bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of Isoimmunization. I. The Transplacental Passage of Fetal Erythrocytes in Homospecific Pregnancies
Authors: COHEN FLOSSIE , ZUELZER WOLF W. , GUSTAFSON DAVID C. , EVANS MARGARET M.
Published: October 2019

A critical evaluation and discussion of certain technical aspects of the acid elution method and the immunofluorescent technic for the demonstration of fetal erythrocytes in maternal blood is presented. With appropriate precautions a close agreement between the two methods was obtained. Using one or both methods as applicable, base line data concerning transplacental passage were obtained in 622 unselected women, compatible with their offspring in the ABO system and not sensitized against the Rh factor. The intermittent entry of fetal erythrocytes into the maternal blood in small quantities was found to be a physiologic event. Postpartum, fetal erythrocytes were demonstrated in 50 per cent of the mothers. In approximately 10 per cent of the series, large fetal losses estimated to range from 0.5 to 40 ml. were observed. Massive transplacental hemorrhage was detected in nearly 1 per cent of the cases by examination of the maternal blood and usually but not always by overt anemia in the fetus. It was found to be the cause of stillbirth in one case. The evidence suggested that fetal bleeds usually began well before the onset of labor.

Though labor itself under pathologic circumstances may be associated with transplacental hemorrhage, under ordinary conditions it was found to be of little or no significance with regard to the entry of fetal erythrocytes into the maternal circulation.

Survival of fetal erythrocytes in the maternal circulation after delivery was generally found to correspond to the expected life span of red corpuscles. Apparent shortening of survival observed in several instances was probably due to the occurrence of the original spill some time before delivery. In two instances persistence of fetal erythrocytes well beyond the normal life span was observed. Both cases involved massive transplacental hemorrhage and fetal anemia with marked erythroblastemia, and mother and child were compatible to an exceptional degree with respect to blood group factors. The findings suggested the successful transplant of replicable erythroid precursor cells from fetus to mother with prolonged maternal tolerance, an interpretation supported by the results of skin homografts from offspring to mother in one case. The implications of these findings are discussed.
Simplified Determination of Blood Adenosine Triphosphate Using the Firefly System
Authors: BEUTLER ERNEST , BALUDA MARYELLEN C.
Published: October 2019

A simplified method is described for the determination of red cell ATP using the firefly lantern extract method. Variables investigated include the effect of the time of reading, dilution of firefly extract and the effective range of the method. Excellent recoveries were obtained. Optimal extraction of ATP from red cells was achieved with a hypotonic buffer at pH 9.2. The method could be used with acid-citrate-dextrose, heparin or EDTA as an anticoagulant. The method was found to be highly specific when the nucleotides found in normal human blood were investigated; only adenosine diphosphate and guanosine triphosphate gave slight readings, neither of which would significantly affect ATP determinations of human blood. Normal human values were found to be 5.45 µmoles of ATP/Gm. of hemoglobin or 1.83 µmoles/ml. red cells in heparinized blood samples. This method is believed to be more rapid, more reproducible and more accurate than any previously described method of ATP determination.
Cellular Activities in Tissue Cultures of Leukemic Human Bone Marrow
Authors: SINKOVICS JOSEPH G. , HOWE CLIFTON D. , SHULLENBERGER C. C.
Published: October 2019

1) The growth from human leukemic bone marrow particles begins with the emigration of cells having the morphologic characteristics of erythrocytic, granulocytic, monocytic and lymphocytic elements. Proliferation of fibroblastic-like cells replaces these elements within 3 to 4 weeks. Various types of immature leukocytes occur in larger numbers, and persist longer, in tissue cultures of human leukemic bone marrow than in bone marrow cultures from patients with no hematological disease.

2) Lymphocytes from either leukemic or non-leukemic bone marrow cultures often appear to enter the cytoplasm of fibroblast-like cells, but those derived from cultures of chronic lymphocytic leukemic bone marrow appeared intracellularly in much larger numbers and persisted there longer. One of the mechanisms of this phenomenon may be the feeder layer principle. Extensive injury of certain fibroblast-like cells in relation to relatively few small lymphocytes suggests the possibility of an autoimmune attack. It is possible that both the lymphocytes and the "target cells" may disintegrate.

3) Two types of multinucleated giant cells have been observed. One type is syncytial in structure, suggesting a viral mechanism of initiation. Another type resembles the polyploid giant cells which are commonly seen in old tissue cultures of whatever origin, and in various malignant diseases in vivo as well as in vitro.

4) At times, poorly differentiated round cells may persist in old fibroblastic cultures. These cells may be derived from the original explant which continued to produce them, or they may originate from fibroblast-like cells reconverted into a morphologically undifferentiated mesenchymal cell type.
Granulocytopoiesis. I. Senescence and Random Loss of Neutrophilic Granulocytes in Human Beings
Authors: FLIEDNER T. M. , CRONKITE E. P. , ROBERTSON J. S.
Published: October 2019

Tritiated thymidine labeling of DNA with a subsequent autoradiographic and cytologic study of the peripheral blood and oral lavages reveal:

1. Direct cytologic evidence for a random loss of granulocytes from the blood into the oral cavity is given. Presumably there are larger random losses in the gastrointestinal tract. This observation supports the conclusions based upon disappearance of radioactivity from the blood after autotransfusion of DFP32 labeled granulocytes.

2. The delayed appearance of label in the pyknotic granulocytes (Ab-bauformen) is strong evidence that those cells are older degenerating granulocytes and that it takes about 24-30 hours for labeled granulocytes to age to the point of becoming pyknotic senescent granulocytes.

