bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Hemoglobin Abraham Lincoln (β 32 leu → pro)
Authors: Honig George R. , Mason R. George , Vida Loyda N. , Shamsuddin Mir
Published: October 2019

Globin chain synthesis was studied in vitro with reticulocytes from a patient heterozygous for Hb Abraham Lincoln, an unstable beta chain variant. Synthesis of α-chains by the reticulocytes exceeded total β-chain synthesis, and a substantial fraction (about 16%) of radioactivity incorporated into globin was recovered from the cells as uncombined α subunits. In a time-course study, the ratio of α : β-chain specific activity was found to increase progressively in a nearly linear manner, suggesting that a fraction of newly synthesized β-chains had undergone rapid destruction. The specific activity of the abnormal β-chain was nearly three times that of βA. The rate of synthesis of the β-chain of Hb Abraham Lincoln appeared to be approximately half that of the β-chain of Hb A.
The Metabolism of Transferrin-bound 111In and 59Fe in the Rat
Authors: Beamish Michael R. , Brown Elmer B.
Published: October 2019

The metabolism of transferrin-bound indium and iron were compared by in vivo studies in the rat. Rats were injected with serum transferrin labeled with 111In and 59Fe, and, at intervals ranging from 20 min to 5 days after injection, they were killed. They were perfused through the portal vein with 200 ml of 0.9% saline, and the residual radioactivity, expressed as a percentage of the injected dose, was measured in liver, spleen, kidney, muscle, washed red cells, red marrow, and femur. At 5 days, 76% of the injected 59Fe was recovered in the red cell mass; only 1%-2% of 111In could then be recovered. Uptake and release of the 111In label by the femur was markedly less than that of the 59Fe. Whereas 85% of the injected 59Fe could be recovered from the circulating red cells, liver, and spleen, only about 15% of the injected 111In could be so recovered. Approximately 35% of the injected 111In was excreted, and 43% was recoverable from the carcass. The subcellular distribution of the two isotopes in the liver at timed intervals following intravenous injection was studied. While 35% of the 59Fe activity in the homogenate was associated with ferritin, only 4% of the 111In could be so identified. The results indicate a significant difference between the metabolism of 111In and 59Fe in the rat and make it unlikely that the metabolism of In in man bears much similarity to that of iron.
Acute Leukemia Following Localized Irradiation for Carcinoma of the Larynx
Authors: Karchmer Richard K. , Caldwell Glyn G. , Chin Tom D. Y.
Published: October 2019

During a 5-yr leukemia surveillance study in the metropolitan Kansas City area, four patients who had previously received irradiation therapy for carcinoma of the larynx developed acute leukemia. The frequency of occurrence represents a significant increase of the observed over the expected. These findings indicate that, even with such localized radiotherapy, the possibility of irradiation-induced leukemia must be considered in therapeutic decisions.
Effects of Degree of Thrombocytopenia on Thrombocytopoietic Response
Authors: Odell T. T. , Murphy J. R.
Published: October 2019

Rats were exchange transfused with platelet-poor blood to reduce the number of circulating platelets. When thrombocytopenia was moderate, the rate of platelet increase toward normal levels was relatively slow, whereas after severe thrombocytopenia an early slow rate of increase was followed by a rapid rate. It seems likely that the rapid platelet increase that begins about 36-48 hr after acute, severe thrombocytopenia is engendered by a ploidy shift among megakaryocytes and by an increased input of cells into the maturing population. The basis of the moderate increase in circulating platelets before 48 hr in severely thrombocytopenic rats and for about 5 days in moderately thrombocytopenic rats is less clear. Both peripheral changes in the age distribution of the platelet population and in platelet depots, as well as hemopoietic changes in the marrow, probably contribute.
Ultrastructural Changes in Human Platelets During Arachidonic Acid-induced Aggregation
Authors: Sedar Albert W. , Silver Melvin J. , Smith J. Bryan , Ingerman Carol M. , Kocsis James J.
Published: October 2019

This study was undertaken to visualize the sequence of ultrastructural changes occurring in human platelets during aggregation induced by arachidonic acid. Aggregometer recordings were obtained up to the time of adding glutaraldehyde to begin fixation of platelets for electron microscopy. A correlation was shown between the degree of aggregation and changes in the fine structure of human platelets which had been allowed to aggregate for 15, 30, 90, or 180 sec. The pattern of ultrastructural changes found in the platelets aggregating in response to arachidonic acid was similar to that reported previously for other aggregating agents such as collagen or ADP. Amorphous material was observed within the dilated canalicular system of platelets, supporting the thesis that its channels serve as a pathway for the products released during aggregation. The dilatation of the canalicular system of platelets induced by arachidonic acid could be mediated by an intermediate in prostaglandin synthesis.
Antibodies to Factor VIII: Specificity and Kinetics of Iso- and Hetero-antibodies in Hemophilia A
Authors: Allain J. P. , Frommel D.
Published: October 2019

Time course inactivation of isologous and heterologous AHF preparations induced by anti-factor VIII antibodies from hemophiliacs followed two major patterns: one was consistent with a second-order reaction, the other more complex. The second-order type, characterized by a plateau of residual factor VIII activity occuring after 2-4 hr of incubation, was observed in the interaction of factor VIII with its corresponding and specific antibody. The complex type, showing a gradual decline of factor VIII activity following a rapid initial fall, was detected in antigen-antibody-reactions relying predominantly on cross-reactions. It is proposed that reactions of the second-order type reflect the formation of stable antigen-antibody complexes, while reactions of the complex-order type express a tendency to spontaneous dissociation of antigen-antibody complexes.
Independence of Iron Absorption From the Rate of Erythropoiesis
Authors: Peschle C. , Jori G. P. , Marone G. , Condorelli M.
Published: October 2019

