bluuebunny/crossref_metadata_2025_split huggingface dataset:
PATHOLOGY OF THE RUPTURED SPLEEN IN ACUTE VIVAX MALARIA
Authors: LUBITZ JOSEPH M. 
Published: October 2019

Abstract
1. Opportunity to study the pathologic changes in ruptured spleen of acute vivax malaria was afforded by splenectomy.
2. Subcapsular hematoma precedes rupture.
3. The capsular tear is an obvious consequence of the changes in the spleen occurring in acute malaria. Small hemorrhages occur in the vicinity of the capsule or deep in the tissues.
4. A rapidly enlarging spleen with underlying vascular alteration predisposes to rupture. Minimal trauma may be a precipitating element.
5. Diffuse cellular hyperplasia, subintimal and adventitial leukopoiesis, dilated sinuses and occasional thrombosis and infarction constitute the characteristic pattern in malaria.
6. Changes in the left lung base may serve as a diagnostic aid in cases in which the diagnosis of splenic rupture is considered.
Elevated adenosine deaminase and purine nucleoside phosphorylase activity in peripheral blood null lymphocytes from patients with acquired immune deficiency syndrome
Authors: Murray JL , Loftin KC , Munn CG , Reuben JM , Mansell PW , Hersh EM 
Published: October 2019

Abstract
The purine metabolic enzymes adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) are important in lymphocyte differentiation, and genetic deficiencies of either enzyme have been associated with hereditary immunodeficiency states. Both ADA and PNP activity were measured in null cell-enriched and T cell-enriched peripheral blood lymphocytes from 16 patients with the acquired immune deficiency syndrome (AIDS), seven patients with the AIDS-related symptom complex (ARC), and seven asymptomatic homosexuals. ADA activity in nmol/10(6) lymphocytes/h was significantly elevated in null lymphocytes from AIDS (161 +/- 12) as compared with 23 healthy heterosexual controls (127 +/- 8;P less than .025). PNP activity was also significantly increased in null lymphocytes from AIDS patients (96 +/- 10;P less than .005) as well as those from ARC patients (84 +/- 11:P less than .025) relative to controls (61 +/- 5). No significant differences in enzyme activity were noted in T cell-enriched cells in any group. Along with elevated enzyme activity, AIDS patients had small yet significant increases in the percentages of HLA-DR (P less than .025), terminal deoxynucleotidyl transferase (TdT) (P less than .0001), and peanut agglutinin receptor (P less than .0001) positive lymphocytes in the null fraction compared with controls. TdT-positive cells appeared morphologically as large lymphoblasts with irregular nuclei. The data imply that the cellular immune deficiency in AIDS is not a result of deficiencies in lymphocyte ADA or PNP activity, but is more likely associated with an increase in an immature and/or activated lymphocyte subset.
Rapid recovery from cytopenia in hairy cell leukemia after treatment with 2-chloro-2'-deoxyadenosine (CdA): relation to opportunistic infections
Authors: Juliusson G , Liliemark J 
Published: October 2019

Abstract
Sixteen patients with symptomatic hairy cell leukemia were treated with a single course of 2-chloro-2′-deoxyadenosine (CdA), 0.7 mg/kg total dose. Twelve patients achieved complete remission (CR). One patient with a CD19+/CD5+/CD25- phenotype and one with a pentostatin-treated CD19+/CD25- variant form had minor responses. Two patients with advanced disease and poor performance status died early from invasive mycosis. Three patients recovered from infections caused by cytomegalovirus and by candida. No patient had infections caused by bacteria or by unknown organisms. The median time to full recovery from anemia and thrombocytopenia was 6 and 2 weeks from start of therapy, respectively. Patients with infections, however, recovered at 13 and 5 weeks, respectively. Neutrophil, monocyte, and lymphocyte counts returned to normal at a median of 5, 5, and 10 weeks, respectively. Infections developed more frequently in pancytopenic patients than in those with one or more blood cell count within the normal range (P less than .01). All patients with one or no previous therapy had a CR, whereas those with more than one previous regimen had a lower CR rate (P less than .01). Thus, 1 week of CdA therapy frequently induced CR also in patients resistant to interferon. Toxicity was limited, and recovery from cytopenia was faster than what is reported during interferon therapy.
Differential Incorporation of Ara-C, Gemcitabine, and Fludarabine Into Replicating and Repairing DNA in Proliferating Human Leukemia Cells
Authors: Iwasaki Hiromichi , Huang Peng , Keating Michael J. , Plunkett William 
Published: October 2019

