bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship of the properties of antihemophilic factor (factor VIII) that support ristocetin-induced platelet agglutination (factor VIIIR:RC) and platelet retention by glass beads as demonstrated by a monoclonal antibody
Authors: Ogata K , Saito H , Ratnoff OD 
Published: October 2019

Abstract
A monoclonal antibody to human antihemophilic factor (AHF, factor VIII) was derived from BALB/c mouse spleen cells fused with P3x63Ag8 mouse plasmacytoma cells. This antibody, harvested from culture medium or ascites fluid, reacted with purified AHF and with plasmas with normal subjects or classic hemophiliacs, as measured by enzyme-linked immunosorbent assay (ELISA), but not with plasmas from patients with severe von Willebrand's disease. The antibody possessed only IgG, heavy chains and kappa light chains. It blocked ristocetin-induced platelet agglutination and, to a lesser degree, platelet retention by glass bead columns, but it did not inhibit the procoagulant activity of AHF significantly. An amount of rabbit antiserum against AHF that provided equivalent inhibition of ristocetin-induced platelet agglutination inhibited glass bead retention much more effectively than the mouse monoclonal antibody. This difference was exaggerated in studies of the corresponding Fab fragments. These data suggest that the site or sites on the AHF complex molecule that are associated with ristocetin-induced platelet agglutination differ quantitatively or qualitatively from those associated with enhancement of platelet retention by glass beads. ELISA titers of immunoreactive AHF, using the monoclonal antibody, were closely correlated to those using rabbit antiserum against AHF in normal, hemophilic, and most von Willebrand's disease plasma.
Studies with a murine monoclonal antibody that abolishes ristocetin- induced binding of von Willebrand factor to platelets: additional evidence in support of GPIb as a platelet receptor for von Willebrand factor
Authors: Coller BS , Peerschke EI , Scudder LE , Sullivan CA 
Published: October 2019

Abstract
A murine monoclonal antibody directed at or near a platelet membrane receptor for the von Willebrand factor was produced by the hybridoma technique. Purified F(ab')2 fragments and/or intact antibody completely blocked the agglutination of platelets induced by both ristocetin and bovine von Willebrand factor and the binding of von Willebrand factor antigen to platelets. The antibody also decreased platelet retention, prevented the reduction in platelet electrophoretic mobility caused by bovine von Willebrand factor, and decreased the serum prothrombin time. Radiolabeled F(ab')2 fragments bound to or approximately 2.5 X 10(4) sites on normal platelets with high affinity (KD or approximately 1.5 X 10(-8) M); there was no binding to platelets from 2 patients with the Bernard-Soulier syndrome. Immunoprecipitation and affinity chromatography studies indicated that the antibody binds to glycoprotein lb at a site contained on the externally oriented portion of the GPIb alpha chain (glycocalicin). An unidentified mol wt or approximately 20,000 molecule labeled by periodate/NaB3H4 coprecipitated and copurified with GPIb.
A new life-long hemorrhagic disorder due to excess plasminogen activator
Authors: Booth NA , Bennett B , Wijngaards G , Grieve JH 
Published: October 2019

Abstract
A life-long bleeding disorder is described, characterized by hemorrhage occurring after surgery, injury, or dental extraction, and finally by spontaneous intracerebral bleeding. No abnormality of platelet function or plasma coagulation was demonstrable, but grossly enhanced overall fibrinolytic activity was present. The patient had, additionally, a hyperlipidemia with gross arterial atheroma and a family history of myocardial infarction but not of any hemorrhagic disorder. Laboratory studies led to the conclusion that the enhanced fibrinolysis was due to consistently greatly raised levels of a plasma plasminogen activator physically and immunologically related to that in human tissues and blood vessel endothelium. No deficiency of any known inhibitor of fibrinolysis was detected. Free plasmin was not detectable in functional assays but continuous intravascular plasmin generation clearly occurred as evidenced by presence of plasmin-alpha 2- antiplasmin complexes and of fibrin/fibrinogen-related antigens. Excessive production of plasminogen activator appeared to have occurred throughout life and to be independent of the hyperlipidemia. The pathologically increased fibrinolytic activity may have accounted for the complete absence of detectable thrombotic vascular occlusion at autopsy despite extensive arterial disease with severe narrowing of coronary and cerebral arteries.
Survival of density subpopulations of rabbit platelets: use of 51Cr-or 111In-labeled platelets to measure survival of least dense and most dense platelets concurrently
Authors: Rand ML , Packham MA , Mustard JF 
Published: October 2019

