bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current status of lymph node‐positive prostate cancer
Authors: Swanson Gregory P. , Thompson Ian M. , Basler Joseph 
Published: June 2006

AbstractIn early surgical series, the incidence of positive lymph nodes in patients with prostate cancer was approximately 40%. In the modern era of screening and improved patient selection, the incidence is now <10%, although most series excluded patients with higher risk disease. The risk of having positive lymph nodes is influenced by disease stage, prostate‐specific antigen level, and tumor grade and by the aggressiveness of lymph node dissection. Many of the same factors predict the outcome of these patients. Although the percentage of patients with positive lymph nodes has declined, there remain significant numbers of patients with lymph node‐positive prostate cancer, and it remains a therapeutic dilemma. Cancer 2006. © 2006 American Cancer Society.
The chemokine receptor CCX‐CKR mediates effective scavenging of CCL19 in vitro
Authors: Comerford Iain , Milasta Sandra , Morrow Valerie , Milligan Graeme , Nibbs Robert 
Published: June 2006

AbstractThe chemokines CCL19, CCL21 and CCL25, by signalling through the receptors CCR7 or CCR9, play critical roles in leukocyte homing. They also bind another heptahelical surface protein, CCX‐CKR. CCX‐CKR cannot couple to typical chemokine receptor signalling pathways or mediate chemotaxis, and its function remains unclear. We have proposed that it controls chemokine bioavailability. Here, using transfected HEK293 cells, we have shown that both CCX‐CKR and CCR7 mediate rapid CCL19 internalisation upon initial chemokine exposure. However, internalised CCL19 was more efficiently retained and degraded after uptake via CCX‐CKR. More importantly, CCR7 rapidly became refractory for CCL19 uptake, but the sequestration activity of CCX‐CKR was enhanced. These properties endowed CCX‐CKR with an impressive ability to mediate progressive sequestration and degradation of large quantities of CCL19, and conversely, prevented CCR7‐expressing cells from extensively altering their chemokine environment. These differences may be linked to the routes of endocytosis used by these receptors. CCX‐CKR, unlike CCR7, was not critically dependent on β‐arrestins or clathrin‐coated pits. However, over‐expression of caveolin‐1, which stabilises caveolae, blocked CCL19 uptake by CCX‐CKR while having no impact on other chemokine receptors, including CCR7. These data predict that CCX‐CKR scavenges extracellular chemokines in vivo to modify responses through CCR7.See accompanying commentary: http://dx.doi.org/10.1002/eji.200636327
Duration of CTL activation regulates IL‐2 production required for autonomous clonal expansion
Authors: Spierings Diana C. J. , Lemmens Edward E. , Grewal Kirpal , Schoenberger Stephen P. , Green Douglas R. 
Published: June 2006

AbstractThe extent and magnitude of CD8+ T lymphocyte (CTL) clonal expansion in vivo depends on the duration of stimulation provided during primary activation, whereas expansion under conventional in vitro conditions fails to reveal this. The molecular details of this differential programming are unclear. We developed a low‐density culture system that recapitulates in vivo conditions and enables analysis of both proliferation and survival/apoptosis during primary expansion. We found that CTL given a prolonged stimulus produced more IL‐2 and for a longer period than briefly activated CTL, and the IL‐2 produced during the expansion phase was essential for cell proliferation and accumulation at low densities. CTL given a short stimulation and plated at low density followed the fate of briefly stimulated cells in vivo and underwent an abortive expansion and apoptosis, unless IL‐2 was exogenously provided. Inhibition of apoptosis did not replace the requirement for IL‐2 to drive clonal expansion. CTL primed for prolonged periods but in the absence of costimulation similarly behaved as though “partially programmed”, undergoing abortive expansion at low densities. These results indicate that the nature and duration of antigenic stimulation regulate the autonomy of CTL expansion via the production of autocrine IL‐2.
Distinct roles for IL‐6 and IL‐12p40 in mediating protection against Leishmania donovani and the expansion of IL‐10+ CD4+ T cells
Authors: Stäger Simona , Maroof Asher , Zubairi Soombul , Sanos Stephanie L. , Kopf Manfred , Kaye Paul M. 
Published: June 2006

