bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of plasminogen activator inhibitor-1 in promoting fibrin deposition in rabbits infused with ancrod or thrombin
Authors: Krishnamurti C , Bolan C , Colleton CA , Reilly TM , Alving BM 
Published: October 2019

Abstract
The role of defective fibrinolysis caused by elevated activity of plasminogen activator inhibitor-1 (PAI-1) in promoting fibrin deposition in vivo has not been well established. The present study compared the efficacy of thrombin or ancrod, a venom-derived enzyme that clots fibrinogen, to induce fibrin formation in rabbits with elevated PAI-1 levels. One set of male New Zealand rabbits received intravenous endotoxin to increase endogenous PAI-1 activity followed by a 1-hour infusion of ancrod or thrombin; another set of normal rabbits received intravenous human recombinant PAI-1 (rPAI-1) during an infusion of ancrod or thrombin. Thirty minutes after the end of the infusion, renal fibrin deposition was assessed by histopathology. Animals receiving endotoxin, rPAI-1, ancrod, or thrombin alone did not develop renal thrombi. All endotoxin-treated rabbits developed fibrin deposition when infused with ancrod (n = 4) or thrombin (n = 6). Fibrin deposition occurred in 7 of 7 rabbits receiving both rPAI-1 and ancrod and in only 1 of 6 receiving rPAI-1 and thrombin (P “ .01). In vitro, thrombin but not ancrod was inactivated by normal rabbit plasma and by purified antithrombin III or thrombomodulin. The data indicate that elevated levels of PAI-1 promote fibrin deposition in rabbits infused with ancrod but not with thrombin. In endotoxin-treated rabbits, fibrin deposition that occurs with thrombin infusion may be caused by decreased inhibition of procoagulant activity and not increased PAI-1 activity.
Fibrinogen Mitaka II: a hereditary dysfibrinogen with defective thrombin binding caused by an A alpha Glu-11 to Gly substitution
Authors: Niwa K , Yaginuma A , Nakanishi M , Wada Y , Sugo T , Asakura S , Watanabe N , Matsuda M 
Published: October 2019

Abstract
A new type of A alpha Glu-11 to Gly substitution has been identified in a congenitally abnormal fibrinogen, fibrinogen Mitaka II, derived from a 14-year-old female suffering from easy bruising since childhood. Plasma of the patient and fibrinogen purified therefrom were found to clot slowly by thrombin but in a normal fashion by ancrod, a thrombin- like snake venom enzyme. The ancrod-clotted fibrin gels were normally solid and turbid, whereas the thrombin-clotted gels were initially fragile and transparent but became gradually normalized during further incubation. On reverse-phase high-performance liquid chromatography, there was an additional peptide group eluted distinctly later than the corresponding normal fibrinopeptide A in the clot-liquor of the patient's samples. Sequence analysis of these aberrant peptides and isolated A alpha chains of the patient's fibrinogen showed that Glu at position 11 of the abnormal A alpha chain had been replaced by Gly. Studies using 125I-labeled thrombin showed that the binding with thrombin was evidently reduced for her fibrinogen and the aberrant fibrinopeptide A as compared with that for the normal controls, indicating that A alpha Glu-11 may be critical for the fibrinogen- thrombin interaction. Indeed, A alpha Glu-11 of fibrinogen has recently been proposed to stabilize the local conformation, including the beta- turn, and to form a salt bridge between its side-chain carboxyl group and the guanidino group of Arg-173 of thrombin based on crystallographic analyses using analogs of fibrinopeptide A complexed with thrombin (Stubb et al, Eur J Biochem 206:187, 1992 and Martin et al, J Biol Chem 267:7911, 1992).
Prophylaxis against a Melanesian variant of human T-lymphotropic virus type I (HTLV-I) in rabbits using HTLV-I immune globulin from asymptomatically infected Japanese carriers
Authors: Tanaka Y , Ishii K , Sawada T , Ohtsuki Y , Hoshino H , Yanagihara R , Miyoshi I 
Published: October 2019

