bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene Cloning of Rat and Mouse Platelet Glycoprotein V: Identification of Megakaryocyte-Specific Promoters and Demonstration of Functional Thrombin Cleavage
Authors: Ravanat Catherine , Morales Martine , Azorsa David O. , Moog Sylvie , Schuhler Simone , Grunert Pierre , Loew Damarys , Van Dorsselaer Alain , Cazenave Jean-Pierre , Lanza François 
Published: October 2019

AbstractPlatelet glycoprotein (GP) V is a major surface protein cleaved during thrombin-induced platelet activation. GPV associates noncovalently with the GPIb-IX complex to form GPIb-V–IX, a receptor for von Willebrand factor and thrombin. We describe the cloning of the genes coding for rat and mouse GPV and compare them with the human gene. The two rodent genes have a similar structure and resemble the human GPV gene with a coding sequence (≈1,700 nucleotides) entirely contained in one exon and a single intron (≈900 nucleotides) in the 5′ untranslated region. Both genes have megakaryocyte-type promoters with conserved tandem Ets and GATA recognition motifs and lack a TATA box. The mature rat and mouse proteins comprise 551 amino acids, have 70% sequence identity, and contain an additional 8–amino acid intracellular segment as compared with the human protein. As in human GPV, there is an NH2 -terminal leucine-rich region of 15 repeats and a thrombin cleavage recognition sequence. Whereas the rat and human thrombin cleavage sites are similar, the mouse cleavage site resembles that of the human thrombin receptor. Functionality of these sites was demonstrated by thrombin cleavage of synthetic peptides and analysis by high-performance liquid chromatography (HPLC) or mass spectrometry. Cleavage of native rat GPV was confirmed by means of a polyclonal antibody directed against the new NH2 -terminal peptide exposed after thrombin cleavage. This antibody specifically recognized thrombin-activated rat platelets by fluorescence-activated cell sorting (FACS) analysis. In addition, we raised monoclonal antibodies specific for rat GPV (88 kD), which recognized the NH2 -terminal soluble fragment (70 kD) liberated after thrombin cleavage. Knowledge of these rodent GPV genes and availability of species-specific peptides and antibodies will be essential to further studies aiming to define the exact in vivo function of platelet GPV using animal models of thrombosis and gene inactivation experiments.
Variable Immortalizing Potential and Frequent Virus Latency in Blood-Derived T-Cell Clones Infected With Human T-Cell Leukemia Virus Type I
Authors: Richardson J.H. , Höllsberg P. , Windhagen A. , Child L.A. , Hafler D.A. , Lever A.M.L. 
Published: October 2019

AbstractHuman T-cell leukemia virus type I (HTLV-I)-infected T cells expanded in vitro by single-cell cloning provide a unique system for investigating virus-cell interactions in nonimmortalized T cells. By analysis of clones generated randomly from the blood of virus carriers, we confirm that CD4 T cells are the major reservoir of HTLV-I in vivo and show that most infected cells contain a single integrated provirus. Contrary to the situation in HTLV-I immortalized cell lines, the HTLV-I provirus was found to be transcriptionally silent in a high proportion of randomly generated T-cell clones and could not be reactivated by mitogenic stimulation. The spontaneous proliferation previously documented in HTLV-I–infected T-cell clones was not observed in silently infected cells, and therefore correlates directly with the expression of tax and other viral genes. The only cytokine mRNA found to be significantly elevated in the virus-producing clones was interleukin-6; however, receptor-blocking experiments argue against a role for IL-6 in the virus-induced cell proliferation. We observed a striking variation in the ability of individual HTLV-I–producing clones to immortalize fresh peripheral blood lymphocytes. This ability did not correlate with the levels of viral mRNA expression, gag p24 production, spontaneous proliferation, or tax-transactivation, possibly suggesting a role for host cell factors as determinants of viral infectivity or immortalization. Studies to elucidate the basis of this phenotypic heterogeneity should enhance our understanding of viral spread and pathogenesis.
Hodgkin’s Specific Cells in Bone Marrow Aspirations
Authors: BAYED EDWIN D. , PAULSON GORDON S. , HARGRAVES MALCOLM M. 
Published: October 2019

