bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Adrenalin (Epinephrin) Test as Applied to Hematologic Disorders
Authors: CHATTERJEA JYOTI B. , DAMESHEK WILLIAM , STEFANINI MARIO 
Published: October 2019

Abstract
1.The epinephrin test was performed in 12 normal subjects and 63 patients with various hematologic disorders to evaluate its role in the diagnosis of hypersplenic syndromes and aplastic anemias. Attention was directed solely to the early phases of the reaction, that is to the pre-adrenocortical stimulatory effect, which has been claimed to reflect the functional activity of the spleen and bone marrow.
2. The epinephrin response in normal subjects was characterized by transitory pancytosis. Leukocytosis and thrombocytosis were conspicuous features whereas erythrocytosis and reticulocytosis were not regularly seen. Leukocytosis was due to an increase of mature forms of neutrophils, lymphocytes, monocytes and eosinophils. The Arneth count did not show any significant variation after epinephrin. There was no correlation in different cases between the degree of hemopoietic response and the degree of rise of blood pressure, although in each case the time of maximum cellular response usually ran parallel to the time of maximum rise of blood pressure.
3. The response in splenectomized individuals was essentially similar to or slightly greater than that seen in normal subjects. In splenomegalic conditions there was no correlation between the degree of splenic contraction and the degree of hemopoietic response.
4. Results of epinephrin injection into the splenic artery showed that the increase of cellular elements was in general pancellular in type, and not confined to any particular cell deficient in the peripheral blood; it was obviously independent of the nature and degree of peripheral cytopenia.
5. The splenic contraction following epinephrin may possibly be due to a marked constriction of the splenic artery and in its intrasplenic branches with the resultant passive deflation of the organ.
6. In each case there was a close correlation between the epinephrin response and the functional activity of the bone marrow.
7. The epinephrin test per se is not diagnostic of any clinical condition. In the hypersplenic syndromes interpretation of negative tests may actually be misleading. At most, the test provides indirect corroborative evidence regarding the functional status of the blood forming tissues and to some extent of the "reservoir" of blood cells present not only in the bone marrow, but in various tissues and organs throughout the body. The exact degree of splenic participation in the epinephrin response is not known, but our studies indicate that it is minimal.
Some Aspects of the Metabolism of Antimegaloblastic Substances in Man
Authors: GIRDWOOD RONALD H. 
Published: October 2019

Abstract
1. When the sera of pernicious anemia patients or controls were heated at 100 C. for 30 minutes, they developed the ability to support the growth of L. leichmannii by virtue of some substance other than vitamin B12. It seemed likely, however, that following the administration of the vitamin, such heating also liberated free B12 in the serum from a combined form.
2. The L. leichmannii assay did not appear to be satisfactory for showing possible difference in the levels of vitamin B12 in the urines or sera of pernicious anemia patients and controls.
3. Parenterally administered vitamin B12 did not cause any measurable rise in the serum level of folic acid or citrovorum factor in pernicious anemia patients or controls.
4. The synthetic folic acid conjugates pteroyldiglutamic acid and pteroyltriglutamic acid appeared in the sera and urines of pernicious anemia patients as pteroylglutamic acid or some related substance with folic acid activity for S. faecalis.
5. Orally administered citrovorum factor appeared to be largely converted by the gastric juice to folic acid if free hydrochloric acid was present. When administered parenterally, however, citrovorum factor was excreted in the urine largely unchanged.
Hemolytic Disease of the Newborn Due to Anti-A
Authors: CRAWFORD HAL , CUTBUSH MARIE , MOLLISON P. L. 
Published: October 2019

Abstract
Eleven cases of hemolytic disease of the newborn are described in which the only blood group antibody in the mother's serum, incompatible with the infant's cells, was anti-A. The direct antiglobulin (Coombs) test on the infant's red cells was weakly positive in 7 cases and negative in 4 cases. In every case the mother's serum displayed immune characteristics, in particular the ability to lyse A cells.
Osmotic fragility was increased in 10 out of 11 cases. This finding is contrasted with those in a series of cases of hemolytic disease of the newborn due to anti-Rh.
Production of Nucleophagocytosis by Rabbit Antileukocytic Serum
Authors: ZIMMERMAN HYMAN J. , WALSH JOHN R. , HELLER PAUL 
Published: October 2019

