bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glycosaminoglycans in human neutrophils and leukemic myeloblasts: ultrastructural, cytochemical, immunologic, and biochemical characterization
Authors: Parmley RT , Hurst RE , Takagi M , Spicer SS , Austin RL 
Published: October 2019

Abstract
Chondroitin sulfate is known to be present in normal and leukemic myeloid cells; however, its definitive subcellular location and association with other glycosaminoglycans (GAGs) has not been demonstrated. We have studied the type and distribution of GAGs in neutrophil granule subpopulations of normal and leukemic myeloid cells using ultrastructural, cytochemical, immunologic, and biochemical methods. At the ultrastructural level, high-iron diamine- thiocarbohydrazide-silver proteinate (HID-TCH-SP) stained sulfated glycoconjugates selectively in immature primary granules of normal promyelocytes and Auer rods and immature granules of leukemic myeloblasts. Staining was weak or absent in mature primary granules, whereas tertiary granules stained moderately. Primary granule staining with HID-TCH-SP was greatly diminished by prior treatment of the specimens with chondroitinase ABC and/or nitrous acid, indicating the presence of chondroitin sulfate and N-sulfated glycosaminoglycan. Immunostaining of myeloid cells with a rabbit antichondroitin 4-sulfate and ferritin-conjugated goat anti-rabbit IgG sequence resulted in staining of most primary granules. Biochemical analysis of GAGs from leukemic myeloblasts containing primary granules and Auer rods, but lacking secondary and tertiary granules, revealed 8 x 10(-17) mole of uronic acid/cell and electrophoretic and sulfaminohexose analysis showed 60%-70% chondroitin sulfate AC of heterogeneous molecular weight, 20%-30% of a GAG that most closely resembled heparan sulfate, and 10% dermatan sulfate. The lack of significant HID-TCH-SP staining of sulfate iin sites other than Auer rods and primary granules in leukemic myeloblasts indicates that these granules contain the chondroitin, dermatan, and heparan sulfate isolated from the same specimen. Similar GAGs are present in primary granules of normal cells as evidenced by their cytochemical and immunostaining properties. Thus, these studies demonstrate a heterogeneous population of GAGs not previously identified and localize these substances to the primary granule of leukemic and normal cells.
The significance of transferrin for intestinal iron absorption
Authors: Huebers HA , Huebers E , Csiba E , Rummel W , Finch CA 
Published: October 2019

Abstract
A mechanism is proposed by which apotransferrin is secreted from mucosal cells, loaded with iron in the intestinal lumen, and then the intact complex is taken into the cell. Within the cell, iron is released and transferred to the blood stream, whereas iron-free transferrin returns to the brush border to be recycled. We have investigated this hypothesis by measuring intestinal absorption of radioiron and 125I-labeled plasma transferrin using tied-off gut segments in normal and iron-deficient rats. There was no absorption of diferric transferrin from the ileum, but high absorption from the duodenum and jejunum segments. Jejunal absorption occurred as a function of the dose offered and showed saturation kinetics. In normal animals, 4 micrograms of the 50 micrograms of transferrin iron was absorbed over 1 hr. In iron-deficient animals, mean values as high as 13 micrograms were observed. Radioiron content of the jejunal mucosa bore a linear relationship to the dose administered and was inversely proportional to the amount of iron entering the plasma. Recycling of transferrin was indicated by the presence of labeled apotransferrin in the lumen, first observed between 15 and 60 min after the injection of diferric transferrin. A high resistance of diferric and apotransferrin to proteolytic degradation within the gut lumen was demonstrated. Comparative studies with lactoferrin and ferritin disclosed poor availability of their iron for absorption. The small amount that was absorbed did not relate to the iron status of the recipient animal. These studies support the role of mucosal transferrin as a shuttle protein for iron absorption.
Efficacy and morbidity of central nervous system "prophylaxis" in childhood acute lymphoblastic leukemia: eight years' experience with cranial irradiation and intrathecal methotrexate
Authors: Inati A , Sallan SE , Cassady JR , Hitchcock-Bryan S , Clavell LA , Belli JA , Sollee N 
Published: October 2019