3. The process of senescence truncates the exponential curves of random disappearance of granulocytes from the blood.

4. A model showing the relationship between random loss and senesence is constructed and discussed.

5. A mathematical description of this model is presented. The equations developed are highly sensitive to variations in input data thus limiting their practical usefulness for computations unless precise measurements are possible and are made on each subject studied for each variant in the equation.
The Effect of Amelioration of Anemia on the Synthesis of Fetal Hemoglobin in Sickle Cell Anemia
Authors: REED L. JUDEN , BRADLEY THOMAS B. , RANNEY HELEN M.
Published: October 2019

Two adult patients with sickle cell anemia of blood group A and A2B respectively, received sufficient transfusions of group O blood to maintain nearly normal hemoglobin concentrations for 4 months or longer.

Serial samples of the erythrocytes of each recipient were obtained by agglutination with anti-A (and anti-B) serum. The proportion of Hb F in the agglutinated erythrocytes was determined. Early in the transfusion period, a marked rise in the proportion of Hb F was noted. This rise was attributed to prolonged survival of erythrocytes which contained larger proportions of Hb F. In the later part of the transfusion period, the proportion of fetal hemoglobin declined to pre-transfusion levels or below. However, significant amounts of fetal hemoglobin in the erythrocytes of each patient were demonstrated throughout the period of study, and Fe59 incorporation into Hb F in vivo was demonstrated in one patient after 4 months of transfusion therapy. Under the conditions of these studies, synthesis of Hb F continued despite prolonged correction of the anemia. A decline in the proportion of Hb F in the erythrocytes of one patient after 5 months of transfusions suggested that Hb F synthesis may ultimately be depressed by transfusions. It was suggested that the proportion of fetal hemoglobin observed in the erythrocytes might in certain diseases reflect the degree of anemia present many months before.
The Histochemical Study of Zinc Content in Granulocytes in Normal Adults and in Hematologic Disorders
Authors: SZMIGIELSKI STANISLAW , LITWIN JOANNA
Published: October 2019

Zinc in granulocytes was determined using a dithizone histochemical method. Investigations were performed in both bone marrow and in peripheral blood from ten healthy adults and in 62 patients with various hematologic disorders. In bone marrow, zinc appears in metamyelocytes. The amount increases with maturation. In the granulocytes of peripheral blood, zinc values are about 30 per cent higher than in bone marrow.

Zinc is significantly decreased in granulocytes in chronic granulocytic leukemia, acute myeloblastic leukemia, multiple myeloma and Hodgkin’s and increased in chronic lymphocytic leukemia and osteomyelosclerosis.
In Vivo Localization of Heterologous Anti-Erythrocyte Antibodies in the Rat Bone Marrow and Their Effect on the Proliferative Capacity of Immature Erythroid Cells
Authors: KUROYANAGI TAKEO , SAITO MASANOBU , KURISU AKIRA
Published: October 2019

The in vivo localization of heterologous anti-erythrocyte antibodies in the rat bone marrow was determined by the I131-labeled antibody technic. I131-labeled anti-erythrocyte antibodies localized specifically in the bone marrow indicating the presence of localizing antibody. Both the localizing antibody and the incomplete antibody were thermostable, whereas hemolysins and hemagglutinins were thermolabile. Following an intravenous injection of antierythrocyte antibodies in rats, hemolysins and hemagglutinins were cleared rapidly from the plasma. The incomplete antibodies became attached to circulating red cells within 6 hours and red cell sensitization persisted for 1 week. The localizing antibody localized in the bone marrow within 30 minutes, leaving no activity in plasma.

The anti-erythrocyte antibodies markedly reduced the uptake of tritiated thymidine by erythroblasts in vitro, demonstrating their inhibitory effect on the proliferative capacity of erythroblasts.
Some Properties of Serum Obtained from Rabbits Immunized with Human Urinary Erythropoietin
Authors: SCHOOLEY JOHN C. , GARCIA JOSEPH F.
Published: October 2019

Sera obtained from rabbits after immunization with human urinary ESF can neutralize the biological activity of human urinary, sheep, rat, and rabbit plasma ESF. Such sera can depress erythropoiesis in normal mice. The neutralizing ability of such sera is found in the γ-globulins. The finding that absorptions of the immune sera with a wide variety of proteins did not alter the neutralizing ability suggests that considerable immunologic specificity is involved in the neutralization reaction. This suggestion is further supported by the finding that immune sera against a variety of proteins do not effect the erythropoietic response elicited by the injection of exogenous erythropoietin. The injection or addition of antisera against proteins or protein hormones known to be of importance in normal erythropoiesis has little or no effect on the ability of exogenous ESF to stimulate erythropoiesis in polycythemic mice. One exception is anti-ovine thyrotropin, which significantly decreased the erythropoietic response seen in polycythemic mice after the injection of sheep ESF. The finding that mild acid hydrolysis destroyed the biological activity of human urinary ESF and altered antigenic determinants on the ESF molecule suggests that the groups necessary for biological activity may be specific antigenic determinants.

