bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunologic studies of human coagulation factor XI and its complex with high molecular weight kininogen
Authors: Bouma BN , Vlooswijk RA , Griffin JH 
Published: October 2019

Abstract
Coagulation factor XI was purified from human plasma using ion-exchange chromatography and affinity chromatography on high molecular weight kininogen-Sepharose. A monospecific precipitating antiserum was prepared and used to study factor XI antigen. Factor XI did not migrate during electrophoresis at pH 8.3. High molecular weight kininogen (HMWK), an alpha globulin, reversibly associates with factor XI. Complex formation between HMWK and factor XI was observed under conditions of crossed-immunoelectrophoresis. Using Laurell rocket immunoelectrophoresis, it was shown that the isolated alkylated light chain of kinin-free HMWK formed a complex with factor XI. In contrast to previous studies of prekallikrein, titrations of factor XI with increasing amounts of HMWK did not give a simple titration curve, suggesting that factor XI dissociates from the complex during electrophoresis. Prekallikrein and factor XI were shown to compete for the same HMWK molecules under the conditions of immunoelectrophoresis, and prekallikrein appeared to have a higher affinity for binding to HMWK than factor XI. Quantitative determinations of factor XI antigen in plasma by rocket immunoelectrophoresis were made. The average amount of factor XI measured in plasma samples from 20 normal individuals was 4.5 micrograms/ml (range 3–6). No factor XI antigen was detected in plasma from a patient deficient in factor XI. Normal factor XI antigen levels were detected in 3 different HMWK-deficient plasmas only if the plasmas were reconstituted with purified HMWK (2 U/ml). Addition of HMWK to normal plasma resulted in an increase of the factor XI antigen rocket. At HMWK levels of 2 U/ml, no further increase of the factor XI antigen rocket was observed. Therefore, accurate measurement of factor XI antigen by rocket immunoelectrophoresis is possible only if an excess of HMWK is present.
Autoplex versus proplex: a controlled, double-blind study of effectiveness in acute hemarthroses in hemophiliacs with inhibitors to factor VIII
Authors: Lusher JM , Blatt PM , Penner JA , Aledort LM , Levine PH , White GC , Warrier AI , Whitehurst DA 
Published: October 2019

Abstract
In view of uncontrolled observations and anecdotal reports suggesting that the activated PCC, Autoplex, was much more effective than standard (non-activated) PCC in controlling bleeding in hemophiliacs with inhibitors, a controlled double-blind study was designed to compare the effectiveness of Autoplex and Proplex. Acute hemarthrosis was chosen for study as this common but non-life-threatening lesion lends itself well to controlled study. A single dose of “unknown” product (Autoplex 75 FECU/kg; Autoplex 50 FECU/kg; or Proplex 75 FIX U/kg) was given, and effectiveness was judged at 6 hr. By all criteria of efficacy, there were no significant differences between the products. It is noteworthy that a single dose of PCC was judged effective in 50% of episodes, a figure that is consistent with other published clinical trials. In this model, no additional benefit was derived from using the activated PCC, Autoplex, in either dosage.
Marrow transplantation for patients with acute lymphoblastic leukemia: a long-term follow-up
Authors: Thomas ED , Sanders JE , Flournoy N , Johnson FL , Buckner CD , Clift RA , Fefer A , Goodell BW , Storb R , Weiden PL 
Published: October 2019

Abstract
Twenty-two patients with acute lymphoblastic leukemia in second or subsequent remission and 26 with acute lymphoblastic leukemia in relapse were given cyclophosphamide (60 mg/kg on each of 2 days), total body irradiation (920 rad), and marrow transplants from HLA-identical siblings. With a minimum follow-up of more than 5 yr, an actuarial analysis shows a survival and apparent cure of 27% of the patients transplanted in remission and 15% of the patients transplanted in relapse.
Molecular heterogeneity of hereditary pyropoikilocytosis: identification of a second variant of the spectrin alpha-subunit
Authors: Lawler J , Palek J , Liu SC , Prchal J , Butler WM 
Published: October 2019

