Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of NOD2 in Paneth cells: a possible link to Crohn’s ileitis

Background and aims: Genetic variation in NOD2 has been associated with susceptibility to Crohn’s disease (CD) and specifically with ileal involvement. The reason for the unique association of NOD2 mutations with ileal disease is unclear. To identify a possible link, we tested expression of NOD2 in intestinal tissue of CD patients and controls. Patients and methods: Fifty five specimens of ileum or colon from 21 CD patients, seven ulcerative colitis (UC) patients, and five controls with pathology other than CD or UC were stained for NOD2 using an immunoperoxidase method. Results: Using a monoclonal antibody against NOD2 developed in our laboratory, we detected uniform expression of NOD2 in terminal ileum Paneth cells from controls and patients as well as in metaplastic Paneth cells in the colon. Mechanical purification showed enriched expression of NOD2 mRNA in ileal crypts. In Paneth cells, NOD2 was located in the cytosol in close proximity to the granules that contain antimicrobial peptides. We detected minimal NOD2 in the villous epithelium of the ileum or in the colonic epithelium from both CD patients and controls. Conclusions: These results suggest a role for NOD2 in the regulation of Paneth cell mediated responses against intestinal bacteria and a plausible mechanism to explain the selective association of NOD2 mutations with ileal disease. The impaired capacity of CD associated mutations to sense luminal bacteria may result in increased susceptibility to certain gut microbes.
Intracellular Signaling Molecules Activated by Epstein-Barr Virus for Induction of Interferon Regulatory Factor 7

ABSTRACT Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) is the principal oncogenic protein in the EBV transformation process. LMP-1 induces the expression of interferon regulatory factor 7 (IRF-7) and activates IRF-7 protein by phosphorylation and nuclear translocation. LMP-1 is an integral membrane protein with two regions in its C terminus that initiate signaling processes, the C-terminal activator regions 1 (CTAR-1) and CTAR-2. Here, genetic analysis of LMP-1 has determined that the PXQXT motif that governs the interaction between LMP-1 CTAR-1 and tumor necrosis factor receptor-associated factors (TRAFs) is needed to induce the expression of IRF-7. Mutations in the PXQXT motif in CTAR-1 that disrupt the interaction between LMP-1 and TRAFs abolished the induction of IRF-7. Also, dominant-negative mutants of TRAFs inhibited the induction of IRF-7 by CTAR-1. The last three amino acids (YYD) of CTAR-2 are also important for the induction of IRF-7. When both PXQXT and YYD were mutated (LMP-DM), the LMP-1 mutant failed to induce IRF-7. Also, LMP-DM blocked the induction of IRF-7 by wild-type LMP-1. These data strongly suggest that both CTAR-1 and CTAR-2 of LMP-1 independently induce the expression of IRF-7. In addition, NF-κB is involved in the induction of IRF-7. A superrepressor of IκB (sr-IκB) could block the induction of IRF-7 by LMP-1, and overexpression of NF-κB (p65 plus p50) could induce the expression of IRF-7. In addition, we have found that human IRF-7 is a stable protein, and sodium butyrate, a modifier of chromatin structure, induces IRF-7.
Happiness from social capital: An investigation from micro data in rural Thailand

Abstract Happiness is a mental or emotional state of wellbeing defined by positive or pleasant emotions ranging from contentment to intense joy. This article aims to investigate the impacts of social capital on individual wellbeing using happiness level (0–10 = highest) as a measure of subjective wellbeing and analyzing micro-level data from rural Thailand. We find significant effects of the perception of individual’s social capital, while the effects of community-level social capital are found to have insignificant effects on happiness. Our findings confirm that living in a household or community in which other members are, on average, happy, would cause the person to be happy. The findings suggest that an individual’s subjective perceptions of social capital, especially trusting others and participating in community public meetings, are important indicators that affect happiness at the individual level.
Hypovitaminosis D correction and high-sensitivity C-reactive protein levels in hypertensive adults.

