Acquired A amyloidosis from injection drug use presenting with atraumatic splenic rupture in a hospitalized patient: a case report

<p>Abstract</p> <p>Introduction</p> <p>Little is known about splenic rupture in patients who develop systemic acquired A amyloidosis. This is the first report of a case of atraumatic splenic rupture in a patient with acquired A amyloidosis from chronic injection drug use.</p> <p>Case presentation</p> <p>A 58-year-old Caucasian man with a long history of injection drug use, hospitalized for infective endocarditis, experienced atraumatic splenic rupture and underwent splenectomy. Histopathological and microbiological analyses of the splenic tissue were consistent with systemic acquired A amyloidosis, most likely from injection drug use, that led to splenic rupture without any recognized trauma or evidence of bacterial embolization to the spleen.</p> <p>Conclusion</p> <p>In patients with chronic inflammatory conditions, including the use of injection drugs, who experience acute onset of left upper quadrant pain, the diagnosis of atraumatic splenic rupture must be considered.</p

Receptors for Hyaluronic Acid and Poliovirus: A Combinatorial Role in Glioma Invasion?

Background: CD44 has long been associated with glioma invasion while, more recently, CD155 has been implicated in playing a similar role. Notably, these two receptors have been shown closely positioned on monocytes. Methods and Findings: In this study, an up-regulation of CD44 and CD155 was demonstrated in established and earlypassage cultures of glioblastoma. Total internal reflected fluorescence (TIRF) microscopy revealed close proximity of CD44 and CD155. CD44 antibody blocking and gene silencing (via siRNA) resulted in greater inhibition of invasion than that for CD155. Combined interference resulted in 86 % inhibition of invasion, although in these investigations no obvious evidence of synergy between CD44 and CD155 in curbing invasion was shown. Both siRNA-CD44 and siRNA-CD155 treated cells lacked processes and were rounder, while live cell imaging showed reduced motility rate compared to wild type cells. Adhesion assay demonstrated that wild type cells adhered most efficiently to laminin, whereas siRNA-treated cells (p,0.0001 for both CD44 and CD155 expression) showed decreased adhesion on several ECMs investigated. BrdU assay showed a higher proliferation of siRNA-CD44 and siRNA-CD155 cells, inversely correlated with reduced invasion. Confocal microscopy revealed overlapping of CD155 and integrins (b1, avb1 and avb3) on glioblastoma cell processes whereas siRNAtransfected cells showed consequent reduction in integrin expression with no specific staining patterns. Reduced expression of Rho GTPases, Cdc42, Rac1/2/3, RhoA and RhoB, was seen in siRNA-CD44 and siRNA-CD155 cells. In contrast t

Integrating isotopes and documentary evidence : dietary patterns in a late medieval and early modern mining community, Sweden

We would like to thank the Archaeological Research Laboratory, Stockholm University, Sweden and the Tandem Laboratory (Ångström Laboratory), Uppsala University, Sweden, for undertaking the analyses of stable nitrogen and carbon isotopes in both human and animal collagen samples. Also, thanks to Elin Ahlin Sundman for providing the δ13C and δ15N values for animal references from Västerås. This research (Bäckström’s PhD employment at Lund University, Sweden) was supported by the Berit Wallenberg Foundation (BWS 2010.0176) and Jakob and Johan Söderberg’s foundation. The ‘Sala project’ (excavations and analyses) has been funded by Riksens Clenodium, Jernkontoret, Birgit and Gad Rausing’s Foundation, SAU’s Research Foundation, the Royal Physiographic Society of Lund, Berit Wallenbergs Foundation, Åke Wibergs Foundation, Lars Hiertas Memory, Helge Ax:son Johnson’s Foundation and The Royal Swedish Academy of Sciences.Peer reviewedPublisher PD

Noninvasive assessment of asthma severity using pulse oximeter plethysmograph estimate of pulsus paradoxus physiology

