bluuebunny/crossref_metadata_2025_split huggingface dataset:
Density heterogeneity of neutrophilic polymorphonuclear leukocytes: gradient fractionation and relationship to chemotactic stimulation
Authors: Pember SO , Barnes KC , Brandt SJ , Kinkade JM Jr 
Published: October 2019

Abstract
When elicited murine peritoneal exudate cells were subjected to Percoll density gradient centrifugation, polymorphonuclear neutrophils (PMN) were found to distribute over a broad spectrum of buoyant densities (1.10–1.06 g/ml). PMN isolated between approximately 1.10 and 1.085 g/ml were referred to as high density PMN (HD-PMN), and those isolated at approximately 1.085–1.06 g/ml were designated intermediate density PMN (ID-PMN). Cells were characterized on the basis of morphology and specific markers: PMN by lactoferrin immunocytofluorescence and macrophages by nicotinamide adenine dinucleotide glycohydrase activity. Macrophages banded near the top of the gradient with a peak at 1.04 g/ml. At increasing times following elicitation, the ratio of HD to ID- PMN decreased. Decreased density of either murine HD-PMN or human peripheral blood PMN could be induced in vitro by exposure of the cells to endotoxin-activated serum. A decrease in buoyant density of human PMN was also demonstrated in vitro using the synthetic chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP). The response was time dependent, related to dose, and appeared to be mediated by the cell membrane receptor for FMLP. A competitive antagonist of FMLP binding, carbobenzoxy-phenylalanyl-methionine, inhibited the density change with a calculated Kd similar to that reported for inhibition of FMLP-induced aggregation, degranulation, locomotion, and superoxide production. The FMLP-induced decrease in PMN density was shown to be directly correlated with increases in relative mean cell volume. The density response is a new measurement of PMN interaction with specific chemotactic factors, which may be important in the generation of PMN heterogeneity observed in elicited peritoneal exudate cells. In addition, this approach offers a means of physically separating “activated” from “resting” PMN and of studying resultant biochemical differences between these cell populations using both in vivo and in vitro systems.
Intensive therapy followed by bone marrow transplantation for patients with acute lymphocytic leukemia in second or subsequent remission: determination of prognostic factors (a report from the University of Minnesota Bone Marrow Transplantation Team)
Authors: Woods WG , Nesbit ME , Ramsay NK , Krivit W , Kim TH , Goldman A , McGlave PB , Kersey JH 
Published: October 2019

Abstract
Fifteen patients with acute lymphocytic leukemia (ALL) in second or subsequent remission received intensive therapy with cyclophosphamide and single dose, rapid rate (26 cGy/min) total body irradiation (TBI) followed by bone marrow transplantation (BMT) from a histocompatible sibling match. Outcome was compared to that of 23 conventionally treated control patients in second ALL remission who presented to the same institution during the same time period but had no available transplant donor. The 15 BMT patients and 23 control patients had similar characteristics, with the exception that the BMT patients were significantly older at the time of ALL diagnosis (12.6 yr versus 5.7 yr, p = 0.01). BMT patients had a significantly increased chance of remaining disease-free for 36 mo from time on study (43% actuarial versus 5%, p = 0.004) and a greater overall survival rate at 48 mo (47% actuarial versus 9%, p = 0.27) than the conventionally treated patients. In all, 5 of the bone marrow transplant patients (33%) remain alive and free of disease 24–48 + mo from transplantation. Several pre- and posttransplant characteristics were analyzed to determine predictive factors for a successful BMT outcome for patients with ALL in second or subsequent remission. Significant risk factors for predicting leukemic relapse included initial white blood count (WBC) greater than 50,000/microliters at ALL diagnosis (100% relapse rate versus 37% for patients with lower WBCs, p = 0.001) and presence of any extramedullary disease pre-BMT (100% relapse rate versus 37% for patients without extramedullary disease, p = 0.03). All 5 disease-free BMT survivors had initial WBCs less than 50,000/microliters and no evidence of extramedullary disease pretransplantation. Maintenance chemotherapy with 6-mercaptopurine (6MP) and methotrexate was given to four patients starting 100 days after bone marrow transplantation. Use of maintenance chemotherapy was associated with a significantly increased chance of remaining disease free (100% of patients surviving leukemia-free versus 17% for patients not receiving maintenance chemotherapy, p = 0.02). Presence of graft-versus-host disease (GVHD) did not influence leukemia-free survival. These results confirm that intensive therapy followed by bone marrow transplantation is the treatment of choice for patients with ALL in second or subsequent remission who have a histocompatible sibling match. Furthermore, the data suggest that a controlled trial to evaluate the efficacy of maintenance chemotherapy post-BMT for ALL patients is warranted.
Myeloperoxidase-mediated modulation of chemotactic peptide binding to human neutrophils
Authors: Lane TA , Lamkin GE 
Published: October 2019