CONTEXT Hypovitaminosis D has been implicated as a possible risk factor for the development of cardiovascular disease. High-sensitivity C-reactive protein (hs-CRP) has been one of the most extensively studied biomarkers for cardiovascular inflammation as an indicator of disease and event risk, independent of traditional risk factors. To date, it is unclear if correction of hypovitaminosis D leads to a reduction of hs-CRP in human subjects. OBJECTIVES To assess laboratory validity of 25-hydroxyvita-min D (25-OH-vitamin D) and hs-CRP measurements and to determine whether hs-CRP levels in adults with well-controlled hypertension and comorbid low vitamin D levels changed after hypovitaminosis D correction to a serum 25-OH-vitamin D level greater than 30 ng/mL. DESIGN Prospective study using an unblinded design. RESULTS One hundred eight subjects who were vitamin D insufficient or deficient completed this study. The mean 25-OH-vitamin D level was 20.07 ng/mL before treatment and 43.92 ng/mL after treatment. Posttreatment vitamin D levels were in the normal range for 91% of the subjects. No statistically significant changes in hs-CRP level were detected after the vitamin D treatment was administered and a posttreatment vitamin D level above 30 ng/mL was confirmed. CONCLUSION We did not detect a statistically significant difference in hs-CRP after correction of hypovitaminosis D. Twelve weekly oral doses of 50,000 IU of ergocalciferol corrected the hypovitaminosis D in more than 90% of cases.
Adsorption of Extracellular Chromosomal DNA and Its Effects on Natural Transformation of Azotobacter vinelandii

ABSTRACT To better understand the influence of environmental conditions on the adsorption of extracellular chromosomal DNA and its availability for natural transformation, the amount and conformation of adsorbed DNA were monitored under different conditions in parallel with transformation assays using the soil bacterium Azotobacter vinelandii. DNA adsorption was monitored using the technique of quartz crystal microbalance with dissipation (QCM-D). Both silica and natural organic matter (NOM) surfaces were evaluated in solutions containing either 100 mM NaCl or 1 mM CaCl2. The QCM-D data suggest that DNA adsorbed to silica surfaces has a more compact and rigid conformation in Ca2+ solution than in Na+ solution and that the reverse is true when DNA is adsorbed to NOM surfaces. While the amounts of DNA adsorbed on a silica surface were similar for Ca2+ and Na+ solutions, the amount of DNA adsorbed on an NOM-coated surface was higher in Ca2+ solution than in Na+ solution. Transformation frequencies for dissolved DNA and DNA adsorbed to silica and to NOM were 6 × 10−5, 5 × 10−5, and 2.5 × 10−4, respectively. For NOM-coated surfaces, transformation frequencies from individual experiments were 2- to 50-fold higher in the presence of Ca2+ than in the presence of Na+. The results suggest that groundwater hardness (i.e., Ca2+ concentration) will affect the amount of extracellular DNA adsorbed to the soil surface but that neither adsorption nor changes in the conformation of the adsorbed DNA will have a strong effect on the frequency of natural transformation of A. vinelandii.
Skin–epidural distance in children

The skin–epidural distance was measured in 274 children to assess the usefulness of 1 mm . kg–1 as a guideline. Children aged between 2 days and 16 years, weighing between 2 and 43 kg were investigated. Lumbar epidurals were performed under general anaesthesia using a midline approach in the L3‐4 interspace with the patient in the left lateral position. Good correlation between skin‐epidural distance and age and weight was demonstrated. No statistical difference was shown when plotting the best fit regression line: skin‐epidural distance (mm) = 0.8 weight (kg) + 3.93 (R2= 0.74) and its 95% confidence limits and skin‐epidural distance (mm) = weight (kg) for children between 6 months and 10 years. Poor correlation was noted below 6 months (n = 22) and over 10 years (n = 19). No dural puncture or bloody tap occurred. One mm. kg‐1 body weight was shown to be a useful guideline for children between 6 months and 10 years of age.
Matrix Metalloproteinase-9 in Peripheral Blood Eosinophils

