bluuebunny/crossref_metadata_2025_split huggingface dataset:
Erythrocyte Glycolysis in Patients with Malignant Neoplasms and Other Chronic Diseases
Authors: ULTMANN JOHN E. , HYMAN GEORGE A. , HARVEY JANE L. , DENTE ANTHONY R. 
Published: October 2019

Abstract
The rate of erythrocyte glycolysis of blood from normal volunteers was 12.0 mg.% glucose consumed/hr with 5 x 106 Rbc/cu.mm. The mean glycolytic rate of blood from tumor patients (14.5 mg.% glucose consumed/hr. with 5 x 106 Rbc/cu.mm.) and from patients with other chronic diseases (17.4 mg.% glucose consumed/hr. with 5 x 106 Rbc/cu.mm.) was found to be greater to a statistically significant degree than that of normals in the absence of reticulocytosis. This suggests that the red cell population of the patients with neoplastic and chronic diseases may be younger than that of normal subjects and that only some of the young cells have demonstrable reticulum.
Alkali Resistant Type of Hemoglobin in Women with Molar Pregnancy
Authors: BROMBERG YEHUDA M. , SALZBERGER MACCABI , ABRAHAMOV ABRAHAM 
Published: October 2019

Abstract
In 4 patients with molar pregnancy the fetal Hb blood concentration was found to be significantly higher than that found in control groups of normal early pregnancy and in imminent and incomplete abortions. Following the molar abortion the fetal Hb decreased gradually and reached normal vlaues within three to five months.
It is assumed that the increased production of fetal Hb in these patients is due to the reactivation of fetal erythropoietic activity by either excessive amounts of chorionic gonadotropin, stress due to a rapidly growing tumor or to some other unknown factors.
Clot Firmness
Authors: WEINER MURRAY , WEISBERG LOUIS G. 
Published: October 2019

Abstract
1. The relative firmness of clots in different systems is not necessarily directly correlated with the speed of clot formation.
2. Thrombin will hasten the development of full clot firmness, but will not significantly alter the degree of clot firmness of citrated plasma specimens, although the firmness of "purified" fibrinogen preparations clotted by thrombin is increased with increasing thrombin concentration.
3. Citrate and/or calcium concentration influence clot firmness.
4. Fibrinogen preparations develop greater firmness on clotting with thrombin than do citrated plasma preparations.
5. A platelet factor influences clot firmness of recalcified plasma, but not of thrombin-activated or coagulase-activated plasma.
6. Clot firmness of recalcified citrated plasma is reduced by storage. This reduction in firmness is more rapid if the specimen is deep frozen as compared to unfrozen aliquots at 6 C.
The Diego System—Steps in the Investigation of a New Blood Group System. Further Studies
Authors: LAYRISSE MIGUEL , ARENDS TULIO 
Published: October 2019

Abstract
The distribution of the Diego factor has been studied in various Mongoloid, Caucasian and Negroid populations. In six South American Indian stocks, one Canadian Indian stock and two groups of Asiatic Mongoloids it was present in high incidence. In Caucasians tested, negative results were found. In two groups of Venezuelan Negroes with probable Indian admixture the factor was also present.
The Diego antigen was inherited in single dose (heterozygous) in 41 families studied and could be followed through several generations with no sex-linkage.
The first samples of anti-Diego serum reacted only in the indirect anti-globulin test to a titer between 1:256 and 1:512. The enzymes papain and trypsin gave no advantage. It is more active at room temperature (25 C. and 37 C.) than at cold temperature (4 C. and 18 C.). The most suitable pH range is from 5.0 to 8.0.
The Diego factor can be considered as part of a new blood group system (the Diego system) which could be classified as the tenth firmly established blood system.
Viability and Distribution of Leukocytes Following Cross-Circulation Experiments Between Leukemic and Normal or Irradiated Rats
Authors: HOLLINGSWORTH J. W. , FINCH STUART C. , CHALTAS MARY 
Published: October 2019

