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Microarray Study (microarray + study)
Selected AbstractsGene Expression Profiling in Cluster Headache: A Pilot Microarray StudyHEADACHE, Issue 10 2006Christina Sjöstrand MD Background.,Cluster headache (CH) is a primary neurovascular headache disorder characterized by attacks of excruciating pain accompanied by ipsilateral autonomic symptoms. CH pathophysiology is presumed to involve an activation of hypothalamic and trigeminovascular systems, but inflammation and immunological mechanisms have also been hypothesized to be of importance. Objective.,To identify differentially expressed genes during different clinical phases of CH, assuming that changes of pathophysiological importance would also be seen in peripheral venous blood. Methods.,Blood samples were drawn at 3 consecutive occasions from 3 episodic CH patients: during attacks, between attacks and in remission, and at 1 occasion from 3 matched controls. Global gene expression was analyzed with microarray tehnology using the Affymetrix Human Genome U133 2.0 Plus GeneChip® Set, covering more than 54,000 gene transcripts, corresponding to almost 22,000 genes. Quantitative RT-PCR on S100P gene expression was analyzed in 6 patients and 14 controls. Results.,Overall, quite small differences were seen intraindividually and large differences interindividually. However, pairwise comparisons of signal values showed upregulation of several S100 calcium binding proteins; S100A8 (calgranulin A), S100A12 (calgranulin C), and S100P during active phase of the disease compared to remission. Also, annexin A3 (calcium-binding) and ICAM3 showed upregulation. BIRC1 (neuronal apoptosis inhibitory protein), CREB5, HLA-DQA1, and HLA-DQB1 were upregulated in patients compared to controls. The upregulation of S100P during attack versus remission was confirmed by quantitative RT-PCR analysis. Conclusions.,The S100A8 and S100A12 proteins are considered markers of non-infectious inflammatory disease, while the function of S100P is still largely unknown. Furthermore, upregulation of HLA-DQ genes in CH patients may also indicate an inflammatory response. Upregulation of these pro-inflammatory genes during the active phase of CH has not formerly been reported. Data from this pilot microarray study provide a basis for further studies in CH. [source] The Th1/Th2 immune-type response of the recurrent aphthous ulceration analyzed by cDNA microarrayJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 3 2004R. C. Borra Background:, The reduced ability to activate oral tolerance plays a role in the pathogenesis of some gastrointestinal inflammatory diseases. This activation may reflect a preferential reduction of a T-helper (Th)2- or Th3-type response. In recurrent aphthous ulceration (RAU), genetic and environmental factors may contribute to low tolerance, permitting a cytotoxic reaction against the oral epithelium. The cytokine profile has not permitted the definition of RAU as resulting from enhanced Th1 or Th2 responses. A cDNA microarray study would allow the identification of differentially expressed genes and provide a basis for classification of the immune response. Methods:, The cDNA from 29 samples of aphthae and from 11 samples of normal mucosa from aphthae-free volunteers were hybridized on microarray membranes with 1176 genes. Results:, Forty-one differentially expressed genes were identified, and a higher expression level of the Th1 gene cluster in RAU was found. Conclusions:, Microarrays permitted us definition of the gene expression profile of the lesion and identify an increased Th1 activity in RAU lesions. [source] Role of nitric oxide synthesized by nitric oxide synthase 2 in liver regenerationLIVER INTERNATIONAL, Issue 6 2008Takafumi Kumamoto Abstract Background/Aims: Nitric oxide synthase 2 (NOS2) is expressed during liver regeneration after a partial hepatectomy (PHx); NOS2 subsequently synthesizes nitric oxide (NO). However, the role of NOS2-synthesized NO in post-PHx liver regeneration remains unclear. We investigated the role of NOS2-synthesized NO in liver regeneration. Methods: NOS2 knockout (NOS2 -KO) mice and control mice were subjected to PHx. Liver mass recovery and serum alanine aminotransferase (ALT) levels were then evaluated. The expressions of Ki-67 and single-strand DNA were also evaluated in remnant liver specimens. Differences in the gene expression profiles of the two groups of remnant liver specimens were analysed using a microarray and were validated using a reverse transcription-polymerase chain reaction (RT-PCR). Results: In NOS2 -KO mice, liver regeneration was delayed and apoptosis and serum ALT levels were higher than the levels in the control mice. A microarray study and RT-PCR revealed that heat shock protein 70 family (HSP70 family), haeme oxygenase 1 (Hmox1), neuropilin 1 (Nrp1) and epidermal growth factor receptor (EGFR) were downregulated in NOS2 -KO mice. Conclusions: NOS2-synthesized NO may improve hepatocyte viability through the induction of the HSP70 family and Hmox1 and may sensitize the remnant liver to growth factors through the induction of Nrp1 and EGFR post-PHx. [source] Expression of double-stranded RNA-activated protein kinase in small-size peripheral adenocarcinoma of the lungPATHOLOGY INTERNATIONAL, Issue 11 2005Mee Sook Roh The authors investigated the protein expression of double-stranded RNA-activated protein kinase (PKR), which was identified by using a previous cDNA microarray study, to discover PKR's correlations with several pathological parameters and to elucidate its role in neoplastic transformation and progression of lung adenocarcinomas. Immunohistochemistry for PKR was performed and a semiquantitative scoring method was calculated based on staining intensity and percentage of immunoreactive tumor cells (high vs low) for one bronchioloalveolar carcinoma (BAC), 16 adenocarcinomas consisting of BAC