bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chloroma (granulocytic sarcoma) without evidence of leukemia: facilitated light microscopic diagnosis
Authors: McCarty KS Jr , Wortman J , Daly J , Rundles RW , Hanker JS 
Published: October 2019

Abstract
Localized tumors composed of immature cells of the myelogenous series have been recognized for many years as an uncommon manifestation of granulocytic leukemia. The histologic diagnosis of chloroma (granulocytic sarcoma) may be extremely difficult when the myeloblastic cells are poorly differentiated and the tumor lacks the characteristic green color. The diagnostic difficulty may be further compounded when the granulocytic sarcoma develops before there is peripheral blood or bone marrow evidence of leukemia. Previous criteria for the diagnosis of chloroma have been ambiguous because of the capricious nature of the hydroperoxidase activity and the lack of definitive histochemical criteria. In this case, a combination of Sudan black B and myeloperoxidase histochemical staining and ultrastructural evaluation was applied. The light microscopic histochemical studies suggested the presence of Phi bodies and rods both in the formalin-fixed tumor and in the cells derived from the subsequent pleural effusion; this was confirmed by electron microscopy, which demonstrated the peridicity of the crystalline rod substructure. These observations show that light microscopic histochemical studies can facilitate the diagnosis of granulocytic sarcoma or chloroma in the absence of peripheral blood or bone marrow manifestations of leukemia.
Long-term human bone marrow cultures
Authors: Hocking WG , Golde DW 
Published: October 2019

Abstract
Pronlonged in vitro growth of murine bone marrow has been achieved using a flask culture system. We report the adaption of the technique to the growth of human bone marrow. In this system, CFU-GM and CFU-E are maintained for 4–9 wk. Morphologically recognizable granulopoiesis occurs for 4–6 wk and erythropoiesis for 1.5–2.5 wk. Functional T lymphocytes are maintained for at least 5 wk. The adherent population is composed of macrophages, fibroblast-like cells, and flat pavement- like cells. Fat-containing cells are not prominant. This culture system provides a means to study human hematopoietic cell proliferation and differentiation in vitro, as well as to examine interactions between stromal cells and hematopoietic and lymphoid progenitors.
Mixed lymphoblastic-myelomonoblastic leukemia in treated Hodgkin's disease
Authors: Prentice AG , Smith AG , Bradstock KF 
Published: October 2019

Abstract
In a case of acute leukemia occurring 5.5 yr after diagnosis of Hodgkin's disease, a mixture of lymphoid and myelomonocytoid blasts was identified by morphological, cytochemical, and immunologic methods. The majority of blasts were characterised as lymphoid by their strong expression of nuclear terminal transferase (TdT) enzyme. In contrast, a minor blast population was identified as myelomonocytoid by the strong nonspecific esterase positivity and lack of TdT. The two distinct blast cell populations showed different sensitivity to the various chemotherapeutic protocols used.
Thrombocytopenia in septicemia: the role of disseminated intravascular coagulation
Authors: Neame PB , Kelton JG , Walker IR , Stewart IO , Nossel HL , Hirsh J 
Published: October 2019

Abstract
The mechanism of isolated thrombocytopenia in septicemia is unknown, but compensated disseminated intravascular coagulation (DIC) has been suggested as a possible cause. To investigate this possibility, platelet counts and sensitive assays for in vivo thrombin and plasmin generation, including fibrinogen gel chromatography and fibrinopeptide A (FPA) assays, were obtained on 31 septicemic patients. Fifteen of 17 patients with gram-negative septicemia and 8 of 14 patients with gram- positive septicemia had thrombocytopenia. Platelet survival studied demonstrated a decreased platelet survival. In 11 of 12 patients with severe thrombocytopenia (platelet count less than 50,000mul), there was laboratory evidence of intravascular coagulation. In contrast, there was little evidence of intravascular coagulation in 8 of 11 patients with moderate thrombocytopenia (platelet counts 50,000 to less than 150,000/mul) or in 7 of 8 patients with normal platelet counts. This report indicates that while DIC accompanies thrombocytopenia in many patients with severe thrombocytopenia, there is frequently little evidence for intravascular coagulation in patients with moderate thrombocytopenia. It is apparent that factors other than intravascular thrombin must play a role in producing the thrombocytopenia of septicemia.
G gamma and A gamma globin-chain biosynthesis by adult and umbilical cord blood erythropoietic bursts and reticulocytes
Authors: Terasawa T , Ogawa M , Porter PN , Karam JD 
Published: October 2019