These properties of the immune sera are consistent with the concept, which we previously proposed, that the neutralization of the biological activity of ESF by anti-ESF is the result of an immunologic reaction. The availability of such immune sera offers a potent tool for investigating many of the current problems on the role of ESF in the regulation of erythropoiesis.
Gastrointestinal Absorption, Plasma Transport, Surface Distribution, and Urinary and Fecal Excretion of Radioactive Vitamin B12 in Iron Deficiency
Authors: COOK J. D. , VALBERG L. S.
Published: October 2019

No evidence of vitamin B12 deficiency or of any mechanism which might lead to vitamin B12 deficiency, such as defective absorption or increased urinary or fecal excretion of the vitamin, has been found in iron-deficient subjects in whom gastric acid secretion and gastric biopsies were normal. It is concluded that when vitamin B12 deficiency occurs in iron-deficient subjects it is the result of gastric atrophy. An unexplained finding was delayed disappearance of an intravenous dose of Co58-B12 from the plasma in iron-deficient subjects.
Chromosomal Aberrations in Pernicious Anemia
Authors: KIOSSOGLOU KOSMAS A. , MITUS W. J. , DAMESHEK WILLIAM
Published: October 2019

Numerical and morphologic chromosomal aberrations were demonstrated in three cases of pernicious anemia in relapse. The morphological abnormalities including chromatid breaks, gaps and "giant" chromosomes were reduced in remission following vitamin B12 therapy. The numerical changes consisted of aneuploidy (45 and 44 chromosomes) with the most common finding encountered (6 to 100 per cent of the cells) being monosomy involving the G 21 chromosome. This was present, not only in the marrow cells, but also in other tissues, e.g., peripheral blood and possibly skin fibroblasts, thus suggesting a more generalized disorder. The numerical anomalies persisted in remission. It is postulated that the structural anomalies, namely chromatid breaks, gaps, acentric fragments and "giant" chromosomes are related to vitamin B12 deficiency and are correctable. The cause of the aneuploidy, since it was not correctable by treatment, is not clear. Since the patients were not studied before the disease had ensued, a congenital or acquired predisposition to megaloblastosis on the basis of G 21 monosomy cannot be excluded. The origin and significance of the extra chromatin material translocated onto the short arms of G 21 chromosomes in cases 1 and 3 remains unexplained.
An Electron Microscopic Description of Basophilic Stippling in Red Cells
Authors: JENSEN WALLACE N. , MORENO GIULIANA D. , BESSIS MARCEL C.
Published: October 2019

Red cells which contain ribosomes presumably have the potential to form stippled cells. The ribosomes in cells from animals with phenylhydrazine and postphlebotomy anemia may form stippling when blood films are dried slowly or when stained supravitally with dilute concentrations of New Methylene Blue dye. The ribosomes of cells from animals with lead intoxication have a greater propensity to form aggregates and therefore to result in stippling.

Since the formation of stippling in cells is dependent on the dessication of cells, they are not seen in plasma suspended cells nor in cells prepared in routine fashion for electron microscopy. The basophilic stippled material produced in certain blood cells by the action of supravital dye consists exclusively of ribosomes. The association of nonheme iron with basophilic stippling is usually the consequence of the presence of two separate morphologic structures within the cells which may not be resolved, one from the other, in light or phase microscopy, but may be distinguished by the use of electron microscopy.

The "spontaneous" occurrence of the basophilic stippling may be interpreted as evidence of ribosomal abnormality, but the multiplicity of cellular injuries induced by lead, other chemicals, drugs or disease processes may indicate that ribosomal aggregation results from alteration of nonribosomal organelles or other cellular constituents.
Megakaryocytopoiesis in the Rat
Authors: EBBE SHIRLEY , STOHLMAN FREDERICK , Donovan Janet , Howard Donald
Published: October 2019

Labeling of rat megakaryocytes was observed after a single intravenous injection of tritiated thymidine, and the following conclusions were made.

1. Morphologic appearance of megakaryocytes corresponded to their stage of maturation.

2. Only the youngest recognizable megakaryocytes (stage I) appeared to have a DNA synthetic period.

3. Megakaryocytes did not undergo permanent cellular division.

4. There was probably some degree of ineffective megakaryocytopoiesis.

5. The average total maturation time of rat megakaryocytes was estimated to be 43-75 hours wih 8-14 hours in stage I, 11-19 hours in stage II, and 24-42 hours in stage III.

6. There was continuous influx into the megakaryocyte compartment from a precursor compartment. The immediate precursor cell was morphologically unrecognizable, but it appeared to have a generation time of ∼16 hours, a DNA synthesis period of ∼10 hours and a post-synthetic maturation time of ∼2 hours.

7. Reutilization of tritium probably accounted for maintenance of a high degree of labeling of megakaryocytes for a period of 1.5-4 days.
The Persistence of Extramedullary Leukemic Infiltrates during Bone Marrow Remission of Acute Leukemia
Authors: NIES BOYD A. , BODEY GERALD P. , THOMAS LOUIS B. , BRECHER GEORGE , FREIREICH EMIL J.
Published: October 2019

Leukemic cell infiltrates were found at autopsy in the tissues of 10 of 15 patients with acute leukemia dying during "complete bone marrow remission." The kidney was the most common site of leukemic cell infiltrates followed by the liver, testes, bowel, lung, central nervous system, and lymph nodes.

These findings indicate that leukemic cells are not completely eradicated by current chemotherapy even in patients in whom no leukemic cells can be identified in the bone marrow.

