Ezh2 and Runx1 Mutations Collaborate to Initiate Lympho-Myeloid Leukemia in Early Thymic Progenitors

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Cyclophosphamide treatment induces rejection of established P815 mastocytoma by enhancing CD4 priming and intratumoral infiltration of P1E/H‐2Kd‐specific CD8+ T cells

There is increasing evidence that the effect of chemotherapy on tumor growth is not cell autonomous but relies on the immune system. The objective of this study was therefore to decipher the cellular and molecular mechanisms underlying the role of innate and adaptive immunity in chemotherapy‐induced tumor rejection. Treatment of DBA/2 mice bearing P815 mastocytoma with cyclophosphamide induced rejection and long‐term protection in a CD4‐ and CD8‐dependent manner. A population of inflammatory‐type dendritic cells was dramatically expanded in the lymph nodes of mice that rejected the tumor and correlated with CD4‐dependent infiltration, in tumor bed, of tumor‐specific CD8⁺ T lymphocytes. Our data point to a major role of CD4⁺ T cells in inducing chemokine expression in the tumor, provoking migration of tumor‐specific CXCR3⁺ CD8⁺ T lymphocytes. Importantly, the analysis of CD8⁺ T cells specific to P1A/H‐2L^d and P1E/H‐2K^d revealed that cyclophosphamide altered the P815‐specific CD8 T repertoire by amplifying the response specific to the mutated P1E antigen.     

Human bone morphogenetic protein‐7 does not counteract aristolochic acid‐induced renal toxicity

Aristolochic acids (AA) are nephrotoxic and profibrotic agents, leading to chronic kidney disease. As some controversial studies have reported a nephroprotective effect of exogenous recombinant human bone morphogenetic protein (rhBMP)‐7 in several models of renal fibrosis, we investigated the putative effect of rhBMP‐7 to prevent progressive tubulointerstitial damage after AA intoxication in vitro and in vivo. In vitro, the toxicity of AA on renal tubular cells was demonstrated by an increase in vimentin as well as a decrease in β‐catenin expressions, reflecting a dedifferentiation process. Increased fibronectin and interleukin‐6 levels were measured in the supernatants. Enhanced α‐SMA mRNA levels associated to decreased E‐cadherin mRNA levels were also measured. Incubation with rhBMP‐7 only prevented the increase in vimentin and the decrease in β‐catenin expressions. In vivo, in a rat model of AA nephropathy, severe tubulointerstitial lesions induced by AA after 10 and 35 days (collagen IV deposition and tubular atrophy), were not prevented by the rhBMP‐7 treatment. Similarly, rhBMP‐7 did not ameliorate the significant increase in urinary concentrations of transforming growth factor‐β. In summary, our in vitro data demonstrated a poor beneficial effect of rhBMP‐7 to reverse cell toxicity while, in vivo, there was no beneficial effect of rhBMP‐7. Therefore, further investigations are needed to confirm the exact role of BMP‐7 in progressive chronic kidney disease. Copyright © 2015 John Wiley & Sons, Ltd.     

Significance of physicochemical forms of storage in microalgae in predicting copper transfer to filter-feeding oysters (Crassostrea gigas)

Copper distribution has been examined in two microalgae (Haslea ostrearia, Diatom; Tetraselmis suecica, Prasinophyceae) exposed to Cu at 30 microg/L(-1). Exchangeable copper linked at the cell surface was desorbed using 8-hydroxyquinoline-5-sulfonate as complexing agent. Then, incorporated copper was separated between soluble and insoluble fractions. In addition, algae were resuspended in acid solutions, the pHs of which covered the range existing in the digestive tract of bivalves. Considering that the soluble fraction is the most easily transferred in the food chain and that exchangeable Cu is easily desorbed, the percentages of Cu potentially available in microalgae have been assessed. These percentages have been compared with those retained in oysters Crassostrea gigas fed with contaminated microalgae in previous studies. In H. ostrearia, the potentially available fraction of Cu (90%) was very similar to the percentage retained by oysters (93%) when the bivalves were acclimated to this food for 3 weeks. Only half (21%) of the potentially available Cu of T. suecica (42%) was readily assimilated in oysters after 3 weeks. This is in agreement with the results of the desorption tests at physiological pHs which showed that only 15-25% of Cu was lost, despite solubilization of other constituents of T. suecica as demonstrated by the decrease in their dry weight. Bioavailability determined from metal speciation in food allows a relevant prediction of the trophic transfer in the case of H. ostrearia, but caution is recommended in generalizing this mode of assessment as shown in the case of T. suecica.     

