bluuebunny/crossref_metadata_2025 huggingface dataset:
Naturally Occurring Human Antibodies to Pepsin-digested IgA
Authors: WILSON I. D. , SOLTIS R. D. , WILLIAMS R. C.
Published: October 2019

Human serum antibodies which react only with antigenic determinants revealed by digestion of IgA with pepsin were found in 29.2 per cent of the sera from 369 hospitalized patients studied. These antibodies were shown to be specific for sites on the F(ab')2a fragment of IgA and were dependent upon intact disulfide bonds for antigenicity. Considerable variability in reactivity with different pepsin-digested IgA proteins was found in individual sera but no relationship to either IgA subgroups or genetically determined IgA antigens was discerned. The presence of these anti-IgA antibodies was not found to be related to specific disease processes or to alterations in serum immunoglobulin concentrations.
A Neonate with Down’s Syndrome and Transient Abnormal Myelopoiesis: Serial Blood and Bone Marrow Studies
Authors: NAGAO TAKESHI , LAMPKIN BEATRICE C. , HUG GEORGE
Published: October 2019

Observations were made of the blood and bone marrow of a male infant with Down’s syndrome during the first year of life. At 4 days of age there were 36,500 myeloblasts/cu.mm. in the blood and 10.8 per cent myeloblasts in the marrow. Initially it appeared the patient had acute myeloblastic leukemia. However, the clinical course and kinetic and electron microscopic studies of his bone marrow cell population indicate he did not have acute leukemia.
Brief Report: Microcytic Anemia with Erythroblastosis in Offspring of Magnesium-deprived Rats
Authors: COHLAN SIDNEY Q. , JANSEN VALERIE , DANCIS JOSEPH , PIOMELLI SERGIO
Published: October 2019

Magnesium deprivation of pregnant rats produces in their offspring depression of intrauterine growth and severe anemia. The anemia is characterized by microcytosis, red cell fragmentation, increase in number of normoblasts and markedly decreased osmotic fragility.
Observations on Regulation of Erythropoiesis During Prolonged Periods of Hypoxia
Authors: FRIED W. , JOHNSON C. , HELLER P.
Published: October 2019

The experiments reported in this paper were designed to explain the phenomenon that plasma erythropoietin (Ep) levels reach peak titers after 8 hours of hypoxia and then fall to barely detectable levels after 72 hours. No single factor was found responsible for the decline of these levels with continued hypoxia, but both increase in the rate of erythropoiesis and increase in the hematocrit contribute to this phenomenon. No decrease in the rate of clearance of injected erythropoietin was observed in hypoxic rats, therefore, it is likely that the production of Ep decreased.

The fall in the plasma Ep level with continued hypoxia is not associated with decrease in the rate of erythropoiesis, suggesting that the initiation of increased erythropoiesis requires higher Ep levels than its maintenance during continued hypoxia. The reason for this difference remains speculative.
A Study of Vitamin B12 Requirements in a Patient With Pernicious Anemia and Thyrotoxicosis: Evidence of an Increased Need for Vitamin B12 in the Presence of Hyperthyroidism
Authors: ALPERIN JACK B. , HAGGARD MARY E. , HAYNIE THOMAS P.
Published: October 2019

The response to small doses of vitamin B12 was studied in a woman with pernicious anemia and thyrotoxicosis. No response to 1 µg. per day occurred, but she did respond to 10 µg. per day. Fourteen months later when she was euthyroid, the patient did respond to 1 µg. per day. In another study, serum vitamin B12 levels were significantly lower in a group of patients with hyperthyroidism than in a group of normal subjects. Seventeen of 20 patients with hyperthyroidism exhibited significantly higher serum vitamin B12 levels 5-8 months after becoming euthyroid. The results of these studies provide evidence for increased vitamin B12 requirements in the presence of hyperthyroidism. The greater need for vitamin B12 appears to be related to increased utilization and/or accelerated turnover imposed by increased metabolism.
Clinical Review: Iron Depletion Without Anemia: A Controversial Subject
Authors: VERLOOP M. C.
Published: October 2019

Iron depletion is considered to be present when staining of bone marrow fragments for hemosiderin gives a negative result; anemia may be absent in that case. Several other methods of investigation which can render iron depletion probable are discussed. Iron depletion without anemia, especially in infants and women, seems to be quite common in affluent societies such as exist in North America and Western Europe. In these cases it is often transient, as is illustrated with some examples. It is also shown that in males who have been gastrectomized usually no anemia arises although iron depletion frequently develops. Women with iron depletion in the reproductive age, however, run a rather great risk of developing irondeficiency anemia because of menstrual blood loss and pregnancies. In iron depletion without anemia, a decrease of iron-containing enzymes has been found in some tissues; it has not been demonstrated, however, that this decrease has any pathological significance. Neither has it been shown that iron depletion as such causes clinical symptoms. Until now no practical methods have been developed to artificially enrich food elements satisfactorily with iron. At present the best way to prevent iron-deficiency anemia in women, particularly in pregnancy, seems to be to strive for a well-balanced diet with an adequate amount of iron-rich constituents. In pregnancy, however, regular controls of the blood picture remain necessary to ensure early diagnosis and adequate treatment of anemia.
Stem Cell Migration and Proliferation During Severe Anemia
Authors: RENCRICCA NICHOLAS J. , RIZZOLI VITTORIO , HOWARD DONALD , DUFFY PETER , STOHLMAN FREDERICK
Published: October 2019

