bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute mixed lineage leukemia: clinicopathologic correlations and prognostic significance
Authors: Mirro J , Zipf TF , Pui CH , Kitchingman G , Williams D , Melvin S , Murphy SB , Stass S 
Published: October 2019

Abstract
The frequency and clinical significance of acute leukemia displaying both lymphoid and myeloid characteristics was determined in 123 consecutive children using a panel of lineage-associated markers. The leukemic blasts from 18 of 95 children (19%) with the diagnosis of acute lymphoblastic leukemia (ALL) by standard diagnostic criteria expressed myeloid-associated cell surface antigens. Despite immunological evidence of lymphoid differentiation (17 CALLA + and one T cell-associated antigen +) and findings of immunoglobulin gene rearrangement, blasts from these patients reacted with one to five monoclonal antibodies identifying myeloid-associated cell surface antigens (My-1, MCS.2, Mo1, SJ-D1, or 5F1). Dual staining with microsphere-conjugated antibodies and analysis by flow cytometry confirmed that some blasts were simultaneously expressing lymphoid- and myeloid-associated antigens. Conversely, blasts from seven of 28 patients (25%) with acute nonlymphocytic leukemia (ANLL), diagnosed by otherwise standard morphological and cytochemical criteria, expressed lymphoid-associated surface antigens. Dual staining of individual blasts demonstrated simultaneous expression of myeloperoxidase (MPO) (including Auer rods) in association with either T-11, CALLA, or terminal deoxynucleotidyl transferase. Blasts from one patient with ANLL demonstrated T cell receptor gene rearrangement, while blasts from another patient demonstrated characteristics associated with T (T-11), B (CALLA and heavy-chain immunoglobulin gene rearrangement), and myeloid (MPO) lineage. There were no consistent cytogenetic abnormalities, and no patient demonstrated independent leukemic clones. Each patient with typical ALL, except for myeloid-associated antigens, achieved complete remission with conventional induction therapy for ALL. By contrast, three of the seven children with ANLL whose blasts expressed the T-11 surface antigen failed ANLL induction therapy. These three patients subsequently achieved remission with ALL therapy.
The genotype and phenotype of T cell and non-T, non-B acute lymphoblastic leukemia
Authors: Aisenberg AC , Wilkes BM 
Published: October 2019

Abstract
We used Southern blot analysis to investigate the T cell receptor and immunoglobulin (Ig) genes in tumor DNA derived from 13 patients with acute lymphoblastic leukemia (ALL). Rearrangement of both alleles of the T cell receptor beta chain gene was demonstrated in the three individuals with T cell ALL, while the Ig genes remained in germline configuration. In contrast, in nine of ten patients with non-T, non-B ALL (seven common ALL antigen [CALLA]-positive), Ig genes were rearranged while the T cell receptor genes were intact: the noteworthy exception was a CALLA-positive individual in whom one allele of the T cell receptor was rearranged and in whom a minor rearranged Ig band was detected as well. This exception indicates that CALLA-positive non-T, non-B ALL includes proliferations that have undergone an initial genetic step toward T cell differentiation. With probes now available for both the Ig and T cell receptor genes, analysis of genomic tumor DNA is useful in all variants of ALL.
Hepatitis B virus DNA is enriched in polymorphonuclear leukocytes
Authors: Hoar DI , Bowen T , Matheson D , Poon MC 
Published: October 2019

Abstract
DNA hybridization and cell separation techniques were used to determine which blood components contained hepatitis B viral DNA sequences. Free monomer-length hepatitis B virus was found in large amounts in the polymorphonuclear leukocyte cell fraction in two of five HBsAG-positive patients. In these two patients, viral DNA sequences were not detected in the plasma or platelet fraction, whereas the mononuclear cell DNA contained small amounts of a 7.2 kb size unintegrated hepatitis B genome. These studies indicate that the major reservoir of unit-length viral DNA in the asymptomatic hepatitis B carriers studied here was in the polymorphonuclear leukocyte fraction. The basis for the presence of the viral DNA within these cells is presently unknown, but may relate to viral replication within, or phagocytosis of virus by, these cells.
Normal cycling patterns of hematopoietic stem cell subpopulations: an assay using long-term in vivo BrdU infusion
Authors: Pietrzyk ME , Priestley GV , Wolf NS 
Published: October 2019

