bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor necrosis factor increases the production of plasminogen activator inhibitor in human endothelial cells in vitro and in rats in vivo
Authors: van Hinsbergh VW , Kooistra T , van den Berg EA , Princen HM , Fiers W , Emeis JJ 
Published: October 2019

Abstract
The vascular endothelium plays an important role in fibrinolysis by producing tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI). The monokine tumor necrosis factor (human recombinant TNF) increased the production of PAI by cultured human endothelial cells from umbilical vein (twofold) and from foreskin microvessles (four to eight fold). This was demonstrated by titration of endothelial cell-conditioned medium with t-PA, by reverse fibrin autography, and by immunoprecipitation of [35S]PAI-1 by anti-PAI-1 IgG. TNF also induced a marked increase of PAI-1 messenger RNA (mRNA) in the cells. The stimulation of PAI activity by TNF was seen at 4 U/mL and reached a maximum at 500 U/mL. Human recombinant lymphotoxin and interleukin-1 (alpha and beta) also stimulated the production of PAI activity, while interleukin-6 was ineffective. Separate additions of TNF or interleukin-1 (IL-1) at optimal concentrations (500 U/mL and 5 U/mL, respectively) resulted in a comparable stimulation of PAI production by endothelial cells. The simultaneous addition of both mediators resulted in an additive effect. The effect of TNF could not be prevented by the addition of polymyxin B or by anti-IL-1 antibodies. Therefore, it is unlikely that TNF acts through the induction of IL-1 secretion by endothelial cells. Two hours after a bolus injection of 250,000 U/kg TNF into rats, a fivefold increase in circulating PAI levels was found. In the next ten hours, the levels returned to normal. Blood platelets do not significantly contribute to the increase in circulating PAI, because the number of platelets did not change after TNF injection and the amount of PAI in blood platelets is not sufficient for several hours during an increase in PAI activity. The acute phase reactants, fibrinogen and alpha 2-antiplasmin in rat plasma, were altered little if any two to 24 hours after injection of 250,000 U/kg TNF. In vitro, TNF did not change PAI production by human and rat hepatocytes in primary monolayer culture. Therefore, it is most likely that vascular endothelial cells contribute to the increased amount of circulating PAI induced by TNF in vivo. This increase in PAI activity might decrease fibrinolysis.
Platelet glycoprotein IIb/IIIa complex in cultured cells. Localization in focal adhesion sites in spreading HEL cells
Authors: Ylanne J , Hormia M , Jarvinen M , Vartio T , Virtanen I 
Published: October 2019

Abstract
A panel of mouse monoclonal antibodies (MoAbs) was raised that react with platelet glycoproteins (GP) IIb or IIIa. On immunofluorescence, the MoAbs reacted with 30% to 40% of the human erythroleukemia (HEL) cells. When the HEL cells were induced to spread on fibronectin in the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA), the MoAbs reacted with the focal adhesion sites. Only some of the GPIIIa MoAbs reacted with cells other than platelets, megakaryocytes, or HEL cells, and these showed focal adhesion sites in cultured human endothelial cells, fibroblasts, and epithelial cells from normal kidney tubules. They did not react, however, with transformed fibroblasts, fibrosarcoma cells, cultured cells from hypernephromas, or cultured human amnion epithelial cells. The results suggest that the platelet-type GPIIb/IIIa complex is only expressed in cells showing an ability to define megakaryoblastic differentiation. Localization of the GPIIb/IIIa complex at the induced focal adhesion sites in HEL cells and localization of the GPIIIa-like molecules in other cells suggest their direct role in the adhesion process and in the actomyocin organization of adherent cells.
Allogeneic bone marrow transplantation for acute nonlymphocytic leukemia in first remission
Authors: McGlave PB , Haake RJ , Bostrom BC , Brunning R , Hurd DD , Kim TH , Nesbit ME , Vercellotti GM , Weisdorf D , Woods WG 
Published: October 2019