The pluripotential stem cell (CFU) compartment of marrow and spleen was evaluated in mice subjected to an intense erythroid stimulus associated with phenylhydrazine-induced anemia. Erythroid hyperplasia occurred in both marrow and spleen. CFU in the marrow gradually declined to approximately 50 per cent of control levels (day 5) while their numbers in the spleen increased (fourfold) by day 3 and were maintained at this level for several days. These changes in numbers of marrow and splenic CFU were not associated with CFU proliferation. Thereafter, CFU in the marrow, but not in the spleen, entered active cell cycle. The data suggest that CFU migrate from marrow to spleen during the demands of severe anemia. The induction of marrow CFU into cycle further suggests a negative feedback, which, perhaps through cell-cell interaction, maintains stem cells at a critical compartment size. The failure of splenic CFU to cycle may reflect the converse effect, i.e. an inhibition on stem cell proliferation in the wake of an expanded stem cell pool.
Colony Growth of Human Peripheral White Blood Cells In Vitro
Authors: KURNICK JOHN E. , ROBINSON WILLIAM A.
Published: October 2019

Peripheral blood from normal humans and patients with circulating atypical mononuclear cells have been studied for their ability to form granulocytic colonies in vitro in the agar-gel method of hematopoietic cell culture. WBC from patients with chronic lymphocytic leukemia failed to proliferate. Normal human white blood cells gave rise to 0.5-8 colonies per 1 x 106 cells plated, while peripheral blood containing large mononuclear cells gave rise to 15 to 120 colonies per 1 x 106 cells plated, depending upon the number of such cells plated. Colonies averaged 500 cells in size by day 20 of culture and appeared to be granulocytic.
The Kinetics of the Normal, the Megaloblastic and the Sideroachrestic Erythropoiesis Estimated by Colchicine Blocking In Vitro
Authors: BOLL I. T. M. , KOENIGS H.-P.
Published: October 2019

By adding colchicine to bone marrow cultures we developed further parameters for kinetics in normal, megaloblastic and sideroachrestic bone marrow. The increased regeneration in megalopoiesis is demonstrated by an increased mitotic index, an increased stathmokinetic index, a shortened cell doubling time and the prolongation of the divisable pool to the oxyphile erythroblasts which only mature in the normal state. To get ineffective erythropoiesis, the maturation in vivo must have been delayed by an increased number of generations up to the formation of megalocytes. From the stathmokinetic test in vitro, the maturation in megalopoiesis is accelerated as a result of the inhibition of α-2 α-divisions. In normal erythropoiesis stopping mitoses by colchicine probably causes a delayed maturation because the next maturation stage cannot be reached without the regular n-2n-division. In sideroachrestic anemia, the maturation behaves normally but the stathmokinetic test is very high. We conclude that the maturation and mode of division in sideroachrestic anemia is nearly normal.
Electron and Light Microscopic Study of the Erythroblasts of Patients With Congenital Dyserythropoietic Anemia
Authors: HEIMPEL HERMANN , FORTEZA-VILA JERONIMO , QUEISSER WOLFGANG , SPIERTZ EGON
Published: October 2019

The morphological changes of erythroblasts in congenital dyserythropoietic anemia type I have been analyzed by light and electron microscopy. The results support our earlier assumption, that this hereditary disorder of erythropoiesis is a disease entity and is not identical with any of the previously described hereditary hematological diseases. Characteristic morphological aberrations consist of widening of nuclear membrane pores, condensation, vacuolization and disintegration of the nuclear chromatin, structural changes of the nucleolus, appearance of myelin figures, and final autolysis of the cells. All changes are restricted to erythroblastic cells beyond the stage of the proerythroblast. The biochemical basis of this abnormality is not known. It leads to severe ineffective erythropoiesis with anemia, increased total hemoglobin turnover, and secondary hemochromatosis.
Reutilization of Thymidine in Various Groups of Rat Bone Marrow Cells
Authors: HEINIGER H. J. , FEINENDEGEN L. E. , BüRKI K.
Published: October 2019

Thymidine reutilization was studied in single cells of the rat bone marrow. Using 3H-TdR in parallel with 125I-UdR in conjunction with the autoradiographic technique, cells of the erythrocytic series, the megakaryocytic group, and the lymphoid cells were analyzed. Reutilization of thymidine was observed only in those cells known to synthesize DNA. An estimate of the amounts of the thymidine reutilized by the salvage pathway indicated that approximately 40-60 per cent of the thymidine in the blast cells is supplied from DNA of dead cells. This value is similar to that reported previously for whole bone marrow cell populations, suggesting the presence of a common thymidine pool within the bone marrow.
Suppression of an Antibody to Factor VIII by a Combination of Factor VIII and Cyclophosphamide
Authors: GREEN DAVID
Published: October 2019

A 54-year-old woman with a 20-year history of generalized, severe psoriasis presented with diffuse ecchymoses, melena, and vaginal bleeding. The whole blood clotting time was 59 minutes and the plasma factor VIII concentration was less than 1 per cent of normal. Incubation of the patient’s plasma with cryoprecipitate containing one unit of factor VIII resulted in the rapid disappearance of factor VIII activity from the mixture. The major antifactor VIII activity of the patient’s plasma was associated with an immunoglobulin of the IgG class. The patient was initially treated with a combination of methotrexate, azathioprine, and cyclophosphamide. No improvement occurred, and after 6 weeks of therapy the drugs were discontinued. Eight months later, she presented with an expanding sublingual hematoma. Bleeding was controlled by the rapid administration of 10,000 units of factor VIII, and an intravenous dose of cyclophosphamide given concurrently resulted in a prompt decline in antibody titer. Factor VIII levels subsequently became normal and have remained normal during 7 months of follow-up observation.
Transmission of Toxoplasmosis by Leukocyte Transfusion
Authors: SIEGEL STUART E. , LUNDE MILFORD N. , GELDERMAN ALBERT H. , HALTERMAN ROGER H. , BROWN JAMES A. , LEVINE ARTHUR S. , GRAW ROBERT G.
Published: October 2019

