bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro infection of human macrophages with human T-cell leukemia virus type 1
Authors: de Revel T , Mabondzo A , Gras G , Delord B , Roques P , Boussin F , Neveux Y , Bahuau M , Fleury HJ , Dormont D 
Published: October 2019

Abstract
The tropism of the human T-cell leukemia virus type 1 (HTLV-1) for the cells of monocyte-macrophage lineage was evaluated by the coculture of blood monocyte-derived macrophages, with irradiated cells of HTLV-1 producing cell lines MT2 or C91/PL. The susceptibility to HTLV-1 was assessed by the detection of viral DNA using the polymerase chain reaction method. HTLV-1 gene expression in the cells was detected using in situ hybridization and by immunofluorescent staining of viral antigen. The presence of type C virus-like particles detected by electron microscopy and the ability to infect normal cord blood lymphocytes demonstrated that the infected macrophages produced infectious virus. These results indicate that human macrophages are susceptible in vitro to productive HTLV-1 infection, and thus might be involved in the pathogenesis of HTLV-1-related diseases.
Autologous bone marrow transplantation after a long first remission for children with recurrent acute lymphoblastic leukemia
Authors: Billett AL , Kornmehl E , Tarbell NJ , Weinstein HJ , Gelber RD , Ritz J , Sallan SE 
Published: October 2019

Abstract
Fifty-one children with acute lymphoblastic leukemia (ALL) in second or subsequent remission after a first remission of at least 24 months underwent purged, autologous bone marrow transplantation (ABMT). Bone marrow was harvested in remission and purged in vitro with monoclonal antibodies specific for leukemia-associated antigens. Ablative chemotherapy included cytarabine, teniposide, and cyclophosphamide followed by total body irradiation. Of the 51 patients treated between November 1980 and June 1991, 5 died of treatment-related complications, 18 relapsed, 1 died of a second tumor at 6.7 years, and 27 remained in continuous complete remission for a median of 39 months (range, 9+ to 124+). Event-free survival (EFS) (+/- SE) at 3 years after ABMT was 53% +/- 7%. Leukemia-free survival (LFS) was 58% +/- 8%. In multivariate analysis, the most significant predictors of EFS were duration of longest pre-ABMT remission and remission duration immediately before ABMT. For LFS, the most significant predictors were cell dose per kilogram of marrow reinfused and duration of longest pre-ABMT remission. We conclude that ABMT for this population is an effective therapy available to the majority of children with relapsed ALL.
Bone marrow stroma in humans: anti-nerve growth factor receptor antibodies selectively stain reticular cells in vivo and in vitro
Authors: Cattoretti G , Schiro R , Orazi A , Soligo D , Colombo MP 
Published: October 2019

Abstract
Two anti-nerve growth factor receptor (LNGFR or p75NGFR) antibodies, Me20.4 and Me8211, label stromal cells with dendritic features in fresh smears and in formalin-fixed, paraffin-embedded human bone marrow (BM). The LNGFR+ cells have an oval nucleus, a scanty cytoplasm with long dendrites that intermingle with the hematopoietic cells, line the abluminal side of sinus endothelial cells, and provide the scaffold for the hematopoietic marrow. At the electron microscopy level, the immunogold tag labels the body and the long branching dendrites of fibroblast-like cells with scanty cytoplasm containing mitochondria, endoplasmic reticulum, and dense bodies. The LNGFR+ cells are positive for alkaline phosphatase, reticulin, collagen III, vimentin, TE-7, and CD13 but negative for endothelial (vWF, CD34, Pal-E), neural (CD56, neurofilament) and leukocyte markers (CD45, CD68). The LNGFR+ stromal cells appear in the fetal BM before the hematopoietic activity begins, originate from the vessel adventitia, and radiate in the Bm cavity. Long-term BM culture (LTBMC) in vitro contain LNGFR+ stromal cells. We document the presence of RNA message for the low- (LNGFR) and the high- affinity NGF receptor (NTRK1) by using RT-PCR on fresh BM aspirate and on LTBMC. BM biopsies from patients with hematologic fibrogenic diseases and in cytokine-treated cancer patients are evaluated for LNGFR+ cells: the amount of stained cells is correlated with the traditional reticulin stain in cases of myelofibrosis, therapy-related myelodysplasia, leukemia, and detected an increase of stromal cells in cytokine-treated patients. The anti-LNGFR antibodies represent a specific membrane marker for the adventitial reticular cells (ARC) of the human marrow and allow precise evaluation and quantitation of this important BM microenvironment component in vivo and in vitro.
Infection with human T-lymphotropic viruses leads to constitutive expression of leukemia inhibitory factor and interleukin-6
Authors: Lal RB , Rudolph D , Buckner C , Pardi D , Hooper WC 
Published: October 2019

