bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maintenance of fetal hemoglobin (HbF) elevations in the baboon by prolonged erythropoietic stress
Authors: DeSimone J , Biel M , Heller P 
Published: October 2019

Abstract
We have previously shown that acute erythropoietic (Ep) stress by hemolysis or hypobaric hypoxia causes elevations of HbF in the baboon. The magnitude of these elevations is genetically determined, ranging from 3% to 60% (low, intermediate, and high responders). These genetic differences in HbF levels among animals are mainly due to differences in the number of HbF-containing cells (“F-cells”). The present study was undertaken to study the influence of prolongation and of the severity of Ep stress on HbF levels and the number of F-cells. The packed cell volume (PCV) of the blood of 4 animals, approximately 3 yr old, was maintained at 20% by daily phlebotomies, and the animals were exposed to varying degrees of hypobaric hypoxia for up to 40 days. In these experiments, the number of F-cells increased rapidly and reached individually constant levels ranging from 60% to 80%, when the PCV reached 20%, and no further increase was observed regardless of the subsequent degree of hypoxia. On the other hand, HbF levels, and with it the values for HbF per F-cell, increased proportionally to the severity of the Ep stress and could be maintained at a constant level dependent on the degree of the hypoxia, e.g., at 19,000 feet HbF levels of one animal remained 20%-25% throughout the duration of the exposure of 14 days. These data are indicative of separate control of F-cell numbers and of the levels of HbF per F-cell. It appears that with the increase of Ep stress, those Ep stem cells that have retained the HbF program are mobilized into maturation. A model, attempting to explain this phenomenon is presented.
Impairment of platelet aggregation in hemolytic uremic syndrome: evidence for platelet "exhaustion"
Authors: Fong JS , Kaplan BS 
Published: October 2019

Abstract
Thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure are the hallmarks of hemolytic-uremic syndrome (HUS). This report presents the results on platelet studies from 10 consecutive HUS patients in childhood. During their acute illness, they all displayed a characteristic pattern of impaired platelet function: no aggregating responses to epinephrine, some to ADP, and moderate to collagen. In addition, platelet contents of beta-thromboglobulin (beta TG) were markedly reduced. As these patients improved clinically, their platelet- aggregating responses also normalized despite their uremic state. Incubation of platelets with uremic plasma or guanidino-succinic acid, a uremic toxin, had minor effects on platelet-aggregating activity. Since low levels of platelet beta TG suggest that these platelets were in an exhausted state, in vitro experiments were performed to exhaust normal platelets by incubation at 37 degrees C. A proportional impairment of platelet-aggregating responses and decreasing levels of platelet beta TG were noted. Furthermore, the pattern of impairment was similar to that found in the platelet-aggregating activities of HUS patients. Thus, “exhaustion,” in addition to azotemia and thrombocytopenia, are factors that contribute to the functional impairment of platelets in these patients. Further studies to reveal mechanisms that lead to platelet exhaustion in HUS are of fundamental importance in the understanding of this illness.
Monocyte-macrophage-derived acidic isoferritins: normal feedback regulators of granulocyte-macrophage progenitor cells in vitro
Authors: Broxmeyer HE , Bognacki J , Ralph P , Dorner MH , Lu L , Castro-Malaspina H 
Published: October 2019

Abstract
The recent identification of a leukemia-associated inhibitory activity (LIA) against granulocyte-macrophage progenitor cells (CFU-GM) as acidic isoferritins has now led to detection of this activity in normal bone marrow and blood cells. Detection of this activity depends on stimulation of CFU-GM by granulocyte-macrophage colony stimulatory factors (GM-CSF), and some conditioned media (CM) sources of GM-CSF (human placental and monocyte, mouse macrophage and WEHI-3) contained low levels of acidic isoferritin that lowered colony formation. Inactivation or removal of this activity increased the stimulatory capacity of the CM. CM depleted of acidic isoferritins or CM originally devoid of this activity (human GCT, 5637, Mo, lymphocytes: mouse L cells or pokeweed-mitogen-stimulated spleen cells) increased the sensitivity of the assay to detect acidic isoferritin inhibitory activity. This activity was selectively contained and released from normal monocytes and macrophages. Restriction of this activity to mononuclear phagocytes was substantiated, as only continuous cell lines of monocytes and macrophages or lines capable of induction to this lineage contained and released acidic isoferritin inhibitory activity. The cells of origin and target cells of action suggest that acidic isoferritin-inhibitory activity can be considered as a negative feedback regulator, at least in vitro.
Nonprogressive course of non-A, non-B chronic hepatitis in multitransfused hemophiliacs
Authors: Mannucci PM , Colombo M , Rizzetto M 
Published: October 2019

