bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fructose-1,6-biphosphate and nucleoside pool modifications prevent neutrophil accumulation in the reperfused intestine
Authors: Sola Anna , Panés Julián , Xaus Carme , Hotter Georgina 
Published: March 2003

Abstract
Fructose-1,6-biphosphate (F16BP) attenuates ischemia/reperfusion (I/R) injury by inhibiting microvascular leukocyte adhesion or reducing neutrophil-derived oxygen free-radical production, but the causes of this action, the mechanisms in vivo, and the possible implication of nucleoside pool modifications are still controversial issues. We explored whether F16BP’s inhibition of free-radical production and neutrophil recruitment is a result of its effect on adenosine (Ado) accumulation during intestinal I/R injury. The effects of F16BP administration were tested on the nucleotide/nucleoside metabolism at the end of the ischemic period and on microvascular neutrophil recruitment and free-radical production after reperfusion in vivo, in the presence or absence of Ado deaminase (ADA). Infusion of F16BP markedly increaed endogenous Ado, decreased xanthine accumulation during the ischemic period, and inhibited neutrophil recruitment and subsequent neutrophil free-radical generation during reperfusion. Administration of ADA reversed these processes. The results provide strong evidence that F16BP prevents neutrophil accumulation and neutrophil free-radical generation during intestinal I/R by a key mechanism that modifies the nucleoside pool, leading to an endogenous accumulation of Ado and to a reduction of xanthine during ischemia.
Interleukin-18
Authors: Gracie J Alastair , Robertson Susan E , McInnes Iain B 
Published: March 2003

Abstract
Interleukin-18 (IL-18), a recently described member of the IL-1 cytokine superfamily, is now recognized as an important regulator of innate and acquired immune responses. IL-18 is expressed at sites of chronic inflammation, in autoimmune diseases, in a variety of cancers, and in the context of numerous infectious diseases. This short review will describe the basic biology of IL-18 and thereafter address its potential effector and regulatory role in several human disease states including autoimmunity and infection. IL-18, previously known as interferon-γ (IFN-γ)-inducing factor, was identified as an endotoxin-induced serum factor that stimulated IFN-γ production by murine splenocytes [1]. IL-18 was cloned from a murine liver cell cDNA library generated from animals primed with heat-killed Propionibacterium acnes and subsequently challenged with lipopolysaccharide [2]. Nucleotide sequencing of murine IL-18 predicted a precursor polypeptide of 192 amino acids lacking a conventional signal peptide and a mature protein of 157 amino acids. Subsequent cloning of human IL-18 cDNA revealed 65% homology with murine IL-18 [3] and showed that both contain n unusual leader sequence consisting of 35 amino acids at their N terminus.
Possible contribution of apoptosis-inducing factor (AIF) and reactive oxygen species (ROS) to UVB-induced caspase-independent cell death in the T cell line Jurkat
Authors: Murahashi Hideaki , Azuma Hiroshi , Zamzami Naoufal , Furuya Ko-ji , Ikebuchi Kenji , Yamaguchi Miki , Yamada Yoshiko , Sato Norihiro , Fujihara Mitsuhiro , Kroemer Guido , Ikeda Hisami 
Published: March 2003

Abstract
We analyzed the mechanism of UVB-induced cell death using the Jurkat T cell line. Apoptosis was assessed by measuring phosphatidylserine (PS) externalization, caspase activity, the decrease in mitochondrial membrane potential (ΔΨm), nucleosomal DNA fragmentation, and morphological changes such as chromatin condensation. The mitochondrio-nuclear translocation of apoptosis-inducing factor (AIF) was evaluated by confocal laser microscopy. The cell death pattern of UVB-irradiated cells was similar to the Fas-induced cell death pattern. However, zVAD-fmk inhibited the nucleosomal fragmentation of DNA but not the externalization of PS, decrease in ΔΨm, or mitochondrio-nuclear translocation of AIF. N-acetyl L-cysteine significantly inhibited the translocation of AIF induced by UVB. These results suggested that caspase-dependent and -independent pathways were involved in UVB-induced cell death in Jurkat cells, and the mitochondrio-nuclear translocation of AIF was associated with the latter pathway. In addition, reactive oxygen species generated by UVB might be involved in inducing the mitochondrio-nuclear translocation of AIF.
Accessibility control and machinery of immunoglobulin class switch recombination
Authors: Zhang Ke 
Published: March 2003

