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:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of our study was to determine the frequency of EGF-receptor-gene rearrangement in relation to tumour-growth behaviour in an unselected group of glioma patients. We investigated 73 glial tumours with different grades of malignancy (17 low-grade gliomas, 14 anaplastic variants, and 42 GBM) by Southern analysis, reverse transcriptase PCR (RT-PCR) amplification of mRNA, and Western analysis. An amplification of the EGF-receptor gene was present in 19/42 GBM but in only 1 anaplastic astrocytoma. By RT-PCR, 4/19 GBM with gene amplification showed a specific amino-terminal aberrant splice mutation of 801 bp in addition to undeleted mRNA. By Western analysis, 27/42 GBM showed expression of the EGF-receptor protein. Protein levels, however, varied among individual tumours. Four GBM containing an aberrant splice mutation exhibited an immunoreactive protein of 130 kDa MW in addition to the normal EGF-receptor protein p170. All GBM patients underwent surgery followed by a standard course of radiotherapy. Neuroradiological follow-up in 31/42 GBM patients consisted of bimonthly MRI examinations. There was a statistically significant difference in the mean latency period until tumour regrowth of patients suffering from GBM with and without EGF-receptor-gene amplification (9 weeks vs. 32 weeks). Our data indicate more rapid tumour regrowth kinetics of GBM with amplified EGF receptor genes in vivo.
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PMID:Amplification of the epidermal-growth-factor-receptor gene correlates with different growth behaviour in human glioblastoma. 826 81

Melanoma frequently metastasizes to the central nervous system (CNS). The diagnosis of CNS metastases typically is made following the onset of clinical symptoms. Thus, more sensitive diagnostic approaches are needed to identify subclinical CNS metastases. Currently, standard cytologic analysis of the cerebrospinal fluid (CSF) is limited by its poor sensitivity. A more sensitive assay was therefore developed using multiple reverse transcriptase-polymerase chain reaction (RT-PCR) markers. CSF was collected and assessed by RT-PCR for three known melanoma-associated markers (MAGE-3, MART-1, and tyrosinase) to detect occult metastatic melanoma cells in the CSF of 37 American Joint Committee on Cancer (AJCC) stage IV melanoma patients. Cytologic analysis of CSF was performed on all patients, and immunohistochemistry (IHC) analysis was performed on 33 CSF samples using anti-S100 and anti-HMB-45 antibodies. Only one patient (3%) had tumor-positive CSF cytology and IHC upon entry into the study, whereas 12 patients (32%) were positive for at least one RT-PCR marker. The correlation between CSF RT-PCR positivity of MART-1 and/or MAGE-3 and the development of CNS metastases at 3 mo was significant (p = 0.04). Fifteen of 37 patients (41%) had either positive MRI and/or positive RT-PCR results. Multimarker RT-PCR is more informative and sensitive than cytology/IHC in assessing the CSF of melanoma patients.
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PMID:Molecular detection of metastatic melanoma cells in cerebrospinal fluid in melanoma patients. 1151 19

Contrast-enhanced magnetic resonance imaging (CE-MRI) is a valuable technique for the diagnosis of liver diseases. As gadocoletic acid trisodium salt (B22956/1), a new contrast agent showing high biliary excretion, may be potentially advantageous in hepatobiliary imaging, the aim of the study was to investigate the molecular mechanisms of hepatic transport of the B22956 ion in a cellular model of hepatic tumor. B22956 ion uptake was measured in tumoral (HepG2) and nontumoral (Chang liver) hepatic cell lines. Absolute quantitative real-time reverse transcriptase (RT)-polymerase chain reaction (PCR) analyses, using cloned PCR products as standards, were performed on total RNA of both cell lines and normal liver to evaluate the transcription of 12 transport genes: SLCO1A2, SLCO2B1, SLCO1B1, SLCO3A1, SLCO4A1, SLCO1B3, SLC22A7, SLC22A8, SLC22A1, SLC10A1, SLC15A1, and SLC15A2. B22956 transport was more efficient in Chang liver than in HepG2 cells and was inhibited by cholecystokinin-8, a specific substrate of OATP1B3. Real-time RT-PCR analyses revealed different transcription profiles in the tumoral and nontumoral cell lines. Compared with normal liver, the expression of SLCO1B1, SLCO3A1, and SLCO1B3 was greatly repressed in HepG2 cells, whereas SLCO2B1, SLC22A7, and SLC22A8 expression was either maintained or increased. On the contrary, in Chang liver cells, SLC22A7 and SLC22A8 genes were undetectable, whereas the expression of SLCO3A1, SLCO4A1, and SLCO1B3 was similar to normal liver. Transport studies and gene expression analyses indicated that B22956 ion is a good substrate to the liver-specific OATP1B3, reported to be poorly expressed or absent in human liver tumors. Therefore, B22956 may be helpful in detecting hepatic neoplastic lesions by CE-MRI.
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PMID:Molecular determinants in the transport of a bile acid-derived diagnostic agent in tumoral and nontumoral cell lines of human liver. 1689 78