Abstract
Methionine-containing chemotactic peptides, such as formyl-methionyl- leucyl-phenylalanine (FMLP), are inactivated via a neutrophil-derived, myeloperoxidase-mediated oxidation of the methionine residue. We report that extracellular inactivation of FMLP by myeloperoxidase modulates the apparent binding of methionine-containing chemotactic peptides to their surface receptors. Inhibitors of myeloperoxidase enhanced FMLP binding. At subsaturating concentrations of 3H-FMLP (20 nM), 1 mM cyanide (KCN) increased the binding of 3H-FMLP to human neutrophils (PMN) by 51% +/- 12%. Similar increases occurred with 0.1 mM azide and 10 mM aminotriazole (ATZ). KCN had little effect on maximal 3H-FMLP binding to PMN at saturation (control-17,040 +/- 910 receptors/PMN; KCN- 16,820 +/- 1,940 receptors/PMN), but decreased the concentration of 3H- FMLP required to half-saturate the PMN receptors (control-39 +/- 3 nM; KCN-17 +/- 1 nM). ATZ gave similar results. The binding to PMN of the non-methionine-containing chemotactic peptide 125I-formyl-norleucyl- leucyl-phenylalanyl-norleucyl-tyrosyl-lysine (125I-FNLPNTL) was unaltered by KCN. Also, the binding of 3H-FMLP to myeloperoxidase- deficient PMN was unaltered by KCN. Both KCN and ATZ decreased the oxidation of FMLP by PMN. Finally, ATZ (but not KCN) enhanced the chemotactic migration of PMN in response to submaximal concentrations of FMLP. These studies show that intact PMN inactivate methionine- containing chemotactic peptides by a pathway that is sensitive to myeloperoxidase inhibitors and is absent in myeloperoxidase-deficient PMN. This action results in an apparent decrease in the affinity of the chemotactic peptide receptor for methionine-containing chemotactic peptides, which may modulate chemotatic events in inflammatory loci.
Restoration of responsiveness of chronic myeloid leukemia granulocyte- macrophage colony-forming cells to growth regulation in vitro following preincubation with prostaglandin E
Authors: Pelus LM , Gold E , Saletan S , Coleman M 
Published: October 2019

Abstract
The ability to modulate granulocyte-macrophage colony-forming unit (CFU- GM) Ia-antigen expression and response to growth inhibition in vitro was investigated in normals and patients with chronic myeloid leukemia (CML). The hyporesponsiveness of CML CFU-GM to inhibition by prostaglandin E and acidic isoferritins in vitro and their associated diminished capacity for Ia-antigen expression could be reversed following suspension culture of bone marrow cells in the presence of prostaglandin E prior to soft agar culture. Suspension preculture with prostaglandin E for 24 hr resulted in the detection of a population of CFU-GM that were equivalent to normal CFU-GM in both response to inhibition by prostaglandin E and acid isoferritins and in their pattern of Ia-antigen expression. Cytogenetic analysis of the progeny of CFU-GM proliferating in cultures established from marrow cells, cultured directly upon isolation or following suspension culture in the absence or presence of prostaglandin E for 24 hr, indicated that the responding cell population belonged to the Ph1-positive leukemic clone. Antigen detection on these CFU-GM resulted both from Ia-antigen reexpression and the induction of noncycling cells into S-phase with coincident expression of Ia-antigens. These studies provide further evidence for a direct regulatory association between Ia-antigen and control of granulocyte-macrophage progenitor cell proliferation, offer a possible explanation for the disordered regulatory responses observed in patients with CML, and indicate that abnormal growth phenotypes can be modulated, at least in vitro.
Genetic transformation of murine bone marrow cells to methotrexate resistance
Authors: Carr F , Medina WD , Dube S , Bertino JR 
Published: October 2019