Abstract
The origin of the density heterogeneity of platelets was studied by measuring the survival of density subpopulations of rabbit platelets separated by discontinuous Stractan density gradient centrifugation. When a total population of 51Cr-labeled platelets was injected into recipient rabbits, the relative specific radioactivity of the most dense platelets decreased rapidly. In contrast, that of the least dense platelets had not changed 24 hr after injection, and then decreased slowly. To distinguish between the possibilities that most dense platelets are cleared from the circulation more quickly than least dense platelets or that platelets decrease in density as they age in the circulation, the concurrent survival of least dense and most dense platelets, labeled with either 51Cr or 111In-labeled total platelet populations, determined concurrently in the same rabbits, were identical, calculated from 1 hr values as 100%. However, the 1-hr recovery of 111In-labeled platelets was slightly but significantly less than that of 51Cr-labeled platelets. Therefore, we studied the survival of 51Cr-labeled least dense and 111In-labeled most dense platelets as well as that of 111In-labeled least dense and 51Cr-labeled most dense platelets. Mean 1-hr recovery of least dense platelets, labeled with either isotope (78% +/- 7%, SD) was similar to that of most dense platelets, labeled with either isotope (77% +/- 8%; SD). Mean survival of least dense platelets was 47.3 +/- 18.7 hr (SD), which was significantly less than that of most dense platelets (76.1 +/- 21.6 hr; SD) (p less than 0.0025). These results indicate that platelets decrease in buoyant density as they age in the circulation and that most dense platelets are enriched in young platelets, and least dense in old. Thus, the events that affect platelets as they age in the circulation contribute to platelet density heterogeneity, although they may not be the sole cause of it.
Characteristics and requirements of the interaction between human monocytes and tumor cells on the single cell level
Authors: Golightly MG , Fischer DG , Ohlander C , Koren HS 
Published: October 2019

Abstract
Highly purified (97%-99%) and viable (99%) peripheral blood monocytes obtained by EDTA-reversible adherence to autologous-serum-precoated plastic surfaces could rapidly lyse a variety of tumor cells in a 3–4 hr 51Cr release assay. Using these monocytes as effectors, a short-term agarose/conjugate assay was utilized, permitting us to examine the interaction between fresh human monocytes and neoplastic target cells on a single cell level. That the tumor-bound effector cells were indeed monocytes was confirmed by employing the monocyte-specific monoclonal antibody 61D3, which stained 95%-99% of the mononuclear cells bound to conjugated and killed K562 tumor targets. The binding of monocytes to target cells appeared to be temperature dependent and was extremely rapid, reaching a plateau after 5 min at 30 degrees C. Our findings demonstrated for the first time that only a proportion of human blood monocytes can bind to a particular target cell and that only a fraction of the binding cells have the intrinsic potential to kill those neoplastic targets. The proportion of monocytes capable of binding and killing varies between individuals and also depends on the tumor cell used, indicating heterogeneity in the monocyte and tumor cell populations. The highest proportion of monocytes bind to the human erythromyeloid leukemia K562 cell line (13%-50%). The frequency of monocytes capable of killing K562 tumor cells is relatively low (7%- 13%). The system described here should be useful to study the heterogeneity of mononuclear phagocytes and to analyze the molecular basis of the interaction between those effector cells and neoplastic target cells.
A comparison of surface marker analysis and FAB classification in acute myeloid leukemia
Authors: van der Reijden HJ , van Rhenen DJ , Lansdorp PM , van't Veer MB , Langenhuijsen MM , Engelfriet CP , von dem Borne AE 
Published: October 2019

