Interaction of RNA-binding protein HuR and miR-466i regulates GM-CSF expression.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by T helper 17 (Th17) cells plays an essential role in autoimmune diseases. Transcriptional regulation of Th17 cell differentiation has been extensively studied, but post-transcriptional regulation of Th17 cell differentiation has remained less well characterized. The RNA-binding protein HuR functions to promote the stability of target mRNAs via binding the AU-rich elements of the 3\u27 untranslated region (3\u27UTR) of numerous pro-inflammatory cytokines including IL-4, IL-13, IL-17 and TNF-α. However, whether HuR regulates GM-CSF expression in Th17 cells has not been fully investigated. Here we showed that HuR conditional knockout (KO) Th17 cells have decreased GM-CSF mRNA in comparison with wild-type (WT) Th17 cells, and that HuR binds directly to GM-CSF mRNA 3\u27UTR. Interestingly, HuR deficiency increased the levels of certain microRNA expression in Th17 cells; for example, miR-466i functioned to mediate GM-CSF and IL-17 mRNA decay, which was confirmed by in vitro luciferase assay. Furthermore, we found that HuR promoted Mxi1 expression to inhibit certain miRNA expression. Taken together, these findings indicate that interaction of HuR and miR-466i orchestrates GM-CSF expression in Th17 cells

Examining properties of arc sprayed nanostructured coatings

The article presents the results of examining properties of arc sprayed coating obtained with nano-alloy on the iron matrix with a high amount of fine carbide precipitates sprayed on non-alloyed steel plates intended for high temperature operation. Powder metal cored wire EnDOtec DO*390N 1,6 mm diameter, was used to produce, dense, very high abrasion and erosion resistant coatings approx. 1,0 mm thick. Nano-material coatings characterization was done to determine abrasion resistance, erosion resistance, adhesion strength, hardness as well as metallographic examinations. Results have proved high properties of arc sprayed nano-material coatings and have shown promising industrial applications

Diagnostic Laparoscopy for Small Intestinal Intussusception in a Horse

Laparoscopy is a low-invasive diagnostic and surgical technique for examining and performing surgical procedures in the equine peritoneal cavity. This article is a case study of a horse with weakly expressed, irregular symptoms of colic occurring over a period of four weeks. Diagnostic laparoscopy was performed, and liver and spleen tissue samples were collected for a histopathological analysis. An endoscopic examination of the abdominal cavity ruled out small intestinal intussusception, and a histopathological analysis supported the identification of the causes of colic

Antigenic mapping of an H9N2 avian influenza virus reveals two discrete antigenic sites and a novel mechanism of immune escape

H9N2 avian influenza virus is a major cause of poultry production loss across Asia leading to the wide use of vaccines. Efficacy of vaccines is often compromised due to the rapid emergence of antigenic variants. To improve the effectiveness of vaccines in the field, a better understanding of the antigenic epitopes of the major antigen, hemagglutinin, is required. To address this, a panel of nine monoclonal antibodies were generated against a contemporary Pakistani H9N2 isolate, which represents a major Asian H9N2 viral lineage. Antibodies were characterized in detail and used to select a total of 26 unique ‘escape’ mutants with substitutions across nine different amino acid residues in hemagglutinin including seven that have not been described as antigenic determinants for H9N2 viruses before. Competition assays and structural mapping revealed two novel, discrete antigenic sites “H9-A” and “H9-B”. Additionally, a second subset of escape mutants contained amino acid deletions within the hemagglutinin receptor binding site. This constitutes a novel method of escape for group 1 hemagglutinins and could represent an alternative means for H9N2 viruses to overcome vaccine induced immunity. These results will guide surveillance efforts for arising antigenic variants as well as evidence based vaccine seed selection and vaccine design

The results of postoperative radiotherapy in patients with renal cell carcinoma in third stage of clinical advancement based on data of Greatpoland Cancer Centre

The role of complementary radiotherapy in patients with stage III renal cell carcinoma after radical nephrectomy still remains a matter of discussion. In connection with lack of alternative solutions the treatment is still conducted in many centres. In Greatpoland Cancer Centre in period 1985–1991 complementary radiotherapy was carried out in 169 patients with infiltration of adipose capsule and/or renal stalk or metastases in closest lymph nodes confirmed during operation.The patients were irradiated from two opposite fields including a bed of the removed kidney and regional lymph nodes. Total dose amounted 50 Gy (25 fractions), 2 Gy daily, five times a week.Early complications after radiotherapy like lack of appetite, diarrhoea and moderate leucopenia, disappearing after pharmacologhical treatment, were observed in 20% of patients and did not cause interruption in treatment. No late complications were observed.5-year survival without recurrence was achieved in 47% of thease patients. In the whole group only four local recurrences were found. The reasons of treatment failure were distant metastases. We proved that teleradiotherapy turned out to be efficient method protecting against local recurrence of disease but did not influence significantly 5-year survival rate

69 Wstępna ocena wyników leczenia oszczędzającego w latach 1993–1995 w Wielkopolskim Centrum Onkologii

W latach 1993–1995 w Wielkopolskim Centrum Onkologii leczonych było metodą oszczędzającą gruczoł piersiowy 66 kobiet. Wiek chorych wahał się od 28–73 lat, średni 40,8. Do leczenia były kwalifikowane chore z guzem w piersi do 3 cm i niepalpacyjnymi węzłami pachowymi. Nowotwór u 37 chorych zlokalizowany był w piersi prawej, u 29 w piersi lewej. Najczęściej był umiejscowiony w kwadracie górnym zewnętrznym. W 53 przypadkach stwierdzono raka przewodowego, 4 DCIS, 4 molekularnego, 7 zrazikowego.U 18 pacjentek stwierdzono w ocenie histologicznej przerzuty w węzłach dołu pachowego. Okres obserwacji naszych chorych jest jeszcze stosunkowo krótki. Wśród naszych pacjentek u 4 powodu wznowy miejscowej konieczne mastectomii, 3 kobiety zmarły z powodu przerzutów odległych (jedna w 1 roku obserwacji, dwie w 2 roku obserwacji)