Abstract
Molecular variants of human T-lymphotropic virus type I (HTLV-I), which diverge significantly from the so-called cosmopolitan prototypes, have been discovered in Melanesia. In this study, HTLV-I IgG (I-IgG) prepared from seropositive healthy Japanese carriers was evaluated for its protective effect against a Melanesian isolate, HTLV-IMEL5, in rabbits. Normal IgG (N-IgG) prepared from seronegative healthy Japanese was used as control. Both preparations contained 50 mg/mL of IgG and I- IgG had a high neutralizing antibody titer, as determined by vesicular stomatitis virus--HTLV-I pseudotype assay. Of four experimental groups (A, B, C, and D), each with three rabbits, groups A and B were infused with 10 mL of N-IgG and I-IgG, respectively, and animals were challenged immediately by transfusion of 5 mL of blood from a rabbit infected with HTLV-IMEL5. Animals in groups C and D were immunized with 10 mL of I-IgG 24 and 48 hours, respectively, after being transfused with 5 mL of blood from the virus-infected rabbit. HTLV-I infection, as determined by seroconversion and verified by polymerase chain reaction, occurred in all rabbits in groups A and D after 2 to 6 weeks, but in none of the animals in groups B and C. These data indicate that I-IgG is protective against HTLV-IMEL5 infection when administered before or within 24 hours of transfusion with virus-contaminated blood. Moreover, our study shows that the neutralizing domains of the so-called cosmopolitan and Melanesian strains of HTLV-I are functionally indistinguishable.
CD34-expressing human thymocyte precursors proliferate in response to interleukin-7 but have lost myeloid differentiation potential
Authors: Schmitt C , Ktorza S , Sarun S , Blanc C , De Jong R , Debre P 
Published: October 2019

Abstract
CD34 is a marker for pluripotent stem cells also present on lineage- committed hematopoietic progenitors from bone marrow and a subpopulation of immature thymocytes. To characterize these early immature thymocytes, we have studied 24 pediatric thymus samples for CD34/7 expression. Three subpopulations could be defined from these T- cell receptor (TcR-) immature thymocytes: CD34+7++ (12.0 +/- 5.8), CD34- 7++ (12.6 +/- 8.6), and CD34-7+ (71.5 +/- 17.0%). CD7++ represents upregulation of this antigen and is expressed by cells of a blast-like morphology. Three-color flow cytometric analysis of these three subsets suggests the following ordered differentiation sequence: CD34+7++1-4-8- 45RA+-->CD34+7++1+ 4+8-45RA+/- -->CD34-7++1+4+8-+45RO+-->CD34- 7+1++4+8+45RO+. Early immature thymocyte cell division is essential in the thymus to generate a large number of precursors before the initiation of the selection process. We observed that both CD2 as well CD28 activation pathways were inefficient to serve as costimulant with phorbol ester 12-O-tetradecanoyl phorbol 13-acetate or interleukin-2 (IL-2) to induce the proliferation of the three CD34/7 subsets isolated by cell sorting. However, whereas IL-1, IL-2, IL-3, IL-4, granulocyte colony-stimulating factor, and granulocyte-macrophage colony- stimulating factor were ineffective, IL-7 was a potent cytokine, alone or in synergy with stem cell factor (SCF) to induce immature thymocyte proliferation. The proliferation induced by IL-7 or IL-7 + SCF is restricted to the CD34+ cells and, after 4 or 8 days of culture with IL- 7, some CD34+7++ acquire the expression of CD4 and/or CD8, but remain CD3/TcR-. We also tested the myeloid differentiation capacity of these CD34 immature thymocytes. Using two different approaches, myeloid colony formation in methylcellulose and limiting dilution analysis in the presence of myeloid growth factors, we were unable to detect myeloid differentiation capacity from CD34+ early thymocytes, whereas CD34+7+ from bone marrow contained about 10% of the clonogenic cells present in the CD34+7- fraction. Together, these data support the concept that thymic CD34+7++ represents the earliest thymic subset of fully committed T-lineage cells, capable of proliferating specifically to IL-7.
Infection of peripheral blood mononuclear cells by hepatitis C virus in mixed cryoglobulinemia
Authors: Ferri C , Monti M , La Civita L , Longombardo G , Greco F , Pasero G , Gentilini P , Bombardieri S , Zignego AL 
Published: October 2019

