bluuebunny/crossref_metadata_2025_split huggingface dataset:
The correlation of breakpoint cluster region rearrangement and p210 phl/abl expression with morphological analysis of Ph-negative chronic myeloid leukemia and other myeloproliferative diseases
Authors: Wiedemann LM , Karhi KK , Shivji MK , Rayter SI , Pegram SM , Dowden G , Bevan D , Will A , Galton DA , Chan LC 
Published: October 2019

Abstract
The chromosome 22 derivative, the Philadelphia (Ph) chromosome, results from a reciprocal translocation t(9;22) (q34;q11) and is associated with chronic myeloid leukemia (CML). The translocation can be identified at the DNA level in Ph-positive CML by using a probe to the breakpoint cluster region (bcr). In addition, as a result of this translocation an abl-related 210-kd protein with protein tyrosine kinase (PTK) activity is produced. We analyzed 28 cases of Ph-negative CML for rearrangement of the chromosome 22 sequences and found that eight of the 28 show rearrangement of the bcr. When 12 of the Ph- negative cases were independently reviewed, five were indistinguishable from Ph-positive CML on the basis of morphology, peripheral blood film and clinical details. These five also showed bcr rearrangement. The other seven were reclassified as six atypical CML (aCML) and one chronic myelomonocytic leukemia (CMML). None of these seven showed bcr rearrangement. In addition 11 cases of bcr- CML were assayed for abl- related PTK, and no detectable activity was present, whereas p210 phl/abl PTK was observed both in Ph-positive (three cases examined) and Ph-negative, bcr + (four cases examined) CML. Therefore, bcr + CML, whether or not the Ph chromosome is cytogenetically apparent, involves a similar molecular alteration and produces the 210-kd protein with enhanced PTK activity. Furthermore, these cases can be distinguished from Ph-negative bcr- CML by careful evaluation of clinical and hematologic data.
In vivo control of differentiation of myeloid leukemic cells by recombinant granulocyte-macrophage colony-stimulating factor and interleukin 3
Authors: Lotem J , Sachs L 
Published: October 2019

Abstract
The normal myeloid hematopoietic regulatory proteins include one class of proteins that induces viability and multiplication of normal myeloid precursor cells to form colonies (colony-stimulating factors [CSF] and interleukin 3 [IL-3], macrophage and granulocyte inducing proteins, type 7 [MGI-1]) and another class (called MGI-2) that induces differentiation of normal myeloid precursors without inducing cell multiplication. Different clones of myeloid leukemic cells can differ in their response to these regulatory proteins. One type of leukemic clone can be differentiated in vitro to mature cells by incubating with the growth-inducing proteins granulocyte-macrophage (GM) CSF or IL-3, and another type of clone can be differentiated in vitro to mature cells by the differentiation-inducing protein MGI-2. We have now studied the ability of different myeloid regulatory proteins to induce the in vivo differentiation of these different types of mouse myeloid leukemic clones in normal and cyclophosphamide-treated mice. The results show that in both types of mice (a) the in vitro GM-CSF- and IL- 3-sensitive leukemic cells were induced to differentiate to mature cells in vivo in mice injected with pure recombinant GM-CSF and IL-3 but not with G-CSF, M-CSF, or MGI-2; (b) the in vitro MGI-2-sensitive leukemic cells differentiated in vivo by injection of MGI-2 and also, presumably indirectly, by GM-CSF and IL-3 but not by M-CSF or G-CSF; (c) in vivo induced differentiation of the leukemic cells was associated with a 20- to 60-fold decrease in the number of blast cells; and (d) all the injected myeloid regulatory proteins stimulated the normal myelopoietic system. Different normal myeloid regulatory proteins can thus induce in vivo terminal differentiation of leukemic cells, and it is suggested that these proteins can have a therapeutic potential for myeloid leukemia in addition to their therapeutic potential in stimulating normal hematopoiesis.
Cytogenetic studies in patients with secondary leukemia/dysmyelopoietic syndrome after different treatment modalities
Authors: Whang-Peng J , Young RC , Lee EC , Longo DL , Schechter GP , DeVita VT Jr 
Published: October 2019