Four patients with acute leukemia developed toxoplasmosis following leukocyte transfusions from donors with chronic myelogenous leukemia. Serologic data, obtained from the donors retrospectively, revealed elevated antitoxoplasma antibody titers, suggesting that the transfused leukocytes were the source of the organism in the recipients.
The Hydrogen Peroxide Fragility Test and Serum Tocopherol Level in Anemias of Various Etiologies
Authors: MELHORN DAVID K. , GROSS SAMUEL , LAKE GORDON A. , LEU JAMES A.
Published: October 2019

Increased in vitro erythrocyte sensitivity to the hemolytic effects of hydrogen peroxide (H2O2) in the H2O2 fragility test has been widely associated with vitamin E deficiency. In the present study, H2O2 red cell fragility was abnormally elevated in many types of acquired and congenital anemias in children who were tocopherol sufficient. In addition to abnormal red cell H2O2 sensitivity known to occur in vitro in conditions involving defects in cellular devices for disposal of peroxides, it is likely that a wide variety of erythrocyte dysfunctions result in increased in vitro H2O2 hemolysis even in situations where the usually adequate mechanisms for peroxide detoxification are present.
Patterns of Proliferation and Differentiation of Hematopoietic Stem Cells After Compartment Depletion
Authors: CHERVENICK PAUL A. , BOGGS DANE R.
Published: October 2019

The time of onset and rate of self-replication in the irradiation depleted pluripotential hematopoietic stem cell compartment of mice was measured by a split-dose irradiation method. Mice were irradiated to reduce the compartment size and at daily intervals thereafter were again irradiated; 10 days after the second irradiation the number of endogenous spleen colonies was determined. As irradiation interval was lengthened, colonies increased in an exponential fashion with no apparent lag interval after the first irradiation. The doubling time of the colony-forming cell compartment was calculated as 16 hr if severely reduced in size by 300 R or more but was slower if less irradiation was given. The time of resumption of erythropoiesis following irradiation was measured after 100-900 R by determining uptake of radioactive iron into marrow, spleen, and circulating red cells each day after irradiation. With 200 R or less, erythropoiesis was not abolished. With higher doses there was an interval of no apparent erythropoiesis which increased by 1.6 days for each increment of 100 R. These results are compatible with a pluripotential stem cell compartment, which (1) begins self replication almost immediately following compartment size reduction, and (2) will not differentiate if reduced in size below approximately 10% of normal.
Pure Red Cell Aplasia and Carcinoma
Authors: MITCHELL A. B. S. , PINN G. , PEGRUM G. D.
Published: October 2019

A patient presented with pure red cell aplasia, which responded to corticosteroids. Thirteen months later, a malignant pleural effusion developed, with subsequent death from adenocarcinomatosis. The reports of cases in which pure red cell aplasia has been associated with carcinomata are reviewed. An autoimmune mechanism can be postulated in these circumstances, and the complete response to corticosteroids in the present case would support this hypothesis.
Homozygous Delta-Thalassemia First Discovered in Japanese Family With Hereditary Persistence of Fetal Hemoglobin
Authors: OHTA YOSHIRO , YAMAOKA KOTARO , SUMIDA IKUO , FUJITA SHIGERU , FUJIMURA TOSHIHIRO , YANASE TOSHIYUKI
Published: October 2019

A family with δ-thalassemia has been discovered, in which five members are thought to be δ-thalassemia homozygotes with complete deficiency of Hb A2, and three members are probably heterozygotes with low levels of Hb A2 (1.2-1.6%). In four members among these, persistence of fetal hemoglobin of Swiss type was observed. The formal genetics of these two entities was discussed. The proposita showed first thalassemia-like stigmata with iron deficiency anemia, but after iron therapy administered over 2 months, the stigmata disappeared. All the other members of the family were free from clinical symptoms with normal morphology, MCH, and osmotic fragility of the red cells.
Increased Permeability of Erythrocyte Membrane in Thalassemia
Authors: CIVIDALLI GABRIEL , LOCKER HILA , RUSSELL ALEX
Published: October 2019

Increased sodium efflux is demonstrated in vitro in thalassemic red blood cells (and in those of patients with some other hemolytic conditions). This increase, in the presence of either normal or augmented sodium accumulation, must reflect an increased sodium leak into the cells. In vivo, the intracellular content of sodium and potassium is nearly normal. In vitro, however, thalassemia major RBC incubated for 24 hr undergo increased sodium gain, with somewhat more potassium loss. The resultant loss of cations presumably leads to intracellular dehydration. The converse obtains in hereditary spherocytosis, insofar as a sodium gain greater than the potassium loss leads to accumulation of water. It is concluded that increased permeability of the erythrocyte membrane often reflects an underlying hemolytic process. It is postulated that inability to maintain a normal composition of cations and water plays a part in the pathogenesis of hemolysis in thalassemia.
Leukocyte Labeling With 51Chromium. II. Leukocyte Kinetics in Chronic Myelocytic Leukemia
Authors: SCOTT JAMES L. , MCMILLAN ROBERT , DAVIDSON J. GARY , MARINO JOSEPH V.
Published: October 2019