Abstract
In hereditary pyropoikilocytosis (HPP), the red cell membrane skeletons exhibit a mechanical instability that can be correlated to defective self-association of spectrin heterodimers. To determine the underlying molecular defect, we have subjected HPP spectrin to limited tryptic digestion, followed by one- and two-dimensional separations of the peptides. Two of the HPP kindreds exhibited a marked decrease in 80,000- dalton peptide (previously identified as the spectrin dimer-dimer contact domain of the alpha-subunit) and a concomitant increase of the 74,000-dalton polypeptide (presumably derived from the 80,000-dalton domain) and a decrease in a 22,000-dalton polypeptide. We now report tryptic digests of two other HPP kindred that are characterized by a decrease or complete absence of the 80,000-dalton tryptic fragment, with a concomitant increase in fragments at 46,000 and 17,000 daltons. The 46,000-dalton fragment separated into multiple spots on isoelectric focusing, ranging in isoelectric point from 5.25 to 5.35, and the 17,000-dalton fragment focused to a single spot at 5.4. Minor fragments at 56,000 and 22,000 daltons were also decreased, while a 38,000-dalton fragment increased. Limited tryptic digestion of the separated alpha- and beta-subunits revealed that the 74,000-dalton fragment in the first group of patients and the 46,000-dalton fragment in the second group of patients were derived from the alpha-subunit. Both subtypes exhibited a similar defect of spectrin self-association, with 30%-38% of spectrin dimers in O degrees C extracts. The results indicate that at least two distinct forms of structurally defective spectrin may give rise to the clinical presentation of HPP.
Quinidine-induced thrombocytopenia and leukopenia: demonstration and characterization of distinct antiplatelet and antileukocyte antibodies
Authors: Chong BH , Berndt MC , Koutts J , Castaldi PA 
Published: October 2019

Abstract
A patient with the rare syndrome of simultaneous quinidine-induced thrombocytopenia and leukopenia was studied. A quinidine-dependent antiplatelet antibody was detected in her serum by platelet aggregometry and by indirect platelet-suspension immunofluorescence. A drug-dependent antileukocyte antibody was demonstrated by leukoagglutination and by granulocyte immunofluorescence. Both antibodies were found to belong to the IgG class by immunofluorescence using monospecific antisera. There appeared to be two distinct antibodies, since the antibody eluted off sensitized platelets reacted only with platelets and that eluted off sensitized granulocytes reacted only with granulocytes. In addition, the patientxy's serum and quinidine gave a negative reaction on immunofluorescence with platelets from a patient with Bernard-Soulier syndrome (BSS), which lack glycoprotein lb (GPlb) complex, but gave a positive reaction with BSS granulocytes. The quinidine-dependent antiplatelet antibody immunoprecipitated GPlb and a glycoprotein of molecular weight 22,000 (GPlb complex) from Triton- solubilized, periodate-labeled platelets. Similar attempts to identify the granulocyte surface receptor/antigen were unsuccessful. Factor VIII/von Willebrand factor was not required for binding of the drug- dependent antibody to platelets.
Normal titer of functional and immunoreactive protein-C inhibitor in plasma of patients with congenital combined deficiency of factor V and factor VIII
Authors: Suzuki K , Nishioka J , Hashimoto S , Kamiya T , Saito H 
Published: October 2019

Abstract
Protein-C inhibitor (PCI) is a newly described plasma inhibitor directed against a vitamin-K-dependent serine protease, activated protein-C, which is involved in the inactivation of factor V and factor VIII. Marlar and Griffin have reported that PCI activity is absent in the plasma of patients with congenital combined factor V/VIII deficiency. We have measured the levels of PCI in the plasma of seven unrelated patients with this disorder using both functional and immunologic methods. The rate at which the amidolytic activity of activated protein-C was neutralized in the patients' plasma was essentially identical to that observed in normal plasma. The titer of PCI antigen, as measured by an electroimmunoassay using a monospecific anti-PCI serum, was 5.3 +/- 1.6 micrograms/ml in the patients' plasma and was not significantly different from that of normal plasma (5.3 +/- 2.7 micrograms/ml, n = 30). The levels of factor-V-related antigen, factor V coagulant antigen, and factor VIII coagulant antigen were low in all patient plasma and were in good agreement with their respective coagulant activity. Our results do not appear to support the hypothesis that combined factor V/VIII defect is due to a lack of PCI.
Fibrinogenolytic afibrinogenemia after envenomation by western diamondback rattlesnake (Crotalus atrox)
Authors: Budzynski AZ , Pandya BV , Rubin RN , Brizuela BS , Soszka T , Stewart GJ 
Published: October 2019

