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- Gobl, Anders E, et al.
(författare)
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Menin represses JunD-activated transcription by a histone deacetylase-dependent mechanism
- 1999
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Ingår i: Biochimica et Biophysica Acta. - 0006-3002 .- 1878-2434. ; 1447:1, s. 51-56
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Tidskriftsartikel (refereegranskat)abstract
- Recently the multiple endocrine neoplasia type 1 (MEN-1) tumor suppressor gene was cloned. MEN-1 encodes a nuclear protein, called menin, of hitherto unknown function. In order to investigate the biological function of menin we employed the yeast two-hybrid system to identify menin-interacting proteins. Here we report that menin functions as a transcriptional repressor through interaction with the transcription factor JunD. The interaction is mediated via the N-terminal transcription activation domain of JunD, and the C-terminal part of menin. In transient co-transfection experiments, expression of menin leads to specific repression of JunD transcriptional activity, which is dependent on the integrity of the menin C-terminal region. C-Terminal truncations of the protein not only abolish repression, but increase JunD transcriptional activity, implying the existence of a functional domain separate from the JunD-binding region. Menin-mediated repression is relieved by the histone deacetylase inhibitor trichostatin A, indicating that deacetylation of histones is an essential component of this repression mechanism, as has recently been demonstrated for the retinoblastoma protein. Missense, in-frame deletions, frameshift and nonsense mutations lead to inactivation of menin or possibly to truncated proteins. This would result in loss of repression of menin/JunD target genes, as well as non-target genes through indirect mechanisms, deregulation of cellular growth control and endocrine tumorigenesis.
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- Gundersen, Kjell Gunnar
(författare)
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Computerised Three-Dimensional Analysis of Optic Nerve Head Topography in Normal and Glaucomatous Eyes
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Evaluation of the optic nerve head topography is one of the most important methods to diagnose and monitor patients with glaucoma. Until recently, optic nerve head topography has most often been judged by either ophthalmoscopy or from optic disc photographs. These methods are subjective and examiners do not have access to absolute measurements of the optic disc size and cup depth. The result of such analysis has been shown to vary substantially even among expert observers. Using two different instruments for three-dimensional imaging, scanning laser tomography and raster tomography, we have studied the optic nerve head topography in a large and representative group of normal subjects (450 eyes) and in a large groups of patients with manifest glaucoma (296 eyes). Measurements of the optic nerve head topography varied widely among normal eyes, but were not influenced by age or gender. Multiple regression analysis demonstrated that up to 80% of this variability of neuroretinal rim area measurements could be explained by variations in disc size, cup depth and cup shape. The distribution of global optic disc parameters like the neuroretinal rim area or cup area showed a large overlap between normal and glaucomatous eyes, which seriously hampered the discrimination between the two groups. Single sector analysis varied widely between different regions of the optic disc. Only measurements of sectors located close to the vertical meridian of the disc (superior and inferior pole) yielded acceptable discrimination between normal and glaucomatous eyes, achieving combinations of specificity and sensitivity of over 91%. If sectors located in the temporal region of the disc were included in the analysis, the discrimination deteriorated significantly. The best single sector located close to the inferior pole of the disc achieved better separation between normal and glaucomatous eyes than any global parameter. Although scanning laser and raster tomography apply completely different imaging principles, both instruments gave very similar results. This implies that results of analysis with one method may have more general validity.
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- Gundersen, Kjell Gunnar, et al.
(författare)
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Sensitivity and specificity of structural optic disc parameters in chronic glaucoma
- 1996
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907. ; 74:2, s. 120-125
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Tidskriftsartikel (refereegranskat)abstract
- We studied different structural optic disc parameters and their ability to discriminate between normal and glaucoma eyes using computerized raster tomography. Two hundred and seventy-six eyes of 138 normal subjects and 146 eyes of 102 glaucoma patients were examined with a raster tomographic imaging system (The Glaucoma-Scope®, Ophthalmic Imaging Systems, Sacramento, CA). Glaucoma eyes were classified into four groups according to their perimetric mean deviation values. Minimum rim width within the 60° and 90° sectors across the vertical meridian, vertical and horizontal cup-disc ratio, rim and cup area were calculated for each optic disc. Receiver operating characteristics curves were set up for comparisons of the different parameters. Representing localised changes of the optic disc, minimum rim width 60° and 90° showed the best separating characteristics with sensitivity values of 91% at a feued specificity of 90%, followed by vertical cup-disc ratio. Global indices like cup and rim area and horizontal cup-disc ratio showed the poorest separation. These differences were particularly obvious in the group with mild to moderate glaucomatous visual field defects. Thus, global parameters were less likely to detect early focal glaucomatous optic nerve head changes, than parameters representing localised changes.
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- Jansson, Tomas, et al.
(författare)
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Ultrasound Doppler Vector Tomography - Measurements of Directional Blood Flow
- 1997
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Ingår i: Ultrasound in Medicine and Biology. - 0301-5629. ; 23:1, s. 47-57
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Tidskriftsartikel (refereegranskat)abstract
- An experimental system has been developed to verify the possibility of detecting flow activity using a technique called ultrasound Doppler vector tomography. A tomography algorithm is used to reconstruct blood flow vector fields using data from computer-controlled ultrasound continuous-wave Doppler scanning equipment. The result is a picture in which the brightness variations represent the reconstructed values of the curl of the velocity field (del x v). Continuous ultrasound is transmitted into a region with flow activity and the Doppler-shifted signals are received. To obtain measurement data suited for fan beam tomography, the scanning is performed in a plane from points encircling the region. Reconstructions have been achieved using measurement data from two different flow phantoms. A comparison between the experimental results and simulations shows good conformity. Copyright (C) 1997 World Federation for Ultrasound in Medicine & Biology.
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