bluuebunny/crossref_metadata_2025 huggingface dataset:
A Red Cell Enzyme Method for the Diagnosis of Acute Intermittent Porphyria
Authors: Magnussen C. Richard , Levine Joel B. , Doherty Joyce M. , Cheesman Judy O. , Tschudy Donald P.
Published: October 2019

A method has been devised for the measurement of uroporphyrinogen I synthetase ih red cells. By using trichloroacetic acid as a protein precipitant, heme is removed from the final solution, allowing accurate measurement of porphyrins. The method is highly reproducible and adaptable to varying incubation volumes and enzyme preparations. It is of great value as an enzyme diagnostic method for acute intermittent porphyria and appears capable of detecting patients with the latent disease who have normal urinary δ-aminolevulinic acid and porphobilinogen excretion. It also appears to distinguish other types of porphyria from acute intermittent porphyria. The mean value of the enzyme in red cells of patients with acute intermittent porphyria was approximately 50% that of normals, indicating that the mutation causes complete lack of catalytic activity in the mutant enzyme.
Effects of erythropoietin on erythroid colony formation in uremic rabbit bone marrow cultures
Authors: Moriyama Y , Fisher JW
Published: October 2019

Erythropoietin-responsive stem cell (ERC) kinetics in anephric uremic rabbits were studied in vitro using the growth of erythroid colonies in a methyl cellulose system in cultures with and without the addition of erythropoietin (ESF). Approximately 68 hr after bilateral nephrectomy, an increase in BUN and decreases in hematocrit and marrow erythroid cellularity were seen. However, the numbers of erythroid colonies formed in response to ESF on plates inoculated with 2 times 10–5 cells were greater in anephric rabbit marrows than in normal controls. In addition, the numbers of erythroid colonies produced by the uremic and normal marrows in the presence of ESF were increased in proportion to the number of precursors plated. These findings suggest that, in uremia, the concentration of ERC is increased and that the ERC are capable of responding normally to ESF. The increase in the number of erythroid colonies of uremia may be due to the undisturbed flow of uncommitted hematopoietic stem cells into the ERC compartment in the presence of a delay of differentiation of ERC into heme-synthesizing nucleated erythroid cells due to a lack of ESF.
Selective damage to erythroblasts by 55-Fe
Authors: Reincke U , Burlington H , Cronkite EP , Hillman M , Laissue J
Published: October 2019

The low energy and short range of 55-Fe Auger electrons were utilized in mice to deliver lethal intracellular radiation to iron-incorporating erythropoietic precursors with minimal radiation damage to other bone marrow cells. The ensuing intramedullary, selective erythropoietic death was demonstrated by absolute and differential bone marrow cell counts and by decreased blood uptake of 59-Fe. The decreased number of colony-forming units in spleen colony assay and the decreased ability of tranplanted bone marrow to protect fatally irradiated mice shows that the bone marrow was partially depleted of pluripotent stem cells. These data are interpreted to indicate an increased pluripotent stem cell utilization in response to increased demand for differentiation of stem cells along the erythropoietic pathway.
The presence of hemoglobin S and C Harlem in an individual in the United States
Authors: Moo-Penn W , Bechtel K , Jue D , Chan MS , Hopkins G , Schneider NJ , Wright J , Schmidt RM
Published: October 2019

The first reported case of hemoglobin S and C Harlem in an individual is described. The patient, a 35-yr-old female, had numerous crises during adolescence and early adulthood, but these occurred more infrequently as she grew older. Chemical evidence is presented for the characterization of both variant hemoglobins. The clinical course of this individual with Hb S in combination with Hb C Harlem appears to be similar to that for persons with sickle cell anemia.
Unregulated growth of murine leukemic cells and suppression of normal granulocyte growth in diffusion chamber cultures
Authors: Miller AM , Marmor JB , Page PL , Russell JL , Robinson SH
Published: October 2019

The patterns of proliferation of C1498 mouse acute leukemic cells have been studied using the diffusion chamber technique of cell culture. These malignant cells grow to the same maximal cell concentration irrespective of initial cell input. Leukemic cells proliferate equally well with or without the stimulus of prior host irradiation. When cells cultured for several days are diluted to the original input concentration and recultured, they rapidly proliferate back to maximal cell number. All of these findings are in sharp contrast to the behavior of granulocytes from normal mouse marrow grown in the same culture system. Co-culutre of equal numbers of normal marrow cells and leukemic cells results in virtually complete inhibition of normal marrow cells and leukemic cells results in virtually complete inhibition of normal granulocyte growth. These experiments provide a means of studying malignant growth of leukemic cells, as compared to the controlled growth and differentiation of normal granulocytes, and mechanisms by which leukemic cells suppress normal granulocyte development.
Applicability of an enzymatic quantitation of methylmalonic, propionic, and acetic acids in normal and megaloblastic states
Authors: Frenkel EP , Kitchens RL
Published: October 2019