Abstract
The literatutre concerning the observations of Sternberg-Reed cells in smears of bone marrow aspirate has been briefly reviewed and the cytology of node imprint preparations has been noted.
Two cases of Hodgkin’s disease in which Sternberg-Reed cells were observed in marrow smears are recorded with accompanying photomicrographs. No such cells were seen in the course of routine examination of more than six thousand, five hundred other bone marrow smears or in a special review of thirty cases of proved Hodgkin’s disease.
Oxygen Consumption of Erythrocytes from Patients with Various Thyroid Conditions Related to Their Respective Serum Protein—Bound Iodine Concentrations
Authors: ANGELONE LUIS , WATKINS DAVID H. , ANGERER CLIFFORD A. 
Published: October 2019

Abstract
Blood was obtained from patients who were divided into four groups: (A) euthyroid, (B) untreated hyperthyroid, (C) iodine-treated hyperthyroid and (D) hypothyroid. The erythrocytes from each patient group were washed and resuspended in Krebs-phosphate solution for study by the Warburg respirometric technic. When the erythrocytes obtained from patient groups B, C and D are compared with group A (control), a +92 per cent, +23 per cent and -15 per cent change is noted, respectively, in their mean QOO2 values when QOO2 values for erythrocytes for each patient in each patient group (excluding group C) are plotted relative to their respective serum PBI concentration (µg. per cent), a curve of exponential order appears to be the curve of best probable fit for these data. The mean QOO2 value for the iodine-treated hyperthyroid group falls on the ordinate of this curve (fig. 1) between the euthyroid and untreated hyperthyroid groups, though the mean serum PBI value (abscissa), of course, has no meaning for this group.
Hematological Effects of Certain 2,4-Diaminopyrimidines, Antagonists of Folic Acid Metabolism
Authors: HAMILTON LEONARD , PHILIPS FREDERICK S. , STERNBERG STEPHEN S. , CLARKE DONALD A. , HITCHINGS GEORGE H. , WHEELOCK BARBARA , DEBLIEUX ANN 
Published: October 2019

Abstract
1 . The administration of 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine (50-197) and 2,4-diamino-5-(3',4'-dichlorophenyl) pyrimidine (50-11) to mice and rats produced delayed effects characteristic of folic acid deficiency; 50-197 amid 2,4-diamino-5-p-chlorophenyl-6-ethylpyrimidine (50-63) produced similar effects in dogs. LD50 values have been calculated.
2. The diaminopyrimidines caused ileitis amid colitis with diarrhea in mice, rats, and dogs, and stomatitis in dogs; animals lost weight and became dehydrated. Microscopic changes found in gastrointestinal tract, lymphatic tissue, and bone marrow have been described.
3. The hematologic manifestations observed were (a) granulocytopenia and reticulocytopenia in rats and dogs; there was a relatively less severe lymphocytopenia, (b) alterations in dog marrow which included an appreciable proportion of erythroid development via the megaloblast series, numerous and varied mitotic abnormalities, nuclear fragments, giant metamyelocytes, hypersegmented polymorphonuclear cells and a change its nuclear chromatin of myeloid series corresponding to megaloblastosis in erythroid development.
4. Doses of the diaminopyrimidines in excess of the LD50 produced convulsions in mice and rats (50-197 and 50-11); acute convulsant effects were also produced in cats given 50-197 and in dogs given 50-63. This acute convulsant actions could be prevented by means of anesthetic barbiturates. It is a property of alkyl substituted 2,4-diaminopyrimidines and 2-methyl-4-aminopyrimidines and is not specifically related to anti-folic activity.
5. The delayed death of some, but not all, mice following the diaminopyrimidines could be prevented by the simultaneous administration of citrovorum factor. This suggests, on the analogy of 4-amino-PGA and PGA, that there might be another factor or factors its the folic-folinic acid reaction chain as yet unidentified in cells.
Polycythemia Vera Terminating with Myeloblastic Leukemia
Authors: WILLIAMS MARJORIE J. , MENDEL JULIUS L. 
Published: October 2019

Abstract
A case of somewhat atypical polycythemia vera with marked leukocytosis and terminal myeloblastic leukemia has been studied hematologically and biochemically. The biochemical studies consisted of repeated estimations of the leukocytic alkaline and acid phosphatase activities during the last nine months of the patient’s life. These studies suggested that, except during the terminal myeloblastic leukemia, there was a leukemoid reaction rather than chronic myelogenous leukemia associated with polycythemia. The significance of these findings is briefly discussed and it is suggested that the widespread application of similar biochemical studies to cases of polycythemia vera with marked leukocytosis might be of value its helping to determine the true incidence of myelogenous leukemia in this disease.
Sideroblasts
Authors: KAPLAN EUGENE , ZUELZER WOLF W. , MOURIQUAND CLAUDE 
Published: October 2019

