bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sallust in Julian of Aeclanum
Authors: Lössl Josef 
Published: June 2004

AbstractThe importance of Cicero in the debate between Augustine of Hippo and Julian of Aeclanum has been extensively studied. This includes Augustine's and Julian's use of the Catilinarian speeches in their polemics against each other. In comparison the use of Sallust, the other classical authority on Catiline, especially by Julian of Aeclanum, has been neglected. This paper intends to remedy that situation. Textual evidence may be meagre: barely two literal citations in three of the extant fragments of Julian's writings. But Julian's use of these, also compared with Jerome's and Augustine's, and the way his use of Sallust is reflected in the rest of his extant writing and thought gives the impression that he may have been far more deeply influenced by Sallust than has hitherto been thought.
Thrombopoietin responsiveness reflects the number of doublings undergone by megakaryocyte progenitors
Authors: Paulus Jean-Michel , Debili Najet , Larbret Frédéric , Levin Jack , Vainchenker William 
Published: June 2004

AbstractTo assess the variation of thrombopoietin (TPO) responsiveness associated with megakaryocyte (MK) progenitor amplification, TPO dose-response curves were obtained for normal human, single-cell plated CD34+CD41+ cells. The number of MKs per well was determined in situ and expressed as number of doublings (NbD). Dose-response curves of the mean frequency of clones of each size versus log TPO concentration showed highly significant differences in the TPO concentration needed for half-maximum generation of clones of different sizes (TPO50): 1.89 ± 0.51 pg/mL for 1 MK clones; 7.75 ± 0.81 pg/mL for 2 to 3 MK clones; 38.5 ± 5.04 pg/mL for 4 to 7 MK clones, and 91.8 ± 16.0 pg/mL for 8 to 15 MK clones. These results were consistent with a prediction of the generation-age model, because the number of previous doublings in vivo was inversely correlated with the number of residual doublings in vitro. TPO responsiveness decreased in vitro by a factor of 3.5 per doubling, reflecting the recruitment of progressively more ancestral progenitors. In support of this hypothesis, the more mature CD34+CD41+CD42+ cell fraction had a lower TPO50 (P &lt; .001), underwent fewer NbD (P &lt; .001), and expressed a 2.8-fold greater median Mpl receptor density (P &lt; .001) than the CD34+CD41+CD42– fraction. Progenitors that have completed their proliferative program have maximum factor responsiveness and are preferentially induced to terminal differentiation.
An endothelial laminin isoform, laminin 8 (α4β1γ1), is secreted by blood neutrophils, promotes neutrophil migration and extravasation, and protects neutrophils from apoptosis
Authors: Wondimu Zenebech , Geberhiwot Tarekegn , Ingerpuu Sulev , Juronen Erkki , Xie Xun , Lindbom Lennart , Doi Masayuki , Kortesmaa Jarkko , Thyboll Jill , Tryggvason Karl , Fadeel Bengt , Patarroyo Manuel 
Published: June 2004

AbstractDuring extravasation, neutrophils migrate through the perivascular basement membrane (BM), a specialized extracellular matrix rich in laminins. Laminins 8 (LN-8) (α4β1γ1) and 10 (LN-10) (α5β1γ1) are major components of the endothelial BM, but expression, recognition, and use of these laminin isoforms by neutrophils are poorly understood. In the present study, we provide evidence, using a panel of novel monoclonal antibodies against human laminin α4 (LNα4) chain, that neutrophils contain and secrete LN-8, and that this endogenous laminin contributes to chemoattractant-induced, αMβ2-integrin–dependent neutrophil migration through albumin-coated filters. Phorbol ester–stimulated neutrophils adhered to recombinant human (rh) LN-8, rhLN-10, and mouse LN-1 (mLN-1) (α1β1γ1) via αMβ2-integrin, and these laminin isoforms strongly promoted chemoattractant-induced neutrophil migration via the same integrin. However, only rhLN-8 enhanced the spontaneous migration. In addition, recruitment of neutrophils into the peritoneum following an inflammatory stimulus was impaired in LNα4-deficient mice. rhLN-8 also protected isolated neutrophils from spontaneous apoptosis. This study is the first to identify a specific laminin isoform in neutrophils and provides evidence for the role of LN-8 in the adhesion, migration, extravasation, and survival of these cells.
Identifying and characterizing a novel activating mutation of the FLT3 tyrosine kinase in AML
Authors: Jiang Jingrui , Paez J. Guillermo , Lee Jeffrey C. , Bo Ronghai , Stone Richard M. , DeAngelo Daniel J. , Galinsky Ilene , Wolpin Brian M. , Jonasova Anna , Herman Paula , Fox Edward A. , Boggon Titus J. , Eck Michael J. , Weisberg Ellen , Griffin James D. , Gilliland D. Gary , Meyerson Matthew , Sellers William R. 
Published: June 2004