Abstract
1. Recipient rats were observed following periods of circulatory mixing with normal or leukemic donor animals.
2. The normal rat tail appears to store leukocytes in its vascular channels, as evidenced by a progressively falling leukocyte count from a tail incision as the tail is "milked."
3. Comparison of irradiated rat tail and arterial blood leukocyte counts during and after cross-circulation revealed the tail values to be consistently higher than the simultaneous arterial levels. This observation excludes a major removal and destructive mechanism by some organ such as the lung as a major cause of the rapid decrease in arterial blood leukocyte levels noted in irradiated rats after the cross-circulation procedure.
4. Tail blood leukocyte counts of irradiated, cross-transfused rats remained higher than those of control irradiated rats for at least three days.
5. After cross-circulation with leukemic donor rats, leukemic cells were identified in the tail blood of normal rats for at least three days.
6. Prolonged observations revealed that 2 irradiated Sprague-Dawley strain recipients of leukemic cells from Sherman strain leukemic donors survived the severe radiation damage but developed leukemia. This observation suggests that transfused leukemic white blood cells protect against radiation damage.
7. Five normal Sherman strain rats developed leukemia after cross-circulation with leukemic Sherman donors. This incidence (50 per cent) of transmission to adult animals is much higher than has been reported by conventional methods of transfer.
8. The observations reported support the concept of viability of leukocytes transfused in rats by this method, and suggest that at least one site of noncirculating transfused leukocytes is within sluggish vascular channels.
Recent Advances in the Knowledge of Total Red Cell Volume, Production and Destruction
Authors: BERLIN NATHANIEL I. , LAWRENCE JOHN H. , ELMLINGER PAUL J. 
Published: October 2019

Abstract
Since anemia or polycythemia can result only from a change in rate of formation of red cells or a change in the life span of the red cells, a determination of the total red cell volume, Fe59 studies to estimate the rate and site of production of red cells, and C14-labeled glycine or Fe59 studies to determine the life span of red cells permit a description of the pathogenesis of any alterations in the erythropoietic state. This has been of great value in clinical hematology from the stand-point of understanding the basic nature of the various diseases and, in particular, the selection of patients with unusual anemias possibly related to hypersplenism who might benefit from splenectomy. Splenic erythropoiesis can be easily differentiated from splenic red cell destruction.
Since two of these methods—the determination of the blood volume and the Fe59 studies—are now possible in general commumnity hospitals and since modifications of the Fe59 method permit the determination of the life span of the red cell, adequate evaluation of the erythropoietic state is now possible in general hospitals.
Chronic Myelosis Following the Use of Thorotrast
Authors: NETOUSŠEK M. , BORESŠ J. , DVORŘAÁK K. 
Published: October 2019

Abstract
Following hepatolienography which was carried out in a woman aged 52 in 1931, for a tumor of the right kidney which was removed at operation, chronic myelosis developed in 1954. This was remarkable for the absence of splenomegaly, a relatively mild course and a paradoxic reaction to x-ray irradiation of the spleen, when instead of the expected decrease there was a doubling in the number of leukocytes. A causal relationship of myeloid leukemia to the thorotrast administered 23 years previously cannot be excluded.
Morphology and Cytochemistry of the Granule-Vacuole Body of Leukemic Cells
Authors: ACKERMAN G. ADOLPH 
Published: October 2019

Abstract
A rare and hitherto undescribed vacuole-like structure, the granule-vacuole body, found in the cytoplasm of certain cells of granulocytic and monocytic leukemia has been described morphologically and cytochemically. This inclusion has been compared with the cytoplasmic granules and Auer bodies occurring in leukemic cells.
Some Observations on the New Human Blood Factor Dia
Authors: LEVINE PHILIP , ROBINSON ELIZABETH A. 
Published: October 2019

Abstract
Evidence is presented that the Diego antigen is independent of 15 other low-incidence blood factors and is not genetically related to 4 high-incidence factors. In all cases of low incidence antigens, similar comprehensive studies with a panel of essential test cells are required to exclude possible serologic or genetic relationship to other blood factors.
Microdrepanocytic Disease in Greece
Authors: CHOREMIS C. , ZANNOS L. 
Published: October 2019

Abstract
Among the 57 patients with the hematologic picture of sickle cell anemia, examination of the parents revealed that 44 were suffering from the microdrepanocytic disease and 13 from sickle cell anemia. The much more frequent occurrence of microdrepanocytic disease was expected since the microcytemia trait appears to be much more frequent in Greece than the sickle cell trait.
Most patients with sickle cell anemia originated from areas where the trait has been found in a very high frequency. In contrast, the geographical distribution of patients with microdrepanocytic disease is much wider.
A Comparative Evaluation of the Sensitivity of the L.E. Cell Test Performed Simultaneously by Different Methods
Authors: DUBOIS EDMUND L. , FREEMAN VIVIAN 
Published: October 2019