Abstract
A striking association between hepatitis C virus (HCV) infection and mixed cryoglobulinemia (MC) has been shown; thus, HCV seems to play an important etiopathogenetic role in this lymphoproliferative disorder. Because HCV is both a hepatotropic and lymphotropic virus, this study aimed to investigate the prevalence of HCV infection of peripheral blood mononuclear cells (PBMCs) in a series of 16 patients with type II (IgMk) MC. Antibodies against HCV were detected by commercially available kits (Second Generation Chiron enzyme-linked immunosorbent assay [ELISA] and recombinant-based immunoblot assay [RIBA]), and the presence of HCV RNA was evaluated in both sera and isolated PBMCs using the polymerase chain reaction technique. A previous exposure to HCV was shown by ELISA and confirmed by RIBA in all cases (100%). Moreover, HCV RNA was present in the sera of 8 of 16 patients (50%), whereas its frequency markedly increased (13 of 16 [81%]) when genomic sequences were detected in peripheral lymphocytes. HCV RNA was never detected in the PBMCs of 20 control subjects. These findings showed that HCV infection, alone or in combination with other factors, may be responsible for the clonal B-cell expansion underlying the systemic manifestations of MC, and may explain the appearance of a malignant non- Hodgkin's lymphoma in some subjects.
Alteration in cytoadherence and rosetting of Plasmodium falciparum- infected thalassemic red blood cells
Authors: Udomsangpetch R , Sueblinvong T , Pattanapanyasat K , Dharmkrong-at A , Kittikalayawong A , Webster HK 
Published: October 2019

Abstract
Hemoglobinopathies have a protective role in malaria that appears to be related to alterations in red blood cell (RBC) properties. Thalassemic RBCs infected with Plasmodium falciparum showed greatly reduced cytoadherence and rosetting properties as well as impaired growth and multiplication. A significant decrease in the levels of falciparum antigens associated with the membrane of infected beta-thalassemic RBCs was observed at trophozoite/schizont stage, but not young ring stage. This reduction was shown when a cytoadherence inhibitory monoclonal antibody, but not a noninhibitory pooled immune serum, was used. These observations suggest that protection against malaria in thalassemia is caused by both reduced parasitemias and altered adherence properties of the infected thalassemic RBCs that promote enhanced clearance of the parasite from the circulation.
Peripheral blood progenitor cell transplantation in lymphoma and leukemia using a single apheresis
Authors: Pettengell R , Morgenstern GR , Woll PJ , Chang J , Rowlands M , Young R , Radford JA , Scarffe JH , Testa NG , Crowther D 
Published: October 2019

Abstract
Myeloablative treatment and peripheral blood progenitor cell (PBPC) transplantation are increasingly used for lymphomas and leukemias. We have sought to optimize conditions for priming, collection, and engraftment of the leukapheresis product. Fifty-four consecutive adult patients were eligible, 31 with high-grade non-Hodgkin's lymphoma of poor prognosis, 12 with Hodgkin's disease in chemosensitive relapse, and 11 with poor prognosis acute lymphoblastic leukemia. Filgrastim was administered after routine chemotherapy with VAPEC-B or HiCCOM to mobilize PBPC. A rapidly increasing white blood cell count was used to predict the time of peak PBPC release and plan leukapheresis. Forty- five patients underwent leukapheresis. A median of 14 L of blood was processed at a single apheresis. A median of 2.4 x 10(8)/kg mononuclear cells (MNCs), 1.04 x 10(6)/kg granulocyte-macrophage colony-forming cells (GM-CFCs), and 10.6 x 10(6)/kg CD34+ cells were obtained. Slightly fewer MNCs were obtained from the heavily pretreated Hodgkin's disease group. There were no other significant differences in the size or composition of the leukapheresis harvest in the three patient groups. Forty patients underwent high-dose therapy and PBPC transplantation. Filgrastim was administered by daily subcutaneous injection until the absolute neutrophil count was > or = 1 x 10(9)/L for 2 consecutive days. Rapid and sustained hematopoietic engraftment occurred in all patients. The median time to achieve a neutrophil count > or = 0.5 x 10(9)/L was 9 days (range, 8 to 16 days); to achieve a platelet count > or = 20 x 10(9)/L was 10 days (range, 6 to 88 days); and to achieve a platelet count > or = 50 x 10(9)/L was 15.5 days (range, 10 to 100 days). Neutrophil recovery was faster than that of a historical control group treated with autologous bone marrow transplantation and filgrastim, but platelet recovery times were halved in the PBPC group. There was no secondary engraftment failure. Requirements for blood and platelet transfusions, antibiotic use, and parenteral nutrition were similar in the three patient groups. The median number of days in the hospital was 13 (range, 10 to 55) in the PBPC patients, compared with 19 (range, 14 to 51) in the historical controls. Leukapheresis yields (MNC, GM-CFC, and CD34+ cell numbers) were not useful for predicting the times to engraftment. We have shown that sufficient PBPC for transplantation can be obtained at a single leukapheresis after mobilization with routine chemotherapy and filgrastim in patients with non-Hodgkin's lymphoma, Hodgkin's disease, and acute lymphoblastic leukemia, even those heavily pretreated.(ABSTRACT TRUNCATED AT 400 WORDS)
In vivo administration of stem cell factor to mice increases the absolute number of pluripotent hematopoietic stem cells
Authors: Bodine DM , Seidel NE , Zsebo KM , Orlic D 
Published: October 2019