Abstract
It was found in a long-term bromodeoxyuridine (BrdU) infusion study that two or more different subpopulations of bone marrow stem cells exist in mice. One of these subpopulations appears to be noncycling and forms approximately 10% of eight-day CFU-S. Another one, a subpopulation of slowly cycling bone marrow cells, is represented as 14- day CFU-S. The 14-day CFU-S have a regular increment in the percentage of the subpopulation entering the cycle over time, with a cell generation half-time of 21 days. The cycling status in these experiments was ascertained by in vivo continuous long-term BrdU infusion. An improved method is presented for long-term BrdU infusion with UV killing of cycled cells.
Clinical and biologic features predict a poor prognosis in acute lymphoid leukemias in infants: a Pediatric Oncology Group Study
Authors: Crist W , Pullen J , Boyett J , Falletta J , van Eys J , Borowitz M , Jackson J , Dowell B , Frankel L , Quddus F 
Published: October 2019

Abstract
Analysis of remission induction rates for 1,117 children 18 months to 10 years of age (group 1) and 90 infants less than 18 months of age (group 2) with acute lymphoid leukemia (ALL) and of duration of continuous complete remission (CCR) for 454 in group 1 and 33 in group 2 revealed that infants fared significantly worse in both measures of outcome (P = .03 and P less than .0001). To examine potential reasons for the poor prognosis of affected infants, clinical and biologic features of their ALL were compared. Infants had higher WBC counts (P less than .001), a higher incidence of massive splenomegaly (P less than .001), massive hepatomegaly (P less than .001), more central nervous system (CNS) disease at diagnosis (P less than .01), and lower platelet counts (P less than .001). Also, their blasts were less often PAS+ (P = .02). The incidence of non(T, B, pre-B), T and pre-B immunophenotypes of ALL did not differ significantly between the two groups. However, in patients with non(T, B, pre-B) ALL, the majority (51%) of infants had common ALL antigen (CALLA)-negative blasts, as compared with only 7% in group 1 (P less than .001). Furthermore, infants with non(T, B, pre-B) cell ALL who were less than 12 months of age were almost always CALLA- (18 of 21). The blasts of children from both groups usually expressed Ia-like antigens. These data illustrate that infants with ALL have extensive and bulky disease more often than do older children and are more often affected with a prognostically unfavorable phenotype of acute leukemia (AL) which expresses Ia-like antigens but is more often PAS- and CALLA-. We believe that these clinical and biological differences predict and explain in part the observed poor response to treatment of infants with ALL.
Modulation of human neutrophil effector functions by monoclonal antibodies against surface membrane molecules of 94,000 and 180,000 molecular weight
Authors: King CH , Peck CA , Haimes CS , Kazura JW , Spagnuolo PJ , Sawyer JA , Olds GR , Mahmoud AA 
Published: October 2019

Abstract
Function-related antigens on the neutrophil (PMN) surface were identified using two newly developed PMN-specific mouse monoclonal antibodies. These IgG antibodies, designated Ab 1–14 and Ab 1–15, were selected for detailed study after initial testing revealed their significant inhibition of PMN superoxide generation in response to N- formyl-Met-Leu-Phe (FMLP) (64% for 1–14 and 64% for 1–15; P less than .05). In further experiments, Ab 1–14 augmented PMN adhesion (by 111%; P less than .01) and degranulation (by 52%; P less than .05) in response to FMLP, while Ab 1–15 inhibited these responses by 42% and 29%, respectively (P less than .05). Ab 1–14 reduced PMN chemotaxis in response to FMLP by 37% (P less than .02), and unlike Ab 1–15, Ab 1–14 significantly reduced unstimulated PMN binding of complement-coated sheep red blood cells. Ab 1–14 and Ab 1–15 significantly reduced PMN superoxide production in response to phorbol myristate acetate (PMA) (14% and 23%, respectively; P less than .05). Whereas 1–14 was found to increase PMA-induced cell degranulation significantly (175%), Ab 1–15 did not alter degranulation response to PMA. Immunoprecipitation showed that Ab 1–14 and Ab 1–15 recognized respective surface antigens of 94,000 mol wt and 130,000 to 180,000 mol wt. Our findings suggest that the surface molecules identified by these two monoclonal antibodies play a significant role in neutrophil activation by both FMLP and PMA.
Disparities in estimates of IgG bound to normal platelets
Authors: Blumberg N , Masel D , Stoler M 
Published: October 2019