The regulation of iron absorption is only partially understood. A cause and effect relationship between the erythropoietic and the absorption rates has been postulated, but not firmly established. Experiments in polycythemic mice were undertaken in an attempt to separate the effect of hypoxia on iron absorption from that on the erythropoietic activity. The latter parameter was evaluated on the basis of per cent values of peripheral reticulocytes, nucleated red cells in red pulp of spleen, and/or RBC-59Fe incorporation. In the first series of experiments the erythroid response to an 18- or 96-hr period of hypoxia was selectively suppressed by administration of antierythropoietin (anti-Ep) serum. However, the enhancement of iron absorption induced by an equivalent hypoxic stimulus was not significantly modified by anti-Ep. In additional studies, polycythemic mice were subjected to either fractionated Ep administration or hypoxic stimuli, lasting 24, 48, or 72 hr. The stimulatory effect on erythropoiesis induced by Ep was either greater or equivalent to that of hypoxia. However, although these hypoxic stimuli induced a four- to sixfold increase in iron absorption, Ep administration evoked either little or no enhancement of iron absorption. These experiments provide evidence against concepts linking the primary regulation of iron absorption to the erythropoietic rate.
Azurophil and Specific Granules of Blood Neutrophils in Chronic Myelogenous Leukemia: An Ultrastructural and Cytochemical Analysis
Authors: Ullyot Joan L. , Bainton Dorothy F.
Published: October 2019

That most patients with chronic myelogenous leukemia (CML) have either very low levels or no leukocyte alkaline phosphatase activity (LAP) is an established fact. In view of our new findings7 that normal mature human polymorphonuclear leukocytes (PMN) contain two types of granules, azurophils (1/3) and specifics (2/3), and that alkaline phosphatase is present only in specific granules, we undertook the present studies to determine whether these neoplastic PMN lack a specific granule population or simply lack the enzyme. The cellular buffy coats of five patients with CML (Ph1+, LAP-) were fixed in glutaraldehyde, incubated for peroxidase to identify the azurophil population, and examined by electron microscopy. It was found that the specific granule population was present in all mature PMN. Counts of both azurophil and specific granules per cell were slightly lower than normal but were within an 80%-90% overlap of the normal range. We therefore conclude that the low level of LAP in patients with CML reflects a deficiency of the enzyme rather than a missing granule population. Although the mature PMN appeared relatively normal (with few exceptions), circulating myeloblasts and promyelocytes revealed several abnormalities, the most notable being the presence of large bundles of cytoplasmic microfilaments. The blood of two patients in the terminal phase of disease was reexamined. Most of their cells were immature, with aberrations similar to those in myeloblasts and promyelocytes in the chronic phase of the disorder. In addition, however, we discovered three adnormal populations of mature PMN: (1) PMN containing both populations of granules but lacking peroxidase, (2) PMN lacking specific granules, and (3) PMN lacking azurophil granules. Our findings emphasize the value of electron microscopy and cytochemistry in detecting abnormalities of maturation in the cytoplasm of leukemic PMN.
Improved Plasma Culture System for Production of Erythrocytic Colonies In Vitro: Quantitative Assay Method for CFU-E
Authors: McLeod David L. , Shreeve Mona M. , Axelrad Arthur A.
Published: October 2019

An improved plasma culture system is described for the production of erythrocytic colonies by mammalian adult hemopoietic cells in vitro under the influence of erythropoietin. The concentration of fetal calf serum in the medium used for dilution of the cells was critical for erythrocytic colony formation when low numbers of cells were plated. Optimal concentrations were found for plasma, fetal calf serum, bovine serum albumin, and L-asparagine in the culture medium, and the colony-forming efficiency was shown to depend on the concentration of erythropoietin. With erythropoietin at plateau concentration, the number of erythrocytic colonies produced was directly proportional to the number of bone marrow or spleen cells plated, over a wide range of cell concentrations. Colony numbers per culture conformed to a Poisson distribution. Thus, the improved plasma culture system may be used for the quantitative assay of CFU-E. The method is rapid (2 days), reliable, convenient, and inexpensive. Since the improved plasma culture system also supports granulocytic colony formation by bone marrow cells in the presence of conditioned medium (CSA), and the number of granulocytic colonies produced is proportional to the number of cells plated, the same hemopoietic cell suspensions can be simultaneously assayed for CFU-E and CFU-C under virtually identical conditions.
Effect of Erythropoietin on RNA Synthesis by Normal and Leukemic Bone Marrow and Spleen Cell Suspensions In Vitro
Authors: Handler Evelyn E. , Mendelsohn Naomi , Handler Eugene S.
Published: October 2019

Erythropoietin (EPO) induced a 42% increase in 3H-uridine incorporation into RNA after a 5-hr culture of normal bone marrow cell suspensions. Bone marrow cells obtained from rats 3-5 days after the initiation of a myelogenous leukemia exhibited a decreased responsivity to EPO. At this time incorporation of the isotope into RNA in the presence of EPO was approximately 50% of controls. Rats rendered leukemic 8-10 days prior to culture showed no bone marrow response to EPO even in those instances where leukemic cells comprised a relatively small percentage of the marrow compartment. EPO had little or no effect on RNA synthesis by spleen cells obtained from normal and leukemic rats. This was noted even in those leukemic spleens in which erythropoiesis was observed. The data suggest that the anemia associated with myelogenous leukemia may, in part, be due to a loss of EPO-responsive cells and/or a loss of sensitivity of these elements to normal humoral control.
Changes in Platelet Shape and Structure After Freeze Preservation
Authors: Crowley James P. , Rene Anthony , Valeri C. Robert
Published: October 2019

