bluuebunny/crossref_metadata_2025_split huggingface dataset:
The LCMV gp33-specific memory T cell repertoire narrows with age
Authors: Bunztman Adam , Vincent Benjamin G , Krovi Harsha , Steele Shaun , Frelinger Jeffrey A 
Published: August 2012

AbstractBackgroundThe memory response to LCMV in mice persists for months to years with only a small decrease in the number of epitope specific CD8 T cells. This long persistence is associated with resistance to lethal LCMV disease. In contrast to studies focused on the number and surface phenotype of the memory cells, relatively little attention has been paid to the diversity of TCR usage in these cells. CD8+T cell responses with only a few clones of identical specificity are believed to be relatively ineffective, presumably due to the relative ease of virus escape. Thus, a broad polyclonal response is associated with an effective anti-viral CD8+T cell response.ResultsIn this paper we show that the primary CD8+T cell response to the LCMV gp33-41 epitope is extremely diverse. Over time while the response remains robust in terms of the number of gp33-tetramer+T cells, the diversity of the response becomes less so. Strikingly, by 26 months after infection the response is dominated by a small number TCRβ sequences. In addition, it is of note the gp33 specific CD8+T cells sorted by high and low tetramer binding populations 15 and 22 months after infection. High and low tetramer binding cells had equivalent diversity and were dominated by a small number of clones regardless of the time tested. A similar restricted distribution was seen in NP396 specific CD8+T cells 26 months after infection. The identical TCRVβ sequences were found in both the tetramerhiand tetramerlobinding populations. Finally, we saw no evidence of public clones in the gp33-specific response. No CDR3 sequences were found in more than one mouse.ConclusionsThese data show that following LCMV infection the CD8+gp33-specific CD8 T cell response becomes highly restricted with enormous narrowing of the diversity. This narrowing of the repertoire could contribute to the progressively ineffective immune response seen in aging.
Imbalance of placental regulatory T cell and Th17 cell population dynamics in the FIV-infected pregnant cat
Authors: Boudreaux Crystal E , Chumbley Lyndon B , Scott Veronica L , Wise Dwayne A , Coats Karen S 
Published: August 2012

Abstract

Background
An appropriate balance in placental regulatory T cells (Tregs), an immunosuppressive cell population, and Th17 cells, a pro-inflammatory cell population, is essential in allowing tolerance of the semi-allogeneic fetus. TGF-β and IL-6 are cytokines that promote differentiation of Tregs and Th17 cells from a common progenitor; aberrant expression of the cytokines may perturb the balance in the two cell populations. We previously reported a pro-inflammatory placental environment with decreased levels of FoxP3, a Treg marker, and increased levels of IL-6 in the placentas of FIV-infected cats at early pregnancy. Thus, we hypothesized that FIV infection in the pregnant cat causes altered placental Treg and Th17 cell populations, possibly resulting in placental inflammation.

Methods
We examined the effect of FIV infection on Treg and Th17 populations in placentas at early pregnancy using quantitative confocal microscopy to measure FoxP3 or RORγ, a Th17 marker, and qPCR to quantify expression of the key cytokines TGF-β and IL-6.

Results
FoxP3 and RORγ were positively correlated in FIV-infected placentas at early pregnancy, but not placentas from normal cats, indicating virus-induced alteration in the balance of these cell populations. In control cats the expression of IL-6 and RORγ was positively correlated as predicted, but this relationship was disrupted in infected animals. TGF-β was reduced in infected queens, an occurrence that could dysregulate both Treg and Th17 cell populations. Co-expression analyses revealed a highly significant positive correlation between IL-6 and TGF-β expression in control animals that did not occur in infected animals.

Conclusion
Collectively, these data point toward potential disruption in the balance of Treg and Th17 cell populations that may contribute to FIV-induced inflammation in the feline placenta.
Neuroendocrine tumor in gastric adenoma: a diagnostic pitfall mimicking invasive adenocarcinoma
Authors: Lee Sun-Mi , Ahn Soomin , Lee Yun Kyung , Jang Kee-Taek , Park Cheol Keun , Kim Kyoung-Mee 
Published: August 2012

