Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Highly ordered mesoporous silver, which exhibits well-defined mesopores, high surface area and pore volume, has been successfully obtained using a cubic mesoporous silica, KIT-6, with controlled surface hydrophobicity as the hard template.
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PMID:Facile synthesis of highly ordered mesoporous silver using cubic mesoporous silica template with controlled surface hydrophobicity. 1932 10

A 50-year-old man presented with an asymptomatic, 1.5 x 1.5 cm, dark-brown noduloplaque with a rubbery consistency (Fig. 1) on the lateral aspect of the left lower leg of uncertain duration. His general condition was healthy, and he did not recall any trauma or insect bite at this site. No similar skin lesions were found elsewhere and no lymphadenopathy was observed. The lesion revealed a nonencapsulated, but well-circumscribed, deep dermal nodule with several lymphoid aggregates and germinal center-like structures within the tumor and also at the periphery, when examined microscopically at scanning power (Fig. 2a). The epidermis showed no remarkable changes, except for basal hyperpigmentation. At higher power, a mixed inflammatory infiltrate composed of histiocytes, foamy histiocytes (Fig. 2b), lymphocytes, and abundant plasma cells (Fig. 2c) with Russell bodies was revealed. The stroma contained mainly hyalinized and sclerotic collagen fibers (Fig. 2d). Prominent venules were noted, especially in the sclerotic areas, and some were surrounded by dense collagen fibers. No vasculitis or emperipolesis was found. No foreign materials were observed by polarization microscopy, and no organisms could be identified by periodic acid-Schiff (PAS), Grocott methenamine silver (GMS), Giemsa, Gram, acid-fast, or fite stains. The results of testing for infection by Epstein-Barr virus (EBV) (latent membrane protein 1, LMP-1) were negative. No spindle cells were found in the lesion. Immunohistochemical studies demonstrated mature plasma cells stained with CD138, and polyclonality was confirmed by the expression of both kappa and lambda light chains. The germinal center-like lymphoid aggregates were found to be B cells, which reacted positively with CD20. Scarce S100-positive cells and even rarer CD1a-positive cells were detected. Test results for smooth muscle actin (SMA) and anaplastic lymphoma kinase (ALK) were negative. Abundant CD68+ macrophages were observed within the lesion (Fig. 3a), and about 50-75% of the inflammatory cells were found to express cyclooxygenase-2 (COX-2) (Fig. 3b). The patient's condition was diagnosed as cutaneous plasma cell granuloma (CPCG). One year after excision, no evidence of recurrence was observed.
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PMID:Cutaneous plasma cell granuloma: report of a case with novel histologic and immunohistochemical findings. 1933 29

In diet-induced obese rats, leptin-mediated natural killer (NK) cell activation has been demonstrated to be impaired by abrogated intracellular JAK2-STAT3 signaling. The contribution of the obese microenvironment to this NK cell dysfunction and its reversibility remains elusive. In this study, the functions of NK cells from diet-induced obese rats after adoptive transfer into lean littermates were investigated using in vivo and in vitro approaches. Endogenous NK cells of normal-weight and diet-induced obese F344 rats were depleted in vivo. Then, NK cells from either normal-weight or obese donors were transferred. The numbers of peripheral blood NK cells were analyzed by fluorescence-activated cell sorting (FACS) and the distribution pattern of NK cells in lung and spleen by immunohistochemistry. Ob-R expression was evaluated by immunohistology and activation of intracellular target proteins of Ob-R by immunoblotting. The numbers of NK cells in blood and lung were significantly higher in obese animals compared to lean ones after transfer of NK cells from obese F344 rats. This was correlated with increased postreceptor signaling (JAK-2p, PKBpT308, ERK-2p) without altered Ob-R expression in those NK cells transferred to lean (ob-->nw) vs. obese (ob-->ob) animals. These results show for the first time that the altered phenotype of NK cells from obese rats can be normalized by generation of a physiological (metabolic) environment of lean rats.
Obesity (Silver Spring) 2009 Oct
PMID:Altered phenotype of NK cells from obese rats can be normalized by transfer into lean animals. 1944 29

Existing darkfield illumination schemes are incompatible with many types of samples and/or procedures. We present a darkfield epi-illumination scheme which addresses these incompatibilities by providing illumination through the imaging objective. We validate the system performance using silver nanospheres in varying refractive index environments, characterize the intensity distribution of the darkfield illumination, and demonstrate system capabilities through a preliminary study of functionalized gold nanosphere interactions with cancer cells in culture. We observe a broadened scattering spectrum from unconjugated nanoparticles, as compared with anti-EGFR conjugated nanoparticles, upon incubation with cancer cells, and discuss the implications of this observation.
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PMID:Epi-illumination through the microscope objective applied to darkfield imaging and microspectroscopy of nanoparticle interaction with cells in culture. 1951 30