Abstract
We examined gamma-globin-chain biosynthesis by adult and umbilical cord blood or erythropoietic bursts in methylcellulose clonal culture and gamma-chain synthesis by cord blood reticulocytes. Globin chains were labeled with 14C-amino acids and guantitated by using autoradiography or fluorography. Alpha, beta, and G gamma and A gamma chains were separated by isoelectric focusing in polyacrylamide gels containing 8 M urea and 3% Nonidet P-40 (a nonionic detergent). Time course examinations of the gamma-chains synthesized by the bursts revealed no changes in the G gamma:A gamma ratio between days 10 and 18 of culture. The ratio of G gamma/(G gamma + A gamma) in cultures of adult circulating erythroid precursors was 0.38 +/- 0.09, which corresponds to the known ratio in adult peripheral blood erythrocytes. The relative G gamma-chain biosyntheses in the cord blood bursts and reticulocytes were 0.56 +/- 0.02 and 0.66 +/- .008, respectively. Both are intermediate between the accepted newborn and adult ratios. Natal erythropoietic precursors appear to be in the transitional stage with respect to the switching of G gamma-A gamma ratios.
Studies on levamisole--induced agranulocytosis
Authors: Thompson JS , Herbick JM , Klassen LW , Severson CD , Overlin VL , Blaschke JW , Silverman MA , Vogel CL 
Published: October 2019

Abstract
Widespread clinical trials of leavo-tetramisole (levamisole) as an immunopotentiating agent in rheumatoid arthritis, metastatic carcinoma, and immunodeficiency states have been complicated by agranulocytosis (AGC) in 2.5%–13% of patients. Other than a relationship with prolonged high dosage, very little is known regarding the pathogenesis of levamisole-induced AGC. Whereas leukoagglutination was negative, fluorochromatic microgranulocytotoxicity (GCY) tests were positive with serum from 10 of 10 acutely neutropenic patients. The antibody was IgM, reacted with 100% of unrelated granulocytes, but not with T or B lymphocytes. Some sera also reacted with monocytes and the myeloid cell line, K-562. Tests for antigen-antibody complexes or cold autoantibodies were negative. Although clinical evidence strongly suggests a haptene (drug) mechanism, in vitro mixing experiments were also negative. An alternative choice parallels the model of aldomet- induced Coombs'-positive hemolytic anemia. Finally, GCY first became positive 2–3 mo prior to the onset of AGC on two patients, suggesting the possibility of identifying those at risk well before the onset of neutropenia.
Prenatal diagnosis of hemophilia B by an immunoradiometric assay of factor IX
Authors: Holmberg L , Gustavii B , Cordesius E , Kristoffersson AC , Ljung R , Lofberg L , Stromberg P , Nilsson IM 
Published: October 2019

Abstract
An immunoradiometric assay of factor IX was developed based on homologous antibodies that arose in a hemophilic patient. With this assay, 11 of 12 patients with severe hemophilia B had factor IX antigen levels below 1 U/dl and 6 patients with mild hemophilia B had various levels. Factor IX antigen in 8 fetuses (16th–20th gestational week) aborted for therapeutic reasons ranged from 1.8 to 10.0 U/dl. Six amniotic fluids contained 0.28–1.2 U/dl factor IX antigen. Using the immunoradiometric assay, we could diagnose hemophilia B prenatally in one fetus at risk. No factor IX antigen (< 0.2 U/dl) was detectable in the fetoscopic sample. After termination of the pregnancy, analysis of blood from the abortus confirmed the diagnosis of severe hemophilia B. We conclude that very sensitive immunologic assays, such as the one described here, will prove useful in prenatal diagnosis of severe hemophilia B, since determination of factor IX activity in fetoscopic samples is unrealiable because of possible contamination with thromboplastic material.
Plasmic degradation of crosslinked fibrin. I. Structural analysis of the particulate clot and identification of new macromolecular-soluble complexes
Authors: Francis CW , Marder VJ , Martin SE 
Published: October 2019