Abstract
The FLT3 receptor is activated by juxtamembrane insertion mutations and by activation loop point mutations in patients with acute myeloid leukemia (AML). In a systematic tyrosine kinase gene exon resequencing study, 21 of 24 FLT3 exons were sequenced in samples from 53 patients with AML, 9 patients with acute lymphoblastic leukemia (ALL), and 3 patients with myelodysplasia samples. Three patients had novel point mutations at residue N841 that resulted in a change to isoleucine in 2 samples and to tyrosine in 1 sample. Introduction of FLT3-N841I cDNA into Ba/F3 cells led to interleukin-3 (IL-3)–independent proliferation, receptor phosphorylation, and constitutive activation of signal transducer and activator of transcription 5 (STAT5) and extracellular regulatory kinase (ERK), suggesting that the N841I mutation confers constitutive activity to the receptor. An FLT3 inhibitor (PKC412) inhibited the growth of Ba/F3-FLT3N841I cells (IC50 10 nM), but not of wild-type Ba/F3 cells cultured with IL-3. PKC412 also reduced tyrosine phosphorylation of the mutant receptor and inhibited STAT5 phosphorylation. Examination of the FLT3 autoinhibited structure showed that N841 is the key residue in a hydrogen-bonding network that likely stabilizes the activation loop. These results suggest that mutations at N841 represent a significant new activating mutation in patients with AML and that patients with such mutations may respond to small-molecule FLT3 inhibitors such as PKC412.
Inhibition of iron transport across human intestinal epithelial cells by hepcidin
Authors: Yamaji Sachie , Sharp Paul , Ramesh Bala , Srai Surjit Kaila 
Published: June 2004

AbstractWe investigated the effects of the iron regulatory peptide hepcidin on iron transport by the human intestinal epithelial Caco-2 cell line. Caco-2 cells were exposed to hepcidin for 24 hours prior to the measurement of both iron transport and transporter protein and mRNA expression. Incubation with hepcidin significantly decreased apical iron uptake by Caco-2 cells. This was accompanied by a decrease in both the protein and the mRNA expression of the iron-response element containing variant of the divalent metal transporter (DMT1[+IRE]). In contrast, iron efflux and iron-regulated gene1 (IREG1) expression were unaffected by hepcidin. Hepcidin interacts directly with a model intestinal epithelium. The primary effect of this regulatory peptide is to modulate the apical membrane uptake machinery, thereby controlling the amount of iron absorbed from the diet. (Blood. 2004;104:2178-2180)
Rescue of lethal c-KitW/W mice by erythropoietin
Authors: Waskow Claudia , Terszowski Grzegorz , Costa Céline , Gassmann Max , Rodewald Hans-Reimer 
Published: June 2004

Abstract
Homozygous natural white-spotted (W) mutations in the gene encoding the receptor tyrosine kinase c-Kit are associated with hypoplastic bone marrow, severe macrocytic anemia, and lethality during early postnatal life. c-KitW/W mice can be rescued by wild-type hematopoietic stem cells (HSCs), but it is not known whether the lethality of c-KitW/W mice is the result of HSC failure or defects specific for erythropoiesis. Here we show that transgenic expression of erythropoietin (EPO) can overcome the lethality caused by the c-KitW/W mutation. In W mutant mice rescued by EPO, termed WEPO, erythrocyte colony-forming units (CFU-Es) are rescued to normal frequencies. Hence, Epo receptor signals can partially bypass the strict requirement for c-Kit signaling in erythropoiesis in the absence of c-Kit in vivo. Using a series of W and rescue mouse strains, we define here the erythropoietic threshold permitting survival in vivo. The lethality of c-KitW/W mice has precluded analysis of this crucial receptor-ligand pair in adult stem/progenitor cells. Our strategy to generate viable c-KitW/W mice will be useful to analyze the role of this important receptor tyrosine kinase in adult life in vivo. (Blood. 2004; 104:1688-1695)
Immediate post-operative effects of tracheotomy on respiratory function during mechanical ventilation
Authors: Amygdalou Argyro , Dimopoulos George , Moukas Markos , Katsanos Christos , Katagi Athina , Mandragos Costas , Constantopoulos Stavros H , Behrakis Panagiotis K , Vassiliou Miltos P 
Published: June 2004

Abstract
Introduction
Tracheotomy is widely performed in the intensive care unit after long-term oral intubation. The present study investigates the immediate influence of tracheotomy on respiratory mechanics and blood gases during mechanical ventilation.