Abstract
1) A group of at least three types of L.E. cell tests should be performed in order to adequately screen strongly suspected cases of SLE. This battery consists of the sieved two hour clot, the Snapper-Nathan ring method and the Zinkham-Conley rotary glass bead technic. Utilizing these three methods in studying a group of 47 proven cases of SLE both treated and untreated, 63 batteries were performed. In 42 of these batteries there was at least one positive test. In 5 batteries only the rotary method was positive, in 4 the clotted method and in 2 the ring method. The largest numbers of L.E. cells and hematoxylin bodies were found by the rotary method. If only one test is to be performed this latter technic is the method of choice.
2) The use of excessive amounts of heparin over 0.75 mg./10 cc. of blood resulted in a depression of the L.E. phenomenon. The technic of adding "small amounts" of heparin to blood or "heparinizing a syringe" to draw specimens for L.E. studies is to be avoided.
3) The explanation for the augmentation of the L.E. phenomenon by clotting or rotation with glass beads seemed to be the production of leukocyte trauma by either method. This explained the poor results obtained when the clotted blood specimen is broken up with wooden applicator sticks rather than macerated through a fine sieve. The clotting mechanism itself probably has little to do with the increased numbers of L.E. cells.
4) With adequate treatment the L.E. cells disappeared in many patients. Forty patients with positive L.E. cell tests treated two months or more had a simultaneous battery performed on them as described above. All the tests were negative in eighteen patients, seven patients had fewer than 5 L.E. cells per 500 leukocytes and fifteen patients had more than that number.
An Explanation of the Discrepancy between Direct and Indirect Platelet Counts
Authors: FITCH HARRY J. 
Published: October 2019

Abstract
The indirect platelet count is higher than the direct count because the red cells, which are used as a point of reference in the indirect method, are not randomly distributed beneath the coverslip. The red cells are concentrated at the edge of the coverslip so that the true ratio of red cells to platelets cannot be accurately established. Indirect platelet counts based on the ratio in the central areas of the coverslip are too high.
In Vitro Incorporation of C14—DL-Leucine into Normal and Leukemic White Cells
Authors: BAKER W. H. , ZAMECNIK P. C. , STEPHENSON M. L. 
Published: October 2019

Abstract
Normal white blood cells and cells from patients with leukemia are able to incorporate C14-DL-leucine into proteins in vitro. Cells from individuals with chronic myelogenous leukemia were able to incorporate significantly greater amounts of the amino acid, and they were able to maintain this incorporation for a longer period of time than the control cells.
Both types of cells had the same in vitro survival time of four days, following storage at 3 C.
The incorporation was partially decreased in the presence of dinitrophenol, as well as in an atmosphere of nitrogen.
AML Bone Marrow Microenvironment Impairs Dendritic Cell Maturation and Antigen Presentation
Authors: Wagner Bettina , Rebmann Vera , May Tobias , Duehrsen Ulrich , Göthert Joachim Rudolf , Horn Peter A , Opalka Bertram 
Published: October 2019

Abstract
Abstract 1491
In hematopoietic malignancies the bone marrow (BM) stroma has been reported to be in dynamic contact with neoplastic cells in a way that malignant cells are supported by various mechanisms including blocking of apoptosis, induction of resistance to therapeutic drugs, and suppression of potential anti-tumorigenic immunity. Here, we studied the immunomodulatory properties of cellular factors derived from BM stroma cells and their influence on maturation of dendritic cells (DC). To circumvent the inter-individual heterogeneity often observed with primary stroma, novel BM stroma cell lines derived from BM stroma of two AML patients (before and after chemotherapy) and one healthy donor were established. The surface marker profile of the cell lines is in accordance with an MSC pattern. Furthermore, differential expression patterns were observed for molecules such as HLA-G, MICA, MICB, ULBP2, ILT-4 and intracellular IL-10 known to be implicated in the regulatory network of the immune system. To monitor DC maturation in presence and absence of BM stroma cell fragments, obtained by ultra-sonication, surface markers including CD40, CD80, CD83, CD86, and CD274 were investigated before maturation on monocytes, three days after BM stroma fragment addition and on terminal differentiated DCs. In addition, the expression of classical (HLA class I, HLA-DR) and non-classical immunoregulatory molecules (HLA-G, HLA-E) were determined. For terminal differentiation of DCs on day seven, the medium was exchanged and 1000 U/ml IL-4, 1000 U/ml GM-CSF, 2.0 U/ml IL-1β and 0.2 U/ml TNFα were added to complete the maturation process by giving a “danger” signal. A markedly decreased expression of differentiation (up to −36%) and antigen presentation molecules (up to −68%) of DCs cultured in presence of AML BM stroma cell fragments was observed compared to DC maturation without AML BM stroma cell fragments. In particular, the decreased HLA-DR expression could not be restored by the addition of the pro-inflammatory cytokines at day seven. In comparison, the addition of BM stroma cell fragments derived from AML stroma had a higher impact on the decrease of HLA-DR expression than BM stroma cell fragments of the healthy donor cells. This indicates that molecules derived from the AML stroma cells are implicated in mechanisms impairing DC maturation and function, which may promote immune escape during leukemia development.

