 2019

Microspectrophotometric quantification of the periodic acid-Schiff (PAS) reaction has been performed in about 3,000 individual mature neutrophil leukocytes from 20 normal subjects and 23 patients with chronic myelocytic leukemia (CML), of whom 10 were untreated or in relapse and 13 in partial remission or remission.

The PAS reaction was taken as a quantitative measure of the cellular amount of PAS reactive material (PASMa), most probably equivalent to glycogen. The mean amount of PASMa in neutrophils from untreated and relapse cases of CML was 43 per cent less than in normal neutrophils. The frequency distribution of PASMa per cell was normal in individual cases. In clinical remission after Myleran treatment, the neutrophils contained normal amounts of PASMa.
Detection and Quantitation of Minor Erythrocyte Populations in an Admixture by Means of Fluorescent Antibody: Rhesus Monkey
Authors: BOGDEN ARTHUR E. , GRAY JAMES H. , Najemy Rosemary , Giofreda Sheryl
Published: October 2019

The five rabbit antirhesus monkey erythrocyte specificities of Owen and Anderson1 have been confirmed. An additional specificity, designated "F," has been found in 91.2 per cent of rhesus animals tested. Antiserum reagents with the A and B reactivities have been used in the indirect fluorescent antibody technic to detect and quantitate minor rhesus erythrocyte populations in admixture with a major population. Specific fluorescence was achieved with wet, unfixed preparations and was "all-or-none." A rapid method for the estimation of minor to major cell population ratios well above 1:1000 is presented.
Brief Note Nuclear Projections in Neutrophils
Authors: MÉHES K.
Published: October 2019

All these findings and the contradictory data in the literature show that the different types of nuclear projections in neutrophils, excluding the genetically determined drumsticks and sessile nodules, are nonspecific pseudosegments of the leukocytes. Their appearance depends on the segmentation, aging, and metabolism of the neutrophils. These features might be influenced by many factors, including possible hormonal effects. Our observations have shown, for instance, that androgens might induce an increase in the number of nuclear appendages. Although the appearance of these figures may be associated with certain diseases, it should not be regarded as a specific sign for a single pathologic or physiologic condition.
Urinary Iron Excretion and Renal Metabolism of Hemoglobin in Hemolytic Diseases
Authors: SEARS DAVID A. , ANDERSON PEARL R. , FOY ARTHUR L. , WILLIAMS HAROLD L. , CROSBY WILLIAM H.
Published: October 2019

Quantitative and qualitative studies of urinary iron excretion were performed in 12 patients with hemolytic disease and in one normal subject given an intravenous infusion of hemoglobin. In 9 patients with significant intravascular hemolysis, increased urinary excretion of nonhemoglobin iron was observed with amounts as high as 10.75 mg. pen 24 hours. In 7 of 8 patients in whom fractions of the urinary iron were studied, the majority of the iron was in the sediment (hemosiderin). Ferritin was demonstrated in the urine by immunologic and electrophoretic technics and accounted for a significant percentage of iron excreted. In several patients, day-night variations in hemolysis were associated with parallel fluctuations in iron excretion.

The results were analyzed in relation to current concepts of glomerular clearance and renal tubular metabolism of hemoglobin. The significance to body iron balance of the massive "iron diuresis" occurring in some of these patients was discussed.
Plasma Infusions in Immunologic Deficiency States: Metabolic and Therapeutic Studies
Authors: STIEHM E. RICHARD , VAERMAN J.-P. , FUDENBERG H. HUGH
Published: October 2019

Serial immunologic measurements were used to study the metabolic behavior of the immune globulins (γG-, γM- and γA-globulins) in patients with agammaglobulinemia after plasmapheresis and plasma infusion and in newborn infants after exchange transfusion. These studies were supplemented by metabolic and distribution studies of I131-labeled γA-globulin (isolated from serum or breast milk) and I131-labeled γG-globulin in normal and agammaglobulinemic subjects. The therapeutic benefit of periodic plasma infusions in patients with agammaglobulinemia and the Aldrich syndrome was also assessed.

In the agammaglobulinemic patients, the mean half-lives of γG-, γM- and γA-globulin were 32, 9.6 and 5.9 days, respectively. In the transfused infants, the mean half-lives of γM- and γA-globulins were 7.4 and 4.3 days, respectively. Agreement existed between simultaneously determined immunologic and radioactive survival times, except when I131-labeled γA-globulin isolated from serum was used; this preparation had a shorter half-life than the γA-globulin of infused plasma, probably as a result of denaturation during the isolation procedure. Studies on 2 normal and 3 agammaglobulinemic subjects showed that 65 to 85 per cent of breast milk I131-labeled γA-globulin was distributed within the tissues. I131-labeled γA-globulin was not demonstrable in the breast milk of 2 lactating women or in the saliva of 2 normal subjects. No γA-globulin could be demonstrated in the saliva of an agammaglobulinemic patient after plasma infusion which raised the serum γA-globulin concentration to 50 mg./100 ml.