Methods
Tracheotomy was performed in 32 orally intubated patients for 10.5 ± 4.66 days (all results are means ± standard deviations). Airway pressure, flow and arterial blood gases were recorded immediately before tracheotomy and half an hour afterwards. Respiratory system elastance (Ers), resistance (Rrs) and end-expiratory pressure (EEP) were evaluated by multiple linear regression. Respiratory system reactance (Xrs), impedance (Zrs) and phase angle (φrs) were calculated from Ers and Rrs. Comparisons of the mechanical parameters, blood gases and pH were performed with the aid of the Wilcoxon signed-rank test (P = 0.05).

Results
Ers increased (7 ± 11.3%, P = 0.001), whereas Rrs (-16 ± 18.4%, P = 0.0003), Xrs (-6 ± 11.6%, P = 0.006) and φrs (-14.3 ± 16.8%, P = <0.001) decreased immediately after tracheotomy. EEP, Zrs, blood gases and pH did not change significantly.

Conclusion
Lower Rrs but also higher Ers were noted immediately after tracheotomy. The net effect is a non-significant change in the overall Rrs (impedance) and the effectiveness of respiratory function. The extra dose of anaesthetics (beyond that used for sedation at the beginning of the procedure) or a higher FiO2 (fraction of inspired oxygen) during tracheotomy or aspiration could be related to the immediate elastance increase.
cAMP protects neutrophils against TNF-α-induced apoptosis by activation of cAMP-dependent protein kinase, independently of exchange protein directly activated by cAMP (Epac)
Authors: Krakstad Camilla , Christensen Anne Elisabeth , Døskeland Stein Ove 
Published: June 2004

AbstractIt is unclear by which receptor cyclic adenosine monophosphate (cAMP) acts to promote neutrophil survival. We found that 8-(4-chlorophenylthio)-2′-O-methyl-cAMP, a specific activator of the recently discovered cAMP receptor, cAMP-regulated guanosine 5′-triphosphate exchange protein directly activated by cAMP, failed to protect human neutrophils from cell death. In contrast, specific activators of cAMP-dependent protein kinase type I (cA-PKI) could protect against death receptor [tumor necrosis factor receptor 1 (TNFR-1), Fas]-mediated apoptosis as well as cycloheximide-accelerated “spontaneous” apoptosis. A novel “caged” cA-PK-activating analog, 8-bromo (8-Br)-acetoxymethyl-cAMP, was more than 20-fold more potent than 8-Br-cAMP to protect neutrophils chalenged with TNF-α against apoptosis. This analog acted more rapidly than forskolin (which increases the endogenous cAMP production) and allowed us to demonstrate that cA-PK must be activated during the first 10 min after TNF-α challenge to protect against apoptosis. The protective effect was mediated solely through cA-PK activation, as it was abolished by the cA-PKI-directed inhibitor Rp-8-Br-cAMPS and the general cA-PK inhibitor H-89. Neutrophils not stimulated by cAMP-elevating agents showed increased apoptosis when exposed to the cA-PK inhibitors Rp-8-Br-cAMPS and H-89, suggesting that even moderate activation of cA-PK is sufficient to enhance neutrophil longevity and thereby contribute to neutrophil accumulation in chronic inflammation.
Unique phenotype of human uterine NK cells and their regulation by endogenous TGF-β
Authors: Eriksson Mikael , Meadows Sarah K , Wira Charles R , Sentman Charles L 
Published: June 2004