Abstract
Dried buffy coat layer of the blood from a patient with granulocytic leukemia was injected into a rabbit. Serum from this rabbit, when mixed with the buffy coat layer of the blood from the same patient, resulted in the production of nucleophagocytosis. The serum of the rabbit also showed the ability to produce marked conglutination and destruction of the neutrophilic polymorphonuclear leukocytes.
Bone Marrow Changes in Patients with Chronic Leukemia Treated by Splenic X-irradiation
Authors: GUNZ F. W. 
Published: October 2019

Abstract
1. Following therapeutic x-irradiation of the spleen in patients suffering from chronic myeloid leukemia alterations in the composition of the bone marrow have been noted in a high proportion of cases. These consisted of a decrease in the number of immature myeloid cells or an increase in that of the immature erythroid cells or both.
2. Eighty minutes after local irradiation of the leukemic spleen with therapeutic doses of x-rays there was found a diminution in the number of mitoses among myeloid cells in the bone marrow.
Acquired Hemolytic Anemia
Authors: DACIE J. V. 
Published: October 2019

Abstract
Eighteen patients with acquired hemolytic anemia were studied with particular reference to the direct and indirect antiglobulin (Coombs) reaction. The abnormal antibodies present were of the warm type in eleven patients and of the cold type in seven patients.
With warm antibodies a well marked zone of inhibition was usually observed when sensitized red cells were suspended in high concentrations of antiglobulin serum, and the reaction was readily inhibited by the previous addition of very small amounts of human γ globulin to the antiglobulin serum. Acidification of the serum to pH 6.5 caused in most cases a moderate increase in the intensity of sensitization in the indirect antiglobulin test. Previous heating of the serum at 56 C. for 30 minutes did not prevent sensitization.
With cold antibodies, on the other hand, no inhibition of the antiglobulin reaction took place in the highest concentration of antiglobulin serum used, and the reaction was not inhibited by the previous addition of small amounts of human γ globulin to the antiglobulin serum. Acidification of the serum to pH 6.5 caused, in most cases, a considerable increase in the intensity of the reaction. Previous heating of the serum at 56 C. for 30 minutes completely prevented sensitization.
The separation of the abnormal antibodies of acquired hemolytic anemia into warm and cold types cuts across clinical classification. Warm antibodies were found in the majority of idiopathic cases; cold antibodies were present in some idiopathic cases and in hemolytic anemia following virus pneumonia. Splenectomy was followed by sustained remissions in some of the idiopathic cases of both the warm antibody and cold antibody varieties.
Secondary Hemochromatosis
Authors: AUFDERHEIDE ARTHUR C. , HORNS HOWARD L. , GOLDISH ROBERT J. 
Published: October 2019

Abstract
1. Secondary hemochromatosis has been sharply separated from simple hemosiderosis by defining the former as "a condition acquired as a consequence of anemia, blood transfusions, or both, and characterized by increased hepatic and total body iron content and unequivocal portal cirrhosis of the liver."
2. Previously reported cases are critically reviewed in the light of this definition.
3. Two new cases of secondary (exogenous) hemochromatosis are reported.
4. Anemia is postulated as the basic etiologic factor in secondary hemochromatosis by causing increased iron absorption; iron introduced in the form of blood transfusions probably only accelerates a process already in progress.
5. Prolonged futile oral iron therapy may be harmful.
6. A plea is made for a strict concept of secondary hemochromatosis as well as for thorough documentation of future reports.
Deletion of chromosome 20q in myelodysplasia can occur in a multipotent precursor of both myeloid cells and B cells
Authors: White NJ , Nacheva E , Asimakopoulos FA , Bloxham D , Paul B , Green AR 
Published: October 2019