Abstract
The absence of fibrinogen and the presence of plasmic fragments X, Y, D, and E were demonstrated in a patient bitten by a western diamondback rattlesnake, Crotalus atrox. The factor VIII level and the platelet count were within normal limits. There were distinct changes of protease inhibitors in the patient's plasma. Alpha-1-protease inhibitor was elevated. Antithrombin-III was only slightly decreased after the envenomation, but alpha 2-antiplasmin and alpha 2-macroglobulin were initially significantly lowered, returning to normal values in 38 and 3 days, respectively. Plasmin-alpha 2-antiplasmin complex was present until day 10 after the envenomation. However, purified plasminogen was not activated in vitro by the venom. Cultured endothelial and smooth muscle cells from human blood vessels released an increased amount of plasminogen activator upon incubation with the venom. The release did not result from cell lysis. Platelets in normal human platelet-rich plasma were aggregated by 10 micrograms/ml of the venom, without serotonin secretion. The aggregation kinetics and serotonin secretion induced by adenosine diphosphate (ADP) or arachidonate were not significantly affected by the venom at 1–10 micrograms/ml. It is concluded that the predominant mechanism of afibrinogenemia in the patient after Crotalus atrox bite resulted from primary fibrinogenolysis and not from a consumptive coagulopathy. The lytic state seemed to be induced through an indirect activation of plasminogen by vascular plasminogen activator, which was probably released from endothelial cells and smooth muscle cells by the snake venom.
Phenotypic analysis of established diffuse histiocytic lymphoma cell lines utilizing monoclonal antibodies and cytochemical techniques
Authors: Winter JN , Variakojis D , Epstein AL 
Published: October 2019

Abstract
Ten diffuse histiocytic lymphoma (DHL) cell lines were extensively characterized with monoclonal antibodies and histochemical techniques. The original biopsy specimens, representing nine of ten cases from which the cell lines were derived, were reviewed utilizing the International Working Formulation. Eight of ten cell lines reacted with anti-immunoglobulin reagents and/or a subset of B-lymphocyte surface markers, supporting a B-cell derivation. Only U-937, a monocytoid DHL cell line reactive with OKT4 and 6, displayed any T-cell markers. Cytochemical analysis alone proved to be of little value in the subclassification of the DHLs. The pathologic review revealed that, despite disparate immunologic phenotypes, five of the diffuse large cell lymphomas were subclassified as large, noncleaved lymphomas. Our analysis confirms the phenotypic diversity of this subgroup of malignant lymphomas and underscores the value of monoclonal reagents for the immunologic evaluation of the hematologic malignancies. These well characterized cell lines constitute a valuable resource for the laboratory investigation of the lymphomas.
Quantification of platelet-bound IgG by 125I-Staphylococcal protein A in immune thrombocytopenic purpura and other thrombocytopenic disorders
Authors: Shaw GM , Axelson J , Maglott JG , LoBuglio AF 
Published: October 2019

Abstract
In this report we describe the use of an 125I-Staphylococcal protein A (SPA) assay to measure platelet-bound IgG in the evaluation of 62 thrombocytopenic patients. Platelets from 150 normal subjects were found to bind 146 +/- 112 molecules of SPA per platelet (mean +/- 2 SD). Nineteen of 20 patients with untreated immune thrombocytopenia had platelet IgG values above this range, with 15 of 20 having values above 1,000 molecules of SPA per platelet. Patients with immune thrombocytopenic purpura by clinical criteria, but who had failed conventional therapy (corticosteroids or splenectomy), had a wide range of platelet IgG levels: 4 of 20 had normal values, 6 of 20 had minimally elevated levels in the range seen with nonimmune thrombocytopenia, and 10 of 20 had much higher values. Fifteen patients with thrombocytopenia of apparent nonimmune origin and 7 others with chronic stable thrombocytopenia of unknown etiology were found to have platelet IgG levels within or only slightly above the normal range. Because of its simplicity, accuracy, and clinical correlation, the 125I- SPA assay provides an important new approach for studying platelet IgG in thrombocytopenic states. The data obtained with this technique are similar to those found in immune hemolytic anemia and suggest that the platelet-bound IgG so measured has pathophysiologic relevance in immune thrombocytopenic purpura.
Effect of transfusion therapy on arteriographic abnormalities and on recurrence of stroke in sickle cell disease
Authors: Russell MO , Goldberg HI , Hodson A , Kim HC , Halus J , Reivich M , Schwartz E 
Published: October 2019