Abstract
Immunoglobulin (Ig) class switching is a process by which B lymphocytes shift from production of IgM to other Ig classes and subclasses via Ig class switch recombination (CSR). Multiple cellular and molecular processes are involved in CSR. Induction of a given IgH germline transcription initiates CSR processes. Ig germline transcription is selectively activated and induced by specific cytokine(s) via cytokine-specific signal pathways, synergized by CD40 signaling, and optimized by the 3′ Igα enhancers through locus control region function. Following Ig germline transcription, the switch-region DNA undergoes conformational changes so that it can serve as an appropriate substrate for nicking and cleavage by switch recombination machinery. Finally, the double-strand breaks in donor and acceptor switch DNAs are processed, repaired, and ligated through a general nonhomologous end join pathway. CSR generates a new transcriptional unit for production of a class-switched Ig isotype.
M-CSF induced differentiation of myeloid precursor cells involves activation of PKC-δ and expression of Pkare
Authors: Junttila Ilkka , Bourette Roland P , Rohrschneider Larry R , Silvennoinen Olli 
Published: March 2003

Abstract
Macrophage-colony stimulating factor (M-CSF) regulates proliferation and differentiation of cells belonging to the monocytic lineage. We investigated the mechanisms of M-CSF differentiation signaling in follicular dendritic cell-P1 cells and analyzed the catalytic activation of different protein kinase C (PKC) isoforms. M-CSF induced rapid catalytic activation of PKC-δ and membrane transocation of the tyrosine phosphorylated form of PKC-δ. Mutation of tyrosine 807 in the M-CSF receptor (Fms) abrogates cell differentiation but not a proliferative response to M-CSF, and FmsY807F failed to activate PKC-δ. We also investigated the downstream signaling pathways from PKC-δ. A cyclic adenosine monophosphate-regulated Ser/Thr kinase gene, protein kinase X (PRKX), has been associated with macrophage differentiation in human cells. We found that M-CSF and PKC-δ induced the expression of the PRKX murine homologue: PKA-related gene. Taken together, our results indicate that PKC-δ functions as a critical mediator of M-CSF-induced differentiation signaling.
Telomere shortening in leukocyte subpopulations from baboons
Authors: Baerlocher Gabriela M , Mak Jennifer , Röth Alexander , Rice Karen S , Lansdorp Peter M 
Published: March 2003

Abstract
To address questions about telomere length regulation in nonhuman primates, we studied the telomere length in subpopulations of leukocytes from the peripheral blood of baboons aged 0.2–26.5 years. Telomere length in granulocytes, B cells, and subpopulations of T cells all decreased with age. Overall, telomere length kinetics were lineage- and cell subset-specific. T cells showed the most pronounced, overall decline in elomere length. Levels of telomerase in stimulated T cells from old animals were lower than in corresponding cells from young animals. Memory T cells with very short telomeres accumulated in old animals. In contrast, the average telomere length values in B cells remained relatively constant from middle age onward. Individual B cells showed highly variable telomere length, and B cells with very long telomeres were observed after the ages of 1–2 years. In general, cell type-specific telomere kinetics in baboons were remarkably similar to those observed in humans.
Short cytoplasmic SDYMNM segment of CD28 is sufficient to convert CTLA-4 to a positive signaling receptor
Authors: Yin Li , Schneider Helga , Rudd Christopher E 
Published: March 2003

Abstract
CD28 and cytotoxic T-lymphocyte antigen (CTLA)-4 are key coreceptors on the surface of T cells that have opposing effects on T cell activation. Although CD28 enhances proliferation, CTLA-4 markedly inhibits the activation process. These opposing roles are particularly surprising given the structural similarity of the cytoplasmic residues of the two receptors. These include the related CD28SDYMNM and CTLA-4GVYVKM motifs. In this study, we have directly addressed whether these related motifs may play different roles in the activation process by swapping the CTLA-4GVYVKM motif with the CD28SDYMNM motif. Remarkably, stable transfectants of the T cell hybridoma DC27.10 showed that substitution of CTLA-4GVYVKM was sufficient to convert CTLA-4 from a negative signaling coreceptor to a positive CD28-like coreceptr. CD28SDYMNM is therefore sufficient to convey positive signals within CTLA-4. These results demonstrate that CD28SDYMNM and CTLA-4GVYVKM motifs contain sufficient information to distinguish positive versus negative coreceptor signaling in T cells.
Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit the production of inflammatory mediators by activated microglia
Authors: Delgado Mario , Leceta Javier , Ganea Doina 
Published: March 2003