Abstract
Genetic transformation of murine bone marrow stem cells to methotrexate resistance was achieved using a modified calcium phosphate-DNA coprecipitation procedure. Bone marrow cells were transformed by DNA derived from methotrexate-resistant mouse 3T6 cells. In vivo selection of drug-resistant bone marrow cells resulted from thrice weekly injections of methotrexate (MTX) for a period of 6–8 wk. Following selection, dihydrofolate reductase activity encoded by the donor DNA species was easily detectable in extracts of recipient mouse spleens. In addition, selection of methotrexate-resistant cells was indicated by the persistence of spleen colony-forming units (CFU-S) in drug-treated animals. Also, changes in ratios of mixed syngeneic bone marrow cells derived from CBA and CBA/T6T6 mice resulted from initial treatment of either cell type with 3T6 DNA. These results confirm and extend the observations of Cline and coworkers that normal bone marrow cells can be genetically transformed to methotrexate resistance.
Combined modality therapy of advanced non-Hodgkin's lymphoma: an analysis of remission duration and survival in 95 patients
Authors: Sullivan KM , Neiman PE , Kadin ME , Dahlberg S , Farewell VT , Rudolph RH , Bagley CM Jr , Appelbaum FR , Thomas ED 
Published: October 2019

Abstract
Ninety-five patients with advanced non-Hodgkin's lymphoma were treated with four courses of cyclophosphamide, adriamycin, vincristine and prednisone, with or without procarbazine [CHOP(P)] chemotherapy; either 150 rad total body irradiation (for “extensive” disease) or 3,500 rad local radiation therapy (for “limited” disease); and a final four courses of CHOP(P) chemotherapy. Sixty-four patients had stage IV, 22 stage III, and 9 abdominal stage II disease. Histologic material was available in 80 patients for review according to the new Working Formulation: 16 had low grade, 38 intermediate grade (20 large cell, 18 diffuse small cleaved and mixed cell), and 26 high grade (12 lymphoblastic, 8 immunoblastic, 6 small noncleaved) malignancies. Complete remission was achieved in 78% of 92 evaluable patients. The remission duration curve for diffuse large cell lymphoma patients showed a plateau at 72% after 2 yr, but a pattern of continued relapse (median 3 yr) was seen in the other histologies. Multivariate analysis showed that “B” symptoms, bulky abdominal masses, and stage IV disease adversely affected survival. Overall survival by Kaplan-Meier analysis showed that 67% of diffuse small cleaved and mixed cell, 49% of large cell and immunoblastic, and 44% of lymphoblastic lymphoma patients survive 6 yr after diagnosis. When compared to reported remission duration and survival with CHOP chemotherapy alone, these data suggest a possible advantage for combined modality treatment.
Does treatment with ARA-C in low dosage cause differentiation of leukemic cells?
Authors: Castaigne S , Daniel MT , Tilly H , Herait P , Degos L 
Published: October 2019

Abstract
A series of 21 patients (5 refractory anemias with an excess of blasts in transformation and 16 acute leukemias) were treated with small doses of ARA-C (10 mg/sq m/12 hr for 15–21 days). Improvement was noted in 15 cases (71%) and complete remission observed in 12 (57%). Complete remission was obtained after one course of treatment in 8 cases. The fact that these patients entered remission relatively slowly and did not suffer marrow aplasia suggests that low-dose ARA-C may function in vivo as it does in vitro, i.e., by inducing differentiation of leukemic blasts.
Insulin receptors on leukemia and lymphoma cells
Authors: Chen PM , Kwan SH , Hwang TS , Chiang BN , Chou CK 
Published: October 2019

Abstract
Tumor cells obtained from leukemia and lymphoma patients were investigated for specific insulin receptors. Using radioactive 125I- labeled insulin, specific insulin binding sites were demonstrated on most acute lymphocytic leukemia (ALL) and acute myelocytic leukemia (AML) cells, including acute promyelocytic leukemia (APL), chronic myelocytic leukemia (CML), and acute monocytic leukemia (AMoL) cells. Insulin receptors were not found on chronic lymphocytic leukemia (CLL) and malignant lymphoma (ML) cells. Specific insulin binding sites were also found on monocytes and thymocytes after treatment with phytohemagglutinin (PHA-P), but not on inactivated tonsil cells, peripheral blood lymphocytes, or thymocytes. There was no inverse correlation between the content of insulin receptors and the basal level of circulating insulin. These data suggest that the insulin receptor may be a new marker of acute leukemia and chronic myelocytic leukemia.
Hematopoietic precursors in disease induced by the myeloproliferative sarcoma virus
Authors: Klein B , Akouala JJ , Le Bousse-Kerdiles C , Smadja-Joffe F , Jasmin C 
Published: October 2019