Sequential or simultaneous leukocyte kinetic studies using radioactive diisopropylfluorophosphate and radiochromate (51Cr) yielded similar or identical blood leukocyte disappearance curves in seven patients with chronic myelocytic leukemia (CML). Body surface 51Cr counting regularly showed a rise in the spleen counting rate during the first hours after infusions of granulocyte populations of mixed maturity. Epinephrine-induced leukocytosis was associated with a fall in the spleen counting rate, lesser decreases over the liver and marrow, rises in the heart and lung counting rates, and an unchanged blood leukocyte disappearance curve. These changes are consistent with the mobilization by epinephrine of a marginal granulocyte pool (MGP), which is largely localized in the spleen and is in equilibrium with the circulating pool. Immature CML granulocyte fractions were cleared from the blood more rapidly than mixed cell populations. The immature cells failed to equilibrate with the splenic MGP, and instead accumulated in the marrow and later recirculated into the blood as mature cells. These findings indicate that the delayed and variably contoured blood granulocyte disappearance curves found in CML are composites resulting from the recirculation of immature granulocytes in the presence of an enlarged total blood pool of mature cells.
The Effect of Imidazole on Human Platelet Aggregation
Authors: DAVIS JAMES W. , PHILLIPS PHYLLIS E.
Published: October 2019

Since imidazole buffers have been used in platelet function tests and the compound has been reported to alter several biochemical activities of platelets, it seemed important to determine whether imidazole influenced platelet aggregation. ADP-induced, collagen-induced, and norepinephrine-induced platelet aggregations were tested in platelet-rich plasma by turbidimetric techniques. Glass bead-induced platelet aggregation in whole blood was tested by a method dependent upon platelet counts. Imidazole, in concentrations of 5mM or less, inhibited aggregation induced by each of these four agents and had negligible effect on the pH of platelet-rich plasma. The second phase of both ADP- and norepinephrine-induced aggregation was inhibited or abolished by imidazole, and 5mM imidazole also inhibited the first phase of norepinephrine-induced aggregation. As little as 0.5 mM imidazole inhibited collagen-induced aggregation in some plasmas. Imidazole appears to be unsuitable for use as a buffer in platelet function tests.
Monocytic Vitamin B12-binding Protein
Authors: CARMEL RALPH , COLTMAN CHARLES A.
Published: October 2019

In Monocytic Vitamin B12-binding Protein, by Carmel and Coltman (Blood: No. 3, March, 360-366, 1971), Table 2, columns 2 and 3, the electrophoretic mobility of both monocyte and granulocyte binders should read α and not α1.
Red Cell Production in the Mouse Following Treatment With Vinblastine
Authors: TWENTYMAN P. R. , BLACKETT N. M.
Published: October 2019

Dose response and time response curves have been obtained for the action of vinblastine on the repopulating cells and on the maturing erythroid cells of the mouse. VLB leads to a complete elimination of 59Fe uptake at 2 days but an overshoot to above normal levels at 5 days. The overshoot is due to an elevated reticulocyte count, and red cell production is normal at this time. The repopulating cells are much less sensitive to VLB than the maturing precursors. VLB has only little effect on numbers of bone marrow reticulocytes but reduces their rate of incorporation of iron.
Hematologic and Cytogenetic Remission of Blastic Transformation in Chronic Granulocytic Leukemia
Authors: CANELLOS GEORGE P. , DEVITA VINCENT T. , WHANG-PENG JACQUELINE , CARBONE PAUL P.
Published: October 2019

Thirty patients in the blastic phase of chronic granulocytic leukemia were treated with a combination of vincristine, 2.0 mg/sq m weekly, and prednisone, 60 mg/sq m orally each day. Remission was achieved in nine patients (30%), six of whom had a complete remission, and three had a good partial remission. The survival of responding patients was significantly improved over the nonresponders. Cytogenetic studies were performed on all patients in the chronic phase of the disease, and in 28 during the blastic phase. All were Philadelphia chromosome-positive throughout their course. Aneuploidy developed in 68% of the patients entering the blastic phase. Complete hematologic remission was accompanied by disappearance of aneuploid blast cell lines in the five patients in which they were detected, with return of the chromosomal constitution to that which characterized the chronic phase of their disease. Hypodiploidy in blastic transformation of CGL appeared to predict for a favorable response to vincristine and prednisone. Subsequent relapse of the disease in previously remitted patients was associated with further degrees of aneuploidy, suggesting clonal evolution of a resistant cell line.
Antibody to Transcobalamin II and B12 Binding Capacity in Patients Treated With Hydroxocobalamin
Authors: SKOUBY ARNE P. , HIPPE ERIK , OLESEN HENRIK
Published: October 2019

Thirty-two patients treated for B12 deficiency with one or two initial depot series of five i.m. injections of 1 mg hydroxocobalamin on alternate days followed by i.m. injection of 1 mg hydroxocobalamin every third month for maintenance therapy were examined after more than 2 yr of treatment. Antibody to TC II demonstrable after agar gel electrophoresis was detected in 5 of 12 patients given two depot series 1-3 mo apart, while antibody to TC II detectable only after the more sensitive immunoelectrophoresis occurred in 2 of 20 patients given one initial depot series or two series 6 or 12 mo apart. No anti-TC II was observed in serum from untreated patients with pernicious anemia.
Leukemic Reticuloendotheliosis
Authors: TRUBOWITZ SIDNEY , MASEK BERTHA , FRASCA JULIO M.
Published: October 2019

In Leukemic Reticuloendotheliosis, by Trubowitz, Masek, and Frasca Blood: No. 3, September, 288-298, 1971) on page 295, Fig. 8 should read Fig. 9; Fig. 9 should read Fig. 8.
A Study of Aplastic Anemia in an Autopsy Series With Special Reference to Atomic Bomb Survivors in Hiroshima and Nagasaki
Authors: KIRSHBAUM JACK D. , MATSUO TAKESHI , SATO KAZUO , ICHIMARU MICHITO , TSUCHIMOTO TAISO , ISHIMARU TORANOSUKE
Published: October 2019