Abstract
Cytogenetic studies of 68 patients who developed secondary leukemia (SL)/dysmyelopoietic syndrome (DMS) after extensive chemotherapy and/or radiation therapy as well as patients who developed SL/DMS without such treatment showed that those patients who received radiation alone or with chemotherapy had more extensive numerical and structural abnormalities than those who received only chemotherapy. In terms of the specific chromosomal abnormalities, there are no differences between the various treatment groups. Hypodiploidy is the most common form of aneuploidy in these patients, with the most common numerical abnormality being the loss of chromosome 7. The most common structural abnormalities involved chromosomes 3 and 5. When compared with patients with de novo leukemia and DMS, the chromosomal abnormalities in these patients are more complex and extensive. Serial studies revealed that cytogenetic abnormalities do not precede the development of hematologic changes by significant time periods.
Cell cycle progression of B-chronic lymphocytic leukemia cells induced to differentiate by TPA
Authors: Carlsson M , Totterman TH , Matsson P , Nilsson K 
Published: October 2019

Abstract
The cell cycle transition and differentiation-associated surface antigen expression was studied in a clone of B cell chronic lymphocytic leukemia (B-CLL) with phenotypic properties similar to those of resting B lymphocytes. Differentiation was induced with TPA (12-O-tetradecanoyl- phorbol-13-acetate) and defined and quantitated by morphological and functional markers. Changes in the cell cycle position were determined by flow cytometry of acridine orange-stained cells. The uninduced B-CLL cells represented a homogeneous population with the same cell cycle position (GO) as resting normal peripheral blood lymphocytes. After five days of TPA stimulation, 56% of the B-CLL cells were found in G1A, 9% in G1B, and 3% in the S + G2/M phase, of which 2% was accounted to proliferating T cells. The cell cycle transition of the differentiating B-CLL cells was also examined using cell cycle-associated surface antigens as markers. HLA-DR and CD23 antigens were present already on noninduced cells. The former had a high constant expression, while the amount of CD23 increased upon induction. The 4F2 antigen was absent on noninduced cells but present on 86% of the induced cells. HH1 (CD37) was expressed by the majority of the cells before TPA treatment and decreased to almost undetectable levels within 24 hours. Two antigens related to late stages of the cell cycle, the interleukin 2 (IL 2; CD25) and the transferrin receptor, were present on about 20% of the induced cells. Experiments with enriched T cells showed that T but not B cells incorporated 3H-thymidine. Taken together these results and previous work on the induction of the protooncogene c-myc and c-fos suggest that this B-CLL clone represents GO cells that undergo differentiation without concomitant proliferation when exposed to TPA.
Genetically determined polymorphism of the circulating human breast cancer-associated DF3 antigen
Authors: Hayes DF , Sekine H , Marcus D , Alper CA , Kufe DW 
Published: October 2019

Abstract
The murine monoclonal antibody (MAb) DF3 was prepared against a human breast carcinoma. Previous studies have demonstrated that DF3 antigen levels are elevated in plasma of patients with breast cancer. Furthermore, MAb DF3 reacts with circulating glycoproteins of different molecular weights ranging from approximately 300 to 450 kd. The present study demonstrates that plasma DF3 antigen is comprised of at least four moieties with slow (S), intermediate (I), rapid (R) and very rapid (VR) electrophoretic mobilities. The electrophoretic mobility patterns for circulating DF3 antigen differ among individuals. Moreover, DF3 antigen is detectable in urine, and the electrophoretic mobility of the urinary moieties is similar, but not identical, to that in the plasma. Studies in family members suggest that the electrophoretic heterogeneity of plasma DF3 antigen is determined by codominant expression of multiple alleles at a single locus. This locus may code for the core protein of DF3 antigen. These findings thus identify a genetically determined polymorphism of a circulating tumor-associated glycoprotein.
The effect of the plasticizer di-2-ethylhexyl phthalate on the survival of stored RBCs
Authors: AuBuchon JP , Estep TN , Davey RJ 
Published: October 2019

Abstract
Recent in vitro studies have shown that di-2-ethylhexyl-phthalate (DEHP) inhibits the deterioration of RBCs during refrigerated storage in containers that use this compound as a plasticizer. The experiments described in this report were designed to assess whether this in vitro protective effect of DEHP would result in a prolonged in vivo survival of RBCs infused into normal human recipients. Whole blood collected from ten normal donors was stored for 35 days in citrate-phosphate- dextrose-adenine (CPDA-1) anticoagulant contained in polyvinylchloride (PVC) bags plasticized with DEHP or a trimellitate compound that is known to have low leachability. Aliquots of RBCs from each container were then labeled with chromium-51 and were reinfused into the original donors. For blood stored in DEHP-plasticized PVC bags, 24% more red cells survived in vivo 24 hours after reinfusion than was observed when the blood had been stored in trimellitate-plasticized bags (P less than .001). Whole blood stored in glass bottles showed a similar improvement in in vivo survival when DEHP was added in weekly increments to mimic the accumulation of this plasticizer seen during storage in plastic containers. Survival of packed red cells stored in the presence of DEHP increased by 14% compared with storage in trimellitate-plasticized bags (P less than .05). In agreement with previous studies, hemolysis and microvesicle formation were also reduced in the presence of DEHP. These results suggest that proposed new storage systems lacking DEHP should be carefully evaluated to determine whether adequate post-transfusion survival of RBCs may be achieved.
The molecular basis of alpha thalassemia in India. Its interaction with the sickle cell gene
Authors: Kulozik AE , Kar BC , Serjeant GR , Serjeant BE , Weatherall DJ 
Published: October 2019