Abstract
Granulocyte and macrophage precursors (GM-CFU-C-), which differentiate in vitro without added granulocyte and macrophage colony stimulating factor (GM-CSF), can be detected in the hematopoietic organs of mice infected with myeloproliferative sarcoma virus (MPSV). Retransplantation experiments have shown that the GM-CFU-C- are incapable of autonomous growth and depend on a factor present in medium conditioned by MPSV spleen cells (MPSV-CM). This factor is not MPSV and is not produced by spleen cells of noninfected mice. Two classical sources of GM-CSF, lung GM-CSF and GM-CSF contained in the plasma of endotoxin-treated mice, cannot replace the MPSV factor. Inversely, MPSV- CM does not stimulate the growth of retransplanted clusters induced in normal bone marrow with lung GM-CSF, whereas lung GM-CSF does. Two conditioned media containing activity promoting the in vitro proliferation and differentiation of hematopoietic stem cells in the mixed colony assay stimulate the growth of MPSV clusters: one medium was conditioned by pokeweed-mitogen-stimulated spleen cells, the other by the WEHI 3 cell line. The implication of the results in the comprehension of MPSV disease is discussed.
Cyclic neutropenia: amplification of granulocyte oscillations by lithium and long-term suppression of cycling by plasmapheresis
Authors: von Schulthess GK , Fehr J , Dahinden C 
Published: October 2019

Abstract
A patient with well documented cyclic neutropenia (CN) was given chronic lithium therapy as well as a short course of plasmapheresis with therapeutic intention. While on lithium therapy, an increase in the amplitude of the granulocyte oscillations was observed, but recurrent agranulocytotic periods persisted. A 2-wk course of plasmapheresis (total exchange 17 liters) resulted in a gradual decrease of granulocyte oscillations, with the granulocyte count remaining above 500/cu mm at all times, and the patient became asymptomatic. The improvements in the clinical state of the patient have now persisted for more than 9 mo. Quantitative analysis of the oscillation period and the phase lags between peak counts of the hematologic cell lines revealed a 20-day cycle for granulocytes, monocytes, reticulocytes, and platelets, but not for lymphocytes. The observed phase lags, together with the literature values for the intramarrow maturation times of the hematologic cell lines, suggest that the feedback regulation abnormality, believed to be at the basis of CN, primarily affects the stem cell that is still capable of differentiating into granulocytes and monocytes, but that the oscillations of reticulocytes and platelets are the result of a stem cell competition for uncommitted precursor cells by the primarily oscillating granulocyte and monocyte production.
Delta +-thalassemia in Sardinia
Authors: Pirastu M , Galanello R , Melis MA , Brancati C , Tagarelli A , Cao A , Kan YW 
Published: October 2019

Abstract
We have defined a new type of delta-thalassemia in which beta-globin chain synthesis is incompletely suppressed. Homozygotes have unusually low HbA2 levels, and double heterozygosity for this delta-thalassemia gene and beta-thalassemia normalizes the HbA2 level. The delta- thalassemia occurs on a chromosome that is identifiable using polymorphic restriction endonuclease sites. We call this condition delta +-thalassemia, to distinguish it from the previously described delta 0-thalassemia syndromes in which no delta-globin chain synthesis occurs.
Proliferative potential of subpopulations of granulocyte-macrophage progenitor cells in normal subjects and chronic myelogenous leukemia patients
Authors: Strife A , Lambek C , Wisniewski D , Arlin Z , Thaler H , Clarkson B 
Published: October 2019

