bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemotherapy of Mouse Myeloma: Quantitative Cell Cultures Predictive of Response In Vivo
Authors: Ogawa M. , Bergsagel D. E. , McCulloch E. A. 
Published: October 2019

Abstract
The effects of chemotherapeutic agents on mouse myeloma and bone marrow precursor cells were studied using cell culture and spleen colony assay techniques, and the results were assessed for their values in predicting therapeutic effectiveness. For cyclophosphamide, nitrogen mustard, and 1,3 bis (2 chloroethyl)-1-nitrosourea (BCNU), selective toxic effects on mouse myeloma (Adj. PC-5) cells were seen while no such differential effect was observed for 5-fluorouracil. The differential effects of these agents could not be explained by the cell cycle effects but appeared to be dependent on the intrinsic properties of the two cell classes. Marked differences were noted in the sensitivity of three mouse myelomas to melphalan. The ratio of the melphalan dose required to reduce marrow CFU to 37% (D37) to the dose required to reduce myeloma CFU equally was 75 for Adj. PC-5, 18 for MOPC 46B, and 7 for MOPC 460D. These results predict that melphalan would be more effective than 5-fluorouracil for Adj. PC-5 and that melphalan would be relatively ineffective for MOPC 460D. These predictions were confirmed by survival tests.
The Hemolytic Anemia of Magnesium Deficiency in Adult Rats
Authors: Piomelli Sergio , Jansen Valerie , Dancis Joseph 
Published: October 2019

Abstract
The administration of a Mg-deficient diet to adult rats for 4-5 wk causes anemia. The RBC are slightly smaller and flatter, and have a reduced hemoglobin component and a decreased osmotic fragility. 51Cr survival time is shortened when the affected cells are infused into normal adult rats. In vitro synthesis of heme and globin, as measured with 14C-glycine was the same as in control rats with "reticulocytosis-rich" anemia produced by bleeding or immunologically. The activity of a series of enzymes associated with energy production also failed to yield findings specific for Mg deficiency. It is suggested that the anemia of Mg deficiency is hemolytic and results from the combination of a reversible extrinsic defect and of an irreversible structural defect in the RBC.
Histone Biosynthesis in Pernicious Anemia Proerythroblasts and Megaloblasts
Authors: Kass Lawrence 
Published: October 2019

Abstract
Histone biosynthesis was investigated in proerythroblasts and megaloblasts obtained from patients with untreated pernicious anemia. Radioautography, using tritium-labeled L-arginine, L-lysine, and L-trytophane, acrylamide gel electrophoresis of histone fractions, acrylamide gel radioautography, uptake of radioisotopes into lysine-rich and arginine-rich histone fractions, and amino acid analysis of histone fractions, was performed. In untreated pernicious anemia proerythroblasts and megaloblasts, there was a small uptake of arginine and lysine as seen radioautographically, and incorporation into isolated histone fractions was scant. Amino acid analyses showed these histones to be lysine rich. After these erythroid precursors were exposed to cyanocobalamin in vivo or to coenzyme B12 in vitro, there was a marked (up to 100-fold) incorporation of only tritium-labeled L-arginine into erythroid nuclei, as seen radioautographically, and into isolated histone fractions as well. Amino acid analyses demonstrated that the histones had become more arginine rich. These studies indicate that vitamin B12 facilitates the biosynthesis of arginine-rich histones in vitamin B12-deficient erythroid precursors.
IgG Cryoglobulinemia Associated With Amyloidosis
Authors: Maldonado Jorge E. , McNutt D. R. , Kyle Robert A. , Baggenstoss Archie H. , Fudenberg H. H. 
Published: October 2019

Abstract
A patient with symptomatic primary cryoglobulinemia was followed for 9 yr and was found at autopsy to have generalized amyloidosis. There was a monoclonal serum protein spike of IgG kappa type that was cryoglobulin. The cryoglobulin was further characterized as IgG2 kappa Gm (n-). This case constitutes, to our knowledge, the first example of amyloidosis associated with monoclonal IgG cryoglobulinemia, with characterization of the monoclonal serum cryoglobulin, and also the first reported case of successful symptomatic treatment of cryoglobulinemia by plasmapheresis.
Membrane-mediated Synthesis of Tissue Factor (Thromboplastin) in Cultured Fibroblasts
Authors: Zacharski Leo R. , McIntyre O. Ross 
Published: October 2019