In A Study of Aplastic Anemia in an Autopsy Series With Special Reference to Atomic Bomb Survivors in Hiroshima and Nagasaki, by Kirshbaum et al. (Blood: No. 1, July, 17-26, 1971) page 21, Table 5, the top part of the table under the heading should read as follows:

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Thrombocytopathia Due to Abnormalities in Platelet Release Reaction—Studies on Six Unrelated Patients
Authors: Weiss Harvey J. , Rogers John
Published: October 2019

The prolonged bleeding time in six unrelated patients ages 24-63, was attributed to impaired platelet aggregation; this could be accounted for by the decreased release of platelet adenosine diphosphate (ADP) that was obtained in all patients. As a consequence of this "platelet release abnormality," collagen-induced platelet aggregation was impaired, the second wave of epinephrine-induced aggregation was decreased (although not invariably absent), and the normal initial wave of ADP-induced aggregation was followed by rapid disaggregation at 37°C. In four patients, the abnormality in collagen-induced aggregation and ADP release appeared to be different than the defect produced by aspirin, whereas two patients appeared to have an "aspirinlike defect." The platelets of all patients adhered normally to connective tissue fibers but were poorly retained in glass bead filters. Other abnormalities included impaired kaolin-induced platelet factor 3 availability in four patients, large platelets (which aggregated normally with bovine fibrinogen) in two, and small platelets in one patient. The general term thrombocytopathia is suggested to describe abnormalities in platelet function; where a specific defect in the release reaction has been demonstrated, "platelet release abnormality" is suggested as an appropriate, specific term.
Guanidinosuccinic Acid on Human Platelet Effects of Exogenous Urea, Creatinine, and Aggregation In Vitro
Authors: Davis James W. , McField James R. , Phillips Phyllis E. , Graham Barbara A.
Published: October 2019

Patients with severe uremia may have a bleeding tendency associated with a prolonged bleeding time and an adequate platelet count. We have tested the effects on platelet aggregation of three compounds that are found in increased concentration in the blood of patients with renal failure. The addition of urea was followed by an immediate, but transient, increase in optical density of platelet-rich plasma. This precluded the use of turbidimetric techniques for the measurement of platelet aggregation after addition of urea, until the optical density became stable. Adenosine diphosphate-, collagen-, and norepinephrine-induced platelet aggregation were shown to be inhibited 1 hr after urea was added to platelet-rich plasma to produce urea nitrogen increments of 100-300 mg/ 100 ml. Increasing concentrations of creatinine by 10 or 20 mg/100 ml did not inhibit platelet aggregation. Guanidinosuccinic acid, in a concentration in the range found in uremic plasma, also had no effect on platelet aggregation. Through inhibition of platelet aggregation, elevated blood concentrations of urea may be one of the causes of the bleeding tendency of uremic platients.
Congenital Methemoglobinemia: The Result of Age-dependent Decay of Methemoglobin Reductase
Authors: Feig Stephen A. , Nathan David G. , Gerald Park S. , Zarkowski Harold S.
Published: October 2019

Methemoglobin reductase activity (MHR), measured by the Hegesh assay, decreases as normal red cells age. This probably accounts for the slighlty increased concentration of methemoglobin in older red cells. Exaggeration of normal MHR age lability was demonstrated in several individuals with various molecular abnormalities of NADH-diaphorase and was associated with more striking accumulation of methemoglobin in the older red cells of those patients. Diaphorase activity, measured by the Scott assay, does not exhibit age lability in normal red cells or the cells of affected patients. While diaphorase uses either NADH or NADPH as a cofactor, methemoglobin reductase requires NADH. Methemoglobin reductase is found in hemolysates but not in membrane preparations, while approximately 1% of total red cell NADH-diaphorase activity is membrane-associated. The specific activity of NADH-diaphorase is approximately 60 times greater than that of methemoglobin reductase. Whether the two activities represent distinct enzyme proteins or differing substrate affinities of the same enzyme awaits adaptation of the Hegesh assay to enzyme electrophoresis.
Glucose-metabolizing Enzymes of the Mouse Erythrocyte: Activity Changes During Stress Erythropoiesis
Authors: Hutton John J.
Published: October 2019

Many features of normal and abnormal erythropoiesis have been described in the inbred mouse, but no systematic studies of enzymatic activities in mouse erythrocytes have been reported. The activities of 14 enzymes of glycolysis and the hexose monophosphate shunt have been measured in mouse erythrocytes formed under normal conditions and during hemopoietic stress induced by phenylhydrazine treatment. The responses of inbred strains A/J and C57L/J were compared. In normal cells of each strain the activity of hexokinase was lowest, that of triosephosphate isomerase the highest, and the rank order of other enzymatic activities in the mouse was similar to that reported for the human erythrocyte. All enzymatic activities increased during the reticulocytosis accompanying stress erythropoiesis, with phosphofructokinase, aldolase, phosphoglycerate mutase, and glucose 6-phosphate dehydrogenase (G6-PD) showing the greatest relative elevations. Enzymatic activities declined rapidly during the 2-wk period following the initial reticulocytosis, suggesting that large numbers of immature erythrocytes with high enzymatic activities and shortened life spans had been produced during the response to erythropoietic stress. In normal hemolysates heated at 50°C, the most labile enzymes were glucose 6-phosphate dehydrogenase, enolase, and glyceraldehyde phosphate dehydrogenase. In the presence of erythrocyte stromata, glucose 6-phosphate dehydrogenase was more thermolabile in hemolysates of strain C57L/J than in those of A/J. This difference correlates both with the markedly lower activity of G6-PD in normal erythrocytes of C57L/J mice compared to erythrocytes of A/J mice and with the more rapid decrease in G6-PD dehydrogenase activity in aging erythrocytes of C57L/J.
Endotoxin Stimulation in Patients With Lymphoma: Correlation With the Myelosuppressive Effects of Alkylating Agents
Authors: DeConti Ronald C. , Kaplan Stephen R. , Calabresi Paul
Published: October 2019