Abstract
Bone marrow specimens from a large group of infants and children were studied with the prussian blue stain. Iron-staining granules were present in the normoblasts of all the subjects studied, including normal individuals and those with a large variety of hematologic disorders. The term sideroblast was proposed for normoblasts with nonstaining inclusions. The profound decrease in sideroblasts in iron deficiency anemia and their prompt increase following both iron therapy in vivo and the addition of iron to marrow cultures in vitro indicated that the estimation of normoblast iron granules provides a sensitive index of the availability of iron. In thalassemia and in lead poisoning, hemoglobindeficient erythrocytes were found despite the presence of abundant iron granules within the normoblasts.
The presens of stainable nonhemoglobin iron in red cell precursors is a normal phenomenon and provides a useful adjunct for the study of iron metabolism.
Erythroleukemia, with Special Emphasis on the Acute or Incomplete Variety
Authors: MARTIN WILLIAM J. , BAYRD EDWIN D. 
Published: October 2019

Abstract
Five cases of erythroleukemia of the acute or incomplete variety form the basis of this report. Four of the patients were women. The ages of these five patients ranged from 19 to 73 years at time of admission to the Mayo Clinic. Studies were made on the blood and peripheral marrow for varying periods throughout the course of the disease. All five patients had anemia and extreme immaturity of the erythrocytes in the peripheral blood and bone marrow. Leukopenia was eventually present in four cases as was thrombopenia. Splenectomy was performed on one patient.
One patient lived six years after the condition developed, two died within thirteen months of the time of diagnosis, one was not followed, and the fifth was still living at last report.
Relatively few cases of erythroleukemia have been reported in the literature and most of those reported have been cases of the chronic variety. The erythrocytic picture in the chronic variety differs from that in the acute variety. In the acute type acute erythremia is associated with leukemia and in the chronic type polycythemia is associated with it. Either the erythrocytic abnormality or the leukocytic may appear first. Our studies and those reported in the literature suggest excessive activity of the blast cell in two directions.
Hemolysis and Alimentary Lipemia
Authors: SWANK ROY L. , ROTH ESTHER S. 
Published: October 2019

Abstract
1. Following ingestion of cream fat, cod liver oil, and glyceryl trioleate, hemolysis occurred when lipemic whole blood samples were shaken. The degree of hemolysis was roughly proportional to the degree of visible lipemia of the plasma. Blood samples from fasting dogs similarly shaken were not hemolyzed. The amount of hemolysis increased with increasing speed or duration of shaking.
2. This hemolysis was not due to an altered fragility of the erythrocytes per se, but to the chylomicra in the plasma or to substances in the plasma associated closely with the chylomicra.
3. Injections of heparin were followed by a rapid disappearance of lipemia and in many instances by a parallel decrease in hemolysis. At times, however, an early and transient increase in the amount of hemolysis followed injection of heparin in cod liver oil and trioleate-fed dogs. It was also shown that following heparin injection there was a slight increase in the amount of hemolysis produced by the particulate-free, usually inactive, subnatant plasma. Protamine injection caused a return of visible lipemia and an increase in the amount of hemolysis on shaking.
4. Incubation studies with whole blood and with plasma showed that the amount of hemolysis on shaking rapidly increased with incubation of preheparin lipemic blood. After heparin injection, incubation brought about either a decrease in hemolysis on shaking, a slight increase, or an increase followed by a decrease.
5. Possible mechanisms of the hemolysis are discussed.
The Combined Study of Agglutination, Hemolysis and Erythrophagocytosis
Authors: BONNIN JAMES A. , SCHWARTZ LAWRENCE 
Published: October 2019

Abstract
1. A method for the combined demonstration of erythrophagocytosis, agglutination, and hemolysis was developed and applied to the study of a series of antierythrocytic antibodies under varying conditions of temperature and pH, using normal, trypsinized, and PNH corpuscles. Erythrophagocytosis was observed supravitally and in fixed preparations.
2. Only those antibodies which were potentially or actually hemolytic produced phagocytosis under the experimental conditions employed. The conditions necessary for the production of the two phenomena were similar except in the case of anti-A. In titration experiments, erythrophagocytosis occurred in higher serum dilutions than did hemolysis.
3. All the antibodies producing opsonization required the presence of thermolabile components of fresh serum for optimal activity. Except with anti-A, appreciable erythrophagocytosis was not produced by heat-inactivated sera. Hemolysis produced by systems other than antibody and complement was unaccompanied by phagocytosis.
4. It is suggested that hemolysis and erythrophagocytosis may both result from the same type of alteration of the red cell surface.
Serum Concentrations of Vitamin B12 in Patients Suffering from Leukemia
Authors: BEARD MARION F. , PITNEY W. R. , SANNEMAN E. H. 
Published: October 2019

