Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The DNA mismatch repair genes MSH2 and MLH1 have been shown to account for a major share of hereditary non-polyposis colorectal cancer (HNPCC). We searched for germline mutations in these genes in 35 HNPCC kindreds fulfilling the Amsterdam diagnostic criteria and in a further 20 kindreds with an average of four affected members per family but not meeting the formal criteria. We first screened for truncations by reverse transcriptase (RT)-PCR. If no mutation was found, we screened genomic DNA by a novel application of two-dimensional (2-D) DNA electrophoresis that allows the simultaneous study of all exons of each gene. All abnormalities were followed up by sequencing. Eight different pathogenic germline mutations were found, two in MSH2 and six in MLH1. We report three major conclusions. First, these mutations together accounted for 86% (30/35) of the kindreds meeting the Amsterdam criteria, but only 30% (6/20) of the remaining kindreds, suggesting differences in etiology. Second, MLH1 was involved in > 90% (34/36) of kindreds with a known predisposing mutation, suggesting that mutations in the MLH1 gene are responsible for most HNPCC kindreds in Finland. Third, our results indicate that the successive application of RT-PCR and 2-D DNA electrophoresis is a sensitive and efficient method for mutation screening in typical HNPCC.
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PMID:DNA mismatch repair gene mutations in 55 kindreds with verified or putative hereditary non-polyposis colorectal cancer. 877 90

Interleukins 6 (IL-6) and 12 (IL-12), and the chemoattractant chemokine RANTES were studied in ethmoidal mucosa, using reverse transcriptase polymerase chain reaction. The 49 patients had chronic sinusitis or nasal/paranasal polyposis, and some also allergy. To the best of our knowledge, this is the first study that demonstrates RANTES and IL-12 on mRNA level in human sinonasal mucosa in situ. mRNA for IL-6, IL-12 and RANTES were detected in 2, 8 and 6 patients with chronic sinusitis, respectively, and in mucosa from patients with polyposis a positive expression was observed in 4, 14 and 10 cases. There were no statistically significant differences. Analysing the entire group of 49 patients, disregarding type of mucosal disease, the number of patients with positive RANTES was significantly higher than that for IL-6. Similarly, IL-12 positivity was more frequently expressed than IL-6. mRNA for IL-6 was expressed in only 2 of the allergic patients. The cytokine production studied thus seems to be unrelated to the clinically defined entities. There is thus a local production in human diseased sinonasal mucosa of RANTES, as well as of IL-6 and IL-12. The local production of RANTES is an important prerequisite for recruitment and migration of inflammatory cells into the tissue. IL-12 is a co-stimulator of antigen-specific responses of established T helper 1 (Th1) clones, and regulates the responsiveness of the clones to a number of T cell growth factors. The study supports a shift towards Th1 cells in these disease entities.
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PMID:Positive identification in situ of mRNA expression of IL-6, and IL-12, and the chemotactic cytokine RANTES in patients with chronic sinusitis and polypoid disease. Clinical relevance and relation to allergy. 883 50

We have isolated from mouse intestine a full-length cDNA clone that encodes an 86-amino acid precursor protein containing a 26-amino acid signal sequence. As deduced from its sequence, the mature 60-aa protein named MPGC60 belongs to the Kazal type of secreted trypsin inhibitors. The MPGC60 peptide has 58% homology with the PEC-60 peptide isolated from pig intestine. In the gut of adult mice, an increasing rostrocaudal gradient in MPGC60 mRNA levels was observed by Northern analysis. In situ hybridization analysis demonstrated strong Mpgc60 expression in Paneth cells and in a subset of goblet cells in the differentiated gut. During postnatal differentiation of the gut, a strong increase in Mpgc60 expression was detected in both small and large intestine. However, in small intestine activation of the Mpgc60 gene occurred earlier than in the large intestine. Apart from the intestinal tract, MPGC60 mRNA was also detectable in the mesenchyme surrounding the uterine epithelium and in endothelia of some blood vessels. However, in contrast to the situation observed in pig, no Mpgc60 expression was detectable by Northern, in situ and reverse transcriptase polymerase chain reaction (RT-PCR) analysis in cells of the immune system, that is, in monocytes, macrophages, peripheral blood and in spleen. Northern blot analysis on mRNA isolated from porcine and murine intestine showed a single transcript in mouse, but several transcripts in pig. Southern blot and fluorescent in situ hybridisation (FISH) analysis demonstrated the presence of a single gene situated in band A of chromosome 4. This region is syntenic with human chromosome regions 6q, 8q and 9p. The gene responsible for human hereditary mixed polyposis syndrome has been localized to human 6q. This raises the possibility that Mpgc60 is a candidate gene for this human disorder.
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PMID:Molecular cloning and characterization of murine Mpgc60, a gene predominantly expressed in the intestinal tract. 981 Jul 7