<p>Abstract</p> <p>Background</p> <p>Pulsus paradoxus estimated by dynamic change in area under the oximeter plethysmograph waveform (PEP) might provide a measure of acute asthma severity. Our primary objective was to determine how well PEP correlates with forced expiratory volume in 1-second (%FEV₁) (criterion validity) and change of %FEV₁(responsiveness) during treatment in pediatric patients with acute asthma exacerbations.</p> <p>Methods</p> <p>We prospectively studied subjects 5 to 17 years of age with asthma exacerbations. PEP, %FEV₁, airway resistance and accessory muscle use were recorded at baseline and at 2 and 4 hours after initiation of corticosteroid and bronchodilator treatments. Statistical associations were tested with Pearson or Spearman rank correlations, logistic regression using generalized estimating equations, or Wilcoxon rank sum tests.</p> <p>Results</p> <p>We studied 219 subjects (median age 9 years; male 62%; African-American 56%). Correlation of PEP with %FEV₁demonstrated criterion validity (r = - 0.44, 95% confidence interval [CI], - 0.56 to - 0.30) and responsiveness at 2 hours (r = - 0.31, 95% CI, - 0.50 to - 0.09) and 4 hours (r = - 0.38, 95% CI, - 0.62 to - 0.07). PEP also correlated with airway resistance at baseline (r = 0.28 for ages 5 to 10; r = 0.45 for ages 10 to 17), but not with change over time. PEP was associated with accessory muscle use (OR 1.16, 95% CI, 1.11 to 1.21, P < 0.0001).</p> <p>Conclusions</p> <p>PEP demonstrates criterion validity and responsiveness in correlations with %FEV₁. PEP correlates with airway resistance at baseline and is associated with accessory muscle use at baseline and at 2 and 4 hours after initiation of treatment. Incorporation of this technology into contemporary pulse oximeters may provide clinicians improved parameters with which to make clinical assessments of asthma severity and response to treatment, particularly in patients who cannot perform spirometry because of young age or severity of illness. It might also allow for earlier recognition and improved management of other disorders leading to elevated pulsus paradoxus.</p

Metadherin Mediates Lipopolysaccharide-Induced Migration and Invasion of Breast Cancer Cells

BACKGROUND: Breast cancer is the most prevalent cancer in women worldwide and metastatic breast cancer has very poor prognosis. Inflammation has been implicated in migration and metastasis of breast cancer, although the exact molecular mechanism remains elusive. PRINCIPAL FINDINGS: We show that the pro-inflammatory endotoxin Lipopolysaccharide (LPS) upregulates the expression of Metadherin (MTDH), a recently identified oncogene, in a number of breast cancer lines. Stable knockdown of MTDH by shRNA in human breast MDA-MB-231 cells abolishes LPS-induced cell migration and invasion as determined by several in vitro assays. In addition, knockdown of MTDH diminishes Nuclear Factor-kappa B (NF-κB) activation by LPS and inhibited LPS-induced IL-8 and MMP-9 production. CONCLUSIONS: These results strongly suggest that MTDH is a pivotal molecule in inflammation-mediated tumor metastasis. Since NF-κB, IL-8 and MMP-9 play roles in LPS-induced invasion or metastasis, the mechanism of MTDH-promoted invasion and metastasis may be through the activation of NF-κB, IL-8 and MMP-9, also suggesting a role of MTDH in regulating both inflammatory responses and inflammation-associated tumor invasion. These findings indicate that MTDH is involved in inflammation-induced tumor progression, and support that MTDH targeting therapy may hold promising prospects in treating breast cancer