Background: Matrix metalloproteinases (MMPs) are major contributors to tumor invasion, remodeling of connective tissue and infiltration of inflammatory cells and may be important mediators in developing allergic inflammation. Overexpression of MMP-9 mRNA by eosinophils in the asthmatic airways has been reported. To clarify the relative significance of MMP as an inflammatory mediator from eosinophils, we determined the content of MMP-9 in the peripheral blood eosinophils and compared it with the other leukocyte fractions. Methods: Peripheral blood eosinophils, neutrophils, and mononuclear cells were purified from normal and allergic donors with Percoll gradient centrifugation and CD16 negative selection. Cell lysate and culture supernatants stimulated with IL-5, PAF, and PMA were tested for MMP-9 with gelatin zymography and ELISA. Results: The amount of MMP-9 in highly purified eosinophils, neutrophils, and mononuclear cells was 2.5 ± 0.9, 4,073 ± 581, and 7.6 ± 1.4 ng/5 × 106 cells, respectively. There was no difference in MMP-9 content of eosinophils between normal donors and patients with asthma. Culture of peripheral blood eosinophils with IL-5 for 4 days did not induce MMP-9 production. The stimulation of eosinophils with PMA and other secretogogues caused only small amounts of MMP-9 secretion as compared with neutrophils. Conclusions: These findings suggest that circulating eosinophils normally have only small amounts of MMP-9 and that eosinophils may need complex activation signals to produce significant amounts of MMP as seen in tissues of allergic inflammation.
Advance Directives for Health Care among Older Community Residents

Advance directives (ADs) for healthcare are useful planning tools for older people. In addition, the utilization of ADs is important for health and human services planners, administrators, and policy makers to understand because whether or not people have an AD, and what types of ADs they have can dramatically influence the treatment trajectories and the well-being of older people who can longer make decisions for themselves. Using telephone survey data with a random sample of Oklahoma residents age 60 and older, we examined the prevalence of four measures of AD use. Prior to the implementation of this survey in 2002, the Oklahoma Aging Services Division was very active in promoting two types of AD—the living will and the durable power of attorney for healthcare. More than half of those interviewed had a living will, two-fifths had a durable power of attorney for healthcare, and one-third had both ADs. Older age and higher levels of education were consistently associated with having ADs.
Tree-structured vector quantization of CT chest scans: image quality and diagnostic accuracy

The authors apply a lossy compression algorithm to medical images, and quantify the quality of the images by the diagnostic performance of radiologists, as well as by traditional signal-to-noise ratios and subjective ratings. The authors' study is unlike previous studies of the effects of lossy compression in that they consider nonbinary detection tasks, simulate actual diagnostic practice instead of using paired tests or confidence rankings, use statistical methods that are more appropriate for nonbinary clinical data than are the popular receiver operating characteristic curves, and use low-complexity predictive tree-structured vector quantization for compression rather than DCT-based transform codes combined with entropy coding. The authors' diagnostic tasks are the identification of nodules (tumors) in the lungs and lymphadenopathy in the mediastinum from computerized tomography (CT) chest scans. Radiologists read both uncompressed and lossy compressed versions of images. For the image modality, compression algorithm, and diagnostic tasks the authors consider, the original 12 bit per pixel (bpp) CT image can be compressed to between 1 bpp and 2 bpp with no significant changes in diagnostic accuracy. The techniques presented here for evaluating image quality do not depend on the specific compression algorithm and are useful new methods for evaluating the benefits of any lossy image processing technique.
Reactive microglia in cerebral ischaemia: an early mediator of tissue damage?