A rapid sensitive spectrophotometric assay for the measurement of methylmalonic and propionic acids in urine is described. The assay is based upon the quantitation of propionic acid using acetyl coenzyme A synthetase isolated from baker's yeast. This enzyme is highly specific for acetate and propionate, and acetate interference is eliminated by conversion to citrate. Methylmalonic acid was assayed by converting it to propionate by heat decarboxylation and then measuring the propionate increment over the endogenous amount in the noncarboxylated sample. Studies of urine obtained from normal subjects (by isolation, partial purification, and then assay by the isotope dilution technique) demonstrated urinary excretion of less than 1 mg of propionic acid and 1–5 mg of methylmalonic acid per day. In 22 consecutive patients with documented vitamin B12 deficiency, methylmalonic acid excretion in excess of 30 mg/24 hr was found. In four other patients, with only neurologic involvement methylmalonic aciduria aided in identifying B12 deficiency as an etiologic factor. Methylmalonic acid excretion was measured by direct assay of an aliquot of urine, requiring neither a valine load nor special extraction procedures. Propionic aciduria was variably increased in B12 deficiency and did not correlate either with the severity of the deficit or degree of methylmalonic aciduria. The assay was performed on urine, but it is potentially applicable to tissue extracts. In addition, this assay method can be utilized for the quantification of urine acetate levels as well.
Rabbit factor VIII: identification of size heterogeneity
Authors: Rick ME , Wampler DE , Hoyer LW
Published: October 2019

Two forms of rabbit factor VIII procoagulant activity, distinguishable by size on gel filtration and ultracentrifugation, have been identified in normal rabbit plasma. These studies have been carried out with citrate-anticoagulated rabbit plasma obtained by cardiac puncture. Two peaks of factor VIII activity were obtained on agarose gel chromatography, using physiologic ionic strength buffers: a high molecular weight peak eluting at the void volume and a second peak eluting with smaller plasma proteins. The presence of high and low molecular weight factor VIII activities was confirmed by sucrose density gradient centrifugation. The two peaks of factor VIII activity remained distinct when proteolytic inhibitors were added to the plasma and eluting buffers. Both the high and low molecular weight factor VIII procoagulant activities were inhibited by antibodies to human and rabbit factor VIII, and both were activated by thrombin. The identification of size heterogeneity of factor VIII in normal rabbit plasma, in the absence of any modification by ionic strength, may permit more satisfactory study of the relationship of factor VIII size to function.
THE ONE-STAGE PROTHROMBIN CONSUMPTION TEST
Authors: STEFANINI MARIO , CROSBY WILLIAM H.
Published: October 2019

1. The results of the one-stage prothrombin consumption test, performed in a group of patients with various abnormalities of the hemostatic mechanism, are reported. It appears that the test accurately identifies those conditions such as hemophilia and thrombocytopenic purpura which involve a deficiency of available thromboplastin. Other conditions examined in which a hemorrhagic tendency may develop (hypoprothrombinemia, polycythemia vera, pseudohemophilia) showed a normal consumption of prothrombin. In the hypoprothrombinemia due to dicumarol therapy, the limited amount of available prothrombin appears to have been well utilized during the process of coagulation.

2. It appears that correction of the results obtained for accelerator activity of serum is hardly ever necessary, since this effect is not of such magnitude as to modify the results of the prothrombin consumption test to any extent. A formula for such correction is given.
THE INTESTINAL CONTENT IN PERNICIOUS ANEMIA OF FACTORS FOR THE GROWTH OF STREPTOCOCCUS FAECALIS AND LACTOBACILLUS LEICHMANNII
Authors: GIRDWOOD RONALD H.
Published: October 2019

The gastric juice and small intestinal secretions of three cases of untreated pernicious anemia and two control patients obtained during a period of fasting contained only very small amounts of pteroylglutamic acid or of factors for the growth of L. leichmannii, which include vitamin B12; there was no evidence of a consistent increase or decrease of these factors along the intestine.

Both pteroylglutamic acid and vitamin B12 appear to be synthesized in relatively large amounts in the large intestine; in a patient with pernicious anemia, the daily output in the stools may be about 5 micrograms of vitamin B12 and 0.5 mg. of pteroylglutamic acid. Similar quantities may be present in patients not suffering from this disorder.
INTRAVASCULAR HEMAGGLUTINATION
Authors: DAY RICHARD , PERRY ELISE
Published: October 2019

Severe degrees of intravascular red cell agglutination have been observed during life in rats injected with anti-rat red cell serum and in a patient of 11 months with chronic acquired hemolytic anemia. There was no significant fall in the tissue oxygen tension or in the total oxygen consumption of the rats. Neither the rats nor the infant developed kernicterus. In a baby dying with kernicterus no true hemagglutination was observed, although there was slight sludging such as is seen in many illnesses. Additional support for the belief that the red cells in this case were not clumped lies in the fact that in vitro clumping was not observed; furthermore, the sedimentation rate was only 1 mm. in one hour. The blood of the injected rats and of the other infant who did not develop kernicterus sedimented extremely rapidly and displayed spontaneous agglutination in vitro. These observations indicate that intravascular agglutination has little if any bearing on the development of kernicterus in erythroblastosis fetalis.
CIRCULATING ANTICOAGULANTS IN HEMOPHILIA AND IN HEMOPHILIA-LIKE DISEASE
Authors: SINGER KARL , MOND ERNEST , HYMAN JULIAN , LEVY ROBERT C.
Published: October 2019

Hemophilia-like disease may be defined as a hemorrhagic diathesis characterized by a prolonged clotting time and the presence of a circulating anticoagulant. Clinical data, such as occurrence in females or onset late in life in males, are of great value in establishing the diagnosis. It is to be distinguished from hemophilia complicated by the development of an anticoagulant following blood transfusions. Differentiation of these disorders is of practical significance because hemophilia-like disease is not hereditary and the clotting anomaly may disappear spontaneously.