AbstractNatural killer (NK) cells are a major population of lymphocytes in the human endometrium (EM), and NK cells can be a significant source of cytokines that alter local immune responses. The aim of this study was to determine the expression of NK cell receptors in situ and to test whether uterine NK (uNK) cells produce cytokines and how this activity may be regulated by transforming growth factor-β (TGF-β). We observed that human uNK cells were CD56+, CD3−, CD57−, CD9+, CD94+, killer inhibitory receptor+, and CD16+/− in situ by confocal microscopy. We examined cytokine production by uNK cells and uNK cell clones derived from human EM. Stimulation of uNK cells with interleukin (IL)-12 and IL-15, both of which are expressed in the human EM, induced interferon-γ (IFN-γ) and IL-10 production. IFN-γ production by uNK cell clones was completely inhibited by TGF-β1 in a dose-dependent manner with an inhibitory concentration 50% value of 20 pg/ml. IL-10 secretion by uNK cell clones was also inhibited by TGF-β1 at similar concentrations. Furthermore, blocking endogenous TGF-β in fresh human endometrial cell cultures increased the production of IFN-γ by uNK cells. These data indicate that uNK cells have a unique phenotype that is distinct from blood NK cells. Further, data demonstrate that uNK cells can produce immunoregulatory cytokines and that inhibition of uNK cells by locally produced TGF-β1 is a likely mechanism to regulate NK cell function in the human EM.
Loss of lineage antigens is a common feature of apoptotic lymphocytes
Authors: Diaz D , Prieto A , Barcenilla H , Monserrat J , Prieto P , Sánchez M A , Reyes E , Hernandez-Fuentes M P , de la Hera A , Orfao A , Alvarez-Mon M 
Published: June 2004

AbstractThe analysis of apoptosis in cell populations involves the detection of their specific lineage antigen (LAg) expression. This experimental approach relies on their assumed constant expression, but it is unclear whether such expression is actually maintained during cell death. We examined whether the loss of LAgs is a common feature of apoptotic lymphocytes and whether some might completely lose their LAgs. The changes in the expression of CD3, CD5, CD8, CD4, CD28, CD56, and CD19 were monitored in highly purified lymphocyte populations obtained by negative selection in a fluorescence-activated cell sorter. These were cultured for 24 h with or without phytohemagglutinin or staurosporin. For each LAg-positive subset studied, apoptosis was consistently more common among cells showing partial or total loss of LAg expression compared with cells maintaining their initial LAg levels. The kinetics of expression loss was rapid for CD8, CD56, and CD28, and more than 80% of initial expression was lost in the early stages of apoptosis but was slower for CD3, CD5, and CD4. For CD3 and CD5, expression was dependent on the apoptotic stimulus used. It is interesting that loss of antigen expression was independent of cell size. This phenomenon was also found in nonmanipulated, highly pure CD19 B lymphocytes of peripheral blood mononuclear cells from B chronic lymphocytic leukemia patients. Loss of LAg expression appeared to be a common feature of apoptotic lymphocytes under all the conditions assayed. The different kinetic patterns of LAg loss suggest apoptotic cells might actively regulate this process.
I-TAC/CXCL11 is a natural antagonist for CCR5
Authors: Petkovic Vibor , Moghini Christian , Paoletti Samantha , Uguccioni Mariagrazia , Gerber Basil 
Published: June 2004

AbstractThe selective CXC chemokine receptor 3 (CXCR3) agonists, monokine induced by interferon-γ (IFN- γ)/CXC chemokine ligand 9 (CXCL9), IFN-inducible protein 10/CXCL10, and IFN-inducible T cell α chemoattractant (I-TAC)/CXCL11, attract CXCR3+ cells such as CD45RO+ T lymphocytes, B cells, and natural killer cells. Further, all three chemokines are potent, natural antagonists for chemokine receptor 3 (CCR3) and feature defensin-like, antimirobial activities. In this study, we show that I-TAC, in addition to these effects, acts as an antagonist for CCR5. I-TAC inhibited the binding of macrophage-inflammatory protein-1α (MIP-1α)/CC chemokine ligand 3 (CCL3) to cells transfected with CCR5 and to monocytes. Furthermore, cell migration evoked by regulated on activation, normal T expressed and secreted (RANTES)/CCL5 and MIP-1β/CCL4, the selective agonist of CCR5, was inhibited in transfected cells and monocytes, respectively. In two other functional assays, namely the release of free intracellular calcium and actin polymerization, I-TAC reduced CCR5 activities to minimal levels. Sequence and structure analyses indicate a potential role for K17, K49, and Q51 of I-TAC in CCR5 binding. Our results expand on the potential role of I-TAC as a negative modulator in leukocyte migration and activation, as I-TAC would specifically counteract the responses mediated by many “classical,” inflammatory chemokines that act not only via CCR3 but via CCR5 as well.
American Society of Clinical Oncology Recommendations for the Initial Hormonal Management of Androgen-Sensitive Metastatic, Recurrent, or Progressive Prostate Cancer
Authors: Loblaw D. Andrew , Mendelson David S. , Talcott James A. , Virgo Katherine S. , Somerfield Mark R. , Ben-Josef Edgar , Middleton Richard , Porterfield Henry , Sharp Stewart A. , Smith Thomas J. , Taplin Mary Ellen , Vogelzang Nicholas J. , Wade James L. , Bennett Charles L. , Scher Howard I. 
Published: June 2004