The distribution of residual leukemic cells demonstrates that the central nervous system is not the only reservoir of leukemic cells in patients during bone marrow remission.
Evidence for a New Plasma Thromboplastin Factor I. Case Report, Coagulation Studies and Physicochemical Properties
Authors: HATHAWAY WILLIAM E. , BELHASEN LORETTA P. , HATHAWAY HELEN S.
Published: October 2019

Studies of defective plasma thromboplastin formation in four siblings indicated a defect which was different from any of the known coagulation factor deficiency states. Although none of the children had any history of hemorrhagic tendencies, a prolonged whole blood clotting time in an 11-year-old girl led to the findings of a markedly prolonged partial thromboplastin time (PTT), abnormal thromboplastin generation test (TGT), and a normal prothrombin time in the patient and in three of her ten siblings. The abnormal PTT and TGT were corrected by aluminum hydroxide adsorbed fresh plasma and by serum. Using the kaolin-PTT system, equal mixtures of plasma from the patients and normal plasma produced a normal time. In addition, plasmas deficient in plasma thromboplastin antecedent (PTA), Hageman factor (HF), antihemophilic factor (AHF), or plasma thromboplastin component (PTC) corrected the abnormality.

Physical and chemical properties of plasma correcting the defect in vitro indicated that the defect is closely related to that found in PTA and HF deficient plasma.
Human Bone Marrow Chromosomes in Megaloblastic Anemia
Authors: POWSNER EDWARD R. , BERMAN LAWRENCE , MacLeod Alma Irene
Published: October 2019

The long-recognized difference between chromosomes of megaloblastic and normal human marrow cells can be measured in the cells studied by us. The chromosomes from patients with megaloblastic erythropoiesis are approximately one-third longer than the corresponding normal chromosomes.
In Vitro DNA and RNA Synthesis in Human Bone Marrow Cells: A Study of 12 Normal Subjects and 12 Patients with Lymphoplasmocytic Disorders
Authors: SCHMID JAKOB R. , KIELY JOSEPH M. , TAUXE W. NEWLON , OWEN CHARLES A.
Published: October 2019

In 12 normal subjects, DNA and RNA synthesis by individual marrow cells was studied in vitro by autoradiography after short-term incubation with tritiated nucleosides. The DNA labeling index and RNA synthesis rate were highest in normal immature cells. The DNA index was zero in all mature cells, including small lymphocytes and plasma cells. In the most actively proliferating normal immature cells, the RNA synthesis rate was about 5 times higher than in normal plasma cells. Since both normal immature cells and plasma cells are characterized by a high content of RNA and active protein synthesis, the results of the present study suggest that a high RNA turnover may not be necessary for protein synthesis to proceed in nonproliferating, protein-producing marrow cells.

In 10 patients with myeloma and in two patients with primary macroglobulinemia, the abnormal plasma cells were found to be labeled with H3thymidine in each instance. The RNA synthesis rate was about 3 times greater in plasmocytoid myeloma cells than in mature plasma cells of normal marrows, and also about 3 times greater in lymphocytoid myeloma cells than in mature lymphocytes of normal marrows. The abnormal cells in the lymphoplasmocytic disorders apparently differ from their counterparts in normal marrows not only by a higher proliferative potential, but also by a much greater rate of RNA synthesis.

In actively dividing normal bone marrow cells, high values for both DNA and RNA synthesis were found. By contrast, in the neoplastic lymphoplasma cells studied, a discrepancy was noted between relatively low values of DNA synthesis and high values of RNA synthesis. Production of abnormal proteins within long-lived neoplastic plasmocytic cells may account for this finding.
DNA Polymerase and Carbohydrate Metabolizing Enzyme Content of Normal and Leukemic Glass Column Separated Leukocytes
Authors: RABINOWITZ YALE , Flynn Ann L. , Wilhite Betty A. , Bazeluk Walter
Published: October 2019

1. Enzymes of normal and leukemic glass column separated leukocytes were assayed with fluorometric (glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, lactic dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase and isocitric dehydrogenase) and radioisotope (DNA polymerase) micromethods.

2. Most results were obtained by direct assay of the specific cell type. Some required simple calculation. It was demonstrated that the enzyme activity of mixed cell suspensions was the sum of the enzyme content of the component cells, at least for the enzymes studied.

3. Assays of mixed cell suspensions may give an erroneous picture. Thus changes in differential cell counts, as well as alterations in enzyme content of individual cells, must be taken into account for correct interpretation.

4. Changes in enzyme content of mixed cell suspensions after therapy were due chiefly to alterations in the differential cell count rather than to changes in the enzyme content of individual cell types.

5. The patterns of assays of the carbohydrate metabolizing enzymes studied, except isocitric dehydrogenase, paralleled each other. Highest values were found in mature PMN leukocytes and lowest in blasts. With isocitric dehydrogenase absolute values were much lower, while the highest assays were found in myelocytes.

6. DNA polymerase content correlated well with the ability of a cell to divide. It was highest in blasts and lowest in mature PMN leukocytes.
The Response of Free Erythrocyte Protoporphyrin to Pyridoxine Therapy in a Patient with Sideroachrestic (Sideroblastic) Anemia
Authors: LEE G. R. , CARTWRIGHT G. E. , WINTROBE M. M.
Published: October 2019

Studies of a patient with acquired sideroachrestic anemia and metastatic carcinoma of the prostate are presented. Although the administration of pyridoxine did not elicit a hematologic response, the administration of this vitamin was associated with a remarkable accumulation of protoporphyrin within the erythrocytes. It is suggested that there were two defects in the hemoglobin biosynthetic pathway: impaired incorporation of protoporphyrin into hemoglobin and defective delta-aminolevulinic acid synthesis. Pyridoxine had no effect on the former hut partially corrected the latter.
The Intravascular Survival of Transfused Canine Pelger-Huet Neutrophils and Eosinophils
Authors: CARPER H. A. , HOFFMAN PHYLLIS L.
Published: October 2019

1. A case history of the Pelger-Huët leukocyte anomaly in the dog is presented. The trait appears similar to that observed in humans and rabbits.

