bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biologic and prognostic significance of the presence of more than two mu heavy-chain genes in childhood acute lymphoblastic leukemia of B precursor cell origin
Authors: Kitchingman GR , Mirro J , Stass S , Rovigatti U , Melvin SL , Williams DL , Raimondi SC , Murphy SB 
Published: October 2019

Abstract
We examined the arrangement of the mu heavy-chain immunoglobulin (Ig) genes in the leukemic blast cell DNA of 93 children with acute lymphoblastic leukemia (ALL). All cases met morphologic and cytochemical criteria for ALL, lacked detectable T cell surface antigens, and expressed HLA-DR (Ia) antigens. Eighty-three of the 93 patients (89%) were positive for the common acute lymphoblastic leukemia antigen (CALLA), and 20 of 91 (22%) tested had detectable cytoplasmic immunoglobulin. As expected, the heavy-chain lg gene was rearranged in all cases, and the pattern of rearrangements was variable; 23 had one allele rearranged and one in the germ line configuration; 15 had one rearranged and one deleted; and 37 had two rearranged. Unexpectedly, in 18 patients the presence of more than two mu gene-hybridizing bands was detected. Combinations of enzymes and heavy-chain gene probes were used to confirm that the extra bands were not the result of underdigestion of the DNA or DNA restriction site polymorphism. In eight of the 18 patients, we identified an extra chromosome 14 as a possible cause of the extra bands' hybridizing to the mu heavy-chain constant-region probe. In the remaining ten patients, the presence of three or four bands hybridizing with the mu probe suggests the presence of two populations of leukemic cells that may have arisen either by separate leukemic transformation events or by clonal evolution of one clone into two related lines. Although preliminary (2-year follow-up), our data suggest that childhood ALL of B lineage with more than two mu heavy-chain genes, but without extra copies of chromosome 14, may be more resistant to therapy.
Hemoglobin switching during murine embryonic development: evidence for two populations of embryonic erythropoietic progenitor cells
Authors: Wong PM , Chung SW , Reicheld SM , Chui DH 
Published: October 2019

Abstract
Explants of normal mouse embryonic tissues and disaggregated embryonic single cells were cultured in vitro to study the erythropoietic progenitor cells present during embryonic development. The results indicate that there are two populations of erythropoietic progenitor cells committed to different hemoglobin synthetic programs. These progenitor cells are present at an early gestational stage prior to the formation of the fetal hepatic primordium. One population of progenitors can be stimulated by erythropoietin alone to form usually small erythroid colonies after culture for six days in vitro. These erythroblasts primarily synthesize embryonic hemoglobins, but produce some adult hemoglobins as well. The other population of progenitors requires stimulation by both erythropoietin and adult spleen cell- conditioned medium, and usually forms large erythroid colonies after culture for six days in vitro. These erythroblasts produce only adult hemoglobins.
Hydroxyurea induction of hemoglobin F production in sickle cell disease: relationship between cytotoxicity and F cell production
Authors: Dover GJ , Humphries RK , Moore JG , Ley TJ , Young NS , Charache S , Nienhuis AW 
Published: October 2019

Abstract
Initial alterations in fetal hemoglobin (HbF) production among eight sickle cell anemia subjects treated with hydroxyurea (Hu) are summarized. Four of these subjects had been previously treated with 5- azacytidine (5-aza). All subjects treated with Hu (50 mg/kg/d for three to five days) had suppression of their total reticulocyte counts by seven days, whereas the four subjects previously treated with 5-aza (2 mg/kg/d for three to five days) had increased reticulocyte counts at day 7. The effect of Hu on increasing the number of HbF-containing reticulocytes (F reticulocytes) is extremely variable, ranging from ten- to less than onefold differences in maximal posttherapy v pretherapy levels. Recovery from marrow suppression did not result in greater than twofold increases in F reticulocyte counts. Mean day 7 F reticulocyte levels in the four subjects treated with both Hu and 5-aza were 4.1 X 10/microL and 15.4 X 10(4)/microL, respectively. Among Hu-treated subjects, increased F reticulocyte production was correlated with low serum creatinine levels and rapid removal of Hu from the plasma. Furthermore, suppression of CFU-E colony formation on day 2 of therapy with Hu was inversely correlated with maximal F reticulocyte response. We conclude that where Hu treatment results in marrow toxicity (decreased reticulocyte counts, decreased CFU-E colony formation) HbF production is less likely to increase. Those sickle cell anemia subjects with minimal renal dysfunction (serum creatinine level, greater than 1.0 mg/dL) exhibit the most cytotoxicity and least F reticulocyte response to Hu.
Mixed hematologic chimerism after allogeneic marrow transplantation for severe aplastic anemia is associated with a higher risk of graft rejection and a lessened incidence of acute graft-versus-host disease
Authors: Hill RS , Petersen FB , Storb R , Appelbaum FR , Doney K , Dahlberg S , Ramberg R , Thomas ED 
Published: October 2019