About 60% of the platelets freeze preserved in 6% dimethylsulfoxide retained the discoid shape characteristic of fresh platelets. The remainder were sphered. Platelet sphering occurred during freezing and thawing and was not related to the addition or removal of the cryoprotective agent. Platelets that retained the disc shape had a well-preserved ultrastructure, but sphered platelets showed extensive ultrastructural changes.
Complement-independent Clearance of IgG-sensitized Erythrocytes: Inhibition by Cortisone
Authors: Atkinson John P. , Frank Michael M.
Published: October 2019

The effect of corticosteroid administration on the complement-independent clearance of IgG-sensitized erythrocytes was examined in guinea pigs. 51Cr-labeled guinea pig erythrocytes coated with a known amount of high-avidity IgG antibody were injected into control and cortisone-treated C4-deficient guinea pigs, and cell survival was determined. In these animals with a genetically controlled total deficiency of the fourth complement component, cell-bound antibody does not activate the biologically active complement components; clearance is therefore complement independent. At low levels of sensitization, cortisone completely inhibited the splenic sequestration of IgG coated red cells. As the amount of antibody coating the red cell was increased, higher cortisone doses were required to decrease the rate and magnitude of clearance. Eventually a level of erythrocyte sensitization was reached where cortisone did not significantly alter the clearance pattern compared to untreated controls. The cortisone effect was present by 3 days but required 5-7 days before it was maximal. No evidence was found to suggest that cortisone decreased the affinity of the antibody for the red cell membrane. Rather, the most likely explanation for these results is that cortisone affects the interaction between IgG on the erythrocyte surface and its receptor on splenic and hepatic macrophages. This experimental model of immune hemolytic anemia parallels those cases of warm-antibody-mediated disease in which complement plays no role. These findings suggest that a major clinical effect of cortisone therapy may be to decrease complement-independent erythrocyte clearance, thereby inducing a remission even in the presence of a positive antiglobulin test.
The Frequency of Heterozygosity for S and C Hemoglobins in Western Pennsylvania
Authors: Boggs Dane R.
Published: October 2019

The frequency of AS and AC type hemoglobin was studied by hemoglobin electrophoresis in 26,882 residents of Western Pennsylvania. In the black population, the frequency of S trait was estimated at 7.4% and the frequency of C trait at 1.8%. Reasons for variation in frequency from one to another subpopulation are discussed. The frequency of S and C trait was independent of age, suggesting little or no mortality can be attributed to these traits. Sickle trait was no more common in outpatients than in the general population, suggesting little or no significant trait-associated morbidity.
A New Abnormal Hemoglobin O Padova, α 30 (B11) Glu → Lys, and a Dyserythropoietic Anemia With Erythroblastic Multinuclearity Coexisting in the Same Patient
Authors: Vettore L. , De Sandre G. , Di lorio E. E. , Winterhalter K. H. , Lang A. , Lehmann H.
Published: October 2019

A patient with a not previously described abnormal hemoglobin (α30Glu → Lys) and dyserythropoietic anemia with erythroblastic multinuclearity is reported. The heat stability and the functional properties of the new abnormal hemoglobin, named hemoglobin O Padova, are normal, although the replacement lies in the α1β1 interchain contact. The hemolytic condition, which was much improved by splenectomy, therefore appears to be linked to the hereditary erythroblastic multinuclearity similar to hereditary erythroblastic multinuclearity with positive acidified serum test (HEMPAS). In addition to the leading features observed in published cases of this entity, our case exhibited some immunologic peculiarities.
Methemoglobin Reductase (Cytochrome b5 Reductase) Deficiency in Congenital Methemoglobinemia
Authors: Kitao Takeshi , Sugita Yoshiki , Yoneyama Yoshimasa , Hattori Kenichi
Published: October 2019

Two NADH diaphorases, diaphorase I and II, were isolated from normal red cells and congenital methemoglobinemic red cells by CM-cellulose and DE 32 column chromatography. For methemoglobinemic sample, activities of diaphorase I and diaphorase II were 80% and less than 5% of those for the normal red cells, respectively. Only diaphorase II showed cytochrome b5 reductase activity. The cytochrome b5 reductase deficiency seems to manifest methemoglobinemia through the decrease in the enzymatic reduction of cytochrome b5 and subsequent nonenzymatic reduction of methemoglobin by the reduced cytochrome b5. The methemoglobinemic diaphorase II was found similar to the normal enzyme with respect to Kms for the dye and NADH, heat stability, effect of pH, and electrophoretic pattern. The ratio of the diaphorase activity to the cytochrome b5 reductase activity was the same for both enzymes. Although the production of an abnormal enzyme molecule can not be excluded, it is possible that in this case the rate of enzyme formation is decreased.
Vitamin B12 transport in blood. I. Congenital deficiency of transcobalamin II
Authors: Gimpert E , Jakob M , Hitzig WH
Published: October 2019