Abstract
Plasmic degradation of crosslinked fibrin has been studied to identify the proteolytic cleavages that convert the clot into a soluble lysate and also to identify the derivatives that are likely to circulate during clot dissolution. Initial polypeptide chain cleavages do not disrupt the solid clot matrix. With continued exposure to plasmin, high molecular weight derivatives are produced that remain attached to the clot by noncovalent forces. Further degradation then results in the liberation into solution of several large, noncovalently bound complexes. Progressive degradation of the largest, initially liberated complexes to the terminal derivatives, DD/E, DD, and E, occurs in solution after their release from the clot. As the fibrin clot is exposed to plasmin for longer intervals, progressive dissolution occurs, but the structure of the covalently bound insoluble fibrin core, the noncovalently attached derivatives, and the liberated complexes remains constant. Since much of the initially liberated protein is in complexes larger than DD/E, these derivatives probably represent the more prevalent plasmic degradation products of crosslinked fibrin in vivo.
Hemoglobin switching in sheep: a comparison of the erythropoietin- induced switch to HbC and the fetal to adult hemoglobin switch
Authors: Barker JE , Pierce JE , Nienhuis AW 
Published: October 2019

Abstract
Stimulation of sheep erythropoietic progenitor cells by erythropoietin (epo) has been studied with regard to its effect on the pattern of hemoglobin production. An analysis of hemoglobin (Hb) synthesis in BFU- E- and CFU-E-derived colonies from fetuses either homozygous for HbA (AA) (homozygous also for the beta c gene responsible for HbC production) or HbB (BB) (lacking the beta c gene) indicated the following. Colonies derived from precursor cells from 51- and 89-day fetuses exhibited small but detectable increments of HbB synthesis with prolonged incubation in vitro. This response was not dependent on the epo concentration. Erythropoietic precursor cells from a 124-day BB fetus were already committed to HbB synthesis, since HbF production was replaced by HbB on successive days in vitro as erythroid colonies matured; this switch was not affected by varying the epo concentration. In contrast, progenitor cells from a 124-day AA fetus responded to higher doses of epo by forming colonies in which more HbC was made at the expense of both HbF and HbA. Erythropoietic stress did not result in induction of HbF in vivo or in erythroid colonies derived from CFU-E in young adult BB sheep, whereas our prior studies had shown induction of HbC synthesis under analogous conditions in colonies derived from young adult AA sheep. We conclude that the epo-induced HbF (or HbA) to HbC switch and the fetal to adult hemoglobin switch are regulated by different mechanisms.
Host defense deficiency in hairy cell leukemia and its correction by leukocyte transfusion
Authors: Hersh EM , Murphy S , Zander A , Dicke K , Stewart DJ , Toki H , Latreille J 
Published: October 2019

Abstract
A similar defect host defense mechanisms in hairy cell leukemia was defined in two patients. Surface-adherent monocytes were not detected in the peripheral blood nor were monocytes that mediate antibody- dependent cell-mediated cytotoxicity (ADCC) to isoantibody-coated human erythrocytes. In addition, lymphocytes of both patients failed to show blastogenic responses to concanavalin A (Con-A) and pokeweed mitogen (PWM) but showed a vigorous response to phytohemagglutinin (PHA). Other immunologic abnormalities were present but were either moderate in degree or were not present in both patients. In vitro lymphocyte blastogenic responses were fully restored by incubation of patients' leukocytes with a normal donor's adherent monocytes. One patient received daily allogeneic leukocyte transfusion for 4 days. This resulted in complete normalization of monocyte adherence and ADCC that persisted for several months after transfusion and was associated with hemotalogic improvement. Therapy in case 1 resulted in correction of the blastogenic responses to Con-A and PWM. Thus, a host defense defect in hairy cell leukemia has been defined in 2 patients and a preliminary result suggests that therapy with leukocyte transfusions may be useful in the postsplenectomy patient with an infectious complication and should be explored further.
In vivo release and turnover of secreted platelet antiheparin proteins in rhesus monkey (Macaca mulatta)
Authors: Musial J , Niewiarowski S , Edmunds LH Jr , Addonizio VP Jr , Nicolaou KC , Colman RW 
Published: October 2019