Abstract
Eleven hemophiliacs with chronic liver disease were studied prospectively for 6 yr, with liver function tests and liver biopsies carried out at intervals of 3 yr. The second series of biopsies, compared with the first series, showed continuation of chronic persistent hepatitis in four patients, change to chronic lobular hepatitis in two, and spontaneous improvement of the disease in the four cases who had had chronic active hepatitis characterized by moderate piecemeal necrosis. One patient with active cirrhosis died of liver failure during the follow-up period. Study of the serum and intrahepatic markers for hepatitis B and delta viruses suggests that chronic liver disease is nonprogressive in hemophiliacs who have no intrahepatic viral marker.
A simple laboratory alternative to irreversibly sickled cell (ISC) counts
Authors: Clark MR , Mohandas N , Embury SH , Lubin BH 
Published: October 2019

Abstract
Irreversibly sickled cells (ISC) are considered to be a hallmark of sickle cell disease, yet their number in peripheral blood smears varies greatly among different homozygous SS patients. This variation has suggested a role for ISC in the varying clinical manifestations of the disease. Efforts to determine the role of ISC have been complicated by the difficulty in standardizing the quantification of these cells. For this reason, we have attempted to develop an alternative method of quantification that would be less variable than the microscopic counting of cells on blood smears. Because ISC are dehydrated dense cells, a measurement based on cell density seemed an attractive alternative approach. Analysis of whole blood samples on a simple, 2- step density gradient, spun in a microhematocrit centrifuge, showed a strong correlation between the proportion of high density cells and the percentage of morphologically identified ISC. Parallel ektacytometric measurements of cell deformability, another parameter that reflects the low water content and high MCHC of ISC, were also strongly correlated with ISC counts. These findings suggest that either of these measurements, sensitive to the special physical properties of ISC, could be used as an objective substitute for the microscopic counting of ISC.
Evaluation of E-rosetting human lymphocytes with OKT11 and other monoclonal antibodies
Authors: Ip SH , Rittershaus CW , Struzziero CC , Hoxie JA , Hoffman RA , Healey KW , Lifter J 
Published: October 2019

Abstract
Monoclonal antibody OKT11 was found to compete with sheep red blood cells for binding sites on human lymphocytes. Preincubation of lymphocytes with OKT11 eliminated E-rosette formation. In a study of 142 peripheral blood samples ranging from 1% to over 90% E-rosette- positive cells, comparison to the percent OKT11-positive cells yielded a correlation coefficient of 0.93. In normal donors, subsets of OKT11+ cells were identified using two-color immunofluorescent staining methods with OKT3, OKT4, and OKT8. On the average, approximately 13% of OKT11+ lymphocytes were OKT3- and 13% of OKT11+ lymphocytes were OKT4- and OKT8-. Based on our double antibody fluorescence intensity data, low antigen density OKT11+ lymphocytes were OKT3-. OKT4+ and OKT8+ lymphocytes in normal peripheral lymphocytes have similar OKT11 antigen density.
Expression of Ia-like antigens defined by monoclonal OKIal antibody of hemopoietic progenitor cells in cord blood: a comparison with human bone marrow
Authors: Koizumi S , Yamagami M , Miura M , Horita S , Sano M , Ikuta N , Taniguchi N 
Published: October 2019

Abstract
Expression of Ia antigens on granulocyte/macrophage colony-forming cells (CFU-GM) in human cord blood was compared with that in bone marrow with the use of monoclonal OKIal antibody. Mononuclear cells prepared from cord blood and bone marrow were pretreated with OKIal antibody plus complement, and, thereafter, the ability of cord blood and bone marrow cells to form colonies of CFU-GM was assayed in semisolid agar culture. Consistent reduction in the number of CFU-GM in cord blood to 58.8% +/- 13.0% (mean +/- SD) of controls treated with complement alone was shown after elimination of Ia-antigen-bearing CFU- GM, but was significantly remarkable than that in bone marrow (18.0% +/- 5.6%). Although the reduction of both granulocyte (CFC-G) and macrophage colony (CFC-M) types of cord blood, characterized by the double staining for esterase activity, was shown following treatment with OKIal antibody plus complement, the relative inhibition of CFC-G weas significantly greater than that of CFC-M (p less than 0.02). These results suggest some differences in the characteristics of Ia-antigen- bearing CFU-GM between cord blood and bone marrow cells. Furthermore, it is suggested that Ia-dependent regulatory mechanisms might participate in the differentiation of CFU-GM to CFC-G and CFC-M.
Cytokinetically based induction chemotherapy and splenectomy for childhood acute nonlymphocytic leukemia
Authors: Dahl GV , Kalwinsky DK , Murphy S , Look AT , Amadori S , Kumar M , Novak R , George SL , Mason C , Mauer AM , Simone JV 
Published: October 2019