Abstract
Neuroendocrine tumor (NET) in adenoma of the gastrointestinal tract is a rare mixed glandular-endocrine neoplasm and has uncommonly been described mostly in the colon. Histologically, this tumor is composed of a predominant proportion of benign adenomatous component and a small portion of well-differentiated NE component. Only three cases of NET in gastric adenoma have been reported in the literature. We present 4 cases of NET in gastric adenoma mimicking invasive adenocarcinoma. The NETs were 0.62 mm to 4.1 mm in size and located at the basal lamina propria, muscularis mucosa and submucosa. Histologically, NETs consisted of nests, cords, tubules, and clusters of cells that predominantly interposed between the foveolar base without disturbing the overall polyp architecture. The lesions were completely removed by endoscopic submucosal dissection in three cases and in one case, subtotal gastrectomy was performed because endoscopic biopsy was invasive adenocarcinoma. The patients’ clinical course was uneventful without an evidence of recurrence or metastasis. The recognition of NET in gastric adenoma will help avoid potential diagnostic pitfalls masquerading as invasvie adenocarcinomas posed by their infiltrative pattern into submucosa.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1688552293761001
Implication of protein kinase R Gene quantification in hepatitis C Virus Genotype 4 induced Hepatocarcinogenesis
Authors: Mohamed Amal A , Nada Ola H , El Desouky Mohamed A 
Published: August 2012

AbstractBackgroundProtein kinase RNA (PKR-regulated) is a double-stranded RNA activated protein kinase whose expression is induced by interferon. The role of PKR in cell growth regulation is controversial, with some studies supporting a tumour suppressor function and others suggesting a growth-promoting role. However, it is possible that the function of PKR varies with the type of cancer in question.MethodsWe report here a detailed study to evaluate the function of PKR in hepatitis C virus genotype 4 (HCV-4) infected patients. PKR gene was quantitated in HCV related malignant and non-malignant liver tissue by RT-PCR technique and the association of HCV core and PKR was assessed.ResultsIf PKR functions as a tumour suppressor in this system, its expression would be higher in chronic hepatitis tissues. On the contrary our study demonstrated the specific association of HCV-4 with PKR expressed in hepatocellular carcinoma (HCC) tissues, leading to an increased gene expression of the kinase in comparison to chronic hepatitis tissues. This calls into question its role as a tumour suppressor and suggests a positive regulatory role of PKR in growth control of liver cancer cells. One limitation of most of other studies is that they measure the levels rather than the quantitation of PKR gene.ConclusionThe findings suggest that PKR exerts a positive role in cell growth control of HCV-4 related HCC, obtaining a cut-off value for PKR expression in liver tissue provides the first evidence for existence of a viral activator of PKR.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1267826959682402.
Analysis of naltrexone and its metabolite 6-beta-naltrexol in serum with high-performance liquid chromatography
Authors: Heinälä Pekka , Lahti Tuuli , Sinclair David , Ariniemi Kari , Lillsunde Pirjo , Alho Hannu 
Published: August 2012

Abstract

Background
Naltrexone has been proven to be an effective treatment option for the treatment of alcohol dependency. In this article we introduce a reliable and simple method developed for the simultaneous determination of naltrexone and 6-β-naltrexol in human serum by using high-performance liquid chromatography (HPLC).

Findings
Liquid-liquid extraction with butyl acetate from basic solutions (pH 9) was chosen for extraction with nalorphine as an internal standard (IS). Analytes were back-extracted from organic solvent into perchloric acid. The acid extract was chromatographed by HPLC with a reverse-phase ODS-column and electrochemical detector. The mobile phase was a NaH2PO4-solution with acetonitrile as an organic modifier and octanesulphonic acid and tetraethylammonium hydrogen sulphate as ion-pair reagents. The recovery of the extraction method was 48% for naltrexone and 75% for 6-β-naltrexol. The limit of quantification was 5.0 ng/ml for naltrexone and 1.0 ng/ml for 6-β-naltrexol. The analysed concentrations of naltrexone differed from the theoretic concentrations by 0.7 to 2.3% and those of 6-β-naltrexol by 2.6%. The relative standard deviation of within-day assay was from 0.9 to 5.7% for naltrexone and from 0.8 to 4.2% for 6-β-naltrexol; for the between-day assay it was 5.7% and 4.2%, respectively.

