bluuebunny/crossref_metadata_2025_split huggingface dataset:
Granulocyte-macrophage colony-stimulating factor synergizes with interleukin-6 in supporting the proliferation of human myeloma cells [see comments]
Authors: Zhang XG , Bataille R , Jourdan M , Saeland S , Banchereau J , Mannoni P , Klein B 
Published: October 2019

Abstract
The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the growth of multiple myeloma (MM) was investigated in 21 patients with MM. In 17 patients with proliferating myeloma cells in vivo, recombinant GM-CSF significantly increased the endogenous-IL-6-mediated spontaneous myeloma cell proliferation occurring in 5-day cultures of tumor cells in vitro (P less than .01). Furthermore, GM-CSF was detected in 5-day culture supernatants of myeloma bone marrow cells. This endogenous GM-CSF was produced by the myeloma bone marrow microenvironment but not by myeloma cells and contributed to the spontaneous myeloma-cell proliferation observed in 5-day cultures. In fact, this proliferation was partially blocked (67%) by anti-GM-CSF monoclonal antibodies. The stimulatory effect of rGM-CSF was mediated through IL-6 because it was abrogated by anti-IL-6 monoclonal antibodies. rGM-CSF did not reproducibly increase the endogenous IL-6 production in short-term cultures of bone marrow cells of MM patients. Using an IL-6-dependent myeloma cell line (XG-1 cell line), rGM-CSF was shown to act directly on myeloma cells stimulating by twofold their IL- 6 responsiveness. rGM-CSF did not induce any IL-6 production in XG-1 cells, nor was it able to sustain their growth alone. Although no detectable GM-CSF levels were found in the peripheral or bone marrow blood of MM patients, it is possible that GM-CSF, produced locally by the tumoral environment, enhances the IL-6 responsiveness of myeloma cells in vivo in a way similar to that reported here in vitro.
Impaired transendothelial migration by neonatal neutrophils: abnormalities of Mac-1 (CD11b/CD18)-dependent adherence reactions
Authors: Anderson DC , Rothlein R , Marlin SD , Krater SS , Smith CW 
Published: October 2019

Abstract
In order to evaluate the functions of lymphocyte function antigen-1 (LFA-1) (CD11a/CD18) and Mac-1 (CD11b/CD18) on neonatal neutrophils, we examined neutrophil adhesion to and migration through human umbilical vein endothelial cell (HUVEC) monolayers in vitro. Transendothelial migration of adult neutrophils was greatly enhanced by preincubation of HUVEC with interleukin-1 (IL-1). This migration was significantly inhibited by monoclonal antibodies (MoAbs) against LFA-1 (CD11a) and Mac-1 (CD11b) subunits. Migration of neonatal neutrophils was markedly diminished compared to adult neutrophils, and MoAbs against LFA-1 further reduced migration. In contrast, anti-Mac-1 MoAb was not inhibitory. Adhesion of adult neutrophils was significantly enhanced by prestimulation of HUVEC with IL-1, and was significantly inhibited by MoAbs against LFA-1. Adhesion of neonatal neutrophils was near adult levels and comparably inhibited by anti-LFA-1 MoAb. In addition, adhesion of neonatal and adult neutrophils to purified ICAM-1 in artificial planar membranes was comparable and almost completely inhibited by anti-LFA-1 MoAb. Chemotactic stimulation induced Mac-1- dependent adhesion of adult neutrophils to endothelial cells, purified intercellular adherence molecule-1 (ICAM-1) and protein-coated glass. In marked contrast, adhesion of neonatal neutrophils to these substrates was not significantly increased by chemotactic stimulation. These findings indicate that diminished transendothelial migration by neonatal neutrophils is related to abnormal interactions of Mac-1 with ICAM-1 and possibly other endothelial ligands. These functional deficits may contribute to impaired inflammation and infectious susceptibility in human neonates.
Human immunodeficiency virus infection of human bone marrow stromal fibroblasts
Authors: Scadden DT , Zeira M , Woon A , Wang Z , Schieve L , Ikeuchi K , Lim B , Groopman JE 
Published: October 2019

Abstract
The human immunodeficiency virus (HIV) preferentially infects CD4 positive T cells and monocytes. Other human cell types have been reported to be infectable with HIV, including cells of mesenchymal origin. In this report, we show that both primary human bone marrow stromal fibroblasts and an immortalized human stromal fibroblast line are susceptible to HIV infection. These cells are capable of passing HIV to cells of lymphoid or myeloid lineage, and may thereby act as a reservoir of virus. This in vitro system may be a useful model for assessing the pathophysiology of hematopoietic dysfunction in AIDS patients.
Glycoprotein Ib, von Willebrand factor, and glycoprotein IIb:IIIa are all involved in platelet adhesion to fibrin in flowing whole blood
Authors: Hantgan RR , Hindriks G , Taylor RG , Sixma JJ , de Groot PG 
Published: October 2019

