bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Hydroxyurea on Elevated Pulmonary Artery Pressures in Children with Sickle Cell Disease
Authors: Pashankar Farzana , Manwani Deepa , Lee Margaret , Green Nancy S. 
Published: October 2019

Abstract
Abstract 4841

Background:
Pulmonary hypertension (PHT) is a significant complication of sickle cell disease. Studies in children report a 16–30% prevalence of elevated pulmonary artery pressures, as estimated by measurement of tricuspid regurgitant jet velocity (TRV) on echocardiography. The pathogenesis of elevated pulmonary artery pressures is multifactorial, with hemolysis induced endothelial dysfunction playing a major role. More recent studies highlight the role of inflammation in the pathogenesis. Hydroxyurea is a well established treatment for sickle cell disease. It acts primarily by induction of fetal hemoglobin, thereby reducing hemolysis, with possible additional effects on vascular and endothelial function. The aim of this study was to determine if early detection and treatment with hydroxyurea will decrease elevated pulmonary artery pressures in children with sickle cell disease.

Methods:
The study was conducted at 3 centers. Children with Hb SS and Hb Sb0 thalassemia between the ages of 5–21 years, with a screening echocardiogram showing a TRV ≥ 2.5 m/sec were identified. An echocardiogram was repeated to confirm elevated TRV. Subjects with persistent elevation of TRV ≥ 2.5 m/sec on repeat echocardiogram, were consented and started on hydroxyurea at 20 mg/kg/d with escalation to a maximum tolerated dose or a total daily dose of 30 mg/kg/d. Laboratory data and echocardiograms were repeated at 6 and 12 months to measure effect of hydroxyurea on TRV. Additionally blood and urine samples were also collected pre treatment, at 6 and 12 months post treatment for biomarker analysis, which will be performed later. Baseline and 6 month laboratory and echocardiogram data were compared using paired t test.

Results:
Twelve patients were enrolled. Mean age was 12.25 years (range 6–19 years) with a M:F ratio of 2:1. Average follow up is 11 months. Patients tolerated hydroxyurea well, and in 90% of patients the dose was escalated to 30 mg/kg/d. 1 patient achieved MTD at 20 mg/kg/d. Two patients went off study at 4 and 5 months respectively.
As shown in Table 1, six months after starting hydroxyurea there was a significant increase in mean oxygen saturation, hemoglobin, mean corpuscular volume and fetal hemoglobin. There was a significant decrease in mean reticulocyte count, LDH and white blood cell count. There was no significant change in TRV six months after treatment with hydroxyurea.

Conclusion:
Hydroxyurea significantly decreased measures of hemolysis in children with sickle cell disease. Six months after treatment with hydroxyurea, there was no significant change in estimated pulmonary artery pressures measured on echocardiography. The study is ongoing to see if hydroxyurea affects pulmonary artery pressures with a longer duration of treatment.

Disclosures:
No relevant conflicts of interest to declare.
Cytotoxic Effects of Curcumin At Various Concentrations and Role of Curcumin on Lipid Peroxidation and Activities of Antioxidant Enzymes of the Rat Peripheral Blood Lymphocytes
Authors: Desai Nisarg , Finosh G T , Panicker N G , Ramachandran R , Varghese Alex 
Published: October 2019

Abstract
Abstract 4933

Background:
Curcumin (diferuloylmethane) is an active ingredient of turmeric and has been suggested to have antiproliferative, pro-oxidant and cytotoxic effects (Das R, Apoptosis 2008). Curcumin has also been shown to have antioxidant effects (Rastogi M, Free Radic Res 2008). Our aim was to assess the cytotoxic, pro-oxidant and antioxidant effects of curcumin on rat peripheral blood lymphocytes (RPL) in culture.

Methods:
Different concentrations of curcumin (0.325 μM, 0.65 μM, 1.3 μM) were analyzed for cytotoxic effects on rat peripheral lymphocytes. The cytotoxic effect of curcumin was assessed by measuring cell viability using Trypan blue exclusion assay. DNA damage by curcumin (at 0.65 μM) was confirmed by the COMET assay. The effect of curcumin (at 0.65 μM) on oxidation was assessed by measuring the activity of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and lipid peroxidation (LP) by spectrophotometry. RPLs were cultured for 72 hr in vitro. The pro-oxidant effect of curcumin was determined by comparing LP induction in control (PBS treated) vs curcumin treated RPLs. Parameters were measured at 0, 24 and 48 hrs of curcumin exposure. Reactive oxygen species (ROS) generated by treatment with FeCl3 (10 mM) and H2O2 (5 mM) (Fe/H) were used to demonstrate the ROS scavenging effect of curcumin. Lymphocyte cultures were treated with either Fe/H alone or in combination with Curcumin. Oxidation levels were assessed as described above at 0, 24, 48 hrs following exposure.