Abstract
Deletions of the long arm of chromosome 20 are associated with several myeloid malignancies and, in particular, with myeloproliferative disorders and myelodysplastic syndromes (MDS). Together with deletions of chromosome 5q and chromosome 7q, chromosome 20q deletions have previously been thought to be restricted to myeloid cells in patients with MDS. We report here that deletion of chromosome 20q in MDS can arise in a multipotent precursor of both myeloid cells and B cells. Clonal Epstein-Barr virus (EBV)-transformed cell lines, both with and without a 20q deletion, have been isolated from a patient with MDS. Moreover, these cell lines have been shown to provide a useful physical mapping tool and have been used to confirm the interstitial nature of the 20q deletion. Microsatellite polymerase chain reaction (PCR) and PCR analysis of PGK gene methylation have been used to study highly purified populations of peripheral blood cells. The 20q deletion was detectable by microsatellite PCR in peripheral blood granulocytes and monocytes but not in B cells or T cells. Clonality of the different lineages followed the same pattern as the 20q deletion. This represents the first report in which a chromosome abnormality associated with MDS has been immortalized in an EBV-transformed lymphoblastoid cell line. Furthermore, our data show that patients with apparent myeloid restriction of a chromosome deletion may in fact have a disease arising in a multipotent cell with both myeloid and lymphoid potential.
Detection of 14q32 translocations in B-cell malignancies by in situ hybridization with yeast artificial chromosome clones containing the human IgH gene locus
Authors: Taniwaki M , Matsuda F , Jauch A , Nishida K , Takashima T , Tagawa S , Sugiyama H , Misawa S , Abe T , Kashima K 
Published: October 2019

Abstract
Partner sites of 14q32 translocations found in B-cell malignancies were detected by fluorescence in situ hybridization (FISH) using yeast artificial chromosome (YAC) clones, Y20 and Y6, containing the human Ig heavy chain (IgH) gene locus. Y20 spans a 160-kb upstream and 40-kb downstream region of the JH segments on chromosome band 14q32.33. Y6 is 300-kb upstream of Y20, and spans a further 320-kb telomeric region. The human DNA sequences amplified by Alu polymerase chain reaction of the YAC clones were used as probes for FISH to study six patients with non-Hodgkin's lymphoma (NHL), one patient with acute lymphoblastic leukemia, and one cell line FR4 established from a plasmacytoma. Three telomeric YAC clones each specific for 3q, 8q, and 18q were also used to further characterize 14q32 translocations. The IgH YACs were successfully applied to detect cytogenetically invisible subtelomeric translocation of the IgH gene locus to each partner site in t(14;18), t(8;14), and t(14;19), and to identify t(3;14) (q27;q32.33) in three patients with 14q32 translocation of unknown origin. Furthermore, complex translocations involving more than three chromosomes were detected in an NHL patient with t(8;14), and t(3;12), and in the FR4 with der(14)t(8;14), der(8)dic(1;8), and del(1)(q21). The technique would be a useful tool in elucidating the mechanisms of a 14q32 translocation in B-cell malignancies.
Serum procollagen type III is an early and sensitive marker for veno- occlusive disease of the liver in children undergoing bone marrow transplantation
Authors: Heikinheimo M , Halila R , Fasth A 
Published: October 2019

Abstract
Veno-occlusive disease of the liver (VOD) is a life-threatening complication occurring in patients undergoing bone marrow transplantation (BMT). Although clinical signs and laboratory parameters such as elevation of serum bilirubin often suggest this condition, it would be useful to identify early biochemical markers for VOD. Fibrous alterations in the hepatic venules and small lobular veins occur during development of VOD; these changes are accompanied by the deposition of types I and III collagen in the liver tissue. Since the N- terminal propeptide of type III procollagen (PIIINP) is a sensitive marker of liver and lung fibrosis, we undertook a study to evaluate the usefulness of measurements of serum PIIINP in children with VOD. Seven of the 28 children who underwent BMT, both allogenic and autologous, developed VOD. All seven had an increase of more than 100 ng/mL in the serum PIIINP level, whereas only one of the remaining 21 children not affected by VOD had an increment of PIIINP more than 100 ng/mL (P = .0001). The levels of serum PIIINP were higher in the VOD group during the follow-up period of up to 91 days after BMT. The elevation of PIIINP also occurred at a stage of the disease usually preceding any other laboratory or clinical signs of VOD. Serum concentration of PIIINP thus seems to be of value as an early marker for VOD in children undergoing BMT.
Genetic marking shows that Ph+ cells present in autologous transplants of chronic myelogenous leukemia (CML) contribute to relapse after autologous bone marrow in CML
Authors: Deisseroth AB , Zu Z , Claxton D , Hanania EG , Fu S , Ellerson D , Goldberg L , Thomas M , Janicek K , Anderson WF 
Published: October 2019