2. Disappearance from the circulation of transfused Pelger-Huët neutrophils was exponential with a T1/2 value of 4.8 hours.

3. Transfused PelgerHuët eosinophils rapidly disappeared from the circulation with a T1/2 value approaching 30 minutes.
The Iron Content of Jejunal Mucosa Obtained by Crosby’s Biopsy in Hemochromatosis and Hemosiderosis
Authors: ASTALDI G. , MEARDI G. , LISINO T.
Published: October 2019

Perls’ test for iron (Prussian blue) has been performed on duodenal and jejunal specimens obtained by the Crosby capsule from healthy persons, as well as from patients affected with congenital hemochromatosis or acquired hemosiderosis (transfusion type). The small intestine was biopsied after an 18 hour fast.

As far as normal human beings are concerned, no hemosiderin was found in the epithelial cells of duodenum or jejunum, nor in the tunica propria of duodenum. On the other hand, the tunica propria of a number of jejunal villi showed siderotic macrophages which seemed to be storing or moving iron from the tips of the villi into the gut lumen.

In hemosiderosis, iron granulations were never found in the columnar epithelium, whereas siderotic macrophages, storing or removing iron, were much more numerous and iron-positive than in the normal, and these macrophages were not only in the tunica propria of jejunum, but also in that of the duodenum.

In hemochromatosis, the columnar epithelium of some duodenal villi had iron-containing granules, and many villi had siderotic macrophages in the tunica propria. These macrophages were not confined to the tips of villi, but were randomly distributed in the tunica propria. Furthermore, no macrophages appeared to be traversing the columnar epithelium or outside it.
Effects of Erythroid Hyperplasia on Patterns of Glycin-2-C14 Uptake in Heme and Globin of Human Peripheral Blood in Vivo
Authors: NATHAN DAVID G. , GARDNER FRANK H. , Lemire Virginia B.
Published: October 2019

The rate of appearance of C14 in the heme and globin of peripheral blood following intravenous administration of glycine-2-C14 has been measured in normals and in patients with androgen-induced erythrocytosis, polycythemia vera (iron deficiency) and virilizing Cushing’s disease with polycythemia. In all these cases of accelerated erythropoiesis a common alteration of the globin specific activity curve was observed. Heme specific activity curves were not affected.

The changes in the globin specific activity curves are best explained by consideration of the marrow erythroid cellularity during erythrocytosis.
The Binding of Cr51 to Hemoglobin
Authors: PEARSON HOWARD A.
Published: October 2019

In vivo elution rates of Cr51 from red cells containing Hb C and from placental red cells containing large amounts of Hb F have been determined. These were found to be 1.8 and 0.85 per cent per day, respectively, and do not differ greatly from those of normal adult red cells. Therefore, no special correction factors for elution need be used in evaluating Cr51 survival curves in these clinical situations. The in vivo elution rate of 3.5 per cent/day observed for Hb C-S is significantly greater than that of normal red cells.
The Ultrastructure of Negatively Stained Platelets
Authors: BULL BRIAN S.
Published: October 2019

Negative staining of whole mounts of platelets preserves several structures not previously described. External to the plasma membrane there is a coat which contains electron dense bodies of varying shape. External to the coat is a region which stains intensely with phosphotungstate. Platelet granules coexist with tubules in the granulomere as well as with a large number of other membraneous structures.

A speculative interpretation of the function served by these structures in platelet physiology is proposed. The PTA halo denotes a cloud of adsorbed plasma proteins, including fibrinogen maintained in the platelet environment by the coat. During viscous metamorphosis, coagulation is catalyzed by discharge of the contents of the granules and shedding of the coat.
Analytical Review: Leukemia or Lymphoma Occurring Subsequent to an Autoimmune Disease
Authors: OLEINICK ARTHUR
Published: October 2019

The hypothesis of undue susceptibility to leukemia or lymphoma in individuals with autoimmune disease is evaluated by an analysis of case reports and an analysis of the mortality experience of series of patients with systemic lupus erythematosus or rheumatoid arthritis. No direct support for the hypothesis is found. The difficulty in accumulating a sufficient number of person years at risk in series of individuals with autoimmune disease is noted and alternative approaches to validating this hypothesis are discussed.
Disseminated Eosinophilic Collagen Disease
Authors: PIERCE LAWRENCE E. , HOSSEINIAN ABDOL H. , CONSTANTINE ANTHONY B.
Published: October 2019

A patient with disseminated eosinophilic collagen disease as reported in the Scandanavian and European literature and perhaps described under various titles—such as eosinophilic leukemia, Loeffler’s syndrome, parietal endocarditis,16 and allergic granulomatosis17—is presented. The major clinical findings are dermal edema and erythema with pruritus and scaling; skeletal muscle pain, tenderness, and weakness; severe arthralgias and stiffness of small and weightbearing joints; hepatomegaly; and conspicuous lack of adenopathy. Blood examination shows normochromic anemia with intense neutrophilic leukocytosis and eosinophilia. Granulocytic leukemoid features eventually appear resembling chronic to subacute myelogenous or eosinophilic leukemia. Cardiac failure or infection is the usual cause of death. At autopsy there is generalized eosinophilic and neutrophilic with lesser mononuclear infiltrations of many organs, particularly the skin, myocardium, and skeletal muscle. The etiology is unknown. Environmental toxicities and hyperimmunity perhaps to drugs, bacterial products, or sustained autoantigenic stimuli are suggested possible explanations. Corticosteroids afford some symptomatic stabilization but the disease pursues a persistent downhill course.
Iron-Laden Mitochondria in Reticulum Cells of Hypersiderotic Human Bone Marrows
Authors: TANAKA YASUKAZU
Published: October 2019