Abstract
Estimates of the number of IgG molecules bound to normal platelets have ranged from several hundred to several tens of thousands. The lower estimates were generated from direct binding assays and stoichiometric assumptions. The higher values derive from competitive binding assays, in which platelet-associated IgG (PAIgG) is calculated from a standard curve using soluble IgG standards. Using a kinetic-ELISA (enzyme-linked immunosorbent assay) antiglobulin assay, we measured normal platelet IgG to be 21,200 +/- 9,400 molecules per platelet when a competitive assay and soluble IgG standards were used. Direct measurement of bound antiglobulin by kinetic-ELISA and stoichiometric assumptions yielded a measurement of 259 +/- 117 IgG molecules per platelet. Soluble IgG and PAIgG are not comparable in their ability to bind anti-IgG. Disparities in estimates of normal PAIgG are probably due to methodological differences. The estimate most likely to be correct is several hundred IgG or less per normal platelet.
Immunohistochemical localization of membrane and alpha-granule proteins in human megakaryocytes: application to plastic-embedded bone marrow biopsy specimens
Authors: Beckstead JH , Stenberg PE , McEver RP , Shuman MA , Bainton DF 
Published: October 2019

Abstract
Using a new technique for antigen localization, we have demonstrated platelet proteins in megakaryocytes in plastic-embedded biopsy specimens of normal human bone marrow. In a series of 25 specimens, megakaryocytes showed labeling with antibodies to the integral membrane glycoproteins IIIa, IIb, and the IIb-IIIa complex; granule membrane protein 140; and five alpha-granule matrix proteins: thrombospondin, factor VIII-related antigen, beta-thromboglobulin, platelet factor 4, and fibrinogen. The antibodies to the membrane glycoproteins IIIa, IIb, and IIb-IIIa produced diffuse cytoplasmic staining and heavier staining on the plasma membrane, whereas the antibodies to the alpha-granule matrix proteins produced a distinct granular staining within the cytoplasm. Staining for granule membrane protein 140 was also granular in distribution. Rare mononuclear cells consistent with megakaryocyte precursors were labeled with these markers. Other enzyme histochemical and lectin-binding studies showed that the enzyme alpha-naphthyl acetate esterase, the lectin Ulex europaeus I, and the periodic-acid Schiff reaction were consistent, but not specific, markers of megakaryocytes. This immunohistochemical technique should facilitate the examination of qualitative and quantitative changes in megakaryocytes in a variety of physiologic and pathologic processes.
Influence of the calcium-sensitive fluorophore, Quin 2, on platelet function
Authors: Rao GH , Peller JD , Semba CP , White JG 
Published: October 2019

Abstract
Recent investigations using Quin 2, a fluorophore used to monitor cytosolic free calcium shifts, have shown that strong agonists cause a dramatic dose-dependent increase in platelet fluorescence. However, weak agonists stimulated little or no increase in light emission of Quin 2-loaded platelets, suggesting that calcium flux is not involved in activation by these agents. The present study has sought an alternative explanation for the failure of weak stimuli to cause a rise in cytosolic free calcium in platelets containing Quin 2. Conditions used to prepare, wash, load, gel-filter, and evaluate the fluorophore- filled cells were examined for their compatibility with retention of sensitivity to activation by weak agonists. The technique used to measure shifts in cytosolic calcium with Quin 2 requires multiply washed, unstirred platelets. Under these conditions, platelets do not aggregate or secrete in response to weak agonists. Quin 2, at concentrations greater than 40 mumol/L, inhibits the response of platelets to strong agonists, and completely blocks their reaction to weak agonists. Quin 2 inhibition of platelet function appears related to high buffering capacity for free calcium, although other mechanisms cannot be ruled out. This suggestion is supported by the observation that Quin 2-induced blockade can be overcome by membrane modulation, which is a calcium-dependent process. However, since both agonists are weak, significant elevation in cytosolic calcium concurrent with functional restoration could not be demonstrated under the experimental conditions used for monitoring calcium. Thus, the conditions used to prepare platelets for Quin 2 evaluation and Quin 2 itself appear to be responsible for the failure of weak agonists to cause evidence of a calcium shift in fluorophore-loaded cells.
Clinical and hematologic characteristics in acute leukemia with 11q23 translocations
Authors: Kaneko Y , Maseki N , Takasaki N , Sakurai M , Hayashi Y , Nakazawa S , Mori T , Sakurai M , Takeda T , Shikano T 
Published: October 2019