Abstract
Ninety-six patients with severe aplastic anemia who received a sex- mismatched, HLA-identical allogeneic sibling marrow transplant had sequential cytogenetic analyses performed to determine the incidence and implications of posttransplant mixed hematologic chimerism. Of the 96 patients, 56 (58.3%) became mixed chimeras with coexisting host and donor cells detected in peripheral blood or marrow 14 days or later after transplant, and 40 patients (41.7%) were complete chimeras with 100% donor-type hematopoietic cells. The incidence of mixed chimerism was independent of prior blood production transfusions and infusion of donor buffy coat. The rejection rate was significantly increased in the mixed chimeric group, particularly in patients not receiving buffy coat (14 of 36 rejecting), although overall, the majority (69.7%) retained their first graft. Rejection was seen almost exclusively in patients exposed to multiple transfusions before transplantation. If patients who reject their first graft are censored, the overall incidence of grades II through IV acute graft-v-host disease (GVHD) was significantly reduced in those with mixed chimerism. Transfused patients with mixed chimerism in particular were less likely to develop grades II through IV acute GVHD. The incidence of chronic GVHD was similar in the two groups and did not significantly influence survival. In this study, mixed chimerism persisted for up to 395 days posttransplant, either the first graft being rejected or, more commonly, hematopoiesis reverting to 100% donor-type cells. Mixed lymphohematopoietic chimerism may persist in patients with aplastic anemia who have received matched allogeneic marrow transplants for significant periods before hematopoiesis reverts to donor cell type.
Immunoglobulin gene rearrangements in remission bone marrow specimens from patients with acute lymphoblastic leukemia
Authors: Zehnbauer BA , Pardoll DM , Burke PJ , Graham ML , Vogelstein B 
Published: October 2019

Abstract
Recombinant DNA probes for the joining (JH) segment of the immunoglobulin heavy chain gene were used to detect molecular rearrangements of this gene in the DNA of bone marrow cells obtained during remission of acute lymphoblastic leukemia (ALL). This molecular approach was optimized and found to exceed the sensitivity of conventional morphologic screening for detecting residual leukemia cells; one leukemic cell in 500 normal nucleated bone marrow cells was easily detected using this approach. In the present study, bone marrow from three of seven patients in complete clinical remission (defined morphologically) contained leukemic cells in these proportions. This analysis may be of use in evaluating the status of clinical remission in selected ALL patients.
Monoclonal antibodies binding to the human neutrophil C3bi receptor have disparate functional effects
Authors: Hickstein DD , Locksley RM , Beatty PG , Smith A , Stone DM , Root RK 
Published: October 2019

Abstract
Three monoclonal antibodies (MAb)--OKMI, 7C3, and 60.3-- immunoprecipitated a common 170-kd neutrophil membrane antigen closely associated with, or identical to, the C3bi receptor (CR3). Despite binding to a common receptor, these antibodies displayed marked differences in their effects on C3bi-mediated neutrophil function as assessed by the binding and ingestion of opsonized zymosan and the subsequent triggering of the respiratory burst. Antibody 7C3 caused a time-dependent, irreversible inhibition of the neutrophil oxidative response to opsonized zymosan that correlated with capping of the bound antibody. In contrast, antibody 60.3 caused an immediate inhibition of the neutrophil oxidative response to opsonized zymosan that required the continuous presence of exogenous antibody to achieve the maximal inhibitory effect. Antibody OKMI demonstrated minimal inhibition of O2- release. Despite their functional differences, binding of either 7C3 or 60.3 led to up-regulation of new antigen, presumably from intracellular sites as previously described using OKMI. Crossed immunoprecipitations of radiolabeled neutrophil lysates indicated that each MAb bound to different antigens near or within the CR3 complex. Thus three MAb binding to the neutrophil CR3 receptor each caused receptor up- regulation but had markedly different functional effects on the cell.
Reevaluation of cytochrome b and flavin adenine dinucleotide in neutrophils from patients with chronic granulomatous disease and description of a family with probable autosomal recessive inheritance of cytochrome b deficiency
Authors: Ohno Y , Buescher ES , Roberts R , Metcalf JA , Gallin JI 
Published: October 2019