Abstract
The alpha globin genotype of a total of 282 Indians from Orissa state has been analyzed. The overall alpha thalassemia gene frequency is 0.29, most frequently caused by the -alpha 3.7 and -alpha 4.2 deletions. In one family a novel -alpha 3.5 deletion removing the alpha 1 globin gene with some of its flanking sequences has been found, suggesting further sequence homology of the alpha globin gene cluster 3′ to the alpha 1 globin gene. Patients with sickle cell disease and alpha thalassemia had higher hemoglobin (Hb) levels, RBC counts, and Hb A2 levels, and lower reticulocyte counts, MCV, MCH, and Hb F levels than those with a normal alpha genotype. The frequency of splenomegaly was not influenced by the alpha globin genotype. A higher prevalence of alpha thalassemia was found in patients greater than or equal to 10 years of age than in the younger group, suggesting a possible advantageous effect of alpha thalassemia on the survival of patients with sickle cell disease.
Cytoplasmic expression of the CD3 antigen as a diagnostic marker for immature T-cell malignancies
Authors: van Dongen JJ , Krissansen GW , Wolvers-Tettero IL , Comans-Bitter WM , Adriaansen HJ , Hooijkaas H , van Wering ER , Terhorst C 
Published: October 2019

Abstract
The expression of cytoplasmic CD3 (CyCD3) was analyzed in 45 leukemias, five thymus cell samples, five peripheral blood (PB) samples, and ten cell lines. All T cell acute lymphoblastic leukemias (T-ALL) that did not express surface membrane CD3 (SmCD3) appeared to express CyCD3. Furthermore, the majority of SmCD3+ T-ALL also expressed CyCD3. Analogous results were obtained with thymus cell samples in that about 95% of the thymocytes expressed CyCD3 whereas 60% to 75% of the thymocytes also expressed SmCD3. In normal peripheral blood only prominent SmCD3 expression was found. These data indicate that immature T cells express CyCD3 only, that the combined expression of CyCD3 and SmCD3 is characteristic for intermediate differentiation stages, and that mature T cells express prominent SmCD3. All (precursor) B cell leukemias, acute myeloid leukemias, and non-T cell lines tested did not express CyCD3. On the basis of these data, we conclude that CyCD3 expression is restricted to the T cell lineage and can be used as a diagnostic marker for immature SmCD3- T cell malignancies. Therefore, we evaluated which fixative is optimal for CyCD3 staining, and we determined by immunofluorescence staining and Western blotting which anti-CD3 monoclonal antibody (MoAb) can be used for the detection of CyCD3. In our opinion, acid ethanol was the best fixative for the cytocentrifuge preparations. Furthermore, we demonstrated that CyCD3 can be easily detected by use of MoAbs raised against denaturated CD3 chains such as those of the SP series (SP-6, SP-10, SP-64, and SP-78). In addition we tested 22 anti-CD3 MoAbs of the Oxford CD3 panel that were raised against native SmCD3, and it appeared that only four (UCHT1, VIT-3b, G19–41 and SK7/Leu-4) of them were able to detect CyCD3. In Western blot analysis all four MoAbs recognized the CD3- epsilon chain only.
Heme arginate: effects on hemostasis
Authors: Volin L , Rasi V , Vahtera E , Tenhunen R 
Published: October 2019

Abstract
Hematin, the drug used for acute porphyric attacks, has been shown to cause disturbances in hemostasis, mainly because of its degradation products. Lately a new heme compound, heme arginate, has been developed for the treatment of porphyrias. In experimental animal studies as well as in clinical use it has proved to be well tolerated. To find out whether heme arginate has any effects on hemostasis we have studied a number of parameters of coagulation and fibrinolysis after a heme arginate infusion in seven healthy volunteers. All parameters studied remained practically unchanged except the coagulation factor X, which showed a transient, insignificant decrease during the maximal heme concentration. We believe that the lack of side effects is due to a better stability of heme arginate, the degradation rates being 1% for heme arginate and 61% for hematin in four hours. Our data favor the use of heme arginate in acute porphyrias as well as in other deficiency states of heme.
Canine model for gene therapy: inefficient gene expression in dogs reconstituted with autologous marrow infected with retroviral vectors
Authors: Stead RB , Kwok WW , Storb R , Miller AD 
Published: October 2019