Abstract
The studies described compare the subpopulations of granulocyte- macrophage progenitor cells present in normal marrow with those derived from the marrow of patients with Ph1-positive chronic myelogenous leukemia (CML). The subpopulations were separated on the basis of size by velocity sedimentation and measured for their proliferative capacity by the colony formation technique. A pattern of development of colonies in the individual fractions was obtained by assaying the absolute number of colonies present at time intervals from 3 to 21 days. The number of colonies present at 3 days was taken as 100%, and the percentage of increase or decrease from this value was determined on subsequent days. In the fractions containing the most rapidly sedimenting large cells, the pattern of development of colonies derived from normal and CML marrow was similar. The CML colony-forming units in culture (CFU-C) began to show a deviation from the normal CFU-C pattern of development in the fractions containing CFU-C intermediate in size, and this deviation became progressively more pronounced in the slowest sedimenting small cell fractions. In these latter fractions, the CFU-C derived from CML marrow decreased in number at a rate similar to those arising from the more rapidly sedimenting fractions. This is in contrast to CFU-C derived from normal marrow, which increased in number in the more slowly sedimenting fractions and in the intermediate fractions, remained constant in number, or decreased at a rate slower than those arising from the more rapidly sedimenting fractions. The most likely explanation for these findings is accelerated maturation of the early small granulocyte-macrophage progenitor cells in CML so that these cells show the same limited proliferative capacity as do the later larger progenitor cells.
Initial chemotherapy for clinically localized lymphomas of unfavorable histology
Authors: Miller TP , Jones SE 
Published: October 2019

Abstract
Forty-five patients with localized non-Hodgkin's lymphoma of unfavorable histologic type (41 patients had diffuse histiocytic, 2 had nodular mixed, and 2 had minimally nodular histiocytic lymphoma) were treated with initial chemotherapy (28 patients), including cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP), or with initial CHOP followed by involved field radiotherapy (17 patients). Patients were clinically staged and found to have stage I (7 patients), stage IE (8), stage II (12), and stage IIE (18). Despite the presence of potentially adverse prognostic factors, including age older than 65 yr (11 patients), bulky disease (17), gastrointestinal involvement (9), and “B” symptoms (4), 44 of 45 patients (98%) achieved a complete response. Forty-two patients (93%) are alive with a median follow-up time of 41 mo (range 3–128 mo). Thirty-eight patients (84%) remain continuously free of disease. Neither the pretreatment clinical features nor the type of treatment significantly influenced the outcome for patients treated with initial chemotherapy. Patients who failed treatment relapsed at distant sites or in initially involved sites whether or not they received radiotherapy. Initial treatment for localized lymphomas of unfavorable histology with chemotherapy regimens of proven curative potential in advanced disease is a successful treatment strategy and obviates the need for extensive staging. The role of involved field radiotherapy following initial chemotherapy needs to be defined.
Expression of multiple isozymes of granulocyte, monocyte, and macrophage esterases in polycythemic Friend erythroleukemia cells
Authors: Woytowicz JM , Daoust PR , Andre-Schwartz J , Levy SB 
Published: October 2019

Abstract
We examined the expression of cytochemical markers of myeloid and monocyte-macrophage differentiation in conjunction with ultrastructural studies of different malignant erythroleukemic cells isolated from mice infected with the Friend polycythemic virus complex (FLV-P). The amounts of fluoride-sensitive and resistant nonspecific esterase activity increased with the progression of malignancy. Isoelectric focusing resolved this enzyme activity into 13 isozymes in the most malignant Friend cell type tested. These same isozymes were found in the adherent cell population of normal spleens. Two of these isozymes were shown to have chloroacetate esterase activity characteristic of granulocytes. Despite these myeloid and monocyte characteristics, light and electron microscopy showed no morphological evidence of differentiation in either of these lineages. This study demonstrates that the Friend erythroleukemic cell contains markers of three different hemopoietic cell types. The expression of myeloid, monocytic, and erythroid traits in these erythroleukemic cells can be used to monitor their malignant progression.
The effect of thrombin on the density distribution of blood platelets: detection of activated platelets in the circulation
Authors: van Oost B , van Hien-Hagg IH , Timmermans AP , Sixma JJ 
Published: October 2019

Abstract
The buoyant density of human platelets is decreased after they have been aggregated and induced to secrete their granule content by thrombin. This change in density was detected by discontinuous density gradient centrifugation using arabinogalactan (Stractan) solutions. The density decrease was dependent on the thrombin concentration and paralleled the extent of serotonin and beta-thromboglobulin secretion. The degranulated platelets maintained their integrity, and many of their functional properties. Mixtures of degranulated platelets and normal platelets could be resolved by Stractan gradient centrifugation and the number of degranulated platelets quantitated. Using this method, increased levels of less dense platelets were shown to occur after cardiopulmonary bypass. Assay of changes in platelet density by Stractan gradient centrifugation is a useful method for detection of activated platelets in vitro and in vivo.