Results:
Cytotoxic effects were seen at different curcumin concentrations (Table 1). Viability of RPLs were 42% at 0.64 μM concentration vs 72% at 0.325 μM. 30% decrease in cell viability of RPLs were seen at 0.65 μM concentration compared to 0.325 μM. Hence, 0.65 μM concentration was used for further experiments. There was a significant increase in DNA damage in curcumin exposed lymphocytes at 48hr (table 2). There was a significant increase in LP in curcumin exposed RPLs compared to control lymphocytes. By contrast, there was no significant change in LP values in presence of Fe/H at all time points compared to control. There was a significant decrease in LP when RPL cultures were incubated with curcumin for 48 hr compared to 0 hr of incubation. There was significant increase in activities of SOD, catalase and GPx in presence of curcumin and Fe/H (table 3 and 4).

Conclusions:
Dose dependent cytotoxic and DNA damage effects of curcumin are seen in RPLs. Treatment with curcumin alone increases lipid peroxidation, However in the presence of oxidative stress, curcumin may act as an antioxidant (ROS scavenging effect) by stimulating activities of antioxidant enzyme and preventing lipid peroxidation.

Disclosures:
No relevant conflicts of interest to declare.
Gemcitabine Is An Active Agent In Acquired Human Immunodeficency HIV Related Lymphomas
Authors: Jajeh Ahmad 
Published: October 2019

Abstract
Abstract 4951
Gemcitabine is a cell cycle phase specific cytotoxic agent. It's phosphorylated products inhibit ribonucleotide reductase an enzyme responsible for DNA synthesis. It also competes with the incorporation of deoxycytosine triphospate (dCTP) into the DNA strands. After Gemcitabine is incorporated into the DNA the growing DNA strands will stop. Gemcitabine has proven to be an active cytotoxic agent in the treatment of lymphomas, either as a single agent or in combination with platinum and dexamethsone. Gemcitabine efficacy has not been investigated in the treatment of HIV patients with Lymphomas. The purpose of this abstract is to show our experience with this agent in HIV related lymphomas. This summarize the experience with three patients. First patient is 42 years old white male with diffuse large B cell type Non-Hodgkin's Lymphoma involving the right psoas muscle and invading the pelvic nerve roarts causing intractable pain that has not been resonsive to CHOP (four cycles), the third patient is a 55 years old hispanic female with stage IV Hodgkin's Lymphoma (mixed cellularity) that has failed ABVD × 6 cycles and progressed in less than two months from completion of treatment. This patient presented with B symptoms and cachexia at relapse. The third patient is 50 years old black male with stage III Immunoblastic B Cell Lymphoma who failed EPOCH. All patients were on HAART medication and viral load were undetectable in two of these patient (2,3). The first patient received Gemcitabine alone. With two weekly doses of 1000mg/M2 the pain resolved and he stopped narcotics and was refered to other institution for autologus bone marrow transplant. The second patient received two cycles of Gemcitabine, Cisplatin and Decadron within one dose the B symptoms and the sever bony pain have disappeared completely. The third patient completed six cycles of treatment; each cycle is of twenty eight days duration; Gemcitabine 1000mg/M2 given IV on week one and two(day1) and Cisplatinum 80/M2 mg given IV on day one with decadron 40 mg po with each chemotherapy treatment. This patient has been in complete remisson and is alive after three years. In conlusion: Gemcitabine is an active agent that can be used safely in HIV/AIDS patients with lymphomas with good results.