AbstractAdoptive dendritic cell (DC) immunotherapy provides a useful experimental tool to evaluate immunoregulation in vivo and has previously been successfully used to enhance host resistance in a variety of experimental models of leishmaniasis. Here, we used this approach to identify IL‐6 and IL‐12p40 as critical cytokines that cooperate to mediate host protection to Leishmania donovani but which act independently to regulate expansion of IL‐10+ CD4+ T cells, shown here for the first time to be associated with this infection. Adoptive transfer of LPS‐activated bone marrow‐derived DC (BMDC) from wild‐type mice was therapeutically beneficial and led to enhanced resistance as measured by spleen parasite burden. In contrast, IL‐6‐ or IL‐12p40‐deficient BMDC had no protective benefit, indicating that production of both cytokines was essential for the therapeutic efficacy of DC. IL‐10 production by CD25– FoxP3– IL‐10+ CD4+ T cells is a strong correlate of disease progression, and BMDC from wild‐type mice inhibited expansion of these cells. Strikingly, IL‐12‐deficient BMDC could also inhibit the expansion of this T cell population whereas IL‐6‐deficient BMDC could not, indicating that IL‐6 played a key role in this aspect of DC function in vivo. Breadth of cytokine production is thus an important factor when considering strategies for DC‐based interventions.
Src kinase Lyn is crucial for Pseudomonas aeruginosa internalization into lung cells
Authors: Kannan Shibichakravarthy , Audet Aaron , Knittel Jessica , Mullegama Saman , Gao George F. , Wu Min 
Published: June 2006

AbstractLyn is an important B cell signaling kinase of the Src tyrosine kinase family with a broad range of functions from cytoskeletal changes to induction of apoptosis. However, the role of Lyn in infectious diseases is not clear. Here, we demonstrate that Lyn activation by phosphorylation significantly impacted invasion of an alveolar epithelial cell line, primary lung cells, and rat lungs by Pseudomonas aeruginosa (PA), a common opportunistic lung pathogen affecting individuals with deficient lung immunity. Our results indicate that activation of Lyn and its interaction with rafts and TLR2, played an important role in the initial stages of PA interaction with host cells. The role of Lyn was further evaluated using the pharmacologic Src‐specific inhibitor PP2, a dominant negative mutant, and finally confirmed with Lyn‐deficient (Lyn–/–) bone marrow‐derived mast cells. Inhibition of Lyn's function by above approaches prevented PA internalization. Moreover, blocking of Lyn also affected downstream events: induction of inflammatory cytokines and apoptosis. This report brings out a new role of Lyn in infectious diseases and indicates potential new targets for prevention and treatment of infections.
Follicular B helper T cell activity is confined to CXCR5hiICOShi CD4 T cells and is independent of CD57 expression
Authors: Rasheed Ata‐Ur , Rahn Hans‐Peter , Sallusto Federica , Lipp Martin , Müller Gerd 
Published: June 2006

AbstractThe generation of high‐affinity antibody‐secreting plasma cells critically depends on the presence of CD4 T cells during the germinal center (GC) reaction. GC T cells are so far incompletely characterized in terms of phenotype and function. Here, we show that human follicular B helper T (TFH) cells are characterized by high expression of the homeostatic chemokine receptor CXCR5 and the costimulatory molecule ICOS, but not CD57 expression. CXCR5hiICOShi CD4 T cells are the most potent inducers of IgG production that also secrete large amounts of the B cell‐attracting chemokine CXCL13. CXCR5hiICOShi CD4 T cells differ from other tonsillar CD4 T cell subsets in their stimulatory activity, proliferative capacity and susceptibility to apoptosis. Large‐scale gene expression analysis revealed that TFH cells are only distantly related to CXCR5– and CXCR5+ central memory T (TCM) as well as effector memory T (TEM) cells present in the periphery. CXCR5hiICOShi CD4 T cells appear to be terminally differentiated T helper cells that express a unique set of transcription factors related to the Notch signaling pathway and thus differentiate independent of other T helper cell populations.See accompanying commentary: http://dx.doi.org/10.1002/eji.200636334
How T lymphocytes switch between life and death
Authors: Arnold Rüdiger , Brenner Dirk , Becker Mareike , Frey Christian R. , Krammer Peter H. 
Published: June 2006