Abstract
Between 1972 and 1979, 214 children with acute lymphoblastic leukemia and no evidence of central nervous system (CNS) disease prior to CNS prophylaxis were treated with 2400 rad cranial irradiation and concurrent intrathecal methotrexate. Only nine children developed CNS leukemia; five of them in the CNS only and four concurrently in the CNS and another site. Major acute effects of CNS prophylaxis were seizures in seven patients (3%). Sixty-nine children who had a minimum follow-up of 4 yr were evaluable for late effects of therapy. Small cataracts, incomplete regrowth of hair, and learning disabilities were noted. The latter occurred in 18% of patients, an incidence similar to that encountered in a normal community of school-age children. However, the incidence of learning disabilities in patients who were under 5 yr of age at the time of diagnosis was much higher, 35%. We conclude that the combination of cranial irradiation and intrathecal methotrexate was highly efficacious. The incidence and severity of neuropsychologic abnormalities, the principal late morbidity of this treatment program, varies among reporting institutions. Prospective longitudinal studies of neuropsychologic function are necessary to better define the incidence of abnormalities. Future programs should attempt to decrease late morbidity, but must also assure equal efficacy and improve overall disease-free survival.
Response to splenectomy in 65 patients with hairy cell leukemia: an evaluation of spleen weight and bone marrow involvement
Authors: Golomb HM , Vardiman JW 
Published: October 2019

Abstract
Sixty-five patients with hairy cell leukemia underwent splenectomy; 27 had a complete remission as defined by a return in WBC, RBC, and platelet counts to a defined level, and 38 had a partial remission with a return of only one or two of these parameters to the defined level. The 5-yr actuarial survival for all patients is 68%; for CR patients it is 76%, and for PR patients 62%. The response to splenectomy did not correlate with the spleen weight. Seventeen patients had a postsplenectomy platelet count of less than 200 x 10(9)/liter, and 34 patients had a postsplenectomy platelet count of 200 x 10(9)/liter or greater. A presplenectomy bone core biopsy hairy cell index (HCI) was calculated by multiplying the percent marrow cellularity by the percent of hairy cells in the marrow for 51 patients. The difference in the mean HCI between the two platelet response groups is statistically significant (p less than 0.05). Of the 15 patients with a presplenectomy HCI of 0.7 or greater, 9 (60%) did not have a satisfactory platelet response to splenectomy, whereas of 36 patients with an HCI of 0.7 or less, only 8(22%) did not have a satisfactory platelet response to splenectomy (p less than 0.01). The HCI appears to indicate the significance of underproduction of platelets as a result of marrow replacement by hairy cells.
Effect of aspirin and sodium salicylate on thrombosis, fibrinolysis, prothrombin time, and platelet survival In rabbits with indwelling aortic catheters
Authors: Cattaneo M , Chahil A , Somers D , Kinlough-Rathbone RL , Packham MA , Mustard JF 
Published: October 2019

Abstract
We have studied the effect of different doses of aspirin on platelet function, PGI2 formation, platelet survival, thrombosis, fibrinolysis, and prothrombin time in rabbits with indwelling aortic catheters. The thrombi formed around indwelling aortic catheters were found to have a large fibrin component, and their formation was inhibited by heparin administration. Thus, in these experiments we examined the effect of aspirin (a weak inhibitor of thrombin-mediated platelet aggregation) under conditions in which thrombin was a major factor in the initiation and growth of the thrombi. Only very high doses of aspirin tended to inhibit thrombus formation over the 5-day period of observation, and a statistically significant inhibition of thrombus formation was produced by equivalent concentrations of sodium salicylate. The failure of high doses of aspirin to achieve a significant inhibition of thrombosis under the conditions of these experiments (whereas an equivalent dose of sodium salicylate was inhibitory) could be due to aspirin inhibition of PGI2 formation. Shortened platelet survival was not affected by aspirin treatment or the dose sodium salicylate that inhibited thrombus formation. The tendency to inhibit thrombus formation appeared to be unrelated to an effect on platelets but was associated with prolongation of the one-stage prothrombin time and increased whole blood fibrinolytic activity; doses of aspirin that inhibited platelet aggregation in response to sodium arachidonate or collagen, and PGI2 formation by the vessel wall, did not have a significant effect on the amount of thrombus present at 5 days. However, the high doses of aspirin that inhibited PGI2 formation were associated with a tendency to increased thrombus formation during the first 3 hr after insertion of the catheter. The results of these experiments show that when thrombin is an important factor in the formation of thrombi, aspirin is a weak inhibitor of thrombosis unless doses are used that provide sufficient salicylate to interfere with blood coagulation and promote whole blood fibrinolytic activity. These results also show that thrombus formation can be inhibited without an apparent change in platelet survival.
The expression of myeloid-specific antigens on myeloid leukemia cells: correlations with leukemia subclasses and implications for normal myeloid differentiation
Authors: Ball ED , Fanger MW 
Published: October 2019