Disclosures:
No relevant conflicts of interest to declare.
Ethnic Differences in the Incidence of Leukemia
Authors: MACMAHON BRIAN , KOLLER ERNEST K. 
Published: October 2019

Abstract
A series of 1636 patients with leukemia, representing the white residents of Brooklyn diagnosed in the period 1943-52, is compared with selected census data for the population. After standardization for age differences in the two populations, the incidences of leukemia in the native-born and foreign-born populations of the borough are 45.3 and 61.0 per million per annum, respectively. The data suggest that a high incidence of leukemia in the Russian-born population accounts for the higher rate in the foreign-born group.
Using affiliation of cemetery of burial as an index of religion, a series of 1368 deaths from leukemia is compared with a systematic one in 200 samples of all deaths in the same area. Leukemia is recorded as cause of death twice as frequently among Jews, as among others. This relationship is seen in both native-born and foreign-born groups, in males and females, at all ages and in all the common pathologic varieties of leukemia. No difference in leukemia incidence is seen between predominantly Catholic and predominantly Protestant groups.
Evidence from United States vital statistics is used to show that the commonly observed difference between whites and Negroes imi leukemia death rates is closely associated with social differences between the two groups. Little or no difference in leukemia death rate exists between these two groups in Brooklyn, when allowance is made for the apparently high rate in the white Jewish population.
Immunologic Features of Erythrocyte Sensitization
Authors: VAUGHAN JOHN H. , WALLER MARION V. 
Published: October 2019

Abstract
It has been shown that red cells sensitized with anti-Rh antibody are agglutinated by anti-γ-globulin sera, regardless of the "order" of Rh antibody activity. Red cells sensitized with anti-Lewis antibody, on the other hand, are agglutinated by anti-sera to non-γ-globulin substances. Of six other blood group antibodies studied, five provided γ-globulin red cell coating materials and one, an anti-Kidd, a non-γ-globulin material. The participation of complement, or complement-like, substances was shown in some instances.
Various pitfalls in the technics employed in absorbing Coombs sera so as to render them immunochemically specific are discussed.
Studies of Plasma Erythropoietic Factor in Anemic Human Patients
Authors: PRENTICE T. C. , MIRAND E. A. 
Published: October 2019

Abstract
Nine patients with anemia of varied origin have been studied. The relationship between erythron response and the content of erythropoietic factor in the plasma has been observed in these patients. Wide discrepancies between these variables were seen to exist. Further investigation of this aspect of the problem is needed.
The Effect of Irradiation on the Plasma Erythropoietic Stimulating Factor
Authors: LINMAN JAMES W. , BETHELL FRANK H. , TASCOTT HELENA K. 
Published: October 2019

Abstract
1) Protein-free plasma extracts from rabbits made anemic by the administration of phenylhydrazine immediately following total body x-irradiation are capable of stimulating erythropoiesis in the normal rat as demonstrated by erythrocytosis, reticulocytosis, and increased marrow erythropoietic activity.
2) Plasma extracts from rabbits made anemic by total body x-irradiation alone contain an erythropoietic stimulating factor.
3) These data would indicate that the stimulating factor is not produced by hemopoietic or other radiosensitive tissue and its formation is not dependent upon a regenerative marrow.
Combinations of Hemoglobin G, Hemoglobin S and Thalassemia Occurring in One Family
Authors: SCHWARTZ H. C. , SPAET T. H. , ZUELZER W. W. , NEEL J. V. , ROBINSON A. R. , KAUFMAN S. F. 
Published: October 2019

Abstract
1. A Caucasian family is described in which, on the basis of clinical, hematologic and biochemical findings, it is postulated that the genes responsible for hemoglobins S and G and for the thalassemia defect are present.
2. On the basis of the study of this family, it is concluded that:
a. The genes responsible for hemoglobins G and S cannot be alleles.
b. The genes responsible for hemoglobin G and thalassemia cannot be alleles.
c. The absence of hemoglobin A in individuals heterozygous for two "hemoglobin genes" does not provide critical evidence concerning the allelic relations of such genes.
d. In this family, heterozygosity for the gene responsible for hemoglobin G results in an asymptomatic trait condition, in which some 40% of the hemoglobin is abnormal. When the gene responsible for G is combined with a hemoglobin S gene or a thalassemia gene, or both, the presence of hemoglobin G does not significantly alter the expression of these genes on their combinations. For example, an individual of the phenotype SG, whose hemoglobin contained no demonstrable A, was clinically a sickle cell trait, in that he showed no evidence of physiologic handicap.
e. Individuals heterozygous for both the G and thalassemia genes may show on electrophoresis only hemoglobin G. This illustrates the unreliability in some cases of diagnosing genotype on the basis of electrophoretic findings.
f. On the basis of these findings, hemoglobin G should probably be regarded as a normal variant of hemoglobin rather than as an abnormal type of hemoglobin.
The Bone Marrow in Pregnancy and the Puerperium
Authors: LOWENSTEIN LOUIS , BRAMLAGE CATHERINA A. , LALONDE MADELEINE 
Published: October 2019