2. Two cases with circulating anticoagulants are reported. In the first patient with hemophilia-like disease the anticoagulant was dialyzable and present for a limited period of time only. In the second patient, a 4 year old boy, the distinction between hemophilia-like disease due to an anticoagulant and pre-existing hemophilia with a complicating anticoagulant could not be made.

3. Analysis of the mode of action of the anticoagulants in these 2 cases showed interference with the formation of thromboplastin, although some antithromboplastic activity could not be excluded.

4. A simple technic for testing for circulating anticoagulants is described. It is recommended that this test be performed routinely in all patients with a bleeding tendency and a prolonged clotting time.
THE ACTION OF PTEROYLGLUTAMIC ACID ON BLOOD DYSCRASIAS INDUCED BY THIOURACIL AND PROPYLTHIOURACIL
Authors: DELOR R. A. , PETERING H. G.
Published: October 2019

Thiouracil and propylthiouracil fed to rats on purified diets produced severe granulocytopenia, and general leukopenia.

These blood dyscrasias were prevented by simultaneous administration of pteroylglutamic acid or liver in amounts to furnish at least 50 γ per cent of folic acid activity.

The leukopenia and granulocytopenia due to thiouracil could not be altered by excessive administration of pyridoxine hydrochloride.

The anemia in rats due to propylthiouracil was not appreciably influenced by folic acid.
CHANGES IN CIRCULATING LEUKOCYTES FOLLOWING THE ADMINISTRATION OF ADRENAL CORTEX EXTRACT (ACE) AND ADRENOCORTICOTROPIC HORMONE (ACTH) IN INFECTIOUS MONONUCLEOSIS AND CHRONIC LYMPHATIC LEUKEMIA
Authors: SAUNDERS RICHARD H. , ADAMS ELIJAH
Published: October 2019

Reduction in absolute numbers of circulating lymphocytes and eosinophils was observed after administering 25 cc. intravenous doses of aqueous ACE to normal adults. Such changes did not occur after a comparable intravenous dose of physiologic saline. Patients with infectious mononucleosis showed hematologic responses to ACE and ACTH both qualitatively and quantitatively similar to those observed in normal persons, while a small group of persons with chronic lymphatic leukemia failed to respond with a characteristic fall in lymphocytes either after ACTH or after doses of ACE twice as great as those effective in normal persons and in patients with infectious mononucleosis. A single individual with Addison’s disease responded to 25 cc. of ACE by vein with a more prominent lymphocyte reduction than was observed in any of the normal subjects studied. No changes in heterophile antibody titers or titers of enteric agglutinins were noted in persons with infectious mononucleosis or normal subjects within eight hours after the administration of ACTH or aqueous ACE.
THE EFFECT OF CYSTEINE ON THE PERIPHERAL BLOOD OF THE IRRADIATED RAT
Authors: PATT HARVEY M. , SMITH DOUGLAS E. , JACKSON EUGENIA
Published: October 2019

A single injection of cysteine (950 mg. per Kg., I.V.) 5 minutes before total-body exposure of rats to x-rays (800 r) significantly modified the radiation-induced hematologic changes. Depression of the heterophils, lymphocytes, and erythrocytes was less severe and recovery more rapid. The hematologic observations are consistent with the thesis that cysteine reduces the biological effectiveness of the radiation.
LEUKEMIA IN A THREE MONTH OLD INFANT
Authors: JONES FRANCIS S. , NUMAINVILLE LEON J. , HAUSE WELLAND A.
Published: October 2019

A case of myelogenous leukemia with chloromatous tumors in a three month old female infant is described and briefly discussed. Search through the literature revealed only 2 cases of chloroma which occurred in infants younger than the case presented.
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
Authors: CROSBY WILLIAM H. , DAMESHEK WILLIAM
Published: October 2019

1. Paroxysmal nocturnal hemoglobinuria is a hemolytic anemia of obscure origin, characterized by a defect of the erythrocytes which makes them susceptible to hemolysis by a normal plasma or serum factor.

2. The hemolytic reaction does not involve a complement-antibody reaction but is rather an enzyme-like reaction which is related to the coagulation mechanism of the blood.

3. Evidence suggests that the heat-labile hemolytic factor in PNH, if not identical with the serum coagulation accelerator, resembles it in many aspects. The hemolytic factor is present in plasma as an inert precursor which is activated by thrombin.

4. The action of this enzyme in vivo is discussed. Its possible relationship to various other manifestations of the disease is mentioned.

5. Dicumarol was able to inhibit hemolysis in a patient with PNH. Therapeutically, the drug was disappointing. It did not reduce the hemolytic precursor and did not prevent hemolytic crises. However, its use was not dangerous, suggesting that it may be of value during crises of this disease when thrombosis is a threat. It is possible that as yet undiscovered dicumarol-like drugs which would inhibit the production of serum Ac-globulin factor and of the hemolytic factor might offer a means of treatment for patients with paroxysmal nocturnal hemoglobinuria.

6. Dilute heparin facilitates the activation of the hemolytic enzyme by thrombin. The use of heparin in paroxysmal nocturnal hemoglobinuria may be dangerous.

7. Lysis of PNH cells by a substance related to clotting mechanism offers a new approach to the study of the coagulation problem.
MICROSCOPIC AND HISTOCHEMICAL STUDIES ON THE AUER BODIES IN LEUKEMIC CELLS
Authors: ACKERMAN G. ADOLPH
Published: October 2019

(1) Seventeen cases of acute leukemia with Auer bodies have been reported. Studies were carried out on 7 cases of acute monocytic leukemia and 3 cases of subacute myelogenous leukemia.