Abstract
Leukemia inhibitory factor (LIF), similar to interleukin-6 (IL-6), is a glycoprotein growth factor and differentiation regulator that has pleiotropic activity in several cellular systems. Recent reports of constitutive IL-6 production from spontaneously proliferating cells from human T-cell leukemia virus (HTLV)-infected individuals led us to examine the expression of IL-6 and LIF during HTLV infection. In vitro infection of peripheral blood lymphocytes with HTLV-I was associated with production of both soluble LIF and IL-6 in conjunction with the increasing HTLV antigen concentration. Northern blot analysis of T-cell lines generated from individuals infected with HTLV-I (MT-2, HuT-102, FS, EG, SP) and HTLV-II (Mo-T, H2A, H2E) demonstrated a marked increase in constitutive expression of LIF and IL-6 transcripts, as compared with uninfected cell lines (HuT-78, Jurkat). The constitutive expression of LIF and IL-6 was independent of presence of IL-2 in the culture medium, as both IL-2-independent (MT-2, HuT-102, SP, Mo-T) and IL-2-dependent (FS, EG, H2A, H2E) cell lines expressed LIF and IL-6 transcripts. Furthermore, LIF and IL-6 RNA expression in an HTLV-I- infected cell line (MT-2) was enhanced by phorbol ester stimulation via mechanisms that appear to be dependent on the posttranscriptional regulatory controls. These results show that both LIF and IL-6 are produced by HTLV-I- and HTLV-II-infected cells, which could potentially alter the transcriptional regulation of HTLV gene expression by inducing certain early response genes.
Myeloid but not lymphoid cells carry the 5q deletion: polymerase chain reaction analysis of loss of heterozygosity using mini-repeat sequences on highly purified cell fractions
Authors: Kroef MJ , Fibbe WE , Mout R , Jansen RP , Haak HL , Wessels JW , Van Kamp H , Willemze R , Landegent JE 
Published: October 2019

Abstract
Interstitial deletions of the long arm of chromosome 5 are among the most characteristic abnormalities observed in myeloid disorders. To assess the lineage involvement of peripheral blood cells from patients with a 5q--anomaly, purified neutrophils, monocytes, T lymphocytes, and B lymphocytes were analyzed for loss of heterozygosity using six different highly polymorphic mininucleotide and dinucleotide (CA) repeat sequences from the 5q31 to 5q33 region. Ten patients were screened by polymerase chain reaction (PCR) amplification and proved to be informative for at least one marker. Six patients showed a complete or partial disappearance of an allele in myeloid cells, whereas cells of lymphoid lineages exhibited full heterozygosity. The other patients displayed no allelic loss, indicating that the informative markers were located outside the deleted chromosomal segments. In addition, three female patients who were also polymorphic for the BstXI site in the PGK- 1 gene were analyzed for the methylation status of this gene. Clonality of hematopoiesis, as determined by non-random X-chromosome inactivation, followed the same cell pattern as the 5q-specific allelic losses. In conclusion, using tumor-specific and clonal markers, we have demonstrated that the 5q- anomaly is restricted to cells of myeloid origin, leaving lymphoid cells unaffected.
Experiences of the first 493 unrelated marrow donors in the National Marrow Donor Program
Authors: Stroncek DF , Holland PV , Bartch G , Bixby T , Simmons RG , Antin JH , Anderson KC , Ash RC , Bolwell BJ , Hansen JA 
Published: October 2019