Conclusions
Our results indicate that the developed method is suitable for determination of naltrexone and 6-β-naltrexol in human serum.
Contribution of uric acid to cancer risk, recurrence, and mortality
Authors: Fini Mehdi A , Elias Anthony , Johnson Richard J , Wright Richard M 
Published: August 2012

AbstractTwo risk factors for the development and progression of cancers that are amenable to life style modification are chronic inflammation and the metabolic syndrome. This review proposes two new targets that may mechanistically integrate inflammation and metabolic syndrome, have been largely ignored, and are known to be druggable. Recent evidence has demonstrated that elevated serum uric acid (hyperuricemia) is associated with excess cancer risk, recurrence, and mortality. Although uric acid (UA) can function as a systemic antioxidant, its pro‐inflammatory properties have been postulated to play an important role in the pathogenesis of cancer. Furthermore, obesity, Type 2 Diabetes Mellitus (T2DM), and the metabolic syndrome (MetS) are also associated with excess cancer, chronic inflammation, and with hyperuricemia, suggesting that UA may represent an important link between these disorders and the development of cancer. While pharmacological modulation of hyperuricemia could in principal augment anti‐cancer therapeutic strategies, some cancer cells express low intracellular levels of the enzyme Xanthine Oxidoreductase (XOR) that are associated with increased cancer aggressiveness and poor clinical outcome. Thus, systemic pharmacological inhibition of XOR may worsen clinical outcome, and specific strategies that target serum uric acid (SUA) without inhibiting tumor cell XOR may create new therapeutic opportunities for cancer associated with hyperuricemia. This review will summarize the evidence that elevated SUA may be a true risk factor for cancer incidence and mortality, and mechanisms by which UA may contribute to cancer pathogenesis will be discussed in the hope that these will identify new opportunities for cancer management.
Activity of the neuroendocrine axes in patients with polymyalgia rheumatica before and after TNF-α blocking etanercept treatment
Authors: Kreiner Frederik Flindt , Galbo Henrik 
Published: August 2012

Abstract
Introduction
In this study, we evaluated the activity of the neuroendocrine axes in patients with polymyalgia rheumatica (PMR) before and after tumor necrosis factor (TNF)-α-blocking etanercept treatment, which previously has been shown to reduce interleukin 6 (IL-6) and C-reactive protein (CRP) markedly in PMR.

Methods
Plasma samples were collected from 10 glucocorticoid-naïve patients with PMR and 10 matched controls before and after etanercept treatment (25 mg biweekly for 2 weeks). The primary end points were pre- and posttreatment levels of adrenocorticotropic hormone (ACTH), cortisol, adrenaline, thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), prolactin, and insulin-like growth factor 1 (IGF-1).

Results
Before TNF-α-blocking treatment, plasma TNF-α, ACTH, and cortisol levels were higher in patients versus controls (P < 0.05 and P < 0.001, respectively); during TNF-α blockade in patients, levels of both hormones decreased (P < 0.05 and P < 0.01, respectively), whereas levels in controls increased (P < 0.05), abolishing the pretreatment differences. Pretreatment adrenaline levels were more than twice as high in patients than in controls (P < 0.01); after treatment in patients, levels had decreased (P < 0.05) but remained higher versus controls (P < 0.05). Levels of the other hormones never differed significantly between groups (P > 0.05).

Conclusions
In PMR, TNF-α may increase the activities of the hypothalamic-pituitary-adrenal and the hypothalamic-sympthoadrenomedullary axes. Secretion of TSH, FSH, prolactin, and IGF-1 is not clearly changed in PMR.

Trial registration
ClinicalTrials.gov (NCT00524381).
Staphylococcus aureus Panton-Valentine leukocidin induces an inflammatory response in human phagocytes via the NLRP3 inflammasome
Authors: Holzinger Dirk , Gieldon Laura , Mysore Vijayashree , Nippe Nadine , Taxman Debra J , Duncan Joseph A , Broglie Peter M , Marketon Kristina , Austermann Judith , Vogl Thomas , Foell Dirk , Niemann Silke , Peters Georg , Roth Johannes , Löffler Bettina 
Published: August 2012