Abstract
Microglia play a central role in the regulation of immune and inflammatory activities, as well as tissue remodeling in the central nervous system. However, activation of microglia is a histopathological hallmark of several neurodegenerative diseases. Pathological microglial activation is believed to contribute to progressive damage in neurodegenerative diseases through the release of proinflammatory and/or cytotoxic factors, including tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, IL-12, and nitric oxide (NO). Hence, it is important to unravel mechanisms regulating microglia activation of inflamed brain parenchyma to provide insights into efficient therapeutic intervention. This study examines the role of two anti-inflammatory neuropeptides, the vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase-activating polypeptide (PACAP) on the production of various proinflammatory factors by endotoxin-stimulated miroglia. VIP and PACAP inhibit TNF-α, IL-1β, IL-6, and NO production by lipopolysaccharide (LPS)-activated microglia. The specific type 1 VIP receptor mediates the inhibitory effect of VIP/PACAP, and cyclic adenosine monophosphate is the major, second messenger involved. VIP and PACAP regulate the production of these proinflammatory factors at a transcriptional level by inhibiting p65 nuclear translocation and nuclear factor-κB-DNA binding. This effect is mediated, as neuropeptides stabilize the inhibitor IκB by inhibiting LPS-induced IκB-kinase activity. Therefore, the inhibitory effects on the production of proinflammatory mediators define VIP and PACAP as “microglia-deactivating factors” with significant, therapeutical potential for inflammatory/degenerative brain disorders.
Adherence influences monocyte responsiveness to interleukin-10
Authors: Petit-Bertron Anne-France , Fitting Catherine , Cavaillon Jean-Marc , Adib-Conquy Minou 
Published: March 2003

Abstract
We studied the effects of adherence on the properties of interleukin (IL)-10 on monocyte-enriched peripheral blood mononuclear cells. We found that the decrease of CD11b expression induced by IL-10 was enhanced by adherence. Toll-like receptor (TLR)2 and TLR4 mRNA, as well as TLR4 surface expression, were significantly up-regulated by IL-10 in adherent cells. The absence of adherence prevented the inhibitory effects of IL-10 on lipopolysaccharide-induced tumor necrosis factor (TNF) and granulocyte-colony stimulating factor production and increased IL-1β production and soluble TNF receptor II release in IL-10-pretreated cells. Similarly, the absence of adherence amplified the enhancement of phagocytosis induced by IL-10. Tyk2 and signal transducer and activator of transcription 3 (STAT3) phosphorylation and suppressr of cytokine signaling 3 (SOCS3) expression were induced by IL-10 in both conditions, but a longer activation and/or expression were observed in adherent monocytes. Finally, heme oxygenase-1, an anti-inflammatory molecule, was induced by IL-10 in adherent monocytes, whereas its expression remained low in nonadherent cells. Altogether, these data illustrate that adherence modulates the properties and the anti-inflammatory effects of IL-10.
The improved survival of hematopoietic cells cultured with a fusion protein of insulin-like growth factor II (IGF-II) and interleukin 3 (IL-3) is associated with increases in Bcl-xL and phosphatidylinositol-3 kinase activity
Authors: DiFalco Marcos R , Ali Suhad , Congote Luis Fernando 
Published: March 2003

Abstract
We compared the antiapoptotic activity of a recombinant chimera of insulin-like growth factor II (IGF-II) and interleukin (IL)-3 with the corresponding equimolar mixture of the individual components based on changes in several factors associated with survival in the CD34+ human hematopoietic cell line TF-1. Propidium iodide-stained cells analyzed by fluorescein-activated cell sorter indicated that the chimera was more effective than the corresponding equimolar mixture in decreasing the amounts of apoptotic cells and increasing the proportion of cells in the S-phase of the cell cycle. The chimera was more effective in increasing the antiapoptotic protein BclxL and produced a significant increase in signal transducer and activator of transcription-5 posphorylation and in phosphatidylinositol-3 kinase (PI-3K) activity. The PI-3K inhibitor LY294002 specifically inhibited cell survival in the presence of the chimera, suggesting a key role of this enzyme in the potentiation of survival caused by the linkage of IGF and IL-3. This potentiation of survival and its preferential inhibition by LY294002 were also observed in a nontransformed, primary culture of human umbilical cord endothelial cells.
Inhibition of actin polymerization by peroxynitrite modulates neutrophil functional responses
Authors: Clements Mark K , Siemsen Daniel W , Swain Steve D , Hanson Angela J , Nelson-Overton Laura K , Rohn Troy T , Quinn Mark T 
Published: March 2003