Abstract
Chronic granulomatous disease (CGD) is a genetically heterogeneous syndrome characterized by a microbial killing defect of polymorphonuclear leukocytes (PMNs) due to lack of superoxide O2-. 2 generation. Recent studies indicate that the neutrophil O2-.-generating system consists of at least two components, flavoprotein--flavin adenine dinucleotide (FAD)--and cytochrome b. We evaluate the cytochrome b and FAD content in PMN from 30 CGD patients. The method for quantitating cytochrome b was modified by using PMN sonicates incubated with azide plus hydrogen peroxide. With this approach, several absorption peaks corresponding to myeloperoxidase and eosinophil peroxidase, which overlap with peaks of cytochrome b, were obliterated from reduced-minus-oxidized spectra, whereas the peaks of cytochrome b were not and could be readily quantitated. Cytochrome b was detected in PMNs from all 24 normal adults (47.4 +/- 2.9 pmol/7.5 X 10(6) cells), was absent in PMNs from 11 male CGD patients and one female CGD patient but was present in normal amounts in PMNs from nine male and nine female CGD patients. Stimulated nitroblue tetrazolium (NBT) tests performed on PMNs from mothers of CGD patients indicated that cytochrome b deficiency was associated with X-linked inheritance, except in one case in which probable autosomal recessive inheritance was demonstrated. The PMN NBT test of the mother of another male patient without cytochrome b deficiency suggested an X-linked form of inheritance. In related studies, the FAD content in PMN particulate fractions was reduced in 4 of 28 CGD patients studied. All four CGD patients with reduced FAD lacked cytochrome b. However, three patients with cytochrome b deficiency had normal FAD. Thus, the results indicate that PMN cytochrome b deficiency is observed in most X-linked and in some autosomal recessive CGD, that cytochrome b deficiency may be associated with FAD deficiency, and that cytochrome b and FAD are normal in most patients with non-X-linked CGD.
Cytomegalovirus infection after bone marrow transplantation: an association with acute graft-v-host disease
Authors: Miller W , Flynn P , McCullough J , Balfour HH Jr , Goldman A , Haake R , McGlave P , Ramsay N , Kersey J 
Published: October 2019

Abstract
Among 181 patients undergoing allogeneic bone marrow transplantation over a five-year period (1978 through 1982), cytomegalovirus (CMV) infection was a frequent and often lethal complication. Recipient pretransplant serology was the most important predictor of posttransplant CMV infection. CMV infection occurred in 26/137 seronegative recipients and in 28/44 seropositive recipients (P less than .001). Among patients who developed CMV infection, the time to infection was identical in seronegative and seropositive patients (median, 71 days post transplant). Bone marrow donor CMV serology did not significantly influence CMV infection rate. CMV infection was strongly associated with acute graft-v-host disease (AGVHD), occurring in 34/81 patients with AGVHD and 20/100 without GVHD (P less than .001). AGVHD preceded CMV infection by 33.7 days (mean) in patients developing both complications. Patients who developed CMV infections had also received more cellular blood products post transplant. These data suggest that CMV infection may occur through reactivation of latent virus (in seropositive recipients) or through exogenous exposure, possibly through transfused blood products, but that duration of immunoincompetence may be more critical than route of exposure in timing of clinically evident CMV infection. Prophylaxis tailored to the likely infectious source and more effective GVHD prevention both may be critical in preventing CMV infection after bone marrow transplantation.
Macrophage colony formation supported by purified CSF-1 and/or interleukin 3 in serum-free culture: evidence for hierarchical difference in macrophage colony-forming cells
Authors: Koike K , Stanley ER , Ihle JN , Ogawa M 
Published: October 2019