(2) Histochemical studies showed the Auer bodies to be oxidase, peroxidase, and periodic acid-Schiff positive; sudanophilic, slightly metachromatic and to give positive tests for acetal lipids and ribonucleic acid.

(3) The Auer bodies were negative for acid and alkaline phosphatase, lipase, glycogen, desoxyribonucleic acid and were non-birefringent.

(4) A change in the chemical nature of the Auer body from an acid condition to a more neutral state was noted. This change corresponded with the changes of the normal cytoplasmic granulation of the myelocytes and monocytes during maturation.

(5) The effects of cellular movements, trauma, and temperature changes upon the Auer bodies were studied.

(6) Several leukemic cells, containing Auer bodies, were studied during the process of mitosis.

(7) A theory as to the formation and disintegration of the Auer bodies has been presented.
Effect of phagocytosis on the reduced soluble sulfhydryl content of human granulocytes
Authors: Mendelson DS , Metz EN , Sagone AL Jr
Published: October 2019

The role of reduced glutathione in relation to hexose monophosphate shunt activity and peroxide detoxification has been well established in human erythrocytes. Less is known about the content of reduced glutathione in phagocytic leukocytes and the changes that occur during functional activity. We have measured the reduced sulfhydryl content of normal resting human granulocytes and of cells isolated from a patient with chronic granulomatous disease. Normal cells and those from the patient with chronic granulomatous disease contained similar concentrations of reduced sulfhydryls. Stimulation of a phagocytic response by incubation with opsonized zymosan particles resulted in prompt and nearly complete depletion of intracellular glutathione from normal granulocytes. This fall in reduced glutathione concentration was dependent on the phagocytic load. Exposure of chronic granulomatous disease granulocytes to a similar phagocytic load resulted in a slower and less complete fall in reduced glutathione. In normal cells, those from the chronic granulomatous disease patient, and those from an obligate carrier of the disease, the decrement in reduced glutathione during phagocytosis was correlated with oxidation of 14C-1-glucose and 14C-formate, nitroblue tetrazolium reduction, and the chemiluminescence phenomenon.
Effect of anti-P1A1 antibody on human platelets. II. Mechanism of the complement-dependent release reaction
Authors: Schreiber AD , Cines DB , Zmijewski C , Colman RW
Published: October 2019

We studied the mechanism by which complement activated by anti-P1A1 antibody elicits the platelet release reaction. Anti-P1A1 antibody mediates its action through the classic complement pathway, and its effect depends on the concentration of IgG antibody on the platelet surface. At relatively high concentrations of anti-P1A1 antibody the release reaction was mediated by a mechanism in part independent of extracellular ADP and metabolic energy and inhibited by only high concentrations of PGE1. However, at lower concentrations of anti-P1A1 antibody the release reaction was dependent on metabolic energy and ADP, and the concentration of PGE1 required to inhibit platelet release was similar to that required to inhibit ADP-induced release. The cyclooxygenase inhibitor acetylsalicylic acid inhibited the release reaction at all nonlytic antibody levels studied. None of the agents studied inhibited the induction of platelet lysis by very high concentrations of anti-P1A1 antibody, and no effect of antibody on platelet 14C-serotonin uptake was observed at antibody concentrations that did not mediate direct in vitro alteration. These studies suggest the possible use of pharmacologic agents in modifying some complement- mediated platelet alterations.
Granulocyte function during lithium therapy
Authors: Cohen MS , Zakhireh B , Metcalf JA , Root RK
Published: October 2019

Random migration, chemotaxis, phagocytosis, and bactericidal ability of neutrophils from 5 patients receiving lithium carbonate were compared with those of neutrophils from healthy donors. These cells functioned normally in all respects. Neither sera from patients receiving lithium carbonate nor the addition of lithium chloride to control cells in vitro significantly altered their functional capacity. These findings suggest that neutrophil function in patients receiving lithium therapy is preserved, and they support the potential utility of this drug as a leukopoietic agent in neutropenic states.
Fetal hemoglobin in polycythemia vera: cellular distribution in 50 unselected patients
Authors: Hoffman R , Papayannopoulou T , Landaw S , Wasserman LR , DeMarsh QB , Chen P , Stamatoyannopoulos G
Published: October 2019

Fetal hemoglobin was studied in 50 unselected patients with polycythemia vera with chemical determinations of Hb F and measurements of F-cell levels using fluorescent anti-Hb F antibodies. Although in the majority of the patients Hb F production did not differ from that in normal controls, in 20% of the patients F-cell values were above the normal range. There was no correlation between F-cell values and duration of disease, treatment modality, presence of myelofibrosis, or hematologic parameters at the time of study. In 5 of 50 patients 30%-- 45% of the erythrocytes contained Hb F; such striking elevations of F cells may reflect a distorted differentiation of erythroid precursor cells in certain patients with this disorder.
Studies on the Effect of Splenectomy on the Total Leukocyte Count in the Albino Rat
Authors: PALMER J. G. , KEMP ILEEN , CARTWRIGHT G. E. , WINTROBE M. M.
Published: October 2019

1. Following splenectomy in the albino rat, the total leukocyte count increased approximately 100 per cent in seven days, and remained significantly elevated for seventy to ninety days, after which time time leukocytes returned to normal levels. This increase in circulating leukocytes was due to an increase in both neutrophils and mononuclear cells. Partial omentectomy and unilateral nephrectomy produced increases of less magnitude and much shorter duration than those which followed splenectomy.