Microglial cell activation is a rapidly occurring cellular response to cerebral ischaemia. Microglia proliferate, are recruited to the site of lesion, npregulate the expression of several surface molecules including major histocom‐patibility complex class I and II antigens, complement receptor and the amyloid precursor protein (APP) as well as newly expressed cytokines, e.g. interleukin‐1 and transforming growth factor pl. The ischaemia‐induced production of APP may contribute to amyloid deposition in the aged brain under conditions of hypofusion. Ultra‐structurally, microglia transform into phagocytes removing necrotic neurons but still respecting the integrity of eventually surviving neurons even in the close vicinity of necrotic neurons. Microglial activation starts within a few minutes after ischaemia and thus precedes the morphologically detectable neuronal damage. It additionally involves a transient generalized response within the first 24 hours post‐ischaemia even at sites without eventual neuronal cell death. In functional terms, the microglial reaction appears to be a double‐edged sword in ischaemia. Activated microglia may exert a cytotoxic effector function by releasing reactive oxygen species, nitric oxide, proteinases or inflammatory cytokines. All of these cytotoxic compounds may cause bystander damage following ischaemia. Pharmacological suppression of microglial activation after ischaemia has accordingly attenuated the extent of cell death and tissue damage. However, activated microglia support tissue repair by secreting factors such as transforming growth factor βl which may limit tissue damage as well as suppress astroglial scar formation. In line with ultrastructural observations microglial activation in ischaemia is a strictly controlled event. By secreting cytokines and growth factors activated microglia most likely serve seemingly opposed functions in ischaemia, i.e. maintenance as well as removal of injured neurons. Post‐ischaemic pharmacological modulation of microglial intervention in the cascade of events that lead to neuronal necrosis may help to improve the structural and functional outcome following CNS ischaemia.
Neurogenic marker abnormalities in the hippocampus in dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is associated with alpha synuclein pathology and slowly progressive dementia. Progenitor abnormalities have previously been reported in the subventricular zone (SVZ) adjacent to the lateral ventricle. To evaluate changes in neural stem cells and progenitors in the hippocampal neurogenic niche, immunohistochemistry (IHC) using the neural stem cell markers Musashi 1, nestin, proliferating cell nuclear antigen (PCNA), doublecortin, and glial fibrillary acidic protein (GFAP) were examined in age‐matched control and DLB groups. Staining was quantified in the hippocampal SVZ, subgranular layer (SGL) and ependymal cell layer (EPL). There was a significant loss in DLB of Musashi 1 (P < 0.01) in all areas, an increase in PCNA in hippocampal SVZ (P = 0.01) and SGL (P = 0.05), and an increase in doublecortin in the hippocampal SVZ (P = 0.04) and EPL (P = 0.02). This is the first report of the changes in neurogenic markers in the hippocampal SVZ and EPL in DLB and may offer the potential for understanding disease pathology and in the devising of treatment. ©2010 Wiley‐Liss, Inc.
Impact of the duration of platelet storage in critically ill trauma patients.

BACKGROUND There is increasing evidence that the duration of red blood cell (RBC) storage negatively impacts outcomes. Data regarding prolonged storage of other blood components, however, are lacking. The aim of this study was to evaluate how the duration of platelet storage affects trauma patient outcomes. METHODS Trauma patients admitted to a Level I trauma center requiring platelet transfusion (2006-2009) were retrospectively identified. Apheresis platelets (aPLT) containing ≥3 × 10(11) platelets/unit were used exclusively. Patients were analyzed in three groups: those who received only aPLT stored for ≤3 days, 4 days, and 5 days. The outcomes included mortality and complications (sepsis, acute respiratory distress syndrome, renal, and liver failure). RESULTS Three hundred eighty-one patients were available for analysis (128 received aPLT ≤3 days old; 109 = 4 days old; and 144 = 5 days old). There were no significant demographic differences between groups. Patients receiving aPLT aged = 4 days had significantly higher Injury Severity Score (p = 0.022) and were more likely to have a head Abbreviated Injury Scale ≥3 (p = 0.014). There were no differences in volumes transfused or age of RBC, plasma, cryoprecipitate, or factor VIIa. After adjusting for confounders, exposure to older aPLT did not impact mortality; however, with increasing age, complications were significantly higher. The rate of sepsis, in particular, was significantly increased (5.5% for aPLT ≤3 days vs. 9.2% for aPLT = 4 days vs. 16.7% for aPLT = 5 days, adjusted p = 0.033). For acute respiratory distress syndrome and renal and liver failure, similar trends were observed. CONCLUSIONS In critically ill trauma patients, there was a stepwise increase in complications, in particular sepsis, with exposure to progressively older platelets. Further evaluation of the underlying mechanism and methods for minimizing exposure to older platelets is warranted.
DNA damage and nonhomologous end joining in excitotoxicity: Neuroprotective role of DNA‐PKcs in kainic acid‐induced seizures

