bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toxic Effects of High-Dose Cyanate Administration in Rodents
Authors: Alter Blanche P. , Kan Yuet Wai , Nathan David G. 
Published: October 2019

Abstract
Cyanate inhibits hemoglobin synthesis in vitro. In vivo studies were performed to determine the effect of the drug on erythropoiesis. Adult female rats received daily intraperitoneal injections of 400 µmoles of cyanate, leading to over 3 CNO/Hb by 3 wk. Controls received sodium chloride. DPG was measured in a small number of animals and declined from 5.5 to 4.1 mmoles/liter (p < 0.02). At 4 wk, Hb, Hct, and red cell counts in cardiac blood of the treated group were all higher (p < 0.05); MCHC was normal. Mean plasma iron was 175 in treated versus 129 µg/100 ml in controls. Plasma iron turnover in mg/day increased from 0.143 to 0.260 (p < 0.01), as did erythron iron turnover, from 0.096 to 0.195 mg/day (p < 0.05). Thus the erythroid marrow of cyanate-treated animals could respond to carbamylation-induced increase in oxygen affinity, though the adequacy of the response with respect to the increase in oxygen affinity is difficult to assess. Furthermore, severe clinical toxicity was observed. Treated animals lost a mean of 62 g, compared with a gain of 25 g in controls. Twenty-five per cent died by 4 wk. The neuromuscular system appeared to be more sensitive to high-dose in vivo cyanate administration than the erythropoietic system.
Protein - Quinone Interaction: In Vitro Induction of Indirect Antiglobulin Reactions With Methyldopa
Authors: Gottlieb Arlan J. , Wurzel Harold A. 
Published: October 2019

Abstract
Methyldopa-treated gamma globulin can be demonstrated serologically on either the red cell surface or on latex beads by the indirect antiglobulin reaction. The development of a positive antiglobulin reaction was related to methyldopa concentration and the length and temperature of incubation of methyldopa with protein and could be partially inhibited by the addition of albumin to the incubation mixtures. After more prolonged incubation, antiglobulin positivity also developed with plasma-treated with methyldopa. 14C-methyldopa was covalently bound to gamma globulin. Aggregation of gamma globulin following treatment with methyldopa could be demonstrated by both sedimentation velocity and molecular weight determinations employing low-speed equilibrium centrifugation. Protein aggregation was a function of time, temperature, and methyldopa concentration. Detectability by the antiglobulin reaction, the darkening noted in solutions to which methyldopa or hydroquinone had been added, as well as the aggregation of protein was inhibited by a reducing agent which prevented formation of a quinone from the hydroquinone. Some of the immunologically atypical features of the sensitization of red cells by methyldopa or its structural analogues are explicable by the adherence, in vivo, of chemically modified, nonantibody gamma globulin which renders the red cell directly antiglobulin positive.
Macroglobulinemia in a Child With Acute Leukemia
Authors: Čejka Jan , Bollinger Robert O. , Schuit Henrica R.E. , Lusher Jeanne M. , Chang Chung-Ho , Zuelzer Wolf W. 
Published: October 2019

Abstract
A 12-yr-old boy with acute leukemia was found to have paraproteinemia and Bence-Jones proteinuria. The paraprotein was characterized as immunoglobulin M, type κ and the Bence Jones protein as free κ-chains. Increased amounts of β2-microglobulin were found in the patient’s serum and urine. Electron microscopic and immunofluorescence studies provided evidence of the presence of lymphoid leukemia cells apparently responsible for the production of the paraprotein.
Granulocyte Function in the Chediak-Higashi Syndrome of Mice
Authors: Gallin John I. , Bujak Joseph S. , Patten Ethel , Wolff Sheldon M. 
Published: October 2019

Abstract
Granulocyte function was evaluated using peritoneal exudate granulocytes from a strain of beige mice with the Chediak-Higashi syndrome (CHS). Defective granulocyte chemotaxis of CHS cells (43% normal) was documented. There was no abnormality in the ability of CHS serum to function as a chemotactic stimulus. Phagocytosis of 14C-labeled Staphylococcus aureus by CHS granulocytes was normal. However, there was reduced bactericidal activity of S. aureus and group D streptococcus by CHS cells through 90 min of incubation. The bactericidal defect was most pronounced at early time periods and was related to impaired intracellular killing. These defects of CHS mice granulocytes were analogous to those reported in man and it is concluded that the CHS mouse is a most convenient and representative model of the CHS of man.
Familial Thrombosis Due to Antithrombin III Deficiency
Authors: Marciniak Ewa , Farley Claude H. , DeSimone Philip A. 
Published: October 2019