Abstract
More than 410,000 people participated in the National Marrow Donor Program (NMDP) as of October 1, 1991, and more than 850 volunteers had donated marrow. While the incidence of serious morbidity as a result of bone marrow donation is rare, the incidence of lesser complications and the long-term consequences of marrow donation are not known. To determine the incidence of donor complications and measure the recovery time of volunteer, unrelated marrow donors, we analyzed the results of surveys of the first 493 persons who donated marrow through the NMDP. The marrows were collected at 42 centers. The median age of the donors was 37.9 years (range 19.1 to 55.6 years). The median volume of marrow collected was 1,050 mL (range 180 to 2,983 mL). Autologous red blood cells were transfused to 89.8% (439) of donors but only 0.6% (3) of donors received allogeneic blood. Acute complications related to the collection procedure occurred in 5.9% of donors; but a serious complication, apnea during anesthesia, occurred in only one donor. When donors were questioned approximately 2 days following discharge from their hospitalization, most donors described symptoms related to the collection; 74.8% experienced tiredness, 67.8% experienced pain at the marrow collection site, and 51.6% of the donors experienced low back pain. Donors were surveyed repeatedly until they felt that they had recovered completely. Mean recovery time was 15.8 days; however, 42 (10%) donors felt that it took them > or = 30 days to recover fully. The duration of the marrow collection procedure and duration of anesthesia both positively correlated with donor pain and/or fatigue following the collection; but the duration of the collection procedure had the highest correlation with post-collection pain and fatigue. The volume of marrow collected per unit of donor weight was more weakly correlated with donor pain and/or fatigue than the anesthesia and collection times. When multivariate analysis was used to analyze the correlation between donor recovery time and these variables, only the duration of the collection was found to correlate significantly with donor recovery time (P = .001). This analysis demonstrates that marrow donation is well tolerated with few complications. To decrease further the incidence of donor discomfort and recovery time following donation, the duration of the collection procedure, and probably the duration of anesthesia, and the volume of marrow collected, should be kept to a minimum.
Initial assessment of the beneficial effect of partial splenectomy in hereditary spherocytosis
Authors: Tchernia G , Gauthier F , Mielot F , Dommergues JP , Yvart J , Chasis JA , Mohandas N 
Published: October 2019

Abstract
Clinical manifestations of hereditary spherocytosis (HS), the most common red blood cell (RBC) membrane disorder, can be abrogated or markedly reduced by splenectomy. However, concerns regarding risks from overwhelming infections after splenectomy have restricted its use, especially in children. This study was designed to determine if partial splenectomy can decrease the hemolytic rate while maintaining phagocytic function of the spleen. Partial splenectomy was performed in 11 children (age 2 to 13) with HS. The effect on hemolytic rate was assessed by comparing the presurgical and postsurgical values for hemoglobin, reticulocyte number, and RBC life span. The residual splenic phagocytic function was assessed using technetium 99m scans and by enumerating the percentage of pitted RBCs in circulation. There were no complications from the surgical procedure in any of the 11 individuals. Following partial splenectomy, hemoglobin increased on the average by 3 g/dL, reticulocyte count decreased by 300 x 10(6)/L, and RBC life span was substantially prolonged. Normal technetium uptake was noted in the splenic remnant and the percentage of pitted RBCs was in the normal range. Partial splenectomy is effective in decreasing the hemolytic rate while maintaining residual splenic phagocytic function of the spleen in HS. We conclude that the use of this procedure as treatment for RBC membrane disorders warrants consideration, especially in infants under 5 years of age who need frequent transfusions.
Granulocyte colony-stimulating factor "mobilized" peripheral blood progenitor cells accelerate granulocyte and platelet recovery after high-dose chemotherapy
Authors: Chao NJ , Schriber JR , Grimes K , Long GD , Negrin RS , Raimondi CM , Horning SJ , Brown SL , Miller L , Blume KG 
Published: October 2019

Abstract
Hematopoietic growth factors have been used to accelerate engraftment after bone marrow transplantation and to “mobilize” peripheral blood progenitor cells (PBPC). We report on the data in 85 consecutive patients with Hodgkin's disease who were treated in a single institution using different methods to obtain PB progenitor cells. Use of granulocyte colony-stimulating factor for mobilization resulted in a significantly accelerated time to recovery of granulocytes (10 days v 12 days, P < .01) when compared with “nonmobilized” PBPC recipients. Similarly, use of mobilized PBPC resulted in a significantly accelerated time to platelet engraftment (13 days v 30 days, P < .001) when compared with “nonmobilized” recipients. Moreover, there was a statistically significant difference in total costs in favor of the group receiving “mobilized” PBPC.
Glanzmann's thrombasthenia caused by homozygosity for a splice defect that leads to deletion of the first coding exon of the glycoprotein IIIa mRNA
Authors: Simsek S , Heyboer H , de Bruijne-Admiraal LG , Goldschmeding R , Cuijpers HT , von dem Borne AE 
Published: October 2019

