Intramucosal leiomyosarcoma of the stomach following hereditary retinoblastoma in childhood – a case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Leiomyosarcomas of the stomach are very rare. At the time of primary diagnosis the tumors are most often in advanced stage and the patients complain of abdominal pain due to large tumor size. Endosonographically, the tumors impress as submucous mass with suspicion to malignancy. Sarcomas following hereditary retinoblastoma in childhood are in generally located in the soft tissue. Structural alterations of the <it>retinoblastoma </it>gene (<it>RB1</it>) seem to be involved in the pathogenesis.</p> <p>Case presentation</p> <p>A 37-year-old german male suffered from reflux disorder. In endoscopic examination a small polypous tumor was detected in the stomach. The resection specimen revealed an intramucosal leiomyosarcoma. At the age of one year, the patient had a retinoblastoma.</p> <p>Conclusion</p> <p>This is the unique report of an intramucosal gastric leiomyosarcoma and the first account of a gastric leiomyosarcoma after retinoblastoma in childhood. A careful clinical follow-up is advised because of increased risk of developing further metachronous malignancies.</p

MAPK Kinase Kinase-1 Is Essential for Cytokine-Induced c-Jun NH2-Terminal Kinase and Nuclear Factor-κB Activation in Human Pancreatic Islet Cells

OBJECTIVE—The transcription factor nuclear factor-κB (NF-κB) and the mitogen-activated protein kinases (MAPKs) c-Jun NH2-terminal kinase (JNK) 1/2 are known to play decisive roles in cytokine-induced damage of rodent β-cells. The upstream events by which these factors are activated in response to cytokines are, however, uncharacterized. The aim of the present investigation was to elucidate a putative role of the MAPK kinase kinase-1 (MEKK-1) in cytokine-induced signaling

Gene Expression Profiles of Beta-Cell Enriched Tissue Obtained by Laser Capture Microdissection from Subjects with Type 2 Diabetes

Background: Changes in gene expression in pancreatic beta-cells from type 2 diabetes (T2D) should provide insights into their abnormal insulin secretion and turnover. Methodology/Principal Findings: Frozen sections were obtained from cadaver pancreases of 10 control and 10 T2D human subjects. Beta-cell enriched samples were obtained by laser capture microdissection (LCM). RNA was extracted, amplified and subjected to microarray analysis. Further analysis was performed with DNA-Chip Analyzer (dChip) and Gene Set Enrichment Analysis (GSEA) software. There were changes in expression of genes linked to glucotoxicity. Evidence of oxidative stress was provided by upregulation of several metallothionein genes. There were few changes in the major genes associated with cell cycle, apoptosis or endoplasmic reticulum stress. There was differential expression of genes associated with pancreatic regeneration, most notably upregulation of members of the regenerating islet gene (REG) family and metalloproteinase 7 (MMP7). Some of the genes found in GWAS studies to be related to T2D were also found to be differentially expressed. IGF2BP2, TSPAN8, and HNF1B (TCF2) were upregulated while JAZF1 and SLC30A8 were downregulated. Conclusions/Significance: This study made possible by LCM has identified many novel changes in gene expression tha

Effect of fibrous diet and vitamin C inclusion on uniformity, carcass traits, skeletal strength, and behavior of broiler breeder pullets