The use of plasma instead of commercial γ-globulin for the therapy of immunologic deficiency states has several advantages. Plasma contains all three immune globulins, provides greater quantities of γG-globulin than can be given by intramuscular injections, and is more acceptable to the patient. Because of the risk of serum hepatitis, this mode of therapy in the routine management of agammaglobulinemia is endorsed only if special precautions are taken. A therapeutic trial of plasma infusions in 2 patients with the Aldrich syndrome gave promising results.
The Effects of Allografts of Thymic Epithelial Reticular Cells on the Lymphoid Tissues of Neonatally Thymectomized Mice
Authors: HAYS ESTHER FINCHER
Published: October 2019

Neonatal thymus placed in a Millipore diffusion chamber for one week loses its cortical cells, while the epithelial reticular cells remain viable. Grafts of these remnants in neonatally thymectomized mice are completely reconstituted from cells of the thymectomized host. Evidence is presented which suggests that the bone marrow may be a source of cells which reform the thymus cortex.

These remnant grafts result in lymphoid reconstitution of neonatally thymectomized mice. The grafted animals also reject allografts of skin and lymphoma cells in a normal manner. However, these C3H mice, neonatally thymectomized and reconstituted with allografts of AKR thymic epithelial reticular cells, are tolerant to grafts of AKR lymphoma cells.
The Influence of Hemoglobin Concentration on the Distribution Pattern of the Volumes of Human Erythrocytes
Authors: WEED ROBERT I. , BOWDLER ANTHONY J.
Published: October 2019

1. Studies of the volume distributions of normal human, canine, and chicken erythrocytes through the use of a Model B Coulter electronic particle counter and plotter of 400 channel analyzer have confirmed that the instrument provides a true reflection of cell volume, independent of the conductivity of the medium, independent of the shape of the erythrocyte, independent of the buffers, and independent of the anticoagulants employed.

2. The non-Gaussian distribution pattern of normal human cells has been confirmed, but no evidence has been found for a distinct bimodal distribution pattern in cells which have been freshly collected, pipetted, and examined.

3. Swelling of human erythrocytes in 0.5 per cent NaCl alters the volume distribution pattern to that of a normal distribution, and the distribution pattern of hemoglobin-free ghosts in 1 per cent NaCl is more nearly symmetric than that of normal intact red cells in 1 per cent NaCl.

4. The Gaussian distribution of erythrocyte volumes in 0.5 per cent NaCl suggests a normal distribution pattern for both the critical volume and ionic content of red cells.

5. The asymmetry of red cell volume distribution at the tonicity of plasma appears related to higher intracellular osmotic activity in the smaller cells, based on the anomalous osmotic coefficient of hemoglobin. It is suggested, therefore, that skewing of the curve is related to asymmetry of the distribution pattern at the lower end of the volume spectrum, rather than the upper end.
The Relation of Blood Platelet Survival and Distribution to 14C-Serotonin Distribution and Excretion
Authors: HEYSSEL R. M. , SILVER L. J. , WASSON MARIE , BRILL A. B.
Published: October 2019

1. The distribution of 14C-5-HT following infusion is different from that of endogenous serotonin. One hour after infusion it is, in major part, a function of the distribution of blood platelets.

2. The spleen in rats is the site of a pool of platelets. Based on both 14C and platelet recovery data in normal and splenectomized animals, this pool approximates 40 per cent of the total circulating platelets.

3. Postsplenectomy thrombocytosis may relate to removal of a platelet reservoir with shift of the platelets normally contained therein to the peripheral circulation.

4. The shape of platelet survival curves in rats is neither strictly linear nor curvilinear but normally is determined primarily by age-related processes in the platelet. Platelet survival curves tend to become curvilinear in thrombocytopenic animals, indicating that there is probably an additional small, fixed random loss of platelets from the circulation.