Abstract
1. Vitamin B12 serum concentrations have been investigated in various types Of leukemia.
2. The concentration in chronic myeloid leukemia is approximately 15 times normal. In chronic lymphatic leukemia it is normal. In acute leukemia it is variable.
3. In chronic myeloid leukemia, the serum vitamim B12 exists in the bound form and the binding capacity for added B12 is increased.
4. Electrophoretic studies indicate that serum vitamims B12 in chronic myeloid leukemia is bound in the alpha globulin fractions.
5. Some correlation was found between serum vitamin B12 concentrations and total white cell counts in chronic myeloid leukemia. The possible significance of this is discussed.
A Serologic and Genetic Analysis of an r'r' (dCe/dCe) Patient Producing Anti-D and Anti-c
Authors: LEVINE PHILIP , COOPER MARY B. , KOCH ELIZABETH A. 
Published: October 2019

Abstract
A most unusual combination of antibodies, anti-D and anti-c produced by a transfusion and pregnancy, respectively, was identified by cross-absorption experiments. The immunized mother (propositus), whose husband was of genotype dce/dce, possessed the very rare genotype dCe/dCe, each of her parents, who were related to each other as fourth cousins, contributing the rare chromosome dCe.
The critically affected male infant was successfully treated by early replacement transfusion with the mother’s plasma-free red cells and her sibling’s rare compatible blood. The infant made a complete recovery although the preceding pregnancy ended in a macerated fetus.
Mild PTC (Plasma Thromboplastin Component) Deficiency Occurring in Two Brothers
Authors: BERGSAGEL D. E. , SETNA S. S. , CARTWRIGHT G. E. , WINTROBE M. M. 
Published: October 2019

Abstract
1. Thirteen cases of plasma thromboplastin component (PTC) deficiency or Christmas disease are reviewed and summarized. Of these cases, only in one were the whole blood coagulation time and prothrombin consumption normal.
2. Two cases of a mild bleeding disorder, occurring in brothers with slightly prolonged whole blood coagulation times and normal prothrombin consumption are described.
3. In these two cases, the thromboplastin generation test revealed the deficiency of a serum factor essential for normal thromboplastin generation. A mild deficiency of PTC was demonstrated by the correction of the serum deficiency by the addition to the patients’ serum of a partially purified preparation of PTC.
4. The differentiation of PTC deficiency from hemophilia is discussed.
5. Mild bleeding disorders due to a moderate reduction of antihemophilic globulin (AHG) or PTC can be differentiated by the use of the thromboplastin generation test.
A Recombinant Human scFv Anti-Rh(D) Antibody With Multiple Valences Using a C-Terminal Fragment of C4-Binding Protein
Authors: Libyh M. Tonye , Goossens D. , Oudin S. , Gupta N. , Dervillez X. , Juszczak G. , Cornillet P. , Bougy F. , Reveil B. , Philbert F. , Tabary T. , Klatzmann D. , Rouger P. , Cohen J.H.M. 
Published: October 2019

AbstractMonomeric recombinant molecules prove generally unsatisfactory for in vivo use. Most biological systems are indeed multivalent either structurally, associating different chains, or functionally, when cross-linked by their ligands. Mimicking natural molecules for immune intervention implies the need for multimerizing systems to create multivalent molecules capable of interfering with physiological processing. A multivalent anti-Rh(D) recombinant protein has been designed by reconstructing the antibody binding site of a human monoclonal anti-Rh(D) antibody as a single chain Fv mini antibody, then multimerizing it by inserting at its C-terminal end the C-terminal part of the C4 binding protein (C4bp) alpha chain, which is responsible for the octamer multimerization of that molecule. This soluble multivalent recombinant molecule was functional, bound red blood cells (RBCs), agglutinated them, and did not activate complement. This demonstration model opens the way for future in vivo use of multivalent molecules associating antibody valences and other functional molecules for cell targeting, imaging, or removal of cells such as Rh(D)-positive RBCs for preventing Rh alloimmunization.
Evidence for Copurification of HERV-K–Related Transcripts and a Reverse Transcriptase Activity in Human Platelets From Patients With Essential Thrombocythemia
Authors: Boyd Mark T. , Foley Brian , Brodsky Isadore 
Published: October 2019