Abstract
We have investigated the molecular basis of thrombus formation by measuring the extent of platelet deposition from flowing whole blood onto fibrin-coated glass coverslips under well-defined shear conditions in a rectangular perfusion chamber. Platelets readily and specifically adhered to fibrin-coated coverslips in 5 minute perfusion experiments done at either low (300 s-1) or high (1,300 s-1) wall shear rates. Scanning electron microscopic examination of fibrin-coated coverslips after perfusions showed surface coverage by a monolayer of adherent, partly spread platelets. Platelet adhesion to fibrin was effectively inhibited by a monoclonal antibody (MoAb) specific for glycoprotein (GP) IIb:IIIa. The dose-response curve for inhibition of adhesion by anti-GPIIb:IIIa at both shear rates paralleled that for inhibition of platelet aggregation. Platelet aggregation and adhesion to fibrin were also blocked by low concentrations of prostacyclin. In contrast, anti- GPIb reduced adhesion by 40% at 300 s-1 and by 70% at 1,300 s-1. A similar pattern of shear rate-dependent, incomplete inhibition resulted with a MoAb specific for the GPIb-recognition region of von Willebrand factor (vWF). Platelets from an individual with severe von Willebrand's disease, whose plasma and platelets contained essentially no vWF, exhibited defective adhesion to fibrin, especially at the higher shear rate. Addition of purified vWF restored adhesion to normal values. These results are consistent with a two-site model for platelet adhesion to fibrin, in which the GPIIb:IIIa complex is the primary receptor, with GPIb:vWF providing a secondary adhesion pathway that is especially important at high wall shear rates.
Properties of factor VIIa/tissue factor complexes in an umbilical vein model
Authors: Almus FE , Rao LV , Fleck RA , Rapaport SI 
Published: October 2019

Abstract
An umbilical vein model was designed in which washed vein segments are filled with a reaction mixture containing factor VIIa, Ca(+)+, and a substrate, either 3H-factor IX or 3H-factor X. The vein wall provides the tissue factor (TF) for factor VIIa/TF complexes that activate the substrates as measured by activation peptide release. The model was developed to study TF induced on venous endothelium in situ. However, unlike previous studies with TF expressed on cultured umbilical vein endothelial cells, factors IX and X were activated without first having to expose the vein wall to a perturbing stimulus. Histologic studies revealed that washing the vein and mixing the reaction mixture before subsampling had disrupted the endothelium. Immunostaining with anti-TF antibodies revealed no staining of endothelium but intense staining in extensions of Wharton's jelly penetrating fenestrations of the muscularis media of the vein. Thus, the model provided data on factor VIIa/TF formed, not on endothelium, but within the mucoid connective tissue of Wharton's jelly. It is known that factor VIIa/TF formed with TF in suspension or with TF expressed on the surface of cultured cells activates factor X more rapidly than factor IX. In contrast, in the umbilical vein model, when each substrate was present in an 88 nmol/L concentration, factors IX and X were activated at equivalent rates (mean activation rate for factor IX, 18.8 +/- 3.6 nmol/L/h; for factor X, 17.8 +/- 2.9 nmol/L/h; n = 9 paired vein segments). These data strengthen the evidence that factor VIIa/TF activation of factor IX represents a key initial reaction of coagulation in tissues. These results also show that data obtained with factor VIIa/TF complexes formed on the surface of cultured cells need not hold for factor VIIa/TF complexes formed in extracellular matrix.
A clinical, hematologic, and immunologic analysis of 21 HTLV-II- infected intravenous drug users [published erratum appears in Blood 1990 Nov 1;76(9):1901]
Authors: Rosenblatt JD , Plaeger-Marshall S , Giorgi JV , Swanson P , Chen IS , Chin E , Wang HJ , Canavaggio M , Hausner MA , Black AC 
Published: October 2019