AbstractThe major actions of nucleoside analogs such as arabinosylcytosine (ara-C) and fludarabine occurs after their incorporation into DNA, during either replication or repair synthesis. The metabolic salvage and DNA incorporation of the normal nucleoside, deoxycytidine, is functionally compartmentalized toward repair synthesis in a process regulated by ribonucleotide reductase. The aim of this study was to investigate the metabolic pathways by which nucleoside analogs that do (fludarabine, gemcitabine) or do not (ara-C) affect ribonucleotide reductase are incorporated into DNA in proliferating human leukemia cells. Using alkaline density-gradient centrifugation to separate repaired DNA from replicating DNA and unreplicated parental DNA strands, approximately 60% of ara-C nucleotide in DNA was incorporated by repair synthesis in CCRF-CEM cells; the remainder was incorporated by replication. In contrast, fludarabine and gemcitabine, nucleosides that inhibit ribonucleotide reductase and decreased deoxynucleotide pools, were incorporated mainly within replicating DNA. Hydroxyurea also depleted deoxynucleotide pools and increased the incorporation of ara-C into DNA by replicative synthesis. Stimulation of DNA repair activity by UV irradiation selectively enhanced the incorporation of all nucleosides tested through repair synthesis. These findings suggest that the pathways by which therapeutically useful nucleoside analogs are incorporated into DNA are affected by cellular dNTP pools from de novo synthesis and by the relative activities of DNA repair and replication. The antitumor activity of these drugs may be enhanced by combination with either ribonucleotide reductase inhibitors to increase their incorporation into replicating DNA or with agents that induce DNA damage and evoke the DNA repair process.
Enzyme Therapy in Gaucher Disease Type 1: Effect of Neutralizing Antibodies to Acid β-Glucosidase
Authors: Ponce Elvira , Moskovitz Jay , Grabowski Gregory 
Published: October 2019

AbstractGaucher disease type 1, a non-neuronopathic lysosomal storage disease, is caused by mutations at the acid β-glucosidase locus. Periodic infusions of macrophage-targeted acid β-glucosidase reverse hepatosplenomegaly, hematologic, and bony findings in many patients. Two patients receiving enzyme therapy developed neutralizing antibodies to acid β-glucosidase that were associated with a lack of improvement or progressive disease. After initial improvement, case 1 had no additional response to 2 years of high-dose (50 U/kg every 2 weeks) enzyme therapy. Similarly, case 2 initially showed a favorable response to enzyme therapy that plateaued after 1 year of treatment. Both patients developed minor allergic reactions and antibodies to acid β-glucosidase within the first 6 months of treatment. Enzyme therapy was discontinued in case 1, with resultant disease progression and need for splenectomy. An immunosuppression/tolerization protocol was initiated in case 2 because of disease progression and stable neutralizing antibody titers. The IgG neutralizing antibodies rapidly and completely inactivated the wild-type, but not the N370S, acid β-glucosidase in vitro. Antibodies to human serum albumin and chorionic gonadotropin also developed. The finding of neutralizing antibodies to acid β-glucosidase during enzyme therapy for Gaucher disease has significant implications for monitoring the therapeutic responses and for potential alternative future therapies for Gaucher disease.
Receptor Protein Tyrosine Phosphatase Gamma, Ptpγ, Regulates Hematopoietic Differentiation
Authors: Sorio Claudio , Melotti Paola , D'Arcangelo Daniela , Mendrola Jeannine , Calabretta Bruno , Croce Carlo M. , Huebner Kay 
Published: October 2019

AbstractMurine embryonic stem (ES) cells have been a useful model system for the study of various aspects of hematopoietic differentiation. Because we had observed a sharp peak of expression of the receptor tyrosine phosphatase gamma (Ptpγ) gene between 14 and 18 days of ES-derived embryoid body differentiation, we investigated the effect of perturbation of expression of the Ptpγ gene on ES cell differentiation, first by analyzing the effect of Ptpγ overexpression. The murine full-length Ptpγ cDNA in an expression vector was transfected into ES-D3 cells and stably transfected clones were isolated. Ptpγ was expressed as an approximately 230-kD cell surface protein, and differentiating ES clones that overexpressed Ptpγ gave rise to a normal number of hematopoietic colonies, approximately 1 CFU per 100 cells. There was, however, a significant increase of expression of early hematopoietic markers in colonies from Ptpγ overexpressing ES cells. To confirm that the pertubation of hematopoietic differentiation was a result of Ptpγ overexpression, we isolated ES stem cell clones expressing Ptpγ antisense constructs and assayed embryoid bodies for the presence of hematopoietic precursors. We observed a complete absence of methylcellulose colonies, indicating absence of hematopoietic lineages. Results of these experiments point to an essential role for Ptpγ in hematopoietic differentiation.
Serum Levels of Substance P Are Elevated in Patients With Sickle Cell Disease and Increase Further During Vaso-Occlusive Crisis
Authors: Michaels Lisa A. , Ohene-Frempong Kwaku , Zhao Huaqing , Douglas Steven D. 
Published: October 2019

