842 research outputs found
Obstructed umbilical hernia in a child with Hurler's syndrome
Case Report- Hurler's syndrome (MPS I-H) is a lysosomal storage
disorder characterized by physical deformities and developmental
anomalies and premature death. Deficiency of the enzyme
alfa-L-Idronidase results in intralysosomal accumulation of dermatan
sulfate and heparan sulfate resulting in cell dysfunction. It manifests
as progressive hepatosplenomegaly, cardiac disease, severe skeletal
abnormalities, hydrocephalus and mental retardation. Umbilical and
inguinal hernias are common in this disorder. Obstruction of hernia in
these children is rare because of wide hernial ring. This is a
discussion on a child with Hurler's syndrome who presented with
obstructed umbilical hernia. Surgery was performed under general
anaesthesia after relieving the obstruction conservatively. Surgical
and anaesthetic problems in this syndrome are discussed in the present
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Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics.
Progress in the management of patients with myelodysplastic syndromes (MDS) has been hampered by the inability to detect cytogenetic abnormalities in 40-60% of cases. We prospectively analyzed matched pairs of bone marrow and buccal cell (normal) DNA samples from 51 MDS patients by single nucleotide polymorphism (SNP) arrays, and identified somatically acquired clonal genomic abnormalities in 21 patients (41%). Among the 33 patients with normal bone marrow cell karyotypes, 5 (15%) had clonal, somatically acquired aberrations by SNP array analysis, including 4 with segmental uniparental disomies (UPD) and 1 with three separate microdeletions. Each abnormality was detected more readily in CD34+ cells than in unselected bone marrow cells. Paired analysis of bone marrow and buccal cell DNA from each patient was necessary to distinguish true clonal genomic abnormalities from inherited copy number variations and regions with apparent loss of heterozygosity. UPDs affecting chromosome 7q were identified in two patients who had a rapidly deteriorating clinical course despite a low-risk International Prognostic Scoring System score. Further studies of larger numbers of patients will be needed to determine whether 7q UPD detected by SNP array analysis will identify higher risk MDS patients at diagnosis, analogous to those with 7q cytogenetic abnormalities
Intracranial hypotension secondary to spinal arachnoid cyst rupture presenting with acute severe headache: a case report
<p>Abstract</p> <p>Introduction</p> <p>Headache is a common presenting complaint and has a wide differential diagnosis. Clinicians need to be alert to clues that may suggest an underlying secondary aetiology. We describe a novel case of headache secondary to intracranial hypotension which was precipitated by the rupture of a spinal arachnoid cyst.</p> <p>Case report</p> <p>A 51-year-old Indian female presented with sudden onset severe headache suggestive of a subarachnoid haemorrage. Investigations including a computed tomography brain scan, cerebrospinal fluid examination and a magnetic resonance angiogram were normal. The headache persisted and magnetic resonance imaging revealed bilateral thin subdural collections, a spinal subarachnoid cyst and a right-sided pleural effusion. This was consistent with a diagnosis of headache secondary to intracranial hypotension resulting from spinal arachnoid cyst rupture.</p> <p>Conclusions</p> <p>Spinal arachnoid cyst rupture is a rare cause of spontaneous intracranial hypotension. Spontaneous intracranial hypotension is a common yet under-diagnosed heterogeneous condition. It should feature significantly in the differential diagnosis of patients with new-onset daily persistent headache.</p
Accreting Black Holes
This chapter provides a general overview of the theory and observations of
black holes in the Universe and on their interpretation. We briefly review the
black hole classes, accretion disk models, spectral state classification, the
AGN classification, and the leading techniques for measuring black hole spins.