Abstract
A four-drug regimen, based on cell kinetic principles, induced complete remissions in 68 of 95 children (72%) with acute nonlymphocytic leukemia (ANLL). Patients entered remission after 2–5 weekly cycles of vincristine-daunorubicin (day 1) followed by sequential cytosine arabinoside and 6-azauridine (days 4–7). With continuation therapy of monthly vincristine-doxorubicin-cyclophosphamide, weekly cytosine arabinoside, and daily 6-mercaptopurine, the median duration of complete remission was 10 mo and the median survival time 21 mo. Portal triaditis, evident in 11 of 23 patients with liver biopsies, was associated with long remissions. A larger spleen size (greater than 5 cm) and a higher myeloblast labeling index (greater than 10%) at diagnosis were clearly related to shorter durations of remission. Splenectomy within 1 mo of remission had no statistically significant effect on the frequency of relapse or length of remission. Patients without central nervous system (CNS) leukemia at diagnosis, all treated prophylactically with intrathecal methotrexate, had a low frequency of initial CNS relapse (3/56, 5%). The 2-yr disease-free survival rate is 29% (20 of 68 patients attaining complete remission). fifteen patients have completed 2.5 yr of therapy, and each remains in continuous complete remission, off treatment, for 1+ -36+ mo. This induction chemotherapy was as effective as more intensive regimens, with the advantage of less toxicity and shorter periods of hospitalization.
Prognostic importance of chromosome number in 136 untreated children with acute lymphoblastic leukemia
Authors: Williams DL , Tsiatis A , Brodeur GM , Look AT , Melvin SL , Bowman WP , Kalwinsky DK , Rivera G , Dahl GV 
Published: October 2019

Abstract
Leukemia cell karyotypes were determined at diagnosis for 136 of 159 consecutive patients with acute lymphoblastic leukemia (ALL) who were followed for up to 35 mo. Ninety patients (67%) had abnormal karyotypes. Five chromosome categories were designated, based on the distribution of modal numbers: hyperdiploid greater than 50 (n = 41), hyperdiploid 47–50 (n = 18), pseudodiploid (n = 28), normal (n = 46), and hypodiploid (n = 3). Treatment response was assessed for the categories in terms of time to failure (induction failure, first relapse, or death). Children in the hyperdiploid greater than 50 category had the best responses to treatment, with only 2 failures, and those in the pseudodiploid category had the poorest (p less than 0.001). The remaining 3 chromosome categories had intermediate responses and formed a third prognostic group. This same influence of chromosome number on time to failure was evident within the 2 clinical prognostic groups: high risk, signified by a leukocyte count greater than 100 X 10(9)/liter, meningeal leukemia, mediastinal mass, or the presence of blasts that formed rosettes with sheep erythrocytes at 37 degrees C, and standard risk, indicated by the absence of these features. The influence of chromosome number on time to failure was also the same within the historically favorable prognostic group that had common ALL. Results of a multivariate analysis indicated that chromosome number was the strongest single predictor of outcome (p less than 0.001) and was the only variable that added significant prognostic information to leukocyte count (p less than 0.001). The combination of chromosome number and leukocyte count should more clearly distinguish patients with ALL at low or high risk of relapse.
Further studies on the interaction between human platelet membrane glycoproteins IIb and IIIa in triton X-100
Authors: Pidard D , Rosa JP , Kunicki TJ , Nurden AT 
Published: October 2019