Abstract
The expression of three distinct myeloid-specific cell surface antigens detected by monoclonal antibodies (PMN 6, PMN 29, and AML-2–23) on acute and chronic myeloid leukemia cells is correlated with blast cell morphology and normal myeloid cell antigen display. In studies on normal peripheral blood cells, monoclonal antibodies PMN 6 and PMN 29 have previously been shown to react exclusively with neutrophils while AML-2–23 reacts with both neutrophils and monocytes. The present report demonstrates that these antigens are absent from blast cells of patients with acute myelocytic leukemia (AML) classified as M1 and M2 in the French-American-British system and chronic myelocytic leukemia in myeloid blast crisis. However, leukemia cells with myelomonocytic morphology (M4) expressed all three antigens, while cells with pure monocytic features (M5) were generally only positive for AML-2–23. Based on the absence of these antigens on both leukemic and normal myeloblasts and granulocyte-monocyte progenitors and their characteristic patterns of display on more differentiated leukemic and normal cells, we propose a modified concept of normal myelopoiesis. In this hypothesis, the myeloblast is an uncommitted cell that gives rise to a series of intermediate precursors that acquire committment to either the granulocytic or monocytic lineage marked by the acquisition of specific cell surface markers.
Extracellular matrix production by the adherent cells of long-term murine bone marrow cultures
Authors: Zuckerman KS , Wicha MS 
Published: October 2019

Abstract
We have studied the deposition of extracellular matrix proteins in the adherent stroma of long-term murine bone marrow cultures. Stable hematopoiesis was maintained for greater than 12 wk. At selected intervals, culture dishes were sacrificed by removing all nonadherent cells and air drying the dishes. The adherent stromal layer was analyzed for the presence of intracellular and extracellular collagen, fibronectin, and laminin using double immunofluorescent staining with specific antisera against these matrix components. In cultures examined during the first 2 wk, large numbers of stromal cells contained collagen, fibronectin, and laminin. Over the next 2 wk, an extensive extracellular network of fibronectin, laminin, and collagen was deposited on the dishes, which persisted throughout the life of the cultures. In contrast to a previous report, we detected substantial numbers of endothelial cells by means of immunofluorescent staining of stromal cells with antisera to type IV collagen, laminin, and factor VIII antigen. Although deposition of these extracellular matrix proteins coincides with onset of active hematopoietic cell production, the relative roles of the stromal cells and the extracellular matrix in supporting hematopoiesis in murine bone marrow cell cultures remain to be determined.
Circulating lymphocyte populations in Hodgkin's disease after mantle and paraaortic irradiation
Authors: Posner MR , Reinherz E , Lane H , Mauch P , Hellman S , Schlossman SF 
Published: October 2019

Abstract
The effect of mantle and paraaortic radiation on peripheral blood lymphocytes was studied in 11 previously untreated patients with early stage Hodgkin's disease using a series of monoclonal antibodies defining immunoregulatory lymphoid cells. Immediately following the completion of radiotherapy, there was a significant reduction in the number of lymphocytes and the percent of circulating T cells. This acute decrease in T cells was due to a marked diminution in the number of inducer T cells, while the fraction of suppressor T cells remained constant. These changes persisted for up to 12 mo and were accompanied by a later increase in the fraction of circulating B lymphocytes and cells bearing surface Ia. It thus appears that mantle and paraaortic radiotherapy causes a relatively selective reduction in the inducer T- cell population. The implications of a change in the ratio of inducer to suppressor T cells is discussed.
Basophil/mast cell precursors in human peripheral blood
Authors: Denburg JA , Richardson M , Telizyn S , Bienenstock J 
Published: October 2019

