Charcot-Leyden crystals in a prostatic adenocarcinoma

A transrectal needle biopsy from a 63-year-old man was decided because of a high prostatic spesific antigen in the blood, and a hard right lobe in rectal examination. 10 examples were taken from each lobe. In 1 of 4 of the examples from the left lobe, which contained a small focus of adenocarcinoma, numerous eosinophils were observed to surround the carcinomatous focus and attack the carcinoma cells. Uniquely, at the same focus Charcot-Leyden crystals could be seen in the intraluminal space and stromal area. A carcinoma oriented eosinophil accumulation, and Charcot-Leyden crystals in prostate was not described before

Reviewing the review:a qualitative assessment of the peer review process in surgical journals

Abstract Background Despite rapid growth of the scientific literature, no consensus guidelines have emerged to define the optimal criteria for editors to grade submitted manuscripts. The purpose of this project was to assess the peer reviewer metrics currently used in the surgical literature to evaluate original manuscript submissions. Methods Manuscript grading forms for 14 of the highest circulation general surgery-related journals were evaluated for content, including the type and number of quantitative and qualitative questions asked of peer reviewers. Reviewer grading forms for the seven surgical journals with the higher impact factors were compared to the seven surgical journals with lower impact factors using Fisher’s exact tests. Results Impact factors of the studied journals ranged from 1.73 to 8.57, with a median impact factor of 4.26 in the higher group and 2.81 in the lower group. The content of the grading forms was found to vary considerably. Relatively few journals asked reviewers to grade specific components of a manuscript. Higher impact factor journal manuscript grading forms more frequently addressed statistical analysis, ethical considerations, and conflict of interest. In contrast, lower impact factor journals more commonly requested reviewers to make qualitative assessments of novelty/originality, scientific validity, and scientific importance. Conclusion Substantial variation exists in the grading criteria used to evaluate original manuscripts submitted to the surgical literature for peer review, with differential emphasis placed on certain criteria correlated to journal impact factors

Eosinophilic myocarditis mimicking acute coronary syndrome secondary to idiopathic hypereosinophilic syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>Eosinophilic myocarditis is a rare form of myocarditis. It is characterized pathologically by diffuse or focal myocardial inflammation with eosinophilic infiltration, often in association with peripheral blood eosinophilia. We report a case of eosinophilic myocarditis secondary to hypereosinophilic syndrome.</p> <p>Case presentation</p> <p>A 74-year-old Caucasian woman with a history of asthma, paroxysmal atrial fibrillation, stroke and coronary artery disease presented to the emergency department of our hospital with chest pain. Evaluations revealed that she had peripheral blood eosinophilia and elevated cardiac enzymes. Electrocardiographic findings were nonspecific. Her electrocardiographic finding and elevated cardiac enzymes pointed to a non-ST-elevated myocardial infarction. Echocardiogram showed a severe decrease in the left ventricular systolic function. Coronary angiogram showed nonobstructive coronary artery disease. She then underwent cardiac magnetic resonance imaging, which showed neither infiltrative myocardial diseases nor any evidence of infarction. This was followed by an endomyocardial biopsy which was consistent with eosinophilic myocarditis. Hematologic workup regarding her eosinophilia was consistent with hypereosinophilic syndrome. After being started on steroid therapy, her peripheral eosinophilia resolved and her symptoms improved. Her left ventricular ejection fraction, however, did not improve.</p> <p>Conclusion</p> <p>Eosinophilic myocarditis can present like an acute myocardial infarction and should be considered in the differential diagnosis of acute coronary syndrome in patients with a history of allergy, asthma or acute reduction of the left ventricular function with or without peripheral eosinophilia.</p

Habitual Physical Activity in Mitochondrial Disease

Mitochondrial disease is the most common neuromuscular disease and has a profound impact upon daily life, disease and longevity. Exercise therapy has been shown to improve mitochondrial function in patients with mitochondrial disease. However, no information exists about the level of habitual physical activity of people with mitochondrial disease and its relationship with clinical phenotype.Habitual physical activity, genotype and clinical presentations were assessed in 100 patients with mitochondrial disease. Comparisons were made with a control group individually matched by age, gender and BMI. = −0.49; 95% CI −0.33, −0.63, P<0.01). There were no systematic differences in physical activity between different genotypes mitochondrial disease.These results demonstrate for the first time that low levels of physical activity are prominent in mitochondrial disease. Combined with a high prevalence of obesity, physical activity may constitute a significant and potentially modifiable risk factor in mitochondrial disease

Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.

Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology

Mechanisms of leukocyte lipid body formation and function in inflammation

An area of increasingly interest for the understanding of cell signaling are the spatio-temporal aspects of the different enzymes involved in lipid mediator generation (eicosanoid-forming enzymes, phospholipases and their regulatory kinases and phosphatases) and pools of lipid precursors. The compartmentalization of signaling components within discrete and dynamic sites in the cell is critical for specificity and efficiency of enzymatic reactions of phosphorilation, enzyme activation and function. We hypothesized that lipid bodies - inducible non-membrane bound cytoplasmic lipid domains - function as specialized intracellular sites of compartmentalization of signaling with major roles in lipid mediator formation within leukocytes engaged in inflammatory process. Over the past years substantial progresses have been made demonstrating that all enzymes involved in eicosanoid synthesis localize at lipid bodies and lipid bodies are distinct sites for eicosanoid generation. Here we will review our current knowledge on the mechanisms of formation and functions of lipid bodies pertinent to inflammation

Decitabine immunosensitizes human gliomas to NY-ESO-1 specific T lymphocyte targeting through the Fas/Fas Ligand pathway

<p>Abstract</p> <p>Background</p> <p>The lack of effective treatments for gliomas makes them a significant health problem and highlights the need for the development of novel and innovative treatment approaches. Immunotherapy is an appealing strategy because of the potential ability for immune cells to traffic to and destroy infiltrating tumor cells. However, the absence of well-characterized, highly immunogenic tumor-rejection antigens (TRA) in gliomas has limited the implementation of targeted immune-based therapies.</p> <p>Methods</p> <p>We hypothesized that treatment with the demethylating agent, decitabine, would upregulate the expression of TRA on tumor cells, thereby facilitating enhanced surveillance by TRA-specific T cells.</p> <p>Results and Discussion</p> <p>Treatment of human glioma cells with decitabine increased the expression of NY-ESO-1 and other well characterized cancer testes antigens. The upregulation of NY-ESO-1 made these tumors susceptible to NY-ESO-1-specific T-cell recognition and lysis. Interestingly, decitabine treatment of T98 glioma cells also sensitized them to Fas-dependent apoptosis with an agonistic antibody, while a Fas blocking antibody could largely prevent the enhanced functional recognition by NY-ESO-1 specific T cells. Thus, decitabine treatment transformed a non-immunogenic glioma cell into an immunogenic target that was efficiently recognized by NY-ESO-1--specific T cells.</p> <p>Conclusions</p> <p>Such data supports the hypothesis that agents which alter epigenetic cellular processes may "immunosensitize" tumor cells to tumor-specific T cell-mediated lysis.</p

IFN-γ-inducible protein of 10 kDa upregulates the effector functions of eosinophils through β2 integrin and CXCR3

<p>Abstract</p> <p>Background</p> <p>Eosinophils play an important role in the pathogenesis of bronchial asthma and its exacerbation. Recent reports suggest the involvement of IFN-γ-inducible protein of 10 kDa (IP-10) in virus-induced asthma exacerbation. The objective of this study was to examine whether CXCR3 ligands including IP-10 modify the effector functions of eosinophils.</p> <p>Methods</p> <p>Eosinophils isolated from the blood of healthy donors were stimulated with CXCR3 ligands and their adhesion to rh-ICAM-1 was then measured using eosinophil peroxidase assays. The generation of eosinophil superoxide anion (O₂^-) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) release was evaluated to determine whether CXCR3 ligands induced eosinophil degranulation. Cytokine and chemokine production by eosinophils was examined using a Bio-plex assay.</p> <p>Results</p> <p>Eosinophil adhesion to ICAM-1 was significantly enhanced by IP-10, which also significantly induced eosinophil O₂^-generation in the presence of ICAM-1. Both the enhanced adhesion and O₂^-generation were inhibited by an anti-β₂integrin mAb or an anti-CXCR3 mAb. Other CXCR3 ligands, such as monokine induced by IFN-γ (Mig) and IFN-inducible T cell α chemoattractant (I-TAC), also induced eosinophil adhesion and O₂^-generation in the presence of ICAM-1. IP-10, but not Mig or I-TAC, increased the release of EDN. IP-10 increased the production of a number of cytokines and chemokines by eosinophils.</p> <p>Conclusions</p> <p>These findings suggest that CXCR3 ligands such as IP-10 can directly upregulate the effector functions of eosinophils. These effects might be involved in the activation and infiltration of eosinophils in the airway of asthma, especially in virus-induced asthma exacerbation.</p