Some characteristics of vitamin B12 binding and transport in the serum of an infant with congenital hereditary transcobalamin II (TC II) deficiency were studied using the following parameters and methods: vitamin B12 level and binding capacity; electrophoretic mobility in polyacrylamide gel electrophoresis; various immunodiffusion and absorption experiments, using a specific anti-TC II antiserum and the patient's serum as antigen. The results of these studies point to a deficient synthesis of TC II. Parenteral administration of high doses of vitamin B12 was followed by rapid and complete clinical remission and the appearance of vitamin B12 binder in the alpha 2 region which is similar to “fetal binder.” Thus, very high concentrations of vitamin B12, either carrier free or bound to this alpha 2 binder, were able to correct the disturbed physiology of TC II deficiency, presumably by normalization of DNA-thymine synthesis.
Prothrombin complex proteins as cofactors in platelet aggregation. I. Inhibition of aggregation by antiserum
Authors: Miale JB , Kent JW
Published: October 2019

Data are presented to support the concept that the vitamin K-dependent coagulation factors are adsorbed onto the platelet membrane and that these make up part of the “plasma atmosphere” necessary for the aggregation of platelets by various agents. Together with evidence that other coagulation factors also are part of the plasma atmosphere, it is suggested that the aggregation reaction is part of the coagulation sequence. The immunologic approach to demonstrating constituents of the platelet membrane promises to be a highly specific technique for studying further the constituents of the platelet membrane and their reactions in hemostasis.
Measurement of vitamin B12-binding proteins of plasma. I. Technique
Authors: Begley JA , Hall CA
Published: October 2019

The unsaturated binding capacities (UBBC) of individual vitamin B12- binding proteins in plasma were measured by a two-step procedure. Transcobalamin II (TC II) was separated by precipitation with ammonium sulfate; the “R”-type binders remaining soluble were then divided into two components by bath separation with anion exchange on DEAE- cellulose. The two R components were designated alpha1-R (TC 1) and alpha2-R (third binder, fetal binder, PV binder, TC III). Ten normal sera were studied by this technique giving a separation into TC III and total plasma R identical to that obtained simultaneously by gel filtration. The mean UBBC of TC II was 969 plus or minus 204 pg of 57 Co B12 per ml of serum. The mean contamination of the precipitated TC III with plasma R was 3%. The UBBCs of alpha 2-R and alpha 1-R were 127 plus or minus 42 and 40 plus or minus 12 pg/ml, respectively. The mean contamination of the R fraction by TC II was 14% as evaluated by gel filtration. By isoelectric focusing it was found that the alpha1-R contained principally those components isoelectric at pH isoelectric at pH of 2.9–3.2, while alpha2-R was made up of those components isoelectric at pH of 3.6 or greater.
Red cell iron uptake in hereditary microcytic anemia
Authors: Edwards JA , Hoke JE
Published: October 2019

The iron uptake in vitro of red cells from mice with hereditary microcytic anemia (gene symbol mk) was studied to examine the hypothesis of a generalized impairment of cellular iron uptake in this conidition. Reticulocyte-rich red cells from anemic (mk/mk) and acutely bled normal (+/+) mice were incubated in 59Fe-labeled mouse plasma and the radioiron uptake measured. The 59Fe uptake of the mk/mk and +/+ cells was related in the same way to the reticulocyte concentration, the duration of incubation, and the percentage saturation of the plasma iron-binding capacity. However, under the same conditions, the iron uptake of red cells from normal (+/+) mice was greater than that by red cells from anemic (mk/mk) mice. Furthermore, the cellular loss of radioiron on exposure to EDTA was greater for the mk/mk red cells, although the proportion of the radioiron taken up that was incorporated into heme was the same for mk/mk and +/+ red cells. These results support the hypothesis of a generalized impairment of cellular iron uptake in hereditary microcytic anemia and suggest that there might be a defect in red cell receptor sites for transferrin in this condition.
Intensive leukapheresis as initial therapy for chronic granulocytic leukemia
Authors: Lowenthal RM , Buskard NA , Goldman JM , Spiers AS , Bergier N , Graubner M , Galton DA
Published: October 2019

Intensive leukapheresis has been used as the initial treatment of chronic granulocytic leukemia (CGL) in six patients. The number of leukaphereses ranged from 3 in 7 days to 13 in 39 days (mean, 8 in 22 days). The procedures were well tolerated, and in all patients there was improvement in hematologic values, in most cases with considerable reduction in the peripheral leukocytosis and thrombocytosis and in the proportion of immature granulocytic cells in the circulation. Splenomegaly decreased considerably in the four patients who had more than four leukaphereses. Symptoms of sweating, malaise, and pain due to splenomegaly were rapidly relieved. Problems due to hyperuricemia did not occur, but four patients required blood transfusions for correction of anemia. This method of initial treatment of CGL appears to give more rapid relief of symptoms than does conventional chemotherapy; it incurs no risk of hyperuricemia and lessens that associated with thrombocytosis. In addition, large quantities of granulocyte-rich plasma are made available for the treatment of infections in neutropenic patients. Intensive leukapheresis deserves more widespread evaluation as the initial treatment of CGL.
Hemin reversal of benzene-induced inhibition of reticulocyte protein synthesis
Authors: Forte FJ , Cohen HS , Rosman J , Freedman ML
Published: October 2019