Estimates of the bone marrow granulocyte reserve were made in 97 patients with lymphoma utilizing the endotoxin Pyrexal. Normal granulocyte responses were observed in most patients who had not received prior myelosuppressive therapy. Patients with lymphosarcoma responded as well as those with Hodgkin’s Disease. All patients with leukopenia due to previous therapy or marrow infiltration failed to respond. In the absence of leukopenia only 47% of previously treated patients achieved normal responses. The severity of granulocytopenia produced by intravenous alkylating agent therapy was correlated with pretreatment Pyrexal responses. Patients with normal granulocyte reserves, as demonstrated by this test, tolerated subsequent chemotherapy with significantly less severe granulocytopenia (p <0.02) than patients with abnormal test responses. Nadir granulocyte values below 1000 cells/cu mm developed in 7 of 33 patients with normal Pyrexal responses and in 11 of 15 abnormal responders, despite comparable pretreatment granulocyte values.
Factor IX Deficiency and Bleeding in a Patient With Sheehan’s Syndrome
Authors: Brown Clarence H. , Kvols Larry K. , Hsu Tah-Hsiung , Levin Jack
Published: October 2019

Factor IX deficiency was associated with a hemorrhagic disorder in a woman who previously had experienced postpartum hypotension resulting in Sheehan’s syndrome. There was no family history of Christmas disease, and other known causes of factor IX deficiency were excluded. Plasma levels of factor IX were partially corrected by therapy with thyroid hormones and completely restored to normal by the administration of cortisone. The response of factor IX to plasma infusion resembled the response of factor VIII in patients with von Willebrand’s disease who receive plasma. Normal hemostasis and levels of factor IX have been maintained by the administration of physiologic dosages of thyroid and adrenal hormones. Blood coagulation was studied in several other patients with pituitary or thyroid dysfunction. All were normal, indicating that this patient represents an unusual example of the effects of an endocrine dysfunction on a single blood coagulation factor.
Studies on Human Erythrocyte Nucleotide Metabolism. I. Monisotopic Methodologies
Authors: Valentine William N. , Kürschner Klaus K.
Published: October 2019

Methods were developed to assay the activities of ribosephosphate pyrophosphokinase (RPK, PRPP synthetase, E.C. 2.7.6.1) and adenine phosphoribosyltransferase (APRT, AMP pyrophosphorylase, E.C. 2.4.2.7) in hemolysates of human erythrocytes. RPK activity was determined by measuring the production of phosphoribosyl pyrophosphate (PRPP) and the formation of adenosine mononucleotide (AMP), the two products of the reaction. The Km for adenosine triphosphate (ATP) was 0.12 mM with the PRPP method and 0.1 mM with the AMP method. The Km for ribose-5-phosphate (R-5-P) was 0.14 mM with the former method and 0.033-0.042 mM with the latter. The pH optimum with the PRPP method was between 7.6 and 8.2. The mean RPK activity of hemolysates of normal mature erythrocytes was 30.5 ± 3.78 µmoles of PRPP or 30.6 ± 3.82 µmoles of AMP produced/hr per 1010 erythrocytes at 37° C. Although RPK activity of normal mature erythrocytes did not appear to be markedly age dependent, activity was substantially increased in reticulocyte-rich blood. APRT activity was assayed by measuring the AMP produced in a system linked to the generation of oxidized nicotinamide adenine dinucleotide (NAD). The activity of normal mature erythrocytes was 3.38 ± 0.37 µmoles of AMP formed/hr per 1010 erythrocytes at 37° C. Enzyme activity was significantly elevated in reticulocyte-rich blood and in the erythrocytes of a patient with the Lesch-Nyhan syndrome. These methods obviated the need for isotopic techniques and were readily applicable to small samples of blood.
Abnormal Erythroid Maturation Following Acute Lead Toxicity in Mice
Authors: Morse Bernard S. , Germano Gerald J. , Giuliani Dennis G.
Published: October 2019

Acute lead (Pb) toxicity in mice, produced by a single i.v. injection of Pb acetate, was associated with transient erythroid hypoplasia and impaired utilization of RBC 59Fe for heme synthesis. The mechanism of this Pb-induced erythroid hypoplasia was further investigated in posthypoxic plethoric mice. When Pb and erythropoietin (EP) were administered simultaneously, the resultant erythroid response was diminished relative to EP-treated controls. Twelve hours after the simultaneous EP and Pb injection, the number of early (pro) normoblasts was comparable to EP-treated controls. By 24 hr, there was a reduction of intermediate normoblasts followed by a decreased transition of these cells to late normoblasts. Excess nonheme iron was demonstrated by cytochemical technique in the cytoplasm of intermediate normoblasts in Pb-treated mice. Administration of Pb at intervals before and after EP resulted in a depressed reticulocyte response relative to EP-treated controls. The nadir of this response was observed when Pb was given 16 hr after EP. From these studies, we would suggest that the effects of Pb on erythropoiesis are best explained by the intramedullary death of intermediate normoblasts. A decrease in the conversion of early to intermediate forms, with subsequent intramedullary death of early normoblasts, may also contribute to the depression of the erythroid response. The mechanism for erythroid hypoplasia in some cases of human plumbism could be, in large measure, attributable to this process.
Thrombocytopathia Due to Abnormalities in Platelet Release Reaction—Studies on Six Unrelated Patients
Authors: Weiss Harvey J. , Rogers John
Published: October 2019

