bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of the largest von Willebrand factor multimers from the plasma of patients with congenital cardiac defects
Authors: Gill JC , Wilson AD , Endres-Brooks J , Montgomery RR 
Published: October 2019

Abstract
We identified a consecutive series of 12 children with noncyanotic congenital cardiac lesions with loss of the largest plasma von Willebrand factor (vWF) multimers determined by SDS-agarose electrophoresis. Seven had previous histories of mucocutaneous hemorrhage; ten had a prolonged bleeding time. Analysis of the factor VIII molecular complex revealed that six patients had reduced vWF measured both immunologically (vW:Ag) and by ristocetin cofactor assay (vW:rist). All had normal or borderline normal factor VIII procoagulant (F VIII) concentrations. Three children had prolonged partial thromboplastin times due to concurrent factor XII deficiency; none had laboratory evidence of intravascular coagulation. Five of the children were restudied after surgical correction of their cardiac lesions. Four had normalization of vWF multimers; the fifth, whose vWF was abnormal postoperatively, had a residual pressure gradient across a previous pulmonary artery banding site. Multimeric abnormalities were not found in the parents of three patients. Thus some patients with noncyanotic congenital heart disease may have an acquired abnormality of vWF that is normalized with correction of the abnormal hemodynamic state.
Effect of acidic and basic isoferritins on in vitro growth of human granulocyte-monocyte progenitors
Authors: Dezza L , Cazzola M , Piacibello W , Arosio P , Levi S , Aglietta M 
Published: October 2019

Abstract
Acidic isoferritins have been previously found to be highly potent inhibitors of hematopoietic progenitors at concentrations of 10(-16) to 10(-18) mol/L, and it has been suggested that acidic isoferritin inhibitory activity plays a role in the regulation of normal hematopoiesis and also in the pathogenesis of leukemia. To characterize the ferritin species that affect the in vitro growth of human colony- forming unit-granulocyte-macrophage (CFU-GM), we tested different preparations of basic (L-subunit-rich) and acidic (H-subunit-rich) isoferritins. Three preparations of human liver (basic) ferritin did not show any effects on CFU-GM growth at concentrations up to 10(-9) mol/L, irrespective of the degree of glycosylation. Acidic isoferritins were purified both from HeLa cells and human heart. HeLa cell ferritin did not affect in vitro colony formation. One of two preparations of human heart ferritin, containing 5% glycosylated ferritin, showed a mean inhibition of 26% +/- 8% of the control at 10(-9) mol/L (P less than .02), whereas the other preparation, which contained no glycosylated ferritin, did not show any effect of CFU-GM growth. A preparation enriched for glycosylated acidic isoferritins from human heart was found to produce a mean inhibition of 32% +/- 11% of the control at 10(-9) mol/L (P less than .01), whereas another one was ineffective. A significant part of the inhibitory activity was removed by preincubation with the monoclonal antibody 2A4 directed against human heart ferritin. The present findings indicate that basic isoferritins, ie, the predominant ferritin type in human blood, have no effect on the growth of human CFU-GM, and this is in keeping with indirect clinical evidence. Inhibition of colony formation may be obtained by some preparations of acidic isoferritins that are rich in H subunits and bind to concanavalin A. The mechanism(s) responsible for this are not clear, but the effective concentrations are higher than those found in human blood both under normal conditions and in leukemia. At present, the physiologic significance of the observed inhibitory activity is uncertain.
Development of a radioimmunoassay for the fibrinogen-derived peptide B beta 1-42
Authors: Weitz JI , Koehn JA , Canfield RE , Landman SL , Friedman R 
Published: October 2019