Abstract
We have examined the effects of administration of stem cell-factor (SCF) on the number and distribution of pluripotent hematopoietic stem cells (PHSC) in normal mice. Using the competitive repopulation assay we found that in vivo administration of SCF increases the absolute number of PHSC per mouse threefold. The increased numbers of PHSC are found in the peripheral blood and spleen of the SCF-treated animals. The spleen and peripheral blood stem cells completely repopulated the erythroid, myeloid, and lymphoid lineages of irradiated or W/Wv hosts, similar to bone marrow PHSC. PHSC from the peripheral blood of SCF- treated mice have a lineage marker-negative, c-kit-positive phenotype that is indistinguishable from that of bone marrow PHSC. The increase in the absolute number of spleen PHSC is associated with efficient gene transfer to these cells without prior treatment with 5-fluorouracil. This is a US government work. There are no restrictions on its use.
Platelets lacking functional CD36 (glycoprotein IV) show reduced adhesion to collagen in flowing whole blood
Authors: Diaz-Ricart M , Tandon NN , Carretero M , Ordinas A , Bastida E , Jamieson GA 
Published: October 2019

Abstract
A parallel-plate perfusion chamber has been used to evaluate the contribution of the adhesive membrane glycoprotein CD36 (GPIV) to platelet adhesion on type I collagen in flowing whole blood at a shear rate of 800 s-1. In one series of experiments, reconstituted normal blood (hematocrit 0.4; platelet count 1.5 x 10(5)/microL) was prepared from washed red blood cells, plasma, and washed platelets that had been incubated with Fab fragments of a monospecific polyclonal anti-CD36 antibody (50 micrograms/mL, 30 minutes, 37 degrees C). Percent surface coverage of collagen-coated coverslips using reconstituted blood with antibody-blocked platelets, as compared with paired reconstituted controls (100%), was 50% at 2 minutes, 87% at 5 minutes, and 90% at 10 minutes. Further studies were performed by perfusion of whole blood from a healthy donor of the Naka-negative phenotype, whose platelets constitutively lack CD36, over collagen-coated coverslips. In this case, percent surface coverage was 55% of normal controls at 2 minutes, 76% of controls at 5 minutes, and 72% of controls at 10 minutes. In both preparations, platelets lacking functional CD36 had a statistically significant decrease (P < .005) in adhesion after 2 minutes and 10 minutes perfusion but not at 5 minutes. These results show that functional CD36 facilitates the rapid adhesion of platelets to collagen and that this effect is seen at the earliest time points of their interaction.
C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor
Authors: Cermak J , Key NS , Bach RR , Balla J , Jacob HS , Vercellotti GM 
Published: October 2019

Abstract
The acute inflammatory response is frequently accompanied by serious thrombotic events. We show that C-reactive protein (CRP), an acute- phase reactant that markedly increases its serum concentration in response to inflammatory stimuli, induced monocytes to express tissue factor (TF), a potent procoagulant. Purified human CRP in concentrations commonly achieved in vivo during inflammation (10 to 100 micrograms/mL) induced a 75-fold increase in TF procoagulant activity (PCA) of human peripheral blood mononuclear cells (PBM), with a parallel increase in TF antigen levels. CRP-induced PCA was completely blocked by a monoclonal antibody against human TF but not by irrelevant murine IgG. Dot blot analysis showed a significant increase of TF mRNA after 4 hours of incubation with CRP, followed by a peak of PCA within 6 and 8 hours. Actinomycin D and cycloheximide blocked CRP-stimulated PCA, suggesting that de novo TF protein synthesis was required. Endotoxin (LPS) contamination of CRP was excluded as the mediator of TF synthesis because: (1) CRP was Limulus assay negative; (2) induction of TF PCA by CRP was not blocked by Polymyxin B, in contrast to LPS- induced PCA; (3) antihuman CRP IgG inhibited CRP-induced PCA, but not LPS-induced PCA; (4) CRP was able to stimulate TF production in LPS- pretreated PBM refractory to additional LPS stimulation; and, (5) unlike LPS, CRP was incapable of inducing TF in human umbilical vein endothelial cells. We suggest that CRP-mediated TF production in monocytes may contribute to the development of disseminated intravascular coagulation and thrombosis in inflammatory states.
Variable morphology of human immunodeficiency virus-associated lymphomas with c-myc rearrangements. The French Study Group of Pathology for Human Immunodeficiency Virus-Associated Tumors, I
Authors: Delecluse HJ , Raphael M , Magaud JP , Felman P , Alsamad IA , Bornkamm GW , Lenoir GM 
Published: October 2019