Abstract
Stroke is a relatively frequent and severe complication of sickle cell disease. We performed cerebral arteriograms in 30 patients with sickle cell disease to evaluate the cause of acute neurologic deficits and to assess the effects of transfusion therapy given for a year or more after the acute episode. Twenty-three patients with motor and speech deficits had multiple abnormalities of major cerebral arteries. The internal carotid and anterior and middle cerebral arteries showed stenosis and/or occlusion at their common junction. Irregular luminal surfaces suggested that endothelial damage and intimal hyperplasia were the basis of stroke. Prolonged transfusion therapy nearly stopped progression of stenosis and markedly decreased the irregularity of the luminal surfaces; in 4 untransfused patients, the degree of stenosis doubled and the luminal abnormalities persisted. Prior to transfusion, 90% of patients had recurrence of stroke. With transfusion therapy, only 10% of patients had recurrence despite persistent arterial abnormalities. Clinical recurrences per patient-month decreased 75- fold. The patients tolerated prolonged transfusion therapy well, despite progressive iron accumulation. Seven patients with smooth abnormalities of a single artery, nonocclusive changes, or with normal arteriograms did not receive transfusions. Only one of this group had recurrence of symptoms.
Specific globin mRNAs in human erythroleukemia (K562) cells
Authors: Miller CW , Young K , Dumenil D , Alter BP , Schofield JM , Bank A 
Published: October 2019

Abstract
Specific globin mRNA accumulation was quantitated in several lines of K562 cells in the absence and the presence of hemin. Using specific cloned DNA probes, the amounts of zeta, alpha, epsilon and gamma mRNAs were shown to be increased 2–3-fold in the presence of 20 microM hemin. No delta- or beta-globin mRNAs were detectable in any of the lines. In one line, Bos, there was a marked decrease in epsilon-globin mRNA, which increased with hemin, although still to much lower levels than in the other lines. The decreased epsilon-globin mRNA accumulation in Bos is shown to be due to decreased epsilon-globin gene transcription.
Reduced tocopherol content of B cells from patients with chronic lymphocytic leukemia
Authors: Kayden HJ , Hatam L , Traber MG , Conklyn M , Liebes LF , Silber R 
Published: October 2019

Abstract
The tocopherol content of lymphocytes, erythrocytes, and plasma from patients with chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), and normal subjects was measured by a sensitive high performance liquid chromatographic method. Lymphocytes from patients with CLL had lower values of tocopherol (1.7 +/- 1.0 micrograms/10(9) cells) than lymphocytes from normal subjects (3.8 +/- 0.7 micrograms/10(9) cells). Mononuclear cells from patients with HCL had an increased tocopherol content of 6.2 +/- 1.0 micrograms/10(9) cells. Subfractionation of the lymphocytes from patients with CLL into T- and B-cell subgroups showed that the tocopherol content of T cells was the same as in normal subjects (4.1 +/- 0.5 micrograms/10(9) cells versus 3.5 +/- 1.2), but that the tocopherol content of the B cells was markedly reduced compared to normals (2.6 +/- 1.0 versus 6.0 +/- 1.3).
Localization of the human c-sis oncogene in Ph1-positive and Ph1- negative chronic myelocytic leukemia by in situ hybridization
Authors: Bartram CR , de Klein A , Hagemeijer A , Grosveld G , Heisterkamp N , Groffen J 
Published: October 2019