Abstract
We studied the clinical, morphological, and immunologic characteristics of 11 patients with 11q translocation-associated acute leukemia. There were three patients with t(9;11)(p22;q23), one with a variant of the t(9;11), three with t(11;19)(q23;p13), two with t(1;11)(p32;q23), one with t(10;11)(p15;q22or23), and one with t(11;17) (q23;q25). The breakpoints in chromosome 11 clustered in band q23. The morphological feature was FAB-M5 in two patients, FAB-M2 in one, FAB-L1 in six, and lymphoblastic lymphoma in one. The remaining patient underwent morphological changes from FAB-L1 seen at the time of diagnosis to M5b at relapse. Immunologic marker studies in ten patients revealed that one had T cell type; another pre-B cell type; three CALLA- Ia- non-T, non-B type; two CAL-LA- Ia+ non-T, non-B type; two monocytic type (positive Fc-receptor); and the remaining one underwent phenotypic changes from CALLA+ Ia+ non-T, non-B type to monocytic type. The patients were usually young; five were under 1 year and two were 9 and 13 years. Hyperleukocytosis was observed in eight of the ten patients with acute leukemia, and two of the eight died of intracranial hemorrhage within two days of admission, associated with disseminated intravascular coagulation. These findings indicate that leukemia with the 11q23 translocation share certain characteristics in common, irrespective of the recipient chromosome, even though the latter may have some influence on the morphological and immunologic phenotype. Our data provide a hypothesis that multipotent stem cells are involved in the genesis of the 11q translocation-associated leukemia.
Enhanced survival of sickle erythrocytes upon treatment with glyceraldehyde
Authors: Benjamin LJ , Manning JM 
Published: October 2019

Abstract
Glyceraldehyde has been demonstrated to be an antisickling agent in vitro. In the present investigation, chromium-51 red cell studies were used to investigate the life span in vivo of sickle erythrocytes after treatment with glyceraldehyde in vitro. The mean survival (T1/2) of control cells was 5.8 +/- 1.6 days, whereas cells treated with 10 mmol/L or 20 mmol/L glyceraldehyde survived 9.0 +/- 1.4 (P less than .05) and 11.3 +/- 0.8 (P less than .002) days, respectively. The extent of modification by glyceraldehyde was 0.4 to 1.0 lysine residue per hemoglobin tetramer. These studies demonstrate not only a prolongation of the life span of sickle erythrocytes by treatment with glyceraldehyde but also the absence of any deleterious effects that would be revealed by this study.
Cytogenetic and immunophenotypic analysis of cell lines established from patients with T cell leukemia/lymphoma
Authors: Smith SD , Morgan R , Link MP , McFall P , Hecht F 
Published: October 2019

Abstract
Cell lines were established from five patients with T cell malignancies. Two patients had T cell lymphoblastic lymphoma (T-LL), whereas three patients had T cell acute lymphoblastic leukemia (T-ALL). Both T-LL cell lines expressed cell surface antigens characteristic of midthymocytes (Leu 2, 3, 6+). One T-ALL cell line also expressed this immunophenotype, one expressed suppressor/cytotoxic antigens (Leu 2+; Leu 3, 6-), and one expressed antigens of a mature but uncommitted T cell (Leu 4+; Leu 2, 3, 6-). Cytogenetic analysis showed that each cell line had 46 chromosomes with pseudodiploidy. The three T-ALL cell lines had only a few chromosome changes; one cell line had one deletion, another had two deletions, and the third had a translocation and two deletions (including loss of part of 9p). In comparison, both T-LL cell lines had complex chromosome changes, including most notably a rearrangement of band 14q11.2. The immunophenotypes and chromosome breakpoints showed patterns of interlock between the T-LL and T-ALL cell lines because common abnormalities occurred at six distinct chromosome sites. Cell lines with limited and specific chromosomal abnormalities are important because they can provide the basic material for molecular genetic studies that could elucidate the genetic mechanisms involved in neoplasia.
Cellular ras oncogene expression and cell cycle measured by flow cytometry in hematopoietic cell lines
Authors: Andreeff M , Slater DE , Bressler J , Furth ME 
Published: October 2019