As a mediator of neurogenic inflammation and pain, we hypothesized that levels of the neuropeptide Substance P (SP) would be elevated in patients with sickle cell disease (SCD) with vaso-occlusive pain crisis. SP is a known stimulator of tumor necrosis factor- (TNF-) release and a promoter of interleukin-8 (IL-8), which are reported to be increased in SCD. These cytokines enhance adhesion of leukocytes to endothelium and may play a role in vaso-occlusive events. Serum levels of IL-8, TNF, and SP were studied in three groups of children aged 2 to 18 years: 30 well children with SCD, 21 with SCD in pain crisis, and 20 healthy age-matched controls. Serum levels of SP were elevated in all SCD patients and were highest in patients in pain crisis. The percentage of sera with detectable levels of IL-8 (>5.0 pmol/L) was increased in SCD patients as compared with the control group. IL-8 levels were similar for well SCD patients and those with pain. TNF levels were not significantly different among the three groups. In three children with SCD, SP was measured at baseline and again during pain crisis. In each case, serum levels during pain crisis were higher than they were when the patient was well. We conclude that levels of SP are high in patients with SCD and increase during pain crisis. These results imply that SP plays a prominent role in the pain and inflammation of SCD and may be a measurable laboratory marker of vaso-occlusive crisis. We speculate that neurokinin receptor antagonists may have a therapeutic potential in the treatment of crisis pain.© 1998 by The American Society of Hematology.
Four-Color Flow Cytometric Investigation of Terminal Deoxynucleotidyl Transferase–Positive Lymphoid Precursors in Pediatric Bone Marrow: CD79a Expression Precedes CD19 in Early B-Cell Ontogeny
Authors: Dworzak Michael N. , Fritsch Gerhard , Fröschl Gertraud , Printz Dieter , Gadner Helmut 
Published: October 2019

Terminal deoxynucleotidyl transferase (TdT)-positive cells in human bone marrow (BM) are a phenotypically inhomogeneous population of precursor cells. In their majority, these TdT+ cells are unambiguously committed to the B lineage, as evidenced by CD19 expression. However, TdT+ precursors that lack CD19 also exist and these may encompass a differentiation potential for the B as well as for other lineages. Because recent data suggested that CD19 expression is not the earliest differentiation event in B-cell ontogeny, we sought to reevaluate TdT+ lymphoid precursors in pediatric BM to define the phenotypic denominator of B-lineage affiliation upstream of CD19. Using four-color flow cytometry, we focused on the assessment of the CD79a antigen, which is highly B-cell specific and which may also be expressed very early in B-cell ontogeny. We found that a majority of TdT+ cells coexpressed CD19 and CD79a in addition to CD10 and CD34, whereas, in all investigated samples, some TdT+ precursors lacked CD19 but expressed CD79a, which suggestively indicates also their B-lineage affiliation. In contrast to the CD19+precursors, which were usually CD10hi and CD79b+, these CD19−CD79a+putative B-cell precursors preferentially expressed CD10 at low levels and were CD79b+ in only 41%. About 17% of these TdT+CD19−CD79a+ precursors also coexpressed CD33 and CD7, but not myeloperoxidase, CD14, or cytoplasmic CD3, which is discussed in the light of cellular activation rather than lineage promiscuity. Our data confirm that the earliest differentiation stages of B cells can be dissected upon expression of the lineage antigens CD79a and CD19 and imply that CD79a is earlier expressed than CD19. This raises the chance to follow the sequential events heralding B-cell commitment in the most immature precursors by correlating phenotypic and genetic differentiation markers.© 1998 by The American Society of Hematology.
Accutin, a New Disintegrin, Inhibits Angiogenesis In Vitro and In Vivo by Acting as Integrin vβ3 Antagonist and Inducing Apoptosis
Authors: Yeh Chia Hsin , Peng Hui-Chin , Huang Tur-Fu 
Published: October 2019