Benzene (0.056–0.113 M) rapidly and reversibly inhibited protein synthesis in anucleate human sickle cell and rabbit reticulocytes. Hemin (50 muM) both prevented and reversed this effect of benzene. The inhibition in rabbit reticulocytes was accompanied by a conversion of polyribosomal disaggregation required ribosomal movement along mRNA and was also prevented and reversed by 50 muM hemin. Benzene was also shown to inhibit heme synthesis in rabbit reticulocytes while neither ATP nor GSH levels were altered. A translational repressor (HCR) of reticulocyte cell-free protein synthesis was isolated from intact cells incubated with benzene, while no significant amount of HCR was found in cells incubated with both benzene and hemin. These results indicated that benzene inhibits translation at the heme-dependent site of initiation. The clinical implications of these experiments remain to be elucidated.
Hb Leslie, an unstable hemoglobin due to deletion of glutaminyl residue beta 131 (H9) occurring in association with beta0-thalassemia, HbC, and HbS
Authors: Lutcher CL , Wilson JB , Gravely ME , Stevens PD , Chen CJ , Lindeman JG , Wong SC , Miller A , Gottleib M , Huisman TH
Published: October 2019

A new unstable hemoglobin, Hb Leslie, has been observed in three generations of a Georgia family. The propositus, a 42-yr-old black veteran with hemolytic anemia and splenomegaly, has a hemoglobin variant with an electrophoretic mobility similar to that of hemoglobin F. The variant comprises about 85% of the total hemoglobin and was isolated by chromatography. Chemical analysis has identified the abnormality as a deletion of the glutaminyl residue in position 131 (H9) of the beta-chain. Deletion of this critical residue which participates in the alpha1beta1 contact causes decreased stability of the hemoglobin without significant changes in functional properties or morphologic abnormalities in the erythrocyte. Family studies revealed hemoglobin Leslie occurring in combination with beta0-thalassemia, HbS, and HbC. All persons with the various Hb Leslie combinations, including the propositus, have no clinical manifestations other than anemia. In some the anemia is fully compensated. There is no history of drug- associated hemolysis.
Evidence for significant hematopoiesis in the human thymus
Authors: Taylor CR , Skinner JM
Published: October 2019

Earlier studies on fetal thymus suggested that certain of the large pyroninophilic cells found there might have a hemopoietic role, and it was decided to determine the nature of these cells using histochemical and immunohistochemical methods. Thymic tissue from aborted fetuses, stillbirths, and neonatal deaths was examined histochemically using methods for the detection of chloroacetate esterase, peroxidase, and pseudoperoxidase, and by staining techniques for mast cells and eosinophils. Tissue was also examined using the indirect immunoperoxidase method for the presence of hemoglobin A (HbA) and F (HbF), for lysozyme (muramidase) and immunoglobins alpha, mu, gamma, kappa, lambda. Positive staining to some degree was seen in cells in the connective tissue stroma using all methods, and the cells stained corresponded to one or another of the types of pyroninophilic cells present. The finding of large cells with positive chloroacetate esterase and antilysozyme indicates the presence of granulopoiesis. Similarly, the presence of large nucleated cells with pseudoperoxidase and anti-hemoglobin (A and F) staining indicates the presence of erythropoiesis. Plasma cells were present in small numbers.
Effect of erythropoietin on chromosomal protein synthesis
Authors: Spivak JL
Published: October 2019

The spleen of the exhypoxic polycythemic mouse was employed to study the effect of erythropoietin on the synthesis of chromosomal proteins. At 1, 3, 18, 36, 45, and 72 hr after injection of erythropoietin, spleens were removed, minced, and incubated with 3H-arginine for 1 hr. Chromatin was isolated from the labeled splenic tissue and separated into histone and nonhistone protein (NHP) fractions. An increase in the incorporation of 3H-arginine into NHP occurred within 3 hr and into histones by 18 hr. Incorporation of 3H-arginine into both histones and NHP was maximal by 45 hr and had declined by 72 hr. Total histone specific activity increased fivefold while NHP specific activity increased twofold. Histones and NHP were fractionated on polyacrylamide gels and a double isotope labeling proceudre was used to study the synthesis of the individual histone proteins and NHP. Following administration of erythropoietin, there was a coordinate increase in the specific activity of all five major histone proteins and most of the NHP. The earliest change in specific activity of both histones and NHP occurred prior to the appearance of morphologically identifiable erythroblasts in the spleen.
Allogeneic marrow grafting for treatment of aplastic anemia: a follow- up on long-term survivors
Authors: Storb R , Thomas ED , Buckner CD , Clift RA , Fefer A , Fernando LP , Giblett ER , Johnson FL , Neiman PE
Published: October 2019

Eleven of twenty-four patients with severe aplastic anemia given marrow grafts from HLA-identical siblings between October 1970 and March 1973 are alive with normal marrow function and continued evidence of engraftment 3–5 yr later. Ten have been leading normal lives with no immunosuppressive or other drug therapy since day 100 postgrafting. One has had chronic graft-versus-host disease of the skin which is now slowly improving with no therapy. He returned to full-time employment in the summer of 1975. The long-term well-being of almost half of our initial patients emphasizes the importance of marrow transplantation for the treatment of severe aplastic anemia.
Lymphosarcoma cell leukemia: the contribution of cell surface study to diagnosis
Authors: Aisenberg AC , Wilkes B
Published: October 2019

