Pneumatosis intestinalis versus pseudo-pneumatosis: review of CT findings and differentiation

Pneumatosis intestinalis is defined as the presence of gas within the wall of the gastrointestinal tract. Originally described on plain abdominal radiographs, it is an imaging sign rather than a specific diagnosis and it is associated with both benign and life-threatening clinical conditions. The most common life-threatening cause of pneumatosis intestinalis is bowel ischaemia. Computed tomography (CT) is usually requested to detect underlying disease. The presence of pneumatosis intestinalis often leads physicians to make a diagnosis of serious disease. However, an erroneous diagnosis of pneumatosis intestinalis may be made (i.e. pseudo-pneumatosis) when intraluminal beads of gas are trapped within or between faeces and adjacent mucosal folds. The purpose of this pictorial essay is to review and describe the CT imaging findings of pneumatosis and pseudo-pneumatosis intestinalis and to discuss key discriminatory imaging features

Genome-wide linkage scan for colorectal cancer susceptibility genes supports linkage to chromosome 3q

Background: Colorectal cancer is one of the most common causes of cancer-related mortality. The disease is clinically and genetically heterogeneous though a strong hereditary component has been identified. However, only a small proportion of the inherited susceptibility can be ascribed to dominant syndromes, such as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) or Familial Adenomatous Polyposis (FAP). In an attempt to identify novel colorectal cancer predisposing genes, we have performed a genome-wide linkage analysis in 30 Swedish non-FAP/non-HNPCC families with a strong family history of colorectal cancer.Methods: Statistical analysis was performed using multipoint parametric and nonparametric linkage.Results: Parametric analysis under the assumption of locus homogeneity excluded any common susceptibility regions harbouring a predisposing gene for colorectal cancer. However, several loci on chromosomes 2q, 3q, 6q, and 7q with suggestive linkage were detected in the parametric analysis under the assumption of locus heterogeneity as well as in the nonparametric analysis. Among these loci, the locus on chromosome 3q21.1- q26.2 was the most consistent finding providing positive results in both parametric and nonparametric analyses Heterogeneity LOD score (HLOD) = 1.90, alpha = 0.45, Non-Parametric LOD score (NPL) = 2.1).Conclusion: The strongest evidence of linkage was seen for the region on chromosome 3. Interestingly, the same region has recently been reported as the most significant finding in a genome-wide analysis performed with SNP arrays; thus our results independently support the finding on chromosome 3q

Effect of Lactobacillus acidophilus supernatants on body weight and leptin expression in rats

<p>Abstract</p> <p>Background</p> <p><it>Lactobacillus </it>extracts and supernatants have been used as probiotics in human and veterinary medicine for their ability to enhance wound healing and immunity. Previous data from our laboratory demonstrated that <it>Lactobacillus </it>supernatant (LS) stimulated wound healing, angiogenesis and proliferation of embryonic cells after topical application. This current study shows that LS after its administration into the cerebral ventricles of male rats exerts systemic effects.</p> <p>Methods</p> <p>The right lateral cerebral ventricle of young male rats was accessed through intracerebroventricular cannulation (ICV) under anesthesia and aseptic conditions. One group of control rats received saline solution, a second control group received 0.8 M lactic acid solution (to control for acidity of LS), and a third group received LS. The animals were sacrificed 12, 24, 48, 96 and 120 hours after the injection. Selected tissues were collected, fixed in 10% buffered formalin and used for immunohistochemistry and <it>in situ </it>hybridization. Other tissues were frozen and extracted for immunoblotting</p> <p>Results</p> <p>LS-injected animals had a slight decrease in body weight when compared to their initial weight and to both control groups. Using immunohistochemistry and <it>in situ </it>hybridization leptin expression was studied in multiple brain sections and peripheral adipose tissue of control and LS-injected rats. Strong cytoplasmic stain was observed by both techniques in neurons of the cerebral cortex, thalamus, hypothalamus, hippocampus and, to lesser degree, in the cells of the choroid plexus in the LS-injected rats. Control animals demonstrated much less intense staining in neurons located in the same regions using immunohistochemistry and almost no staining with <it>in situ </it>hybridization technique. Adipose tissue exhibited slight presence of leptin in LS-treated animals. In contrast no immunohistochemical staining for GM-CSF and TNFα was observed in brains from control and treated rats. Western blotting showed mild increase in leptin and leptin receptors in intestines and retroperitoneal adipose tissues of LS-injected rats.</p> <p>Conclusion</p> <p>This study demonstrates that direct administration of LS into rat CNS leads to a decrease in body weight of rats and an increase in the expression of leptin in specific areas of the brain and retroperitoneal adipose tissue.</p

TGFBR1 variants TGFBR1*6A and Int7G24A are not associated with an increased familial colorectal cancer risk