Iron-laden mitochondria were observed in three cases of primary nonhereditary sideroblastic anemia. The cells involved are considered to be a peculiar type of reticulum cell, possibly with erythropoietic potentiality. This feature and the rare presence of iron in mitochondria of reticulum cells which are clearly identifiable as macrophages suggest that an enzymatic defect in hemoglobin synthesis may account for the majority, but probably not all instances, of iron-laden mitochondria.
Appearance of Hydrolase Rich Granules in Human Lymphocytes Induced by Phytohemagglutinin and Antigens
Authors: HIRSCHHORN ROCHELLE , HIRSCHHORN KURT , WEISSMANN GERALD
Published: October 2019

Purified human peripheral blood lymphocytes have been shown to develop acid hydrolase-rich granules between 24 and 48 hours after stimulation by phytohemagglutinin, prior to mitosis. This increase has been measured biochemically as a net increase in total activity of the lysosomal enzymes: acid β-glycerophosphatase, acid phenolpthalein phosphatase, and aryl sulfatase. The subcellular localization of acid hydrolytic enzyme activities has been investigated, and they have been shown to be concentrated in a large granule fraction of sucrose homogenates and to behave as if they were membrane-bounded, in that their activity could be released by lysolecithin. It has also been demonstrated by histochemical technics that stimulation of lymphocytes by antigen (PPD) and by streptolysin S, as well as by phytohemagglutinin, produced an increase in acid phosphatase activity. Chloroquine, an inhibitor of the response to phytohemagglutinin, has also been shown to inhibit the development of acid phosphatase activity. These results are interpreted to suggest that both specific and nonspecific stimulants of lymphocytes induce lysosome-like structures in premitotic cells.
Characterization and Properties of an Inhibitor of Factor VIII in the Plasma of Patients with Hemophilia A Following Repeated Transfusions
Authors: STRAUSS HERBERT S. , MERLER EZIO
Published: October 2019

A circulating anticoagulant, which specifically inhibits Factor VIII (AHF), has been detected in some patients with hemophilia A who had received multiple transfusions. The inhibitor was quantitated by measurement of the degree of inactivation of Factor VIII. The data presented provide strong evidence for the antibody nature of the Factor VIII inhibitor in hemophilia: (1) All specific inhibitory activity of serum was detected in the γG globulin obtained by chromatography of the sera on DEAE cellulose. (2) Fab fragments obtained by digestion of the γG globulin with papain, contained 18-22 per cent of the specific inhibitory activity, while Fc fragments contained 0.4-3 per cent. F(ab')2 fragments obtained by digestion with pepsin contained 36-61 per cent of the specific inhibitory activity of γG globulin. (3) The level of the inhibitor of Factor VIII increased sharply following transfusions of blood and decreased slowly to its preinfusion level. (4) When small amounts of inhibitor were incubated in vitro with excess Factor VIII, the inhibitor activity was decreased. Infusion of Factor VIII into a patient with a low level of inhibitor decreased the inhibitor activity. (5) Clearance of the isologous inhibitor from the circulation of a normal subject was rapid.
Brief Report: The Enhanced Survival of Human Peripheral Lymphocytes in Vitro Using Subthreshold Concentration of Phytohemagglutinin
Authors: NASPITZ CHARLES K. , RICHTER MAXWELL
Published: October 2019

1. It has been demonstrated that human peripheral lymphocytes can be adequately maintained in long-term culture, in a viable state, by the incorporation of a subthreshold concentration of phytohemagglutinin into the medium and changing the medium every 7 days.

2. These cells, after 42 days of culture, are capable of undergoing blastogenesis and mitosis upon incubation with blastogenic doses of phytohemagglutinin.

3. The morphology of these stimulated cells, and the degree of incorporation of isotope, attests to the healthy state of these cells.

4. Cells incubated for 42 days in the presence of a subthreshold concentration of PHA are capable of incorporating three to four times the amount of tritiated thymidine as can cells incubated for 42 days in medium without the subthreshold concentration of PHA.
Ficoll Flotation for the Separation of Blood Leukocyte Types
Authors: NOBLE P. B. , CUTTS J. HARRY , CARROLL K. K.
Published: October 2019

A method for the separation of leukocytes from peripheral blood, using flotation over Ficoll, is described. The method is amenable to considerable variation, and the leukocytes isolated show good preservation of their morphologic integrity, are motile and capable of phagocytosis.
Biochemical Variants of Glucose-6-Phosphate Dehydrogenase Giving Rise to Congenital Nonspherocytic Hemolytic Disease
Authors: BEUTLER ERNEST , MATHAI CLARAMMA K. , SMITH JOSEPH E.
Published: October 2019