We also introduce quasi-periodic oscillations, the shadow of black holes, and
the observations and the theoretical models of jets.Comment: 41 pages, 18 figures. To appear in "Tutorial Guide to X-ray and
Gamma-ray Astronomy: Data Reduction and Analysis" (Ed. C. Bambi, Springer
Singapore, 2020). v3: fixed some typos and updated some parts. arXiv admin
note: substantial text overlap with arXiv:1711.1025
Altered Insulin Receptor Signalling and Ξ²-Cell Cycle Dynamics in Type 2 Diabetes Mellitus
Insulin resistance, reduced Ξ²-cell mass, and hyperglucagonemia are consistent features in type 2 diabetes mellitus (T2DM). We used pancreas and islets from humans with T2DM to examine the regulation of insulin signaling and cell-cycle control of islet cells. We observed reduced Ξ²-cell mass and increased Ξ±-cell mass in the Type 2 diabetic pancreas. Confocal microscopy, real-time PCR and western blotting analyses revealed increased expression of PCNA and down-regulation of p27-Kip1 and altered expression of insulin receptors, insulin receptor substrate-2 and phosphorylated BAD. To investigate the mechanisms underlying these findings, we examined a mouse model of insulin resistance in Ξ²-cells β which also exhibits reduced Ξ²-cell mass, the Ξ²-cell-specific insulin receptor knockout (Ξ²IRKO). Freshly isolated islets and Ξ²-cell lines derived from Ξ²IRKO mice exhibited poor cell-cycle progression, nuclear restriction of FoxO1 and reduced expression of cell-cycle proteins favoring growth arrest. Re-expression of insulin receptors in Ξ²IRKO Ξ²-cells reversed the defects and promoted cell cycle progression and proliferation implying a role for insulin-signaling in Ξ²-cell growth. These data provide evidence that human Ξ²- and Ξ±-cells can enter the cell-cycle, but proliferation of Ξ²-cells in T2DM fails due to G1-to-S phase arrest secondary to defective insulin signaling. Activation of insulin signaling, FoxO1 and proteins in Ξ²-cell-cycle progression are attractive therapeutic targets to enhance Ξ²-cell regeneration in the treatment of T2DM
Using equity premium survey data to estimate future wealth
We present the first systematic methods for combining different experts' responses to equity premium surveys. These techniques are based on the observation that the survey data are approximately gamma distributed. This distribution has convenient analytical properties that enable us to address three important problems that investment managers must face. First, we construct probability density functions for the future values of equity index tracker funds. Second, we calculate unbiased and minimum least square error estimators of the future value of these funds. Third, we derive optimal asset allocation weights between equities and the risk-free asset for risk-averse investors. Our analysis allows for both herding and biasedness in expert responses. We show that, unless investors are highly uncertain about expert biases or forecasts are very highly correlated, many investment decisions can be based solely on the mean of the survey data minus any expected bias. We also make recommendations for the design of future equity premium surveys
Pretreatment Serum Concentrations of 25-Hydroxyvitamin D and Breast Cancer Prognostic Characteristics: A Case-Control and a Case-Series Study
Results from epidemiologic studies on the relationship between vitamin D and breast cancer risk are inconclusive. It is possible that vitamin D may be effective in reducing risk only of specific subtypes due to disease heterogeneity.In case-control and case-series analyses, we examined serum concentrations of 25-hydroxyvitamin D (25OHD) in relation to breast cancer prognostic characteristics, including histologic grade, estrogen receptor (ER), and molecular subtypes defined by ER, progesterone receptor (PR) and HER2, among 579 women with incident breast cancer and 574 controls matched on age and time of blood draw enrolled in the Roswell Park Cancer Institute from 2003 to 2008. We found that breast cancer cases had significantly lower 25OHD concentrations than controls (adjusted mean, 22.8 versus 26.2 ng/mL, p<0.001). Among premenopausal women, 25OHD concentrations were lower in those with high- versus low-grade tumors, and ER negative versus ER positive tumors (pβ€0.03). Levels were lowest among women with triple-negative cancer (17.5 ng/mL), significantly different from those with luminal A cancer (24.5 ng/mL, pβ=β0.002). In case-control analyses, premenopausal women with 25OHD concentrations above the median had significantly lower odds of having triple-negative cancer (ORβ=β0.21, 95% CIβ=β0.08-0.53) than