Abstract
Human hematopoietic malignancies provide an excellent model for the study of the activity of cellular oncogenes in a context of known defects in cell proliferation and differentiation. A flow cytometric immunofluorescence assay was developed to quantitate the expression of the cellular ras oncogenes in relation to the cell cycle in individual leukemic cells. Specific binding of a monoclonal antibody to the 21-kd protein (p21ras) encoded by the Ha-ras, Ki-ras, and N-ras genes was measured by flow cytometry and confirmed by fluorescence microscopy. P21ras was detected in 416B, a murine hematopoietic precursor cell characterized by a high level of Ki-ras expression, and in the human leukemic cell lines P-12 and KG-1. The presence of p21ras in the cell lines was also shown by immunoprecipitation. Cellular DNA content was determined simultaneously to define cell cycle phases. There was an equal distribution of p21ras in G1, S, and G2M, with considerable heterogeneity of ras gene expression in the G1 compartment. The assay allows oncogene expression to be studied in populations of intact single cells in which cell heterogeneity is maintained, requires very few cells per sample, and directly correlates oncogene expression to cell kinetic data.
Acid phosphatase activity in mononuclear phagocytes and the U937 cell line: monocyte-derived macrophages express tartrate-resistant acid phosphatase
Authors: Snipes RG , Lam KW , Dodd RC , Gray TK , Cohen MS 
Published: October 2019

Abstract
Tartrate-resistant acid phosphatase (TRAcP) is used as a marker for osteoclasts, which are believed to be derived from phagocytic cells or phagocyte stem cell precursors. To further investigate the relationship between monocytic phagocytes and osteoclasts, acid phosphatase (AcP) activity was measured by three different techniques in human peripheral blood monocytes, monocyte-derived macrophages, and the U937 cell line. We found that cytochemistry and gel electrophoresis led to similar results, but that the colorimetric assay was inconsistent. Normal human peripheral monocytes expressed both tartrate-sensitive and -resistant AcP. In culture these cells formed polykaryons and expressed TRAcP activity that was further identified as an isoenzyme associated with bone tissue. In contrast, the U937 cells did not express TRAcP activity as measured by gel electrophoresis. Both U937 cells and monocytes possess material that interferes with interpretation of the colorimetric assay of AcP. The presence of TRAcP in monocyte-derived macrophages further supports the relationship between phagocytic cells and bone osteoclasts.
Diffuse large cell lymphoma in a patient with hairy cell leukemia: immunoglobulin gene analysis reveals separate clonal origins
Authors: Downing JR , Grossi CE , Smedberg CT , Burrows PD 
Published: October 2019

Abstract
A 75-year-old man with hairy cell leukemia (HCL) was found to have an immunoblastic lymphoma of the small bowel. Immunologic and genotypic characterization of these neoplasms revealed both the HCL and the immunoblastic lymphoma to be of the B cell lineage. The HCL expressed the HCL-associated antigens detected by the monoclonal antibodies HC-1 and HC-2, whereas the immunoblastic lymphoma failed to react with these antibodies. In addition, surface immunoglobulin light chains could not be accurately determined for the hairy cells, whereas the immunoblastic lymphoma was shown to express only kappa immunoglobulin light chains. These immunophenotype differences were compatible with either the clonal evolution of the HCL into the immunoblastic lymphoma or a separate clonal origin for these two neoplasms. An analysis of tumor DNA by Southern blot hybridization revealed different heavy-chain and kappa light-chain gene rearrangements in these two malignancies. Thus the occurrence of the large cell lymphoma most likely represents the emergence of a second clonally unrelated B cell malignancy.
Carbonyl iron therapy for iron deficiency anemia
Authors: Gordeuk VR , Brittenham GM , McLaren CE , Hughes MA , Keating LJ 
Published: October 2019

Abstract
To determine if elemental carbonyl iron powder is safe and effective therapy for iron deficiency anemia, 20 nonanemic and 32 anemic volunteers were studied. Single doses of 1,000 to 10,000 mg of carbonyl iron (15 to 150 times the 65 mg of iron in the usual dose of ferrous sulfate) were tolerated by nonanemic volunteers with no evidence of toxicity and only minor gastrointestinal side effects. Anemic volunteers (menstruating women who had previously donated blood) were treated with several regimens providing 1,000 to 3,000 mg of carbonyl iron daily in one to three doses for 8 to 28 days. After 12 weeks anemia was corrected in 29 of 32 patients, and serum ferritin was greater than 12 micrograms/L in 14. Hemoglobin regeneration proceeded at a rate similar to that described for therapy with oral iron salts and parenteral iron dextran. There was no evidence of hematologic, hepatic, or renal toxicity, but mild gastrointestinal side effects occurred in a majority of anemic volunteers. Carbonyl iron is an effective, inexpensive treatment for iron deficiency anemia, is accompanied by tolerable side effects and may have an advantage over therapy with iron salts by substantially reducing or eliminating the risk of iron poisoning in children.