Abstract
Infection with human T-cell leukemia virus type II (HTLV-II) has been associated with rare chronic T-cell malignancies and has recently been demonstrated in a significant proportion of American intravenous drug abusers (IVDA). Identification of an HTLV-II-infected cohort of IVDA has allowed analysis of the HTLV-II carrier state. We analyzed clinical, hematologic, and immunologic parameters in 21 HTLV-II- infected IVDA, two HTLV-I-infected IVDA, and 20 uninfected control IVDA identified by serologic screening and by analysis of peripheral blood mononuclear cell (PBMC) DNA by polymerase chain reaction (PCR). An elevated absolute lymphocyte count was observed in 4 of 21 HTLV-II- infected IVDA, 1 of 2 HTLV-I-infected IVDA, and 1 of 20 control IVDA. CD8+ T-cell elevation was observed in three of four HTLV-II IVDA with lymphocytosis and one of two HTLV-I-infected IVDA. Activation of CD8+ T cells in HTLV-II-infected IVDA was suggested by an overall increase in CD8+/HLA-DR+ lymphocytes. Cell fractionation and analysis by PCR of HTLV-II-infected carrier blood showed high levels of HTLV-II provirus in unfractionated PBMC and purified T cells and little or no detectable HTLV-II DNA in B cells or monocytes, indicating that T cells were the most likely target of infection in vivo. The frequency of HTLV-II- infected cells was estimated at approximately 1 in 500 cells or less using dilution analysis by PCR of PBMC DNA. Most HTLV-II-infected IVDA are asymptomatic and have no overt hematologic or immunologic abnormalities, although some manifest benign lymphocytosis.
Selective depletion of CD8+ T lymphocytes for prevention of graft- versus-host disease after allogeneic bone marrow transplantation
Authors: Champlin R , Ho W , Gajewski J , Feig S , Burnison M , Holley G , Greenberg P , Lee K , Schmid I , Giorgi J 
Published: October 2019

Abstract
The effects of selectively depleting CD8+ cells from donor bone marrow were assessed in 36 patients receiving transplantation from an HLA- identical sibling as treatment for leukemia. Donor bone marrow underwent ex vivo treatment using anti-Leu-2 monoclonal antibody and complement. Patients received cyclosporine post-transplant for 6 months. Thirty-three patients had initial engraftment. Three failed to have hematologic recovery, and one patient with initial engraftment had late graft failure. The actuarial incidence of grade greater than or equal to 2 acute graft-versus-host disease was 28% +/- 18% and was usually confined to the skin. Of 33 patients with engraftment, 32 were complete chimeras and one had mixed chimerism. The tempo of hematologic and immunologic recovery was comparable with that reported with transplantation of unmodified bone marrow, although CD4+ and CD8+ T cells recovered at comparable rates. The actuarial rate of leukemia relapse was 11% +/- 10%, occurring in three patients with acute leukemia but in none of 13 patients transplanted for chronic myelogenous leukemia. Actuarial survival was 57% +/- 17% at 2 years. These data indicate that after transplantation of marrow depleted of CD8+ cells, engraftment with prompt hematologic and immunologic recovery generally occurs, with a relatively low rate of acute graft- versus-host disease. Graft failure remains a problem despite retention of CD4+ cells within the donor marrow. The lack of leukemia relapse in patients with chronic myelogenous leukemia suggests retention of a graft-versus-leukemia effect, at least for this malignancy.
Comparison of high-dose therapy and autologous bone marrow transplantation for T-cell and B-cell non-Hodgkin's lymphomas
Authors: Vose JM , Peterson C , Bierman PJ , Weisenburger DD , Linder J , Harrington D , Vaughan WP , Kessinger A , Armitage JO 
Published: October 2019

Abstract
Advanced T-cell non-Hodgkin's lymphoma in adults has been found to have a poor outlook with conventional chemotherapy. To see if this extends to patients treated with high dose therapy and autologous hematopoietic stem cell transplantation, we reviewed the results with this treatment approach at our institution. From October, 1983, to May, 1988, 41 patients who underwent high-dose therapy and autologous hematopoietic stem cell transplant for recurrent non-Hodgkin's lymphoma were re- biopsied before transplantation to determine their immunophenotype. Seventeen of these patients were found to have a T-cell lymphoma, and 24 had a B-cell lymphoma. All patients were included in the intermediate or high grade non-Hodgkin's lymphoma categories, and none were histologically transformed from a low grade lymphoma. Analysis of the response to autologous transplantation in these two patient populations revealed a slightly better complete response rate for patients with T-cell lymphoma (ie, 59% versus 42%, P = NS). The actuarial 2-year survival was 35% in the T-cell group compared with 30% in the B-cell group (P = NS). The 2-year disease-free survival was 28% for the T-cell and 17% for the B-cell patients. Our results with autologous transplantation for salvage therapy revealed equivalent long- term survival and disease-free survival in both relapsed T- and B-cell non-Hodgkin's lymphoma.
Effects of recombinant human granulocyte colony-stimulating factor on the hematologic recovery and survival of irradiated mice
Authors: Tanikawa S , Nose M , Aoki Y , Tsuneoka K , Shikita M , Nara N 
Published: October 2019

