bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intravenous gammaglobulin treatment of chronic idiopathic thrombocytopenic purpura
Authors: Bussel JB , Kimberly RP , Inman RD , Schulman I , Cunningham-Rundles C , Cheung N , Smithwick EM , O'Malley J , Barandun S , Hilgartner MW 
Published: October 2019

Abstract
High-dose intravenous gammaglobulin (IVIgG) was given to 12 children and adults with chronic idiopathic thrombocytopenic purpura (ITP) to avoid splenectomy or because they either failed to respond to or required maintenance with high doses of steroids and/or immunosuppressives. The average platelet count increase to initial therapy was 239,500/microliters (range 23,000–790,000). A concomitant IgG Fc receptor blockade, measured by IgG-sensitized 51Cr-labeled autologous erythrocytes, was seen in 11 of 11 patients tested, both splenectomized and not splenectomized, lasting 3–4 wk. Six or more months after treatment, 2 children are in remission, 2 children and 2 adults are stable requiring no therapy with platelet counts of approximately 50,000 and 30,000, respectively, 3 children require maintenance IVIgG therapy at 2–10-wk intervals, and 1 child and 2 adults have become refractory to further IVIgG. Splenectomy was not performed in 4 children. Two adults were able to discontinue daily prednisone. The 3 patients who became unresponsive to Swiss Red Cross gamma-globulin (IgSRK) therapy did so in conjunction with a markedly elevated platelet-associated IgG and IgM. Serum IgM increased an average of 103 mg/dl after the IVIgG infusions. No significant side effects were seen.
Fetal erythropoiesis in juvenile chronic myelocytic leukemia
Authors: Travis SF 
Published: October 2019

Abstract
Red cell enzymes, 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP), were evaluated in a 23-mo-old boy with juvenile chronic myelocytic leukemia (JCML) at the onset of his illness and 6 mo later during the accelerated phase. The activities of the age-dependent red cell enzymes, hexokinase, aldolase, pyruvate kinase, and glucose-6- phosphate dehydrogenase, were elevated, as were the concentrations of red cell 2,3-DPG and ATP, consistent with a young red cell population metabolizing at an increased glycolytic rate. The activities of the non- age-dependent enzymes, glyceraldehyde-3-phosphate dehydrogenase (G3PD), phosphoglycerate kinase, and enolase, were also increased to levels similar to or greater than those observed in term infants. As the illness progressed, the activity of red cell G3PD increased further, and phosphoglucose isomerase activity increased markedly. These results are consistent with the prior suggestion that JCML represents a reversion to “fetal” erythropoiesis.
Studies of factor IX concentrate therapy in hemophilia
Authors: Hultin MB 
Published: October 2019

Abstract
The effects of factor IX concentrate therapy on hemostasis in hemophilia patients were studied by means of the radiometric factor IXa assay, the coupled amidolytic assay for factor VIIa, and coagulant assays for factors II, IX, and X, and antithrombin III. Both activated and unactivated concentrates contained factors VIIa and IXa, with the highest levels in the activated concentrates. Factors VIIa and IXa were detected in patient plasma after infusion of unactivated concentrates. Increases of 3–5--fold in factors II and X were also found. Major decreases in antithrombin III activity, but not antigen, were found after unactivated concentrate therapy. This functional decrease may be due to the presence of inactive antithrombin III complexes, since a decreased mobility of antithrombin III antigen by crossed immunoelectrophoresis was found. These studies support the possible importance of factors IXa and VIIa as therapeutic agents and suggest that a transient functional deficiency in antithrombin III may be involved in the thrombotic potential of the concentrates.
An enzyme-linked immunosorbent assay for platelet compatibility testing
Authors: Tamerius JD , Curd JG , Tani P , McMillan R 
Published: October 2019

Abstract
The selection of platelet donors for patients who are refractory to random donor platelets often presents a difficult clinical problem. We describe an enzyme-linked immunosorbent assay (ELISA) for evaluating alloantibodies in refractory patients. Platelets from prospective donors are immobilized on microtiter plates and, after incubation with test serum and washing, platelet-bound IgG is detected with enzyme- linked anti-human IgG. Platelets from 46 prospective donors were tested. Twenty-two were judged compatible (reciprocal of the antibody titer less than 16) and, of these, 15 were used as platelet donors; each gave a measurable platelet increment after transfusion. The magnitude of the response was roughly proportional to the assay results. Platelets from donors giving antibody titers less than 4 resulted in platelet increments at 1 hr ranging from 4,890 to 22,200 (median 12,600), while platelets from donors giving titers of 8 or 16 resulted in lesser increments (550–4548). Conversely, 5 of the 24 patients found incompatible by the assay (titer greater than 16) gave no platelet increment, and in 3 instances, the recipient developed fever and chills after the transfusion. The assay is sensitive, simple, and adaptable to the clinical laboratory. Platelets from volunteer donor panels can be plated and stored for up to 6 mo.
Analysis of two new leukemia-associated antigens detected on human T- cell acute lymphoblastic leukemia using monoclonal antibodies
Authors: Naito K , Knowles RW , Real FX , Morishima Y , Kawashima K , Dupont B 
Published: October 2019