In Thrombocytopathia Due to Abnormalities in Platelet Release Reaction —Studies on Six Unrelated Patients, by Weiss and Rogers (Blood: No. 2, February, 187-196, 1971) page 190, the top right-hand column head in Table 2 should read "ADP release (mµM/109 platelets)."
Nature of the Defect in Congenital Factor V Deficiency: Study in a Patient With an Acquired Circulating Anticoagulant
Authors: Fratantoni Joseph C. , Hilgartner Margaret , Nachman Ralph L.
Published: October 2019

An 8-yr-old girl with congenital factor V deficiency and sporadic hemorrhagic episodes developed an anticoagulant to transfused factor V. This clinical complication, not previously reported, was associated with a severe bleeding episode that subsided when the anticoagulant level decreased. Anticoagulant activity was neutralized by antihuman IgG antiserum but not by anti-IgA or anti-IgM, indicating that the anticoagulant was an immunoglobulin of the IgG class. After 6 mo, anticoagulant activity was no longer detectable. At this time, neutralization studies were performed using the patient’s anticoagulant. Normal plasma and serum contained antigenic activity that neutralized the anticoagulant. Such activity was absent from the remission plasma. Thus, the genetic lesion in the case was characterized by parallel diminution of antigenically and functionally active factor V.
Hemichromes in Single Inclusion Bodies in Red Cells of Beta Thalassemia
Authors: Rachmilewitz Eliezer A. , Thorell Bo
Published: October 2019

Inclusion bodies in the red cells of patients with thalassemia syndromes may result from precipitation of those hemoglobin subunits that are produced in relative excess. In hemoglobin H disease, a form of α-thalassemia, the inclusions are precipitated β-subunits, while in the β-thalassemias they are α-subunits. It has been shown that the inclusions in hemoglobin H disease have the spectral characteristics of hemichrome. In the present study, microspectrophotometric examination of single inclusion bodies in ghosts prepared from the red cells of two patients with β-thalassemia major revealed the absorption spectrum of hemichrome. These results suggest that hemichrome formation is an important pathogenetic event in the production of red cell inclusions and consequent hemolysis in the thalassemias.
THE MECHANISM OF PETECHIAL HEMORRHAGE FORMATION
Authors: HUMBLE J. G.
Published: October 2019

1. The capillary resistance test has been studied by a special technic of capillary microscopy.

2. Seventeen cases of hemorrhagic diseases of differing etiology have been thus studied.

3. The site of capillary hemorrhage has been localized to the arteriolar end of the capillary loop.

4. Selective damage to the arteriolar-capillary junction will explain many types of hemorrhagic syndromes.
CHRONIC NEUTROPENIA: FAVORABLE RESPONSE FOLLOWING SPLENECTOMY
Authors: WEISS HARRY A. , COLLINS WILLIAM T.
Published: October 2019

The case of a patient with chronic neutropenia without splenomegaly, but responding favorably to splenectomy is reported. The surgical procedure appeared to be indicated by the following: (1) exclusion of the extrinsic causes of neutropenia; (2) failure of response to the agents commonly employed to stimulate granulopoiesis; (3) demonstration of granulopoiesis in the sternal marrow; (4) increase in the circulating neutrophils following the parenteral administration of epinephrine; (5) the presence of coexisting diabetes with the potential hazard of infection.

The implication of the spleen as the main factor in the causation of the neutropenia in this case seems well established, although the specific mechanism is not apparent. There was no evidence of abnormal phagocytosis in the microscopic examination of the spleen.
LEUKEMOID REACTION DUE TO MIXED MALARIA INFECTION
Authors: RILEY JAMES A. , ROBINS GEORGE M.
Published: October 2019

A case of mixed malarial infection with a leukemoid blood picture is reported. The literature is reviewed.
PREPARATION OF STABILIZED SOLUTIONS OF HEMOGLOBIN
Authors: PENNELL ROBERT B. , SMITH WILLIAM ELLIOTT
Published: October 2019

It is possible to prepare self-stabilizing solutions of hemoglobin from human erythrocytes by the use of dextrose, nicotinic acid amide and ammonia during the preparation and in the final solutions themselves. Co++, Mn++ and Mg++ ions, nile blue and hexose diphosphate contribute to the speed of stabilization of these solutions. Stabilization is obtained by the faculty of the solutions, presumably by enzymic action, to convert the hemoglobin to the reduced form and to maintain it in this form. The hemoglobin solutions described are suitable for intravenous administration.
THE BLOOD AND BONE MARROW IN PATIENTS WITH CIRRHOSIS OF THE LIVER
Authors: BERMAN LAWRENCE , AXELROD ARNOLD R. , HORAN THOMAS N. , JACOBSON SAMUEL D. , SHARP ELWOOD A. , VONDERHEIDE ELMORE C.
Published: October 2019

The peripheral blood and bone marrow findings in patients with cirrhosis of the liver have been analyzed on the basis of a review of the literature and the authors’ study of 25 patients with diagnoses verified by biopsy of the liver.

The principal blood findings are macrocytic or normocytic anemia with normal or elevated mean corpuscular hemoglobin values, lymphopenia and thrombocytopenia in the majority of cases.

