564 research outputs found

    Emphysematous cholecystitis: a case report

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    A 65-year-old Greek man with a history of diabetes mellitus and hypertension was admitted because of right upper quadrant pain, nausea and palpable right quadrant mass. On admission the patient was febrile (38.8Β°C) with a total bilirubin level of 1.99 mg/dl (direct 0.59 mg/dl); SGOT 1.26 mg/dl; Na 135 mmol/l and K 2.9 mmol/l. The white blood count was 15200/ΞΌl with 92.2% neutrophiles. Axial sections of single slice CT imaging (section thickness 10 mm), revealed emphysematous cholecystitis with thickening of gallbladder wall and wall enhancement after iv contrast enhancement, as well as, dilatation of the gallbladder with multiple gallstones precipitate and intraluminal air. The patient underwent subtotal cholecystectomy and a cholecystostomy was placed. The culture of the bile showed positivity to toxin A of Clostridium Difficile and to Escherichia Coli. The postoperative course of the patient was uneventful

    Lung fibroblasts from patients with emphysema show markers of senescence in vitro

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    BACKGROUND: The loss of alveolar walls is a hallmark of emphysema. As fibroblasts play an important role in the maintenance of alveolar structure, a change in fibroblast phenotype could be involved in the pathogenesis of this disease. In a previous study we found a reduced in vitro proliferation rate and number of population doublings of parenchymal lung fibroblasts from patients with emphysema and we hypothesized that these findings could be related to a premature cellular aging of these cells. In this study, we therefore compared cellular senescence markers and expression of respective genes between lung fibroblasts from patients with emphysema and control patients without COPD. METHODS: Primary lung fibroblasts were obtained from 13 patients with moderate to severe lung emphysema (E) and 15 controls (C) undergoing surgery for lung tumor resection or volume reduction (n = 2). Fibroblasts (8E/9C) were stained for senescence-associated Ξ²-galactosidase (SA-Ξ²-Gal). In independent cultures, DNA from lung fibroblasts (7E/8C) was assessed for mean telomere length. Two exploratory 12 k cDNA microarrays were used to assess gene expression in pooled fibroblasts (3E/3C). Subsequently, expression of selected genes was evaluated by quantitative PCR (qPCR) in fibroblasts of individual patients (10E/9C) and protein concentration was analyzed in the cell culture supernatant. RESULTS: The median (quartiles) percentage of fibroblasts positive for SA-Ξ²-Gal was 4.4 (3.2;4.7) % in controls and 16.0 (10.0;24.8) % in emphysema (p = 0.001), while telomere length was not different. Among the candidates for differentially expressed genes in the array (factor β‰₯ 3), 15 were upregulated and 121 downregulated in emphysema. qPCR confirmed the upregulation of insulin-like growth factor-binding protein (IGFBP)-3 and IGFBP-rP1 (p = 0.029, p = 0.0002), while expression of IGFBP-5, -rP2 (CTGF), -rP4 (Cyr61), FOSL1, LOXL2, OAZ1 and CDK4 was not different between groups. In line with the gene expression we found increased cell culture supernatant concentrations of IGFBP-3 (p = 0.006) in emphysema. CONCLUSION: These data support the hypothesis that premature aging of lung fibroblasts occurs in emphysema, via a telomere-independent mechanism. The upregulation of the senescence-associated IGFBP-3 and -rP1 in emphysema suggests that inhibition of the action of insulin and insulin-like growth factors could be involved in the reduced in vitro-proliferation rate

    Zircon ages in granulite facies rocks: decoupling from geochemistry above 850 Β°C?

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    Granulite facies rocks frequently show a large spread in their zircon ages, the interpretation of which raises questions: Has the isotopic system been disturbed? By what process(es) and conditions did the alteration occur? Can the dates be regarded as real ages, reflecting several growth episodes? Furthermore, under some circumstances of (ultra-)high-temperature metamorphism, decoupling of zircon U–Pb dates from their trace element geochemistry has been reported. Understanding these processes is crucial to help interpret such dates in the context of the P–T history. Our study presents evidence for decoupling in zircon from the highest grade metapelites (> 850 Β°C) taken along a continuous high-temperature metamorphic field gradient in the Ivrea Zone (NW Italy). These rocks represent a well-characterised segment of Permian lower continental crust with a protracted high-temperature history. Cathodoluminescence images reveal that zircons in the mid-amphibolite facies preserve mainly detrital cores with narrow overgrowths. In the upper amphibolite and granulite facies, preserved detrital cores decrease and metamorphic zircon increases in quantity. Across all samples we document a sequence of four rim generations based on textures. U–Pb dates, Th/U ratios and Ti-in-zircon concentrations show an essentially continuous evolution with increasing metamorphic grade, except in the samples from the granulite facies, which display significant scatter in age and chemistry. We associate the observed decoupling of zircon systematics in high-grade non-metamict zircon with disturbance processes related to differences in behaviour of non-formula elements (i.e. Pb, Th, U, Ti) at high-temperature conditions, notably differences in compatibility within the crystal structure

    Restoring Coastal Plants to Improve Global Carbon Storage: Reaping What We Sow

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    Long-term carbon capture and storage (CCS) is currently considered a viable strategy for mitigating rising levels of atmospheric CO2 and associated impacts of global climate change. Until recently, the significant below-ground CCS capacity of coastal vegetation such as seagrasses, salt marshes, and mangroves has largely gone unrecognized in models of global carbon transfer. However, this reservoir of natural, free, and sustainable carbon storage potential is increasingly jeopardized by alarming trends in coastal habitat loss, totalling 30–50% of global abundance over the last century alone. Human intervention to restore lost habitats is a potentially powerful solution to improve natural rates of global CCS, but data suggest this approach is unlikely to substantially improve long-term CCS unless current restoration efforts are increased to an industrial scale. Failure to do so raises the question of whether resources currently used for expensive and time-consuming restoration projects would be more wisely invested in arresting further habitat loss and encouraging natural recovery

    Reproductive Schedules in Southern Bluefin Tuna: Are Current Assumptions Appropriate?