Abstract
A large kindred from eastern Kentucky, with extensive history of recurrent venous thrombosis and pulmonary embolism, was studied. Low antithrombin III titers, ranging from 26% to 49% of normal values, were found in plasma of nine members in three consecutive generations; another five members, four of whom were not available for study, are suspected of having the biochemical defect. There was a good correlation between clinical symptoms and antithrombin III deficiency, although three of the younger members with the defect still remained free of thrombosis. In serum of the affected subjects antithrombin III was almost completely utilized, which indicates that stoichiometric binding to coagulation enzymes dominates under biological conditions. Antithrombin and antifactor Xa activities residing in the macroglobulin region of plasma and serum remained unchanged. The responsiveness to heparin in vitro and in vivo confirmed the evidence that antithrombin III is the sole blood component through which heparin exerts its anticoagulant effect. In five affected members therapy with oral anticoagulants increased very significantly the level of antithrombin III in plasma and contributed to a remarkable increase of residual antithrombin III in serum. This objective improvement after warfarin therapy may create significant difficulties in the laboratory diagnosis of antithrombin III deficiency.
Intranuclear Hemoglobin in Erythroblasts of β-Thalassemia
Authors: Yataganas Xenophon , Gahrton Gösta , Thorell Bo 
Published: October 2019

Abstract
The amount and distribution of intranuclear hemoglobin in erythroblasts of normal subjects and patients with homozygous β-thalassemia were studied by microspectrophotometric methods. The mean intranuclear hemoglobin content of the mature erythroblasts represented 33%-40% of the total hemoglobin content both in normal and thalassemic cells. Distinct absorption peaks in transmission scanning lines recorded over thalassemic erythroblasts suggested the presence of intranuclear hemoglobin precipitation in some cells. Similar characteristic absorption peaks of denatured ferric hemoglobin were recorded over large inclusions of the cytoplasm and small intranuclear precipitates. Intranuclear inclusion bodies may be responsible for the disturbance of erythroblast proliferation in thalassemia, thus explaining in part the ineffective erythropoiesis occurring in this disease.
Hemoglobin Rush [β101 (G3) Glutamine]: A New Unstable Hemoglobin Causing Mild Hemolytic Anemia
Authors: Adams J. G. , Winter W. P. , Tausk K. , Heller P. 
Published: October 2019

Abstract
A mild hemolytic anemia in a 43-yr-old black woman was attributed to the presence of an abnormal hemoglobin (Hb Rush) which migrated cathodically to Hb A at pH 8.0. Its structural abnormality was found to be in the β-chain, β101 (G3) glu → gln. Another electrophoretic band at pH 8.0 proved to be a hybrid tetramer (αA2βAβRush). Hb Rush is heat unstable. A likely explanation of the instability is the presence of an uncovered positive charge in the central cavity where normally glutamic acid in position 101 neutralizes arginine in position 104 contributing to the net neutrality in this region. This neutrality is disturbed by the substitution of glutamic acid by glutamine in Hb Rush.
Fetal Rat Utilization of 55Fe Absorbed by Fetal Intestine From Swallowed Amniotic Fluid
Authors: Orlic Donald , Lev Robert , Rosenthal William S. 
Published: October 2019

Abstract
Radioiron(55Fe) injected directly into the amniotic cavity of 21-day rat fetuses is swallowed and rapidly absorbed by the intestine. The radioisotope is then transported from the intestine and is utilized in the liver and spleen, fetal erythropoietic and iron-storing organs. The level of incorporation in intestine, spleen, and liver, as measured by scintillation counting, is relatively low during the first hour, but increases 3 and 6 hr postinjection. Radioautograms at 6 hr demonstrate extensive labeling in the cytoplasm of absorptive cells in the intestinal mucosa. In liver the 55Fe is observed in parenchymal and reticuloendothelial cells and in developing red cells. Erythroid cells are the principal 55Fe-labeled cells in the spleen. Recirculation of some 55Fe occurred between 55Fe-injected fetuses, maternal organs, and control fetuses. Fetal swallowing of 55Fe within amniotic fluid followed by intestinal absorption of the radioisotope demonstrates the existence of a pathway by which nutrients can be delivered to the fetus. This finding is of potential benefit to the human fetus since a number of compounds, including certain drugs, may possibly be administered via this route.
The Determination of Erythrocyte Folate Concentration Using a Two-Phase Ligand-binding Radioassay
Authors: Rothenberg Sheldon P. , da Costa Maria , Lawson John , Rosenberg Zoltan 
Published: October 2019