Abstract
1. The morphologic findings of sternal bone marrow aspirates obtained from thirty healthy women during each of the three trimesters of normal pregnancy, from ten healthy women on each of the first eight puerperal days and from thirty healthy women at six weeks postpartum were compared with the findings of marrow aspirates obtained from 30 non-pregnant normal women of childbearing age.
2. Statistical analysis of the results of differential counts of these aspirates confirmed the impressions obtained from examination of the bone marrow aspirates and their differential smears.
3. Significant quantitative changes occurred in the cellular components of the bone marrow during normal pregnancy, which were maximal in the third trimester. There was a significant increase of normoblastic erythropoiesis and, to a lesser extent, of granulopoiesis during pregnancy, which was associated with an increase of immature cells (shift to the left) of both erythropoietic and of granulopoietic tissues.
4. During the first eight puerperal days the increase of erythropoiesis and of granulopoiesis diminished but did not return to normal non-pregnant normal values. At six weeks postpartum both erythropoiesis and granulopoiesis were more active than in the early puerperium and were significantly increased as compared with the findings in the marrows of normal non-pregnant women.
5. There was some increase of plasma cells and of reticulum cells in the bone marrow during pregnancy and the early puerperium.
6. No megaloblastic or macrogranulocytic changes were found in the two hundred bone marrow aspirates taken from pregnant and puerperal women or in the thirty aspirates taken from non-pregnant normal women.
7. The marrow findings of three women in the early puerperium were reported separately from the above groups. An occasional intermediate macrometamyelocyte was found in the marrows of these patients and in one a few nucleated red cells showed the earliest transitional changes toward megaloblasts. It is believed that these changes represent the earliest morphologic evidence of a deficiency of one or more of the growth factors necessary for normal hemopoiesis.
Electron Microscopic Investigations on Sections from Lymph Nodes and Bone Marrow in Malignant Blood Diseases
Authors: BRAUNSTEINER H. , FELLINGER K. , PAKESCH F. 
Published: October 2019

Abstract
Thin sections from nodes and bone marrow of patients with malignant blood diseases have been investigated with the electron microscope. "Granular bodies" and "vesicular bodies" are found in the cytoplasm of Sternberg cells, and "vesicular bodies" in leukemic cells. An organized ergastoplasm is only to be seen in malignant plasmocytes from myeloma, in isolated plasmocytoma and in lympoid cells from macroglobulinemia. Its development and its relation to protein production and secretion are demonstrated. The submicroscopic organization of cells is described and commented upon.
The Submicroscopic Morphology of Gaucher Cells
Authors: DEMARSH QUIN B. , KAUTZ JEAN 
Published: October 2019

Abstract
The large cells characteristically found in the bone marrow and other organs in Gaucher’s disease have been reinvestigated with the electron microscope, as well as with phase contrast and polarizing microscopes and by standard staining methods. The cytoplasm was filled with a number of dense elongate or crescent shaped bodies. Each of these fibrils was in turn seen with the electron microscope to be bounded by a single dense limiting membrane, and to contain a homogeneous appearing matrix in which were embedded numerous tubular-appearing subunits. These tubular elements measured approximately 130 Å in diameter, and were of very great length. It is suggested that these submicroscopic tubular structures could represent the molecular kerasin or lipoprotein units known from biochemical and histochemical evidence to be present in Gaucher cells.
Some details about the appearance of the ectoplasm in spread cells, and the area near the cell border in cells fixed in situ, are reported. Electron micrographs revealed a complex cell border which was extended into many small pseudopodia and ridge-like projections. Numerous microvesicles about 600 Å in diameter were found in the area near the cell membrane. This is taken as possible evidence of transport of some substance across an active cell membrane. An attempt is made to correlate these morphologic findings with the clinical and biochemical findings of ourselves and others on Gaucher’s disease.
Extrusion of Nuclei of Transfused Avian Erythrocytes in the Mammalian Spleen
Authors: VORHAUS ELAINE F. , TURNER JOSEPH C. 
Published: October 2019

