bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary systemic amyloidosis: multivariate analysis for prognostic factors in 168 cases
Authors: Kyle RA , Greipp PR , O'Fallon WM 
Published: October 2019

Abstract
One hundred sixty-eight patients with primary systemic amyloidosis (AL) were identified. Median survival after diagnosis was 12 months and ranged from 4 months for patients presenting with congestive heart failure to 50 months for those presenting with peripheral neuropathy only. Utilizing the proportional-hazards model in a stepwise multivariate fashion to evaluate the simultaneous influence of putative risk factors as of diagnosis revealed that congestive heart failure, urine light chain, hepatomegaly, and multiple myeloma were the major factors adversely affecting survival during the first year after diagnosis. Serum creatinine, multiple myeloma, orthostatic hypotension, and monoclonal serum protein were the most important variables adversely affecting survival for patients surviving 1 year. These models were used to categorize patients according to the variables in the models into low-, moderate-, and high-risk groups for the first year after diagnosis and separately for subsequent years. The influence of these variables on survival is important in stratification of patients randomized to prospective clinical trials.
The effect of C1 inhibitor upon Hageman factor autoactivation
Authors: Weiss R , Silverberg M , Kaplan AP 
Published: October 2019

Abstract
Using components purified from human plasma, we have examined the effects of C1 inhibitor (C1 INH), the primary inhibitor of activated Hageman Factor (HFa) and Hageman factor fragment (HFf), on Hageman Factor (HF) autoactivation. When Hageman factor was exposed to a negatively charged surface, provided by either a glass cuvette or dextran sulfate, the addition of C1 INH gave a dose-dependent inhibition of the activity observed. The ability of C1 INH to decrease the maximal enzymatic activity generated was markedly temperature dependent with inhibition increasing as the temperature was raised from 4 degrees C to 37 degrees C. Although the rates of both autoactivation and inhibition were decreased at lower temperatures (4 degrees C), the latter rate was more sensitive to temperature modulation. When HF (final concentration 1 mumol/L) was incubated with C1 INH (0.54, 1.07, and 2.14 mumol/L) in the absence of an initiating surface, no increases in enzymatic activity were observed for up to 48 hours regardless of the C1 INH concentration. However, SDS polyacrylamide gel electrophoresis of the incubation mixture revealed that HF autodigestion had occurred by 48 hours despite the presence of C1 INH. In addition, the appearance of a new band suggested that a complex had been formed between the inhibitor and activated HF. Our findings indicate that C1 INH does not prevent HF autoactivation but rather inactivates the products of HF autodigestion.
An in vitro model of erythroid egress in bone marrow
Authors: Waugh RE , Sassi M 
Published: October 2019

Abstract
An in vitro system has been developed that mimics the passage of erythrocytes from the bone marrow to the circulation. Bone marrow egress and its proper regulation are vital physiologic processes. However, because of the inaccessibility of the marrow, it is difficult to evaluate the various factors important in controlling these processes or even to define the precise mechanism by which egress occurs. The in vitro system has been designed to evaluate the importance of different physical parameters in regulating egress. It consists of a thin silicon wafer (thickness approximately equal to 1.0 micron) cemented over the tip of a large (15.0 micron ID) micropipette. The wafer contains a single circular pore. Cells were observed under the microscope as they passed through the pore under controlled pressures. The rate and duration of passage were obtained from videorecordings of the experiment. The measured passage times agreed well with the predictions of a simple analytical model of a cell passing through a thin aperture. The experimental results confirm the conclusion reached from the analysis that the pressures needed to drive a cell through the pore are well within the physiologic range, and the time needed to complete egress is typically less than 1.0 seconds. These results support the hypothesis that erythrocyte egress may be driven by a hydrostatic pressure difference across the pore.
Purification of murine erythropoietin produced in serum-free cultures of erythroleukemia cells
Authors: Qian RL , Chin K , Kim JK , Chin HM , Cone J , Hankins WD 
Published: October 2019