Endothelial integrins play an essential role in angiogenesis and cell survival. Accutin, a new member of disintegrin family derived from venom of Agkistrodon acutus, potently inhibited human platelet aggregation caused by various agonists (eg, thrombin, collagen, and, adenosine diphosphate [ADP]) through the blockade of fibrinogen binding to platelet glycoprotein IIb/IIIa (ie, integrin IIbβ3). In this report, we describe that accutin specifically inhibited the binding of monoclonal antibody (MoAb) 7E3, which recognizes integrin vβ3, to human umbilical vein endothelial cells (HUVECs), but not those of other anti-integrin MoAbs such as 2β1, 3β1, and 5β1. Moreover, accutin, but not the control peptide GRGES, dose-dependently inhibited the 7E3 interaction with HUVECs. Both 7E3 and GRGDS, but not GRGES or Integrelin, significantly blocked fluorescein isothiocyanate-conjugated accutin binding to HUVEC. In functional studies, accutin exhibited inhibitory effects on HUVEC adhesion to immobilized fibrinogen, fibronectin and vitronectin, and the capillary-like tube formation on Matrigel in a dose- and RGD-dependent manner. In addition, it exhibited an effective antiangiogenic effect in vivo when assayed by using the 10-day-old embryo chick CAM model. Furthermore, it potently induced HUVEC apoptotic DNA fragmentation as examined by electrophoretic and flow cytometric assays. In conclusion, accutin inhibits angiogenesis in vivo and in vitro by blocking integrin vβ3 of endothelial cells and by inducing apoptosis. The antiangiogenic activity of disintegrins might be explored as the target of developing the potential antimetastatic agents.© 1998 by The American Society of Hematology.
Alloantigen-Stimulated Anti-HIV Activity
Authors: Pinto Ligia A. , Sharpe Sandra , Cohen David I. , Shearer Gene M. 
Published: October 2019

A number of studies have suggested that an immune response to human leukocyte antigen (HLA) alloantigens may contribute to protection against HIV infection. In the present study, we examined the effect of alloantigen-stimulated cell lines obtained from peripheral blood mononuclear cells (PBMC) of HIV-uninfected (HIV−) individuals and the soluble factors produced by these cell lines on HIV-1 replication. Multiple in vitro restimulation with irradiated allogeneic PBMC from HIV− donors resulted in the expansion of CD8+ T-cell lines that inhibited HIV-1 replication when cocultured with either autologous or heterologous in vitro–infected phytohemagglutinin (PHA) blasts. Supernatants from the alloantigen-stimulated cell lines also inhibited HIV replication in both PHA blasts and a chronically infected cell line. The alloantigen-stimulated cell lines and the factors they produced inhibited both T-cell–tropic (T) and macrophage-tropic (M) isolates of HIV-1. Blocking experiments using anti-chemokine antibodies suggested that this inhibition of HIV replication was not due to the β-chemokines present in cocultures of cell lines with HIV-infected blasts. These results indicate that alloantigen-stimulation of PBMC from HIV−individuals activates CD8+ T cells that produce soluble factor(s) that inhibit HIV replication of a wide spectrum of HIV-1 isolates through a chemokine-independent mechanism.This is a US government work. There are no restrictions on its use.
Human Monocytoid Leukemia Cells Are Highly Sensitive to Apoptosis Induced by 2′-Deoxycoformycin and 2′-Deoxyadenosine: Association With dATP-Dependent Activation of Caspase-3
Authors: Niitsu Nozomi , Yamaguchi Yuri , Umeda Masanori , Honma Yoshio 
Published: October 2019

The adenosine deaminase (ADA) inhibitor 2′-deoxycoformycin (dCF) significantly inhibits the proliferation of leukemia and lymphoma cell lines. When cells were incubated in the presence of both dCF and 2′-deoxyadenosine (dAd), the concentration of dCF required to induce apoptosis of monocytoid leukemia cells was much lower than that required for myeloid, erythroid, or lymphoma cell lines. Among the cell lines tested, U937 cells were the most sensitive to this treatment. The concentration of dCF that effectively inhibited the proliferation of U937 cells was 1/1,000 of that required for lymphoma cell lines, on a molar basis. However, the uptake of dCF or dAd in U937 cells was comparable with that in other leukemia and lymphoma cell lines. The intracellular accumulation of dATP in U937 cells was only slightly higher than that in other leukemia cells in dCF-treated culture. Treatment with dCF plus dAd induced apoptosis in U937 cells at low concentrations, and this apoptosis was reduced by treatment with caspase inhibitors. Induction of caspase-3 (CPP32) activity accompanied the apoptosis induced by dCF plus dAd. No activation of CPP32 was observed in cytosol prepared from exponentially growing leukemia and lymphoma cells. However, dATP effectively induced CPP32 activation in cytosol from monocytoid cells, but not in that from nonmonocytoid cells, suggesting that dATP-dependent CPP32 activation is at least partly involved in the preferential induction of apoptosis in monocytoid leukemia cells. The combination of dCF and dAd may be useful for the clinical treatment of acute monocytic leukemia.© 1998 by The American Society of Hematology.
Coexpression of Erythropoietin and Vascular Endothelial Growth Factor in Nervous System Tumors Associated With von Hippel-Lindau Tumor Suppressor Gene Loss of Function
Authors: Krieg Marion , Marti Hugo H. , Plate Karl H. 
Published: October 2019