Abstract
Human and rhesus monkey platelets secrete at least two antiheparin proteins: platelet factor 4 (PF4) and low affinity platelet factor 4 (LA-PF4). Neither of these proteins showed species-related antigenic differences. As determined by radioimmunoassay, the levels of PF4 and LA-PF4 antigen per 10(9) monkey platelets amounted to 10.7 and 20.3 microgram, respectively. One milliliter of monkey plasma prepared from blood collected into an anticoagulant composed of EDTA, prostaglandin E1, and theophylline solution contained 22.4 ng LA-PF4 and 8.0 ng PF4. Concentrations of these two platelet-specific proteins in monkeys closely resembled levels found in human platelets and plasma. Infusion of prostacyclin (PGI2) (100 or 300 ng/kg/min) into monkeys for 15 min resulted in a significant decrease of plasma levels of LA-PF4 antigen and of PF4 by 40%--60% (p &lt; 0.0001). This decrease was related to the inhibitory effect of PGI2 on the secretion of platelets stimulated by a catheter or by venipuncture. Longer infusion of PGI2 did not produce further significant change. The supernate obtained after aggregation of human platelets stimulated by thrombin was injected into monkeys receiving PGI2 infusion. The disappearance of LA-PF4 antigen in monkey plasma followed a biphasic exponential curve with half-lives for the fast and slow components of 8.4 and 63 min. PF4 disappeared faster but followed the same pattern (half-lives for the fast and slow component of 2.1 and 70 min). Analysis of the experimental data suggests that the low levels of secreted platelet proteins in monkey plasma are related to their minimal in vivo release and to their rapid clearance.
Factor VIII coagulant antigen in hemophilic plasma: a comparison of five alloantibodies
Authors: Reisner HM , Price WA , Blatt PM , Barrow ES , Graham JB 
Published: October 2019

Abstract
Five independent alloantibodies directed to factor VIII coagulant antigen (VIII:CAg) were assessed against normal, von Willebrand's disease, and severe hemophilia A plasmas. Immunoradiometric assays (IRMAs) were developed for each antibody, one of which had arisen “spontaneously” and four in transfused hemophiliacs. The correlations between assays were very high for normal, vWd, and both CRM+ and CRM- hemophiliacs. This suggests that IRMAs maybe developed from almost any reasonably high titered alloantibody and used with confidence in diagnosing CRM- hemophilia A in utero by fetoscopy.
A new preparative method for isolation of human erythropoietin with hydrophobic interaction chromatography
Authors: Lee-Huang S 
Published: October 2019

Abstract
A new preparative method for isolation of human urinary erythropoietin (Ep) has been developed using hydrophobic interaction chromatography on Phenyl-Sepharose CL4B. Crude urine and urine concentrates from anemic patients were used directly without prior manipulation. In addition to facilitating hydrophobic interactions, Phenyl-Sepharose provided pi-pi interactions between its phenyl group on the gel matrix and the aromatic amino acid residues of Ep, and thus contributed to specific resolution. Over 90% of the urinary contaminants were excluded from the column, and Ep was selectively bound. Its activity was eluted with 20% ethylene glycol in 10 mM NaOH containing 4 M guanidine hydrochloride. This single step offered a mean purification factor of 110 with a recovery of 85%.
Aplastic anemia: lack of inhibitory effect of bone marrow lymphocytes on in vitro granulopoiesis
Authors: Sullivan R , Quesenberry PJ , Parkman R , Zuckerman KS , Levey RH , Rappeport J , Ryan M 
Published: October 2019

Abstract
Prompted by previous reports that in certain patients with aplastic anemia, cell-mediated autoimmune suppression of myeloid stem cell proliferation may be demonstrable in vitro, we studied the effects of bone marrow lymphocytes from 18 patients with myeloid aplasia on the proliferation of committed granulocytic-monocytic progenitor cells (CFU- C). When assayed in soft agar cultures, marrow suspensions from 10 patients with aplastic anemia contained significantly fewer viable CFU- C than similar cell preparations from control subjects. To deplete marrow cell suspensions of lymphocytes, we employed rabbit anti-human thymocyte serum (ATS), which after multiple adsorptions exhibited marked cytotoxicity for human B and T lymphocytes but had negligible effect on normal CFU-C proliferation. Preincubation of marrow samples from 12 patients with ATS and complement resulted in no inhibition or enhancement of CFU-C growth. In further experiments, marrow cells from 8 patients were incubated with marrow from control subjects prior to CFU-C culture. No suppression of donor CFU-C proliferation was observed in any of these studies, and in 4 cocultures, mixture of the 2 marrow suspensions resulted in stimulation of CFU-C growth. Using these assays, we detected no evidence of cell-mediated inhibition of CFU-C proliferation in any of the 18 patients that we evaluated. Our data support the conclusion that in the majority of patients with aplastic anemia, an absolute deficiency of hemopoietic stem cells is present within the marrow that does not appear to be effected or sustained by suppressor lymphocytes. Whether the reduction of viable stem cells is the cause or the consequence of the process that leads to marrow failure remains unknown.
Characterization of a suppressor T-cell chronic lymphocytic leukemia with ADCC but not NK activity
Authors: Pandolfi F , Strong DM , Slease RB , Smith ML , Ortaldo JR , Herberman RB 
Published: October 2019

