bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of pulmonary nuclear factor kappa-B decreases the severity of acute Escherichia coli pneumonia but worsens prolonged pneumonia
Authors: Devaney James , Curley Gerard F , Hayes Mairead , Masterson Claire , Ansari Bilal , O'Brien Timothy , O'Toole Daniel , Laffey John G 
Published: April 2013

Abstract
Introduction
Nuclear factor (NF)-κB is central to the pathogenesis of inflammation in acute lung injury, but also to inflammation resolution and repair. We wished to determine whether overexpression of the NF-κB inhibitor IκBα could modulate the severity of acute and prolonged pneumonia-induced lung injury in a series of prospective randomized animal studies.

Methods
Adult male Sprague-Dawley rats were randomized to undergo intratracheal instillation of (a) 5 × 109 adenoassociated virus (AAV) vectors encoding the IκBα transgene (5 × 109 AAV-IκBα); (b) 1 × 1010 AAV-IκBα; (c) 5 × 1010 AAV-IκBα; or (d) vehicle alone. After intratracheal inoculation with Escherichia coli, the severity of the lung injury was measured in one series over a 4-hour period (acute pneumonia), and in a second series after 72 hours (prolonged pneumonia). Additional experiments examined the effects of IκBα and null-gene overexpression on E. coli-induced and sham pneumonia.

Results
In acute pneumonia, IκBα dose-dependently decreased lung injury, improving arterial oxygenation and lung static compliance, reducing alveolar protein leak and histologic injury, and decreasing alveolar IL-1β concentrations. Benefit was maximal at the intermediate (1 × 1010) IκBα vector dose; however, efficacy was diminished at the higher (5 × 1010) IκBα vector dose. In contrast, IκBα worsened prolonged pneumonia-induced lung injury, increased lung bacterial load, decreased lung compliance, and delayed resolution of the acute inflammatory response.

Conclusions
Inhibition of pulmonary NF-κB activity reduces early pneumonia-induced injury, but worsens injury and bacterial load during prolonged pneumonia.
PGI2 signaling inhibits antigen uptake and increases migration of immature dendritic cells
Authors: Toki Shinji , Goleniewska Kasia , Huckabee Matthew M , Zhou Weisong , Newcomb Dawn C , FitzGerald Garret A , Lawson William E , Peebles R Stokes 
Published: April 2013

ABSTRACTPGI2 signaling through IP inhibits allergen-induced inflammatory responses in mice. We reported previously that PGI2 analogs decreased proinflammatory cytokine and chemokine production by mature BMDCs. However, whether PGI2 modulates the function of immature DCs has not been investigated. We hypothesized that PGI2 negatively regulates immature DC function and investigated the effect of PGI2 analogs on immature BMDC antigen uptake and migration in vitro and in vivo. Immature BMDCs were obtained from WT and IPKO mice, both on a C57BL/6 background. The PGI2 analog cicaprost decreased FITC-OVA uptake by immature BMDCs. In addition, cicaprost increased immature BMDC podosome dissolution, pro-MMP-9 production, cell surface CCR7 expression, and chemotactic migration toward CCL19 and CCL21, as well as chemokinesis, in an IP-specific fashion. These in vitro results suggested that cicaprost promotes migration of immature DCs from mucosal surface to draining LNs. This concept was supported by the finding that migration of immature GFP+ BMDCs to draining LNs was enhanced by pretreatment with cicaprost. Further, migration of immature lung DCs labeled with PKH26 was enhanced by intranasal cicaprost administration. Our results suggest PGI2-IP signaling increases immature DC migration to the draining LNs and may represent a novel mechanism by which this eicosanoid inhibits immune responses.
What's your age again? Determination of human neutrophil half-lives revisited
Authors: Tak Tamar , Tesselaar Kiki , Pillay Janesh , Borghans José A M , Koenderman Leo 
Published: April 2013

ABSTRACTNeutrophils are the most abundant white blood cells and are indispensable for host defense. Recently, they have also been implicated in immune regulation and suppression. The latter functions seem hard to reconcile with the widely held view that neutrophils are very short-lived, with a circulatory half-life of &lt;7 h. To reopen the discussion on the average neutrophil half-life, we review and discuss experiments performed in the 1950s, 1960s, and 1970s, as well as recent in vivo labeling experiments. We reappraise the current knowledge on neutrophil half-lives, including their production in the bone marrow, their residency in the circulation and marginated pool, and their exit from the circulation.
At the Bench: Preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy
Authors: Intlekofer Andrew M , Thompson Craig B 
Published: April 2013