We investigated protein abundance in order to differentiate radiation-associated papillary thyroid cancers (PTC) from other etiologies for e.g. forensic purposes. Proteins were extracted from frozen tissues originating from 91 sporadic PTCs and 86 post-Chernobyl PTCs. Proteins were separated gel-electrophoretically, gels were silver stained, spots scanned and their intensity quantified. After excision of spots from the gel and protein digestion, MALDI-TOF mass spectrometry was performed followed by correlation of these results to human proteins using appropriate software and database. After this screening approach, altogether 20 candidate proteins were selected and measured semiquantitatively (Remmele score) using immunohistochemistry. Logistic regression modeling was performed for discriminating the groups. NTRK1, metalloproteinases (MMP-1, MMP-9 and MMP-13) and Cathepsins (-W and -X) proved to be of highest significance for discriminating the groups irrespective of the regression model utilized. When considering age and gender, each of 3 proteins by itself made possible a complete separation of the groups otherwise a combination of 2 of the 5 proteins mentioned was needed. In conclusion, abundance of proteins known to be associated with a more aggressive tumor type (MMPs and Cathepsins) appeared increased in post-Chernobyl PTC compared to sporadic PTC, thus underlining the known aggressiveness of radiation-associated PTC. These proteins make it possible to completely distinguish post-Chernobyl from sporadic PTC using routine immunohistology.
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PMID:Sporadic and radiation-associated papillary thyroid cancers can be distinguished using routine immunohistochemistry. 1963 89

Our purposes were to perform a robust assessment of a new HER2 chromogenic in situ hybridization test and report on concordance of silver in situ hybridization (SISH) data with fluorescence in situ hybridization (FISH) data and on intraobserver and interlaboratory scoring consistency. HER2 results were scored from 45 breast cancers in 7 laboratories using the Ventana (Tucson, AZ) INFORM HER-2 SISH assay and in 1 central laboratory using a standard FISH assay. Overall, 94.8% of cases were successfully analyzed by SISH across the 6 participating laboratories that reported data. Concordance for diagnosis of HER2 amplification by SISH compared with FISH was high (96.0% overall). Intraobserver variability (8.0%) and intersite variability (12.66%) of absolute HER2/chromosome 17 ratios appear to be tightly controlled across all 6 participating laboratories. The Ventana INFORM HER-2 SISH assay is robust and reproducible, shows good concordance with a standard FISH assay, and complies with requirements in national guidelines for performance of diagnostic tests.
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PMID:Chromogenic in situ hybridization: a multicenter study comparing silver in situ hybridization with FISH. 1976 28

In the present paper, ordered mesoporous silica (KIT-6) as support, nanosized TiO2 into KIT-6 was synthesized by titanium tetraisopropoxide hydrolysis. Then silver was loaded by deposition-precipitation method. Ag-TiO2/KIT-6 composite nanosized photocatalyst was firstly synthesized and a series of correlated catalysts were synthesized by the same preparation method. Methyl orange is presently adopted as a representative organic pollutant to evaluate the photocatalytic performance of the as-synthesized catalysts. The order of photocatalytic activity of the as-synthesized samples was found as Ag-TiO2/KIT-6 > Ag/TiO2 > TiO2/KIT-6 > TiO2 > Ag/KIT-6. Detailed characterizations were conducted by techniques including XRD, N2 physical adsorption, XPS, UV-Vis DRS and TEM. It was found that the Ag-TiO2 /KIT-6 sample shows the highest photocatalytic activity, which should be attributed to the Ag-TiO2 heterojunction structure and higher BET surface area of the Ag-TiO2/KIT-6 sample. Ag-TiO2 heterojunction improves the separation of photogenerated electron-hole pairs, thus enhancing the photocatalytic activity; Ag-TiO2/KIT-6 sample possesses high BET surface area, which facilitates adsorption and transportation of dye molecules, also leading to higher photocatalytic activity.
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PMID:[Studies on Ag-TiO2/KIT-6 composite nanosized photocatalyst]. 1983 31