2. Removal of as much as 75 per cent of the spleen resulted in a leukocyte increase resembling in magnitude and duration that of control operations.

3. When small portions (less than 10 per cent) of the spleen were transplanted to other sites, the leukocyte response also resembled that which followed the control operations.

4. When splenectomy was performed in one partner of parabiotic rats, no rise occurred in the leukocyte count of either animal. When the spleen of the second partner was then removed, a rise in the leukocyte count of both animals occurred.

5. When rats were made leukopenic by pteroylglutamic acid deficiency, no rise in the leukocytes in the peripheral blood occurred following splenectomy.

6. It is concluded that in the rat the spleen exerts an influence on the level of circulating leukocytes, and that the results of these experiments support but do not conclusively prove the hypothesis that this organ exerts this influence by controlling the rate of production and/or liberation of leukocytes in the bone marrow. These studies do not exclude the possibility that under certain circumstances the spleen may destroy white cells.
Hereditary Spherocytosis
Authors: YOUNG LAWRENCE E. , PLATZER RICHARD F. , ERVIN DONALD M. , IZZO MARY JANE
Published: October 2019

1. Three patients with hereditary spherocytosis and 1 patient with the Fanconi syndrome (pancytopenia and multiple congenital abnormalities) were transfused prior to splenectomy with normal erythrocytes of types which could be differentiated serologically from those of the recipients. The proportions of donated and patient’s cells in peripheral blood and in blood washed from the minced spleens were determined by differential agglutination, and the osmotic and mechanical fragilities of the two types of cells in peripheral and splenic blood were measured by differential agglutination of the corpuscles remaining in each test tube after partial hemolysis had occurred.

2. In each case of hereditary spherocytosis the proportion of recipient’s cells was much higher in splenic than in peripheral blood, indicating selective retention of the thicker corpuscles within the spleen. Osmotic fragility of thie patient’s red cells was much greater in samples of splenic mince blood than in peripheral venous samples, while the fragility of the donated red corpuscles was normal or nearly normal in both splenic and peripheral blood.

In the patient exhibiting the Fanconi syndrome, on the other hand, neither the patient’s red cells nor donated red cells were retained to any extent in the spleen and the fragility of neither type of cell was altered.

3. Spleens removed surgically from 3 patients with idiopathic thrombocytopenic purpura were perfused with mixtures of normal A or B cells and group O cells drawn from a splenectomized individual with hereditary spherocytosis. During perfusion the spheroidal cells were selectively removed from the mixtures and at the end of each experiment red cells of this type predominated in the blood samples washed from the minced spleens. A fourth excised spleen was perfused with a mixture of two types of normal cells, neither of which was retained to any extent by the spleen during perfusion. The perfusion experiments show that spleens from patients with nonhemolytic disease are also capable of selective trapping of spheroidal cells.

4. The experiments described indicate that the spleen acts as a filter and trap and as an "incubator" in accelerating destruction of red corpuscles in patients with hereditary spherocytosis.
A Simplified Technic of Spectrography and Its Application to the Study of Intracellular Hemoglobin
Authors: METCALF W. K.
Published: October 2019

1. A simplified microspectrograph for use in the visible range is described.

2. A nonrecording microdensitometer for use with the above is discussed.

3. The Soret band of hemoglobin is demonstrable in individual erythrocytes and is not affected by fixing or staining.

4. The ratio of the hemoglobin concentration to cosin staining is constant in erythrocytes and the cytoplasm of immature red cells but not in the nucleus.

5. There is no detectable hemoglobin or verdoperoxidase in the granules present in the eosinophile granulocytes of the camel.

6. Both dried and fixed and stained erythrocytes can take up carbon monoxide from the atmosphere.
Congenital Leukemia
Authors: BERNHARD WILLIAM G. , GORE IRA , KILBY RALPH A.
Published: October 2019

Four new cases of congenital leukemia reported here may be added to the 14 acceptable cases in the literature. In all except 1 of these cases cells of the granulocytic series were involved; males predominated over females in a ratio of more than 2 to 1. Congenital anomalies were present in 3 of the 4 cases we have reported, indicating a growth disturbance early in fetal life. Contrary to the usual finding in childhood leukemia, cells of the granulocytic series in the 4 cases reported here exhibited a fair degree of differentiation and in this respect are similar to those which characterize the chronic form of the disease. It seems likely, therefore, that the leukemia existed during a significant portion of intrauterine life.
The Cholinesterase of Erythrocytes in Anemias
Authors: SABINE JEAN
Published: October 2019

1. Activity-pS curves were determined experimentally for the cholinesterase of the erythrocytes in various human anemias.

2. The data were analyzed to give experimental values for the apparent dissociation constants, K8 of the active enzyme-substrate complex (ES) and K2 of the inactive complex (ES2), and the theoretic limiting velocity V.

3. The analysis showed that the enzyme in the cells of anemia is the same as that in normal cells. The abnormally high enzymic activity (initial velocity at a single substrate concentration) known to occur in various anemias and the change from low activity in pernicious anemia in relapse to high activity during treatment are attributable to changes in concentration of the enzyme.

4. The enzyme in the red cells of pernicious anemia in relapse was not activated by folic acid or liver extract.

5. It was shown experimentally that the reticulocytes and young cells of normal blood and of pernicious anemia during treatment contain much higher concentrations of enzyme than old cells. The increased concentration persists for some time after the reticulum has disappeared.

6. The relative concentration of enzyme in the red cells is a more sensitive indicator of hyperactive hematopoiesis than the reticulocyte count.