Abstract
Seventy-three patients with acute nonlymphocytic leukemia in first complete remission (CR) have received allogeneic bone marrow transplantation (BMT) with non-T-lymphocyte-depleted marrow obtained from matched sibling donors. The first 36 patients received a preparative regimen consisting of cyclophosphamide, 60 mg/kg/d (days -6 and -5), and 750 cGy single-dose total-body irradiation (TBI) (day -1). Subsequently, 37 patients received cyclophosphamide 60 mg/kg/d (days -6 and -5), and 165 cGy fractionated TBI administered twice daily for a total dose of 1,320 cGy (days -4, -3, -2, and -1). Survivors have been followed from 9 to 124 months (median, 40 months). The 61% (95% confidence interval [CI], 45% to 77%) projected disease-free survival (DFS) of 41 children less than 18 years old does not differ significantly from the 62% (95% CI, 49% to 73%) projected DFS of 32 adults at 84 months (P = .89). Similarly, the 15% (95% CI, 1% to 29%) projected relapse rate seen in children does not differ from the 9% (95% CI, 0% to 21%) seen in adults (P = .69). Multivariate Cox regression analysis of presenting features demonstrates that a presenting WBC count greater than 20,000/m3 is associated with decreased DFS (P = .01). When compared with other French-American- British (FAB) subtypes, presentation with FAB M4 or M5 morphology is significantly associated with relapse in multivariate analysis (P = .014). Other presenting features such as preparation with single-dose or fractionated TBI, interval from diagnosis to CR or CR to BMT, donor or recipient sex, and donor or recipient cytomegalovirus serology do not correlate independently with either DFS or relapse. When included in the stepwise multivariate analysis of presenting patient features, two posttransplant events, development of grades 2 to 4 acute graft-v- host disease (GVHD) (P less than .03) and development of interstitial pneumonitis (P less than .001), also correlate independently with poor DFS. Allogeneic BMT provides equivalent, prolonged DFS in both children and young adults when performed in first CR and should be considered the therapy of choice for all first CR patients under 45 years of age with a suitable donor. Continued efforts to prevent and treat acute GVHD and pneumonitis as well as efforts designed to prevent relapse in patients presenting with FAB M4 and M5 morphology should further improve outcome.
Butyrate induces selective transcriptional activation of a hypomethylated embryonic globin gene in adult erythroid cells
Authors: Burns LJ , Glauber JG , Ginder GD 
Published: October 2019

Abstract
An animal model of hemoglobin switching has been developed in which anemic adult chickens are treated with 5-azacytidine and sodium butyrate or alpha-aminobutyric acid, thereby resulting in activation of the embryonic rho-globin gene in adult erythroid cells. In vitro nuclear runoff transcription assays using erythroid nuclei from treated birds show that the mechanism of activation of the rho-globin gene is transcriptional whereas no transcriptional activation of the embryonic epsilon-globin gene occurs. The action of 5-azacytidine appears to be as an inhibitor of DNA methylation because other S-phase active cytotoxic drugs, when substituted for 5-azacytidine, do not cause demethylation of the embryonic globin genes, nor do they allow transcriptional activation to occur. Embryonic rho-globin gene activation in this model is not due to selection of primitive erythroid cells since a subpopulation of primitive erythroid cells is not evident either morphologically or when cells are probed for embryonic and adult globin RNA by in situ hybridization. These studies show that demethylation by 5-azacytidine is a prerequisite but not sufficient cis- regulatory event for a high level of transcriptional activation of the embryonic rho-globin gene in adult erythroid cells in vivo. The possible basis for the selective transcriptional activation by sodium butyrate in this system is discussed.
Cytogenetics of childhood T-cell leukemia
Authors: Raimondi SC , Behm FG , Roberson PK , Pui CH , Rivera GK , Murphy SB , Williams DL 
Published: October 2019