Assessment of ERBB2 (HER2) status in breast carcinomas has become critical in determining response to the humanised monoclonal antibody trastuzumab. The current joint College of American Pathologists and the American Society of Clinical Oncology guidelines for the evaluation of HER2 status in breast carcinoma involve testing by immunohistochemistry and fluorescence in situ hybridisation (FISH). However, neither of these modalities is without limitations. Novel bright field in situ hybridisation techniques continue to provide viable alternatives to FISH testing. While these techniques are not limited to evaluation of the HER2 gene, the extensive number of studies comparing bright field in situ techniques with other methods of assessing HER2 status allow a robust evaluation of this approach. Analysis of the literature demonstrates that, when used to assess HER2 gene status, bright field in situ hybridisation demonstrates excellent concordance with FISH results. The average percentage agreement in an informal analysis of studies comparing HER2 amplification by chromogenic in situ hybridisation with FISH was 96% (SD 4%); kappa coefficients ranged from 0.76 to 1.0. Although a much smaller number of studies are available for review, similar levels of concordance have been reported in studies comparing HER2 amplification by methods employing metallography (silver in situ hybridisation) with FISH. A summary of the advancements in bright field in situ hybridisation, with focus on those techniques with clinical applications of interest to the practicing pathologist, is presented.
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PMID:Out of the darkness and into the light: bright field in situ hybridisation for delineation of ERBB2 (HER2) status in breast carcinoma. 2020 20

The importance of HER2 status in breast cancer management has focused attention on the ability of clinical assays to correctly assign HER2 amplification status. There is no consensus as to the best method for assessing HER2 status. Disadvantages of fluorescence in situ hybridization (FISH) testing include longer time required for staining and scoring slides, requirements for specialized training and fluorescence microscopy, and loss of the signal due to quenching of the fluorescent dye. Silver-enhanced in situ hybridization (SISH) is a rapid fully automated assay providing permanently stained slides that are interpreted by conventional bright field microscopy which enables pathologists to evaluate slides within the context of tissue morphology. This study evaluates the concordance between SISH and FISH assays in determining the status of HER2 gene amplification in a cohort of 298 primary invasive breast carcinomas. Furthermore, we assessed in detail the variables contributing to interobserver interpretive reproducibility of HER2 SISH among 10 pathologists. HER2 was quantified using the ratio of HER2 to CHR17 signals using the conventional historical interpretation scale and also by the American Society of Clinical Oncology/College of American Pathologists reporting scheme. For SISH status determined by consensus among 10 pathologists, overall concordance between SISH and FISH was identified in 288 of 298 cases (96.6%) using the conventional Food and Drug Administration approved criteria. Overall agreement was observed in 282 of 285 cases (98.9%) using the American Society of Clinical Oncology/College of American Pathologists result reporting scheme (with equivocal cases removed). In conclusion, SISH represents a novel approach for the determination of HER2 status in breast cancer. The overall concordance between SISH and FISH is excellent, and the interpretation of SISH results by pathologists is most reproducible using the HER2/CHR17 ratio.
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PMID:Silver in situ hybridization (SISH) for determination of HER2 gene status in breast carcinoma: comparison with FISH and assessment of interobserver reproducibility. 2042 83

TGFbeta signaling is initiated by binding of growth factor ligand to two related single-pass transmembrane receptor serine/threonine kinases, known as the TGFbeta type I (TbetaRI) and type II (TbetaRII-ED) receptors. TbetaRII-ED is essential for all TGFbeta-induced signals. The DNA sequence encoding the extracellular domain of human TbetaRII-ED (TbetaRII-ED, residues 4-136) was synthesized from 20 oligonucleotides by polymerase chain reaction and cloned into plasmid pET-32a downstream to the gene of fusion partner thioredoxin immediately after the DNA sequence encoding enteropeptidase recognition site. High level expression ( approximately 1 gL(-1)) of thioredoxin/TbetaRII-ED fusion was achieved in Escherichia coli BL21(DE3) strain mainly in soluble form. The soluble thioredoxin/TbetaRII-ED fusion has been purified and refolded on Ni-NTA agarose. After cleavage of purified thioredoxin/TbetaRII-ED fusion by recombinant human enteropeptidase light chain (L-HEP) the target protein of TbetaRII-ED was separated from thioredoxin on Ni-NTA agarose. Fourteen milligrams of highly purified TbetaRII-ED without N- or C-terminal tags was yielded from 100mL cell culture. The purified preparation of TbetaRII-ED was highly homogenous, as shown by SDS-PAGE with silver staining, HPLC and mass spectroscopy analysis. The binding of TbetaRII-ED purified from E. coli to TGFbeta1 was shown to be comparable to commercial material purified from NSO cells. Recombinant TbetaRII-ED could be employed as an antagonist of TGFbeta1 and TGFbeta3 in vitro and in vivo as well as for therapy of fibrotic disorders and some types of cancer.
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PMID:An efficient method for expression in Escherichia coli and purification of the extracellular ligand binding domain of the human TGFbeta type II receptor. 2045 68


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