Abstract
A patient with T-cell chronic lymphocytic leukemia (T-CLL) is reported whose cells demonstrate in vitro suppression of normal lymphocyte mitogen stimulation. The patient, who remains in Rai's clinical stage 0 on no therapy after more than 24 mo of observation, has shown a less aggressive clinical course than is usually attributed to T-CLL. His peripheral blood lymphocytes (PBL) were characterized by functional assays as well as surface markers. Over 90% of the patient's PBL formed rosettes with sheep erythrocytes and were lysed by two T-cell-specific antisera plus complement, while less than 1% bore surface immunoglobulins, and only 3% had complement receptors. In addition, 45% of the PBL demonstrated Ia-like antigens, more than 50% expressed a receptor for the Fc portion of IgG(T gamma), and most of the sheep erythrocyte rosettes were inhibited by theophylline. The patient's cells failed to respond to several mitogens and they caused marked suppression of lymphoproliferative responses to normal PBL to phytohemagglutinin (PHA) and concanavalin A (Con-A). The patient's lymphocytes also exhibited antibody-dependent cytotoxic activity (ADCC) against antibody-coated nucleated target cells, but lacked demonstrable natural killer (NK) activity. This patient's T-CLL cells appear to represent the clonal expansion of a subset of T cells with a previously undescribed pattern of suppressor and cytotoxic activities.
Polymorphonuclear motility: measurement by computer-linked image analysis
Authors: Howe GB , Swettenham KV , Currey HL 
Published: October 2019

Abstract
Most methods of measuring neutrophil motility provide information mainly about the performance of a small proportion of the fastest moving cells. Application of a computer-linked image analysis technique, using the “Quantimet,” provides a convenient, automated method of measuring the motility of the whole cell population. This makes it possible to test whether changes in motility represent a homogeneous alteration affecting all cells or a change in the numbers or performance of a subset of cells. In this study the neutrophils from patients with uncomplicated rheumatoid arthritis were found to perform similarly to normals, while cells from patients with Felty's syndrome were markedly slower. This was an overall, homogeneous slowing of the whole cell population, not due to a loss of fast moving cells.
Serial studies in von Willebrand's disease: variability versus "variants"
Authors: Abildgaard CF , Suzuki Z , Harrison J , Jefcoat K , Zimmerman TS 
Published: October 2019

Abstract
The variability of laboratory findings in von Willebrand's disease (vWd) was evaluated by performing serial studies of bleeding time (BT), factor VIII coagulant activity (VIII:C), factor-VIII-related antigen (VIIIR:Ag) and ristocetin cofactor (VIIIR:Rcof) in 50 individuals from 25 families with this disorder. The types of results were characterized from 1 to 16 based on the possible combinations of findings using these four tests. The only patients observed to have consistently abnormal results of all four tests were three individuals with homozygous vWd. Individuals with autosomal dominant vWd were found to have a variety of results and all 16 possible types were observed. Although a consistent pattern was present within some families, others with equivalent history of bleeding demonstrated widely variable types of results. The results within some families, others with equivalent history of bleeding demonstrated widely variable types of results. The results of serial studies of the same tests in 10 normal individuals indicated relative stability, with nearly all values within the usual range of normal, but some independent variation of factor-VIII-related activities was observed. These studies indicate that: (1) the results of BT, VIII:C, VIIIR:Ag, and VIIIR:Rcof vary considerably from time to time in many individuals with vWd, (2) a classification of “variants” of vWd based solely on such studies may be inappropriate, particularly if the tests are not repeated, and (3) repeated testing may be required to establish the diagnosis of vWd in some individuals.