Abstract
A potent procoagulant synthesized by cultured human skin fibroblasts has been identified as tissue factor (factor III, thromboplastin), since it binds factor VII and is blocked by a specific antitissue factor antibody. Fibroblast tissue factor is, at least in part, a labile superficial, membrane-associated substance the synthesis of which is mediated by cell adhesion but is inhibited by actinomycin-D and puromycin. Tissue factor production is related to the shape change that occurs as the cells spread on the floor of the culture vessel, but tissue factor is not synonymous with the configuration on the cell surface responsible for cell adhesion. These observations suggest that cell membranes may play a significant role in hemostasis and thrombosis by virtue of their tissue factor content.
Properties of the Platelet Retention (von Willebrand) Factor and Its Similarity to the Antihemophilic Factor (AHF)
Authors: Weiss Harvey J. , Rogers John , Brand Harvey 
Published: October 2019

Abstract
The abnormal retention of platelets in glass-bead filters in von Willebrand’s disease was corrected by a fraction of normal cryoprecipitate that eluted, along with antihemophilic factor (AHF), in the void volume after chromatography on Bio-Gel 5 M. This platelet retention factor had an apparent molecular weight in excess of 5 x 106, was also present in hemophilic cryoprecipitate, but was not detectable in the void volume fractions of cryoprecipitate prepared from the plasma of a patient with von Willebrand’s disease. The adsorptive and thermal stability properties of the retention (von Willebrand) factor were similar to those of AHF. Platelet retention is the result of a complex interaction between red cells, platelets, and the von Willebrand factor, and it is suggested that the activity of the latter factor may be associated with the same high molecular weight protein that possesses coagulant (AHF) activity in normal subjects but that lacks this activity in hemophiliacs. The deficiency of this protein in von Willebrand’s disease may account for the hemostatic defect in this disorder.
Pyridoxine-responsive Anemia: Influence of Tryptophan on Pyridoxine Responsiveness
Authors: Horrigan Daniel L. 
Published: October 2019

Abstract
This study presents evidence that the indolic amino acid, tryptophan, critically influences pyridoxine responsiveness in a patient with pyridoxine-responsive anemia. Continuing observations for 18 yr on this now 54-yr-old white man have shown responsiveness to oral crude liver extract and to pyridoxine. In addition, remissions of 8-mo duration followed oral administration of fractions of liver extract in doses of 2 mg daily. These nonprotein fractions contained acidic substances characterized as indoles. From 1959 to 1970, oral pyridoxine, in daily doses of 12.5 mg for 5 days, predictably produced prompt reticulocytosis, fall in serum iron content, and rise in hematocrit to nearly normal levels. Such responses to pyridoxine consistently lasted less than 2 mo. More recently, relative refractoriness to this dose of pyridoxine has developed. However, responsiveness has been restored by oral administration of I-tryptophan, 750 mg daily, an amount alone insufficient to maintain the hematocrit at optimal levels. These observations indicate relationships of tryptophan and pyridoxine in erythropoiesis that have not been recognized previously. Addition of I-tryptophan to the therapy of certain pyridoxine-responsive and other sideroblastic anemias might be considered.
Effect of Phenylhydrazine-induced Hemolytic Anemia on Nuclear RNA Polymerase Activity of the Mouse Spleen
Authors: Spivak Jerry L. , Toretti Dennis , Dickerman Herbert W. 
Published: October 2019

Abstract
The DNA-dependent RNA polymerase of nuclei from lymphoid-rich and erythroid-rich mouse spleens was compared in regard to requirements and conditions of the reactions. The inhibition by either actinomycin D or pancreatic DNase indicated that a DNA template was required for the observed reactions. Following the induction of a hemolytic anemia by the administration of phenylhydrazine, there was a tenfold increase in the nuclear polymerase activity per milligram nuclear DNA of the developing erythropoietic spleen when the assays were done at low ionic strength and more than a threefold increase at high ionic strength. The peak rise in polymerase activity precedes the maximal development of the erythropoietic spleen by 3 days.
Comparison of Two Methods of Preventing Central Nervous System Leukemia
Authors: Aur Rhomes J. A. , Hustu H. Omar , Verzosa Manuel S. , Wood Adynel , Simone Joseph V. 
Published: October 2019