Abstract
The karyotypes of 57 cases of childhood T-cell acute lymphoblastic leukemia (ALL) were analyzed to establish the cytogenetic profile in this disease. Three questions were of particular interest. Do the chromosomal changes in T-cell ALL preferentially affect bands where genes encoding the T-cell receptor for antigen (TCR) have been mapped? Do alterations involving the TCR gene regions appear with any notable frequency in B-progenitor ALL? Do chromosomal abnormalities in this disease relate to stage of T-cell ontogeny? A relatively high proportion of cases (65%) had a pseudodiploid karyotype at presentation, the majority (58%) characterized by a translocation. The overall frequency of translocations was 44%, comparable to that among all banded cases of ALL seen in our laboratory. Hypodiploidy and hyperdiploidy were exceedingly rare (only four of 57 cases); 16 cases (28%) had apparently normal karyotypes. In half the cases with a translocation (14 of 24), the breakpoints were in regions to which the alpha and beta chain TCR genes have been mapped. Chromosomal breakpoints that were consistently observed in the vicinity of TCR gene loci were 7q32-q36 (TCR beta chain; n = 8), 14q11-q13 (TCR alpha chain; n = 6); other frequent breakpoints were 9p13-pter (n = 8) and 6q15-qter (n = 9). Chromosomal alterations occurred near TCR gene loci significantly more often in T-cell cases than in a comparison group of 335 patients with B-cell precursor ALL (26% v 1.5%, P = .0001). Stage I thymocyte development (CD7+, CD2+, CD5+, CD1-, CD3-, CD4-, CD8-) was noted in 23 cases, stage II (CD7+, CD2+, CD5+, CD1+, CD3-, CD4 +/-, CD8 +/-) in 25 cases, and stage III (CD9+, CD2+, CD1-, CD5+, CD3+, and either CD4+ or CD8+) in nine cases. The only statistically significant associations between cytogenetic findings and T-cell ontogeny were a higher frequency of normal karyotypes in cases with stage I thymocytes, and of pseudodiploidy in stage II cases. There was no apparent relationship between particular translocations and level of thymocyte maturation. Our findings indicate that most children with T-cell ALL have pseudodiploid karyotypes, although a surprisingly high percentage lack demonstrable abnormal clones. Specific chromosomal changes do not appear to be related to discrete stages of T-cell ontogeny as defined in this study, but they occur preferentially in bands containing TCR genes.
B protein of factor XIII: differentiation between free B and complexed B
Authors: Yorifuji H , Anderson K , Lynch GW , Van de Water L , McDonagh J 
Published: October 2019

Abstract
Plasma factor XIII is a complex of A and B proteins noncovalently linked in a tetramer, A2B2, Enzyme-linked immunosorbent assays (ELISA) were developed to measure the separate factor XIII proteins and the complex. All of the A protein in plasma is in the zymogen complex. The B assay measures the total amount of B protein in plasma (both free B and complexed B). This was confirmed by nondenaturing gel electrophoresis and immunoblotting, which showed two bands for B in plasma with this antibody. Two assays were developed to measure A2B2 complex specifically. One assay used a monoclonal antibody to B to bind antigen and measured B protein in the zymogen complex only and hence the concentration of the complex. The specificity of this antibody was also shown by immunoblotting. In the second assay, the capture antibody was to B and the tag antibody was to A. These two assays gave identical results for the concentration of A2B2 (0.07 mumol/L, 21.6 micrograms/mL in normal plasma). Thus, for the first time, differentiation and quantitation of free B and complexed B in plasma was possible. The assays were used to measure factor XIII proteins in plasma from normal controls, homozygous-deficient factor XIII patients, and their heterozygous relatives. The normal concentration of A in plasma is 0.13 to 0.16 mumol/L (approximately 11 micrograms/mL), all of which is in A2B2. The total B concentration is 0.26 to 0.28 mumol/L (approximately 21 micrograms/mL), half of which is complexed. The free B concentration is 0.13 mumol/L (approximately 10 micrograms/mL). Homozygous-deficient patients have essentially no A protein, but their free B concentration is 0.11 mumol/L. Heterozygotes have decreased A2B2, but their free B is 0.11 mumol/L. These results indicate that the concentration of free B is remarkably constant and does not depend on the concentration of A2 or A2B2.
Immunophenotypic and cytogenetic analysis of Molt-3 and Molt-4: human T- lymphoid cell lines with rearrangement of chromosome 7
Authors: Greenberg JM , Gonzalez-Sarmiento R , Arthur DC , Wilkowski CW , Streifel BJ , Kersey JH 
Published: October 2019