Current diagnostic assays for HIV-1 do not always test for the presence of HIV-2 in the United States. We present the case of a patient from Cape Verde, who was admitted to our hospital with rapidly deteriorating neurological function and multiple white matter lesions on MRI likely secondary to progressive multifocal leukoencephalopathy (PML). Initially, the patient had a positive EIA for HIV, but a negative HIV-1 Western Blot and no viral load detected on a branched-DNA assay. A repeat viral load by reverse transcriptase methodology (RT-DNA) detected 121,000 copies and an HIV-2 Western Blot was positive. The case highlights an extremely rare presentation of HIV-2 with severe neurological disease. We discuss the different tests available for the diagnosis and monitoring of HIV-2 in the United States.
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PMID:HIV-2 diagnosis and quantification in high-risk patients. 1870 Sep 86

Skeletal muscle atrophy and fatty infiltration develop after tendon tearing. The extent of atrophy serves as one prognostic factor for the outcome of surgical repair of rotator cuff tendon tears. We asked whether mRNA of genes involved in regulation of degradative processes leading to muscle atrophy, ie, FOXOs, MSTN, calpains, cathepsins, and transcripts of the ubiquitin-proteasome pathway, are overexpressed in the supraspinatus muscle in patients with and without rotator cuff tears. We evaluated biopsy specimens collected during surgery of 53 consecutive patients with different sizes of rotator cuff tendon tears and six without tears. The levels of corresponding gene transcripts in total RNA extracts were assessed by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Supraspinatus muscle atrophy was assessed by MRI. The area of muscle tissue (or atrophy), decreased (increased) with increasing tendon tear size. The transcripts of CAPN1, UBE2B, and UBE3A were upregulated more than twofold in massive rotator cuff tears as opposed to smaller tears or patients without tears. These atrophy gene products may be involved in cellular processes that impair functional recovery of affected muscles after surgical rotator cuff repair. However, the damaging effects of gene products in their respective proteolytic processes on muscle structures and proteins remains to be investigated.
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PMID:Expression of atrophy mRNA relates to tendon tear size in supraspinatus muscle. 1894 55

This study was undertaken to investigate the in vitro effect of islet labeling with iron oxide nanoparticles for MRI on islet viability, insulin secretion, and gene expression. Isolated rat islets were labeled with Resovist (25-200 microg Fe/mL, a clinically approved MRI contrast agent) in the presence or absence of poly-l-Lysine (PLL, 1.5 microg/mL) for 48 h. The iron content of labeled islets was found to increase in a dose-dependent manner. More than 90% of the islets were labeled with 100 microg Fe/mL. We confirmed the localizations of iron oxide nanoparticles within islet beta-cells by insulin immunostaining. As the concentration of Resovist increased, T(2) values as determined by T(2)-weighted MRI on a 1.5 Tesla MR scanner decreased. Labeling of 100 islets in a medium containing 100 microg Fe/mL of Resovist in the absence of PLL provided sufficient contrast for islet visualization on T(2)-weighted MRI. MTT assays showed that the viability of labeled islets was not different from that of unlabeled islets. No statistical difference was observed between labeled (2.91 +/- 0.36) and unlabeled islets (2.83 +/- 0.61) in terms of the ability to secrete insulin, as determined by the glucose stimulation index. We also evaluated the effect of iron oxide incorporation on the gene expressions in islet cells using RT-PCR (reverse transcriptase PCR). Insulin expression in labeled islets was significantly elevated (1.83 +/- 0.25 fold vs. unlabeled; p = 0.005), but not the expression of somatostatin (1.39 +/- 0.18 fold vs. unlabeled; p = 0.085) or glucagons (1.28 +/- 0.13 fold vs. unlabeled; p = 0.09). Expression of an important transcription factor for insulin gene transcription, BETA2 (beta-cell E-box trans-activator), was increased in labeled islets (1.67 +/- 0.15 fold vs. unlabeled; p = 0.029). The findings of this study indicate that Resovist provides a satisfactory means to image islets and has no deleterious effect on islet function or gene expression.
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PMID:Magnetic resonance imaging and biological properties of pancreatic islets labeled with iron oxide nanoparticles. 1948 18