Cell surface immunoglobulin, complement receptor, and spontaneous rosette formation with sheep erythrocytes were investigated in 43 patients with malignant lymphoma, including 13 with lymphosarcoma cell leukemia, and in 59 patients with chronic lymphocytic leukemia. The quantity of immunoglobulin on the lymphocyte surface was estimated from the intensity of fluorescent staining with fluorescein-conjugated anti- immunoglobulin antisera. At least two, and probably three, B cell species could be recognized by cell surface study. Cells from chronic lymphocytic leukemia and diffuse well-differentiated lymphocytic lymphoma had sparse amounts of surface immunoglobulin, while the cells of diffuse poorly differentiated lymphocytic lymphoma had large quantities of this material. Nodular lymphoma probably represented a third B-cell subtype with intermediate amounts of surface immunoglobulin. The lymphocytes of chronic lymphosarcoma cell leukemia exhibited the intense surface staining, which was characteristic of the underlying poorly differentiated lymphocytic lymphoma (diffuse or nodular), and could be readily distinguished from the faint-staining chronic lymphocytic leukemia cells.
Hydrogen peroxide production and killing of Staphylococcus aureus by human polymorphonuclear leukocytes
Authors: Tsan MF , Douglass KH , McIntyre PA
Published: October 2019

The effects of bacterial neuraminidase on production of hydrogen peroxide (H2O2) and killing of Staphylococcus aureus by human polymorphonuclear leukocytes (PMN) were studied. The concentration of H2O2 was measured by the disappearance of scopoletin fluorescence in the presence of horseradish peroxidase. The results indicated that desialylation of human PMN inhibited the stimulation of H2O2 production during phagocytosis. It also markedly impaired the killing of S. aureus. Impaired killing of S. aureus by desialylated PMN was due to impaired intracellular killing rather than defective phagocytosis.
THE HEMORRHAGIC SYNDROME OF ACUTE IONIZING RADIATION ILLNESS PRODUCED IN GOATS AND SWINE BY EXPOSURE TO THE ATOMIC BOMB AT BIKINI, 1946
Authors: CRONKITE E. P.
Published: October 2019

1. The hemorrhagic syndrome of acute radiation illness in goats and swine has been described. This syndrome is predominantly a result of a combination of "increased vascular fragility" and thrombopenia. Infrequently, a blood coagulalation defect characterized by a prolonged clotting time due to a circulating anticoagulant with heparin-like properties appears, thus confirming under some conditions in goats and swine the work of Allen on "heparinemia" in irradiated dogs.

2. The prolonged blood coagulation time appeared only in fatally irradiated goats and swine.

3. Evidence was presented suggesting that serum fibrinolysins may have been activated.

4. It is concluded on the basis of this work and that of others that a hemorrhagic syndrome can develop in irradiated dogs, goats, swine, rats, chickens and guinea pigs without the appearance of a prolonged clotting time and without a detectible "heparinemia." The biologically most universal phenomena observed in the hemorrhagic syndrome of radiation illness appear to be: (a) increased vascular fragility, (b) thrombopenia, and (c) ulcerations.
OBSERVATIONS ON THE HEMATOLOGIC VALUES OF THE JAPANESE
Authors: SNELL FRED M.
Published: October 2019

Hematologic studies have been made on 935 randomly selected "control" (nonirradiated) Japanese residing in Kure, Japan, as part of an investigation on the irradiated survivors of the Hiroshima atomic bomb. An analysis of the findings with respect to age and sex indicated that there were a number of divergences from the usual Caucasian expectancies. Associated with a slight anemia in those over puberty there is a progressive increase in the mean size and hemoglobin content of the erythrocyte with increasing age, more pronounced in the male. The hemoglobin concentration in the cells is apparently reduced. The leukocyte counts decrease with increasing age and all mean values are somewhat elevated. Plasma protein levels as determined by the copper sulfate specific gravity method are higher than Caucasian normals. Reticulocyte counts are not unusual.

It has been emphasized that this "control" series does not consist entirely of normal healthy individuals, but that a considerable amount of disease is represented especially in regard to parasitic infestation. Also there is an appreciable nutritional imbalance present in the population. These two factors are probably of greatest significance in the interpretation of the observed divergences from Caucasian expectancies, but in view of the complexity of influences and inadequate data relative to each individual studied interpretations must be guarded.
THE OCCURRENCE IN A FAMILY OF SICILIAN ANCESTRY OF THE TRAITS FOR BOTH SICKLING AND THALASSEMIA
Authors: POWELL W. N. , RODARTE J. G. , NEEL J. V.
Published: October 2019

1. A 38 year old male of Sicilian ancestry with a chronic, hemolytic anemia clinically indistinguishable from sickle cell disease is described. Family studies extending over three generations and including all persons indicate that this individual has received from his father a gene for the sickling phenomenon, and from his mother a gene for thalassemia.

2. Three alternative hypotheses are advanced to account for the severity of the anemia present in the patient. The bases whereby a decision can be reached as to which of the three hypotheses is correct are discussed. It is indicated that no decision is possible until the results of studying a number of families comparable to the present are available.

3. It is suggested that many of the reported cases of sickle cell disease in Caucasians actually involve a genetic situation comparable to the one reported in the present paper.
THE SEDIMENTATION DIFFERENTIAL AGGLUTINATION TEST
Authors: STATS DANIEL
Published: October 2019

The sedimentation differential agglutination technic is a modification of the Ashby method by means of which the concentration of immunologically distinct erythrocytes in a mixture can be determined by observing their volume after agglutination and subsequent sedimentation. The method has been applied to the determination of the efficiency of replacement transfusions, the survival of red cells after blood transfusion, and has afforded a method for the determination of production of erythrocytes under certain conditions. The results indicate an almost complete inhibition of erythropoiesis and the frequent presence of excessively rapid hemolysis in "blast" leukemias. In a number of instances in which simultaneous measurements by the sedimentation differential agglutination and radioactive phosphorus technics were made, good correspondence between the two methods was observed.
IRON METABOLISM
Authors: FINCH CLEMENT A. , HEGSTED MARK , KINNEY THOMAS D. , THOMAS E. D. , RATH CHARLES E. , HASKINS DONALD , FINCH STUART , FLUHARTY REX G.
Published: October 2019

On the basis of experimental and clinical observations and a review of the literature, a concept of the behavior of storage iron in relation to body iron metabolism has been formulated.