AbstractWhile insufficient cell death of activated T cells can result in autoimmune disorders, elimination of too many T cells can lead to immunodeficiency. Therefore, T lymphocyte fate is highly regulated and requires that cells can switch from an apoptosis‐resistant towards an apoptosis‐sensitive state. This switch is tightly controlled by various effector molecules. Basically, two separate pathways control the fate of antigen‐activated T cells: activation‐induced cell death (AICD) and activated T cell autonomous death (ACAD). Autoreactive T lymphocytes are eliminated by restimulation via their T cell receptor (TCR) and undergo AICD involving death receptors (extrinsic pathway). In contrast, ACAD can lead to T cell deletion without TCR restimulation, and is determined by the ratio between anti‐ and pro‐apoptotic Bcl‐2 family members at the mitochondria (intrinsic pathway). While the extrinsic and the intrinsic pathway lead to caspase activation, non‐caspase proteases (e.g., cathepsins) can be released by the lysosomes and might contribute to AICD as well as to ACAD. Activated T cells posses cell death escape mechanisms which are needed for survival of (memory) T cells, but are deleterious for autoimmune disorders or progression of T cell lymphomas.
DNA damage and acute toxicity caused by the urban air pollutant 3‐nitrobenzanthrone in rats; Characterization of DNA adducts in eight different tissues and organs with synthesized standards
Authors: Nagy Eszter , Adachi Shuichi , Takamura‐Enya Takeji , Zeisig Magnus , Möller Lennart 
Published: June 2006

Abstract3‐Nitrobenzanthrone (3‐NBA) is an urban air pollutant and rat lung carcinogen that is among the most potent mutagens yet tested in the Salmonella reversion assay. In the present study, 1 mg 3‐NBA was administered orally to female F344 rats and DNA adduct formation was examined in liver, lung, kidney and five sections of the gastrointestinal (GI) tract at 6 hr, and 1, 2, 3, 5, and 10 days after administration. The DNA adduct patterns, analyzed by 32P‐postlabelling followed by HPLC separation, were similar in all tissues and organs. Five of the adduct peaks cochromatographed with synthesized DNA adduct standards. Three of these unequivocally determined standards, dGp‐C8‐N‐ABA, dGp‐N2‐C2‐ABA, and dAp‐N6‐C2‐ABA, were of the nonacetylated type, suggesting that at least part of the pathway for activation of 3‐NBA proceeds through O‐acetylation of the hydroxylamine intermediate. The two other DNA adduct standards, dGp‐C8‐C2‐N‐Ac‐ABA, and dGp‐N2‐C2‐N‐Ac‐ABA, were of the acetylated type, but there was some ambiguity in the characterization of these DNA adducts, since they varied inconsistently between samples and they also aligned with peaks found in controls. At 6 hr after treatment, the level of DNA adducts was highest in glandular stomach (relative adduct labeling (RAL), ∼70 adducts/108 normal nucleotides (NN)); adduct levels in this organ decreased at 24 hr, but increased afterwards. DNA adduct levels in the majority of organs were characterized by an early increase (from 6 hr to 3 days), which was followed by a decrease at 5 days and a maximum level 10 days after administration (RAL ∼120 adducts/108 NN for the lung, kidney and glandular stomach, ∼80 adducts/108 NN for the forestomach and ceacum, and ∼40 adducts/108 NN for the liver, small intestine, and colon). This pattern was consistent with pathological observations during autopsy showing high levels of tissue damage in the GI tract; the tissue damage included hemorrhages, loss of villous surface structure in the small intestine, as well as intestine fragility and oedema of the adipose tissue around the GI‐tract. Tissue damage decreased and DNA adduct levels increased at 10 days after administration. These observations suggest that 3‐NBA not only exerts acute toxic effects, but that the bioavailability is affected by storage in tissues and later becomes available, resulting in the increased DNA adduct levels at the later time points of collection. Environ. Mol. Mutagen., 2006. © 2006 Wiley‐Liss, Inc.
Urinary concentrations of bisphenol A in relation to biomarkers of sensitivity and effect and endocrine‐related health effects
Authors: Yang Mihi , Kim Soo‐Young , Chang Seong‐Sil , Lee In‐Seon , Kawamoto Toshihiro 
Published: June 2006