Abstract
Glanzmann's thrombasthenia (GT) is the result of the absence or of an altered and dysfunctional expression on the platelet membrane of the fibrinogen receptor (glycoprotein [GP] IIb/IIIa complex). Various molecular genetic mechanisms have been found to be responsible for this inherited disease. In a patient with a severe type of GT, we have found a splice variant in the GP IIIa gene that leads to premature chain termination. Immunoprecipitation experiments, using monoclonal antibodies specific for GP IIb/IIIa, showed that GP IIb/IIIa was not detectable on the platelet membrane. Amplification of reversely transcribed platelet GP IIIa mRNA by the polymerase chain reaction and subsequent sequence analysis showed a 86-bp deletion, which corresponds to exon i of the GP IIIa gene. This deletion results in a shift of the reading frame leading to eight altered amino acids followed by a premature termination codon. Analysis of the corresponding genomic DNA fragments showed three mutations in the exon i-intron i boundary region of the GP IIIa gene. One of these mutations is a G-->T transition that eliminates the GT splice donor site in the wild type. This base pair change creates a restriction site for the enzyme Mse I. Allele-specific restriction enzyme analysis (ASRA) with Mse I of amplified genomic DNA of the parents and the proposita showed that both parents (who are first cousins) are heterozygous, whereas the proposita is homozygous for the G-->T substitution.
Generation and characterization of ex vivo propagated autologous CD8+ cells used for adoptive immunotherapy of patients infected with human immunodeficiency virus
Authors: Whiteside TL , Elder EM , Moody D , Armstrong J , Ho M , Rinaldo C , Huang X , Torpey D , Gupta P , McMahon D 
Published: October 2019

Abstract
Cytolytic T lymphocytes play an important role in host defense against viral infections, including human immunodeficiency virus (HIV). In a phase I clinical trial (protocol 080 of the AIDS Clinical Trials Group), generation of CD8+ effector cells from peripheral blood of patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) or AIDS and safety of autologous adoptive transfer of these cells were evaluated. For therapeutic infusions, CD8+ T cells were purified by positive selection on anti-CD8 monoclonal antibody-coated flasks from leukapheresed peripheral blood of seven patients. These CD8+ T cells were cultured in the presence of interleukin-2 and phytohemagglutinin for up to 3 weeks to obtain cells sufficient for therapeutic infusions (10(8) to 10(10)). All 31 cell cultures established from the seven patients and used for therapy were highly enriched in CD8+ (mean, 97%), CD8+HLA-DR+ (50%), cytotoxic CD8+CD11b- (82%), and memory CD29+ (78%) T lymphocytes. In vitro expanded CD8+ cells had excellent cytotoxic function at the time they were used for therapy, including HIV-specific activity against autologous targets infected with vaccinia vectors expressing HIV-IIIb antigens, gag, pol, and env. Anti-HIV activity of cultured CD8+ cells was significantly higher than that of autologous fresh peripheral blood lymphocytes. Our results show that CD8+ T lymphocytes obtained from peripheral blood of symptomatic HIV-infected patients can be purified, cultured to obtain large numbers of cells with enhanced anti-HIV activity, and safely infused into patients with AIDS as a form of immunotherapy.
Post-5-fluorouracil human marrow: stem cell characteristics and renewal properties after autologous marrow transplantation
Authors: Stewart FM , Temeles D , Lowry P , Thraves T , Grosh WW , Quesenberry PJ 
Published: October 2019