Abstract
Molt-3 and Molt-4 are T-cell lines originally derived in 1971 from a patient with T-cell acute lymphoblastic leukemia. An unusual T-cell antigen receptor gamma-chain gene (T-gamma) rearrangement detected by Southern blot analysis of Molt-4 prompted an in-depth study of the immunophenotype and karyotype of both cell lines. Molt-3 and Molt-4 had immunophenotypic characteristics of thymocytes with expression of CD1 and CD5. Both cell lines had a hypertetraploid karyotype with two rearranged no. 7 chromosomes: 2der(7)t(7;7)(p15;q11). The presence of a break in chromosome band 7p15 suggested the involvement of T gamma. We cloned the rearranged BamHI fragments spanning the known T-gamma constant and joining regions. Comparison with germline clones of T gamma did not suggest any of the clones included a breakpoint region. Thus the 7p15 chromosomal abnormality in Molt-3 and Molt-4 is not associated with the currently described joining and constant regions of T gamma.
Molecular analysis of Japanese delta beta-thalassemia
Authors: Shiokawa S , Yamada H , Takihara Y , Matsunaga E , Ohba Y , Yamamoto K , Fukumaki Y 
Published: October 2019

Abstract
A DNA fragment containing the deletion junction region from a Japanese individual with homozygous delta beta-thalassemia has been cloned. A clone containing the normal DNA surrounding the 3′ breakpoint of this deletion and a clone carrying the G gamma- and A gamma-globin genes of this patient were also isolated. Sequences of the deletion junction and both gamma-globin genes were determined. A comparison of these sequences with previously determined sequences of the normal counterparts revealed that the 5′ breakpoint is located between 2,134 and 2,137 base pairs (bp) 3′ to the polyA site of the A gamma-globin gene, the 5′ breakpoint is located just downstream of the 3′ border of the fetal gamma-globin duplication unit, and no molecular defects are evident within the gamma-globin gene region. A comparison between the sequences of the normal DNA surrounding the 3′ breakpoint and the normal DNA surrounding the 5′ breakpoint shows that deletion is the result of a nonhomologous recombination event. There are A+T-rich stretches near the 5′ and 3′ breakpoints in the normal DNA, and a portion of an Aly repeat is located in the region 3′ to the 3′ breakpoint. Southern blot analysis using probes 3′ to the beta-globin gene showed that the deletion extends in the 3′ direction further than any other deletions associated with delta beta-thalassemia and hereditary persistence of fetal hemoglobin (HPFH) heretofore reported. These results are discussed in terms of the mechanism generating large deletions in mammalian cells and three models for the regulation of gamma-globin and beta-globin gene expression in humans.
Identification of risk groups for development of central nervous system leukemia in adults with acute lymphocytic leukemia
Authors: Kantarjian HM , Walters RS , Smith TL , Keating MJ , Barlogie B , McCredie KB , Freireich EJ 
Published: October 2019

Abstract
The risk of development of CNS leukemia was investigated in 153 adults with acute lymphocytic leukemia (ALL) who received systemic combination chemotherapy without CNS prophylaxis. Overall, 31 patients (20%) developed CNS leukemia after a median of 6 months of therapy; the estimated 1-year incidence of CNS leukemia was 21% (SE, 3.9%). Characteristics significantly associated with CNS involvement included the presence of elevated hemoglobin creatinine, alkaline phosphatase, fibrinogen, and lactic dehydrogenase levels; B-cell leukemia; and high leukemic cell proliferative activity. Multivariate analysis identified lactic dehydrogenase levels of greater than or equal to 600 U/L and greater than or equal to 14% of cells in the S + G2M compartment to have independent additive poor prognostic significance. Patients were categorized into different risk groups for CNS leukemia with 1-year incidences ranging from 4% to 55%. While related to a high occurrence of CNS leukemia at diagnosis (33%) and subsequently (100%), the low incidence of B-cell disease excluded it from the multivariate analysis. The use of systemic chemotherapy containing multiple agents with good CNS penetration and in high doses (VAD regimen) in 90 patients was associated with a trend for lower CNS leukemia at 1 year (15% v 31%), especially in the low-risk category. We propose to develop future therapies for adults with ALL that include risk-oriented CNS prophylactic approaches.
Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2
Authors: Waldmann TA , Goldman CK , Bongiovanni KF , Sharrow SO , Davey MP , Cease KB , Greenberg SJ , Longo DL 
Published: October 2019