Study on the effects of some factors that affect sea surface emissivity retrievals

The first aim of this article is to study the impact of some factors (effective wavelength, temperature, and aerial average emission angle) on sea surface emissivity (SSE) retrievals. It is well known that SSE is weakly influenced by these factors when we consider that each one of them acts independently from the others. However, taking them together, these factors are highly significant. The calculation of SSE including these factors has clearly brought out a high level of concordance between a theoretical model and in situ measurements for a wavelength of 11.0 µm especially at observation angles of 55° and 65° for wind speeds of 5 and 10 m s^?1. Wavelengths 8.7 and 12.0 µm also show, in most cases, a near to 0.000 or a negligible negative bias for an observation angle up to 55°. At wavelength 12 µm, the viewing angle of 65° seems to be questionable due to some inconsistencies and element of physics not well determined in practical terms.     

Tejido graso epicárdico,calcificación arterial coronaria y mortalidad en pacientes con enfermedad renal crónica avanzada y hemodiálisis

Introduction and objectivesEpicardial and mediastinal adipose tissue (EAT, MAT) are linked to metabolic syndrome and coronary artery disease. Patients with chronic kidney disease (CKD) have thicker EAT. We assessed if EAT and MAT could be associated with increased mortality and cardiovascular events in patients with advanced CKD and haemodialysis therapy.MethodsA post-hoc study was performed. We analyzed a prospective series of 104 cases. EAT thickness was quantified by a multislice synchronized computed tomography (MSCT).ResultsThe follow-up period was 112.68 (109.94 -115.42) months. The optimal cut-off point of EAT for prediction of total mortality was 11.45 mm (92.86% and 43.75%). EAT thickness was associated with serum albumin levels, serum triglyceride levels, phosphorus and calcium phosphate product. The EAT was greater in haemodialysis patients compared to those with advanced CKD (P<.001). Patients with diabetes mellitus had greater EAT and MAT thickness (P=.018). At the end of follow up, the survival average time of patients with EAT thickness <11.45 mm was 97.48 months vs. 76.65 months for thickness > 11.45 mm (P=.007).ConclusionsA higher EAT and MAT thickness was associated with increased mortality. Furthermore, EAT was associated with lower free survival time to fatal and non-fatal cardiovascular events. The measurement of EAT and MAT by MSCT could be a prognostic tool to predict cardiovascular events and mortality risk in advanced CKD patients.     

Primary breast angiosarcoma: a rare presentation of rare tumor – case report

Background

Primary breast angiosarcoma is defined as malignant proliferation showing endothelial differentiation. It is a very rare tumour (0.05% of primary mammary cancers), whose diagnosis can be difficult.

Case presentation

We report the observation of a patient with no previous history, aged 27 years. The clinical examination finds a right breast discreetly increased in volume. The trucut biopsy was in favour of a lactating tubular adenoma. However, an immunohistochemical complement was requested. An absence of pancytokeratin labelling contrasted with strong expression of CD31, CD34 (endothelial markers) are described. The proliferation index (Ki67) was estimated at 30%. This led to the conclusion that the phenotypic aspect is related to a vascular proliferation that evokes an angiosarcoma. After a multidisciplinary assessment, the patient benefited from an enlarged excision of the tumour. The histopathological examination of the surgical specimen found an infiltrating mesenchymal proliferation made of vessels of variable sizes anastomosed to vascular slits with lesional limits. The immunohistochemical examination on the surgical specimen showed to the same phenotypic profile on biopsy. The final diagnosis was a high-grade mammary angiosarcoma of incomplete excision. The patient refused any additional surgical management; external radiotherapy and close supervision were prescribed. After eight months of evolution, no local or remote recurrence was reported.

Conclusion

Primary breast angiosarcoma is a mesenchymal malignant tumour of rare vascular origin. Our observation is peculiar by the absence of any prior radiotherapy, its clinical presentation, its morpho-phenotypic characteristics, its management and its evolutive aspects.

     

Skeletal manifestations in Behçet's disease. A report of 79 cases

PURPOSE: Our aim is to describe the skeletal manifestations of Behcet's disease (BD) among young adults in a military population. METHODS: We conducted a retrospective study of 176 patients with BD who were followed between 1980 and 2005. All the patients fulfilled the international study group on Behcet's disease diagnostic criteria. RESULTS: Rheumatic manifestations were noticed in 79 out of 176 patients (45%), ranking second after the skin and mucosal manifestations of the disease. Articular manifestations were the first disease manifestation in 16.5% of the patients. Inflammatory arthralgias were the most common manifestation and observed in 81%, interesting mainly the large lower limb joints. Disease course was acute in most of the patients. Arthritis was less common: oligoarthritis (7.5%), monoarthritis (6.5%) and polyarthritis (5%). Axial involvement was also noted: spine pain in 29%, isolated sacroiliitis in 7.5%, and definite ankylosing spondylitis in 5%. CONCLUSION: Joint involvement is common in BD and could be the first manifestation of the disease. Most of the patients present with inflammatory arthralgias of the large lower limb joints. Disease course is usually favourable, spontaneously or with treatment. However, in our study population, skeletal manifestations were responsible for significant disability.     