Abstract
Peroxynitrite, a potent oxidant generated in inflammatory tissues, can nitrate tyrosine residues on a variety of proteins. Based on previous studies suggesting that actin might be a potential target for peroxynitrite-mediated nitration in neutrophils, we investigated the effects of peroxynitrite on actin function. We show here that peroxynitrite and the peroxynitrite generator (SIN-1) modified actin in a concentration-dependent manner, resulting in an inhibition of globular-actin polymerization and filamentous-actin depolymerization in vitro. The effects of peroxynitrite were inhibited by the pyrrolopyrimidine antioxidant PNU-101033E, which has been shown previously to specifically block peroxynitrite-mediated tyrosine nitration. Furthermore, spectrophotometric and immunoblot analysis of peroxynitrite-treated actin demonstrated a concentration-dependent increase in nitrotyrosine, which was also blocked by PNU-101033E. Activation of neutrophils in the presence of a nitric oxide donor (S-nitroso-N-acetylpenicillamine) resulted in nitration of exogenously added actin. Nitrated actin was also found in peroxynitrite-treated neutrophils, suggesting that actin may be an important intracellular target during inflammation. To investigate this issue, we analyzed the effect of peroxynitrite treatment on a number of actin-dependent neutrophil processes. Indeed, neutrophil actin polymerization, migration, phagocytosis, and respiratory burst activity were all inhibited by SIN-1 treatment in a concentration-dependent manner. Therefore, the ability of peroxynitrite to inhibit actin dynamics has a significant effect on actin-dependent, cellular processes in phagocytic cells and may modulate their host defense function.
Alerting and tuning the immune response by extracellular nucleotides
Authors: la Sala Andrea , Ferrari Davide , Di Virgilio Francesco , Idzko Marco , Norgauer Johannes , Girolomoni Giampiero 
Published: March 2003

Abstract
The interplay between pro- and anti-inflammatory mechanisms during inflammatory and immune responses is critical for avoiding excessive tissue damage. Extracellular nucleotides (e.g., adenosine 5′-triphosphate) may represent constitutive signals that can alert the immune system of abnormal cell death. Relatively high doses of nucleotides induce rapid release of proinflammatory mediators and favor pathogen killing. However, recent findings on antigen presenting cells, particularly dendritic cells, revealed a more complex role for these molecules. Chronic exposure to low-dose nucleotides can redirect cellular responses to prototypic activation stimuli, leading to suppressed inflammation and immune deviation.
Dysregulation of transcriptions in primary granule constituents during myeloid proliferation and differentiation in patients with severe congenital neutropenia
Authors: Kawaguchi Hiroshi , Kobayashi Masao , Nakamura Kazuhiro , Konishi Nakao , Miyagawa Shin-ichiro , Sato Takashi , Toyoda Hidemi , Komada Yoshihiro , Kojima Seiji , Todoroki Yukiko , Ueda Kazuhiro , Katoh Osamu 
Published: March 2003

Abstract
We examined the expression of granule constituent genes in myeloid progenitor cells during proliferation and differentiation in patients with severe congenital neutropenia (SCN). The heterozygous mutation of the neutrophil elastase gene was identified in two of four patients. The CD34+/granulocyte-colony stimulating factor receptor (G-CSFR)+ cells of SCN patients showed defective responsiveness to G-CSF in serum-deprived culture. The CD34+/G-CSFR+ cells expressed low levels of the granule constituent mRNAs. The transcription levels of primary granule enzyme genes in CD34+/G-CSFR+ cells were gradually enhanced and then decreased when cells were induced toward myeloid lineage with G-CSF in normal subjects. However, the primary up-regulation and the following down-regulation of these enzyme transcriptions were not clearly observed in SCN patients. No differences in expressions of the lactoferrin gene were seen between normal subjects and patients with SCN. We hypothesize that the abnormal regulation of the transcription in primary granule constituents might involve the defective proliferation and differentiation of myeloid cells in patients with SCN.
OX52 is the rat homologue of CD6: evidence for an effector function in the regulation of CD5 phosphorylation
Authors: Castro Mónica A A , Nunes Raquel J , Oliveira Marta I , Tavares Paula A , Simões Carla , Parnes Jane R , Moreira Alexandra , Carmo Alexandre M 
Published: March 2003