It has been suggested that the formation and growth of nasal polyp require the remodeling of extracellular matrix. Proteoglycans (PGs) are major components of the extracellular matrix that maintain the integrity of structural tissue. The leucine-rich repeat PGs include lumican, decorin and biglycan and have many important biologic activities in various pathologic conditions, including the remodeling of the extracellular matrix. Therefore, these small-PG families may be involved in the formation and growth of nasal polyp. In the present study, surgical specimens of nasal polyps and nasal mucosa were assessed for expression of mRNA coding for lumican, decorin and biglycan using reverse transcriptase-polymerase chain reaction followed by dot blot hybridization. Lumican, decorin and biglycan mRNA were expressed in all tissue samples examined. Semiquantitative dot blot hybridization revealed that the levels of the lumican and biglycan messages are lower in nasal polyp tissues than in nasal mucosa. The decorin messages in nasal polyp were expressed at levels similar to those in nasal mucosa. These results suggest that lumican, decorin and biglycan may be important components of the extracellular matrix in nasal mucosa. Considering the function of these PGs, normal levels of decorin associated with low levels of biglycan and lumican may play a role in the pathogenesis of nasal polyposis.
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PMID:Analysis of proteoglycan gene messages in human nasal mucosa and nasal polyp using dot blot hybridization. 1142 8

Hereditary non-polyposis colorectal cancer (HNPCC), or Lynch syndrome I, is responsible for as high as 10% of all colorectal cancers (CRCs) newly diagnosed in any given year. This disorder has an autosomal dominant inheritance pattern and is almost fully penetrant (>85%). It occurs when there is a mutation in any one of six mismatch repair genes: hMLH1, hMSH2, hPMS1, hPMS2, hMSH3 and hMSH6. Mutations in these genes allow mistakes in tumor suppressor genes and oncogenes to accumulate which eventually leads to cancer. The founder of an HNPCC family in the Creighton University Hereditary Cancer Institute database was known to produce truncated hMLH1 protein, a product of one of the aforementioned mismatch repair genes. Lymphoblasts were isolated from ten members of this HNPCC family (six affected and four unaffected) and two persons from outside this family (both unaffected controls). RNA and DNA were purified from these lymphoblasts which had been transformed by the Epstein-Barr virus (EBV). The hypothesis was that a mutation in the hMLH1 gene perpetuated defects in its mRNA and functional protein. hMLH1 RNA transcripts were detected in reverse transcriptase polymerase chain reactions (RT-PCR) whereby total poly A(+) RNA was converted to a complementary DNA (cDNA), amplified using hMLH1 specific primers, purified and cycle sequenced. Likewise, DNA was employed as template for PCR amplification of hMLH1 exons; PCR products were then directly cycle sequenced. Affected family members were found to produce hMLH1 mRNA lacking exons 6 and 7 (and wild-type mRNA). A splicing mutation at 546--2 (two bases 5' to exon 7) was located in the genomic DNA samples from the six family members with the HNPCC phenotype. This mutation caused deletion of exon 7 from the mRNA. None of the four unaffected family members or the two unaffected persons outside of this family had the above defects in their hMLH1 mRNA and DNA.
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PMID:A hMLH1 genomic mutation and associated novel mRNA defects in a hereditary non-polyposis colorectal cancer family. 1205 1