Abstract
We previously documented that several erythroleukemia cell lines released factors that stimulated erythropoiesis in vivo and in vitro. A simple five-step scheme has been devised that allows purification of this erythropoietic activity to apparent homogeneity. The methods employed included lectin affinity chromatography (wheat germ agglutinin), gel filtration (ultro gel ACA44), ion exchange, hydroxylapatite, and high performance liquid chromatography. Following polyacrylamide gel electrophoresis, biologic activity was recovered in an area corresponding to a molecular weight of 35,000 daltons. Silver staining of a polyacrylamide gel after electrophoresis of our most purified preparation revealed a single band at 35,000 daltons.
Fucose binding lectin for characterizing acute myeloid leukemia progenitor cells
Authors: Delwel R , Touw I , Bot F , Lowenberg B 
Published: October 2019

Abstract
The reactivity of acute myeloid leukemia cells (AML) was determined in 29 patients using the fucose binding lectin Ulex europaeus agglutinin (UEA) as surface marker. We show a marked heterogeneity in the UEA- binding abilities of the cells in these patients as determined by fluorescence analysis of the blasts labeled with the UEA coupled to the fluorescent molecule FITC. The results suggest a correlation between the capability of AML blast cells to bind UEA and cytologic maturation, because in 1 of 10 M1, 3 of 8 M2, 6 of 8 M4, and 1 of 3 M5 cytology types UEA binding to the leukemic cells was apparent. In 13 cases, the cells gave rise to colonies in vitro. The amount of UEA binding to AML colony-forming cells (AML-CFU) was determined by cell sorting and subsequent colony culture of UEA-negative, intermediately positive, and highly fluorescent cells. AML-CFU from none of the four patients with M1 cytology were UEA positive, whereas they showed intense reactivity with the lectin in 1 of 4 cases with M2 cytology and in all 4 cases of M4. In these five cases with strongly UEA positive AML-CFU, the fluorescence distribution of the colony formers differed from that of the total leukemia population, indicating that AML-CFU represent a subpopulation of AML cells with specific UEA-binding properties. Normal bone marrow myeloid and multipotential colony-forming cells (CFU-GM, CFU-GEMM) showed low or no binding of UEA. UEA-FITC appears a useful reagent for membrane analysis of AML-CFU. In certain cases, UEA-FITC labeling may be applied to discriminate AML-CFU from normal hematopoietic progenitors.
Nonrandom involvement of the 12p12 breakpoint in chromosome abnormalities of childhood acute lymphoblastic leukemia
Authors: Raimondi SC , Williams DL , Callihan T , Peiper S , Rivera GK , Murphy SB 
Published: October 2019

Abstract
We studied the presenting clinical and biologic features of 23 children with acute lymphoblastic leukemia (ALL) whose leukemic marrow karyotypes contained abnormalities involving the short arm of chromosome 12. Nineteen of the abnormalities were assigned to the 12p12 breakpoint. The median age of the children was 5 years (range 2 to 13 years) and their initial leukocyte counts ranged from 1,800 to 424,000/microL (median 30,000/microL). Twenty-one patients (91%) had common phenotype ALL (CALLA+, HLA-DR+), including three cases with a pre-B cell phenotype (CIg+). The remaining two cases were T cell in origin. The French-American-British (FAB) morphologic type of lymphoblastic leukemia was L1 in all cases but one. With a median follow-up of 11 months, four patients have relapsed and another failed induction therapy. The modal chromosome number in all cases was less than 50. Three distinct cytogenetic patterns, with apparently similar clinical manifestations, were noted: terminal deletions of chromosome 12 in 10 cases, apparently balanced reciprocal translocations in 6, and unbalanced translocations in 7. All translocations were between the 12p arm and different donor chromosomes except for chromosomes 7, 9, and 17, which participated twice. Only two patients had identical translocations: t(7;12)(q11;p12). This unusual variation in donor chromosomes and breakpoints suggests that translocations involving the 12p are specific with respect to only one member of the translocation pair, namely chromosome 12. The relatively high frequency of the 12p abnormalities in this study (10% of all completely banded cases seen over a 35-month period) warrants further investigation.
Covalent crosslinking of von Willebrand factor to fibrin
Authors: Hada M , Kaminski M , Bockenstedt P , McDonagh J 
Published: October 2019