Abstract
The peptide B beta 1–42 is the initial cleavage product of plasmin- mediated proteolysis of the NH2-terminal region of fibrinogen or fibrin I, while beta 15–42 is the major fragment released by plasmin degradation of fibrin II. Numerous studies have described the measurement of plasma B beta 1–42 levels as an index of plasmin activity. Previous assays were indirect and included quantitation of thrombin-increasable fibrinopeptide B immunoreactivity (TIFPB) or measurement of beta 15–42 with an antiserum (132) which cross-reacted with B beta 1–42. We report on a new antiserum (R142) directed against B beta 1–42 which does not cross-react with beta 15–42 or fibrinopeptide B. Employing this antiserum, a specific assay for B beta 1–42 was developed. This assay was used to measure plasmin-mediated B beta 1–42 release from fibrinogen and its subsequent proteolysis by thrombin. The selectivity constant (Kcat/Km) for thrombin cleavage of the B beta 14–15 bond of B beta 1–42 was 10(5)-fold less than that for proteolysis of the same bond in the intact fibrinogen molecule, thus explaining the stability of this peptide in the presence of thrombin activity in the blood. Similarly, the selectivity constant for plasmin cleavage of the B beta 21–22 bond of B beta 1–42 was 140-fold less than that for proteolysis of the B beta 42–43 bond of fibrinogen, indicating that secondary plasmin attack of the B beta 1–42 molecule is not physiologically important. The specific B beta 1–42 assay provided excellent recovery of peptide added to blood or plasma. Comparison of B beta 1–42 levels with TIFPB values in 37 patient samples yielded good correlation over a wide range of levels (r2 = 0.91). The median plasma B beta 1–42 level in 15 normal individuals was 1.2 pmol/mL. This is similar to the previously reported normal range for TIFPB (1 to 4 pmol/mL) but is higher than the normal level of 0.4 pmol/mL reported with the assay employing antiserum 132. This discrepancy reflects rapid removal of Arg (B beta 42) by plasma carboxypeptidase activity resulting in 50% loss of B beta 1–42 immunoreactivity with antiserum 132 but no loss with R142. To circumvent this problem, we have developed a beta 15–42 antiserum (R154) which, like antiserum 132, cross-reacts with B beta 1–42. However, B beta 1–42/beta 15–42 immunoreactivity with R154 is stable in the presence of carboxypeptidase activity.(ABSTRACT TRUNCATED AT 400 WORDS)
Modulation of in vitro growth of murine myeloid leukemia by an autologous substance immunochemically cross-reactive with insulin and antiinsulin serum
Authors: Vuk-Pavlovic Z , Pavelic K , Vuk-Pavlovic S 
Published: October 2019

Abstract
Murine myeloid leukemia secretes a substance immunochemically cross- reactive with insulin (SICRI) both in vivo and in serum-free media. High SICRI concentrations in peripheral blood of tumorous animals do not affect circulating glucose levels. In culture, DNA synthesis rate per leukemic cell is proportional to cell density and is reduced by antiinsulin serum. Culture medium conditioned by leukemia cells as well as SICRI affinity purified from this medium stimulate DNA synthesis in cultured leukemia cells. It appears that autocrine stimulation of murine myeloid leukemia can be mediated in part by an insulin-related growth factor.
Activation of human granulocytes by arachidonic acid: its use and limitations for investigating granulocyte functions
Authors: Cohen HJ , Chovaniec ME , Takahashi K , Whitin JC 
Published: October 2019

Abstract
The effects of arachidonic acid on human granulocytes (polymorphonuclear neutrophil leukocytes, PMN) were examined with respect to early events associated with activation of the superoxide (O2-)-generating system and its reactivation with other stimuli after the addition of fatty acid-free bovine serum albumin. As with other stimuli, O2- production occurred after a lag that was dependent on the amount of arachidonic acid used. Although the lag, rate, and extent of O2- production were dose dependent, at all concentrations used, the duration of O2- production was four to six minutes. As previously described, when fatty acid-free albumin was added one minute after stimulation of PMN by arachidonic acid, O2- production ceased immediately. The O2(-)-generating system could then be reactivated by the addition of either phorbol myristate acetate (PMA), concanavalin A, or serum-treated zymosan. In previously activated cells, the lag time for reactivation was shorter and the rate of O2- production greater with PMA. PMN membrane potential was depolarized by arachidonic acid. This depolarization was not reversed with the addition of albumin. PMN cytoplasts were also capable of reversible activation by arachidonic acid in a manner identical to whole cells. Divalent cations were found to be necessary for the activation of PMN by arachidonic acid. In the absence of calcium, arachidonic acid caused rapid lysis of the cells, as manifested by the release of lactic acid dehydrogenase. We were unable to measure later events in PMN stimulated by arachidonic acid since even in the presence of divalent cations lactic acid dehydrogenase was released from the cells after five minutes of incubation. We conclude that, in addition to its ability to activate PMN, arachidonic acid is toxic to the cells and cannot be used to study late events in granulocyte activity, and, in the absence of calcium, it may be difficult to interpret its action as a stimulant of the oxidase.
Effect of activated lymphocytes on the regulation of hematopoiesis: enhancement and suppression of in vitro BFU-E growth by T cells stimulated by autologous non-T cells
Authors: Harada M , Nakao S , Kondo K , Odaka K , Ueda M , Shiobara S , Matsue K , Mori T , Matsuda T 
Published: October 2019