Variants of the transforming growth factor-beta receptor type 1 (TGFBR1) gene, TGFBR1*6A and Int7G24A, have been suggested to act as low-penetrance tumour susceptibility alleles with TGFBR1*6A being causally responsible for some cases of familial colorectal cancer (CRC). We performed a case–control study of 262 unrelated familial CRC cases; 83 hereditary non-polyposis colorectal cancer (HNPCC) and 179 non-HNPCC. Patients were genotyped for TGFBR1*6A and Int7G24A and compared with 856 controls. Further, we screened the coding region of TGFBR1 in affected members of a large family with CRC linked to 9q22.32-31.1. TGFBR1*6A allelic frequency was not significantly different in all of the familial cases compared with controls (0.107 and 0.106, respectively; P=0.915). In a subgroup analysis allele frequencies were, however, different between HNPCC and non-HNPCC familial cases (0.157 and 0.084, respectively; P=0.013). TGFBR1*6A genotype did not influence age of onset. Int7G24A allele frequencies were similar in cases and controls. No germ-line mutation was identified in the family with CRC linked to this chromosomal region. Our study provides no substantial support for the hypothesis that the polymorphic variants TGFBR1*6A or Int7G24A contribute to familial CRC risk. We cannot, however, exclude the possibility that TGFBR1 variants have a modifying effect on inherited risk per se

Integrins α2β1 and α11β1 regulate the survival of mesenchymal stem cells on collagen I

Although mesenchymal stem cells (MSCs) are the natural source for bone regeneration, the exact mechanisms governing MSC crosstalk with collagen I have not yet been uncovered. Cell adhesion to collagen I is mostly mediated by three integrin receptors – α1β1, α2β1 and α11β1. Using human MSC (hMSC), we show that α11 subunit exhibited the highest basal expression levels but on osteogenic stimulation, both α2 and α11 integrins were significantly upregulated. To elucidate the possible roles of collagen-binding integrins, we applied short hairpin RNA (shRNA)-mediated knockdown in hMSC and found that α2 or α11 deficiency, but not α1, results in a tremendous reduction of hMSC numbers owing to mitochondrial leakage accompanied by Bcl-2-associated X protein upregulation. In order to clarify the signaling conveyed by the collagen-binding integrins in hMSC, we analyzed the activation of focal adhesion kinase, extracellular signal-regulated protein kinase and serine/threonine protein kinase B (PKB/Akt) kinases and detected significantly reduced Akt phosphorylation only in α2- and α11-shRNA hMSC. Finally, experiments with hMSC from osteoporotic patients revealed a significant downregulation of α2 integrin concomitant with an augmented mitochondrial permeability. In conclusion, our study describes for the first time that disturbance of α2β1- or α11β1-mediated interactions to collagen I results in the cell death of MSCs and urges for further investigations examining the impact of MSCs in bone conditions with abnormal collagen I

Hemolysis Is Associated with Low Reticulocyte Production Index and Predicts Blood Transfusion in Severe Malarial Anemia

Background: Falciparum Malaria, an infectious disease caused by the apicomplexan parasite Plasmodium falciparum, is among the leading causes of death and morbidity attributable to infectious diseases worldwide. In Gabon, Central Africa, one out of four inpatients have severe malarial anemia (SMA), a life-threatening complication if left untreated. Emerging drug resistant parasites might aggravate the situation. This case control study investigates biomarkers of enhanced hemolysis in hospitalized children with either SMA or mild malaria (MM). Methods and Findings: Ninety-one children were included, thereof 39 SMA patients. Strict inclusion criteria were chosen to exclude other causes of anemia. At diagnosis, erythrophagocytosis (a direct marker for extravascular hemolysis, EVH) was enhanced in SMA compared to MM patients (5.0 arbitrary units (AU) (interquartile range (IR): 2.2–9.6) vs. 2.1 AU (IR: 1.3–3.9), p<0.01). Furthermore, indirect markers for EVH, (i.e. serum neopterin levels, spleen size enlargement and monocyte pigment) were significantly increased in SMA patients. Markers for erythrocyte ageing, such as CD35 (complement receptor 1), CD55 (decay acceleration factor) and phosphatidylserine exposure (annexin-V-binding) were investigated by flow cytometry. In SMA patients, levels of CD35 and CD55 on the red blood cell surface were decreased and erythrocyte removal markers were increased when compared to MM or reconvalescent patients. Additionally, intravascular hemolysis (IVH) was quantified using several indirect markers (LDH, alpha-HBDH, haptoglobin and hemopexin), which all showed elevated IVH in SMA. The presence of both IVH and EVH predicted the need for blood transfusion during antimalarial treatment (odds ratio 61.5, 95% confidence interval (CI): 8.9–427). Interestingly, this subpopulation is characterized by a significantly lowered reticulocyte production index (RPI, p<0.05). Conclusions: Our results show the multifactorial pathophysiology of SMA, whereby EVH and IVH play a particularly important role. We propose a model where removal of infected and non-infected erythrocytes of all ages (including reticulocytes) by EVH and IVH is a main mechanism of SMA. Further studies are underway to investigate the mechanism and extent of reticulocyte removal to identify possible interventions to reduce the risk of SMA development

Pretransplant Prediction of Posttransplant Survival for Liver Recipients with Benign End-Stage Liver Diseases: A Nonlinear Model