This experiment studied the effect of broiler breeder nutritional strategies on uniformity, carcass traits, tibia parameters, and behavior during rearing and prebreeder periods (up to 22 wk of age). One-day-old pullets (n = 384) were randomly assigned to 4 treatments arranged as a 2 × 2 factorial, with 2 fiber levels (control vs. fibrous diet, 15% diluted in AMEn and nutrient content) and 2 vitamin C feed inclusions (0 vs. 200 mg/kg). At 6, 15, and 22 wk, blood sampling was carried out (4 birds/replicate) to determine serum alkaline phosphatase (ALP) levels, and behavior was observed by visual scan sampling. At 22 wk, carcass traits, tibia parameters, and intestinal morphology were assessed (2 birds/replicate), and tail- and wing-feather integrity of all birds were scored. Fibrous diet did not modify BW uniformity, mortality, or tibia growth when compared with control diet. Pullets fed the fibrous diet had lower tibia breaking strength, elastic modulus, and ash content values (P < 0.05). They also had lower ALP serum level at 6 and 22 wk (P < 0.05), their breast muscle was less developed (18.5 vs. 19.8%, P < 0.05), and their abdominal fat deposition was higher (1.14 vs. 0.87%, P < 0.05). At 15 and 22 wk, they performed, on average, 97% less grasping feather pecking and 45% less non-food object pecking behaviors, and their wing-feather score was lower (P < 0.05) at 22 wk. Tail- and wing-feather scores of the control treatments were reduced by vitamin C inclusion (tail: 0.30 vs. 1.15, P < 0.05; wing: 0.98 vs. 1.26, P < 0.05) at 22 wk. In conclusion, fibrous diet improves carcass traits (reduces breast muscle and increases abdominal fat deposition), deteriorates bone mineral deposition and thus skeletal strength, and reduces stereotypic behaviors, improving wing-feather integrity. Vitamin C inclusion improves tail- and wing-feather integrity of lower in feed allowance

Circadian regulation of islet genes involved in insulin production and secretion

Both transcription factors albumin site d-binding protein (DBP) and thyrotroph embryonic factor (TEF) are elements of the "cell-clock". Their circadian accumulation in suprachiasmatic nucleus (SCN) and peripheral tissues such as liver, kidney and lung is thought to participate in controlling circadian regulation of downstream genes. TEF and DBP control elements have never been investigated in the insulin-secreting cells, but impairment of the circadian rhythm of the beta-cells might be involved in the development of diabetic state as type 2 diabetics have lost daily temporal variations of insulin secretion. We investigated the expression pattern of TEF and DBP in insulin-secreting cells. TEF and DBP transcripts are expressed at extremely high levels in human pancreatic islets compared to other tissues, suggesting a potentially important circadian regulation of these cells. Both TEF and DPB accumulate in a circadian way in insulin-secreting cells after a serum shock known to restore circadian rhythms in cultured cells. In addition, the expression of islet-specific genes involved in glucose sensing (glucose transporter 2 (Glut2), glucokinase), insulin production (insulin) and secretion (migration inhibitory factor (MIF), somatostatin and syntaxin 1A) were modulated in the same daily rhythm as well. The circadian deregulation of these genes could therefore participate in the diabetic state development

Effects of dicopper oxide and copper sulfate on growth performance and gut microbiota in broilers

ABSTRACT: An experiment was conducted to determine the effects of two sources of copper (Cu) from copper sulfate (CuSO4) and dicopper oxide (Cu2O, CoRouge) at three levels of inclusion (15, 75, and 150 mg/kg) on growth performance and gut microbiota of broilers. A total of 840 one-d-old male chickens (Ross 308) were weighed and randomly allocated to seven dietary treatments: negative control (NC, a basal diet without Cu addition), and the NC supplemented with 15, 75, or 150 mg Cu/kg from CuSO4 or Cu2O (12 replicate pens/treatment, 10 chicks per pen). Broilers were challenged by reusing an old litter with high concentrations in Clostridium perfringens to promote necrotic enteritis. Broiler performance was registered at d 21, 35, and 42. Excreta samples were collected at d 14, 28, and 42 for antimicrobial resistance (AMR) analyses. At d 43, one broiler per pen was euthanized to obtain ileal content for microbial characterization. Body weight d 35 and daily gain d 42 improved (P < 0.05) in Cu2O as Cu dose inclusion increased from 15 mg/kg to 150 mg/kg. Supplementation of 150 mg/kg of Cu from Cu2O decreased the abundance (P < 0.01) of some families such as Streptococcaceae and Corynebacteriaceae and increased the abundance (P < 0.05) of some commensal bacteria like Clostridiaceae and Peptostreptococcaceae. Phenotypic AMR was not different among treatments on d 14 and 28. Isolated Enterococcus spp. from broilers fed the NC diet on d 42 showed higher (P < 0.05) resistance to enrofloxacin, gentamicin, and chloramphenicol compared with Cu treatments. By contrast, the isolated Escherichia coli from broilers fed 150 mg/kg of Cu, either from CuSO4 or Cu2O, showed higher (P < 0.05) resistance to streptomycin and chloramphenicol compared to the NC. This study suggests that supplementing 150 mg/kg of Cu from Cu2O establishes changes in the gut microbiota by regulating the bacterial population in the ileum, which may explain the positive impact on broilers' growth performance