Abstract
Factor XIIIa crosslinks a limited number of substrates via epsilon(gamma-glutamyl)-lysyl bond formation. It crosslinks fibrin to itself, alpha 2-plasmin inhibitor and fibronectin to fibrin, and fibronectin to collagen. Results presented here show that plasma von Willebrand factor (vWF) is a substrate for factor XIIIa and can be crosslinked to fibrin during gel formation. vWF-fibrin crosslinking was studied in purified systems and in plasma with 125I-vWF and 131I- fibrinogen. vWF incorporation into fibrin increased with time or increasing factor XIIIa. After electrophoresis of dissolved clots, distribution of 125I and 131I was measured and showed that vWF was crosslinked to the alpha chain of fibrin and entered the high-mol-wt alpha polymer. vWF-fibrin crosslinking decreased the initial rate of alpha polymer formation. Crosslinking of vWF polymer to itself could not be demonstrated under physiologic conditions but occurred if vWF was reduced first. Factor XIIIa catalyzed incorporation of putrescine into both monomeric and polymeric vWF. Altogether, these studies indicate that factor XIIIa can readily form covalent bonds between glutamine in vWF and lysine in fibrin alpha chains. This reaction occurs readily in vitro when plasma clotting is slow and may occur in vivo under similar conditions.
Defective platelet adhesion on vessel subendothelium in uremic patients
Authors: Castillo R , Lozano T , Escolar G , Revert L , Lopez J , Ordinas A 
Published: October 2019

Abstract
Bleeding time, platelet retention on glass beads, and ristocetin- induced platelet agglutination (RIPA) in platelet-rich plasma were simultaneously determined for 20 patients with chronic renal failure and previous hemorrhagic history. In seven patients chosen at random out of a group of 16 in whom the three tests were abnormal, RIPA of uremic-isolated platelets in presence of normal platelet-poor plasma (PPP) and of normal platelets in presence of patient PPP were performed. In all cases, the first assay showed diminished agglutination, suggesting a platelet defect; however, uremic PPP did not inhibit the agglutination of normal platelets. In the same patients, the interaction of platelets with subendothelium was evaluated using Baumgartner's perfusion method. The subendothelial surface covered by platelets was significantly decreased in experiments with uremic whole blood when compared to normal controls. The interaction of platelets with subendothelium was also decreased when perfusions were carried out with platelet-plasma mixtures containing either normal washed platelets and uremic PPP or uremic washed platelets and normal PPP. These results show an impaired platelet adhesion caused both by a platelet and a plasmatic abnormality. Since uremic PPP decreased the adhesion of normal platelets to subendothelium but did not inhibit RIPA, it seems probable that the plasmatic defect could result in a defective binding between vWF and subendothelium. The influence of the red cell count on the platelet adhesion to subendothelium was reconfirmed by comparing perfusions of reconstituted blood with hematocrit values of 20% to 23% and 40% to 45%. In summary, a defective platelet adhesion to subendothelium has been postulated in uremic patients, caused by platelet and plasmatic alterations that are influenced by a low hematocrit.
Studies on the pathophysiology of posttransfusion purpura
Authors: Kickler TS , Ness PM , Herman JH , Bell WR 
Published: October 2019

Abstract
Posttransfusion purpura typically occurs in PLA1 negative blood recipients who have been previously immunized to the PLA1 antigen. Following transfusion, severe thrombocytopenia develops with the formation of anti-PLA1. Since the patients' platelets lack the PLA1 antigen, one would not expect this antibody to destroy autologous platelets. In this study we show that PLA1 antigen exists in stored blood and can absorb to PLA1 negative platelets making them PLA1 reactive. Incubating PLA1 (-) platelets with ultracentrifuged plasma from PLA1 (+) blood donors allowed anti-PLA1 to bind to PLA1 (-) platelets. Control plasma from PLA1 (-) blood donors did not lead to anti-PLA1 binding. Using an inhibition assay, we showed that stored blood contains PLA1 material that was not removed by ultracentrifugation. The material absorbing to PLA1 (-) platelets represented the PLA1 antigen, which was confirmed by Western blotting. After incubating plasma containing PLA1 antigen with PLA1 (-) platelets, reactivity at 95,000 D was observed. Native PLA1 (+) platelets showed a similar band. When PLA1 (-) platelets were incubated with plasma from a PLA1 (-) donor, this band was not present. These studies show that a soluble form of PLA1 antigen exists in stored blood that can absorb to PLA1 (-) platelets. Consequently, anti-PLA1 can bind to these platelets leading to thrombocytopenia. These observations may explain the autologous destruction of platelets in posttransfusion purpura.
Does the conformation of adsorbed fibrinogen dictate platelet interactions with artificial surfaces?
Authors: Lindon JN , McManama G , Kushner L , Merrill EW , Salzman EW 
Published: October 2019