ABSTRACT
Tumors can avoid immune surveillance by stimulating immune inhibitory receptors that function to turn off established immune responses. By blocking the ability of tumors to stimulate inhibitory receptors on T cells, sustained, anti-tumor immune responses can be generated in animals. Thus, therapeutic blockade of immune inhibitory checkpoints provides a potential method to boost anti-tumor immunity. The CTLA-4 and PD-1Rs represent two T cell-inhibitory receptors with independent mechanisms of action. Preclinical investigations revealed that CTLA-4 enforces an activation threshold and attenuates proliferation of tumor-specific T lymphocytes. In contrast, PD-1 functions primarily as a stop signal that limits T cell effector function within a tumor. The unique mechanisms and sites of action of CTLA-4 and PD-1 suggest that although blockade of either has the potential to promote anti-tumor immune responses, combined blockade of both might offer even more potent anti-tumor activity. See related review At the Bedside: CTLA-4 and PD-1 blocking antibodies in cancer immunotherapy.
Up-Regulation of the Fetal Baboon Hypothalamo-Pituitary-Adrenal Axis in Intrauterine Growth Restriction: Coincidence with Hypothalamic Glucocorticoid Receptor Insensitivity and Leptin Receptor Down-Regulation
Authors: Li Cun , Ramahi Emma , Nijland Mark J. , Choi Jaeyhek , Myers Dean A. , Nathanielsz Peter W. , McDonald Thomas J. 
Published: April 2013

Abstract
Intrauterine growth restriction (IUGR) is an important fetal developmental problem resulting from 2 broad causes: maternal undernutrition and/or decreased fetal nutrient delivery to the fetus via placental insufficiency. IUGR is often accompanied by up-regulation of the hypothalamo-pituitary-adrenal axis (HPAA). Sheep studies show fetal HPAA autonomy in late gestation. We hypothesized that IUGR, resulting from poor fetal nutrient delivery, up-regulates the fetal baboon HPAA in late gestation, driven by hypothalamo-pituitary glucocorticoid receptor (GR) insensitivity and decreased fetal leptin in peripheral plasma. Maternal baboons were fed as ad libitum controls or nutrient restricted to produce IUGR (fed 70% of the control diet) from 0.16 to 0.9 gestation. Peripheral ACTH, cortisol, and leptin were measured by immunoassays. CRH, arginine vasopressin (AVP), GR, leptin receptor (ObRb), and pro-opiomelanocortin peptide expression were determined immunohistochemically. IUGR fetal peripheral cortisol and ACTH, but not leptin, were increased (P &lt; .05). IUGR increased CRH peptide expression, but not AVP, in the fetal hypothalamic paraventricular nucleus (PVN) and median eminence (P &lt; .05). PVN ObRb peptide expression, but not GR, was decreased (P &lt; .05) with IUGR. ObRb and pro-opiomelanocortin were robustly expressed in the anterior pituitary gland, but ∼1% of cells showed colocalization. We conclude that (1) CRH, not AVP, is the major releasing hormone driving ACTH and cortisol secretion during primate IUGR, (2) fetal HPAA activation was aided by GR insensitivity and decreased ObRb expression in the PVN, and (3) the anterior pituitary is not a site for ObRb effects on the HPAA.
Effects of Recombinant Human Growth Hormone for 1 Year on Body Composition and Muscle Strength in Children on Long-Term Steroid Therapy: Randomized Controlled, Delayed-Start Study
Authors: Simon Dominique , Alberti Corinne , Alison Marianne , Le Henaff Loïc , Chevenne Didier , Boizeau Priscilla , Canal Aurélie , Ollivier Gwenn , Decostre Valérie , Jacqz-Aigrain Evelyne , Carel Jean-Claude , Czernichow Paul , Hogrel Jean-Yves 
Published: April 2013

Context:
Recombinant human GH (rhGH) improves growth and body composition in glucocorticoid-treated children. Its effects on muscle strength are poorly evaluated.

Objectives:
Our objective was to evaluate rhGH effects on muscle strength in children receiving long-term glucocorticoid therapy; effects on height SD score (SDS) and body composition were assessed also.

Design and Setting:
A randomized, controlled, delayed-start study of rhGH for 12 months was started after randomization (baseline) or 6 months later (M6).

Patients:
Patients included 30 children with various diagnoses.

Intervention:
rhGH was administered at 0.065 mg/kg/d for 6 months and then in the dosage maintaining serum IGF-I levels below +2 SDS for chronological age.

Main Outcome Measures:
The primary criterion was the between-group difference in composite index of muscle strength (CIMS) change at M6. Secondary criteria included between-group differences in CIMS SDSheight, lean mass (LM), thigh muscle area (MA), and height SDS changes at M6; these parameters were also assessed in the overall population after 1 year of rhGH therapy.