Transversal gene expression panel to evaluate intestinal health in broiler chickens in different challenging conditions

There is a high interest on gut health in poultry with special focus on consequences of the intestinal diseases, such as coccidiosis and C. perfringens-induced necrotic enteritis (NE). We developed a custom gene expression panel, which could provide a snapshot of gene expression variation under challenging conditions. Ileum gene expression studies were performed through high throughput reverse transcription quantitative real-time polymerase chain reaction. A deep review on the bibliography was done and genes related to intestinal health were selected for barrier function, immune response, oxidation, digestive hormones, nutrient transport, and metabolism. The panel was firstly tested by using a nutritional/Clostridium perfringens model of intestinal barrier failure (induced using commercial reused litter and wheat-based diets without exogenous supplementation of enzymes) and the consistency of results was evaluated by another experiment under a coccidiosis challenge (orally gavaged with a commercial coccidiosis vaccine, 90× vaccine dose). Growth traits and intestinal morphological analysis were performed to check the gut barrier failure occurrence. Results of ileum gene expression showed a higher expression in genes involved in barrier function and nutrient transport in chickens raised in healthy conditions, while genes involved in immune response presented higher expression in C.perfringens-challenged birds. On the other hand, the Eimeria challenge also altered the expression of genes related to barrier function and metabolism, and increased the expression of genes related to immune response and oxidative stress. The panel developed in the current study gives us an overview of genes and pathways involved in broiler response to pathogen challenge. It also allows us to deep into the study of differences in gene expression pattern and magnitude of responses under either a coccidial vaccine or a NE.LCM was funded by an FPI PhD grant from the Spanish Ministry of Economy and Competitiveness (BES-2015-075403). This work was also supported by the Agència de Gestió d’Ajuts Universitaris i de Recerca de la Generalitat de Catalunya (PhD Grant 2017FI; NA).Peer reviewe

Recent sedimentation rates in Garaet El Ichkeul Lake, NW Tunisia, as affected by the construction of dams and a regulatory sluice

Purpose Ichkeul National Park, NW Tunisia, is a UNESCO Biosphere Reserve. Garaet El Ichkeul Lake is known for its seasonal variability in water level and salinity. In recent decades, the waterbody has been affected by the construction of new hydraulic structures. To reduce the impacts of dams and to maintain the sustainability of the ecosystem, a sluice was built at the outlet of the lake, and it operated for the first time in 1996. This paper describes an investigation of recent sedimentation dynamics in Ichkeul Lake, determined by radiometric dating of sediment cores. Materials and methods A sediment core was collected with a UWITEC gravity corer at the deepest, central part of the lake in August 2009. Specific activities of unsupported lead-210 (210Pb) and caesium-137 (137Cs) were measured in the core, enabling calculation of recent sediment accumulation rates (SAR). Published radiometric data from nearby sediment cores, collected in 1997 and 1982, provide a comparison. Results and discussion The measured excess 210Pb inventory was 5300 ± 500 Bq m−2, leading to an estimation of constant flux of 165 ± 16 Bq m−2 yr−1, a value higher than the best estimate for local atmospheric fluxes (123 ± 12 Bq m−2 yr−1) and the flux estimated from the core collected in 1982 (48 Bq m−2 yr−1). The 137Cs inventory was 3550 ± 120 Bq m−2, two times higher than the historical 137Cs atmospheric deposition in the area. The 137Cs profile displayed a distinct peak, but the 137Cs depth-distribution did not follow the pattern expected from atmospheric deposition. Application of the constant rate of supply (CRS) model, with the reference point method, produced a chronology and SAR values comparable to those found in previous work. The whole 137Cs profile was quantitatively reconstructed from the historical records of atmospheric deposition, using the system-time-averaged (STA) model. Conclusions The CRS and STA models provide consistent sediment accumulation results for the whole data set, considering the time resolution of the chronology (~6 years) and analytical uncertainties. Results from cores sampled in 1982, 1997 and 2009 reveal an increasing SAR trend, from ~0.25 g cm−2 yr−1 in the early 1940s to ~0.67 g cm−2 yr−1 at present. In the 13 years since installation of sluice gates at Tinja, SAR in the central Ichkeul Lake has not declined. Thus, if siltation continues at the present rate, shallowing of the lake will seriously affect the hydromorphology and ecology of this important lake.International Atomic Energy Agency Research Project RAF7/00