Abstract
Platelet activation by polymer surfaces is thought to require preliminary adsorption of fibrinogen and perhaps changes in fibrinogen conformation. We measured fibrinogen adsorption by a series of polymers by two methods, using either 125I-labeled fibrinogen or 125I-labeled antifibrinogen antibodies, and correlated the results with platelet reactivity (retention and secretion) in columns of beads coated with the polymers. For polyalkyl methacrylates with 1 to 4 carbon side chains, platelet reactivity varied directly with increasing length of the alkyl side chain and with the quantity of bound fibrinogen recognizable by antifibrinogen antibody but not with the total quantity of fibrinogen adsorbed. The same pattern of results was seen with five antibody preparations, including affinity-purified Fab fragments against the D or E domain of fibrinogen. Tests of platelet retention and fibrinogen binding to four polyalkyl acrylates and to three unrelated polymers (polystyrene, polymethyl methacrylate, and a polyether polyurethane) indicated that platelet retention correlated positively with both total fibrinogen binding and with the amount of antibody-recognizable fibrinogen bound. Drugs that block platelet aggregation, but not adhesion, did not alter the hierarchy of platelet retention to the polyalkyl methacrylates. These data suggest that, contrary to previous views, platelet adhesion to artificial surfaces increases with increasing surface coverage of adsorbed fibrinogen if the bound fibrinogen maintains a conformation such that its functional domains remain recognizable by antibody probes.
Correlation of drug sensitivity in vitro with clinical responses in childhood acute myeloid leukemia
Authors: Dow LW , Dahl GV , Kalwinsky DK , Mirro J , Nash MB , Roberson PK 
Published: October 2019

Abstract
Clonogenic cells from 41 children with newly diagnosed acute myeloid leukemia (AML) were tested in vitro for their sensitivity to cytarabine (Ara-C) and daunorubicin (DNR). The findings were then compared with the patients' responses to induction chemotherapy that uniformly included Ara-C and DNR. Light-density marrow cells were incubated with either or both drugs for one hour and cultured over leukocyte feeder layers; clusters and colonies were scored on days 7, 10, and 14. Only the percentage of cell kill in the presence of 1.8 mumol/L DNR was significantly associated with responses to induction therapy: median of 45% (range, 0% to 98%) for patients achieving complete remission v 16% (range, 4% to 23%) for nonresponders (P = .007). The relationship between clonogenic cell kill less than or equal to 23% and clinical responses was striking. Of the 11 evaluable patients with in vitro findings in this category, ten either failed induction therapy or relapsed within 1 year after attaining remission. Kaplan-Meier analysis of relapse-free survival times indicated longer durations of remission for patients whose blast cells showed increased sensitivity in vitro to Ara-C alone, DNR alone, or a combination of the two agents. Seven of 11 patients with cell kills of greater than or equal to 49% in the presence of 1.25 mumol/L Ara-C remain free of leukemia, compared with only one of 12 whose cells were less sensitive to the drug (P = .006). We conclude that the in vitro sensitivity of clonogenic leukemic progenitors to DNR and Ara-C correlates with treatment outcome in children with newly diagnosed AML.
Antibodies to shared idiotypes as agents for analysis and therapy for human B cell tumors
Authors: Stevenson FK , Wrightham M , Glennie MJ , Jones DB , Cattan AR , Feizi T , Hamblin TJ , Stevenson GT 
Published: October 2019

Abstract
Monoclonal anti-idiotypic antibodies generated against idiotypic immunoglobulin (Ig) of neoplastic B lymphocytes can be selected from growing hybridoma clones by their ability to recognize idiotypic but not normal IgM. This group of antibodies can be subdivided into those that bind to the target tumor cells in the presence of normal human serum (approximately 85% of the clones) and those in which binding is inhibited by serum (approximately 15%). The former appear to be specific for private idiotypic determinants whereas the latter recognize cross-reacting idiotypic determinants. Such cross-reactivity is reflected both in recognition of a small percentage of normal Ig and also in binding to other lymphomas. The anti-idiotypes specific for private determinants can be used for therapy, with only idiotypic Ig secreted by tumor cells able to block its access to cells. The cross- reacting anti-idiotypes will face in addition the barrier of the proportion of normal Ig with which it reacts. The attraction of using a single monoclonal reagent for more than one patient has led us to develop an assay that measures the level of such blocking and to propose that those recognizing less than 30 micrograms/mL of normal Ig could be placed in a panel for possible therapy for several patients; less restriction need apply to antibodies for monitoring tumor progress. The assay is described, and examples of such antibodies raised against lymphoma cells from two patients are given together with comparisons with them of anti-idiotypes specific for private determinants.
Lupus anticoagulants: improved diagnosis with a kaolin clotting time using rabbit brain phospholipid in standard and high concentrations
Authors: Rosove MH , Ismail M , Koziol BJ , Runge A , Kasper CK 
Published: October 2019