Abstract
The concentration of folate in erythrocytes was determined using a two-phase ligand-binding radioassay procedure described previously for measuring serum folate. The mean (± SD) folate concentration in erythrocytes of 20 normal subjects was 210 ± 57 ng/ml. In 12 patients clinically folate deficient who had normal serum B12 concentration, the mean (± SD) erythrocyte folate was 71 ± 39 ng/ml. Incubation of the lysed erythrocytes for 2 hr prior to boiling increased the radioassayable folate. The radioassayable folate decreased rapidly if the whole blood was stored at 4°C without ascorbate. Extracts of blood prepared with ascorbate could be stored at -20°C for several days. The radioassayable concentration of erythrocyte folate was similar to the values obtained using Lactobacillus casei when the concentration was 200 ng/ ml or less. With values higher by L. casei, the radioassayable folate was significantly lower even though the normal and folate-deficient groups were distinctly separated. This radioassay provides a rapid and reliable method of measuring erythrocyte folate, a parameter which reflects folate stores more reliably than serum folate concentration.
Plasma Cell Dyscrasia Associated With the Production of Incomplete (? Deleted) IgGλ Molecules, Gamma Heavy Chains, and Free Lambda Chains Containing Carbohydrate: Description of the First Case
Authors: Isobe Takashi , Osserman Elliott F. 
Published: October 2019

Abstract
The clinical, hematologic, and immunoglobulin features of a new form of plasma cell dyscrasia (deleted H and L chain disease) are described. The clinical manifestations are periodic fever and weakness, lymphadenopathy, and hepatosplenomegaly. The hematologic abnormalities are anemia, leukopenia, lymphocytosis, thrombocytopenia, and increased plasma cells in lymph nodes and bone marrow. The protein abnormalities have been identified as (1) monoclonal IgG1λ A serum globulin (5-6 g/100 ml) with deletions in both H and L chains and an estimated mol wt of 110,000; (2) free γ Fc fragment in serum and urine; (3) urinary excretion (10-20 g/day) of deleted λ-chains (Uλ) with an estimated mol wt of 15,000. Uλ and the λL chains of the IgG are apparently identical. Uλ was shown to contain approximately 26 moles of carbohydrate, with an average of 2.2 moles of sialic acid per 15,000 mol wt. Uλ displayed marked electrophoretic heterogeneity which was related to a variable number of sialic acid residues. The N terminus of Uλ is blocked (PCA). The deletions of both the λ- and the H chains were localized to their respective V regions and are of similar magnitudes (approximately 10,000 daltons). Possible genetic mechanisms to explain apparently comparable H- and L-chain deletions in a single IgG molecule are considered.
Neutrophil and Monocyte Kinetics in a Case of Cyclic Neutropenia
Authors: Meuret G. , Fliedner T. M. 
Published: October 2019

Abstract
The kinetics of neutrophilic granulocytes and monocytes were examined simultaneously in a patient suffering from cyclic neutropenia. During the remission phase of the disease the observed kinetic data for both cell types did not deviate significantly from the normal range. At a stage just before the minimal blood granulocyte count was reached, the total blood granulocyte pool was diminished and the granulocyte half disappearance time shortened to 2.3 hr. Moreover, the intravascular granulocyte distribution changed in favor of the marginal granulocyte pool. During the neutropenic phase, the intravascular monocyte pools were Increased and monocyte half-disappearance time was prolonged to 14 hr; the monocyte turnover rate was 2.4-fold higher than during remission.
Ferritin in Serum: Diagnosis of Iron Deficiency and Iron Overload in Infants and Children
Authors: Siimes Martti A. , Addiego Joseph E. , Dallman Peter R. 
Published: October 2019