Previous investigations have shown considerable biochemical heterogeneity in the glucose-6-phosphate dehydrogenase of G-6-PD deficient patients with congenital hemolytic disease. The red cells of four subjects with this disorder and of some family members have been investigated. The G-6-PD of the first subject was different than any previously described mutant enzyme and was named Albuquerque. It resembled the Oklahoma variant of G-6-PD, but the elevation of the Km values for TPN and G-6-PD were less, the pH optimum was slightly different, the enzyme activity of the red cells was much lower, and the enzyme had marked thermal lability. The second patient also showed the presence of a new type of variant, which has been named Duarte. This enzyme was characterized by a marked shift of the pH optimum to the acid side, with otherwise normal kinetic and electrophoretic characteristics. The other two patients were found to have enzymes which appeared to be identical to the previously described Chicago variant and Mediterranean variant. The reasons why patients with Mediterranean variant may sometimes show congenital hemolytic disease are discussed.
The "Tissue" Tension of Oxygen and Its Relation to Hematocrit and Erythropoiesis
Authors: THORLING EIVIND B. , ERSLEV ALLAN J.
Published: October 2019

The variations in oxygen tension in relation to induced changes in the hematocrit, were investigated in mouse pneumoperitoneum and rat skin pockets.

A close to linear relationship was found in the range of hematocrit from 20-60 percent. Above this hematocrit value, the correlation was lost and no further increase in Po2 was noted with increases in the hematocrit. A tendency to a minor fall in Po2 at very high hematocrit values was observed in both systems, however, the fall was never below normal value.

Attempts to induce normovolemic erythrocytosis by exchange transfusions in rat demonstrated that this condition is transient, transforming into a hypervolemic erythrocytosis within hours. In spite of the increasing viscosity of the blood with increases in hematocrit, a hypervolemic erythrocytosis was found to cause a slight increase in tissue Po2 while a normovolemic erythrocytosis did not. Consequently, an accelerated rate of red cell production will have a dual effect on oxygen transport: (1) it will increase the oxygen carrying capacity, and (2) it will increase the blood volume and thereby decrease the peripheral resistance, allowing the heart to transport more oxygen at no extra expense.
In Vitro Effect of Erythropoietin on the Spleen of the Polycythemic Mouse. III: Limited Exposure to Erythropietin and Actinomycin D
Authors: MIURA YASUSADA , MIZOGUCHI HIDEAKI , TAKAKU FUMMIMARO , NAKAO KIKU
Published: October 2019

1. Heme synthesis and appearance of erythroblasts were observed when the spleen fragments from the polycythemic mouse spleen were exposed to erythropoietin only in the earlier period of incubation. The heme synthesis and the number of erythroblasts were increased in proportion to the exposure time to erythropoietin up to 12 hours. Twelve hours exposure to erythropoietin evoked about 70 percent of the maximally stimulated control heme synthesis.

2. The appearance of erythroblasts and the heme synthesis was completely blocked by the addition of 0.01 µg./ml. of actinomycin D. Some population of differentiated erythroblasts became resistant to actinomycin D which was added at 12th and 24th hour of incubation.

3. The heme synthesis within reticulocytes from bled anemic mice were not affected by these doses of erythropoietin, actinomycin D or both of them.

4. The results were discussed in connection with the mechanism of erythropoietin on stem cells.
The Lymphocyte β-Glucuronidase Activity in Lymphoproliferative Disorders
Authors: YAM LUNG T. , MITUS W. J.
Published: October 2019

Lymphocyte β-glucuronidase activity was estimated semi-quantitatively by a cytochemical method. Strong enzyme activity was found to be present in the lymphocytes. In patients with chronic lymphocytic leukemia, lymphosarcoma and some cases of reticulum cell sarcoma, the lymphocyte β-glucuronidase activity was low. This was due to the presence of a large number of lymphocytes with low β-glucuronidase activity. The low β-glucuronidase content in the lymphocytes is usually associated with decreased ability of these cells to undergo transformation upon phytohemagglutinin stimulation; however, this association is not an absolute one.
Leukocyte Histidine Decarboxylase: Properties and Activity in Myeloproliferative Disorders
Authors: KRAUSS STEPHEN , GILBERT HARRIET S. , WASSERMAN LOUIS R. , Lurinsky Gertrude
Published: October 2019

1. Histidine decarboxylase was assayed in extracts from human leukocytes and the properties of the enzyme studied.

2. Leukocyte histidine decarboxylase was found to be substrate-specific, to require pyridoxal phosphate as co-enzyme, and to be inhibited by alpha-hydrazino analog of histidine (MK 785), a selective inhibitor of the specific histidine decarboxylase occuring in rat tissue. A non-specific L-aromatic amino acid decarboxylase was also demonstrated in leukocyte extracts, which possessed little activity toward histidine.

3. Cellular localization studies revealed that mature neutrophils and basophils possessed most of the histidine decarboxylase activity exhibited by mixed leukocyte preparations. Mature eosinophils, small lymphocytes, and immature myeloid cells (myeloblasts and promyelocytes) showed little histidine decarboxylase activity.