Abstract
Oncogenes are a group of evolutionary conserved cellular genes (c-onc) homologous to the transforming genes of oncogenic retroviruses (v-onc). Some of them are localized near the breakpoints of specific chromosomal aberrations occurring in various neoplasms, as for example the Philadelphia translocation, t(9;22)(q34;q11), in chronic myelocytic leukemia (CML). Recently, we localized the human c-abl oncogene to chromosome region 9q34 and demonstrated a translocation of this gene to the Philadelphia chromosome (Ph1,22q-) in various forms of Ph1- positive, but not Ph1-negative, chronic myelocytic leukemia (CML). Another human oncogene, c-sis, is located on chromosome 22 and was recently reported to be transferred to chromosome 9q+ in one CML patient. We have now studied 2 CML patients with classic and variant types of Ph1 translocation, one Ph1-negative case, and a healthy control using in situ hybridization of a c-sis probe to metaphase chromosomes. These studies show that c-sis: (1) is localized to region 22q12.3-q13.1, far away from the breakpoint region 22q11 in CML, (2) segregates with the translocated part of chromosome 22 to different chromosomes in Ph1-positive patients, and (3) remains on chromosome 22 in the Ph1-negative case. Therefore, these data give no support for an active role of the c-sis gene in the generation of CML. Thus, if either of these two oncogenes is involved in the development of Ph1-positive CML, c-abl appears to be the more important one.
Amidolytic assay of human factor XI in plasma: comparison with a coagulant assay and a new rapid radioimmunoassay
Authors: Scott CF , Sinha D , Seaman FS , Walsh PN , Colman RW 
Published: October 2019

Abstract
The traditional coagulant assay for plasma factor XI suffers from a relatively high coefficient of variation, the need for rare congenitally deficient plasma, and a poor correlation between precision and sensitivity. We have developed a simple functional amidolytic assay for factor XI in plasma using the chromogenic substrate PyrGlu-Pro-Arg- p-nitroanilide (S-2366). After inactivation of alpha 1-antitrypsin, CI inhibitor, and other plasma protease inhibitors with CHCI3, plasma was incubated with kaolin, in the absence of added calcium, which limited the enzymes formed to those dependent on contact activation. Soybean trypsin inhibitor was used to minimize the action of kallikrein on the substrate. Once the reaction was complete, corn trypsin inhibitor was used to inactive factor XIIa, the enzyme generated by exposure of plasma to negatively charged surfaces, which had activated the factor XI. The assay is highly specific for factor XI, since plasma totally deficient in that zymogen yielded only 1%-3% of the enzymatic activity in normal plasma under identical conditions. The requirements for complete conversion of factor XI to XIa in plasma within 60 min were, respectively, factor XII, 0.6 U/ml, and high molecular weight kininogen, 0.2 U/ml. Prekallikrein was not an absolute requirement for complete activation but did accelerate the reaction. The intraassay coefficient of variation was 3.4%, and the mean of 35 normal plasmas was 1.00 U +/- 0.24 SD. In addition, a new rapid radioimmunoassay was devised using staphylococcal protein A as the precipitating agent for a complex of factor XI antigen with monospecific rabbit antibody. The mean was 1.01 U +/- 0.30 SD. The correlation coefficients for amidolytic versus coagulant and amidolytic versus radioimmunoassay were r = 0.95 for the former and 0.96 for the latter. Thus, a simple, accurate amidolytic assay and a radioimmunoassay have been devised for measuring factor XI in plasma that correlate well with the coagulant activity of factor XI, as determined in our laboratory.
Mechanisms for the oxidation of reduced gluthathione by stimulated granulocytes
Authors: Sagone AL Jr , Husney RM , O'Dorisio MS , Metz EN 
Published: October 2019

Abstract
We have reported previously that human granulocytes have an irreversible fall in their endogenous reduced soluble sulfhydryls following zymosan stimulation. In the present study, we demonstrate that stimulated granulocytes release one or more reactive oxygen species (ROS) with the capacity to oxidize reduced glutathione (GSH). One or more of these compounds is stable enough to be detected in the supernatant. The formation of these stable oxidants appears to require H2O2 and heme or a heme-containing enzyme. However, once formed, the compound reacts with GSH without these factors. The ROS is not superoxide or hydroxyl radical, since neither superoxide dismutase nor the hydroxyl scavengers, mannitol and benzoic acid, change the rate of the reaction. Methionine has recently been demonstrated to be oxidized to a sulfoxide by a reactive oxygen species that is dependent on H2O2 and heme for its production. We found that methionine could directly react with the same ROS that degrades GSH. The ROS also has the capacity to oxidize iodide and fix halogen to proteins. Our data indicate that stimulated granulocytes release a ROS with the capacity to oxidize GSH, react with methionine, and oxidize and fix I- to protein. The compound, therefore, appears dependent on H2O2 and the myeloperoxidase system for its production, and is either hypochlorous acid (HOCI) or a compound derived from HOCI, such as a chloramine. The capacity of GSH to react with this ROS suggests an additional role for this tripeptide in cellular protection against oxidant injury.