5. The disappearance of 14C-5-HT from blood platelets approximates but is not completely representative of the disappearance of the platelets themselves. It is probable that elution from platelets and possibly reutilization of platelet label occurs.
Radioactive Diisopropyl Fluorophosphate as a Platelet Label: An Evaluation of in Vitro and in Vivo Technics
Authors: BITHELL T. C. , ATHENS J. W. , CARTWRIGHT G. E. , WINTROBE M. M.
Published: October 2019

A technic for the in vitro labeling of human platelets with DFP32 is presented, critically evaluated, and compared to in vivo methods employing DFP32 and to in vitro methods using Cr51. The initial recovery of platelets labeled in vitro with DFP32 averaged 79 per cent, but the survival curve was characterized by an irreversible initial loss of platelet radioactivity. Experiments in which platelets were simultaneously labeled in vitro with both DFP32 and Cr51 suggest that this is not due to elution of DFP32. The survival curve of platelets labeled in vivo with DFP32 shows an initial transient reduction in platelet radioactivity. It is suggested that both of these aberrations in initial survival are the result of platelet injury by DFP32. Significant "tailing" was observed in the survival curves obtained with DFP32, and possible explanations of this phenomenon are discussed. DFP32-labeled platelets circulating after 5 hours apparently survive normally and disappear from the circulation as a rectilinear function over the next 6-8 days. Although both in vitro and in vivo labeling methods employing DFP32 provide a meaningful approximation of platelet lifespan, the initial and terminal aberrations of the survival curves greatly complicate further interpretation. Dextran had no detectable effect on platelet survival, and epinephrine, Mecholyl, and cutaneous vasodilatation did not alter the platelet count or the specific activity of circulating labeling platelets in human subjects. The problem of initial platelet survival and the question of an extravascular or marginal platelet pool is discussed in the light of these data.
Studies on the Regulation of Hemopoietic Spleen Colonies
Authors: BLEIBERG ILAN , LIRON MEIR , FELDMAN MICHAEL
Published: October 2019

The in vivo intrasplenic cloning of haemopoietic cells was used as an experimental system for the study of some aspects concerned with the regulation of erythropoiesis. Experiments on the effects of polycythemia on the formation of erythroid clones demonstrated that the "feedback" suppression of such clones was inhibited if the polycythemic animals were kept under hypoxic conditions. Overloading with oxygen is, thus, an essential factor in the polycythemia-induced suppression of erythroid clones. Polycythemic animals which were transferred to hypoxic conditions for only 48 hours before the termination of the experiment showed the formation of erythroid clones. Analysis of clone formation following such short exposures to hypoxia suggests that the endogenous erythropoietin which had been functioning in this situation acted not upon the single clone-forming cell, but rather on small cell populations which derived from the clone-forming cells in the absence of erythropoietin. There is, therefore, an early, erythropoietin-independent phase of replication of the clone-forming cells. The application of erythopoietin only during this "early" phase of replication resulted in the formation of erythroid clones, which, following the discontinuation of erythropoietin, disappeared from the spleen. Similar results were obtained when the action of endogenous erythropoietin was terminated by subjecting animals to polycythemic conditions a few days after the injection of bone marrow. It appears that in both these cases the reduction in the number of spleen colonies following discontinuation of erythropoietin activity is due to the total maturation of the erythroid colonies, ending in the evacuation from the spleen of the mature red blood cells. The differentiation of the cloned cells is, thus, causally related to the cessation of the replicating effect of erythropoietin.
A New Technic for the Production of an in Vivo Labeled Fibrinogen
Authors: GANS HENRY , MC LEOD JAMES , LOWMAN JAMES T.
Published: October 2019

The fact that in vitro labeled proteins, as a rule, exhibit faster turnover rates than in vivo labeled materials led us to explore means of obtaining in vivo labeled fibrinogen of high specific activity. It was found that defibrination of the rat provides a stimulus for the liver to regenerate fibrinogen at an accelerated rate. Administration of seleno75 methionine shortly after thrombin-induced defibrination of the animal resulted in the incorporation of large quantities of the label. The rate of incorporation was further increased if the amino acid was administered as a slow infusion during the entire period of fibrinogen regeneration. In addition, prior nephrectomy of the animal would appear to result in a slight increase in specific activity of the fibrinogen preparation obtained.

The results of these studies indicate that defibrination, nephrectomy, and the prolonged infusion of the labeled amino acid selenomethionine provided us with a technic for obtaining a biosynthetically labeled, γ-emitting, fibrinogen preparation of high specific activity.
A Method for Counting Phytohemagglutinin-Stimulated Lymphocytes
Authors: STEWART C. C. , INGRAM M.
Published: October 2019

A technic is described for accurately enumerating the number of viable. PHA-stimulated lymphocytes in culture. This technic is both simple and fast.

The technic depends upon the elimination of debris by means of the proteolytic enzyme, pronase, and the removal of cell cytoplasm by cetrimide leaving clean, intact nuclei which can be counted and sized.