Abstract
Two monoclonal antibodies (anti-3–3 and anti-3–40) were produced, which identify two new leukemia-associated antigens. Both antibodies reacted with most cell lines derived from patients with T lymphoblastic leukemia (T-ALL), but were not detected on suspensions of normal hematopoietic cells (including thymocytes) by cytotoxicity, absorption, or indirect immunofluorescence assays. Analysis of fresh leukemic cells indicated that anti-3–3 only reacted with T-ALL cells, while anti-3–40 also reacted with some non-T, non-B ALL cells and a few acute myelocytic leukemia (AML) cells. The 3–40 antigen was also found histopathologically in frozen sections of several normal tissues, including the epithelial cells and a few lymphoid cells of the thymus, and some malignant tissues. The 3–3 antigen was not found in any tissue studied. A “double absorption” assay provided additional serologic evidence that the two antibodies identify different antigenic determinants. Biochemical analysis indicated that the molecules immunoprecipitated by anti-3–3 and anti-3–40 have molecular weights of 35,000–40,000 daltons. This study demonstrated that the 3–3 and 3–40 antigens are markers for human T-ALL and can be used along with the normal T-lymphocyte antigen, 3A1, to discriminate T-ALL from cutaneous T-cell lymphoma (CTCL), adult T-cell leukemia (ATL), and T-cell chronic lymphocytic leukemia (T-CLL).
Determination of functional levels of protein C, an antithrombotic protein, using thrombin-thrombomodulin complex
Authors: Comp PC , Nixon RR , Esmon CT 
Published: October 2019

Abstract
Protein C is a vitamin K-dependent plasma protein. Activated protein C is a potent anticoagulant and enhances blood clot lysis. We have developed a functional assay for protein C in human plasma. The measurement of protein C is accomplished by the addition of thrombomodulin, an endothelial-cell-associated cofactor for protein C activation, and thrombin in a 1:1 molar complex. The activated protein C formed in the plasma is immunoadsorbed with goat anti-human protein C IgG-agarose. The immunoadsorbed activated protein C retains the ability to hydrolyze chromogenic substrates, and after unbound plasma proteins are removed by washing, the bound activated protein C is quantitated by incubation with the substrate H-D-phe-pip-arg-p-nitroanilide (S-2238). Normal individuals have functional protein C levels of 3.9–5.9 micrograms/ml, with a mean value of 4.8 micrograms/ml. Individuals undergoing warfarin anticoagulation and patients with advanced liver diseases have decreased levels, as do certain patients with evidence of intravascular clotting. Functional protein C levels correlate well with immunologic levels of the protein in the patient groups studied. Heparin enhances the rate of activated protein C inhibition, as monitored by recovery of activated protein C by immunoadsorption. A patient with recurrent venous thrombosis and abnormal functional protein C activity, but normal levels of antigen, has been identified.
In vivo interaction of von Willebrand factor with platelets following cryoprecipitate transfusion in platelet-type von Willebrand's disease
Authors: Miller JL , Boselli BD , Kupinski JM 
Published: October 2019

Abstract
Previous studies performed in vitro have indicated that platelets from patients with platelet-type von Willebrand's disease (vWD) have receptors for von Willebrand factor (vWF) already exposed on their surfaces and that the addition of purified vWF or cryoprecipitate to patient platelet-rich plasma under stirring conditions is capable of inducing platelet aggregation and secretion. The present work reports the results of the transfusion of cryoprecipitate in a patient with platelet-type vWD. It is shown that, while factor VIII-related antigen and ristocetin cofactor activities maintain elevated levels for up to 12 hr following transfusion, the highest molecular weight vWF multimers decline rapidly. The platelet count also declines, followed in turn by a rise in the plasma level of platelet factor 4. Shortening of the bleeding time occurs only very transiently. The results of this study provide direct evidence that, in patients with platelet-type vWD, an abnormal interaction of their platelets with plasma vWF occurs in vivo, resulting in the absence of high molecular weight vWF multimers, low platelet counts, and impaired hemostasis that are characteristic of this disease.
Cryopreservation of enucleated human neutrophils (PMN cytoplasts)
Authors: Voetman AA , Bot AA , Roos D 
Published: October 2019