Abstract
Using a serum-free culture system, we examined murine macrophage colony formation from bone marrow cells cultured in the presence of purified CSF-1, interleukin 3 (IL 3) or a combination of the two factors. CSF-1 supported macrophage and neutrophil-macrophage colony formation, whereas IL-3 supported the formation of various types of single lineage and multilineage colonies. CSF-1 supported more macrophage colonies from bone marrow cells of normal mice than IL 3, whereas in cultures of bone marrow cells of 5-fluorouracil-treated mice, IL 3 supported more macrophage colonies. A combination of CSF-1 and IL 3 resulted in granulocyte-macrophage (GM) colony formation that was equal to or greater than the sum of GM colony formation supported by the factors individually. The combination of CSF-1 and IL 3 resulted in significant increases in the size of both macrophage and neutrophil-macrophage colonies. Similar increases in colony size were observed when CSF-1 was added to cultures five days after incubation of marrow cells with IL 3. These data support the concept that some of the macrophage colony- forming cells that respond to IL 3 are more primitive than those that are sensitive to CSF-1.
Separation of the acetylcholinesterase-deficient red cells in paroxysmal nocturnal hemoglobinuria
Authors: Chow FL , Hall SE , Rosse WF , Telen MJ 
Published: October 2019

Abstract
Blood of patients with paroxysmal nocturnal hemoglobinuria (PNH) most often contains two or more populations of erythrocytes--one population with normal sensitivity to lysis by complement (PNH I cells) and a second population of moderately abnormal cells (PNH II cells) or markedly abnormal cells (PNH III cells). PNH II and III cells exhibit moderately and markedly increased sensitivity to lysis by complement, respectively, as well as other membrane defects. We have devised a method for isolating pure, intact PNH II and III cells from mixed populations by use of monoclonal antibodies and cell affinity chromatography. Study of purified cell populations has led to the identification of a further subtype, PNH IIIb, of PNH erythrocytes. PNH IIIb erythrocytes are less sensitive to complement lysis than PNH IIIa cells but are lysed by fluid-phase activation of complement, unlike PNH II erythrocytes.
Synchronized cultures of P falciparum in abnormal red cells: the mechanism of the inhibition of growth in HbCC cells
Authors: Olson JA , Nagel RL 
Published: October 2019

Abstract
It has been previously demonstrated that HbCC cells fail to support growth of P falciparum in asynchronous Jensen-Trager cultures. To define the mechanism of inhibition we have studied synchronous cultures and found that while intraerythrocytic parasite development appeared normal, the liberation of merozoites and/or invasion was impaired. This effect was detected by a normal growth during the first growth cycle but dramatically reduced number of ring forms following the schizont stage. A specific test for the invasion of CC cells by P falciparum merozoites, nevertheless, was normal. The defect found in infected CC cells was not modified by changes in O2 tension (which altered the ligand saturation of Hb C) nor by the extracellular K+ concentration (excluding a K+ leak-dependent mechanism for the growth inhibition). The osmotic lysis of late-staged parasitized red cells revealed that 25% of infected AA cells were lysed when the extracellular medium was 95 mOsm. In contrast, infected CC cells required a decrease to 10 mOsm in the extracellular media to reach 25% lysis. We conclude that CC red cells are unsuitable hosts for the malarial parasite primarily because of their inability to lyse and release merozoites at the appropriate stage of intraerythrocytic development of P falciparum.
Pro-urokinase: a study of its stability in plasma and of a mechanism for its selective fibrinolytic effect
Authors: Pannell R , Gurewich V 
Published: October 2019