Abstract
1. Duck erythrocytes have been injected intravenously into rabbits, mice, and guinea pigs and at intervals thereafter microscopic examination of certain organs has been made.
2. In the guinea pig spleen extrusion of the nuclei of the duck cells has been observed with great regularity.
3. Attempts to reproduce this phenomenon in vitro have failed.
4. It is suggested that nuclear extrusion of this kind is conditioned by (a) the species into which the cells are transfused and (b) an intact spleen.
Studies on the Serum Haptoglobin Level in Hemoglobinemia and Its Influence on Renal Excretion of Hemoglobin
Authors: LAURELL CARL-BERTIL , NYMAN MARGARETA 
Published: October 2019

Abstract
A short survey is given of the literature on haptoglobin, the hemoglobin-binding serum protein, its properties and biologic variations. The principles of an electrophoretic method for quantitative determination of the serum haptoglobin are described.
Electrophoretic studies showed that haptoglobin has a high affinity for hemoglobin at physiologic pH and that every haptoglobin molecule can bind at least 2 hemoglobin molecules.
Observations made following the intravenous injection of hemoglobin showed:
that hemoglobin administered intravenously is bound by the haptoglobin;
that free hemoglobin is not demonstrable until more hemoglobin has been injected than can be bound by the haptoglobin;
that the complex hemoglobin-haptoglobin is eliminated from the plasma after intravascular hemolysis or intravenous administration of hemoglobin without being excreted in the urine;
that the hemoglobin-haptoglobin complex is removed from the plasma at a constant rate during the major part of the elimination period;
that the haptoglobin level will fall to nil within 24 hours, if the amount of hemoglobin injected is sufficient to bind all the haptoglobin available. During the following days the rate of formation of haptoglobin can be studied.
From the data available it can be concluded that hemoglobinuria cannot appear until the amount of hemoglobin administered intravenously or the amount liberated intravascularly exceeds the binding power of the haptoglobin and the reabsorption capacity of the tubules. The variation observed by earlier authors in the so-called renal threshold for hemoglobin on intravenous injection of hemoglobin can be explained among other things by the variation in the haptoglobin content in one and the same subject, i.e., if the haptoglobin level is low, the threshold value will also be low, and vice versa.
The Combined Use of Typhoid Vaccine and P32 Labeling to Assess Myelopoiesis
Authors: PERRY S. , WEINSTEIN I. M. , CRADDOCK C. G. , LAWRENCE J. S. , PAUL GLORIA , BAKER MARY H. , GREEN JEANINE , CIANKO GEORGE 
Published: October 2019

Abstract
1. The intravenous administration of killed typhoid organisms to dogs results in the development of a severe leukopenia which is followed by a marked leukocytosis.
2. The myelopoietic response of dogs to typhoid injections is quite similar to the response following leukopheresis.
3. Leukocyte DNA-P32 studies indicate that in response to typhoid stimulation, as with leukopheresis, the bone marrow constitutes the main reservoir for granulocytes contributing to peripheral blood leukocytosis.
4. Evidence is presented that, under these experimental conditions, leukocytes, after once having left the vascular tree, are unable to re-enter in any significant numbers.
5. The use of typhoid vaccine to stimulate leukocytosis combined with the use of P32 to measure the fate of cells released from the marrow is presented as an accurate and reasonably simple method to measure certain aspects of myelopoiesis in the experimental animal.
Studies on Erythrocytes in Cases with Past History of Favism and Drug-Induced Acute Hemolytic Anemia
Authors: SZEINBERG A. , SHEBA C. , HIRSHORN NINA , BODONYI EVA 
Published: October 2019

Abstract
Studies have been carried out on erythrocytes of cases with past history of acute hemolysis due to Favism, sulpha drugs or PAS.
No indication was found of abnormal osmotic or mechanical fragility, electrophoretic mobility of hemoglobin or its amino acid content. Similarly no abnormal glycolytic or catalase activities were detected.
Glutathione (GSH) deficiency of erythrocytes was discovered in all cases studied. Similarly, glutathione (GSH) deficiency was a frequent finding among the relatives of affected cases.
No such glutathione deficiency could be established in the cases of thalassemia major so far studied, though both patient-groups without any exception belong to the same ethnographic denomination (non-Ashkenazic).
This investigation was aided by a grant from the Israel Research Council.