Abstract
Previously, we have shown that enucleated human neutrophils (PMN cytoplasts), when activated by particulate or fluid stimuli, generate superoxide and hydrogen peroxide at rates comparable (per unit area of plasma membrane) to those observed with intact neutrophils. Moreover, PMN cytoplasts also ingest and, to a certain extent, kill bacteria. We now report that PMN cytoplasts can be cryopreserved with maintenance of their functional activity. The PMN cytoplasts were frozen in a medium with 10% (v/v) fetal calf serum and 10% (v/v) dimethyl sulfoxide, and stored at -70 degrees C. After thawing and washing, the recovery was 75%. The content of alkaline phosphatase and lactate dehydrogenase, the consumption of oxygen and generation of hydrogen peroxide, and the rate of phagocytosis of Staphylococcus aureus bacteria was the same for fresh and cryopreserved PMN cytoplasts. Identical values were obtained after preservation in liquid nitrogen. These results open possibilities to store neutrophil material, allowing longitudinal follow-up of patients, comparative studies between different patients, exchange of material between laboratories, and storage of reference material for experiments in series.
Therapy of essential thrombocythemia with thiotepa and chlorambucil
Authors: Case DC Jr 
Published: October 2019

Abstract
Twenty-seven patients with essential thrombocythemia were treated with combination chemotherapy consisting of weekly intravenous thiotepa (until the platelet count fell below 1,000 X 10(3)/cu mm) and daily chlorambucil (until a sustained remission, platelet count less than 400 X 10(3)/cu mm). All patients responded promptly, platelet counts fell to below 1,000 X 10(3)/cu mm by 1–3 wk, and were less than 400 X 10(3)/cu mm by 2–6 wk. Remission of thrombocytosis was accompanied by an improvement of the patients' symptoms and resolution of the splenomegaly that was present in 21 of the 27 patients. However, daily chlorambucil for more than 1 yr was required to produce a sustained remission in the majority of patients. Nine of 21 patients whose initial treatment was discontinued have required retreatment. To date, 3 patients have expired; 1 patient developed acute leukemia at 36 mo.
Immunoaffinity purification of bovine factor VII
Authors: Bach R , Oberdick J , Nemerson Y 
Published: October 2019

Abstract
Factor VII has been purified to homogeneity from bovine plasma by a procedure that includes affinity purification on an immunoadsorbent column. Recovery was determined by both coagulant assay and liquid scintillation counting, using 3H-factor VII as an internal standard. The purification factor calculated by both methods was approximately 120,000-fold, with a final yield of approximately 18%. Homogeneity was assessed by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis. The material migrated as a single polypeptide chain of 53,000 daltons, and following activation by factor Xa, the one-chain zymogen was quantitatively converted to two-chain factor VIIa. Conversion of affinity-purified factor VII to factor VIIa resulted in up to a 119-fold activation of the coagulant activity, which is 2.7–4 times greater than the activatability reported for factor VII prepared by other methods. Zur et al. calculated that pure factor VII, uncontaminated by traces of factor VIIa, would be activated 123-fold upon conversion to factor VIIa. The close agreement between observed activatability of affinity-purified factor VII and the theoretical prediction suggests that we have isolated factor VII essentially free of factor VIIa. The purification data from three lots of bovine plasma yield an estimate for the plasma concentration of factor VII from 10.1 nM to 18.5 nM.
Incidence of immune responses following 102 infusions of autoplex in 18 hemophilic patients with antibody to factor VIII
Authors: Laurian Y , Girma JP , Lambert T , Meyer D , Larrieu MJ 
Published: October 2019