Storage iron is defined as tissue iron which is available for hemoglobin synthesis when the need arises. This iron is stored intracellularly in protein complex as ferritin and hemosiderin. It would appear that wherever the cell is functionally intact, such iron is available for general body needs.

Iron is transported by a globulin of the serum to and from the various tissues of the body to satisfy their metabolism. Surplus iron carried by this iron-binding protein is deposited chiefly in the liver.

Storage iron may be increased in two ways. The first mechanism results from the inability of the body to excrete significant amounts of iron. Because of this, any decrease in circulating red cell iron (any anemia other than blood loss or iron deficiency anemia) is accompanied by a shift of iron to the tissue compartment. The total amount of body iron remains constant and is merely redistributed.

This is to be contrasted with the absolute increase in body iron and enlarged iron stores which follow excessive iron absorption or parenteral iron administration. Enlarged iron stores in either instance may be evaluated by examination of sternal marrow or determination of the serum iron and saturation of the iron binding protein

In states of iron excess, differences in initial distribution are observed, depending on the route of administration and type of iron compound employed. Iron absorbed from the gastro-intestinal tract and soluble iron salts injected in small amounts are transported by the iron-binding protein of the serum and stored predominantly in the liver. Colloidal iron given intravenously is taken up by the reticulo-endothelial tissue. Erythrocytes appear to localize in greatest concentration in the spleen, while greater amounts of hemoglobin iron are found in the renal parenchyma. These latter differences in distribution reflect the capacity of various body tissues to assimilate different iron compounds, which while present in the plasma are not carried by the iron-binding protein.

Over a period of time an internal redistribution of iron from these various sites occurs through the serum iron compartment. The liver becomes progressively loaded with iron. When the capacity of the liver to store iron is exceeded, the serum iron increases and secondary tissue receptors begin to fill with iron. That iron in large amounts is toxic to tissues is suggested by the occurrence of fibrosis in the organs most heavily laden with iron. This sequence of events, whether following excessive iron absorption or parenteral iron administration is believed to be responsible for the clinical and pathologic picture of hemochromatosis.
THE INFLUENCE OF Rh HAPTEN THERAPY ON THE COURSE OF Rh ISOSENSITIZATION IN PREGNANCY
Authors: SPURLING CARROLL L. , SACKS MILTON S. , JAHN ELSA F.
Published: October 2019

1. Ten Rh-negative sensitized pregnant women were treated with Rh hapten in doses of 100 to 600 mg. weekly for periods varying from seven to twenty-eight weeks antepartum.

2. Three patients with heterozygous husbands delivered Rh-negative infants. Maternal antibody titers were unaffected by hapten therapy.

3. Three patients delivered Rh-positive infants displaying varying degrees of erythroblastosis fetalis.

4. The pregnancies of 4 patients terminated with fetal deaths in utero despite hapten therapy.

5. There does not seem to be any evidence that Rh hapten in the doses and manner employed altered the course or outcome of any of the 10 pregnancies.
THE EFFECT OF FOLIC ACID ON THE CENTRAL NERVOUS SYSTEM OF NORMAL SUBJECTS AND SUBJECTS WITH ANEMIA OTHER THAN PERNICIOUS ANEMIA
Authors: WEISSBERG JONAS , McGAVACK T. H. , VOGEL MILDRED , KENIGSBERG S.
Published: October 2019

1. The administration of 20 mg. of folic acid daily to a group of 26 normal subjects and to a group of 22 subjects with some form of anemia other than pernicious anemia for a period of six to twelve months was not harmful to the central nervous system.

2. Pre-existent neurologic changes in both groups of patients were not altered during the period of treatment with folic acid.

3. Hematologic variations in both groups were not significant during the period of treatment.

4. A sense of well being and a diminished incidence of upper respiratory infections were reported by many of the normal subjects to whom folic acid was administered.
LYMPHOCYTES IN THORACIC DUCT, INTESTINAL AND HEPATIC LYMPH
Authors: MANN JOSEPH D. , HIGGINS GEORGE M. , VAN HOOK EMERY
Published: October 2019

In rats whose intestinal or thoracic duct lymph was drained externally for several days, lymphopenia occurred. Large numbers of cells were collected in the lymph each day, as many, apparently, from the intestinal lymph alone as from the thoracic duct. Hepatic lymph contributed relatively few cells.

Augmentation of lymph flow decreased the concentration of cells in the lymph but did not affect the total number of cells collected each day. Fasting for several days likewise did not decrease the first day’s output. With each day’s lymph flow, however, the daily output of cells spontaneously decreased. The decrease was not prevented by the intravenous injection of fresh lymph or of fresh rat plasma in large amounts. In view of this unexplained effect, one must be cautious in interpreting the results of experiments on the lymph lymphocyte.
ACID AND ALKALINE PHOSPHATASE IN WHITE CELLS DATA FOR THE LYMPHOCYTE AND THE POLYMORPHONUCLEAR LEUKOCYTE OF MAN AND THE RABBIT
Authors: HAIGHT W. F. , ROSSITER R. J.
Published: October 2019

1. The acid and alkaline phosphatase activity has been determined on a series of suspensions of white cells obtained from both man and the rabbit by several different methods.