Abstract
The MRC OX52 monoclonal antibody is a marker of rat T lymphocytes. We have cloned by polymerasechain reaction the rat homologue of CD6, and fluorescein-activated cell sorter analysis and immunoprecipitations using OX52 in COS7 cells transfected with rat CD6 cDNA showed that CD6 is the cell-surface molecule recognized by OX52. Immunoprecipitation analysis showed that CD6 coprecipitated with CD5, which in turn, was coprecipitated equivalently with CD2, CD6, and the T cell receptor (TCR), but the fraction of CD5 associated with CD6 was highly phosphorylated in kinase assays, in marked contrast with the low level of phosphorylation of CD5 associated with TCR or CD2. Examination of protein kinases associating with these antigens showed that paradoxically, CD2 coprecipitated the highest amount of Lck and Fyn. CD6 also associated with Lck, Fyn, and ZAP-70, although at lower levels but additionally coprecipitated the Tec family kinase Itk, which is absent from CD2, CD5, and TCR complexes. Lck together with Itk was the best combination of kinases, effectively phosphorylating synthetic peptides corresponding to a cytoplasmic sequence of CD5. Overall, our results suggest that CD6 has an important role in the regulation of CD5 tyrosine phosphorylation, probably as a result of its unique feature of associating with kinases of different families.
Toxicity of human monocytic THP-1 cells and microglia toward SH-SY5Y neuroblastoma cells is reduced by inhibitors of 5-lipoxygenase and its activating protein FLAP
Authors: Klegeris Andis , McGeer Patrick L 
Published: March 2003

Abstract
To explore whether the proinflammatory products of the 5-lipoxygenase (5-LOX) pathway are involved in microglia-mediated toxicity toward neuronal cells, we evaluated the effects of 5-LOX inhibitors using an in vitro assay system where human neuronal SH-SY5Y cells are exposed to toxic secretions from THP-1 monocytic cells or human microglia. The specific 5-LOX inhibitors, REV 5901, zileuton, and 5-hydroxyeicosatetraenoic acid lactone; the nonselective LOX inhibitors, phenidone and dapsone; the dual 5-LOX/cyclooxygenase inhibitor, tepoxalin; and the selective inhibitor of the 5-LOX-activating protein (FLAP), MK-886, inhibited such toxicity. The toxicity was enhanced by the 5-LOX product leukotriene (LT)D4 and reduced by the selective cysteinyl LT receptor (CysLT1) antagonist MK-571. The mRNAs for 5-LOX and FLAP were detected in THP-1 cells and human microglia but not in SH-SY5Y cells. The data suggest that inhibition of proinflammatory LT production by 5-LOX inhibition could selectively reduce toxicity of microglial cells and thus be beneficial in neuroinflammatory diseases.
Is This Woman Perimenopausal?
Authors: Bastian Lori A. , Smith Crystal M. , Nanda Kavita 
Published: March 2003

ContextPerimenopause is a time of transition for women at midlife. Women want to know whether they are starting this change and physicians need to know the accuracy of a clinical examination in identifying perimenopausal women.These women should be counseled about alleviating climacteric symptoms, using contraception, and preventing diseases such as osteoporosis.ObjectiveTo systematically review the accuracy of self-assessment, symptoms, signs, and laboratory tests in diagnosing women in perimenopause.Data SourcesEnglish-language articles that presented data relevant to diagnosis of perimenopause were identified in a MEDLINE search from 1966 to 2001. References of these articles and other publications also were reviewed.Study SelectionCross-sectional or longitudinal studies of women aged 40 years or older that used the definition of perimenopause as 3 to 11 months of amenorrhea or irregular periods, included a premenopausal control group, and reported a clinical examination finding. Of 1246 articles identified, 16 studies were included in the analysis.Data ExtractionTwo authors independently reviewed articles for quality (L.A.B. and C.M.S.). Discrepancies were resolved by a third author (K.N.).Data SynthesisThe prior probability of perimenopause is directly related to a woman's age. After considering age, the following yielded the greatest positive likelihood ratios (LRs+): self assessment of going through the transition (LR+ range, 1.53-2.13), symptoms of hot flashes (LR+ range, 2.15-4.06), night sweats (LR+ 1.90; 95% confidence interval [CI], 1.63-2.21), vaginal dryness (LR+ range, 1.48-3.79), high follicle-stimulating hormone levels (LR+ 3.06; 95% CI, 2.06-4.54), and low inhibin B levels (LR+ 2.05; 95% CI, 0.96-4.39). Self-assessment of perimenopausal status had the smallest negative LR (range, 0.18-0.36).ConclusionsNo one symptom or test is accurate enough by itself to rule in or rule out perimenopause. Clinicians should diagnose perimenopause based on menstrual history and age without relying on laboratory test results.