Abstract
An activated prothrombin complex concentrate (Autoplex) was infused for the treatment of 102 bleeding episodes in 18 hemophilia A patients with antibody to factor VIII who were previously known as high responders. Among 95 bleeding episodes treated with a single infusion of the concentrate [43–107 factor VIII correcting units (FECU)/kg], only 1 anamnestic response was observed. On the contrary, a significant rise in antibody titer occurred following 2 of 4 double (at 8–12 hr interval) and all 3 multiple (over3 –10 days) infusions of Autoplex. The occurrence of immune responses may be explained by the presence of factor VIII coagulant antigen (VIII:CAg) in the 26 batches of Autoplex tested by two-site immunoradiometric assay (10-–36 U/vial). The anamnestic response was not correlated to the batch used nor to the amount (0.6–7.8 U/kg/day) of VIII:CAg infused per day. However, exposure to the concentrate over several days appeared to be the major predisposing factor for an immune response.
Increased 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesterol biosynthesis in freshly isolated hairy cell leukemia cells
Authors: Yachnin S , Mannickarottu V 
Published: October 2019

Abstract
Freshly isolated hairy cells from the peripheral blood of patients with hairy cell leukemia (HCL) synthesize 3–5-fold greater amounts of cholesterol, lanosterol, and squalene from [1–14C]-acetate than do normal human peripheral blood mononuclear cells under basal conditions of culture (i.e., in the presence of low-density lipoprotein). HCL cells also exhibit an eightfold increase in the activity of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase. These changes cannot be ascribed to increased rates of cellular proliferation in the HCL cells, nor are they a consequence of an increased rate of loss of newly synthesized cholesterol into the culture medium. The increased rate of cholesterol biosynthesis in HCL cells may result in an increase in their total cellular cholesterol content, as well as in an increase in their plasma membrane cholesterol:phospholipid molar ratio. These changes, in turn, are probably responsible for some of the clinical manifestations of this disease.
A pericentric inversion of chromosome 16 is associated with dysplastic marrow eosinophils in acute myelomonocytic leukemia
Authors: Tantravahi R , Schwenn M , Henkle C , Nell M , Leavitt PR , Griffin JD , Weinstein HJ 
Published: October 2019

Abstract
Cytogenetic studies were performed in 18 consecutive children with acute nonlymphocytic leukemia (ANLL) between 1981 and 1983. Three children with acute myelomonocytic leukemia (AMMoL; M4, FAB classification) had the following unique bone marrow morphology and cytogenetic abnormality: eosinophilic precursors with dysplastic violaceous granules and a pericentric inversion of chromosome 16. Surface marker analysis of leukemic cells from these patients, using a panel of monoclonal antibodies, revealed the expression of a series of monocyte markers. The association of an inversion of chromosome 16 with abnormal eosinophil morphology in the M4 subtype of ANLL appears to represent a unique subgroup of patients.
Study of Langerhans cells after allogeneic bone marrow transplantation
Authors: Perreault C , Pelletier M , Landry D , Gyger M 
Published: October 2019

Abstract
We assessed the number of Langerhans cells (LC) before and after bone marrow transplantation (BMT) in 27 patients in order to study the fate and behavior of these dendritic antigen-presenting cells following allogeneic BMT. LC were identified using monoclonal antibody OKT6 on skin biopsies performed on days - 10, 0, 11, 25, 39, 120, and 365. In a control group composed of 15 healthy adults aged 20–37 yr, the mean number of LC (+/- SEM) was 25.6 +/- 1.17/0.1 sq mm of epidermal surface. Our study shows that pretransplant, the number of LC in patients with aplastic anemia or leukemia was lower than that of controls. The finding of low numbers of LC in patients with untreated aplastic anemia is suggestive of a medullary origin of LC in man. Moreover, during the early posttransplant period, nearly all patients present a severe deficit in LC. This deficit may delay the maturation of their immune system. The number of LC reaches nearly normal levels 4– 12 mo after BMT. Finally, we have noted a significant impairment of LC reconstitution in patients with acute graft-versus-host disease (GVHD), providing evidence that this defect may be an important mechanism involved in acute GVHD-related immunodeficiency.
Defective binding of the third component of complement (C3) to Streptococcus pneumoniae in multiple myeloma
Authors: Cheson BD , Walker HS , Heath ME , Gobel RJ , Janatova J 
Published: October 2019