2. A statistical analysis of the results shows that for both species the alkaline phosphatase of white cell suspensions is confined chiefly to the polymorphonuclear leukocyte and the acid phosphatase is chiefly in the lymphocyte, although the polymonphonuclear leukocyte contains lesser concentrations of this enzyme also.

3. Although this qualitative distribution was the same for both species studied, quantitatively the rabbit differed from man. The activity of the alkaline phosphatase of the rabbit polymorphonuclear leukocyte was eight times that of the corresponding human cell, while the activity of the acid phosphatase of the human lymphocyte was more than twice that of rabbit lymphocyte.
HYPERSPLENISM ASSOCIATED WITH FOLLICULAR LYMPHOBLASTOMA REPORT OF A CASE WITH SPLENECTOMY
Authors: BERMAN LAWRENCE , KLEIN ALFRED A. , LINN HERMAN J. , BATES GAYLORD S.
Published: October 2019

A patient with secondary hypersplenism due to follicular lymphoblastoma of the spleen exhibited neutropenia and thrombocytopenia, the latter being of sufficient severity to require splenectomy.

Splenectomy was followed by clinical improvement due to restoration of the platelet count and cessation of purpura, whereas the neturopenia persisted.

The significance of the blood, bone marrow, and splenic findings is discussed in the light of current concepts of the mechanism of the hypersplenic effect on the peripheral blood picture.
THE RELATIONSHIP OF PLASMA PROTHROMBIN CONCENTRATION AND THE DEGRADATION RATE OF SERUM "PROTHROMBIN-CONVERTING FACTOR" DURING DICUMAROL THERAPY
Authors: JACOX RALPH F. , BAYS ROBERT F.
Published: October 2019

A study of serum and plasma of patients receiving dicumarol reveals that a good correlation exists between the "degradation rate" of "prothrombin-converting factor" in the serum and the concentration of prothrombin in the plasma. As prothrombin concentrations falls, the rate of degradation of "prothrombin-converting factor" becomes slower, while a rise in prothrombin concentration is associated with an accelerated "degradation rate."
STUDIES ON THE HISTAMINE CONTENT OF BLOOD, WITH SPECIAL REFERENCE TO LEUKEMIA, LEUKEMOID REACTIONS AND LEUKOCYTOSES
Authors: VALENTINE WILLIAM N. , PEARCE MORTON LEE , LAWRENCE JOHN S.
Published: October 2019

The literature concerning blood histamine has been reviewed, including the evidence that the incorporation of histamine within the myeloid leukocytes may be one of the metabolic functions of myelopoiesis. Data are presented on the histamine content of blood in normal subjects and in subjects with acute leukemia, chronic myelocytic leukemia, erythremia, and with leukocytoses or leukemoid reactions of other etiologies. The changing relationships of total blood histamine to unit myeloid cell histamine in subjects receiving irradiation therapy for chronic myelocytic leukemia are also presented.

The data indicate that total blood histamine in chronic myelocytic leukemia is usually very high in comparison to normal, that the values in erythremia show a definite but less marked tendency in the same direction, while the values in leukocytoses of other etiology are, with few exceptions, normal or low. The blood histamine per million myeloid cells is, on the average, about twice normal in subjects with chronic myelocytic leukemia, within the normal range or a little low in erythremia, and very low on the average in the group of leukocytoses studied. The suggestion is tentatively made that an aberration in this metabolic process (histamine incorporation within myeloid leukocytes) may be an inherent component of chronic myelocytic leukemia, whereas in physiologic leukocytoses and leukemoid reactions this is not the case.
THE EFFECT OF ADMINISTRATION OF EPINEPHRINE ON THE LEUKOCYTE COUNTS OF NORMAL SUBJECTS
Authors: WHITE COLIN , LING TSUIN HWA , KLEIN ARNOLD M.
Published: October 2019

1. Thirty-seven normal subjects were given subcutaneous injections of epinephrine, ranging from 0.25 to 0.5 mg., and the effects on the leukocytes were noted.

2. The neutrophils rose steadily for the three and one-half hours during which blood counts were made. The small lymphocytes rose in the first half hour, then fell below normal and finally returned towards normal. The eosinophils rose at first and then fell below normal for the remainder of the period.

3. The three doses of epinephrine used produced effects which differed quantitatively but not qualitatively. The most readily identified effect of the smallest dose was the one-half hour rise in lymphocytes or the one-half hour rise in total count. A dose of 0.5 mg. is satisfactory for work of this kind.

4. Subjects with a history of allergy showed a greater tendency than the remainder to exhibit a one-half hour rise in the eosinophil count.

5. The changes in the leukocyte count produced by epinephrine are similar to, but not identical with, those produced by adrenocortical hormone or adrenocorticotropic hormone.
HEREDITARY SPHEROCYTIC ANEMIA IN THE NEGRO
Authors: BUTTERWORTH CHARLES E. , KRACKE ROY R. , RISER WILLIAM H.
Published: October 2019

1. A family study is presented in which 12 persons representing four generations of a Negro family were observed. Of these, 2 were cases of spherocytic anemia, 5 were normal and 5 appeared to be carriers of the disease.

2. Several genetic mechanisms are discussed and the suggestion is made that spherocytic anemia in the Negro is due to multiple factors. The high incidence of the disease in females is again pointed out.