Abstract
Surface marker analysis with rosette tests and a large panel of xenoantisera and monoclonal antibodies was done on the malignant cells of 55 patients with acute myeloid leukemia (AML). The diagnosis was made on morphological and cytochemical grounds, and the leukemias were classified according to the quantified FAB criteria. The marker tests included the E- and EA-rosette test, immunofluorescence with rabbit- polyclonal antisera against human Ig, kappa, and lambda light chains, thymocytes, granulocytes, erythrocytes, platelets, lysozyme, (leukemic) myeloblasts, the common ALL antigen, SB cell-line cells (anti-Ia), and a mouse anti-Ia serum. The monoclonal mouse antibodies applied were anti-T-cell antibody (3A1), two anti-granulocyte-monocyte antibodies (OKM1 and B2.12), four antigranulocyte antibodies (MI/N1, UJ 308, B4.3, and B13.9), an antiplatelet antibody (C17.28), anti-HLA heavy chains (w6/32.HLK), anti-Ia antigen (OKI1), and OKT10. AML cells from many patients lacked the expression of myeloid markers, and we found that a correlation existed between the relative maturity of the leukemia subtype and the extent of positivity for these markers. Surface marker analysis discriminated poorly between the “myeloid” and “monocytoid” subtypes; OKT10 and the “T-cell marker” 3A1 were often expressed on AML cells. In two cases of AML, there was an unexpected expression of platelet antigens with the monoclonal antiplatelet antibody. One of them, classified as M1, was ultrastructurally a megakaryoblastic proliferation with a positive reaction for platelet peroxidase. Only with the help of computerized analysis, was it possible to prove a clear correlation between the surface marker profile and the FAB classification.
The secretion of plasminogen activators by human myeloid leukemic cells in vitro
Authors: Wilson EL , Jacobs P , Dowdle EB 
Published: October 2019

Abstract
Peripheral blood cell preparation from 23 normal subjects and 72 patients with acute and 32 patients with chronic myeloid leukemia were cultured in vitro and released plasminogen activators were analyzed. The quantity of plasminogen activator secreted by leukemic cells varied widely and could not be correlated with the clinical severity of the disease. Immunochemical and electrophoretic techniques have been used to show that normal peripheral blood granulocytes released exclusively urokinase-like plasminogen activator, whereas leukemic cells secreted either urokinase or a tissue activator-like enzyme. The molecular species of enzyme released by acute myeloid leukemic cells may serve as a diagnostic marker of relevance to the management of this disease, since patients with acute myeloid leukemia whose cells released only tissue plasminogen activator did not respond to combination chemotherapy. Tissue plasminogen activators released by leukemic cells may display an unusual electrophoretic pattern that resembles that shown by urokinase. Immunochemical procedures are therefore essential for the correct identification of these enzymes.
T-cell surface antigens in a patient with blast crisis of chronic myeloid leukemia
Authors: Griffin JD , Tantravahi R , Canellos GP , Wisch JS , Reinherz EL , Sherwood G , Beveridge RP , Daley JF , Lane H , Schlossman SF 
Published: October 2019

Abstract
There is little evidence to suggest that T lymphocytes are involved in the leukemic process in chronic myeloid leukemia (CML). A case of CML in blast phase is described in which T-cell surface antigens were detected by immunofluorescence on the patient's blasts using monoclonal antibodies. In order to determine that the T-cell blasts were derived from the original CML clone, cells bearing the T3 antigen were isolated by fluorescence-activated cell sorting and chromosome analysis was performed. All metaphases examined had the Philadelphia chromosome, confirming their origin from CML.
A mechanism for the hypoprothrombinemia of the acquired hypoprothrombinemia-lupus anticoagulant syndrome
Authors: Bajaj SP , Rapaport SI , Fierer DS , Herbst KD , Schwartz DB 
Published: October 2019

Abstract
Antibodies that bind prothrombin without neutralizing its coagulant activity were demonstrated in the plasma of two patients with the acquired hypoprothrombinemia-lupus anticoagulant syndrome. The first patient's plasma contained less than 1% prothrombin activity and no detectable prothrombin antigen. The second patient's plasma contained about 6% of both prothrombin activity and antigen. Neither patient's plasma neutralized the prothrombin coagulant activity of normal plasma or of purified prothrombin added in vitro. Nevertheless, double immunodiffusion studies and binding experiments utilizing 125I- prothrombin demonstrated the presence of prothrombin antibodies in each patient's plasma. A Scatchard analysis of the binding data obtained with different concentrations of 125I-prothrombin and the first patient's plasma indicated the presence of a high affinity antibody, apparent Kd approximately 10(-10)M, and a lower affinity antibody, apparent Kd approximately 10(-9)M. Studies utilizing purified cleavage products of prothrombin suggested that the antibodies were directed against an epitope or epitopes located on the carboxyl-terminal, latent thrombin segment of the prothrombin molecule. We postulate that the acquired hypoprothrombinemia in these two patients and in other reported patients with the acquired hypoprothrombinemia-lupus anticoagulant syndrome stems from rapid clearance from the circulation of prothrombin antigen-antibody complexes.
Granulocytes and cultured human fibroblasts express common acute lymphoblastic leukemia-associated antigens
Authors: Braun MP , Martin PJ , Ledbetter JA , Hansen JA 
Published: October 2019