Results:
At M6, rhGH therapy did not significantly affect changes in CIMS or CIMS SDSheight (+17.6% vs +7.5% and +0.14 ± 0.38 vs +0.11 ± 0.62, respectively); the rhGH-treated group had significantly larger changes in height SDS (+0.2 [0.3] vs −0.2 [0.3]; P = 0.003), LM (+7.3% [+3.7%; +21.6%] vs 0% [−4.7%; +3.2%]; P = 0.002), and MA (+8.8% [+5%; +15.6%] vs. −0.6% [−6.3%; +7.7%]; P = 0.01) compared with the untreated group. After 1 year of rhGH, height SDS, LM, and MA increased significantly, CIMS increased by 24.7% (+5.8%; +34.2%), and CIMS SDSheight remained within the normal range.

Conclusions:
rhGH increased height, LM, and MA. However, muscle strength did not improve significantly.
Circulating Levels of FGF-21 in Obese Youth: Associations With Liver Fat Content and Markers of Liver Damage
Authors: Giannini Cosimo , Feldstein Ariel E. , Santoro Nicola , Kim Grace , Kursawe Romy , Pierpont Bridget , Caprio Sonia 
Published: April 2013

Objective:
Fibroblast growth factor (FGF)-21 is highly expressed in the liver and regulates glucose and lipid metabolism in rodents. The effects of obesity and fatty liver on circulating FGF-21 levels have been described mainly in adults. Herein, we measured plasma FGF-21 levels in lean and obese adolescents with low and high hepatic fat content (HFF% &lt;5.5% and HFF% ≥5.5%, respectively) and explored their relationship with hepatic fat content, measures of hepatic apoptosis, and insulin sensitivity.

Methods:
A total of 217 lean and obese adolescents with both low and high HFF% (lean = 31; obese low HFF% = 107; and obese high HFF% = 79) underwent an oral glucose tolerance test, a fast gradient magnetic resonance imaging to measure the %HFF and abdominal fat distribution. Cytokeratin 18 levels were measured as a biomarker of liver apoptosis. A subset of adolescents underwent a 2-step hyperinsulinemic-euglycemic clamp, and a liver biopsy (N = 14), to assess insulin sensitivity and steatohepatitis, respectively.

Results:
Compared to controls, FGF-21 levels were higher in obese youth, especially in those with high HFF (P &lt; .001). FGF-21 significantly correlated with adiposity indexes (P &lt; .001), visceral fat (r2 = 0.240, P &lt; .001), hepatic fat content (r2 = 0.278, P &lt; .001), cytokeratin 18 (r2 = 0.217, P &lt; .001), and alanine aminotransferase (r2 = .164, P &lt; .001). In subjects with steatoheaptitis, FGF-21 levels significantly correlated with the nonalcoholic fatty liver disease activity score (r2 = 0.27, P = .04). Stepwise regression analysis indicated that these relationships are independent of body mass index, visceral fat, and insulin sensitivity. An inverse correlation was documented with insulin, hepatic resistance indexes, and adipose resistance indexes, which disappeared after adjusting for hepatic fat content.

Conclusions:
Plasma FGF-21 levels are increased in obese adolescents, particularly in those with fatty liver. FGF-21 concentrations significantly and independently correlate with hepatic fat content and markers of hepatic apoptosis in obese youths.
Im Fadenkreuz der Stasi: Westliche Spionage in der DDR
Authors: Maddrell Paul 
Published: April 2013

Vorspann
Im geteilten Deutschland tobte bis 1989/90 ein verdeckter kalter Krieg der Spione und Agenten. Was dabei auf dem westlichen „Kriegs“-Schauplatz geschah, ist partiell bekannt, während die Spionagetätigkeit westlicher Dienste im Osten noch immer einem Buch mit sieben Siegeln gleicht. Der renommierte britische Historiker Paul Maddrell greift diese brisante Materie auf, wobei er sich auf neue Stasi-Quellen stützen kann. Das Ergebnis ist frappant: In der DDR wimmelte es vor Spionen, die zwar nur selten so große Scoops landeten wie die Stasispione im Westen, im Großen und Ganzen aber ähnlich erfolgreich arbeiteten.
MEFV Variants in Patients with PFAPA Syndrome in Japan
Authors: Taniuchi Shoichiro , Nishikomori Ryuta , Iharada Anna , Tuji Shoji , Heike Toshio , Kaneko Kazunari 
Published: April 2013