Abstract
We studied the effects of intraperitoneal injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF) according to various administration schedules on the recovery of spleen colony- forming units (CFU-S) and peripheral blood counts, and on the survival of irradiated mice. The sooner and more frequently the mice were injected with rhG-CSF after irradiation, the more enhanced the recovery of CFU-S in bone marrow was obtained on day 7. Twice-daily injections of rhG-CSF from day 0 to day 2 significantly enhanced the recovery of platelets and hematocrit, but two injections of rhG-CSF on only day 0 did not. Twice-daily injections of rhG-CSF from day 0 to day 6 enhanced the recovery of platelets more effectively than twice-daily injections of rhG-CSF from day 1 to day 7, and increased the survival of irradiated mice more effectively than any other examined administration schedules. Twice-daily injections of rhG-CSF from day 0 to day 6 were significantly effective in enhancing the survival of mice irradiated with 8.5-, 9.0-, and 9.5-Gy x-rays, although not effective after irradiation of 10.5-Gy x-rays.
High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy
Authors: Brown RA , Herzig RH , Wolff SN , Frei-Lahr D , Pineiro L , Bolwell BJ , Lowder JN , Harden EA , Hande KR , Herzig GP 
Published: October 2019

Abstract
Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens.
Family studies and prenatal diagnosis in severe von Willebrand disease by polymerase chain reaction amplification of a variable number tandem repeat region of the von Willebrand factor gene
Authors: Peake IR , Bowen D , Bignell P , Liddell MB , Sadler JE , Standen G , Bloom AL 
Published: October 2019

Abstract
We have previously demonstrated within intron 40 of the von Willebrand factor (vWF) gene a region of ATCT repeats that was shown to vary in length between two different DNA clones from unrelated individuals. The polymerase chain reaction (PCR) was used to examine the variability in length of this variable number tandem repeat (VNTR) in 53 normal individuals, using primers to DNA sequence flanking the repeat region. Overall, eight different length allelic bands were seen. These were individually sequenced and shown to contain from 6 to 14 ATCT repeats (a nine-repeat band was not seen). Seventy-five percent of individuals were shown to be heterozygous for this vWF.VNTR, and family studies showed Mendelian inheritance with allelic frequencies from 1% (vWF.VNTR [8] and vWF.VNTR [14]) to 39% (vWF.VNTR [7]). In the family of a patient with type III severe von Willebrand disease (vWD), vWF.VNTR results mirrored the phenotypic data and results with previously reported intragenic vWF restriction fragment length polymorphisms (RFLP). The patient was shown to be a compound heterozygote. In a family with a child with severe type III vWD, prenatal diagnosis by vWF.VNTR analysis on DNA obtained by chorionic villus sampling at 10 weeks gestation during a subsequent pregnancy indicated a severely affected fetus. This diagnosis was confirmed by fetal blood sampling at 18 weeks.
Origin of mutations in two families with X-linked chronic granulomatous disease
Authors: Francke U , Ochs HD , Darras BT , Swaroop A 
Published: October 2019

Abstract
The most common X-linked recessive form of chronic granulomatous disease (X-CGD) is characterized by the absence of cytochrome b558 in neutrophils. In a rare variant form of X-CGD, cytochrome b558 is present but not functional. The gene (locus symbol CYBB) was localized to band Xp21 by studies of patients with small chromosome deletions. The gene was cloned based on its location and found to encode the 91-Kd subunit of the cytochrome b558 complex. Most female carriers for X-CGD can be identified by their X-inactivation mosaicism; on average 50% of their neutrophils express the mutant phenotype and fail to reduce nitroblue tetrazolium (NBT). In 2 of 4 families studied, the maternal grandmothers had normal NBT tests, suggesting either nonrandom X- inactivation or new mutations. Restriction fragment length polymorphism analysis using closely linked flanking markers or the NsiI polymorphism detected by the CYBB probe itself, allowed us to identify the X chromosome carrying the mutation as derived from a healthy NBT-positive maternal grandfather. The mothers of the affected boys must have received a paternal X chromosome carrying a new mutation, consistent with the maternal grandmothers' normal NBT tests. In all of eight potential carriers studied, the results of the NBT and DNA marker testing were in complete agreement. Prenatal diagnosis by DNA testing can be performed in early gestation obviating the need for fetal blood sampling.
Inflammation and cancer: role of phagocyte-generated oxidants in carcinogenesis
Authors: Weitzman SA , Gordon LI 
Published: October 2019

Abstract
We have reviewed some of the data that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. While it is clear that these substances induce phenotypic changes characteristic of those produced by known carcinogens, the precise mechanisms by which these effects are produced require much further study. In vitro, it would appear that phagocyte-generated oxidants could be complete carcinogens, ie, could cause both tumor initiation and promotion. In vivo, however, these substances appear usually to function as tumor promoters or cocarcinogens perhaps because of high levels of endogenous antioxidant defenses. This suggests that there may be even more reason to be optimistic about the potential for positive results in cancer chemoprevention trials in humans, and provides further rationale for the continuing interest in the use of antioxidants and anti- inflammatory drugs in current and future trials. For example, the Chemoprevention Branch of the National Cancer Institute is currently sponsoring seven extramural human efficacy intervention trials testing whether the antioxidant beta carotene can prevent cancer.