Abstract
Semisolid (methylcellulose) hemopoietic cultures revealed the presence of histamine-containing granulocyte colonies derived from precursors (CFU-C) present in human peripheral blood. Light microscopy and histochemical studies of cells in individual histamine-containing colonies demonstrated homogeneous populations of metachromatic basophil/mast cells (BMC) at various stages of maturation. By inverted microscopy, pure BMC colonies were more often found to have the overall appearance of the previously described “eosinophil” (type II), rather than “neutrophil-macrophage” (type I), colony type. Histamine-positive colonies constituted 58% (50/86) of all (type I and type II) granulocyte colonies in repeated cultures from a patient with systemic mastocytosis (SM), and 19% (13/67) of colonies in cultures from 8 patients with chronic myeloid leukemia (CML); this was in contrast to 8% (12/153) of colonies in cultures from 4 patients with urticaria pigmentosa (UP) and 6 normal controls (p less than 0.0001). Calculated frequency of BMC CFU-C was approximately 1 per 2 X 10(6) in normal and 1 per 2 X 10(5) nucleated cells in SM peripheral blood. Taking colony size into account, histamine content per cell in histamine-positive type II colonies in SM cultures was 1.1 +/- 0.19 pg, compared to 0.29 +/- 0.08 pg in CML and less than or equal to 0.10 in normals and UP. Electron microscopy (EM) of individual colonies revealed electron-dense granules with ultrastructural features of BMC in histamine-positive, but not histamine-negative, colonies. Use of these methods may help to further clarify the nature of BMC precursors and the regulation of their proliferation in bone marrow disorders and allergic states.
Endogenous proteolysis of membrane-bound red cell cytochrome-b5 reductase in adults and newborns: its possible relevance to the generation of the soluble "methemoglobin reductase"
Authors: Choury D , Reghis A , Pichard AL , Kaplan JC 
Published: October 2019

Abstract
The problem of the low activity of so-called methemoglobin reductase in red cells from newborns was reinvestigated in view of our current knowledge of this enzyme, i.e., (1) its being cytochrome-b5 reductase and (2) its presence in two forms: soluble and membrane-bound. We found that red cells from cord blood and newborns exhibited a 50% decrease of soluble cytochrome-b5 reductase activity, whereas membrane-bound activity was in the adult range. Ghosts from these cells possessed diminished ability to solubilize membrane-bound cytochrome-b5 reductase in the course of in vitro auto-incubation. This autosolubilizing ability increased with age and reached adult level concomitantly with soluble cytochrome-b5 reductase activity at 6 mo. We conclude that the relative deficiency of soluble cytochrome-b5 reductase observed at birth is due to diminished post-translational processing of the membrane-bound enzyme during erythropoiesis of fetal cells. This processing is calcium-dependent related to calmodulin.
Osmotic gradient ektacytometry: comprehensive characterization of red cell volume and surface maintenance
Authors: Clark MR , Mohandas N , Shohet SB 
Published: October 2019

Abstract
Whole cell deformability of red cells was measured as a continuous function of suspending medium osmolality using the ektacytometer, a laser-diffraction viscometer. Study of normal cells in which water content and membrane surface area had been selectively modified showed that this technique can detect changes in these properties with high sensitivity. The osmotic deformability profiles obtained from this assay provide information about cell water content, surface area, and the heterogeneity in these cellular properties, information that by conventional methods would require several different types of measurements. Application of this approach to a variety of pathologic blood samples showed that various hematologic disorders can be characterized by the shape of this profile and the position of specific features of the profile along the osmolality axis. Measurement of osmotic deformability profiles thus provides a convenient and comprehensive means of identifying abnormalities either in red cell water content or surface area.
Severe deficiency of natural killer activity in the peripheral blood of patients with hairy cell leukemia
Authors: Ruco LP , Procopio A , Maccallini V , Calogero A , Uccini S , Annino L , Mandelli F , Baroni CD 
Published: October 2019

Abstract
Natural killer (NK) activity against K-562 tumor cells was evaluated in peripheral blood leukocytes (PBL) obtained from untreated patients affected by hairy cell leukemia (HCL). NK activity present in PBL from 10 HCL patients was at least six-fold lower (p less than 0.01) than that present in PBL from 15 healthy donors. Decreased NK activity in HCL PBL was not due to dilution of the NK effector cells by the neoplastic cells; in fact, NK activity of PBL from 4 HCL patients with less than 5% circulating neoplastic cells was still five-fold lower (p less than 0.01) than that present in normal PBL. Partial characterization of the NK defect in HCL patients indicated that: (A) defective cytotoxicity was not dependent on the duration of the assay; (B) HCL PBL added to normal PBL during the assay did not exert suppressor activity; (C) the NK activity of HCL PBL could be potentiated in vitro by interferon; and (D) low levels of NK activity were associated with reduced numbers of circulating monocytes (p less than 0.01) and of large granular lymphocytes (LGL) (p less than 0.01). In conclusion, our results indicate that the low levels of NK activity present in the peripheral blood of HCL patients may be related to reduced numbers of circulating effector cells.
Heterogeneity of autoantibodies to factor VIII: differences in specificity for apparently distinct antigenic determinants of factor VIII coagulant protein
Authors: Croissant MP , Zuzel M , Allain JP 
Published: October 2019