AbstractThe impact of endocrine‐disrupting chemicals (EDCs) on human health is not yet clear because of difficulties in ascertaining their biological effects. In the present study, we evaluated exposure to the EDC, bisphenol A (BPA), in 172 Koreans in relation to biomarkers of susceptibility and effect. The subjects completed questionnaires, which documented occupation, education, lifestyle factors, potential sources of BPA‐exposure, and the occurrence of self‐diagnosed endocrine disorders. None of the subjects were occupationallay exposed to BPA; however, urinary levels of conjugated BPA, determined by HPLC/FD, ranged from 0.03–62.4 μg/l (median, 7.86). The frequencies of potential susceptibility biomarkers, theUGT1A6‐Arg184Ser and theSULT1A1‐Arg213His polymorphisms, were not associated with urinary BPA levels, either as single genes or in combination. Indirect effects of BPA exposure on the susceptibility to mutagens were evaluated by comparing urinary BPA concentrations with MNNG‐induced sister‐chromatid exchange (SCE) in lymphocytes cultured from the subjects. BPA exposure showed marginal or significant associations with theSCEs induced by the low doses of MNNG (0–0.4 mM). However, there was no overall association between urinary BPA levels and MNNG‐induced frequency at doses ranging from 0.2–0.6 mM. Finally, we did not detect an association between urinary BPA concentration and endocrine‐related disorders. Even though we were unable to find a strong association between BPA exposure and a biological response, possibly because of the limited number of subjects, we observed that most of the subjects were exposed to BPA. Therefore, continuous biological monitoring of BPA is a prudent measure to prevent possible BPA‐related health risks. Environ. Mol. Mutagen., 2006. © 2006 Wiley‐Liss, Inc.
Influence of the SCGE protocol on the amount of basal DNA damage detected in the Mediterranean mussel, Mytilus galloprovincialis
Authors: Machella Nicola , Battino Maurizio , Pisanelli Barbara , Regoli Francesco 
Published: June 2006

AbstractGenotoxicity studies using the single cell gel electrophoresis (SCGE) assay indicate that basal levels of DNA strand breaks (SBs) in marine invertebrates are higher and more variable than those in marine vertebrates. This elevated level of DNA damage was attributed to a large number of alkali‐labile sites, which are characteristic of the tightly‐packaged DNA in invertebrate cells. To investigate if altering the SCGE protocol can artificially modulate high levels of SBs, SCGE experiments were performed on haemocytes from the Mediterranean mussel (Mytilus galloprovincialis) using proteinase K (PK) digestion in combination with assay buffers containing various concentrations of EDTA. In addition, the effects of Trolox® (soluble antioxidant) and aurintricarboxylic acid (ATA; inhibitor of Ca2+/Mg2+‐dependent nucleases) also were tested. The levels of SBs in M. galloprovicialis cells were compared with SBs in cells from a terrestrial mollusk (the snail Helix aspersa), and a teleost fish (the seabass Dicentrarchus labrax). The integrity of M. galloprovincialis DNA isolated with phenol extractions using EDTA, Trolox, and ATA was further assayed by gel electrophoresis. High SBs in mussel cells were reduced by combining EDTA with PK digestion, or using Trolox® or ATA during cell processing for the SCGE assay. Snails and seabass had lower levels of SBs in the SCGE assay, and the levels were not affected by the protocol modifications. Adding EDTA, Trolox®, or ATA to phenol extractions of M. galloprovincialis genomic DNA also reduced the extent of DNA fragmentation. These results suggest that the internal fluids of M. galloprovincialis may increase the basal levels of DNA SBs through oxidative and/or enzyme‐mediated pathways. M. galloprovincialis is used extensively as a sentinel species for assessing the genotoxic hazard of marine pollutants. Our data suggest that the SCGE protocol should be carefully considered when assessing DNA damage in these species. Environ. Mol. Mutagen., 2006. © 2006 Wiley‐Liss, Inc.
Potential New Solid Oxide Fuel Cell (SOFC) Anode Materials in the La‐Ca‐Cr‐Ti‐Ru‐O System
Authors: Vashook V. , Zosel J. , Müller R. , Shuk P. , Vasylechko L. , Ullmann H. , Guth U. 
Published: June 2006