Background:The pathogenesis of PFAPA (periodic fever, aphthous stomatitis, pharyngitis, adenitis) syndrome is unknown as yet. In order to understand whether genes implicated in other auto-inflammatory diseases might be involved in the pathogenesis of PFAPA, all variants in the genes causing familial Mediterranean fever (FMF), tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS), and Hyper IgD syndrome were analyzed in children with PFAPA.Patients and Methods:All variants inMEFV,TNFRSF1A, andMVKwere analyzed in 20 patients with PFAPA. PFAPA were diagnosed by previous published criteria. The findings of all analyses in PFAPA patients were compared with those of unaffected normal subjects (n=62).Results:In the 13 children of 20 with PFAPA, the heterozygous variants ofMEFV(5 patients:E148Q-L110P, 2 patients:E148Q, 1 patient:E148Q-L110P/E148Q, 1 patient:E148Q-P369S-R408Q-E84K, 1 patient:E148Q-L110P-P369S-A408G, 1 patient:R202Q, 1 patient:P115R) were found. No variants belonging toTNFRSF1Aor MVK were detected in children with PFAPA. The frequency of theE148Q-L110Pvariants in children with PFAPA was significantly higher than that observed in unaffected normal subjects (7/20 versus 8/62). The duration of the episodes of illness in PFAPA children withMEFVvariants was shorter than that of patients without variants.Conclusion:Genes involved in the development and progression ofMEFVmay affect the incidence and the phenotype of PFAPA in children.
Inflammatory Cells in Tissues of Gout Patients and Their Correlations with Comorbidities
Authors: Lai Syeling , Zhou Xiaodong 
Published: April 2013

Background:
The major pathological finding of gout is the deposition of monosodium urate monohydrate (MSU) crystals with inflammatory infiltrate in the tissue. There have been many reports of in vitro analysis of inflammatory mechanism and comorbidities in gout. However, the associations of immune response cells and comorbidities of gout have not been well documented. Our studies aimed to examine the immune cell types and quantity in gout tissues, and to define the association of individual cell type with comorbidities.

Methods:
Surgically resected or biopsied tissues from 48 patients diagnosed as gout were used for this study. Cell count was performed on Hemotoxylin and Eosin stained sections for macrophages, plasma cells, neutrophils and on immunostained slides for T and B lymphocytes.

Results:
Hyperlipidemia, hypertension and diabetes mellitus were seen in 70.8%, 87.5% and 37.5% of patients, respectively. There were 35.6% and 37.8% of patients who admitted history of smoking and alcohol intake, respectively. Mean serum uric acid level was 8.5 mg/dl. The average body mass index was 30.1 kg/m2. H&E stained tissue sections demonstrated the crystalline deposits rimmed by palisading multinucleated giant cells, macrophages, neutrophils, plasma cells, T and B cells. Significant correlations between the clinical features and tissue inflammatory cells were observed in hyperlipidemia with number of T cells (p = 0.0363), hypertension with number of T cells and B cells (p = 0.0138 and 0.0033, respectively), diabetes mellitus with macrophages (p = 0.0016), and uric acid level with giant cells (p = 0.0088).

Conclusion:
Comorbidity factors including hyperlipidemia, hypertension and diabetes are significantly associated with the inflammatory cells in the tissues.
Effect of bevacizumab on angiogenesis and growth of canine osteosarcoma cells xenografted in athymic mice
Authors: Scharf Valery F. , Farese James P. , Coomer Alastair R. , Milner Rowan J. , Taylor David P. , Salute Marc E. , Chang Myron N. , Neal Dan , Siemann Dietmar W. 
Published: April 2013

Abstract
Objective—To investigate the effects of bevacizumab, a human monoclonal antibody against vascular endothelial growth factor, on the angiogenesis and growth of canine osteosarcoma cells xenografted in mice.
Animals—27 athymic nude mice.
Procedures—To each mouse, highly metastasizing parent osteosarcoma cells of canine origin were injected into the left gastrocnemius muscle. Each mouse was then randomly allocated to 1 of 3 treatment groups: high-dose bevacizumab (4 mg/kg, IP), low-dose bevacizumab (2 mg/kg, IP), or control (no treatment). Tumor growth (the number of days required for the tumor to grow from 8 to 13 mm), vasculature, histomorphology, necrosis, and pulmonary metastasis were evaluated.
Results—Mice in the high-dose bevacizumab group had significantly delayed tumor growth (mean ± SD, 13.4 ± 3.8 days; range, 9 to 21 days), compared with that for mice in the low-dose bevacizumab group (mean ± SD, 9.4 ± 1.5 days; range, 7 to 11 days) or control group (mean ± SD, 7. 2 ± 1.5 days; range, 4 to 9 days). Mice in the low-dose bevacizumab group also had significantly delayed tumor growth, compared with that for mice in the control group.
Conclusions and Clinical Relevance—Results indicated that bevacizumab inhibited growth of canine osteosarcoma cells xenografted in mice, which suggested that vascular endothelial growth factor inhibitors may be clinically useful for the treatment of osteosarcoma in dogs.
Impact for Human Medicine—Canine osteosarcoma is used as a research model for human osteosarcoma; therefore, bevacizumab may be clinically beneficial for the treatment of osteosarcoma in humans.
The role of nesfatin-1 in metabolism regulation: an overview / Rola nesfatyny-1 w regulacji metabolizmu: artykuł przeglądowy
Authors: Bulc Michał , Gonkowski Sławomir , Całka Jarosław 
Published: April 2013