Abstract
Activation of the NLRP3-inflammasome contributes to Staphylococcus aureus PVL-associated diseases, such as necrotizing pneumonia.
The Staphylococcus aureus pore-forming toxin PVL is most likely causative for life-threatening necrotizing infections, which are characterized by massive tissue inflammation and necrosis. Whereas the cytotoxic action of PVL on human neutrophils is already well established, the PVL effects on other sensitive cell types, such as monocytes and macrophages, are less clear. In this study, we used different types of human leukocytes (neutrophils, monocytes, macrophages, lymphocytes) to investigate cell-specific binding of PVL subunits and subsequent proinflammatory and cytotoxic effects. In all PVL-sensitive cells, we identified the binding of the subunit LukS-PV as the critical factor for PVL-induced cytotoxicity, which was followed by binding of LukF-PV. LukS-PV binds to monocytes, macrophages, and neutrophils but not to lymphocytes. Additionally, we showed that PVL binding to monocytes and macrophages leads to release of caspase-1-dependent proinflammatory cytokines IL-1β and IL-18. PVL activates the NLRP3 inflammasome, a signaling complex of myeloid cells that is involved in caspase-1-dependent IL-1β processing in response to pathogens and endogenous danger signals. Specific inhibition of this pathway at several steps significantly reduced inflammasome activation and subsequent pyronecrosis. Furthermore, we found that PAMPs and DAMPs derived from dying neutrophils can dramatically enhance this response by up-regulating pro-IL-1β in monocytes/macrophages. This study analyzes a specific host signaling pathway that mediates PVL-induced inflammation and cytotoxicity, which has high relevance for CA-MRSA-associated and PVL-mediated pathogenic processes, such as necrotizing infections.
Recurrence patterns of bladder transitional cell carcinoma after radical cystectomy
Authors: Kim Bohyun , Choi Hyuck Jae , Kim Mi-hyun , Cho Kyung-Sik 
Published: August 2012

Background Multidetector computed tomography (MDCT) is widely accepted as an effective imaging modality in monitoring for bladder cancer recurrence after radical cystectomy. Elucidating the pattern of bladder cancer recurrence on CT can increase the diagnostic accuracy. Purpose To evaluate the recurrence patterns of transitional cell carcinoma of the bladder and the factors associated with cancer recurrence. Material and Methods One hundred and forty-nine consecutive patients (mean age, 66.55 years; range, 32–86 years) who underwent preoperative contrast-enhanced CT and radical cystectomy were included in this study. The presence, site, and time of tumor recurrence were recorded retrospectively by two radiologists in a consensus fashion. The association of tumor recurrence and tumor factors (T stage, lymph node metastasis, nuclear grade, and tumor diameter) were also evaluated using multiple logistic regression analysis and Kaplan-Meier statistics. Results Tumor recurrence occurred in 60 patients (40.3%) with a mean time of 14 months (range, 1–64 months). The sites of recurrence included the operation site ( n = 20), lymph node ( n = 20), bone ( n = 11), liver ( n = 6), lung ( n = 5), upper urinary tract ( n = 4), colon ( n = 3), adrenal gland ( n = 2), peritoneum ( n = 1), abdominal wall ( n = 1), psoas muscle ( n = 1), and penile skin ( n = 1). Tumor recurrence was found to be associated with advanced T stage ( P = 0.002) and lymph node metastasis ( P < 0.001). Conclusion Transitional cell carcinomas of the bladder recur more frequently at the operation site and lymph node, and T-stage and lymph node metastasis are closely associated with tumor recurrence.
Anwendung dynamisch erweiterter Beobachter zur robusten Fehlerisolation
Authors: Wahrburg Arne 
Published: August 2012

Zusammenfassung
Dieser Beitrag befasst sich mit dem Entwurf von dynamisch erweiterten Fehlerisolationsbeobachtern (FIOs). Dazu wird zunächst eine Methode zum Entwurf dynamischer Entkopplungsregler vorschlagen. Basierend auf der Dualität von Entkopplungsregelungen und Fehlerisolationsbeobachtern lässt sich hieraus ein Verfahren zum Entwurf von dynamischen Fehlerisolationsbeobachtern ableiten, welches gegenüber klassischen FIOs zusätzliche Freiheitsgrade bietet. Diese werden in diesem Beitrag dazu genutzt, die Robustheit bezüglich hochfrequenter Störungen zu verbessern.
Entwurf vernetzter ereignisbasierter Regelungssysteme mit Kommunikationsbeschränkungen
Authors: Molin Adam , Hirche Sandra 
Published: August 2012

Zusammenfassung
Der Betrieb komplexer, verteilter Regelungssysteme erfordert eine effiziente Nutzung vorhandener Ressourcen. Kürzlich erzielte Ergebnisse zeigen wesentliche Vorteile einer ereignisbasierten Regelung verglichen mit herkömmlichen Entwurfsmethoden mit periodischer Abtastung, wenn die Kommunikationsbandbreite, der Energieverbrauch oder die Rechenleistung beschränkt sind. Dieser Beitrag beschäftigt sich mit dem Entwurf ereignisbasierter Regelungen mehrerer heterogener Teilsysteme, deren Rückführschleifen über ein gemeinsames Kommunikationssystem verkoppelt sind. Mittels Zustandsaggregation wird eine dezentrale ereignisbasierte Regelungsstruktur entworfen und Stabilitätsbedinungen hergeleitet, unter welchen das Gesamtsystem stochastisch stabil ist. Unter diesen Stabilitätsbedingungen lässt sich zeigen, dass der vorgeschlagene Regelungsentwurf asymptotisch optimal mit zunehmender Anzahl an Teilsystemen ist.
Ansätze zur Berechnung und schnellen Auswertung expliziter modellprädiktiver Regelgesetze
Authors: Kastsian Martin , Jost Michael , Mönnigmann Martin 
Published: August 2012