Effect of nitric oxide on mitochondrial activity of human synovial cells

<p>Abstract</p> <p>Background</p> <p>Nitric oxide (NO) is a messenger implicated in the destruction and inflammation of joint tissues. Cartilage and synovial membrane from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) have high levels of NO. NO is known to modulate various cellular pathways and, thus, inhibit the activity of the mitochondrial respiratory chain (MRC) of chondrocytes and induce the generation of reactive oxygen species (ROS) and cell death in multiple cell types. For these reasons, and because of the importance of the synovial membrane in development of OA pathology, we investigated the effects of NO on survival, mitochondrial function, and activity of fibroblastic human OA synovial cells.</p> <p>Methods</p> <p>Human OA synovia were obtained from eight patients undergoing hip joint replacement. Sodium nitroprusside (SNP) was used as a NO donor compound and cell viability was evaluated by MTT assays. Mitochondrial function was evaluated by analyzing the mitochondrial membrane potential (Δψm) with flow cytometry using the fluorofore DePsipher. ATP levels were measured by luminescence assays, and the activities of the respiratory chain complexes (complex I: NADH CoQ₁reductase, complex II: succinate dehydrogenase, complex III: ubiquinol-cytochrome c reductase, complex IV: cytochrome c oxidase) and citrate synthase (CS) were measured by enzymatic assay. Protein expression analyses were performed by western blot.</p> <p>Results</p> <p>SNP at a concentration of 0.5 mM induced cell death, shown by the MTT method at different time points. The percentages of viable cells at 24, 48 and 72 hours were 86.11 ± 4.9%, 74.31 ± 3.35%, and 43.88 ± 1.43%, respectively, compared to the basal level of 100% (*<it>p </it>< 0.05). SNP at 0.5 mM induced depolarization of the mitochondrial membrane at 12 hours with a decrease in the ratio of polarized cells (basal = 2.48 ± 0.28; SNP 0.5 mM = 1.57 ± 0.11; *<it>p </it>< 0.01). The time course analyses of treatment with SNP at 0.5 mM demonstrated that treatment reliably and significantly reduced intracellular ATP production (68.34 ± 14.3% vs. basal = 100% at 6 hours; *<it>p </it>< 0.05). The analysis of the MRC at 48 hours showed that SNP at 0.5 mM increased the activity of complexes I (basal = 36.47 ± 3.92 mol/min/mg protein, SNP 0.5 mM = 58.08 ± 6.46 mol/min/mg protein; *<it>p </it>< 0.05) and III (basal = 63.87 ± 6.93 mol/min/mg protein, SNP 0.5 mM = 109.15 ± 30.37 mol/min/mg protein; *<it>p </it>< 0.05) but reduced CS activity (basal = 105.06 ± 10.72 mol/min/mg protein, SNP at 0.5 mM = 66.88 ± 6.08 mol/min/mg protein.; *<it>p </it>< 0.05), indicating a decrease in mitochondrial mass. Finally, SNP regulated the expression of proteins related to the cellular cycle; the NO donor decreased bcl-2, mcl-1 and procaspase-3 protein expression.</p> <p>Conclusions</p> <p>This study suggests that NO reduces the survival of OA synoviocytes by regulating mitochondrial functionality, as well as the proteins controlling the cell cycle.</p

p16 Mutation Spectrum in the Premalignant Condition Barrett's Esophagus

Background: Mutation, promoter hypermethylation and loss of heterozygosity involving the tumor suppressor gene p16 (CDKN2a/INK4a) have been detected in a wide variety of human cancers, but much less is known concerning the frequency and spectrum of p16 mutations in premalignant conditions. Methods and Findings: We have determined the p16 mutation spectrum for a cohort of 304 patients with Barrett’s esophagus, a premalignant condition that predisposes to the development of esophageal adenocarcinoma. Forty seven mutations were detected by sequencing of p16 exon 2 in 44 BE patients (14.5%) with a mutation spectrum consistent with that caused by oxidative damage and chronic inflammation. The percentage of patients with p16 mutations increased with increasing histologic grade. In addition, samples from 3 out of 19 patients (15.8%) who underwent esophagectomy were found to have mutations. Conclusions: The results of this study suggest the environment of the esophagus in BE patients can both generate an

Replicative Age Induces Mitotic Recombination in the Ribosomal RNA Gene Cluster of Saccharomyces cerevisiae

Somatic mutations contribute to the development of age-associated disease. In earlier work, we found that, at high frequency, aging Saccharomyces cerevisiae diploid cells produce daughters without mitochondrial DNA, leading to loss of respiration competence and increased loss of heterozygosity (LOH) in the nuclear genome. Here we used the recently developed Mother Enrichment Program to ask whether aging cells that maintain the ability to produce respiration-competent daughters also experience increased genomic instability. We discovered that this population exhibits a distinct genomic instability phenotype that primarily affects the repeated ribosomal RNA gene array (rDNA array). As diploid cells passed their median replicative life span, recombination rates between rDNA arrays on homologous chromosomes progressively increased, resulting in mutational events that generated LOH at >300 contiguous open reading frames on the right arm of chromosome XII. We show that, while these recombination events were dependent on the replication fork block protein Fob1, the aging process that underlies this phenotype is Fob1-independent. Furthermore, we provide evidence that this aging process is not driven by mechanisms that modulate rDNA recombination in young cells, including loss of cohesion within the rDNA array or loss of Sir2 function. Instead, we suggest that the age-associated increase in rDNA recombination is a response to increasing DNA replication stress generated in aging cells