Abstract
We have investigated the expression of the common acute lymphoblastic leukemia antigen (cALLA) by nonlymphoid cells, using a new murine monoclonal antibody (designated 24.1), specific for cALLA. This antibody completely blocks the binding of monoclonal anti-cALLA antibody J-5. Furthermore, antibody 24.1 binds to cALLA with greater affinity and induces a greater degree of antigenic modulation than antibody J-5. With antibody 24.1, we have demonstrated that normal cultured marrow and skin fibroblasts and mature granulocytes express cALLA. By immune precipitation and polyacrylamide gel electrophoresis, cALLA from fibroblasts has a slightly lower molecular weight and cALLA from granulocytes a slightly higher molecular weight than cALLA from cultured human leukemic cell lines. Quantitative studies indicate, however, that cALLA expression is approximately 3-fold and 20-fold lower, respectively, on normal granulocytes and skin fibroblasts than on NALM-6 cells. cALLA may be expressed by cells with widespread distribution in multiple organ systems. These findings emphasize that differentiation markers that appear to be tumor or tissue specific may be found on cells of diverse origin.
Sodium azide enhancement of interleukin-2 production
Authors: Feldman SP , Mertelsmann R , Venuta S , Andreeff M , Welte K , Moore MA 
Published: October 2019

Abstract
The production of large quantities of Interleukin-2 (IL-2) from normal human lymphocytes has been limited by the short production and release period, as well as its absorption by the responsive cell population. We report the utilization of sodium azide (NaN3, 0.01% final concentration) to allow continued production of IL-2 as long as 72–96 hr and thereby increase the yield significantly. Cell cycle analysis performed by flow cytometry indicates that NaN3 blocks cells at the G0- G1 transition and the G1-S transition, depending on the time of addition of NaN3 to the cultures.
Failure of regulation of Tac antigen/TCGF receptor on adult T-cell leukemia cells by anti-Tac monoclonal antibody
Authors: Tsudo M , Uchiyama T , Uchino H , Yodoi J 
Published: October 2019

Abstract
Anti-Tac monoclonal antibody, which blocks the membrane binding and action of human T-cell growth factor (TCGF), is strongly proposed to recognize TCGF receptor. We have demonstrated that anti-Tac antibody reacted with leukemic cells from patients with adult T-cell leukemia (ATL) and reacted with T-cell lines established from ATL cells. Although antigenic modulation, or down-regulation, of Tac antigen on activated normal T cells was induced by anti-Tac antibody, the expression of Tac antigen on ATL cells or T-cell lines was not affected when examined by the fluorescence-activated cell sorter (FACS) and the radioassay using 125I-staphylococcal protein A. These results indicate that regulation of Tac antigen-TCGF receptor is different between normal and malignant T cells, suggesting that failure of down- regulation of Tac antigen on leukemic cells by anti-Tac antibody may play an important role in the malignant proliferation of ATL cells.
Monoclonal antibody characterization of surface antigens in childhood T- cell lymphoid malignancies
Authors: Roper M , Crist WM , Metzgar R , Ragab AH , Smith S , Starling K , Pullen J , Leventhal B , Bartolucci AA , Cooper MD 
Published: October 2019

Abstract
Although childhood T-cell acute lymphocytic leukemia (T-ALL) and T-cell non-Hodgkin's lymphoma (T-NHL) have certain clinical features in common, T-ALL carries a notably poorer prognosis than does T-NHL. To determine whether the malignant cells from patients with these disorders are distinguishable, we examined bone marrow and/or blood from 51 children with T-ALL and tumor biopsy specimens from 17 with T- NHL, using a panel of monoclonal antibodies directed against T-cell differentiation antigens. We found considerable phenotypic heterogeneity in both T-ALL and T-NHL. Of the T-ALL (defined by greater than 25% blasts in the bone marrow) patients, 33% demonstrated a surface antigen pattern consistent with the earliest thymocyte stage of T-cell development (T9+ and/or T10+, or T6-/T4-/T8-/T3-), 37% were of a midthymocyte stage (T6+, and/or simultaneous expression of T4-helper and T8-suppressor antigens), and 30% expressed surface antigen patterns found on mature thymocytes (T3+, variable expression of other antigens). In contrast, tumor cell phenotypes in the 17 T-NHL patients were approximately equally distributed between mid- and mature thymocyte phenotypes. No NHL samples were classified as the early thymocyte phenotype. Clinical features as related to specific T-ALL immunophenotypes are presented, and the implications of these findings in regard to the current understanding of the differences in tumor biology between T-ALL and T-NHL are discussed.
Plasma lactoferrin reflects granulocyte activation in vivo
Authors: Lash JA , Coates TD , Lafuze J , Baehner RL , Boxer LA 
Published: October 2019