DNA repair plays a critical, but imprecisely defined role in excitotoxic injury and neuronal survival throughout adulthood. We utilized an excitotoxic injury model to compare the location and phenotype of degenerating neurons in mice (strain 129‐C57BL) deficient in the catalytic subunit of the DNA‐dependent protein kinase (DNA‐PKcs), an enzyme required for nonhomologous end joining (NHEJ). Brains from untreated adult heterozygous and DNA‐PKcs null mice displayed comparable cytoarchitecture and undetectable levels of cell death. By day 1, and extending through 4 days following kainic acid‐induced seizures, brains from DNA‐PKcs null mice showed widespread neurodegeneration that encompassed the entire hippocampal CA1–CA3 pyramidal cell layer, entorhinal cortex, and lateral septum, with relative sparing of the dentate gyrus granule cell layer and hilus, as judged by toluidine blue, Fluoro‐Jade B, and terminal dUTP nick end labeling staining. In contrast, seizure‐related neurodegeneration in heterozygous littermates was limited to the CA3 region of the hippocampus. NeuN and calbindin staining revealed a selective decrease in the number and density of NeuN‐positive neurons in the pyramidal layers of degenerating regions in both heterozygous and DNA‐PKcs null mice. To elucidate the mechanisms leading to cell death, we examined an involvement of the p53 pathway, known to be induced by DNA damage. Addition of pifithrin‐α, a p53 inhibitor, or expression of a dominant‐negative p53 rescued neurons from kainate‐induced excitotoxic cell death in primary cortical cultures derived from wildtype, DNA‐PKcs heterozygous, or DNA‐PKcs null neonatal mice. Moreover, pifithrin‐α prevented kainate‐induced loss of mitochondrial membrane potential, dendrite degeneration, and cell death. Results suggest that NHEJ plays a neuroprotective role in excitotoxicity, within the perforant, Schaffer collateral, hippocampal‐septal, and temperoammonic pathways, in part by repairing DNA damage that would otherwise result in activation of a p53‐dependent apoptotic cascade. © 2005 Wiley‐Liss, Inc.
Co-Expression of Cancer Stem Cell Markers Corresponds to a Pro-Tumorigenic Expression Profile in Pancreatic Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. Its dismal prognosis is often attributed to the presence of cancer stem cells (CSCs) that have been identified in PDAC using various markers. However, the co-expression of all of these markers has not yet been evaluated. Furthermore, studies that compare the expression levels of CSC markers in PDAC tumor samples and in cell lines derived directly from those tumors are lacking. Here, we analyzed the expression of putative CSC markers—CD24, CD44, epithelial cell adhesion molecule (EpCAM), CD133, and nestin—by immunofluorescence, flow cytometry and quantitative PCR in 3 PDAC-derived cell lines and by immunohistochemistry in 3 corresponding tumor samples. We showed high expression of the examined CSC markers among all of the cell lines and tumor samples, with the exception of CD24 and CD44, which were enriched under in vitro conditions compared with tumor tissues. The proportions of cells positive for the remaining markers were comparable to those detected in the corresponding tumors. Co-expression analysis using flow cytometry revealed that CD24+/CD44+/EpCAM+/CD133+ cells represented a significant population of the cells (range, 43 to 72%) among the cell lines. The highest proportion of CD24+/CD44+/EpCAM+/CD133+ cells was detected in the cell line derived from the tumor of a patient with the shortest survival. Using gene expression profiling, we further identified the specific pro-tumorigenic expression profile of this cell line compared with the profiles of the other two cell lines. Together, CD24+/CD44+/EpCAM+/CD133+ cells are present in PDAC cell lines derived from primary tumors, and their increased proportion corresponds with a pro-tumorigenic gene expression profile.
Genomic analysis of insulin‐like growth factor‐I gene transfer in thermally injured rats

Thermal trauma causes tissue damage by membrane destabilization and energy depletion at the cellular level, resulting in tissue necrosis and inflammation leading to delayed cell death. One therapeutic approach is to block the immediate triggering of the inflammatory cascade that results in prolonged hypermetabolic responses and immune dysfunction while promoting the expression of growth factors. In the present study, we determined hepatic gene expression responses to insulin‐like growth factors‐i (IGF‐I) gene transfer to burned rats using high‐density DNA microarray assays. The expression of 123 out of ~8,800 genes assyed (1.4% of total) were significantly altered. Of these, 42 genes were altered irrespective of treatment by burn trauma (p < 0.05). Changes in gene expression were confirmed by measuring mRNA levels using reverse transcription‐polymerase chain reaction and protein levels by Western blot assays. DNA microarray analyses showed two major mechanisms that mediated beneficial outcomes after IGF‐I gene transfer in the burned rat livers. These mechanisms were the stimulation of IGF binding protein potentiation of peripheral IGF‐I and the inhibition of the burn‐augmented pro‐apoptotic and oxidative mitochondrial metabolites stimulated by thermal trauma.