Abstract
Successful retroviral gene transfer into murine hematopoietic stem cells indicates the potential for somatic gene therapy in the treatment of certain human hereditary diseases. We developed a canine model to test the applicability of these techniques to a preclinical model of human marrow transplantation. Previously we reported that canine CFU-GM could be infected with retroviral vectors carrying either the gene for a mutant dihydrofolate reductase (DHFR) or neomycin phosphotransferase (NEO). This study reports six lethally irradiated dogs transplanted with autologous marrow cocultivated with retroviral vector-producing cells. This procedure conferred drug resistance to 3% to 13% of the CFU- GM. Three dogs infected with either the NEO or DHFR virus engrafted, but we detected no drug-resistant CFU-GM. Three dogs were given marrow infected with a DHFR virus and received methotrexate (MTX) as in vivo selection; all three had evidence of engraftment. In the surviving dog, we detected 0.03% to 0.1% MTX-resistant CFU-GM at 3 to 5 weeks posttransplant during in vivo selection. These results indicate that we can reconstitute lethally irradiated dogs with autologous marrow exposed to retroviral vectors and suggest that gene transfer into hematopoietic cells is feasible on a large scale. However, the low- level transient gene expression indicates that considerable obstacles remain before human gene therapy can be considered.
High-efficiency gene transfer and expression in normal human hematopoietic cells with retrovirus vectors
Authors: Laneuville P , Chang W , Kamel-Reid S , Fauser AA , Dick JE 
Published: October 2019

Abstract
Retroviral vectors containing the selectable bacterial gene for G418 resistance (neo) were used to demonstrate gene transfer into primary human bone-marrow progenitor cells. To obtain populations of cells in which a high proportion of cells were expressing the neo gene, several important modifications were made to earlier procedures. Cells from normal donors were infected in vitro, were exposed to high concentrations of G418 for two days in liquid culture to enrich for cells expressing the neo gene, and were plated in semisolid medium. Gene transfer and expression were detected in colonies arising from progenitors of granulocyte-macrophage and erythroid lineages. Survival curves indicated that a high proportion of progenitor cells, approaching 100%, were G418 resistant. Furthermore, addition of growth factors contained in 5637-conditioned medium to the bone marrow improved the recovery of G418-resistant progenitors twofold to threefold. In addition to these biological measurements of gene expression in progenitor cells, significant levels of neo-specific RNA, similar to the levels of RNA expression in the virus-producing fibroblast cell line, were detected in the bone marrow cells after preselection. These results demonstrate that retrovirus vectors can be used successfully to transfer genes at high efficiency into progenitor cells in the human blood-forming system.
The beta subunit of the interleukin-2 receptor mediates interleukin-2 induction of anti-CD3 redirected cytotoxic capability in large granular lymphocytes
Authors: Colamonici OR , Quinones R , Rosolen A , Trepel JB , Sausville E , Phares JC , Gress R , Poplack D , Weber J , Schechter GP 
Published: October 2019

Abstract
The interleukin 2 (IL 2) receptor was studied in three cases of large granular lymphocyte (LGL) lymphocytosis. All cases were nonreactive with anti-Tac monoclonal antibody (MoAb; recognizing the p55 alpha subunit of the IL 2 receptor). Sodium dodecyl sulfate (SDS)/polyacrylamide gel electrophoretic analysis (PAGE) of cells to which radio-labeled rIL 2 had been chemically crosslinked revealed uniform expression of the p70/75 beta subunit of the IL 2 receptor in the absence of the alpha subunit. Stimulation of this receptor with 2 nmol/L rIL 2 for five days led to acquisition of anti-CD3 redirected cytotoxicity. This was accompanied by a fivefold to tenfold elevation in the activity of intracellular N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl esterase, an LGL granule marker enzyme. These effects of IL 2 did not require induction of the Tac peptide.
Soluble interleukin 2 receptors in sera of Japanese patients with adult T cell leukemia mark activity of disease
Authors: Yasuda N , Lai PK , Ip SH , Kung PC , Hinuma Y , Matsuoka M , Hattori T , Takatsuki K , Purtilo DT 
Published: October 2019