Abstract
This controlled study of children with ALL was designed to determine in a prospective manner the relative efficacy and toxicity of two forms of "prophylactic" CNS therapy for preventing CNS relapse and of periodic vincristine-prednisone "pulses" during multiple agent chemotherapy. Following cranial irradiation (2400 rads) plus intrathecal methotrexate, 3 of 45 patients developed CNS leukemia. Following craniospinal irradiation (2400 rads), 2 of 49 developed CNS leukemia. Craniospinal irradiation was associated with more leukopenia and interruptions of chemotherapy. "Pulses" were not associated with improvement of remission duration. Our current choice of CNS therapy is cranial irradiation plus intrathecal methotrexate because it takes less time and may avoid demonstrated short-term side effects and possible long-term effects of spinal irradiation.
Treatment of Established Graft-Versus-Host Disease in Dogs by Antithymocyte Serum or Prednisone
Authors: Storb R. , Kolb H. J. , Graham T. C. , Kolb H. , Weiden P. L. , Thomas E. D. 
Published: October 2019

Abstract
Marrow grafts after 1200 R of whole-body irradiation were carried out between pairs of unrelated dogs of different breeds that were incompatible for dog histocompatibility antigens. Three groups of recipients were studied. Recipients in all groups were treated with the immunosuppressive agent methotrexate (MTX), 0.4 mg/kg, on days 1, 3, 6, and 11, and then once weekly until day 102 after grafting. Dogs in group 1 were given MTX only. Thirty of 35 recipients died between 11 and 51 days and five survived more than 102 days. Median survival time was 20 days. Dogs in group 2 were treated with rabbit antidog antithymocyte serum (ATS) when graft-versus-host (GVH) disease became established. Eight of ten recipients died between 19 and 76 days and two survived more than 102 days. Median survival time was 45 days. Dogs in group 3 were treated with daily injections of prednisone when GVH disease became apparent. Seven of nine recipients died between 11 and 34 days and two survived more than 102 days. Median survival time was 24 days.
It was concluded that established GVH disease in dogs with histoincompatible marrow grafts can be favorably influenced by ATS with significant (p < 0.01) prolongation of survival. However, there was no evidence that treatment with ATS increased the fraction of long-term survivors in this histoincompatible setting. Prednisone was ineffective and did not prolong survival (p > 0.1).
The Elevation of Adenosine-Triphosphate Levels in Human Erythrocytes
Authors: Warrendorf Elizabeth M. , Rubinstein David 
Published: October 2019

Abstract
It has previously been possible to double the level of ATP in human erythrocytes by incubation of the cells at 37° for 10 hr with glucose and adenine. The present study describes a further increase in the ATP level and some of the possible mechanisms involved. Addition of 5 mM pyruvate to a medium containing 32 mM inorganic phosphate, glucose, and adenine elevated the level of ATP threefold during a 10-hr incubation. Pyruvate could be replaced by inosine but the presence of both limited the elevation of ATP to twice that of fresh cells. This limitation may be overcome by the use of 96 mM phosphate in the incubation medium, in which case the intracellular level of ATP is tripled within 2 hr. The conditions which limit the accumulation of ATP are associated with low intracellular phosphate concentrations and the accumulation of organic phosphates, especially, in the presence of inosine, 2,3-diphosphoglycerate. Utilizing 14C-glucose labeled in carbons 1, 2, or 6, it has been shown that when ATP is being rapidly elevated, the pentose moiety of the adenine nucleotides is mainly supplied (about 80%) by oxidation of carbon 1 of glucose, catalyzed by the dehydrogenases of the hexosemonophosphate shunt. In the presence of pyruvate this activity is doubled. Pyruvate reoxidizes NADPH formed by this pathway, since lactic dehydrogenase has some specificity towards the NADPH. The involvement of the dehydrogenases of the hexosemonophosphate shunt is illustrated by the use of erythrocytes deficient in glucose-6-phosphate dehydrogenase. Incubation of these cells for 5 hr with glucose and adenine results in only a slight increase in ATP formation, and pyruvate has no additional effect. Addition of inosine, however, leads to the same increment in ATP levels seen in normal cells. The ATP and 2,3-diphosphoglycerate levels in 6-wk preserved blood can also be increased to three times that of fresh cells by incubation with glucose, adenine, pyruvate, and inosine in a medium high in inorganic phosphate.
Defective Capacity of Bone Marrow From Nude Mice to Restore Lethally Irradiated Recipients
Authors: Zipori Dov , Trainin Nathan 
Published: October 2019