AbstractSix single phase La1–xCaxCr1–yTiy–γRuγO3–δ (x = 0.1, 0.2, y = 1.0, 0.8 and γ = 0.0, 0.1, 0.2) compositions are prepared by solid state reaction. Oxygen non‐stoichiometry, electrical conductivity, catalytic activity, and electrochemical efficiency of these compositions is investigated over a wide temperature and oxygen partial pressure range. The compositions with the highest electrical conductivity (50 S cm–1) at reducing conditions and highest catalytic activity for the oxidation of hydrocarbons are found. A combination of highly conductive La1–xCaxTiO3–δ in a reducing atmosphere and an intermediate functional film of catalytically active La0.1Ca0.9Ti1–xRuxO3–δ for the oxidation of hydrocarbons could potentially be very useful in a multilayer SOFC anode.
Overexpression of caveolin‐1 results in increased plasma membrane targeting of glycolytic enzymes: The structural basis for a membrane associated metabolic compartment
Authors: Raikar Leena S. , Vallejo Johana , Lloyd Pamela G. , Hardin Christopher D. 
Published: June 2006

AbstractAlthough membrane‐associated glycolysis has been observed in a variety of cell types, the mechanism of localization of glycolytic enzymes to the plasma membrane is not known. We hypothesized that caveolin‐1 (CAV‐1) serves as a scaffolding protein for glycolytic enzymes and may play a role in the organization of cell metabolism. To test this hypothesis, we over‐expressed CAV‐1 in cultured A7r5 (rat aorta vascular smooth muscle; VSM) cells. Confocal immunofluorescence microscopy was used to study the distribution of phosphofructokinase (PFK) and CAV‐1 in the transfected cells. Areas of interest (AOI) were analyzed in a central Z‐plane across the cell transversing the perinuclear region. To quantify any shift in PFK localization resulting from CAV‐1 over‐expression, we calculated a periphery to center (PC) index by taking the average of the two outer AOIs from each membrane region and dividing by the central one or two AOIs. We found the PC index to be 1.92 ± 0.57 (mean ± SEM, N = 8) for transfected cells and 0.59 ± 0.05 (mean ± SEM, N = 11) for control cells. Colocalization analysis demonstrated that the percentage of PFK associated with CAV‐1 increased in transfected cells compared to control cells. The localization of aldolase (ALD) was also shifted towards the plasma membrane (and colocalized with PFK) in CAV‐1 over‐expressing cells. These results demonstrate that CAV‐1 creates binding sites for PFK and ALD that may be of higher affinity than those binding sites localized in the cytoplasm. We conclude that CAV‐1 functions as a scaffolding protein for PFK, ALD and perhaps other glycolytic enzymes, either through direct interaction or accessory proteins, thus contributing to compartmented metabolism in vascular smooth muscle. J. Cell. Biochem. 98: 861–871, 2006. © 2006 Wiley‐Liss, Inc.
Cellular and molecular parameters of mesothelioma
Authors: Ramos‐Nino Maria E. , Testa Joseph R. , Altomare Deborah A. , Pass Harvey I. , Carbone Michele , Bocchetta Maurizio , Mossman Brooke T. 
Published: June 2006