those with levels below the median; and every 10 ng/mL increase in serum 25OHD concentrations was associated with a 64% lower odds of having triple-negative cancer (ORβ=β0.36, 95% CIβ=β0.22-0.56). The differential associations by tumor subtypes among premenopausal women were confirmed in case-series analyses.In our analyses, higher serum levels of 25OHD were associated with reduced risk of breast cancer, with associations strongest for high grade, ER negative or triple negative cancers in premenopausal women. With further confirmation in large prospective studies, these findings could warrant vitamin D supplementation for reducing breast cancer risk, particularly those with poor prognostic characteristics among premenopausal women
Microarray identifies ADAM family members as key responders to TGF-Ξ²1 in alveolar epithelial cells
The molecular mechanisms of Idiopathic Pulmonary Fibrosis (IPF) remain elusive. Transforming Growth Factor beta 1(TGF-Ξ²1) is a key effector cytokine in the development of lung fibrosis. We used microarray and computational biology strategies to identify genes whose expression is significantly altered in alveolar epithelial cells (A549) in response to TGF-Ξ²1, IL-4 and IL-13 and Epstein Barr virus. A549 cells were exposed to 10 ng/ml TGF-Ξ²1, IL-4 and IL-13 at serial time points. Total RNA was used for hybridisation to Affymetrix Human Genome U133A microarrays. Each in vitro time-point was studied in duplicate and an average RMA value computed. Expression data for each time point was compared to control and a signal log ratio of 0.6 or greater taken to identify significant differential regulation. Using normalised RMA values and unsupervised Average Linkage Hierarchical Cluster Analysis, a list of 312 extracellular matrix (ECM) proteins or modulators of matrix turnover was curated via Onto-Compare and Gene-Ontology (GO) databases for baited cluster analysis of ECM associated genes. Interrogation of the dataset using ontological classification focused cluster analysis revealed coordinate differential expression of a large cohort of extracellular matrix associated genes. Of this grouping members of the ADAM (A disintegrin and Metalloproteinase domain containing) family of genes were differentially expressed. ADAM gene expression was also identified in EBV infected A549 cells as well as IL-13 and IL-4 stimulated cells. We probed pathologenomic activities (activation and functional activity) of ADAM19 and ADAMTS9 using siRNA and collagen assays. Knockdown of these genes resulted in diminished production of collagen in A549 cells exposed to TGF-Ξ²1, suggesting a potential role for these molecules in ECM accumulation in IPF
Tissue Microenvironments Define and Get Reinforced by Macrophage Phenotypes in Homeostasis or during Inflammation, Repair and Fibrosis
Current macrophage phenotype classifications are based on distinct in vitro culture conditions that do not adequately mirror complex tissue environments. In vivo monocyte progenitors populate all tissues for immune surveillance which supports the maintenance of homeostasis as well as regaining homeostasis after injury. Here we propose to classify macrophage phenotypes according to prototypical tissue environments, e.g. as they occur during homeostasis as well as during the different phases of (dermal) wound healing. In tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce proinflammatory macrophages by Toll-like receptors or inflammasomes. Such classically activated macrophages contribute to further tissue inflammation and damage. Apoptotic cells and antiinflammatory cytokines dominate in postinflammatory tissues which induce macrophages to produce more antiinflammatory mediators. Similarly, tumor-associated macrophages also confer immunosuppression in tumor stroma. Insufficient parenchymal healing despite abundant growth factors pushes macrophages to gain a profibrotic phenotype and promote fibrocyte recruitment which both enforce tissue scarring. Ischemic scars are largely devoid of cytokines and growth factors so that fibrolytic macrophages that predominantly secrete proteases digest the excess extracellular matrix. Together, macrophages stabilize their surrounding tissue microenvironments by adapting different phenotypes as feed-forward mechanisms to maintain tissue homeostasis or regain it following injury. Furthermore, macrophage heterogeneity in healthy or injured tissues mirrors spatial and temporal differences in microenvironments during the various stages of tissue injury and repair. Copyright (C) 2012 S. Karger AG, Base
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