Manovacuometria realizada por meio de traqueias de diferentes comprimentos

Manovacuometry is a simple, fast, and non-invasive test, with maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) obtained to assist respiratory muscle assessment. Currently, there is a wide variety of models and brands of manovacuometers with different trachea diameters and lengths. However, the interference of these models in the measurements obtained by these equipments needs to be investigated. Thus, this study mainly aimed to verify the influence of tracheal length on maximal respiratory pressures (MRP), obtained by an analog manovacuometer, in healthy individuals. Our secondary objective was to verify the correlation between measurements. Fifty individuals, aged 18 to 30, of both sexes, were evaluated by spirometry and manovacuometry. MIP and MEP were performed using tracheas with same internal diameter (0.5 cm) and 30 cm, 60 cm, and 90 cm length. Significantly lower MIP values were observed when comparing a 90 cm trachea to 30 and 60 cm tracheas (Friedman’s ANOVA test and Wilcoxon test with Bonferroni adjustment). Tracheas with 30, 60, and 90 cm length and same diameter did not affect MIP and MEP values, except the 90 cm trachea for MIP values, which may interfere in the physical therapy clinical practice. Further studies are required to analyze the need for standardizing the trachea length used in manovacuometers.La manovacuometría es una prueba sencilla, rápida y no invasiva por la cual se obtienen la presión inspiratoria máxima (PImax) y la presión espiratoria máxima (PEmax), con el objetivo de ayudar en el examen muscular respiratorio. Hoy día se encuentran una gran variedad de modelos y marcas de manovacuometros, con diferentes diámetros y longitudes de las tráqueas, pero hacen falta estudios sobre la interferencia de estos modelos en las mediciones por este instrumento. En este texto se propone examinar en sujetos sanos, en primer lugar, la influencia en la longitud de las tráqueas en las presiones respiratorias máximas, obtenidas por manovacuometros analógicos, y en segundo lugar comprobar la existencia de correlación entre las mediciones. Se evaluaron a cincuenta sujetos entre 18 y 30 años de edad, tanto varones como mujeres, empleando la espirometría y la manovacuometría. Se midió la PImax y la PEmax empleando tráqueas de mismo diámetro interno (0,5 cm) y con longitudes de 30, 60 e 90 cm. Se observaron valores significativamente menores de PImax con la tráquea de longitud de 90 cm en comparación con las PImax con las tráqueas de 30 y 60 cm (prueba de Friedman’s ANOVA, la de Wilcoxon con ajustes de Bonferroni). Las tráqueas de 30, 60 y 90 cm de longitud y mismo diámetro no influyeron en los valores de la PEmax y de la PImax, con excepción de la tráquea de 90 cm en los valores de la PImax, lo que puede interferir la práctica clínica fisioterapéutica. Se necesitan más estudios para evaluar la necesidad de estándares de la longitud de tráqueas empleadas en manovacuometros.A manovacuometria é um teste simples, rápido e não invasivo por meio do qual a pressão inspiratória máxima (PImáx) e a pressão expiratória máxima (PEmáx) são obtidas, a fim de auxiliar na avaliação muscular respiratória. Atualmente, há grande variedade de modelos e marcas de manovacuômetros, com diferentes diâmetros e comprimentos de traqueias, no entanto, a interferência desses modelos nas medidas obtidas por esses equipamentos necessita de investigação. Desta forma, o objetivo primário deste estudo foi verificar a influência do comprimento de traqueias nas pressões respiratórias máximas, obtidas por meio de manovacuômetro analógico, em indivíduos saudáveis e, secundariamente, se há correlação entre as medidas. Foram avaliados 50 indivíduos, de 18 a 30 anos, de ambos os sexos, por meio da espirometria e manovacuometria. As PImáx e PEmáx foram realizadas com uso de traqueias de mesmo diâmetro interno (0,5 cm) e comprimentos de 30, 60 e 90 cm. Foram observados valores significativamente menores de PImáx obtidos com a traqueia de comprimento de 90 cm comparados às PImáx obtidas com as traqueias de 30 e 60 cm (teste de Friedman’s ANOVA com teste de Wilcoxon com ajuste de Bonferroni). As traqueias de 30, 60 e 90 cm de comprimento e mesmo diâmetro não influenciaram os valores de PEmáx e PImáx, exceto a traqueia de 90 cm para os valores de PImáx, o que pode interferir na prática clínica fisioterapêutica. Novos estudos são necessários para analisar a necessidade de padronização do comprimento da traqueia utilizada em manovacuômetros