Abstract
Analysis of human platelet membrane proteins by crossed immunoelectrophoresis (CIE) in the presence of Triton X-100 (TX-100) has previously shown that glycoproteins (GP) IIb and IIIa are located in a single immunoprecipitate, band 16.2 To investigate whether IIb and IIIa are associated in a complex, we have analyzed TX-100-solubilized 125I-labeled membrane proteins by density gradient ultracentrifugation using 10%-40% sucrose gradients containing the nonionic detergent. studies were performed using soluble proteins derived from membranes isolated in the presence or absence of EDTA. Analysis of gradient fractions by SDS-polyacrylamide gel electrophoresis showed that in the absence of divalent cation chelation, GP IIb and IIIa penetrated well into the gradient (fractions 15–17). Analysis of fractions 15–17 by CIE revealed the presence of band 16. In contrast, when the membrane proteins were incubated with EDTA prior to or after TX-100 solubilization, IIb and IIIa remained near the top of the gradient (fractions 8–11) and gave separate immunoprecipitates during CIE. Incubation of washed platelet lysates with leupeptin, an inhibitor of the Ca2+-dependent protease of human platelets, had no effect on the shape of the band 16 immunoprecipitate. Thus, for the first time, direct evidence has been obtained that GP IIb and IIIa may form a divalent cation-mediated complex. Calibration of the sedimentation profiles using proteins of known molecular weight suggests that the complex is of limited size. Indirect evidence suggests that the complex is a heterodimer.
Erythropoietin production in response to anemia or hypoxia in the newborn rat
Authors: Caro J , Erslev AJ , Silver R , Miller O , Birgegard G 
Published: October 2019

Abstract
Erythropoietin production in response to hypoxic-hypoxia is markedly reduced in the newborn when compared to the adult rat. This response improves steadily with age and reaches adult values at about 4 wk. When animals of the same age are stimulated with anemic-hypoxia, considerably higher levels of erythropoietin are found. The erythropoietin level is proportional to the degree of anemia and independent of the age of the animal. Extraction of erythropoietin from tissue homogenates revealed a parallelism between the plasma and kidney erythropoietin content, while no erythropoietin could be extracted from liver tissue at any age. The lack of response to hypoxia in the newborn appears to be related to the high hemoglobin oxygen affinity during the neonatal period, which facilitates oxygen loading. Newborn rats have a very low intraerythrocytic concentration of 2–3 DPG and a marked shift to the left in the oxygen hemoglobin dissociation curve that slowly increases to adult values at 4 wk of age. The response to anemia on the other hand, appears to be normal and not affected by age or by hemoglobin oxygen affinity. These studies suggest that the newborn rat, when properly stimulated, is able to produce normal amounts of erythropoietin, most likely renal in origin.
Lack of autologous mixed lymphocyte reaction in patients with chronic lymphocytic leukemia: evidence for autoreactive T-cell dysfunction not correlated with phenotype, karyotype, or clinical status
Authors: Han T , Bloom ML , Dadey B , Bennett G , Minowada J , Sandberg AA , Ozer H 
Published: October 2019

Abstract
In the present study, there was a complete lack of autologous MLR between responding T cells or T subsets and unirradiated or irradiated leukemic B cells or monocytes in all 20 patients with CLL, regardless of disease status, stage, phenotype, or karyotype of the disease. The stimulating capacity of unirradiated CLL B cells and CLL monocytes or irradiated CLL B cells was significantly depressed as compared to that of respective normal B cells and monocytes in allogeneic MLR. The responding capacity of CLL T cells was also variably lower than that of normal T cells against unirradiated or irradiated normal allogeneic B cells and monocytes. The depressed allogeneic MLR between CLL B cells or CLL monocytes and normal T cells described in the present study could be explained on the basis of a defect in the stimulating antigens of leukemic B cells or monocytes. The decreased allogeneic MLR of CLL T cells might simply be explained by a defect in the responsiveness of T lymphocytes from patients with CLL. However, these speculations do not adequately explain the complete lack of autologous MLR in these patients. When irradiated CLL B cells or irradiated CLL T cells were cocultured with normal T cells and irradiated normal B cells, it was found that there was no suppressor cell activity of CLL B cells or CLL T cells on normal autologous MLR. Our data suggest that the absence or dysfunction of autoreactive T cells within the Tnon-gamma subset account for the lack of autologous MLR in patients with CLL. The possible significance of the autologous MLR, its relationship to in vivo immunoregulatory mechanisms, and the possible role of breakdown of autoimmunoregulation in the oncogenic process of certain lymphoproliferative and autoimmune diseases in man are discussed.
The significance of megakaryocyte size
Authors: Levine RF , Hazzard KC , Lamberg JD 
Published: October 2019