Variation in T-SPOT.TB Spot Interpretation between Independent Observers from Different Laboratories

T-SPOT.TB is a specific assay for the diagnosis of tuberculosis. The assay needs to be performed with freshly isolated cells, and interpretation requires training. T-SPOT.TB has been used in various clinical-epidemiological settings, but so far no studies have evaluated the effect of interobserver variation in test reading. Our aim was to evaluate variation between different observers in reading T-SPOT.TB results. The study was nested within an ongoing cohort study, in which part of the T-SPOT.TB had been performed with frozen material. Culture plates were read visually by four different observers from two laboratories and by two automated readers. Of 313 T-SPOT.TB assays, 235 were performed with fresh cells and 78 were performed with frozen cells. No significant difference was found between results obtained with fresh cells and those obtained with frozen cells. The percentage of positive results varied between readers by maximally 15%; five/six raters were within a 6% difference in positive results. Analysis of the observed interrater differences showed that some individuals systematically counted more spots than others did. Because test interpretation includes subtraction of background values, this systematic variance had little influence on interindividual differences. The test result as positive or negative varied between independent raters, mainly due to samples with values around the cutoff. This warrants further study regarding determinants affecting the reading of T-SPOT.TB.Roughly a century after the introduction of the tuberculin skin test (TST), the recent development of gamma interferon release assays (IGRA) for specific detection of infection with Mycobacterium tuberculosis has realized a new class of immunodiagnostic tests that have extensively been evaluated for detection both of active tuberculosis (TB) and of latent TB infection (1, 2, 4, 7). T-SPOT.TB and QuantiFERON-TB Gold in-tube are the commercially available and approved IGRA formats, being based on culture of isolated peripheral blood mononuclear cells (PBMCs) and of whole blood, respectively. Numerous studies that evaluated the use of IGRA have been published in the past several years, showing their particular value for detection of latent TB infection in populations with high rates of false-positive TSTs due to Mycobacterium bovis BCG vaccination or exposure to nontuberculous mycobacteria (3, 5). T-SPOT.TB is based on the enzyme-linked immunospot assay technique in which cells responding with gamma interferon production after antigen stimulation are visualized as spots, which must be enumerated. This can be done by use of an automated spot reader or by using a magnifying glass. The assay is performed in four wells with different stimulations: medium as a negative control, phytohemagglutinin as a positive control, and peptides of the TB-specific antigens ESAT-6 (panel A of the assay) and CFP-10 (panel B of the assay). One of the disadvantages of T-SPOT.TB is that it must be performed with fresh material, which may not always be convenient. As the assay is based on single-well culture for each stimulus, random variability cannot be detected. Another disadvantage is that counting the spots might lead to variation when results are read by different observers or automated readers.Thus far, no studies have addressed the interobserver variability of the T-SPOT.TB. In the present study, these issues were addressed by using material obtained within an ongoing cohort study in The Netherlands in which part of the T-SPOT.TB assay was performed with frozen material for logistical reasons (blood arriving in the laboratory on a Friday was frozen since the assay needed to be completed 20 h later). We evaluated the reading of the T-SPOT.TB plates in two laboratories by different observers and by two automated readers. Next, we compared results of T-SPOT.TB obtained with freshly isolated cells to those obtained with frozen and thawed cells.     

Treatment of Chemotherapy-Induced Nausea and Vomiting

Background

Recent improvements in medical oncology include both development of anticancer and supportive therapy. Serotonin receptor antagonists were introduced in clinical practice 20 years ago. Since then, the prevention and treatment of chemotherapy-induced nausea and vomiting allows continuing efficacious chemotherapy that earlier had to be stopped sometimes for intolerance.

Aim

This anniversary review summarises the current antiemetic arsenal focussing on the most potent antiemetic drugs such as serotonin and substance P receptor antagonists.

Result

Antiemetic treatment improves quality of life under chemotherapy and contributes to the survival benefit as well. In spite of the use of these new drugs, a significant number of patients still experience nausea and vomiting. Special complications like delayed emesis can be alleviated by combination therapies.

Conclusion

Prevention and optimal management of chemotherapy-induced nausea and vomiting should be a goal for most patients receiving emetogenic chemotherapy.