Abstract
The proliferative capacity of bone marrow cells from thymus-deprived nude mice was investigated in lethally irradiated recipients. Although the colony-forming capacity of these cells was found to be similar to that of normal littermates, a reduction in the number of nucleated cells was observed in the bone marrow of nude mice. Moreover when the radioprotective effect of such cells was studied, it was found that 5 x 105 or 2 x 106 bone marrow cells from nude mice were less effective in restoring hemopoiesis and establishing permanent chimerism than similar amounts of bone marrow cells of normal controls. In addition, irradiated animals surviving after injection of bone marrow cells from nude mice were found to have lower immune responses to SRBC than normal chimeras. The possibility that mortality of irradiated recipients injected with bone marrow of nude mice is due to the presence of a latent infective agent or of some inhibitory factor of hematopoiesis in the bone marrow of such nude mice is shown to be improbable. Alternatively it is suggested that nude mice suffer from an intrinsic defect in the proliferative capacity of their bone marrow colony-forming cells (CFUs).
Chloroma and Other Myeloblastic Tumors
Authors: Muss Hyman B. , Moloney William C. 
Published: October 2019

Abstract
Fifteen cases (3.1%) of localized myeloblastic tumors occurring among 478 patients with acute granulocytic leukemia (AGL) and chronic granulocytic leukemia (CGL) are described. The majority of tumors were discovered at autopsy. Numerous cases of chloroma associated with AGL have been reported; however, in this series, the incidence of myeloblastic tumors in CGL was twice as high. The importance of employing histochemical methods for myeloperoxidase activity to identify myeloblastic tumors is pointed out. Experience in this group of cases confirm the frequent involvement of the ovary and the common localization of myeloblastic tumors to perineural and epidural structures. With CNS involvement by myeloblastic tumors, pain and compression symptoms may be effectively relieved by laminectomy and local x-ray therapy. After the appearance of a myelogenous tumor in CGL, the course of the disease is rapidly progressive.
Genetic Implications of the Interaction of Two Types of Beta-Thalassemia Genes in a Patient With Thalassemia Major
Authors: Russo Giuseppe , Mollica Florindo , Pavone Lorenzo , Musumeci Salvatore , Baglioni Corrado 
Published: October 2019

Abstract
A patient with thalassemia major is described in which two types of thalassemia genes are present, one that reduces β-chain synthesis and the other that suppresses it completely. The identification of these two types of β-thalassemia genes is based on the presence or absence of HbA in other members of the same family who are also HbC carriers. The genetic implications of the interaction of these two thalassemia genes are discussed in view of recent theories on the nature of the molecular defect characteristic of each type of thalassemia.
Hemoglobin Köln in a Black: Preand PostSplenectomy Red Cell Survival (DF32P and 51Cr) and the Pathogenesis of Hemoglobin Instability
Authors: Pedersen Paul R. , McCurdy Paul R. , Wrightstone R. N. , Wilson J. B. , Smith L. L. , Huisman T. H. J. 
Published: October 2019

Abstract
A 17-yr-old black male with hemolysis and pigmenturia but no anemia was found to have hemoglobin Köln (α2β298 val→met [FG5]). Splenectomy was done because of complicating thrombocytopenia. Thrombokinetic studies with 51Cr tagged platelets suggested hypersplenism, and after surgery the platelet count returned to normal. The red cell t ½ 51Cr was more than doubled, but the red cell life span (DF32P) was more modestly improved (30.6 → 47.2 days). The "elution" of 51Cr from the red cells presplenectomy was 5.6%/day, whereas after surgery it was normal (1.9%/day), accounting for the disparity between the survival methods. Study of the isolated cyanferri derivative of hemoglobin Köln by ultracentrifugation at various salt concentrations and various pH’s indicated an increased tendency to dimer formation under conditions where normal hemoglobin is a tetramer. This results from the site and type of amino acid substitution and accounts in part for its instability.
The Ausria Test: Critical Evaluation of Sensitivity and Specificity
Authors: Alter Harvey J. , Holland Paul V. , Purcell Robert H. , Gerin John L. 
Published: October 2019

Abstract
Ausria was shown to be considerably more sensitive than CEP by comparing titers of HBAg+ sera and by testing selected proficiency panels, sera from hepatitis patients, and sera from experimentally infected rhesus monkeys; CEP+, Ausria-sera were never encountered. However, in testing NIH donors and personnel, 19 of 20 Ausria+, CEP-sera were shown by neutralization studies to be nonspecific for HBAg, i.e., false positives. Nonspecificity was confirmed by an alternate radioimmunoassay procedure and, in one serum, by density-gradiant ultracentrifugation. Testing of 35 additional Ausria+, CEP-sera from New Jersey donors showed 13 specific and 22 (63%) nonspecific reactions. It is mandatory that serum from every Ausria+, CEP-donor undergo specificity testing. In addition to the 14 specific Ausria+, CEP-sera, two sera, subsequently shown to be CEP+, were undetected on the initial CEP test (one was transfused and resulted in hepatitis). These sera were strongly positive by Ausria; sera subject to reader error in CEP are unequivocally positive by Ausria. Ausria tests on CEP-donors suspected of transmitting HBAg failed to implicate a donor in each of eight cases. Some HBAg+ hepatitis will continue to occur despite universal application of Ausria or other tests of equal sensitivity.
Induction of Sustained Hemopoiesis in Fatty Marrow
Authors: Tavassoli Mehdi , Maniatis Alice , Crosby William H. 
Published: October 2019