Abstract
Autologous mixed lymphocyte culture (AMLR) is an immunologic response with memory and specificity and plays a role in immune regulation. Effects of T cells activated by AMLR were studied in the regulation of in vitro erythropoiesis. AMLR-activated T cells were cocultured with autologous non-T, nonphagocytic peripheral blood mononuclear cells for assaying erythroid progenitor cells (BFU-E). T cells activated for 3 days in AMLR showed significant enhancement of in vitro colony growth by BFU-E. In contrast, activated T cells from day 7 AMLR caused significant suppression of BFU-E growth. Both enhancing and suppressing activities of AMLR-activated T cells were mediated by an la-positive and radiosensitive population within the OKT4+ subset. These observations suggest that AMLR-activated T cells may play a role in the immune-mediated regulation of in vitro erythropoiesis. It is also suggested that heterogeneous T-cell subsets may exert regulatory functions in the regulation of in vitro hematopoiesis.
The cofactor role of protein S in the acceleration of whole blood clot lysis by activated protein C in vitro
Authors: de Fouw NJ , Haverkate F , Bertina RM , Koopman J , van Wijngaarden A , van Hinsbergh VW 
Published: October 2019

Abstract
The effect of purified human activated protein C (APC) and protein S on fibrinolysis was studied by using an in vitro blood clot lysis technique. Blood clots were formed from citrated blood (supplemented with 125I-fibrinogen) by adding thrombin and Ca2+-ions; lysis of the clots was achieved by adding tissue-type plasminogen activator. The release of labeled fibrin degradation products from the clots into the supernatant was followed in time. We clearly demonstrated that APC accelerates whole blood clot lysis in vitro. The effect of APC was completely quenched by antiprotein C IgG, pretreatment of APC with diisopropylfluorophosphate, and preincubation of the blood with antiprotein S IgG. This demonstrates that both the active site of APC and the presence of the cofactor, protein S, are essential for the expression of the profibrinolytic properties. At present, the substrate of APC involved in the regulation of fibrinolysis is not yet known. Analysis of the radiolabeled fibrin degradation products demonstrated that APC had no effect on the fibrin cross-linking capacity of factor XIII.
Deficient induction of leukotriene synthesis in human neutrophils by lipoxygenase-deficient platelets
Authors: Kanaji K , Okuma M , Uchino H 
Published: October 2019

Abstract
The effect of human platelets with deficient lipoxygenase activities on leukotriene B4 (LTB4) synthesis by neutrophils was studied. When arachidonic acid (AA) metabolites obtained from the incubation of washed normal neutrophils and platelets with N- formylmethionylleucylphenylalanine (FMLP), cytochalasin B, and AA were analyzed by reversed-phase high-performance liquid chromatography, the synthesis of 5-lipoxygenase products, including LTB4, was remarkably stimulated by platelets, with their maximal effect at a ratio of platelets to neutrophils of 15:1. However, the use of lipoxygenase- deficient platelets obtained from four patients with myeloproliferative disorders instead of normal platelets showed the deficient production of 5-lipoxygenase-derived products, whereas platelets with normal lipoxygenase activities obtained from MPD patients stimulated the 5- lipoxygenase pathway similarly to the way in which normal platelets did. The addition of 12-hydroperoxyeicosatetraenoic acid (12-HPETE), a labile AA metabolite via the platelet lipoxygenase pathway, could activate the 5-lipoxygenase pathway in neutrophils incubated with FMLP, cytochalasin B and AA, but its stable end product, 12- hydroxyeicosatetraenoic acid, could not. Thus, it is suggested that lipoxygenase-deficient platelets did not sufficiently stimulate LTB4 synthesis during platelet-neutrophil interactions because of defective formation of 12-HPETE. This altered interaction between platelets and neutrophils through the lipoxygenase pathway might result in deficient responses at sites of thrombosis or inflammation in patients with deficient platelet lipoxygenase activities.
Homozygous hemoglobin Knossos (alpha 2 beta 227(B9) Ala----Ser): a new variety of beta+-thalassemia intermedia associated with delta degree- thalassemia
Authors: Baklouti F , Dorleac E , Morle L , Laselve P , Peyramond D , Aubry M , Godet J , Delaunay J 
Published: October 2019