Abstract
The interference of antibodies to factor VIII coagulant protein (VIII:C) of 9 nonhemophilic patients with the binding to factor VIII coagulant antigen (VIII:CAg) of a reference hemophilic 125I-Fab' reagent, used in a liquid phase VIII:CAg assay, was studied. The binding competition was estimated from immunoradiometric assay (IRMA) dose-response slope of VIII:CAg present in patient plasma, interference of antibodies with the 125I-Fab' binding to VIII:CAg in normal plasma, and the displacement of antibody from the complexes with VIII:CAg by the 125I Fab'. Antibody populations from three patients were studied in detail; in the VIII:CAg assay, two of them interfered with the 125I- Fab' binding, and one did not (patient 1). The formation of stable complexes between antibodies of each patient and VIII:CAg was demonstrated by protein-A-Sepharose adsorption. The 125I-Fab' binding to VIII:CAg-anti-VIII:CAg IgG complexes indicated that patient 1 antibodies and the 125I-Fab' recognized different antigenic determinants, whereas the other two patient antibodies and 125I-Fab' recognized closely related or identical VIII:CAg determinants. These results demonstrate an apparently selective recognition of at least two distinct VIII:CAg determinants by naturally occurring antibodies, suggesting a possibility of a wider use of these antibodies in studies of the structure and function of factor VIII.
Clinical, morphological, and cell kinetic differences among multiple myeloma, monoclonal gammopathy of undetermined significance, and smoldering multiple myeloma
Authors: Greipp PR , Kyle RA 
Published: October 2019

Abstract
We reviewed the clinical and morphological findings in 43 cases of monoclonal gammopathy of undetermined significance (MGUS), 9 of smoldering multiple myeloma (SMM), and 23 of overt multiple myeloma (MM). In all cases, the patients' physicians had requested a bone marrow examination because of the possibility of MM. In all 75 cases, 3H-thymidine labeling indices were performed. The plasma cell labeling index correctly classified 62 of the 75 cases (83%). A linear discriminant function combining the labeling index and percentage of plasma cells improved the accuracy to 92% (69/75), or to 95% (71/75) if patients in whom MM developed within 6 mo were considered to have MM. The labeling index was most critical for the differential diagnosis of MM from SMM (p less than 0.001). Serum or urine M-protein level, percentage of plasma cells or lymphocytes in the bone marrow, and plasma cell grade, asynchrony, and nucleolar size failed to discriminate the group with SMM from the group with MM. In patients with MGUS or SMM, a plasma cell labeling index greater than 0.4% warned of impending MM. The plasma cell labeling index is a reliable diagnostic test when applied in cases of monoclonal gammopathy, especially when differentiation from MM is difficult using standard clinical criteria.
Low ploidy megakaryocytes in steady-state rat bone marrow
Authors: Tanum G , Engeset A 
Published: October 2019

Abstract
The amount of DNA in individual megakaryocytes (MK) was measured by Feulgen photometry performed on smears of steady-state rat bone marrow. The MK were identified by acetylcholinesterase (ACHE) staining. The method described is particularly suitable in the study of immature MK, hitherto difficult to examine for DNA content. The main MK ploidies were 8N, 16N, and 32N, comprising 33.4% +/- 1.4%, 40.8% +/- 1.4%, and 17.9% +/- 1.3%, respectively, of the total MK numbers. Only 6.7% +/- 1.7% had less than octoploid DNA content. Very few cells were found belonging to the 64N class. Among the immature MK, a relatively large fraction was found between the ploidy levels, indicating a rapid turnover within these ploidy classes. The demonstration of ACHE activity even in MK with a diploid DNA content indicates that the flow from the committed progenitors to differentiated MK occurs at the 2N level.