Abstract
Relapse after autologous bone marrow transplantation for chronic myelogenous leukemia (CML) can be due either to the persistence of leukemia cells in systemic tissues following preparative therapy, or due to the persistence of leukemia cells in the autologous marrow used to restore marrow function after intensive therapy. To help distinguish between these two possible causes of relapse, we used safety-modified retroviruses, which contain the bacterial resistance gene NEO, to mark autologous marrow cells that had been collected from patients early in the phase of hematopoietic recovery after in vivo chemotherapy. The cells were then subjected to ex vivo CD34 selection following collection and 30% of the bone marrow were exposed to a safety-modified virus. This marrow was infused after delivery of systemic therapy, which consisted of total body irradiation (1,020 cGy), cyclophosphamide (120 mg/kg), and VP-16 (750 mg/m2). RT PCR assays specific for the bacterial NEO mRNA, which was coded for by the virus, and the bcr-abl mRNA showed that in two evaluable CML patients transplanted with marked cells, sufficient numbers of leukemia cells remained in the infused marrow to contribute to systemic relapse. In addition, both normal and leukemic cells positive for the retroviral transgenome persisted in the systemic circulation of the patients for at least 280 days posttransplant showing that the infused marrow was responsible for the return of hematopoiesis following the preparative therapy. This observation shows that it is possible to use a replication-incompetent safety-modified retrovirus in order to introduce DNA sequences into the hematopoietic cells of patients undergoing autologous bone marrow transplantation. Moreover, this data suggested that additional fractionation procedures will be necessary to reduce the probability of relapse after bone marrow transplantation in at least the advanced stages of the disease in CML patients undergoing autologous bone marrow transplantation procedures.
Platelet and Megakaryocyte Dense Granules Contain Glycoproteins Ib and IIb-IIIa
Authors: Youssefian Tayebeh , Massé Jean-Marc , Rendu Francine , Guichard Josette , Cramer Elisabeth M. 
Published: October 2019

Abstract
Platelets contain two main types of secretory organelles, the dense granules and the α-granules. P-selectin, a specific receptor for leukocytes that is present in the α-granule membrane, has also been demonstrated to be associated with the dense granule limiting membrane, showing that a relationship exists between these two types of secretory granules. We have previously shown that the plasma membrane receptors glycoproteins (Gp) IIb-IIIa and Ib are also present in the α-granule membrane. To document further the composition of the dense granule membrane, we have used immunoelectron microscopy in the present work to determine if the dense granule membrane also contains these glycoproteins. First, the cytochemical method of Richards and Da Prada (J Histochem Cytochem 25:1322, 1977), which specifically enhances dense body electron density, was combined with immunogold-labeled anti–Gp IIb-IIIa or anti–Gp Ib antibody. A consistent and reproducible labeling for Gp IIb-IIIa, but less for Gp Ib, was found in the membrane of platelet dense granules. Subsequently, double immunogold labeling was performed on frozen thin sections of resting platelets using antibodies directed against the dense body components granulophysin or P-selectin, followed by anti–Gp IIb-IIIa or anti–Gp Ib. Consistent labeling for Gp IIb-IIIa and weaker labeling for Gp Ib were detected in dense bodies. The possibility that the granulophysin-positive structures could be lysosomes was excluded by the presence of P-selectin. Immunogold labeling of isolated dense granule fractions confirmed these results. Identical findings were made on human cultured megakaryocytes using double immunolabeling. In conclusion, this study demonstrates the presence of Gp IIb-IIIa and Gp Ib on the dense granule membrane. This observation provides additionnal evidence of similarities between the α-granule and dense granule membranes and raises the possibility of a dual mechanism responsible for the formation of dense granules similar to that of α-granules, ie, endogenous synthesis as well as endocytosis from the plasma membrane.
Metabolism of Thrombopoietin (TPO) In Vivo: Determination of the Binding Dynamics for TPO in Mice
Authors: Stefanich Eric , Senn Tauri , Widmer Ramon , Fratino Christine , Keller Gilbert-André , Fielder Paul J. 
Published: October 2019