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    Southern bluefin tuna (SBT) appear to comprise a single stock that is assumed to be both mixed across its distribution and having reproductive adults that are obligate, annual spawners. The putative annual migration cycle of mature SBT consists of dispersed foraging at temperate latitudes with migration to a single spawning ground in the tropical eastern Indian Ocean. Spawning migrations have been assumed to target two peaks in spawning activity; one in September-October and a second in February-March. SBT of sizes comparable to that of individuals observed on the spawning ground were satellite tagged in the Tasman Sea region (2003–2008) and demonstrated both migrations to the spawning grounds and residency in the Tasman Sea region throughout the whole year. All individuals undertaking apparent spawning migrations timed their movements to coincide with the second recognised spawning peak or even later. These observations suggest that SBT may demonstrate substantial flexibility in the scheduling of reproductive events and may even not spawn annually as currently assumed. Further, the population on the spawning grounds may be temporally structured in association with foraging regions. These findings provide new perspectives on bluefin population and spatial dynamics and warrant further investigation and consideration of reproductive schedules in this species

    Subcellular Localization of SUN2 Is Regulated by Lamin A and Rab5

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    SUN2 is an inner nuclear membrane protein with a conserved Sad1/UNC-84 homology SUN-domain at the C-terminus. Intriguingly, SUN2 has also been reported to interact with Rab5, which localizes in early endosomes. To clarify the dual subcellular localization of SUN2, we investigated its localization in lamin A/C deficient cells rescued with lamin A or lamin C isoform, and in HeLa cells transfected with Rab5 or its mutants. We found that expression of lamin A but not lamin C partly restored the nuclear envelope localization of SUN2. SUN2 was redistributed to endosomes upon overexpression of Rab5, but remained on the nuclear envelope when the SUN domain was deleted. To explore the physiological function of SUN2 in vesicle trafficking and endocytosis, we demonstrated the colocalization of endogenous SUN2 and Rab5. Moreover, overexpression of SUN2 stimulated the uptake of transferrin while suppression of SUN2 expression attenuated the process. These findings support a role of SUN2 in endocytosis

    The Relationship between Telomere Length and Mortality in Chronic Obstructive Pulmonary Disease (COPD)

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    Some have suggested that chronic obstructive pulmonary disease (COPD) is a disease of accelerated aging. Aging is characterized by shortening of telomeres. The relationship of telomere length to important clinical outcomes such as mortality, disease progression and cancer in COPD is unknown. Using quantitative polymerase chain reaction (qPCR), we measured telomere length of peripheral leukocytes in 4,271 subjects with mild to moderate COPD who participated in the Lung Health Study (LHS). The subjects were followed for approximately 7.5 years during which time their vital status, FEV1 and smoking status were ascertained. Using multiple regression methods, we determined the relationship of telomere length to cancer and total mortality in these subjects. We also measured telomere length in healthy β€œmid-life” volunteers and patients with more severe COPD. The LHS subjects had significantly shorter telomeres than those of healthy β€œmid-life” volunteers (p<.001). Compared to individuals in the 4th quartile of relative telomere length (i.e. longest telomere group), the remaining participants had significantly higher risk of cancer mortality (Hazard ratio, HR, 1.48; pβ€Š=β€Š0.0324) and total mortality (HR, 1.29; pβ€Š=β€Š0.0425). Smoking status did not make a significant difference in peripheral blood cells telomere length. In conclusion, COPD patients have short leukocyte telomeres, which are in turn associated increased risk of total and cancer mortality. Accelerated aging is of particular relevance to cancer mortality in COPD

    Cataloging Coding Sequence Variations in Human Genome Databases

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    BACKGROUND: With the recent growth of information on sequence variations in the human genome, predictions regarding the functional effects and relevance to disease phenotypes of coding sequence variations are becoming increasingly important. The aims of this study were to catalog protein-coding sequence variations (CVs) occurring in genetic variation databases and to use bioinformatic programs to analyze CVs. In addition, we aim to provide insight into the functionality of the reference databases. METHODOLOGY AND FINDINGS: To catalog CVs on a genome-wide scale with regard to protein function and disease, we investigated three representative databases; the Human Gene Mutation Database (HGMD), the Single Nucleotide Polymorphisms database (dbSNP), and the Haplotype Map (HapMap). Using these three databases, we analyzed CVs at the protein function level with bioinformatic programs. We proposed a combinatorial approach using the Support Vector Machine (SVM) to increase the performance of the prediction programs. By cataloging the coding sequence variations using these databases, we found that 4.36% of CVs from HGMD are concurrently registered in dbSNP (8.11% of CVs from dbSNP are concurrent in HGMD). The pattern of substitutions and functional consequences predicted by three bioinformatic programs was significantly different among concurrent CVs, and CVs occurring solely in HGMD or in dbSNP. The experimental results showed that the proposed SVM combination noticeably outperformed the individual prediction programs. CONCLUSIONS: This is the first study to compare human sequence variations in HGMD, dbSNP and HapMap at the genome-wide level. We found that a significant proportion of CVs in HGMD and dbSNP overlap, and we emphasize the need to use caution when interpreting the phenotypic relevance of these concurrent CVs. Combining bioinformatic programs can be helpful in predicting the functional consequences of CVs because it improved the performance of functional predictions
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