Abstract
N-formyl-met-leu-phe (FMLP) causes polymorphonuclear leukocytes (PMN) to secrete and become “sticky” in vitro. We related these events to in vivo FMLP-induced neutropenia. FMLP was intravenously administered to anesthetized rabbits in doses ranging from 0.01 microgram to 1.0 microgram. Controls received phosphate-buffered saline (PBS), the diluent for FMLP. Blood pressure, respiratory rate, and arterial Po2 were monitored. High and intermediate doses of FMLP caused a dramatic but transient decrease in blood pressure and an increase in respiratory rate. Prior to FMLP infusion, plasma lactoferrin level was 6.4 +/- 4.1 micrograms/ml, and the absolute granulocyte account (AGC) was 2008 +/- 1229 (mean +/- SD). There was a positive linear correlation between AGC and plasma lactoferrin level prior to injection of FMLP (R2 = 0.74, p less than 0.01). At 1 min after FMLP injection, the percent change in AGC decreased as an exponential function of dose to as low as 10% of baseline (R2 = 0.86, p = 0.002) and plasma concentration of lactoferrin increased as an exponential function of dose to as high as 30 micrograms/ml (R2 = 0.84, p = 0.006). Thus, FMLP-induced neutropenia is associated with increased levels of plasma lactoferrin, suggesting that PMN are induced to degranulate in vivo.
Anticonvulsant-induced aplastic anemia: increased susceptibility to toxic drug metabolites in vitro
Authors: Gerson WT , Fine DG , Spielberg SP , Sensenbrenner LL 
Published: October 2019

Abstract
A 53-yr-old man sequentially developed aplastic anemia from phenytoin and carbamazepine. Both compounds undergo metabolism to potentially toxic arene oxide intermediates. We tested the hypothesis that the patient's adverse reactions were due to a defect in detoxification of such metabolites by challenging his peripheral lymphocytes with drug metabolites generated by a murine hepatic microsomal system in vitro. The patient's cell viability was normal in the absence of drugs. However, his cells showed greater toxicity from both phenytoin and carbamazepine metabolites than did controls. Toxicity was dependent on microsomes and NADPH. Intermediate toxicity was noted in cells from the patient's mother. The results provide the first evidence for a role of arene oxide drug metabolites in aplastic anemia in humans and suggest that enhanced susceptibility to toxicity may be based on an inherited abnormality in metabolite detoxification.
Human myeloma in vitro colony growth: interrelationships between drug sensitivity, cell kinetics, and patient survival duration
Authors: Durie BG , Young LA , Salmon SE 
Published: October 2019

Abstract
Ninety-seven patients with multiple myeloma evaluated serially had both a tritiated thymidine labeling index of bone marrow plasma cells (LI%) and in vitro myeloma stem cell culture performed. Thirty-three patients with myeloma colony growth had in vitro drug sensitivity testing carried out, 18 having in addition in vitro thymidine suicide determinations. The LI% and the likelihood of in vitro myeloma colony growth were highly correlated: the higher the LI%, the more likely was colony or cluster growth (p less than 0.001). The tritiated thymidine suicide of myeloma stem cells was usually very high. There was excellent correlation between in vitro and in vivo drug sensitivity. Both pretreatment drug resistance and selective sensitivity (e.g., interferon, bisantrene, methotrexate, vinblastine) at the time of relapse were accurately detected and correlated well with survival duration (p = 0.01 Wilcoxan). Although LI% and in vitro sensitivity were clearly independent variables, a high LI% (greater than 3%) plus in vitro resistance were associated with a subsequent survival duration of less than 6 mo. The studies allowed dissection of the complex interrelationship between cell kinetics and drug sensitivity.