Abstract The hypothalamus synthesizes molecules involved in the regulation of feeding behaviour. Nesfatin- 1 is a recently discovered substance expressed in both the brain and peripheral tissues and exerts a strong anorectic action. Nesfatin-1-immunoreactive cell bodies are distributed in arcuate (ARC), paraventricular (PVN) and supraoptic (SON) nuclei, where the peptide has been found to be co-expressed with pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART), oxytocin (OX) and vasopressin (VP). More detailed studies have shown a wide distribution of nesfatin-1-positive neurons in several brain areas, such as the forebrain, hindbrain, brainstem and spinal cord. Moreover, nesfatin-1 has been also expressed in peripheral tissues, colocalizing with ghrelin in the gastric mucosa and insulin in β-cells of the endocrine pancreas and adipose tissue. Functional studies have revealed that exogenous nesfatin-1 administered into the brain ventricles, subcutaneously or intraperitoneally, was able to decrease both food intake in the dark phase as well as body weight gain in a dose-dependent manner. In addition, recent findings suggest the involvement of nesfatin-1 in the control of insulin secretion as well as immune and stress-related responses. However, since there is still a deficiency of data concerning the nesfatin-1 receptor, the possible implementation of nesfatin-1 analogs during human metabolic disorders requires further study.
Performance characteristics of a rapid method for iodine determination in milk / Szybka metoda oznaczania jodu w mleku – walidacja i akredytacja zgodnie z normą ISO/IEC 17025:2005
Authors: Gąsior Robert , Szczypuła Marta , Szybiński Zbigniew 
Published: April 2013

Streszczenie Badania powtarzalności i odtwarzalności przeprowadzono na 72 próbkach. Określono najważniejsze parametry walidacji, w tym składowe niepewności. Wyniki analiz porównano z wartościami referencyjnymi. Powtarzalność i odtwarzalność metody nie przekraczały 8 i 10%, odpowiednio. LOQ w oznaczanym roztworze próbki mleka wynosił 14 μg/L. Zakres roboczy krzywej kalibracji wynosił od 7 do 200 μg/L. Niepewność metody (P≤0,05) uwzględniająca błędy odtwarzalności wewnątrzlaboratoryjnej, odzysku, czystości wzorca oraz błędy szkła miarowego wynosiła (%) 17.8 i 22.8 (n = 2 i n = 1). Podczas wykonywania rutynowych analiz powinien być sprawdzany współczynnik zmienności dla powtarzalności, który nie powinien przekraczać granicy powtarzalności wynoszącej 16%. Metoda cechuje się wystarczającą wiarygodnością, co zostało potwierdzone wynikami walidacji. Procedura jest szybka, prosta i ma niską wartość LOQ. Metodę akredytowano zgodnie z normą ISO/IEC 17025:2005.
Quality of Bus Services Performance: Benefits of Real Time Passenger Information Systems
Authors: Monzon Andres , Hernandez Sara , Cascajo Rocio 
Published: April 2013

One of the main problems in urban areas is the steady growth in car ownership and traffic levels. Therefore, the challenge of sustainability is focused on a shift of the demand for mobility from cars to collective means of transport. For this purpose, buses are a key element of the public transport systems. In this respect Real Time Passenger Information (RTPI) systems help people change their travel behaviour towards more sustainable transport modes.
This paper provides an assessment methodology which evaluates how RTPI systems improve the quality of bus services performance in two European cities, Madrid and Bremerhaven. In the case of Madrid, bus punctuality has increased by 3%. Regarding the travellers perception, Madrid raised its quality of service by 6% while Bremerhaven increased by 13%. On the other hand, the users´ perception of Public Transport (PT) image increased by 14%.