AbstractWe have previously reported that particles resembling retroviral particles and possessing an RNA-directed DNA polymerase activity can be prepared from platelets. Furthermore, we and others have shown that these particles are present at higher levels in patients with essential thrombocythemia and polycythemia vera. We show here that these particles package RNA molecules that encode HERV-K–related pol genes. A subset of the RNA molecules that are packaged are likely to encode the RNA directed DNA polymerase activity and, because these RNAs possess long/full-length open reading frames for the reverse transcriptase and RNaseH (also for part of the integrase domains in genomic clones) of HERV-K, we propose that these transcripts are indeed strong candidates for encoding the enzyme activity found in these particles. Moreover, by using a modification of the polymerase chain reaction-based reverse transcriptase assay in which activated DNA is added during cDNA synthesis to suppress DNA polymerase-mediated RNA-directed DNA synthesis, we have found that the particle-associated enzyme behaves like a retroviral reverse transcriptase, further supporting the conclusion that retrovirus-like, perhaps HERV-K sequences, encode this enzyme activity.
Folate Deficiency Delays the Onset But Increases the Incidence of Leukemia in Friend Virus-Infected Mice
Authors: Koury Mark J. , Park Don J. , Martincic Danko , Horne Donald W. , Kravtsov Vladimir , Whitlock James A. , del Pilar Aguinaga Maria , Kopsombut Prapaporn 
Published: October 2019

AbstractClinical studies have indicated that folate deficiency may enhance the development of various malignancies. In animal studies that examined the effect of folate deficiency on malignancies, conflicting results have been reported. In some studies, folate deficiency increased the development and growth of malignant tumors; in others, it decreased the development and growth of malignancies. We examined the effect of transient folate deficiency on the development of leukemia in mice infected with the anemia-inducing strain of Friend leukemia virus. Friend virus disease can be considered as a model for human acute leukemias that are preceded by a preleukemic period. These include leukemias that develop in patients who received previous chemotherapy and/or radiation therapy, as well as patients with chronic granulocytic leukemia or myelodysplasia. Folate deficiency around the time of Friend virus-infection delayed the onset but increased the incidence of leukemia. The rates of rearrangement of the Spi-1 (PU.1 ) oncogene by provirus integration and alteration of the p53 tumor-suppressor gene were the same in leukemia cell lines derived from folate-deficient mice as they were in cell lines from control mice. These results indicate that folate deficiency did not exert its enhancement of leukemogenesis through changes in either Spi-1 or p53, even though these two genes have been found to be the most frequently altered ones in Friend virus-induced leukemias. Our results suggest that folate deficiency may enhance the development of acute leukemia in patients who are at high risk for this disease.
A Common Prothrombin Variant (20210 G to A) Increases the Risk of Myocardial Infarction in Young Women
Authors: Rosendaal F.R. , Siscovick D.S. , Schwartz S.M. , Psaty B.M. , Raghunathan T.E. , Vos H.L. 
Published: October 2019

Abstract
Using specimens from a population-based case control study among women ages 18 to 44 years in western Washington, we assessed the relationship between carriership of a genetic clotting factor II variant (20210 G→A) and myocardial infarction (MI). The factor II variant was previously shown to be present in 1% to 2% of the population, to increase the levels of factor II, and to be associated with venous thrombotic disease. Personal interviews and blood samples were obtained from 79 women with a first myocardial infarction and 381 control women identified through random-digit telephone dialing. Polymerase chain reaction (PCR) method was used to determine the factor II genotypes. The factor II 20210 G to A transition was present more often in women with MI (5.1%) than among control women (1.6%). The age-adjusted odds ratio for MI was 4.0 (95% confidence interval 1.1 to 15.1). The relative risk was high when another major cardiovascular risk factor was also present, such as smoking (odds ratio 43.3, 95% confidence interval 6.7 to 281), and the risk seemed limited to those with other risk factors. These results, in which the effect of major coronary risk factors is enhanced fourfold to sixfold by the prothrombin variant, are similar to those previously reported for another genetic clotting abnormality, factor V Leiden. We conclude that factor II 20210 G to A increases the risk of myocardial infarction in young women, especially in the women with other major risk factors for coronary heart disease.