Abstract
Patients with multiple myeloma (MM) are at an increased risk for infections with bacteria that require opsonization with complement. Because Streptococcus pneumoniae is the most frequently encountered pathogen in these patients, we investigated the ability of serum from patients with MM to mediate the binding of C3b, the major opsonin of the complement system, to S. pneumoniae. S. pneumoniae types 3, 14, and 25 were chosen for study, since S. pneumoniae type 3 activates primarily the classical complement pathway (CCP), type 25 primarily the alternative complement pathway (ACP), and type 14 both pathways. S. pneumoniae were treated with normal serum or serum from 17 patients with MM, and the bound C3b was quantified with fluorescein-conjugated anti-C3 in a spectrophotofluorometric assay. Despite normal or elevated serum concentrations of C3, total hemolytic complement, and C-reactive protein in all of the MM sera, factor B in 16/17 such sera, and C4 in 14/17 MM sera studied, all 17 sera demonstrated a defect in C3b binding to type 3 (32.7% +/- 6% of normal). In addition, serum from 15/17 patients bound decreased amounts of C3b to types 14 (39.6% +/- 8%) and 25 (52.2% +/- 8%). Mixing normal serum with MM serum restored MM C3b binding activity to all three S. pneumoniae types, suggesting that the defect was related to a deficiency rather than an inhibitor of C3 activation. Although MM patients are unable to produce specific antibodies to bacterial antigens, the addition of anti-S. pneumoniae antibodies to MM serum did not enhance C3b binding to any of the S. pneumoniae types. However, when S. pneumoniae were opsonized in a mixture of MM serum and C3-depleted normal serum, C3b binding was restored to all three S. pneumoniae types, demonstrating that MM C3 functions normally in the presence of other normal serum factors. In the present studies, the MM C3b binding defect appeared to correlate with the incidence of S. pneumoniae infections. Serum from patients with a history of an S. pneumoniae infection bound significantly less C3 (20.5% +/- 4%) than those study patients without a history of an S. pneumoniae infection (55.8% +/- 8%) (p less than 0.0025). Thus, MM serum has a defect in the activation of C3, and this may contribute to the increased susceptibility of MM patients to S. pneumoniae infections.
Fibrin formation, fibrinopeptide A release, and platelet thrombus dimensions on subendothelium exposed to flowing native blood: greater in factor XII and XI than in factor VIII and IX deficiency
Authors: Weiss HJ , Turitto VT , Vicic WJ , Baumgartner HR 
Published: October 2019

Abstract
Fibrin deposition and platelet thrombus dimensions on subendothelium were studied in four groups of patients with coagulation factor deficiencies. Five patients with factor VIII deficiency (APTT 120 +/- 8 sec) and three patients with factor IX deficiency (APTT 125 +/- 11 sec) were severe bleeders, whereas four patients with factor XII deficiency and seven with factor XI deficiency were either asymptomatic or only mild bleeders despite APTT values of 439 +/- 49 and 153 +/- 13 sec, respectively. Everted segments of deendothelialized rabbit aorta were exposed at a shear rate of 650 sec(-1) for 5 and 10 min to directly sampled venous blood in an annular chamber. Blood coagulation was evaluated by measuring fibrin deposition (percent surface coverage) on the subendothelium and post-chamber fibrinopeptide A levels; platelet thrombus dimensions on the subendothelium were evaluated by determining the total thrombus volume per surface area (using an optical scanning technique) and the average height of the three tallest thrombi. Consistent differences were observed among the patient groups for both the 5-min and 10-min exposure times. The larger of the 5- and 10-min exposure-time values was used to calculate group averages. Fibrin deposition in normal subjects was 81% +/- 5% surface coverage, and post- chamber fibrinopeptide A values were 712 +/- 64 ng/ml. Markedly decreased fibrin deposition and fibrinopeptide A levels were observed in factor VIII deficiency (2% +/- 1% and 102 +/- 19 ng/ml) and factor IX deficiency (11% +/- 7% and 69 +/- 11 ng/ml). In contrast, significantly higher values were obtained in patients deficient in factor XI (33% +/- 5% and 201 +/- 57 ng/ml) and factor XII (66% +/- 12% and 306 +/- 72 ng/ml). Differences in thrombus dimensions were also observed. In normal subjects, the value for thrombus volume and average height of the tallest thrombi were 8.3 +/- 1.3 cu micron/sq micron and 145 +/- 11 micron, respectively, and in patients were as follows: FVIII, 2.7 +/- 0.6 and 71 +/- 7; FIX, 4.5 +/- 1.8 and 88 +/- 14; FXI, 11.8 +/- 1.9 and 125 +/- 10; and FXII, 7.9 +/- 3.1 and 130 +/- 25. Platelet thrombus dimensions were normal in a patient with fibrinogen deficiency, indicating that the smaller thrombi in factor VIII and factor IX deficiencies were probably due to impaired evolution of thrombin rather than diminished fibrin formation.(ABSTRACT TRUNCATED AT 400 WORDS)