Abstract
Burkitt lymphoma (BL) and immunoblastic lymphoma (IL) are the most frequent lymphoid tumors encountered in human immunodeficiency virus (HIV)-infected patients. Tumors with a morphology intermediate between BL and IL, and the existence of Burkitt's type translocations in some IL cases makes the classification of these tumors sometimes unclear. We have studied 14 cases of BL and IL in HIV-seropositive individuals with regard to clonality, Epstein-Barr virus (EBV) association, and the presence of c-myc rearrangement. Of seven tumors with morphology of BL, all were monoclonal, six showed a c-myc rearrangement and four were associated with EBV. Five tumors with morphology of IL were associated with EBV and devoid of c-myc rearrangement. Three were polyclonal representing EBV-driven lymphoproliferations similar to those observed in transplant recipients. Two tumors, one with a morphology of IL and the other intermediate between IL and BL were monoclonal, associated with EBV, and harbored a c-myc rearrangement. We propose that these last two tumors represent cases of BL that have adopted an immunoblastic morphotype in the context of acquired immunodeficiency syndrome (AIDS), reflecting the morphologic evolution of Burkitt lymphoma cells observed in culture.
Trisomy 12 in chronic lymphocytic leukemia detected by fluorescence in situ hybridization: analysis by stage, immunophenotype, and morphology
Authors: Que TH , Marco JG , Ellis J , Matutes E , Babapulle VB , Boyle S , Catovsky D 
Published: October 2019

Abstract
Fluorescence in situ hybridization (FISH) with a chromosome 12 specific alpha-centromeric probe was performed on interphase cells from 183 patients with B-cell chronic lymphocytic leukemia (CLL). Twenty one cases with trisomy 12 (11.5%) were detected. The number of trisomic cells ranged from 5.5% to 76% (mean 38.5%). No correlation was found between the presence of trisomy 12 and white blood cell count, hemoglobin level, platelet count, a specific immunophenotype, clinical stage, sex, splenomegaly, or lymphadenopathy. Morphologic review of all cases with trisomy 12 showed seven (33%) with more than 10% prolymphocytes and three (14%) with CLL of mixed cell type. While trisomy 12 is the most common chromosomal abnormality in CLL, it is more frequent in morphologically atypical cases, some of which may be undergoing transformation. There was a statistically significant difference in the incidence of atypical cases between those with (47%) and without (7.6%) trisomy 12 (P < .001). It remains to be determined whether this abnormality is associated with a worse prognosis; this is currently being investigated in the context of a national therapeutic trial. The technique used is more sensitive than conventional cytogenetic analysis, which in this series failed to detect trisomy 12 in six cases. FISH allows the systematic study on a large number of patients without the need of metaphase preparations.
Antisense oligonucleotides to the p65 subunit of NF-kappa B block CD11b expression and alter adhesion properties of differentiated HL-60 granulocytes
Authors: Sokoloski JA , Sartorelli AC , Rosen CA , Narayanan R 
Published: October 2019

Abstract
NF-kappa B is a pleiotropic regulator of a variety of genes implicated in the cellular response to injury. This function has been attributed to the coordinated binding of subunits of NF-kappa B to distinct regions of the promoter elements of numerous genes, including cytokines, growth factor receptors, and adhesion molecules. Antisense phosphorothioate oligonucleotides to the p50 and p65 subunits of the NF- kappa B complex were used to define the physiologic role of this transcription factor in resting and stimulated granulocytes. A reduction in the expression of p65 was produced by treatment with the phosphorothioate antisense oligodeoxynucleotide. This reduction was accompanied by rapid changes in the cellular adhesion of dimethyl sulfoxide-differentiated HL-60 leukemia cells stimulated by 12-O- tetradecanoylphorbol 13-acetate (TPA). These effects were characterized by a marked reduction in CD11b integrin expression on the surface of treated cells. Furthermore, the p65 antisense oligomer effectively abolished an upregulation of CD11b that was produced by formyl-met-leu- phe and TPA. However, the p65 antisense phosphorothioate oligodeoxynucleotide had no significant effect on the production of reactive oxygen intermediates or on phagocytosis by these cells. These findings indicate that antisense oligomers to p65 can be used to define the role of NF-kappa B in the activation pathways of neutrophils.