MicroRNAs (miRNAs) are effective post-transcriptional regulators of gene expression and are important in many biological processes. Although the oncogenic and tumor suppressive functions of several miRNAs have been characterized, the role of miRNAs in mediating tumor invasion and migration remains largely unexplored. Recently, miR-10b was identified as an miRNA highly expressed in metastatic breast cancer, promoting cell migration and invasion. Here, we performed real-time reverse transcriptase polymerase chain reaction (RT-PCR) assays on 43 glioma samples (17 glioblastoma, 6 anaplastic astrocytoma, 10 low-grade astrocytoma, 6 oligodendroglioma and 4 ependymoma) and 6 glioma cell lines. We found that miR-10b expression was upregulated in all glioma samples compared to non-neoplastic brain tissues. The expression levels of miR-10b were associated with higher grade glioma. In addition, mRNA expressions of RhoC and urokinase-type plasminogen activator receptor (uPAR), which were thought to be regulated by miR-10b via HOXD10, were statistically significantly correlated with the expression of miR-10b (p < 0.001, p = 0.001, respectively). Also, protein expression levels of RhoC and uPAR were associated with expression levels of miR-10b (p = 0.009, p = 0.014, respectively). Finally, multifocal lesions on enhanced MRI of 7 malignant gliomas were associated with higher expression levels of miR-10b (p = 0.02). Our data indicated that miR-10b might play some role in the invasion of glioma cells.
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PMID:MicroRNA-10b is overexpressed in malignant glioma and associated with tumor invasive factors, uPAR and RhoC. 1953 18

Enteroviral CNS infection is common and its clinical course is usually benign. In immunocompromised patients, however, it can cause meningoencephalitis, presenting with altered mentality and seizure. We describe a previously healthy female patient with enteroviral meningoencephalitis who showed rapidly progressive aphasia. Examination of her cerebrospinal fluid (CSF) showed pleocytosis with lymphocyte dominance, elevated protein, and normal glucose, findings compatible with viral encephalitis. Fluid-attenuated inversion recovery (FLAIR) brain MRI showed hyperintensity in the left frontal and parietal cortices. Enterovirus in the CSF was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) of the CSF. Although her neurological deficits had progressed to global aphasia, conservative management resulted in complete improvement within 3 months. This case provides unusual clinical manifestations and imaging findings in enteroviral encephalitis.
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PMID:Enteroviral encephalitis presenting as rapidly progressive aphasia. 2263 79

A 3-year-old Filipino girl presented with progressive left-sided ptosis and proptosis after resection of a superomedial orbital tumor 2.5 years ago. She had been followed with serial MRI, which demonstrated interval growth of a recurrent lesion. Repeat resection was undertaken via an eyelid-splitting anterior orbitotomy. The patient's pediatric oncologist and sarcoma specialist did not recommend adjuvant chemotherapy, and the family declined proton radiotherapy. The patient will continue to be monitored with serial imaging. Histopathology, immunohistochemistry, and reverse transcriptase polymerase chain reaction were most consistent with a diagnosis of adult-type fibrosarcoma. This is the first reported case of adult-type fibrosarcoma presenting in the orbit of a child. Fibrosarcoma is a fibroblast-derived tumor that commonly presents in the extremities, usually in patients in their fourth to sixth decades. It is rarely seen in the orbit, with the largest case series to date only including 5 patients.
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PMID:Recurrent orbital adult-type fibrosarcoma in a 3-year-old girl. 2483 62

An 18-year-old woman presented with a progressively worsening headache, photophobia feverishness and vomiting. Three weeks previously she had returned to the UK from a trip to Peru. At presentation, she had clinical signs of meningism. On admission, blood tests showed a mild lymphopenia, with a normal C reactive protein and white cell count. Chest X-ray and CT of the head were normal. Cerebrospinal fluid (CSF) microscopy was normal. CSF protein and glucose were in the normal range. MRI of the head and cerebral angiography were also normal. Subsequent molecular testing of CSF detected enterovirus RNA by reverse transcriptase PCR. The patient's clinical syndrome correlated with her virological diagnosis and no other cause of her symptoms was found. Her symptoms were self-limiting and improved with supportive management. This case illustrates an important example of viral central nervous system infection presenting clinically as meningitis but with normal CSF microscopy.
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PMID:Confirmed viral meningitis with normal CSF findings. 2503 43


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