Abstract
Human T-cell lymphotropic virus I (HTLV-I)-induced adult T-cell leukemia (ATL) cells constitutively express interleukin-2 (IL-2) receptors identified by the anti-Tac monoclonal antibody (MoAb), whereas normal resting cells do not. This observation provided the scientific basis for a trial of intravenous anti-Tac in the treatment of nine patients with ATL. The patients did not suffer untoward reactions and did not have a reduction in the normal formed elements of the blood, and only one of the nine produced antibodies to the anti-Tac MoAb. Three patients had transient mixed, partial, or complete remissions lasting from 1 to more than 8 months after anti-Tac therapy, as assessed by routine hematologic tests, immunofluorescence analysis of circulating cells, and molecular genetic analysis of HTLV-I provirus integration and of the T-cell receptor gene rearrangement. The precise mechanism of the antitumor effects is unclear; however, the use of a MoAb that prevents the interaction of IL-2 with its receptor on ATL cells provides a rational approach for the treatment of this malignancy.
Detection of occult follicular lymphoma by specific DNA amplification
Authors: Stetlet-Stevenson M , Raffeld M , Cohen P , Cossman J 
Published: October 2019

Abstract
To detect occult lymphoma, the polymerase chain reaction (PCR) technique was used to amplify joined bcl-2/JH DNA sequences at the juncture of the t(14:18) translocation in follicular lymphoma. Using the heat-stable DNA polymerase Taq and automated cycling of the reaction, we were able to detect as few as one to two copies of bcl- 2/JH. Under these conditions, PCR proved to be at least 10,000-fold more sensitive than either conventional flow cytometry or Southern blot restriction analysis. In addition, genomic DNA sequences of four lymphomas confirmed that the size of the amplified segment serves as a tumor marker. Direct application of PCR to patient staging revealed occult malignant lymphoma in tissue otherwise considered uninvolved by standard criteria. We conclude that the striking enhancement in diagnostic sensitivity attained by DNA amplification can serve as a valuable adjunct to the staging and clinical monitoring of follicular lymphoma.
Hereditary X-linked thrombocytopenia maps to the same chromosomal region as the Wiskott-Aldrich syndrome
Authors: Donner M , Schwartz M , Carlsson KU , Holmberg L 
Published: October 2019

Abstract
Hereditary X-linked thrombocytopenia occurs either as isolated thrombocytopenia or as a part of the Wiskott-Aldrich syndrome (WAS). We studied X-linked thrombocytopenia in a family with eight affected male members, none of whom exhibited the increased susceptibility to infection that occurs in WAS. We found a significant linkage between thrombocytopenia and DXS 146, a marker on the proximal part of the short arm of the X-chromosome. WAS has previously been mapped to the same chromosomal region. The present findings indicate that X-linked thrombocytopenia and WAS are closely related and may even be caused by different mutations of the same gene. This view is supported by our findings of atopic symptoms and minor deviations in immunologic variables among some of the affected subjects.
The effect of cyclosporine A on infection of susceptible cells by human immunodeficiency virus type 1
Authors: Wainberg MA , Dascal A , Blain N , Fitz-Gibbon L , Boulerice F , Numazaki K , Tremblay M 
Published: October 2019

Abstract
The effect of cyclosporine A (CyA) on the ability of the human immunodeficiency virus type 1 (HIV-1) to infect the H-9 T-cell leukemic line, as well as interleukin-2 (IL-2)-grown human peripheral blood- derived lymphocytes, has been studied. Pretreatment of H-9 cells and human lymphocytes with CyA over 24 hours completely prevented viral infection over a 21-day period, whereas the addition of drug at two hours postinfection with HIV-1 had a significant inhibitory effect on viral replication and expression of the virus-specific antigens p17 and p24. However, if CyA was added at later times to these lymphocytic cells, this inhibitory effect was lost. Indeed, the removal of CyA from cultures that had been treated from two hours after infection led to the rapid production of progeny virus. HIV-1 was able to infect peripheral blood lymphocytes obtained from each of four kidney allograft recipients on long-term CyA antirejection therapy, as long as drug was not included in the culture medium. In addition, we asked what effect pretreatment with CyA of cells of the U-937 monocytic line and primary cultures of human monocytes/macrophages might have on infection by HIV-1. CyA had no demonstrable effect on the ability of HIV-1 to infect cells of either type.