Background: The scarcity of grafts available necessitates a system that considers expected posttransplant survival, in addition to pretransplant mortality as estimated by the MELD. So far, however, conventional linear techniques have failed to achieve sufficient accuracy in posttransplant outcome prediction. In this study, we aim to develop a pretransplant predictive model for liver recipients ’ survival with benign end-stage liver diseases (BESLD) by a nonlinear method based on pretransplant characteristics, and compare its performance with a BESLD-specific prognostic model (MELD) and a generalillness severity model (the sequential organ failure assessment score, or SOFA score). Methodology/Principal Findings: With retrospectively collected data on 360 recipients receiving deceased-donor transplantation for BESLD between February 1999 and August 2009 in the west China hospital of Sichuan university, we developed a multi-layer perceptron (MLP) network to predict one-year and two-year survival probability after transplantation. The performances of the MLP, SOFA, and MELD were assessed by measuring both calibration ability and discriminative power, with Hosmer-Lemeshow test and receiver operating characteristic analysis, respectively. By the forward stepwise selection, donor age and BMI; serum concentration of HB, Crea, ALB, TB, ALT, INR, Na +; presence of pretransplant diabetes; dialysis prior to transplantation, and microbiologically proven sepsis were identified to be the optimal input features. The MLP, employing 18 input neurons and 12 hidden neurons, yielded high predictive accuracy, wit

Genomic Organization, Molecular Diversification, and Evolution of Antimicrobial Peptide Myticin-C Genes in the Mussel (Mytilus galloprovincialis)

Myticin-C is a highly variable antimicrobial peptide associated to immune response in Mediterranean mussel (Mytilus galloprovincialis). In this study, we tried to ascertain the genetic organization and the mechanisms underlying myticin-C variation and evolution of this gene family. We took advantage of the large intron size variation to find out the number of myticin-C genes. Using fragment analysis a maximum of four alleles was detected per individual at both introns in a large mussel sample suggesting a minimum of two myticin-C genes. The transmission pattern of size variants in two full-sib families was also used to ascertain the number of myticin-C genes underlying the variability observed. Results in both families were in accordance with two myticin-C genes organized in tandem. A more detailed analysis of myticin-C variation was carried out by sequencing a large sample of complementary (cDNA) and genomic DNA (gDNA) in 10 individuals. Two basic sequences were detected at most individuals and several sequences were constituted by combination of two different basic sequences, strongly suggesting somatic recombination or gene conversion. Slight within-basic sequence variation detected in all individuals was attributed to somatic mutation. Such mutations were more frequently at the C-terminal domain and mostly determined non-synonymous substitutions. The mature peptide domain showed the highest variation both in the whole cDNA and in the basic-sequence samples, which is in accordance with the pathogen recognition function associated to this domain. Although most tests suggested neutrality for myticin-C variation, evidence indicated positive selection in the mature peptide and C-terminal region. Three main highly supported clusters were observed when reconstructing phylogeny on basic sequences, meiotic recombination playing a relevant role on myticin-C evolution. This study demonstrates that mechanisms to generate molecular variation similar to that observed in vertebrates are also operating in molluscs

Design considerations in a sib-pair study of linkage for susceptibility loci in cancer

<p>Abstract</p> <p>Background</p> <p>Modern approaches to identifying new genes associated with disease allow very fine analysis of associaton and can be performed in population based case-control studies. However, the sibpair design is still valuable because it requires few assumptions other than acceptably high penetrance to identify genetic loci.</p> <p>Methods</p> <p>We conducted simulation studies to assess the impact of design factors on relative efficiency for a linkage study of colorectal cancer. We considered two test statistics, one comparing the mean IBD probability in affected pairs to its null value of 0.5, and one comparing the mean IBD probabilities between affected and discordant pairs. We varied numbers of parents available, numbers of affected and unaffected siblings, reconstructing the genotype of an unavailable affected sibling by a spouse and offspring, and elimination of sibships where the proband carries a mutation at another locus.</p> <p>Results</p> <p>Power and efficiency were most affected by the number of affected sibs, the number of sib pairs genotyped, and the risk attributable to linked and unlinked loci. Genotyping unaffected siblings added little power for low penetrance models, but improved validity of tests when there was genetic heterogeneity and for multipoint testing. The efficiency of the concordant-only test was nearly always better than the concordant-discordant test. Replacement of an unavailable affected sibling by a spouse and offspring recovered some linkage information, particularly if several offspring were available. In multipoint analysis, the concordant-only test was showed a small anticonservative bias at 5 cM, while the multipoint concordant-discordant test was generally the most powerful test, and was not biased away from the null at 5 cM.</p> <p>Conclusion</p> <p>Genotyping parents and unaffected siblings is useful for detecting genotyping errors and if allele frequencies are uncertain. If adequate allele frequency data are available, we suggest a single-point affecteds-only analysis for an initial scan, followed by a multipoint analysis of affected and unaffected members of all available sibships with additional markers around initial hits.</p