Zusammenfassung
Die explizite modellprädiktive Regelung (EMPC) zeichnet sich dadurch aus, dass zur Betriebszeit des Reglers keine numerischen Optimierungsaufgaben gelöst werden müssen. Obwohl die EMPC nur für Systeme niedriger Ordnung mit wenigen Beschränkungen und kurzen Horizonten in Frage kommt, ist sie eine Alternative bei sehr kurzen Abtastzeiten und bei strengen Echtzeitanforderungen. Wir schlagen eine neue Methode zur Berechnung von EMPC Regelgesetzen vor und zeigen einen neuen Ansatz zur Beschleunigung der Auswertung dieser Regelgesetze mit Hilfe von massiv nebenläufigen Schaltnetzwerken auf.
Zur konstruktiven Berechnung flacher Ausgänge für nichtlineare Systeme
Authors: Schöberl Markus , Schlacher Kurt 
Published: August 2012

Zusammenfassung
Dieser Beitrag behandelt ein konstruktives Verfahren zur Berechnung der flachen Ausgänge von nichtlinearen Mehrgrößensystemen. Basierend auf der Systembeschreibung durch Pfaffsche Systeme stellen wir eine spezielle Dreiecksform vor, welche für die systematische Berechnung der flachen Ausgänge zweckmäßig ist. Diese Dreiecksform wird sukzessive durch entsprechende Koordinatentransformationen erzeugt, welche das System in Teilsysteme aufspaltet. Ziel ist es nun, aus einem Teilsystem alle Systemgrößen, die nicht als Ableitungsvariablen auftauchen, auszurechnen, unter der Prämisse, dass eine Lösung des anderen Teilsystems bekannt ist. Durch Wiederholung dieser Vorgehensweise gelangt man schließlich zur gewünschten Dreiecksform.
Incidence and predictors of all-cause and site-specific cancer in type 2 diabetes: the Fremantle Diabetes Study
Authors: Magliano Dianna J , Davis Wendy A , Shaw Jonathan E , Bruce David G , Davis Timothy M E 
Published: August 2012

ObjectiveTo explore the relationship between diabetes and cancer.DesignThe Fremantle Diabetes Study (FDS) was a community-based longitudinal observational study of 1426 subjects, 1294 of which had type 2 diabetes.MethodsThe FDS type 2 cohort and four age-, sex- and postcode-matched controls per case were followed for cancer events from 1993 until mid-2010 and incidence rate ratios (IRRs) were calculated. Competing risks proportional hazards models generated risk factors for incident cancers in the diabetic group.ResultsThere were 309 first cancers over 13 051 patient-years, or 2368 (95% confidence interval (95% CI) 2111–2647)/100 000 patient-years in the diabetes patients vs 1131 over 60 324 patient-years (1875 (1769–1987)/100 000 patient-years) in the controls. For those aged ≥45 years, the risk of all-cause cancer was elevated in type 2 diabetic men (IRRs 1.23, 95% CI 1.04–1.45) and women (1.30, 1.06–1.59). The incidence of colorectal cancer was increased (1.36, 1.01–1.82), especially in diabetic men aged 75–84 years (2.14, 1.22–3.64). Age at diabetes diagnosis (sub-hazard ratio 1.05, 1.02–1.09), calcium channel blocker therapy (2.37, 1.39–4.06), recent exercise (2.11, 1.06–4.20) and serum total cholesterol (0.68, 0.52–0.88) increased colorectal cancer risk. Pancreatic cancer was also more frequent in the diabetic patients (IRR 2.26, 1.20–4.10). Diabetic men and women had similar risks of prostate and breast cancer to those of controls (0.83, 0.59–1.14 and 0.86, 0.52–1.36).ConclusionsType 2 diabetes is associated with a moderately increased cancer risk in well-characterised community-based patients, especially pancreatic cancer and colorectal cancer in older men. Recommended cancer screening should be considered as part of routine diabetes management.