7. Evidence is presented that failure of elevation of enzymic concentration in severe anemia is associated specifically with suppression or malfunction of the hematopoietic system.

8. It is believed that the relative concentration of enzyme can be used as a test of bone marrow function in severe anemias. It is hoped that further investigation may result in a useful test of wider application.
Megaloblastic Erythropoiesis in Patients with Cirrhosis of the Liver
Authors: Movitt E. R.
Published: October 2019

MOVITT, E. R.: Megaloblastic erythropoiesis in patients with cirrhosis of the liver Blood 5: 468-477 (May), 1950. In figure 2, pages 471, parts (a) and (b) were reversed. The upper photomicrograph (a) actually shows bone marrow after treatment; the lower (b) shows marrow before treatment.
Serum Anti-Proteases in the Leukemias
Authors: WEST PHILIP M. , SMITH BETTY W.
Published: October 2019

Quantitative changes in two serum anti-proteases in several types of adult leukemia are described. High anti-chymotrypsin and low anti-rennin concentrations were observed in the acute leukemias while the reverse was found in chronic forms of the disease. The relationship between the enzyme inhibitors and disease activity in leukemia is similar to that reported in cancer patients.
Effects Produced by Trypsin on Certain Properties of the Human Red Cell
Authors: PONDER ERIC
Published: October 2019

Human red cells treated with trypsin in such a way as to become agglutinable in the presence of incomplete antibodies are affected in certain other respects. Their volume is slightly increased, their ghosts are unusually rigid or "volume-occupying," their osmotic and mechanical fragilities are slightly increased and their electrophoretic mobility is reduced. These changes are probably due to effects on the protein components of the red cell surface ultrastructure. Similar effects are also produced by the related enzyme mexacain.
Studies on Abnormal Hemoglobins
Authors: SINGER KARL , CHERNOFF AMOZ I. , SINGER LILY
Published: October 2019

By means of fractional denaturation, it is possible to follow the progress of alkaline degradation of resistant hemoglobins. A characteristic pattern was established for the fetal compound. The alkali resistant hemoglobin fractions in Mediterranean anemia and in some acquired hematologic conditions (acute leukemia and chronic aregenerative anemia) behaved like the fetal pigment. In sickle cell anemia only 4 out of 11 specimens were found to have fetal hemoglobin, whereas the others seem to have a fetal-like compound. Similarly, in 2 members of one family with hereditary spherocytosis, the resistant pigment was also fetal-like. The significance of these findings for the hypothesis that the resistant hemoglobin fractions in these disorders represent either a continuation or a reactivation of the production of the embryonic pigment is discussed.
Hemolytic Disease in Newborn Dogs
Authors: YOUNG LAWRENCE E. , CHRISTIAN RICHARD M. , ERVIN DONALD M. , DAVIS R. WENDELL , O’BRIEN WILLIAM A. , SWISHER SCOTT N. , YUILE CHARLES L. , Izzo Mary Jane , Peters Jane Hogestyn
Published: October 2019

YOUNG, LAWRENCE E., CHRISTIAN, RICHARD M., ERVIN, DONALD M., DAVIS, R. WENDELL, O’BRIEN, WILLIAM A., SWISHER, SCOTT N. AND YUILE, CHARLES L.: Hemolytic disease in newborn dogs. Blood 6: 291-313 (April) 1951.

Page 293, fourth line from bottom should read: "72 parts of M/l5 Na2HPO4" instead of "72 parts of M/12 Na2HPO4."

Page 297, table 1, under observations of pups in litter H, should read: "Two pups suckling mother of litter G during first day" instead of "mother of litter F."
Studies in Rh Sensitization
Authors: WIENER ALEXANDER S. , NAPPI RAFFAELE , GORDON EVE B.
Published: October 2019

The results of repeated Rh antibody titrations on 65 sensitized Rh-negative pregnant woman carrying Rh-positive fetuses are presented and analyzed. Considering that a rise in antibody titer antenatally could result only from a leakage of fetal blood into the maternal circulation, the findings indicate that such a leakage occurs antenatally in about 1 out of every 3 or 4 normal pregnancies. Similarly, evidence is presented indicating that fetal blood leaks into the maternal circulation in about 1 out of 3 deliveries. Since, previously, it has been shown that approximately 40 per cent of Rh-negative individuals can be sensitized by two injections of Rh-positive blood spaced four months apart, one can calculate the chance of sensitization resulting from pregnancy with an Rh-positive fetus. The calculations show that in Rh-negative women who have received a previous injection of Rh-positive blood, there is about one chance in 12 or 13 that the first baby will be erythroblastotic (cf. Levine and Waller).16 In women who have never received any injection of blood which might sensitize them, the chance that the first baby will be erythroblastotic is negligible, because for this to occur it would be necessary for blood to leak into the maternal circulation antenatally on at least two occasions spaced four months apart, once to prime the patient and the second time to stimulate the appearance of antibodies.8 This never occurred in the present series of cases. It was also calculated that in Rh-negative primiparae who have never received an injection of Rh-positive blood, the chance of Rh antibodies appearing after the birth of an Rh-positive baby is approximately 2 out of 45, and, as a matter of fact, this has been found to occur by other workers10 in 2 out of 65 cases. It was further calculated that in Rh-negative women who had never received an injection of Rh-positive blood, the chance of their second baby being erythroblastotic is about 1 in 20, which agrees well with the actual observations. By extending the calculations, one could also estimate the chance of an erythroblastotic baby at the third, fourth, and later pregnancies.