Abstract
Hb Knossos (beta 27 (B9) Ala----Ser) is a recently discovered hemoglobin variant endowed with beta-thalassemic properties (1,2) We present the first homozygous cases. The propositus, a 19-year-old man is originally from northeast Algeria, but is unrelated to other Algerians who have hemoglobin Knossos. He has a beta+-thalassemia intermedia syndrome, including microcytic, hypochromic anemia, enlargement of the spleen, and an increase in the number of reticulocytes. The reduction of beta-chain synthesis is pronounced (alpha/non alpha:2.76). Whole cells containing Hb Knossos have a dramatically low oxygen affinity (P50:38 mm Hg). The propositus also has homozygous delta degrees-thalassemia. The chromosome carrying these mutations is characterized by the DNA haplotype I.
Plasma clearance rates of coagulation factors VIII and IX in factor- deficient individuals
Authors: Noe DA , Bell WR , Ness PM , Levin J 
Published: October 2019

Abstract
The plasma clearance rates of factors IX and VIII were determined in patients with hemophilia A and B who had received factor replacement by prolonged, continuous infusion of factor concentrates. The clearance rates were calculated by dividing the factor infusion rates by the steady-state plasma factor activities corrected for base-line factor activities. The mean factor IX clearance rate in eight factor IX- deficient patients was 233 mL/h (range 159 to 340 mL/h). The mean normalized clearance rate was 3.4 mL/h/kg. The mean factor VIII clearance rate in eight factor VIII-deficient patients was 294 mL/h (range 229 to 361 mL/h) and the mean normalized rate was 5.0 mL/h/kg. Both factors show linear relationships between the factor infusion rates and the steady-state plasma factor activities achieved.
A soluble adenosine triphosphate-dependent proteolytic system in human peripheral red blood cells
Authors: Rieder RF , Ibrahim A , Etlinger JD 
Published: October 2019

Abstract
A soluble adenosine triphosphate (ATP)-dependent proteolytic system has been detected in human peripheral blood erythroid cells. Hemolysates prepared from reticulocyte-rich blood of subjects with autoimmune hemolytic anemia, treated pernicious anemia, and iron deficiency anemia or from pools of red blood cells enriched for reticulocytes by density gradient centrifugation were tested against a radioactive casein standard. Up to 57% of the casein was rendered trichloroacetic acid (TCA) soluble after incubation with such hemolysates for 60 minutes in the presence of 1.0 mmol/L ATP. In the absence of ATP or in hemolysates prepared from reticulocyte-poor blood as little as 6% to 10% of the casein was hydrolyzed. The proteolytic activity was found in the 100,000-g supernatant of active hemolysates and was blocked by hemin, N- ethylmaleimide, and sodium vanadate and thus resembles a previously described activity in rabbit reticulocytes. In the presence of ATP, similar lysates prepared from rabbit reticulocytes preferentially hydrolyzed the abnormal human hemoglobins Leiden and Gun Hill compared with hemoglobin A. These results suggest that there is an active ATP- dependent proteolytic system in young human erythroid cells that can degrade certain abnormal globin chains; the enzymatic activity is lost in the transition from reticulocyte to erythrocyte.
Disappearance of cytogenetic abnormalities and clinical remission during therapy with 13-cis-retinoic acid in a patient with myelodysplastic syndrome: inhibition of growth of the patient's malignant monocytoid clone
Authors: Abrahm J , Besa EC , Hyzinski M , Finan J , Nowell P 
Published: October 2019

Abstract
Median survival is as little as 6 months for patients with refractory anemia with excess blasts who demonstrate an abnormal karyotype in the majority of marrow cells. We treated a patient who presented with 29% marrow blasts and 90% abnormal metaphases with 13-cis-retinoic acid. He achieved a complete clinical and cytogenetic remission during therapy. To determine the mechanism of the response, serial studies were done of the effects of 13-cis-retinoic acid and dexamethasone on in vitro growth of his marrow cells. During clinical remission, when the drug was not administered, marrow growth remained significantly depressed. During relapse, the remission growth pattern was replaced by overgrowth of the karyotypically abnormal monocytoid clone. Clonal growth occurred in cultures containing colony-stimulating activity or dexamethasone but was absent in cultures containing concentrations of 13-cis-retinoic acid achieved in vivo. After the drug was reinstituted, a second clinical stabilization developed. Since 13-cis-retinoic acid inhibits normal monocyte colony growth, we postulate that the patient's unusual clinical responses to the drug were due to in vivo growth inhibition of the malignant monocytoid clone.
Stromal cell-associated erythropoiesis
Authors: Tsai S , Sieff CA , Nathan DG 
Published: October 2019