Abstract
Ferritin in serum was quantitated by radioimmunoassay to determine the usefulness of this assay in reflecting iron stores during normal development and in the diagnosis of iron deficiency and iron overload in infants and children. In the adult, serum ferritin has been reported to correspond to the magnitude of iron stores throughout a wide range. In 573 normal infants and children, we found the concentration of serum ferritin to parallel known changes in iron stores during development. The median serum ferritin concentration was 101 ng/ml at birth, rose to 356 ng/ml at 1 mo of age, and then fell rapidly to a median value near 30 ng/ml (95% confidence limits: 7-142 ng/ml) between 6 mo and 15 yr of age. In the adult, median concentrations diverged according to sex, 39 ng/ml in the female and 140 ng/ml in the male. In 13 children with iron-deficiency anemia, the serum ferritin concentration was 9 ng/ml or less. Overlap with the normal population was small, and no conditions were found to give "false" low values. In children with β-thalassemia major and sickle cell anemia, median values were elevated to 850 and 160 ng/ml, respectively. Possibly misleading, elevated values were obtained in some patients with acute infection and in acute lymphoblastic leukemia. The serum ferritin assay promises to be a useful tool in the evaluation of iron status, particularly in children.
Degradation of Bovine Factor VIII by Plasmin and Trypsin
Authors: Kirby Edward P. , Martin Neil , Marder Victor J. 
Published: October 2019

Abstract
The degradation of bovine Factor VIII by plasmin, trypsin, and thrombin was monitored with polyacrylamide gel electrophoresis in a urea—acetic acid system. The sequences of plasmic and tryptic proteolysis were very similar, proceeding via several intermediate, enzyme-sensitive products to smaller derivatives which were relatively resistant to further degradation. The intermediate degradation products were similar for both enzymes, although prolonged digestion with trypsin produced final products which were smaller than those observed with plasmin. Stages of digestion which reflect the degree of completeness of proteolysis were defined on the basis of the presence or absence of these distinct components in the electrophoretic profiles. Thrombin treatment of Factor VIII caused a loss of coagulant activity but did not yield products small enough to be characterized in this electrophoretic system. During the course of plasmic and tryptic digestion, there was a rapid loss of all coagulant activity without the generation of anticoagulant activity. Agarose chromatography of a 24-hr plasmic digest revealed three major protein peaks, which corresponded to individual electrophoretic bands on polyacrylamide gel electrophoresis in a nondenaturing system at pH 8.8. Upon polyacrylamide gel electrophoresis in the urea—acetic acid system, the components of the first two of these peaks dissociated into two and three separate fragments, respectively. Immunoelectrophoresis demonstrated two major distinct antigenic determinants in these first two elution peaks.
A Syndrome of Platelet-release Abnormality and Mild Hemophilia
Authors: Chesney Carolyn , Colman Robert W. , Pechet Liberto 
Published: October 2019

Abstract
Two families were studied because of a hemorrhagic tendency. The presumptive diagnosis of von Willebrand’s disease was suggested by low factor VIII levels (7.5%-33%), prolonged template Ivy bleeding time (9.5-17 min), low platelet adhesiveness (0%-8%), normal platelet factor 3, and normal clot retraction. Further studies, however, showed abnormal platelet aggregation with ADP, epinephrine, and collagen, and deficient release of platelet antiheparin activity and 14C serotonin. Patients’ platelets, rendered free of plasma by gel filtration, continued to show abnormal aggregation when resuspended in normal plasma. Plasma from the patients contained greater than 200% factor VIII by immunologic assay. The patients’ coagulant factor VIII level returned to base line within 24 hr after plasma or cryoprecipitate transfusions. Unlike von Willebrand’s disease, management of these patients required both platelets and cryoprecipitate to prevent bleeding.
Ultrastructure of Sickled Deer Erythrocytes. II. The Matchstick Cell
Authors: Taylor W. J. , Simpson C. F. 
Published: October 2019

Abstract
The matchstick cell is a unique form of sickled deer erythrocytes which is related to a specific β2-chain type in the white-tailed deer. Like the typical crescent form of sickled cell, it is an in vitro phenomenon which is induced by high pH and POO2 and reverses to the usual discoid form with deoxygenation and lowering of the pH. Transmission electron microscopy revealed a precise intracellular structure with polymerization of the hemoglobin into long filaments which were aligned in one axis of the cell, so that they appeared as long rods at relatively low magnification. A second feature, which contrasts to typical sickle forms of deer or man, is an absence of any type of microtubular structure. This suggests a different mode of intermolecular bonding related to primary structural variations of the β-chains which are associated with the matchstick cells and with typical sickle cells. Elucidation of the various structural differences between these β-chains may give additional clues to the mechanism of hemoglobin aggregation in the human sickle cell.
Agar Culture Studies in 127 Cases of Untreated Acute Leukemia: The Prognostic Value of Reclassification of Leukemia According to In Vitro Growth Characteristics
Authors: Moore M. A. S. , Spitzer G. , Williams N. , Metcalf D. , Buckley J. 
Published: October 2019