4. In the clinical studies, patients with uncontrolled polycythemia vera, "spent" polycythemia, myelofibrosis with myeloid metaplasia, and chronic myelocytic leukemia, showed increased leukocyte enzyme activity when compared to a control group composed of normal subjects and patients with relative polycythemia. This increased activity appears to represent a true increase in enzyme activity per granulocyte, and is believed to account for the elevated leukocyte histamine content demonstrated in patients with myeloproliferative disorders.
An Atypical Immunoglobulin
Authors: LEWIS A. F. , BERGSAGEL D. E. , BRUCE-ROBERTSON A. , SCHACHTER R. K. , CONNELL G. E.
Published: October 2019

A protein of the Ig G family has been isolated from the serum of a patient with a tentative diagnosis of a plasma cell neoplasm. The protein has a lower sedimentation constant (5.4) and a lower molecular weight (125,000) than normal immunoglobulins of the G family. The protein has heavy-chain determinants of type G and light-chain determinants of the κ-type. Heavy and light chains have been prepared by reductive cleavage followed by gel filtration. The heavy-chain preparation is homogeneous in starch gels in acidic buffer containing urea but has a faster mobility than normal Ig G heavy chains. The light-chain preparation is resolved into two components in electrophoresis, and both have slower mobility than normal Ig G light chains. The heavy- and light-chain preparations cross react with normal Ig G heavy and light chains in immunodiffusion analysis. Sedimentation equilibrium studies suggest that both the heavy and light chains have lower molecular weights than their normal counterparts.
Hereditary Hemolytic Anemia Associated with Glucosephosphate Isomerase (GPI) Deficiency— a New Enzyme Defect of Human Erythrocytes
Authors: BAUGHAN MARJORIE A. , VALENTINE WILLIAM N. , PAGLIA DONALD E. , WAYS PETER O. , SIMONS ERNEST R. , DEMARSH QUIN B.
Published: October 2019

A new congenital hemolytic anemia not characterized by spherocytosis has been defined as due to a deficiency in another glycolytic enzyme, glucosephosphate isomerase, the catalyst specific for the second step of the Embden-Meyerhof glycolytic pathway. The leukocytes and the plasma are involved as well as the erythrocytes, but there is no clinical evidence of dysfunction other than the hemolytic anemia. Family studies are consistent with an autosomal-recessive mode of inheritance with the asymptomatic heterozygotes demonstrating an intermediate enzyme deficiency, and the symptomatic homozygote, the propositus, demonstrating a marked enzyme deficiency.
Osmotic Hemolysis of Chemically Modified Red Blood Cells
Authors: BAKER RICHARD F. , GILLIS NAOMI R.
Published: October 2019

The mechanism of osmotic hemolysis of human red blood cells has been investigated after mild fixation in glutaraldehyde. A mass of precipitated hemoglobin (crown) is seen around a single membrane break which may be as large as 2µ in diameter. Ghosts with large holes are not seen and it is believed that membrane repair takes place.

Hemoglobin extrusion by this mechanism takes place only around the rim of the red cell. Both old and young red cells exhibit crown formation, but old cells require longer fixation than do young cells.

A correlation with previous work on mode of osmotic hemolysis of red cells is discussed.
32DFP and 51Cr for Measurement of Red Cell Life Span in Abnormal Hemoglobin Syndromes
Authors: MCCURDY PAUL R.
Published: October 2019

The red cell life span was measured simultaneously using 51Cr and 32DFP in 21 patients with abnormal hemoglobin β chains and in 7 patients with normal hemoglobin. The patients included 9 with sickle cell anemia, 2 with sickle-β-thalassemia disease, 2 with sickle cell-hemoglobin C disease, 3 with homozygous hemoglobin C disease, 4 with sickle cell trait and 1 with hemoglobin C trait. The 51Cr elution rate from red cells carrying abnormal β chains was 1.2 per cent daily (range: 0.1-2.7 per cent; 4 patients had 2-component elution curves, the first of which was quite rapid (4.1-19.5 per cent daily) and could lead to significant error in the 51Cr estimate of red cell survival. The 51Cr elution rate for red cells with normal β chains was 1.3 per cent daily (range: 0.7-1.6 per cent). In the steady state, production of red cells was estimated from the 32DFP life span. Both figures varied with the disease process but erythropoiesis seldom obtained the 6-8 fold increase over normal that is considered to be the capability of normal bone marrow and hence a relative erythropoietic defect seems to be frequently present in patients with abnormal hemoglobin diseases. Two sibling pairs with sickle cell anemia were studied and were found to vary from each other as much as did the other patients with this disorder.
Brief Report: Albumin Warao: New Type of Human Alloalbuminemia
Authors: ARENDS TULIO , GALLANGO MARIA L. , LAYRISSE MIGUEL , WILBERT JOHANNES , HEINEN HAINZ D.
Published: October 2019

A new albumin variant characterized by the slowest electrophoretic migration at both acid and alkaline pH, was found in a Warao Indian family from Venezuela. Thermal instability of an albumin variant is described for the first time.
Toxicity of Anti-dog Lymphocyte Serum to Normal and Leukemic Human Lymphocytes
Authors: SCHREK ROBERT , PRESTON FREDERICK W. , DIETZ ALBERT A.
Published: October 2019

Rabbit anti-dog lymphocyte serum plus rabbit complement had a rapid cytocidal effect on blood lymphocytes from 11 patients with chronic lymphocytic leukemia. The titer of the immune sera varied from 1:42 to 1:530 with a mean titer of 1:100. The sera showed minimal or no toxicity to lymphocytes from normal persons with a titer of > 1:10 in 13 of 18 cases. A similar differential toxicity to normal and leukemic lymphocytes was observed with rat anti-dog lymphocyte serum. However, guinea pig and horse anti-dog lymphocyte sera or globulin were equally toxic to normal and leukemic human lymphocytes. Leukemic lymphocytes incubated with rabbit anti-dog lymphocyte serum and rabbit complement showed early nuclear degenerative changes and paranuclear vacuoles. The cytologic degenerative changes suggested that the nucleus or nuclear membrane may be the first site of action of the immune serum.