Abstract
A novel cover slip-transfer culture system was designed to study the functional roles of stromal cells in hemopoiesis, particularly erythropoiesis. Human bone marrow stromal cell colonies were allowed to develop on small glass cover slips in liquid medium. The cover slips, along with the stromal cell colonies and progenitors attached to them were then transferred to a new tissue culture dish and overlaid with methylcellulose culture medium. No exogenous colony-stimulating factors except erythropoietin were supplied. Large erythroid bursts, comprising multiple subcolonies, developed on the stromal cells. In order to determine if stromal fibroblasts together with erythropoietin and serum proteins could support erythroid development, human bone marrow cells depleted of monocytes, macrophages, and T lymphocytes were allowed to adhere to monolayers of a homogeneous fibroblastoid human stromal cell strain ST-1 grown on cover slips. The cover slips were then washed to remove nonadherent cells, transferred to a new culture dish, and overlaid with methylcellulose culture medium containing fetal calf serum and erythropoietin. In this modified system as well, primitive erythroid progenitors migrated extensively on and within the stroma to form huge colonies of hemoglobinized erythroblasts that proceeded to enucleate. Our results indicate that (1) ST-1 cells together with serum proteins and erythropoietin can support the development of large erythroid bursts; (2) erythroid progenitors and precursors adhere to and migrate on and within the extracellular matrix elaborated by ST-1 cells; (3) erythroid progenitors are more adherent to the ST-1 cells or the extracellular matrix than are the more mature cells and possibly the myeloid progenitors.
Influence of fibrin and liver blood flow on the turnover and the systemic fibrinogenolytic effects of recombinant human tissue-type plasminogen activator in rabbits
Authors: Bounameaux H , Stassen JM , Seghers C , Collen D 
Published: October 2019

Abstract
The influence of the presence of fibrin microclots on the systemic fibrinogenolytic effects of intravenous (IV) recombinant human tissue- type plasminogen activator (rt-PA) was studied by injection of a homogenized fibrin suspension in the femoral vein or artery in rabbits. A linear correlation (P less than .001) was found between the extent of fibrinogen breakdown and the amount of fibrin (0 to 32 mg/kg) injected just prior to the IV infusion of rt-PA at a rate of 10 micrograms/kg/min for 60 minutes. This finding suggests that the systemic activation of the fibrinolytic system observed in some patients during infusion of rt-PA may be due, at least in part, to the presence of fibrin in the vascular bed. The effect of blood flow in the liver on the turnover of rt-PA was measured in rabbits after ligation of the hepatic artery and monitoring of the blood flow in the portal vein with a peristaltic pump. The half-life (t1/2) of rt-PA in plasma was inversely correlated with the logarithm of the rate of the liver blood flow. A doubling of the plasma t1/2 of rt-PA was observed after an eightfold reduction of the liver blood flow, suggesting that delayed clearance of rt-PA may occur in patients with severe cardiovascular failure and impaired liver blood flow.
Interleukin 3 promotes the differentiation of isolated single megakaryocytes
Authors: Ishibashi T , Burstein SA 
Published: October 2019

Abstract
Interleukin 3 (IL3) promotes the proliferation of murine hematopoietic progenitor cells, including the megakaryocytic colony-forming cell (CFU- MK). To determine whether IL3 influences more differentiated cells in the murine megakaryocytic lineage, IL3 was added to microcultures of single megakaryocytes isolated from CFU-MK-derived colonies. After two days of culture, cell diameter and DNA content were analyzed. Eighty- five percent of cells initially between 12 and 20 micron in diameter increased in size in response to IL3, while only 12% of these cells increased in size in its absence. The percentage of cells responding to IL3 varied inversely with the size of the initial cells. The culture procedure did not alter the relatively linear relationship between size and ploidy, suggesting that increments in cell size are accompanied by increased ploidy. After three days of culture, acetylcholinesterase (AchE) activity was assayed. A small but significant increment in AchE activity was observed in the presence of IL3. The data show that, at least in vitro, IL3 is a differentiation-promoting factor of the murine megakaryocytic lineage.