Abstract
Evacuation of the fatty marrow cavity results in a sequence of regeneration which is associated with a phase of hemopoiesis. Hemopoietic activity is, however, transient, being replaced by adipose tissue, so that 6 mo after evacuation the marrow is once again fatty. This phase of transient hemopoiesis can be sustained by phenylhydrazine-induced hemolytic stress. Hemolysis per se does not induce significant hemopoietic activity in nonevacuated totally fatty marrow.
Paroxysmal Nocturnal Hemoglobinuria with Elevated Fetal Hemoglobin
Authors: Rassiga-Pidot Anne L. , Cornwell Gibbons G. , McIntyre O. Ross 
Published: October 2019

Abstract
A persistent elevation of the fetal hemoglobin (Hgb F) level (5%-15%) was observed in a 22-yr-old white male with paroxysmal nocturnal hemoglobinuria (PNH). Acid treatment of the peripheral smear (Betke-Kleihauer technique) demonstrated a heterogeneous distribution of Hgb F in the red cells. As expected, the lowest acetylcholinesterase activity and the most hemolysis after acid stress were found in the low-density, reticulocyte-rich cell fraction. In contrast, the highest Hgb F levels were found in the high-density, reticulocyte-poor fraction. Further evidence for the segregation of these two abnormalties was obtained from the observation that less Hgb F was present in the hemolysate obtained after acid lysis than was present in the mixed blood sample or the remaining nonhemolyzed red cells.
Effect of Cyanate on Erythrocyte Deformability
Authors: Durocher John R. , Glader Bertil E. , Gaines Lelia T. , Conrad Marcel E. 
Published: October 2019

Abstract
Cyanate is undergoing study as a drug to prevent occlusive sickle cell crises. Carbamylation of hemoglobin S increases its oxygen affinity, thereby decreasing its tendency to aggregate at low oxygen tensions. The cell membrane has also been shown to be carbamylated. We studied the effect of carbamylation on deformability of sickle, normal, and stored normal erythrocytes. Deformability was measured as filtration time of erythrocyte suspensions through 3-µ polycarbonate filters. Oxygenated carbamylated sickle erythrocytes had a marked shortening of filtration time that could not be explained by changes in morphology. In addition, normal erythrocytes became more filterable with carbamylation. Decreased filterability after storage at 4°C for 48 hr was returned to normal following carbamylation and incubation with glucose. No correlation was made with changes in either morphology, cell size, or ATP levels. Therefore, it was postulated that carbamylation affected filterability by binding either the cell membrane or cell contents or both.
The Intravascular Survival of Neutrophils Labeled In Vivo
Authors: Vincent Paul C. , Chanana Arjun D. , Cronkite Eugene P. , Joel Darrel D. 
Published: October 2019

Abstract
The survival of blood neutrophils labeled in vivo was studied in the calf. Disappearance of labeled neutrophils from the blood of calves was followed after a period of cross circulation with their chimeric, immunologically tolerant twins, which had been given tritiated thymidine 6½ days previously. Under these conditions, neutrophils were shown to leave the blood in a random exponential fashion, with half-disappearance times of between 6.4 and 7.5 hr. Hydrocortisone given to one calf 48 hr after cross circulation caused a neutrophilic leukocytosis, during which substantial numbers of labeled neutrophils reappeared in the blood.
Fletcher Factor Deficiency: Family Study and Detection
Authors: Abildgaard Charles F. , Harrison Janet 
Published: October 2019

Abstract
Eight of 11 children of a known Fletcher factor-deficient individual were found to have normal activated partial thromboplastin times, normal levels of factors VIII, IX, XI, and XII, and a mean Fletcher factor level of 53% (range 40%-72%), suggesting a heterozygous state for the genecontrolling Fletcher factor production. All partial thromboplastin time reagents containing celite or kaolin were sensitive to Fletcher factor deficiency, while one reagent containing ellagic acid did not detect this abnormality. The finding of an abnormal partial thromboplastin time that is corrected by a 10-min incubation period is presumptive evidence for Fletcher factor deficiency.