Abstract
Serum concentrations of soluble interleukin 2 receptors (sIL 2R) were measured by an enzyme-linked immunosorbent assay (ELISA) in 30 patients with adult T cell leukemia (ATL), in 9 patients with other hematopoietic malignancies, and in 17 asymptomatic individuals seropositive for human T cell leukemia virus type I (HTLV-I). Sixty HTLV-I seronegative, age-matched controls showed a normal range of form 63.2 to 480.8 U/mL. All asymptomatic carriers of HTLV-I had sIL 2R in their sera within the normal range. sIL 2R in sera was not related to the anti-HTLV-I antibody titer. Eleven patients with acute ATL, a clinical phenotype with median survival rate of 4.4 months, had markedly elevated sIL 2R (11,100 to 99,000 U/mL), but eight patients with smoldering ATL had low sIL 2R values (less than 480.8 U/mL) comparable to controls. Eleven patients with chronic ATL had intermediate elevated levels of sIL 2R (480.8 to 37,300.0 U/mL). Serum levels of sIL 2R correlated with the number of ATL cells (r = 0.812) and CD25-positive cells (r = 0.725) circulating in the peripheral blood. Longitudinal studies performed in four patients with ATL showed significant correlation between serum concentration of sIL 2R and activity of the malignancy. These findings suggest that the level of sIL 2R in serum indicated tumor load and, possibly, prognosis.
Platelet-activating factor primes neutrophil responses to agonists: role in promoting neutrophil-mediated endothelial damage
Authors: Vercellotti GM , Yin HQ , Gustafson KS , Nelson RD , Jacob HS 
Published: October 2019

Abstract
During inflammation polymorphonuclear cells (PMNs) are exposed to agonistic stimuli including activated complement, kallikrein, arachidonic acid metabolites, monokines, and platelet-activating factor (PAF). We report that PAF not only directly activates PMNs but in miniscule quantities (10(-12) mol/L) “primes” them as well, that is, permits PMNs to respond to subsequent stimuli that would be otherwise ineffectual. PAF priming of responses including superoxide generation, elastase release, and aggregation is time dependent and is maximal within five minutes. PAF need not be present during the subsequent exhibition of PMN agonists, but priming is inhibited by cold and is also inhibited by the PAF receptor antagonists BN 52021, L-652, and kadsurenone. An intact PAF molecule is required because lyso-PAF and methoxy-PAF do not prime PMN responses. PAF priming is associated with both enhanced expression of the adhesive glycoprotein identified by OKM- 1 antibody and an enhanced rise in intracellular calcium levels in response to the subsequent addition of agonists such as FMLP. PMNs primed with PAF and stimulated with either F-Met-Leu-Phe or phorbol esters are more effective in lysing and detaching cultured human endothelial cells--damage that can also be inhibited by the PAF antagonists. Because PAF is synthesized and exhibited on surfaces of endothelial cells perturbed by coagulation, we suggest that this lipid may potentiate otherwise trivial activators of marginated PMNs so that they become damaging to the PAF-synthesizing endothelium itself. If so, our studies suggest a possible therapeutic role for PAF inhibitors in excessive inflammatory states.
Erythrocyte glycolysis and its marked alterations by muscular exercise in type VII glycogenosis
Authors: Shimizu T , Kono N , Kiyokawa H , Yamada Y , Hara N , Mineo I , Kawachi M , Nakajima H , Wang YL , Tarui S 
Published: October 2019

Abstract
Levels of erythrocyte glycolytic intermediates after the phosphofructokinase (PFK) step, including 2,3-bisphosphoglycerate (2,3- DPG), were decreased at rest in patients from separate families with type VII glycogenosis. The concentration of 2,3-DPG was about half of the normal control value during a period of unrestricted daily activity but was further decreased to one third of normal after a one-day bed rest. Mild ergometric exercise rapidly increased the levels of fructose- 1,6-bisphosphate, dihydroxyacetone phosphate plus glyceraldehyde-3- phosphate, and 2,3-DPG in patients' circulating erythrocytes but did not in those of normal subjects. This indicated that a crossover point at the PFK step in glycolysis disappeared after physical exercise and, consequently, the 2,3-DPG concentration, which had decreased because of blockage of the PFK step, was restored considerably. This apparently exercise-related alteration in intermediary metabolism at the beginning of glycolysis was reproduced in vitro by incubating normal erythrocytes in the presence of inosine or ammonia, both of which have increased levels in circulating blood during and after exercise in this disorder. We conclude that physical activity in addition to a genetic deficiency in erythrocyte PFK affects glycolysis in erythrocytes in type VII glycogenosis and that myogenic factors released from exercising muscles may be responsible for this change.