Abstract
Highly purified pro-urokinase (pro-UK) or single-chain urokinase-type plasminogen activator (scu-PA) was treated with diisopropylfluorophosphate (1 mmol/L) to eliminate traces of two-chain UK activity. This preparation was found to retain a low activity against a chromogenic substrate (S2444), equivalent to 0.1% to 0.5% of the activity of its plasmin-activated derivative. Evidence is presented that the intrinsic activity of pro-UK (scu-PA) was sufficient to activate plasminogen on a fibrin plate or in buffer and was far more reactive against Lys-plasminogen than against Glu-plasminogen. The relative resistance of Glu-plasminogen to activation was overcome by the addition of lysine (25 mmol/L) to the reaction mixture. By contrast, in plasma, pro-UK (scu-PA) was stable and nonreactive for greater than 72 hours when incubated (37 degrees C). Pro-UK (scu-PA) did not form sodium dodecyl sulfate-stable inhibitor complexes, whereas complexation occurred rapidly with UK. Only at high concentrations of pro-UK (scu-PA) (greater than or equal to 250 IU/mL) did plasminogen activation in plasma occur. The relative inertness of pro-UK (scu-PA) in plasma, in contrast to its low-grade enzymatic activity in buffer, was attributed to the effect of inhibitors. The addition of EDTA or the removal of divalent cations by dialysis was associated with a lower threshold for nonspecific plasminogen activation by pro-UK (scu-PA) in plasma. Replacement of Ca++ but not other cations restored baseline conditions. In the presence of a clot, fibrin-selective plasminogen activation and clot lysis were triggered. Lysis was accompanied by less than 10% conversion of pro-UK (scu-PA) to two-chain UK, suggesting that the intrinsic activity of pro-UK (scu-PA) itself may have been responsible for fibrinolysis, although a contribution by the small amount of UK generated could not be excluded. Similarly, pro-UK (scu- PA) supported clot lysis for several days in the same plasma before the effect dissipated as a result of degradation to UK. When Glu- plasminogen in plasma was replaced by Lys-plasminogen, or when lysine was added to normal plasma, nonselective plasminogen activation and fibrinogenolysis occurred. It was concluded that under the experimental conditions, the fibrin specificity of pro-UK (scu-PA) can be explained by its selective activation of fibrin-bound plasminogen and is due to the latter's Lys-plasminogen-like conformation.(ABSTRACT TRUNCATED AT 400 WORDS)
Characterization of murine peritoneal macrophage receptors for fibrin(ogen) degradation products
Authors: Rajagopalan S , Pizzo SV 
Published: October 2019

Abstract
The binding of human fibrinogen degradation fragments D1, E, X, and Y, as well as fibrin fragment D1 dimer, to mouse peritoneal macrophages was examined. A Scatchard plot of fragment D1 binding was biphasic, suggesting two classes of receptors. Fragments D1, D1 dimer, X, and Y in low concentrations bound to macrophages with high affinity (Kd = 23 to 73 X 10(-11) mol/L). Fragment E bound specifically but at a much lower level than the other fragments. Fragment D1 was able to compete for the binding of radiolabeled fragments X and Y but not radiolabeled fragment E. These studies indicate that fragments D and E are recognized by separate receptor systems but that all of the fibrinogen degradation products that contain the D domain are recognized by the same receptor system.
Inhibition of neutrophil cytolysin production by target cells
Authors: Dallegri F , Patrone F , Ballestrero A , Frumento G , Sacchetti C 
Published: October 2019

Abstract
Neutrophils, triggered by heat-aggregated human IgG (Agg.IgG), were found to lyse chicken red blood cells (CRBC) as determined by a 51Cr release method. The lysis was inhibited by azide, catalase, chloride- free medium and amino acids, suggesting the requirement for myeloperoxidase (MPO), hydrogen peroxide (H2O2), chloride ions (Cl-), and hypochlorous acid (HOC1), respectively. These results indicate that neutrophils lyse CRBC through an HOCl-(ie, MPO-H2O2-Cl-) dependent process. Although HOCl can react with neutrophil-derived nitrogenous (N- ) compounds to yield chloramines, the main and well-characterized chloramines did not play a direct role in the lysis of CRBC in our model system. Thus, it appears that lysis is due either to HOCl or to an unknown compound derived from and with characteristics similar to HOCl. When CRBC were replaced with HRBC targets, no lysis could be observed. Treatment of HRBC with carmustine, to inhibit the glutathione cycle, did not affect the cell resistance to lysis by neutrophils. Conversely, the inhibition of HRBC catalase activity with aminotriazole (AT) made the cells susceptible to neutrophil-mediated HOCl-dependent lysis: this suggests that HRBC escape lysis by neutrophils through an AT-inhibitable, ie catalase-dependent, process. Through an identical catalase-dependent process, HRBC were capable of efficiently preventing the H2O2 and HOCl recovery from Agg.IgG-triggered neutrophils, tested under experimental conditions similar to those used for cytolytic assays. Together, these data suggest that HRBC targets, endowed with high catalase activity, escape neutrophil-mediated lysis by consuming (by catalase) neutrophil-derived H2O2, so that HOCl cannot be produced in amounts sufficient to promote lysis. Parallel experiments, performed with AT-treated CRBC, showed that these cells, endowed with a relatively low catalase content, only partially limit neutrophil cytolytic efficiency by a process qualitatively similar to that observed with HRBC targets. The results provide evidence that target cells can restrain neutrophil cytolytic efficiency by interfering with the MPO-H2O2-Cl system through their catalase activity.