Five cases are described in detail in order to illustrate the value of periodic antenatal Rh antibody titrations in the management of sensitized Rh-negative women.
The Use of Adrenocorticotropic Hormone and Cortisone in the Treatment of Leukemia and Leukosarcoma
Authors: ROSENTHAL MARTIN C. , SAUNDERS RICHARD H. , SCHWARTZ LAWRENCE I. , ZANNOS LEDA , SANTIAGO ENRIQUE PEREZ , DAMESHEK WILLIAM
Published: October 2019

Forty-two patients with various diseases of leukocytic proliferation were treated with one or more courses of adrenocorticotropic hormone or cortisone.

Of 13 patients with acute or subacute lymphocytic leukemia who received adequate courses of treatment, 9 (69 per cent) developed objective and hematologic evidence of well defined remissions. Remissions were, however, brief, lasting one to ten weeks. Retreatments produced further remissions but a state of refractoriness was eventually reached.

Of 5 patients with acute granulocytic leukemia only 1 showed a slight clinical improvement with therapy. An actual acceleration of the process occurred in 2 cases.

Two cases of monocytic leukemia showed no response and death seemed to be hastened.

In 5 cases of chronic lymphocytic leukemia, distinct improvement occurred in 4, particularly in those showing terminal leukemia with anemia, exfoliative dermatitis, or symptomatic hemolytic anemia.

All of 5 cases of lymphosarcoma showed some degree of improvement. Features benefited were organ enlargement, symptomatic hemolytic anemia and anemia.

In 5 cases of Hodgkin’s disease, 3 were notably benefited particularly with respect to constitutional symptoms. There was, however, no fundamental alteration of the disease process.

Only 1 case of 5 with multiple myeloma showed a favorable response. Hyperglobulinemia decreased to a variable extent in all cases, as did Bence-Jones proteinuria. The characteristics of remission including reticulocytosis, thrombocytosis, white cell response and marrow picture are detailed. The effect of ACTH on the level of serum globulins, the activity of abnormal hemagglutinins, and sedimentation rate are likewise discussed. The nonspecific effects of adrenocorticotropic therapy are indicated.

Comment is made of the undesirable effects of ACTH therapy. These included psychoses, fluid retention, hypertension, convulsions, porcine, obesity, acne, hirsutes and diabetes mellitus.

The therapeutic effectiveness of ACTH is compared with the existing available methods of therapy in the hematologic conditions under discussion.
5q- chromosome in acute leukemia with lymphoid morphology and expression of myeloid membrane determinants
Authors: Haas OA , Bettelheim P , Schmidmeier W , Gadner H , Ludwig H , Majdic O , Schulz U
Published: October 2019

We present three patients, two children and one adult, with an unusual type of acute leukemia. Whereas the blast cells showed lymphoid morphology with correlating cytochemical staining, immunological phenotyping exhibited a pure myeloid in one patient and a biphenotypic membrane marker profile in the other two patients. Cytogenetic studies revealed a 5q- chromosome as a common marker and additional individual changes. Two of the patients who were treated according to acute lymphoblastic leukemia (ALL) therapy protocols died without remission five and four weeks after diagnosis, respectively. Despite relapsing several times, another patient survived for over eight years. These three patients seem to represent one new subgroup of leukemias that can only be distinguished from typical ALL by both determination of cell surface markers and cytogenetic analysis.
Abnormal adherence-related functions of neutrophils, monocytes, and Epstein-Barr virus-transformed B cells in a patient with C3bi receptor deficiency
Authors: Buescher ES , Gaither T , Nath J , Gallin JI
Published: October 2019

We evaluated a 3-year-old female patient with leukocytosis, recurrent infections, severe periodontal disease, and a history of delayed separation of the umbilical stump. This patient's polymorphonuclear leukocytes (PMNs) had normal membrane depolarization responses, normal oxygen metabolism, normal granule secretion responses, normal bactericidal activity, and normal C3b rosetting. However, by fluorescent cell analysis and C3bi rosetting, it was determined that her cells lacked the C3bi receptor. In addition, the patient's PMNs showed markedly abnormal chemotaxis, adherence, and aggregation responses, and partial abnormalities were detected in PMN spreading and phagocytosis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the subject's neutrophil cytoplasts were missing a 180,000-dalton moiety. Her monocytes also had defective chemotaxis and failed to adhere and grow normally in culture. Epstein-Barr virus- transformed B cells from the patient lacked an aggregation response to phorbol myristate acetate. Laboratory and clinical evaluations of this patient's mother showed no abnormalities. These studies demonstrate that C3bi receptor deficiency can be associated with functional abnormalities in multiple myeloid cells and that the absence of C3bi receptor is associated with abnormal adherence-related functions of these cells.
The regulation of immunoglobulin synthesis after HLA-identical bone marrow transplantation: VI. Differential rates of maturation of distinct functional groups within lymphoid subpopulations in patients after human marrow grafting
Authors: Lum LG , Seigneuret MC , Orcutt-Thordarson N , Noges JE , Storb R
Published: October 2019