Abstract
We utilized a kaolin-activated partial thromboplastin time (APTT) using rabbit brain phospholipid, in which the capacity of a fourfold increased “high” phospholipid concentration (PC) to normalize the abnormal “standard” PC-APTT in patients with lupus anticoagulants is assessed. This system was also used to measure factors VIIIC, IX, and XI. The tissue thromboplastin inhibition test (TTI), a prothrombin time system in which the activity of a lupus anticoagulant is unmasked by the use of dilute thromboplastin, was simultaneously evaluated. Test sensitivity was defined by results on 31 consecutive patients with standard PC-APTT inhibitors and no bleeding tendency. Specificity was based on 94 patients with various other coagulopathies, including coagulation factor inhibitors, severe congenital factor deficiencies, hepatic insufficiency, and warfarin and heparin treatment. Twenty-one patients with lupus erythematosus and standard PC-APTT results within normal limits were also tested. Sensitivity of the APTT system was superior to that of the TTI (97% v 58%); high PC normalized clotting time ratios and factor levels. Positive results were common with both assays in the group of 20 heparinized patients. The APTT system had superior specificity in remaining cases; there were no positive tests among 74 patients. The lupus erythematosus group had a significant decrease in the clotting time ratio with high PC, indicating that low- level lupus anticoagulants are quite prevalent in this group. The kaolin clotting time using rabbit brain phospholipid in standard and high concentrations is a simple, sensitive, and specific technique for diagnosis of lupus anticoagulants.
Thrombin binding and response in platelets from patients with dyslipoproteinemias: increased stimulus-response coupling in type II hyperlipoproteinemia
Authors: Harmon JT , Tandon NN , Hoeg JM , Jamieson GA 
Published: October 2019

Abstract
Platelets were obtained from patients with various hyperlipidemias [type II, type V, lecithin-cholesterol acyltransferase (LCAT) deficiency] and hypolipidemias (abetalipoproteinemia, Tangier disease) to ascertain relationships among plasma lipids, platelet lipids, thrombin binding and thrombin-induced platelet aggregation, and to compare these data with those previously obtained on stimulus-response coupling in platelets following in vitro modification of membrane microviscosity. Washed platelets were studied for their ability to bind 125I-thrombin in the range of 10(-10) to 10(-6) mol/L (10 mU/mL to 100 U/mL) and to aggregate with thrombin at concentrations less than 10(-9) mol/L (100 mU/mL). The values for binding and aggregation in eight patients from six kindred with familial hypercholesterolemia, taken as a group, fell in the low normal range. If divided into two groups, patients with overt cardiovascular disease bound normal amounts of thrombin but were more responsive to it, whereas patients without overt cardiovascular disease bound lower amounts of thrombin but gave an aggregation response in the normal range. These results suggest that platelet hyperresponsiveness in familial hypercholesterolemia arises from an alteration in the coupling mechanism between thrombin binding and response such that platelets from patients with familial hypercholesterolemia are able to respond with lower receptor occupancy than is the case with normal platelets. Thrombin binding and aggregation were within normal ranges for platelets from abetalipoproteinemia patients (N = 4) and type V hyperlipoproteinemia (N = 2), although in the latter case the response appeared to be less at very low thrombin concentrations (less than 30 mU/mL). Thrombin binding was elevated in Tangier disease (N = 3) but with lower responsiveness at lower thrombin concentrations. Thrombin binding was also elevated in LCAT deficiency (N = 2), and one patient showed increased and another showed decreased aggregation responses. In general, increased plasma cholesterol levels resulted in increased stimulus-response coupling (type II), whereas increased triglyceride levels resulted in decreased coupling (type V, Tangier), and there was no apparent alteration in the coupling mechanism with overall reduction in plasma lipid levels as in abetalipoproteinemia.