Abstract
Normal guinea pig and human megakaryocytes in suspension were measured with an optical micrometer. The range of megakaryocyte diameters in both species was from 10 to about 65 micrometer. Approximately 20%-25% of megakaryocytes were smaLler than 20 micrometer in diameter and were mostly missed in past studies. However, virtually the entire population of megakaryocytes was larger than all but a very small percent of the other marrow cells. This size range and the existence of a visual threshold size between the megakaryocytes and nonmegakaryocytes were confirmed by flow cytometric analysis of fresh unfixed cells. On human bone marrow smears there was some flattening of all cell types, but the megakaryocytes were consistently at least minimally greater in size than almost all the nonmegakaryocytes. Normal marrow cells greater than 20 micrometer in diameter were always megakaryocytes. Cells 14–20 micrometer were still noticeably larger than the general marrow population; thus easily found, they could be examined for specific morphological criteria. Size, therefore, is a useful first criterion for the identification of megakaryocytes. The larger sizes of megakaryocytes were related to their greater DNA content per cell (polyploidy) compared to nonmegakaryocytes. The relationship between megakaryocyte size, ploidy, and maturation was examined by the simultaneous measurement for the first time of each of these parameters in the same cell. Maturation was quantitated by the new scheme based on the progressive changes in megakaryocytes nuclear configuration. Within each maturation stage the mean cell volume of guinea pig megakaryocytes doubled with each ploidy doubling. Within each ploidy group, the sizes of megakaryocytes increased with maturation stage. However, maturation and polyploidization appear to be linked; the data showed that 80% of the low ploidy (4N-8N) megakaryocytes were immature and that 95% of the platelet-shedding megakaryocytes were 16N-32N.
The inhibitory effects of exogenous arachidonic acid on rabbit platelet aggregation and the release reaction
Authors: Cattaneo M , Kinlough-Rathbone RL , Perry DW , Chahil A , Vickers JD , Lam SC , Packham MA , Mustard JF 
Published: October 2019

Abstract
Although arachidonic acid causes rabbit platelet aggregation and the release of granule contents in suspensions of washed platelets when used in concentrations of approximately 50–300 microM, higher concentrations (500 microM) cause neither aggregation nor release. Suspensions of platelets from rabbits wee exposed to arachidonic acid (250 microM) for 15 min, allowed to recover in the presence of PGE1 for 30 min, washed, and resuspended; in some experiments, the platelets were treated with aspirin before being exposed to arachidonic acid. Aggregation of platelets pretreated with arachidonic acid was inhibited in response to ADP; this effect was greater with the non-aspirin- treated platelets and persisted for at least 4 hr after resuspension. The association of 125I-fibrinogen with the platelets as a result of ADP stimulation was also inhibited. Aggregation and release of granule contents in response to collagen and low concentrations of thrombin was inhibited, but the inhibition could be overcome by higher concentrations. Thrombin induced further release of granule contents from platelets exposed to arachidonic acid without pretreatment with aspirin. Platelets that had been exposed to arachidonic acid, either with or without pretreatment with aspirin, did not aggregate or undergo further release upon stimulation with arachidonic acid after they were washed and resuspended. Inhibition of the lipoxygenase pathway with eicosatetraynoic acid (ETYA) or nordihydroguaiaretic acid (NDGA) did not affect the inhibition caused by arachidonic acid, so it is unlikely that a product of this pathway is responsible for the inhibition. Mixing experiments indicated that the pretreated platelets did not form a thromboxane-A2-like activity, and that they were unresponsive to aggregation and release induced by products formed from arachidonic acid. Experiments with 3H-arachidonic acid showed that after 45 min of incubation with platelets, only 1.1% of the 3H-arachidonic acid remained as free arachidonic acid in the platelets. Although cyclic-AMP was slightly increased 1 min after the addition of arachidonic acid, the cyclic-AMP concentration was the same as that of control platelets after the platelets were washed and resuspended, indicating that increased cyclic-AMP is not likely to be responsible for the persistent inhibitory effect. Thus, the inhibitory effect of pretreatment with arachidonic acid is a general effect on responses to a variety of aggregating agents that act through different mechanisms, and the inhibition is not related to thromboxane-A2 formation. The possibility of membrane perturbation resulting in the unavailability of receptors may explain the persistent inhibitory effect, but the responsible reactions have not been identified.