Abstract
Agar culture of marrow and blood from 127 cases of acute leukemia (including 108 cases of myeloid leukemia and variants) has revealed a spectrum of abnormalities. The observations of deranged proliferation and maturation of granulocyte—macrophage progenitor cells (in vitro CFC), together with abnormalities in CFC buoyant density, was of considerable diagnostic value. The morphologic, hematologic, and cytogenetic heterogeneity of acute myeloid leukemia did not correlate with heterogeneity of in vitro growth parameters, and grouping of patients by conventional hematologic parameters was of no value in predicting response to therapy. Indeed, the age of the patient was the only significant conventional parameter which influenced remission rate. By in vitro criteria, increase in the number of CFC of abnormally light buoyant density and high in vitro "plating efficiency" of the leukemic blast cells adversely affected remission probability. Reclassification of acute myeloid leukemia by in vitro growth pattern was of greatest prognostic value, and four main growth patterns were recognized: (1) colony forming, (2) large cluster forming (maximum cluster size, 40 cells), (3) small cluster forming (maximum cluster size, 20 cells), and (4) nongrowing. Highly significant differences in remission rate were observed in the different growth types. All cases of AML could be divided on the basis of growth pattern into a good prognosis group of 66 patients with a remission rate of 52% and a poor prognosis group of 42 cases with a 10% remission. The influence of age was evident in both groups, and of 30 patients less than 40 yr of age, remission in the favorable prognosis group was 91% and in the poor prognosis group only 14%. The ability to detect, at first diagnosis, a substantial number of patients whose disease is resistant to present therapeutic protocols could lead to application of alternative forms of therapy that may improve prognosis in this category.
Macrophage-Eosinophil Interactions in the Inflammatory Response to Trichinella spiralis
Authors: Walls Ronald S. , Hersey Peter , Quie Paul G. 
Published: October 2019

Abstract
Little is understood of the reasons why eosinophils accumulate in vivo, although a tissue reaction to administered antigen has been shown to be a prerequisite for the response. The present experiments aim to understand the significance of the tissue reaction to parasitic larvae in the chain of events leading to eosinophilia. Trichinella spiralis larvae were injected intraperitoneally in rats, and the peritoneal exudate was examined at intervals. Eosinophils were closely associated with macrophages rather than with other cell types or with parasites. A striking collection of eosinophils around individual macrophages was noted 48 hr after injection, and in particular following a second challenge. Use of indirect immunofluorescence techniques showed that these coincided with presence of immunoglobulin on macrophage surfaces. Incubation of peritoneal cells in medium containing 0.25% trypsin reduced macrophage surface immunofluorescence and numbers of rosettes. Rosettes could be constituted in vitro by incubation of normal peritoneal cells in medium containing antigen and antibody. These findings suggest that in the tissue reaction to parasitic larvae a close association exists between eosinophils and macrophages.
An Animal Model of Chronic Aplastic Marrow Failure. I. Late Marrow Failure After Busulfan
Authors: Morley Alec , Blake Judith 
Published: October 2019

Abstract
An animal model of chronic aplastic marrow failure was produced by administering busulfan to mice in high dosage for a prolonged period. Mice which survived 60 or more days following cessation of the drug appeared well: in 59% the blood was normal, and in 35% the marrow cellularity was within the normal range; those mice with evident abnormality in the blood and marrow showed only minimal cytopenia in the peripheral blood and moderate decreases in marrow cellularity. Nevertheless, by 240 days 80% of the mice had become ill and died. Sacrifice prior to death showed that aplasia of the marrow and cytopenia (most often pancytopenia) were present in the majority of mice. These syndromes of persistent mild marrow hypoplasia and late severe marrow failure which followed busulfan may be suitable experimental models for studying the late effects of myelotoxic agents and the syndrome of chronic aplastic marrow failure in man.