Anemia may be independent of bleeding, and the severity of anemia or macrocytosis does not appear to be related to the severity of the liver lesion.

The consistent change in the bone marrow is extension of the marrow organ so that active hematopoiesis is found in the shafts of the long bones.

Regardless of the presence or absence of bleeding or anemia, the marrow of the sternum is of normal or increased cellularity, with normal or increased erythrocytogenesis and megakaryocytogenesis in most cases.

Hypocellularity of the marrow is an unusual finding, even in patients with advanced liver lesions.

Macronormoblastic erythropoiesis is seen in patients with macrocytic anemia, but megaloblastic erythropoiesis dces not result from cirrhosis of the liver.

The presence of peripheral cytopenias (anemia and thrombocytopenia) in spite of normal or increased formation of erythroblasts and megakaryocytes in the marrow is suggestive of hypersplenism in patients with hepatic cirrhosis.

In patients with chronic hemorrhage the blood and bone marrow pictures are those of iron deficiency anemia, although other changes such as lymphopenia and thrombocytopenia tend to persist.

The combined peripheral blood and sternal marrow examination is often of value in establishing the diagnosis of cirrhosis of the liver.
BONE MARROW REGENERATION IN EXPERIMENTAL BENZENE INTOXICATION
Authors: STEINBERG BERNHARD
Published: October 2019

Benzene intoxication was induced in a number of rabbits in order to study the factors which regulate production of leukocytes. One or more of the marrows of long bones was completely extirpated. After varying intervals, the animals were killed. The regenerated marrow was studied. Comparisons were made with regeneration in normal animals and with the intact marrow of animals treated with benzene. The appearance of regenerated and intact marrow was correlated with the degree of benzene intoxication.

In normal animals, regeneration of extirpated marrow proceeded in a more or less sequential order. At first there was formation of sheets of primitive reticular cells and bone trabeculae, followed by fat cells and then by myeloid tissue. In severe benzene intoxication, the extirpated marrow regenerated only to the point of formation of primitive reticular cells. Further regeneration was halted at the point of formation of fat cells. Myeloid activity appeared to be predicated upon the presence of fat cells. At least, one part of the mechanism by which benzene induces aplasia of bone marrow is probably the inhibition of cell division and maturation past the level of the primitive reticular cell.
MEDITERRANEAN ANEMIA IN THE NEGRO
Authors: SCHWARTZ STEVEN O. , MASON JACK
Published: October 2019

Four cases of "Mediterranean anemia" are reported in Negroes.

The hematologic and clinical findings of available relatives are presented.

The disease in the Negro resembles the condition as found in people of Mediterranean ancestry in every particular.
THE PARALLEL EFFECTS OF MAGNESIUM ON THE COMPLEMENTARY AND COAGULATIVE ACTIVITIES OF BLOOD SERUM
Authors: MALTANER FRANK , DE ALMEIDA JOSÉ O.
Published: October 2019

Magnesium chloride enhances the coagulation and complement activities of blood serum in parallel degree. These enhancing effects are inhibited by inactivated serum or by disodium phosphate.

Distortion in the results of complement-fixation tests occurs with the addition of ionized magnesium salts to the system. This is due to the antagonistic effect of the inactivated test serum. In the quantitatively standardized test, however, where the titer is expressed as the ratio of the reaction of serum and antigen to that of serum alone, the findings are the same with or without added magnesium salts.
A FACTOR IN SERUM WHICH ACCELERATES THE CONVERSION OF PROTHROMBIN TO THROMBIN
Authors: ALEXANDER BENJAMIN , DE VRIES ANDRE , GOLDSTEIN ROBERT , ADDELSON EUNICE , PROMISEL ELAINE
Published: October 2019

1. The evolution of a factor in serum which accelerates prothrombin conversion to thrombin has been studied in normal subjects.

2. Mechanical agitation of fresh blood or the addition of thromboplastin supplements increases the amount of SPCA evolved and decreases the amount of prothrombin activity remaining in the serum.

3. Retarding coagulation by large doses of heparin or by handling the blood with siliconized apparatus decreases SPCA evolution and increases residual serum prothrombin activity.

4. Hypoprothrombinemic blood resulting from dicumarol administration evolves subnormal amounts of SPCA during its coagulation.
THE EFFECT OF VARIOUS ANTICOAGULANTS ON THE SPECIFIC GRAVITY OF BLOOD AND OF PLASMA, AND ON THE HEMATOCRIT
Authors: MCLAIN PAUL L. , RUHE C. H. WILLIAM , PASTORIUS GEORGE J.
Published: October 2019

The effects of several commonly employed anticoagulant procedures on the specific gravity of blood and of plasma, and on the relative red cell volume, were studied in freshly drawn samples of arterial blood from rabbits. Measurements on treated blood, or its fluid component, were compared with corresponding results on portions of the same samples without treatment and prior to coagulation.

Satisfactory preservation of the specific gravity of whole blood was obtained by defibrination or by the use of ammonium-potassium oxalate mixture.

Satisfactory preservation of the specific gravity of plasma was obtained by defibrination or by the use of heparin solution.

The relative volume of red cells was essentially unaltered by the use of dry heparin, oxalate mixture, 1.6 per cent solution of potassium oxalate, or by defibrination.

Dry potassium oxalate and sodium citrate caused marked changes, increasing the specific gravity of blood and of plasma, and shrinking the red cells.

Dry heparin caused significant increases in the specific gravity of blood and of plasma.

Ammonium-potassium oxalate mixture increased the specific gravity of plasma markedly and consistently.