and invasive carcinoma (mixed) and 21 invasive adenocarcinomas without BAC (invasive). The BAC had high-grade expression and the mixed type tended to more frequently show high-grade expression than the invasive type (P = 0.028). There were no significant associations with age, tumor size, lymph node metastasis, lymphovascular invasion or the pathological stage. The Kaplan,Meier survival curves demonstrated that the patients with high-grade PKR expression had significantly shorter survival periods than those patients with low-grade PKR expression (P = 0.018). These results do not support the concept of PKR as a tumor suppressor in small-size peripheral adenocarcinomas of the lung. [source] Interferon-stimulated gene 15 (ISG15) conjugates proteins in dermatomyositis muscle with perifascicular atrophyANNALS OF NEUROLOGY, Issue 1 2010Mohammad Salajegheh MD Objective We investigated interferon-stimulated gene 15 (ISG15), a poorly understood ubiquitin-like modifier, and its enzymatic pathway in dermatomyositis (DM), an autoimmune disease primarily involving muscle and skin. Methods We generated microarray data measuring transcript abundance for approximately 18,000 genes in each of 113 human muscle biopsy specimens, and studied biopsy specimens and cultured skeletal muscle using immunohistochemistry, immunoblotting proteomics, real-time quantitative polymerase chain reaction, and laser-capture microdissection. Results Transcripts encoding ISG15-conjugation pathway proteins were markedly upregulated in DM with perifascicular atrophy (DM-PFA) muscle (ISG15 339-fold, HERC5 62-fold, and USP18 68-fold) compared with 99 non-DM samples. Combined analysis with publicly available microarray datasets showed that >50-fold ISG15 transcript elevation had 100% sensitivity and specificity for 28 biopsies from adult DM-PFA and juvenile DM patients compared with 199 muscle samples from other muscle diseases. Free ISG15 and ISG15-conjugated proteins were only found on immunoblots from DM-PFA muscle. Cultured human skeletal muscle exposed to type 1 interferons produced similar transcripts and ISG15 protein and conjugates. Laser-capture microdissection followed by proteomic analysis showed deficiency of titin in DM perifascicular atrophic myofibers. Interpretation A large-scale microarray study of muscle samples demonstrated that among a diverse group of muscle diseases DM was uniquely associated with upregulation of the ISG15 conjugation pathway. Exposure of human skeletal muscle cell culture to type 1 interferons produced a molecular picture highly similar to that seen in human DM muscle. Perifascicular atrophic myofibers in DM were deficient in a number of skeletal muscle proteins including titin. ANN NEUROL 2010;67:53,63 [source] The immunohistochemical expression of BNIP3 protein in non-small-cell lung cancer: a tissue microarray studyAPMIS, Issue 8 2010IVO ÜBERALL Überall I, Kolek V, Klein J, Krej,í V, ,,astná J, Radová L, ,karda J, Fridman E. The immunohistochemical expression of BNIP3 protein in non-small-cell lung cancer: a tissue microarray study. APMIS 2010; 118: 565,70. Drug resistance is one of the reasons for chemotherapy failure in non-small-cell lung carcinoma (NSCLC). One of the major mechanisms of drug resistance is the inhibition of chemotherapy-induced apoptosis. Therefore, the study of novel cell death pathways could possibly enable us to overcome resistance to apoptosis in NSCLC. One of the non-caspase types of cell death is autophagy. BNIP3 protein, a Bcl-2 family member, highly expressed in some tumours, plays a key role in the induction of autophagy. In the present study, we investigated the immunohistochemical expression and subcellular localization of BNIP3 in a series of early- and late-stage non-small-cell lung carcinomas and normal bronchial tissues, and correlated this expression with the occurrence of metastasis and survival. BNIP3 was strongly expressed in the nucleus of cancer cells in 16/79 (20.3%) cases. This BNIP3 positivity did not correlate with histological grade, stage, histology type, metastatic potential, or expression of BNIP3 according to median values. No significant correlation was observed between the expression of BNIP3 and the overall survival of NSCLC patients (p = 0.55). Nor did we find any significant correlation between BNIP3 expression and the occurrence of site-specific metastasis (p = 0.85). [source] HER2/neu (c-erbB-2) gene amplification and protein expression are rare in uterine cervical neoplasia: a tissue microarray study of 814 archival specimensAPMIS, Issue 10 2009IANA LESNIKOVA Published studies have reported widely variable incidence of HER2/neu (c-erbB-2) protein expression and HER2/neu (c-erbB-2) gene amplification in cervical carcinoma. We examined tissue microarrays (TMAs) constructed from 814 formaldehyde-fixed paraffin-embedded archival specimens of cervical intraepithelial neoplasia (CIN)1 (n = 262), CIN2 (n = 230), CIN3 (n = 186) and invasive carcinoma (n = 136), for HER2/neu protein expression by immunohistochemistry (IHC) and for HER2/neu gene amplification by chromogenic in situ hybridization (CISH). We found moderate or strong immunohistochemical positivity for HER2/neu in 64 of 814 specimens (7.9%). Using CISH, polysomy of the HER2/neu gene was detected in 87 cases (10.7%), low/borderline amplification in five cases (0.6%) and true amplification in four cases (0.5%). The correlation between IHC and CISH was statistically significant in CIN2, CIN3 and invasive cervical carcinoma specimens. When present, Her-2/neu positivity is more commonly seen in higher grades of cervical dysplasia and in carcinoma. However, this large TMA study shows that HER2/neu oncoprotein expression and HER2/neu gene amplification overall are uncommon events in cervical neoplasia. This provides compelling evidence that HER2/neu plays no major role in the development and progression of cervical neoplasia. [source] | ||||||||||