The pathogenetic findings of rhinopathies show an increase in infiltrating cells including eosinophils. RANTES is a beta chemokine in which the cysteines are adjacent (C-C), and it attracts and activates eosinophil. We hypothesize that RANTES is locally produced within the nasal polyp microenvironment and is responsible for the inflammatory cell recruitment present in nasal polyposis. To test this hypothesis, we evaluated nasal polyps and mucosa from allergic and control, non-allergic patients for RANTES content. The relative levels of RANTES and MCP-1 protein in tissue homogenates were quantified using enzyme-linked immunosorbent assay technology, and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) tests for RANTES and MCP-1 mRNA expression were performed. The results indicate that RANTES expression and production increase in nasal mucosa (septal and turbinate portions) of allergic patients compared to the same mucosa in non-allergic patients. In allergic patients, RANTES levels of nasal polyp homogenates were nearly 12-fold higher than the RANTES levels in mucosa homogenate. In this study, we hypothesize that the particular anatomic structure and physiologic function of the turbinates are more involved in the pathogenesis of rhinitis and may undergo polypoid degeneration in allergic rhinitis than any other anatomical structure of the nose. Our data suggest that RANTES is more involved than MCP-1 in recruiting inflammatory cells in rhinological disease and may reflect the degree of local inflammation as consequence of the specific chemoattractant properties of RANTES. The level of RANTES in nasal polyps could be important in the development of the pathological state.
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PMID:Transcription and translation of the chemokines RANTES and MCP-1 in nasal polyps and mucosa in allergic and non-allergic rhinopathies. 1468 6

MicroRNAs (miRNA), small noncoding RNAs, are potential diagnostic and prognostic markers, as well as therapeutic targets. miRNA profiles of colorectal carcinomas have not been studied extensively in the context of microsatellite instability (MSI) status. We therefore evaluated 55 paired colorectal adenocarcinomas (CRC) and non-neoplastic mucosa samples using a panel of 24 miRNAs selected by literature review and prior studies in our laboratory. Stem-loop reverse transcriptase quantitative (real-time) polymerase chain reaction assays were done on RNA extracted from formalin-fixed, paraffin-embedded tissue of resection specimens. When miRNA expression was compared with clinicopathologic features and MSI status, eleven miRNAs (miR-183, -31, -20, -25, -92, -93, -17, -135a, -203, -133b, and -223) were over-expressed in CRC relative to mucosa, and nine (miR-192, -215, -26b, -143, -145, -191, -196a, -16, and let-7a) were under-expressed in CRC. Relative expression of miR-92, -223, -155, -196a, -31, and -26b were significantly different among MSI subgroups, and miR-31 and miR-223 were overexpressed in CRC of patients with hereditary non-polyposis colorectal cancer syndrome (Lynch syndrome). Our findings indicate that miRNA expression in CRC is associated with MSI subgroups, including low MSI and HNPCC-associated cancers, and that miRNAs may have posttranscriptional gene regulatory roles in these MSI subgroups and possible effects on the clinicopathologic and biomarker characteristics.
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PMID:Association of microRNA expression with microsatellite instability status in colorectal adenocarcinoma. 2041 77

Intestinal adenocarcinomas seen in an inbred herd of farmed sika deer (Cervus nippon) morphologically resembled human hereditary non-polyposis colorectal cancer (HNPCC). Features common to both included multiple de novo sites of tumourigenesis in the proximal colon, sessile and non-polyposis mucosal changes, the frequent finding of mucinous type adenocarcinoma, lymphocyte infiltration into the neoplastic tubules and Crohn's-like lymphoid follicles at the deep margin of the tumour. HNPCC is defined by a germline mutation of mismatch repair (MMR) genes resulting in their inactivation and loss of expression. To test the hypothesis that similar MMR gene inactivation occurs in the deer tumours, the expression of the four most important MMR genes, MSH2, MLH1, MSH6 and PMS2, was examined at the mRNA level by reverse transcriptase polymerase chain reaction (n = 12) and at the protein level by immunohistochemistry (n = 40) in tumour and control tissues. All four genes were expressed equally in normal and neoplastic tissues, so MMR gene inactivation could not be implicated in the carcinogenesis of this tumour in sika deer.
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PMID:Mismatch repair mRNA and protein expression in intestinal adenocarcinoma in sika deer (Cervus nippon) resembling heritable non-polyposis colorectal cancer in man. 2567 23