Disclosures:
May: InSCREENeX GmbH: Employment, Equity Ownership, Patents & Royalties.
T(8;9)(p22;p24)/PCM1-JAK2 Activates SOCS2 and SOCS3 Via STAT5
Authors: Ehrentraut Stefan , Nagel Stefan , Scherr Michaela , Schneider Bjoern , Quentmeier Hilmar , Geffers Robert , Prochorec-Sobieszek Monika , Ketterling Rhett P , Knudson Ryan A , Feldman Andrew L. , Kadin Marshall , Drexler Hans G. , MacLeod Roderick AF 
Published: October 2019

Abstract
Abstract 1567
Fusions of the tyrosine kinase domain of JAK2 with multiple partners occur in leukemia/lymphoma where they are believed to promote JAK2-oligomerization and autonomous signalling although the underlying mechanisms remain unclear. Affected entities are candidates for therapy with JAK2 signalling inhibitors. Among 200 peripheral T-cell lymphomas surveyed, we identified only two with JAK2 amplification and none with JAK2 translocations, confirming their rarity in T-cell neoplasias. Here we describe the genomic, transcriptional and signalling characteristics of PCM1-JAK2 formed by t(8;9)(p22;p24) in cell lines established at indolent and aggressive phases of a cutaneous T-cell lymphoma. To investigate signalling, PCM1-JAK2 was subjected to lentiviral knockdown which inhibited 7 genes most upregulated in t(8;9) cells, notably SOCS2/3. SOCS3, but not SOCS2, was also upregulated in a chronic eosinophilic leukemia bearing PCM1-JAK2. Conversely, expression of GATA3, a key T-cell developmental gene silenced in aggressive phase cells, was partially restored by PCM1-JAK2 knockdown. Activation of the tumor suppressor SOCS3 by PCM1-JAK2 may follow structural alteration of JAK2 affecting the ternary complex it forms with SOCS3 and receptor proteins. Treatment with JAK2 inhibitor (TG101348) to which MAC-1/2A/2B cells were conspicuously sensitive mimicked knockdown results, highlighting JAK2 as the active moiety. PCM1-JAK2 signalling required pSTAT5 as reported for JAK2V617F or ETV6/TEL-JAK2, thus extending the paradigm of STAT5 activation by JAK2 alterations in hematopoietic malignancies. MAC-1/2A/2B are the first JAK2– translocation cell line models. Our data support further investigation of SOCS2/3 as signalling effectors, prognostic indicators and potential therapeutic targets in cancers with JAK2 rearrangements.

Disclosures:
No relevant conflicts of interest to declare.
Alisertib Added to Rituximab and Vincristine Is Synthetic Lethal and Curative of Double Hit Diffuse Large B-Cell Lymphoma in Mice
Authors: Mahadevan Daruka 
Published: October 2019