Abstract
The effect of 5-fluorouracil (5-FU) pretreatment on human bone marrow (BM) progenitor/stem cells and recovery of hematopoiesis after autologous marrow transplant was studied. Twenty-one patients were treated with 5-FU (15 mg/kg to 45 mg/kg) intravenously (IV) for 1 to 3 days administered 6 to 22 days before BM harvest. Post-FU marrow was infused into 15 patients after high-dose cyclophosphamide, carmustine (BCNU), and VP-16 (CBV). Seventeen patients (historical controls) were treated with CBV and autologous BM transplantation but did not receive 5-FU before marrow harvest. The groups were comparable for diagnosis and prior therapy. In the 5-FU-treated group and control group, median recovery times for platelet count to 50,000/mm3 were 20 and 30 days, respectively (P = .007), and for platelet count to 100,000/mm3, 23 and 38 days, respectively (P = .007), while neutrophil recovery was not significantly altered. In vitro cultures with 1 to 7 growth factors (interleukin-1 [IL-1], IL-3, IL-4, IL-6, colony-stimulating factor-1 [CSF-1], granulocyte-macrophage colony-stimulating factor [GM-CSF], and G-CSF) were performed. In 8 of 10 patients whose marrow was studied before and after 5-FU treatment, the numbers of CFU-C responsive to the combination of GM-CSF and IL-3 was increased 6.15-fold by 5-FU pretreatment. In 4 of these patients, thymidine suicide of GM-CSF- and IL-3-stimulated CFU-C ranged from 17% to 42%. High proliferative potential colony-forming cell (HPP-CFC) was observed in low frequency in normal marrow and patient's marrow before 5-FU treatment. In 11 of 16 patients pretreated with 5-FU, increased numbers of HPP-CFC were noted. GM-CSF and IL-3 interacted synergistically to stimulate HPP-CFC. Multifactor combinations, especially GM-CSF + G-CSF + IL-3 + IL-6 + IL- 1 + CSF-1 did not increase total colony count or classic HPP-CFC but did result in altered morphology, producing huge, loose colonies. The marrow from patients pretreated with 5-FU is enriched with multifactor- responsive HPP-CFC, renews in vivo granulopoiesis in a manner comparable with marrow harvests without 5-FU pretreatment, and provides accelerated in vivo platelet recovery. This marrow may be an appropriate target marrow for gene insertion in gene-therapy protocols.
Changes in frequencies of clonable pre B cells during life in different lymphoid organs of mice
Authors: Rolink A , Haasner D , Nishikawa S , Melchers F 
Published: October 2019

Abstract
Progenitor and precursor B lymphocytes with the capacity of long-term proliferation on stromal cells in the presence of interleukin-7 (IL-7) can be cloned ex vivo from fetal liver, neonatal blood, and spleen, and from adult bone marrow (BM) in frequencies that are similar in different strains of mice and that change with age. A wave of clonable cells appears before birth and disappears after birth in liver. Up to 2 weeks after birth, high frequencies of clonable cells are present in spleen but become undetectable at 6 to 8 weeks of age. In BM, high frequencies (1 in 50) of clonable cells are present early after birth, and then decrease continuously to 10- to 20-fold lower levels at 6 to 8 months of age. The earliest clonable cells have at least part of their IgH genes in germline configuration. Clones of pro/pre B cells apparently continue to rearrange DH to JH segments on both chromosomes. Rearrangements without insertion of N-sequences at the DHJH joints are found in fetal liver, while DHJH joints in pre B cells of spleen and BM throughout life have N-regions inserted. At least half of all primary pre B-cell clones develop mitogen-reactive B cells after differentiation to sIg+ B cells. Clonable pro and pre B cells are enriched in B220- c-kit(low) as well as in B220+ c-kit+ and B220+ CD43+ cell populations of BM. The frequencies of clonable cells in the B220- c-kit(low) BM cell population decrease 10- to 20-fold during 8 months of life, while those in the B220+ c-kit+ population remain constant, although their absolute numbers drop 5- to 10-fold during that time. All long-term proliferating clones express the surrogate L chain VpreB/lambda 5 as well as c-kit and CD43 on all cells. The number of total clonable pro and pre B cells is at best 10% of the number of cells required to produce the estimated daily output of 5 x 10(7) B- lineage cells in a mouse. This suggests that the production of a relatively constant number of B cells during adulthood may be effected by precursors, which are not clonable on stromal cells and IL-7 with long-term proliferative capacity. On the other hand, BM transplantation experiments indicate that a mouse retains B220- progenitors throughout life, from which pre B and B cells can be generated in old mice in frequencies characteristic of young mice.