Hemangioblastomas are highly vascular tumors of the central nervous system that overexpress the hypoxia-inducible gene, vascular endothelial growth factor (VEGF), as a consequence of mutational inactivation of the von Hippel-Lindau tumor suppressor gene (VHL). Previous reports showed that hemangioblastomas can also express erythropoietin (Epo), which is also hypoxia-inducible. However, Epo expression in hemangioblastomas was observed only in individual cases, and the analyses were mainly based on indirect determination of erythropoiesis-stimulating activity. Therefore, we analyzed a series of 11 hemangioblastomas for Epo, VEGF, and VHL expression by Northern blot analysis and compared the results with normal brain and glioblastomas. Surprisingly, we observed Epo mRNA expression in all hemangioblastoma specimens analyzed, but in none of four glioblastomas. In contrast, VEGF mRNA was expressed in all hemangioblastomas and all glioblastomas. In situ hybridization revealed neoplastic stromal cells as Epo- and VEGF-producing cells in hemangioblastomas. These results suggest that in the nonhypoxic microenvironment of hemangioblastoma, Epo, similar to VEGF, might be negatively regulated by the VHL gene product.© 1998 by The American Society of Hematology.
Vena caval filters: a comprehensive review
Authors: Streiff Michael B. 
Published: October 2019

AbstractHematologists are often asked to treat patients with venous thromboembolic disease. Although anticoagulation remains the primary therapy for venous thromboembolism, vena caval filters are an important alternative when anticoagulants are contraindicated. To assess the evidence supporting the utility of these devices, a comprehensive review of the English language literature was performed. Except for one randomized trial, the vena caval filter literature consists of case series or consecutive case series. The mean duration of follow-up for each of the 5 filter types varies from 6 to 18 months. All are about equally effective in the prevention of pulmonary embolism (2.6%-3.8%). Deep venous thrombosis (6%-32%) and inferior vena cava thrombosis (3.6%-11.2%) after filter placement vary widely among different filter types primarily because of differences in outcome assessment. Thrombosis at the insertion site is a common complication of filter placement (23%-36%). In view of the absence of randomized comparisons, no filter can be designated as superior in safety or efficacy. Vena caval filters represent a potentially important but poorly evaluated therapeutic modality in the prevention of pulmonary emboli. Randomized trials are necessary to establish the appropriate place for vena caval filters in the treatment of venous thromboembolic disease.
“Emergency” granulopoiesis in G-CSF–deficient mice in response to Candida albicans infection
Authors: Basu Sunanda , Hodgson George , Zhang Hui-Hua , Katz Melissa , Quilici Cathy , Dunn Ashley R. 
Published: October 2019

AbstractGranulocyte colony-stimulating factor (G-CSF) is a glycoprotein believed to play an important role in regulating granulopoiesis both at steady state and during an “emergency” situation. Generation of G-CSF and G-CSF receptor–deficient mice by gene targeting has demonstrated unequivocally the importance of G-CSF in the regulation of baseline granulopoiesis. This study attempted to define the physiologic role of G-CSF during an emergency situation by challenging a cohort of wild-type and G-CSF–deficient mice with Candida albicans. Interestingly, after infection, G-CSF–deficient mice developed an absolute neutrophilia that was observed both in blood and bone marrow. In addition, 3 days after Candida infection increased numbers of granulocyte-macrophage (GM) and macrophage (M) progenitors were observed in the bone marrow of G-CSF–deficient mice. Of the cytokines surveyed, interleukin (IL)-6 levels in serum were elevated; interestingly, levels of IL-6 were higher and more sustained in G-CSF–deficient mice infected with C albicans than similarly infected wild-type mice. Despite the higher levels of serum IL-6, this cytokine is dispensable for the observed neutrophilia because candida-infected IL-6–deficient mice, or mice simultaneously deficient in G-CSF and IL-6, developed neutrophilia. Similarly, mice lacking both G-CSF and GM-CSF developed absolute neutrophilia and had elevated numbers of GM and M progenitors in the bone marrow; thus, G-CSF and GM-CSF are dispensable for promoting the emergency response to candidal infection.