AbstractPrevious in vivo studies have established that plasma thrombopoietin (TPO) levels are regulated by binding to c-Mpl on platelets and that, in vitro, platelets bind and degrade TPO. To determine if the in vivo metabolism of TPO was specific and saturable, we injected normal CD-1 mice IV with trace amounts of 125I-rmTPO with or without a saturating concentration of rmTPO. The amount of radioactivity present in the spleen, blood cell fraction, platelet fraction, tibia/fibula, and femur was significantly greater in the mice receiving 125I-rmTPO alone. Conversely, the amount of radioactivity present in the plasma was significantly greater in the mice receiving both 125I-rmTPO and rmTPO, thus suggesting the uptake of rmTPO by the spleen, platelets, and bone marrow in vivo was saturable. Platelet and spleen homogenates from animals receiving 125I-rmTPO alone showed a degradation pattern of 125I-rmTPO similar to that observed in vitro using mouse platelet rich plasma. To determine the in vivo binding dynamics for rmTPO, mice were injected with 125I-rmTPO alone or with increasing concentrations of rmTPO; spleen and blood cell-associated radioactivity was determined at 2 hours postinjection. A 4-parameter curve fit of the data indicated that the “in vivo binding affinity” for rmTPO was approximately 6.4 μg/kg. These data indicate that after a dose of approximately 6.4 μg/kg, 50% of all c-Mpl receptors will be saturated with rmTPO. Electron microscopy indicated that radioactivity was present bound to and within megakaryocytes and platelets in both sternum and spleen and platelets in circulation. Together these data demonstrate that in vivo, 125I-rmTPO is mainly metabolized by platelets and to a small extent by cells of the megakaryocyte lineage, via a specific and saturable mechanism.
Detection of Trisomy 12 and Rb-Deletion in CD34+ Cells of Patients With B-Cell Chronic Lymphocytic Leukemia
Authors: Gahn B. , Schäfer C. , Neef J. , Troff C. , Feuring-Buske M. , Hiddemann W. , Wörmann B. 
Published: October 2019

Abstract
B-cell chronic lymphocytic leukemia (B-CLL) is a slowly progressive disease characterized by the clonal expansion of CD5+/CD23+ B lymphocytes. The malignant transformation is assumed to occur at the level of mature B lymphocytes. We asked whether CD34+ progenitor cells are involved in the malignant process in B-CLL. Furthermore, we investigated the possibility of aberrant CD34 expression by the malignant B-cell clone. Bone marrow and peripheral blood samples from 75 patients with B-CLL were tested for the presence of trisomy 12 and deletion of the retinoblastoma gene (Rb) by fluorescence in situ hybridization. CD34+ subpopulations were isolated by fluorescence-activated cell sorting and analyzed for the presence of the informative genetic marker. Bone marrow and peripheral blood samples of 10 B-CLL patients were analyzed for coexpression of CD34/CD5/CD20. Trisomy 12 was detected in 15 of 75 (20%) and Rb-deletion was detected in 6 of 30 patients (20%). In 7 patients with trisomy 12, hematopoietic progenitor cells were sorted, with the sort purity being between 85% and 99.8%. The genetic marker was detected in the CD34+/CD38+ cells as well as in the CD34+/38− subsets in 3 patients. Progenitor cells were also sorted in 2 patients with Rb-deletion. In 1 patient, Rb-deletion was present in 10% of CD34+/38+ cells. In the other patient, Rb-deletion was neither detected in the CD34+/38+ nor in the CD34+/CD38− subsets. In all 10 patients investigated for coexpression of CD34/CD5/CD20, we could not find a subpopulation coexpressing these markers. We conclude that trisomy 12 and Rb-deletion are present in a considerable subset of patients with B-CLL. In part of these patients, the genetic marker was detected at the level of CD34+ stem cells. CD34 expression is not related to an aberrant phenotype of the malignant B-cell clone. These results suggest that the malignant transformation in B-CLL may involve early hematopoietic stem cells and place a note of caution on future strategies using autologous stem cell transplantation.