Abstract 159
About one-third of diffuse large B-cell lymphoma (DLBCL) patients develop relapsed/refractory disease, a major cause of morbidity and mortality. Of DLBCL, 5% are double-hit lymphomas (DHLs) with translocations of MYC and BCL2 characterized by poor outcomes with R-CHOP. Auroras (A and B) are a family of mitotic oncogenic serine/threonine kinases required for high fidelity regulation of the mitotic phase of the cell cycle. Aberrant over-expression of Auroras leads to genetic instability, polyploidy and resistance to microtubule targeted agents. Previously we showed Aurora inhibitor (MLN8237, alisertib) [M] plus vincristine [V] plus rituximab [R] is synthetic lethal and a potential curative therapy in a mantle cell lymphoma model (Granta-519) with several cell cycle genetic defects [t (11;14)], ATM (haploinsufficient), p16/p14 (Del)] but p53 (WT). We evaluated ABC-DLBCL cell lines TMD-8 and U-2932 where the BCR/NF-kB pathway is constitutively active. In TMD-8, CD79B is mutated and in U-2932, Bcl2 [3q27] and Bcl6 [18q21] are amplified, p53 (mutated) and c-Myc over-expressed [DHL]. Triple therapy with MVR abolished proliferation, disrupted cell cycle processes and induced apoptosis compared to single agent and doublet treatments. A Mouse xenograft model of U-2932 showed modest activity for M (30 mg kg, PO, QD, 3 weeks), V (0.375 mg/kg, IV, Q1Wx3) and MV with tumor growth inhibition (TGI) of ∼10% (p=0.01) respectively. However, R (10 mg/kg, IV, Q1Wx3) alone induced ∼ 50% TGI (p=0.01) due to effective targeting of Bcl2. Doublets MR and VR led to tumor regression (TR), but relapse soon after stopping therapy. In contrast, MVR demonstrated TR with no relapses >40 days after stopping therapy. All treatments were well tolerated (no weight loss) and Kaplan-Meier analysis showed that mice treated with MR, VR and MVR had a statistically significant improvement in overall survival compared to control, M, V and MV (p<0.0001). Moreover, with MVR, OS was 100% (Figure 1). Gene expression profiling, RT-PCR, IHC and Western blotting of harvested tumors at the end of treatment (3 weeks) has been interrogated to ascertain the mechanistic role of Aurora inhibition when added to R [R Vs MR] and VR [VR Vs MVR]. Thus, addition of R to MV represents a novel therapeutic strategy that is currently under clinical trial evaluation in aggressive B-NHL including double hit lymphomas sponsored by Millennium Pharmaceuticals (C14011).
Figure 1: Kaplan-Meier Survival by Treatment: MLN8237 (M), Rituximab (R), Vincristine (V), MR, MV, VR, MVR in a U-2932 ABC-DLBCL SCID Mouse Xenograft Model Figure 1:. Kaplan-Meier Survival by Treatment: MLN8237 (M), Rituximab (R), Vincristine (V), MR, MV, VR, MVR in a U-2932 ABC-DLBCL SCID Mouse Xenograft Model

Disclosures:
No relevant conflicts of interest to declare.
Monocytosis As Prognostic Factor in Aggressive, Non-Primary Cutaneous Peripheral T-Cell Lymphoma: A Study of 251 Cases
Authors: Beltran Brady E , Cotacallapa Erick , Castillo Jorge J 
Published: October 2019

Abstract
Abstract 1608

Background:
Peripheral T-cell lymphoma (PTCL) is a heterogeneous family of entities with a worse prognosis, stage by stage, than their B-cell counterparts. We have previously reported that an absolute lymphocyte count (ALC) <1000/uL is associated with a worse prognosis in Peruvian patients with PTCL (Castillo et al. 2010). The goal of this study is to investigate the prognostic value of absolute monocyte count (AMC) in the survival of patients with PTCL.

Methods:
A total of 251 cases of aggressive, non-primary cutaneous PTCL diagnosed at our institution between January 1997 and January 2012 were reviewed, reevaluated according to their morphological, immunological and clinical characteristics, and reclassified according to the 2008 WHO classification of lymphoid neoplasms. Characteristics will be presented descriptively. Kaplan-Meier method was used to estimate overall survival (OS) curves, which were compared using the log-rank test. The multivariate analysis was performed using the Cox proportional-hazard regression test.

Results:
According to the new WHO classification of lymphoid neoplasms, 104 cases (41%) were classified as adult T-cell leukemia/lymphoma (ATLL), 103 cases (41%) as PTCL, unspecified (PTCLU), 27 cases (11%) as analplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL), 11 cases (4%) as extranodal NK/T-cell lymphoma (NKTCL), nasal type, 4 cases (2%) as angioimmunoblastic lymphoma (AIL), and 2 cases (1%) were diagnosed with ALK+ ALCL. The median age at diagnosis was 57 years (range 14–92 years); 47% of patients were >60 years. The male-to-female ratio was 1:1. ECOG performance status >1 was seen in 51%, LDH was elevated in 67%, advanced stage was seen in 73%, and >1 extranodal sites were seen in 22% of the patients. Bone marrow involvement was reported in 30% and B symptoms in 64% of patients. An International Prognostic Index (IPI) score 3–5 was seen in 55%, and a Prognostic Index for PTCLU (PIT) score of 2–4 in 63%. The median overall survival (OS) for the whole group was 10 months. The IPI score, the PIT score, ALC <1000/uL and AMC >800/uL (Figure) showed statistical significance in the univariate survival analysis (p<0.001, p<0.001, p=0.001 and p=0.001, respectively). In the multivariate analysis, PIT score and AMC >800/uL showed statistical significance (p=0.006, p=0.046, respectively).

Conclusions:
Monocytosis, defined as AMC >800/uL, and the PIT score were independent prognostic factors for OS in patients with aggressive, non-primary cutaneous PTCL.

Disclosures:
No relevant conflicts of interest to declare.