Purpose To develop a clinical practice guideline for the management of men with metastatic, recurrent, or progressive carcinoma of the prostate. The focus of this document is on the use, combinations, and timing of various forms of androgen deprivation therapy (ADT) for the palliation of men with androgen-sensitive disease. Methods An expert panel and writing committee were formed. The questions to be addressed by the guideline were determined, and a systematic review of the literature was performed, which included a search of online databases, bibliographic review, and consultation with content experts. A priori criteria were used to select studies for analysis and study authors were contacted when necessary. Results There were 10 randomized controlled trials, six systematic reviews, and one Markov model available to inform the guidelines. Conclusion A full discussion between practitioner and patient should occur to determine which therapy is best for the patient. Bilateral orchiectomy or luteinizing hormone releasing hormone agonists are the recommended initial treatments. Nonsteroidal antiandrogen therapy may be discussed as an alternative, but steroidal antiandrogens should not be offered as monotherapy. Patients willing to accept the increased toxicity of combined androgen blockage for a small benefit in survival should be offered nonsteroidal antiandrogen in addition to castrate therapy. Until data from studies using modern medical diagnostic/biochemical tests and standardized follow-up schedules become available, no specific recommendations can be issued regarding the question of early versus deferred ADT. A discussion about the pros and cons of early versus deferred ADT should occur.
Pyruvate Prevents Restraint-Induced Immunosuppression via Alterations in Glucocorticoid Responses
Authors: Neigh Gretchen N. , Bowers Stephanie L. , Pyter Leah M. , Gatien Michelle L. , Nelson Randy J. 
Published: June 2004

AbstractStress-evoked immunosuppression may reflect increased demands on cellular energy signaled via elevated glucocorticoid concentrations. We hypothesized that treatment with pyruvate, an alternative energy source, would ameliorate restraint-induced elevation of glucocorticoids and that this reduction in glucocorticoid exposure will prevent stress-induced immunosuppression. We provided exogenous pyruvate to mice exposed to repeated restraint and then assessed splenocyte counts and splenocyte proliferation in response to the mitogen, concanavalin A as well as IgM production in response to keyhole limpet hemocyanin. Immune function was suppressed in mice undergoing repeated restraint but not in mice exposed to repeated restraint followed by pyruvate treatment. All mice exposed to restraint, regardless of pyruvate supplementation, displayed equivalent occurrences of repeated elevations in corticosterone concentrations; however, the cumulative exposure to corticosterone after one episode of restraint was reduced in those mice treated with pyruvate after restraint. Finally, we tested the immunoprotective ability of pyruvate supplementation in the presence of chronically elevated corticosterone. Mice implanted with restraint-like concentrations of corticosterone after adrenalectomy decreased splenocyte counts, compared with either unmanipulated mice or mice that were implanted with a cholesterol pellet after adrenalectomy, regardless of pyruvate supplementation. These data suggest that pyruvate does not possess immunoprotective properties in the presence of chronically elevated corticosterone. Pyruvate supplementation preserves immune function during exposure to repeated restraint stressors; altered dynamics of corticosterone concentrations after pyruvate administration may mediate this immunoprotection. Pyruvate prevents restraint-induced immunosuppression via alterations in the glucocorticoid response to restraint.
Relationship Between MMR Vaccine and Autism
Authors: Klein Kristin C , Diehl Emily B 
Published: June 2004

OBJECTIVE: To evaluate the proposed link between the administration of the measles, mumps, and rubella (MMR) vaccine and the development of autism. DATA SOURCES: A literature search utilizing MEDLINE (1966–November 2003), with the key terms measles, mumps, rubella, and autism, was conducted. Review of the references listed in the articles identified was also performed. DATA SYNTHESIS: Ten articles that specifically evaluated the possible relationship between the MMR vaccine and autism were identified. Review articles, commentaries, and evaluations of a link between gastrointestinal symptoms in autistic children and MMR immunization were excluded. CONCLUSIONS: Based upon the current literature, it appears that there is no relationship between MMR vaccination and the development of autism.