This investigation uses different polyclonal activators of in vitro immunoglobulin production to elicit immunoregulatory profiles of B cells, T cells, T4 cells, and T8 cells from 25 recipients (13 with and 12 without chronic graft-v-host disease [GVHD] ) after HLA-identical marrow transplantation for aplastic anemia or hematologic malignancy. Pokeweed mitogen, Epstein-Barr virus, herpes simplex type 1 virus, and tetanus toxoid were used to induce immunoglobulin production as measured by a plaque assay. Multiple defects in the various lymphoid subsets were found in both groups of patients. There was defective b cell function, lack of T cell or T4 cell subset helper activity, and increased T cell, T4 cell, or T8 cell suppressor activity after stimulation with the various activators. Inconsistent B, T, T4, and T8 cell functions in the marrow graft recipients provide evidence for (a) different functional groups of cells within each subset responsive to different polyclonal activators; (b) a spectrum of immune capabilities within each phenotype lineage; (c) different patterns of immune reconstitution for each lymphocyte subset after marrow grafting; and (d) chronic GVHD altering recovery of in vitro functional responses to the different polyclonal activators.
Alpha zero-thalassemia due to recombination between the alpha 1-globin gene and an AluI repeat
Authors: Nicholls RD , Higgs DR , Clegg JB , Weatherall DJ
Published: October 2019

A form of alpha zero-thalassemia found in subjects of Mediterranean origin has been analyzed by gene mapping and DNA sequencing. Homozygotes have the hemoglobin Bart's hydrops fetalis syndrome, while compound heterozygotes for this defect and alpha+-thalassemia have hemoglobin H disease. It results from a deletion that removes 20.5 kilobases of DNA from within the alpha-globin gene cluster. Sequence data from the regions adjacent to the breakpoint indicate that the recombination event that caused this deletion occurred between the alpha 1-gene and an unusual AluI sequence located between the embryonic zeta genes.
Biologic properties of molecularly cloned and expressed murine interleukin-3
Authors: Hapel AJ , Fung MC , Johnson RM , Young IG , Johnson G , Metcalf D
Published: October 2019

Interleukin-3 (IL-3) (multipotential colony-stimulating factor [multi- CSF]) is an important regulator of hemopoiesis. We recently isolated a cDNA clone of this gene and describe in this manuscript the biologic properties of the expressed gene product. An SV40 expression vector carrying cDNA encoding murine interleukin-3 was constructed so that expression of the IL-3 gene was placed under the control of the SV40 early promoter. When the expression vector was transfected to COS-1 monkey cells, IL-3 activity was secreted into the medium, reaching maximal levels 72 hours after transfection. The IL-3 produced by the COS-1 cells was partially purified using diethylaminoethyl Sephacel and phenyl-Sepharose, and its chromatographic properties were the same as IL-3 produced by the WEHI-3 cell line. The biologic activities of the “expressed” IL-3 include the “induction”of 20-alpha-hydroxysteroid dehydrogenase (20-alpha-SDH) in splenic lymphocytes from nu/nu mice, proliferative activity for 32D cl-23 and FDC-P1 cell lines, and colony- stimulating activity for granulocyte-macrophage, eosinophil, megakaryocyte, natural killer-like, erythroid, and multipotential colony-forming cells from murine fetal liver and adult bone marrow.
Microtubule reassembly in surface-activated platelets
Authors: White JG , Krumwiede M , Sauk JJ
Published: October 2019

It is generally accepted that a circumferential microtubule supports the discoid shape of resting platelets. The fate of the many-coiled polymer following platelet activation, however, has been a subject of considerable debate. Morphological investigations have suggested that the circumferential coils are constricted into tight rings around centrally concentrated organelles during platelet shape change. Biochemical studies employing colchicine-binding assays, on the other hand, have indicated that the bundle of microtubules dissolves almost completely within seconds after activation and reassembles in a new location one to four minutes later. The present study has accepted the latter hypothesis in order to examine the second part of the disassembly-reassembly theory proposed in biochemical studies. Platelets exposed to low temperatures sufficient to remove all microtubules were placed on glass slides and microscope grids to cause surface activation during rewarming. The combined stimuli of rewarming and surface activation might have been expected to cause more rapid assembly than warming alone or activation alone. This was not the case. Reassembly of microtubules during rewarming and simultaneous surface activation was not accelerated. In contrast to the constriction of microtubule rings observed during activation in control platelets, the diameters of coils that developed in chilled platelets one to two hours after rewarming and surface activation were twice those of control cells.
Tac-positive, HTLV-negative, T helper phenotype chronic lymphocytic leukemia cells
Authors: Pandolfi F , De Rossi G , Ranucci A , Bonomo G , Pasqualetti D , Napolitano M , Manzari V
Published: October 2019

In this report we describe an Italian patient with chronic T cell leukemia whose proliferating cells were mature T lymphocytes with a helper phenotype (T helper phenotype chronic lymphocytic leukemia, or Thp-CLL). Unlike other reported cases of Thp-CLL, fresh leukemic cells from this patient were positive with the anti-Tac monoclonal antibody, which recognizes the receptor for interleukin-2 (IL-2). Thus, the phenotype of these cells was similar to that expressed by Japanese patients with adult T cell leukemia (ATL) (OKT3+, OKT4+, OKT8-, Tac+). However, the Italian patient had Thp-CLL, not ATL, since his cells, unlike ATL cells, lacked human T cell leukemia virus (HTLV-I)-related DNA sequences. The Tac receptor, which appears to be modulated in vitro by the anti-Tac antibody, was biologically inactive, since the patient's cells did not respond in vitro to IL-2. In addition, they also failed to demonstrate in vitro functional activities. The clinical course was aggressive, as usual, for both Thp-CLL and ATL. Taking advantage of the description of this case, some similarities and differences between Thp-CLL and ATL are discussed, focusing on the importance of screening of HTLV-I in the differential diagnosis.