Serially determined absolute lymphocyte counts in cultures with phytohemagglutinin are reported. These show that there is a net gain in both cellularity and number of cells incorporating tritiated thymidine and that there is logarithmic growth throughout the 72-hour culturing interval. Quantitative studies of this lymphocyte response as a function of PHA concentration are in progress.
The Effect of Phytohemagglutinin upon Glucose Catabolism in Lymphocytes
Authors: MACHAFFIE R. A. , WANG C. H. , Woransberg Julia , Spangler Jackie
Published: October 2019

The glucose metabolism in intact lymphocyte cells was found to be altered in the presence of phytohemagglutinin. The operation of the pentose phosphate pathway and, to some extent, the pentose cycle pathway in lymphocytes was found to be significantly enhanced. This finding is interpreted to reflect an additional need of biosynthetic intermediates and TPNH by the lymphocytes to accommodate mitotic activity induced by phytohemagglutinin.
Brief Report: An Evaluation of Human Lymphocyte Nuclear RNA with Acridine Orange
Authors: JOHNSON DAVID M. , PRATT PEYTON T. , RIGBY PERRY G.
Published: October 2019

Lymphocytes from human peripheral blood have been evaluated by fluorescent microscopy using acridine orange-stained preparations. The nuclear RNA has been quantitatively rated and correlated with the diagnoses. These observations were performed on normals and patients with chronic lymphocytic leukemia, pertussis, hypogammaglobulinemia, acute leukemia, uremia, other malignancies, and a miscellaneous group. RNA added to in vitro normal lymphocyte cultures showed an apparent inhibition of cell proliferation in PHA-stimulated cells.
STUDY OF THALASSEMIA MINOR IN THREE GENERATIONS OF AN ITALIAN FAMILY
Authors: HEINLE ROBERT W. , READ MARGARET RUTH
Published: October 2019

1. Three generations of a family of Italian descent were studied. Nine of 13 members were found to have thalassemia minor.

2. Genetic studies indicate that this mild, microcytic hypochromic anemia characterized by the presence of target and elliptical cells and other bizarre forms and by increased resistance to hypotonic saline, results from heterozygosity of an inherited factor, which, when homozygous, produces thalassemia major or Cooley’s Mediterranean anemia.

3. If individuals heterozygous for this factor (thalassemia minor) marry other heterozygous individuals, one quarter of the offspring can be expected to be homozygous (thalassemia major), one half heterozygous (thalassemia minor) and one quarter free of the trait.

4. The presence of thalassemia minor apparently did not interfere with the general health of affected members of this family and did not appear to shorten life expectancy. The importance of the condition lies in its relation to thalassemia major.
PROPHYLAXIS OF HOOKWORM ANEMIA-DEFICIENCY DISEASE
Authors: CRUZ W. O. , DE MELLO R. PIMENTA
Published: October 2019

1. In individuals severely infested with Ancylostoma or Necator, it is possible to maintain the normality of blood value by the administration of a sufficient dose of an iron salt.

2. The minimum dose necessary to maintain normality of the blood in an individual weighing 45 kilograms, with 1051 helminths, was 0.2. Gm. daily of ferrous sulfate, administered in mixture with manioc flour.

3. The patient observed became clinically normal two weeks after the beginning of blood regeneration up to the end of the trial period one year later. In this period, with the various doses of iron tried, hemoglobin varied from 8.0 to 11.0 per 100 ml. of blood.
Childhood Leukemia in Connecticut, 1940-1962
Authors: CUTLER SIDNEY J. , HEISE HERMAN , EISENBERG HENRY
Published: October 2019

This study reviews the experience of all leukemia patients under 20 years of age seen in Connecticut hospitals during the period 1940-1962. The survival experience in this series compares favorably with that in several specialty treatment centers, and improved markedly from the 1940’s to the middle 1950’s. There has been little change in survival since. Improvement in survival was substantially greater among patients with acute lymphocytic compared with patients with acute myelogenous leukemia.

During the period that patient survival increased rapidly, the rate of leukemia incidence increased only moderately. There was little change over time with respect to patient characteristics such as initial white blood cell count and the presence of bleeding and hemorrhage. There was a marked increase in the use of steroid and chemotherapy, but the continued increase in the use of chemotherapy after the middle 1950’s and changes in the specific agents used were not associated with further improvement in patient survival. How the new and modified treatment regimens introduced since 1962 will be reflected in unselected series such as the one in Connecticut remains to be seen.
Production of Granulocytic Progeny by Transplanted Bone Marrow in Irradiated Mice
Authors: HELLMAN SAMUEL , GRATE HELEN E.
Published: October 2019

The production of granulocytic progeny by transplanted mouse bone marrow is described. Normal marrow is injected into lethally irradiated recipients. Seven to 9 days is allowed for stem cells in the marrow to proliferate and differentiate. The granulocytic response to a bacterial endotoxin is then measured. This response bears a linear relationship with the number of bone marrow cells injected and can be used as an assay of granulocytic progenitor cells in bone marrow.