Transversal gene expression panel to evaluate intestinal health in broiler chickens in different challenging conditions

There is a high interest on gut health in poultry with special focus on consequences of the intestinal diseases, such as coccidiosis and C. perfringens-induced necrotic enteritis (NE). We developed a custom gene expression panel, which could provide a snapshot of gene expression variation under challenging conditions. Ileum gene expression studies were performed through high throughput reverse transcription quantitative real-time polymerase chain reaction. A deep review on the bibliography was done and genes related to intestinal health were selected for barrier function, immune response, oxidation, digestive hormones, nutrient transport, and metabolism. The panel was frstly tested by using a nutritional/Clostridium perfringens model of intestinal barrier failure (induced using commercial reused litter and wheat-based diets without exogenous supplementation of enzymes) and the consistency of results was evaluated by another experiment under a coccidiosis challenge (orally gavaged with a commercial coccidiosis vaccine, 90×vaccine dose). Growth traits and intestinal morphological analysis were performed to check the gut barrier failure occurrence. Results of ileum gene expression showed a higher expression in genes involved in barrier function and nutrient transport in chickens raised in healthy conditions, while genes involved in immune response presented higher expression in C.perfringens-challenged birds. On the other hand, the Eimeria challenge also altered the expression of genes related to barrier function and metabolism, and increased the expression of genes related to immune response and oxidative stress. The panel developed in the current study gives us an overview of genes and pathways involved in broiler response to pathogen challenge. It also allows us to deep into the study of diferences in gene expression pattern and magnitude of responses under either a coccidial vaccine or a NE

Intracellular stress signaling pathways activated during human islet preparation and following acute cytokine exposure

Pancreatic islet transplantation may successfully restore normoglycemia in type 1 diabetic patients. However, successful grafting requires transplantation of a sufficient number of islets, usually requiring two or more donors. During the isolation process and following clinical transplantation, islets are subjected to severe adverse conditions that impair survival and ultimately contribute to graft failure. Here, we have mapped the major intracellular stress-signaling pathways that may mediate human islet loss during isolation and following cytokine attack. We found that the isolation procedure potently recruits two pathways consisting of |mitogen-activated protein kinase kinase (MKK)7 --&gt; Jun NH(2)-terminal kinase (JNK)/p38 --&gt; c-fos| and the |nuclear factor-kappaB (NF-kappaB) --&gt; iNOS| module. Cytokines activate the |NF-kappaB --&gt; iNOS| and |MKK4/MKK3/6 --&gt; JNK/p38| pathways without recruitment of c-fos. Culturing the islets for 48 h after isolation allows for the activated pathways to return to background levels, with expression of MKK7 becoming undetectable. These data indicate that isolation and cytokines recruit different death pathways. Therefore, strategies might be rationally developed to avoid possible synergistic activation of these pathways in mediating islet loss during isolation and following grafting