A normal genetic variation modulates synaptic MMP-9 protein levels and the severity of schizophrenia symptoms

Abstract Matrix metalloproteinase 9 (MMP‐9) has recently emerged as a molecule that contributes to pathological synaptic plasticity in schizophrenia, but explanation of the underlying mechanisms has been missing. In the present study, we performed a phenotype‐based genetic association study (PGAS) in > 1,000 schizophrenia patients from the Göttingen Research Association for Schizophrenia (GRAS) data collection and found an association between the MMP‐9 rs20544 C/T single‐nucleotide polymorphism (SNP) located in the 3′untranslated region (UTR) and the severity of a chronic delusional syndrome. In cultured neurons, the rs20544 SNP influenced synaptic MMP‐9 activity and the morphology of dendritic spines. We demonstrated that Fragile X mental retardation protein (FMRP) bound the MMP‐9 3′UTR. We also found dramatic changes in RNA structure folding and alterations in the affinity of FMRP for MMP‐9 RNA, depending on the SNP variant. Finally, we observed greater sensitivity to psychosis‐related locomotor hyperactivity in Mmp‐9 heterozygous mice. We propose a novel mechanism that involves MMP‐9‐dependent changes in dendritic spine morphology and the pathophysiology of schizophrenia, providing the first mechanistic insights into the way in which the single base change in the MMP‐9 gene (rs20544) influences gene function and results in phenotypic changes observed in schizophrenia patients

The results of breast conservative therapy in early breast cancer in Greatpoland Cancer Centre

We are presenting results of our treatment during 3 years (1993–1995) in Greatpoland Cancer Centre.We treated 67 women with early breast cancer performing breast conservative surgery and radiation therapy. For treatment we chose women with breast tumor up to 3 cm in diameter and unpalpable axillary lymph nodes. The therapy consisted of quadrantectomy and axillary dissection and then radiation therapy.Chemotherapy was used for patients with histologically positive lymph nodes metastases. Due to the local recurrence the mastectomy was performed in four patients. Five women were treated with cytostatics because of metastases to the liver and bones.Three women died. The other women remain in the periodical observation in our hospital. These results have a preliminary character, because of the short follow up

91. Early toxicity in 3 D CRT of lung cancer

AimEvaluation the influence of irradiated volume of lung on pneumonitis in 3D radiotherapy.Material/methods and ResultsWe evaluated 49 patients with diagnosis of non-small-cell lung cancer (NSCLC) who were treated in our department between 1999 and 2000. The mean age of patinets was 62 years. The Karnofsky index was documented in all patients before, during and after completion of irradiation. All patients represented IIIA clinical stage of lung cancer. Fourteen patients were irradiated postoperatively due to the residual tumour or massive nodal involvment. Thirty five patients were treated with exclusive radiotherapy. No patients have been treated by chemotherapy. We performed 3D CRT with total dose in range 60 to 66 Gy in daily fractions of 2 Gy prescribed to isocentric point. Clinical and radiological evaluation of pneumonitis was performed. 21 patients of 49 had radiation pneumonitis, but intensity of pneumonitis was moderate. For better estimation the toxicity the dose volume histograms (DVH) were used. The volume of irradiated lung was an important factor for pneumonitis progress.ConclusionsDose volume histograms (DVH) with clinical evaluation can predict pulmonary toxicity (pneumonitis) and colud allow us to evaluate volume of irradiated lung with the highest acceptable dose

HER2 overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy

<p>Abstract</p> <p>Background</p> <p>The response rate of ovarian mucinous carcinomas to paclitaxel/carboplatin is low, prompting interest in targeted molecular therapies. We investigated HER2 expression and amplification, and the potential for trastuzumab therapy in this histologic subtype of ovarian cancer.</p> <p>Methods</p> <p>HER2 status was tested in 33 mucinous carcinomas and 16 mucinous borderline ovarian tumors (BOT)). Five cases with documented recurrence and with tissue from the recurrence available for testing were analyzed to determine whether HER2 amplification status changed over time. Three prospectively identified recurrent mucinous ovarian carcinomas were assessed for HER2 amplification and patients received trastuzumab therapy with conventional chemotherapy.</p> <p>Results</p> <p>Amplification of HER2 was observed in 6/33 (18.2%) mucinous carcinomas and 3/16 (18.8%) BOT. HER2 amplification in primary mucinous carcinomas was not associated with an increased likelihood of recurrence. The prospectively identified recurrent mucinous carcinomas showed overexpression and amplification of HER2; one patient's tumor responded dramatically to trastuzumab in combination with conventional chemotherapy, while another patient experienced an isolated central nervous system recurrence after trastuzumab therapy.</p> <p>Conclusion</p> <p>HER2 amplification is relatively common in ovarian mucinous carcinomas (6/33, 18.2%), although not of prognostic significance. Trastuzumab therapy is a treatment option for patients with mucinous carcinoma when the tumor has HER2 amplification and overexpression.</p