AbstractMalignant mesotheliomas (MM) are neoplasms arising from mesothelial cells that line the body cavities, most commonly the pleural and peritoneal cavities. Although traditionally recognized as associated with occupational asbestos exposures, MMs can appear in individuals with no documented exposures to asbestos fibers, and emerging data suggest that genetic susceptibility and simian virus 40 (SV40) infections also facilitate the development of MMs. Both asbestos exposure and transfection of human mesothelial cells with SV40 large and small antigens (Tag, tag) cause genetic modifications and cell signaling events, most notably the induction of cell survival pathways and activation of receptors, and other proteins that favor the growth and establishment of MMs as well as their resistance to chemotherapy. Recent advances in high‐throughput technologies documenting gene and protein expression in patients and animal models of MMs can now be validated in human MM tissue arrays. These have revealed expression profiles that allow more accurate diagnosis and prognosis of MMs. More importantly, serum proteomics has revealed two new candidates (osteopontin and serum mesothelin‐related protein or SMRP) potentially useful in screening individuals for MMs. These mechanistic approaches offer new hope for early detection and treatment of these devastating tumors. J. Cell. Biochem. 98: 723–734, 2006. © 2006 Wiley‐Liss, Inc.
Ochnaflavone inhibits TNF‐α‐induced human VSMC proliferation via regulation of cell cycle, ERK1/2, and MMP‐9
Authors: Suh Seok‐Jong , Jin Un‐Ho , Kim Sung‐Hoon , Chang Hyeun‐Wook , Son Jong‐Keun , Ho Lee Seung , Son Kun‐Ho , Kim Cheorl‐Ho 
Published: June 2006

AbstractOchnaflavone (c‐3 of apigenin‐0‐c‐4 of apigenin; OC), a biflavonoid present in the human diet, is known to inhibit angiotensin II‐induced hypertrophy and serum‐induced smooth muscle cell proliferation. OC is known to have anti‐fungal and anti‐inflammatory activities. However, it is not known whether OC exerts similar cardioprotective effects in cells treated with tumor necrosis factor (TNF)‐α. In this study, we isolated OC from Lonicera japonica and studied its effect on matrix metalloproteinase‐9 (MMP‐9) gene expression in human aortic smooth muscle cells (HASMC). Furthermore, we investigated whether OC exerts the multiple suppressive effects on cytokine TNF‐α‐induced HASMC. Treatment of OC showed its potent inhibitory effects on DNA synthesis of cultured HASMC in the presence of TNF‐α. These inhibitory effects were associated with reduced extracellular signal‐regulated kinase 1/2 (ERK1/2) activity and G1 cell cycle arrest. Treatment of OC, which induced a cell cycle block in G1‐phase, induced downregulation of cyclins and CDKs and upregulation of the CDK inhibitor p21waf1 expression, whereas upregulation of p27 or p53 by OC was not observed. Because anti‐atherogenic effects need not be limited to anti‐proliferation, we decided to examine whether OC exerts inhibitory effects on MMP‐9 activity in TNF‐α‐induced HASMC. OC inhibited TNF‐α‐induced MMP‐9 secretion on HASMC in a dose‐dependent manner. This inhibition was characterized by downregulation of MMP‐9, which was transcriptionally regulated at nuclear factor (NF)‐κB site and activation protein (AP)‐1 site in the MMP‐9 promoter. These findings indicate the efficacy of OC in inhibiting cell proliferation, G1 to S‐phase cell cycle progress, and MMP‐9 expression through the transcription factors NF‐κB and AP‐1 on TNF‐α‐induced HASMC. The findings of the present study may provide a potential mechanism that explains the anti‐atherogenic activity of OC. J. Cell. Biochem. 99: 1298–1307, 2006. © 2006 Wiley‐Liss, Inc.