| 1. |
- Oohashi, T, et al.
(författare)
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Mouse ten-m/Odz is a new family of dimeric type II transmembrane proteins expressed in many tissues
- 1999
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Ingår i: Journal of Cell Biology. - 0021-9525. ; 145:3, s. 563-577
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Tidskriftsartikel (refereegranskat)abstract
- The Drosophila gene ten-m/odz is the only pair rule gene identified to date which is not a transcription factor. In an attempt to analyze the structure and the function of ten-m/odz in mouse, we isolated four murine ten-m cDNAs which code for proteins of 2,700-2, 800 amino acids. All four proteins (Ten-m1-4) lack signal peptides at the NH2 terminus, but contain a short hydrophobic domain characteristic of transmembrane proteins, 300-400 amino acids after the NH2 terminus. About 200 amino acids COOH-terminal to this hydrophobic region are eight consecutive EGF-like domains. Cell transfection, biochemical, and electronmicroscopic studies suggest that Ten-m1 is a dimeric type II transmembrane protein. Expression of fusion proteins composed of the NH2-terminal and hydrophobic domain of ten-m1 attached to the alkaline phosphatase reporter gene resulted in membrane-associated staining of the alkaline phosphatase. Electronmicroscopic and electrophoretic analysis of a secreted form of the extracellular domain of Ten-m1 showed that Ten-m1 is a disulfide-linked dimer and that the dimerization is mediated by EGF-like modules 2 and 5 which contain an odd number of cysteines. Northern blot and immunohistochemical analyses revealed widespread expression of mouse ten-m genes, with most prominent expression in brain. All four ten-m genes can be expressed in variously spliced mRNA isoforms. The extracellular domain of Ten-m1 fused to an alkaline phosphatase reporter bound to specific regions in many tissues which were partially overlapping with the Ten-m1 immunostaining. Far Western assays and electronmicroscopy demonstrated that Ten-m1 can bind to itself.
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| 2. |
- Martin-Boglind, Lene, et al.
(författare)
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The effect of topical antiglaucoma drugs on the results of high-pass resolution perimetry
- 1991
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Ingår i: American Journal of Ophthalmology. - 0002-9394 .- 1879-1891. ; 11:6, s. 711-714
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a randomly assigned, double-masked, crossover study of the effects of betaxolol, epinephrine, pilocarpine, and timolol on the high-passresolution perimetry results in normal subjects. The influence of topical administration of these intraocular pressure reducing drugs was negligible, which confirmed the reliability of high-pass resolution perimetry results. The method seems appropriate for the diagnosis of glaucoma and the follow-up ofpatients with glaucoma.
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| 3. |
- Sandberg Wollheim, Magnhild, et al.
(författare)
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A long-term prospective study of optic neuritis: evaluation of risk factors
- 1990
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Ingår i: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 27:4, s. 386-393
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Tidskriftsartikel (refereegranskat)abstract
- Eighty-six patients with monosymptomatic optic neuritis of unknown cause were followed prospectively for a median period of 12.9 years. At onset, cerebrospinal fluid (CSF) pleocytosis was present in 46 patients (53%) but oligoclonal immunoglobulin in only 40 (47%) of the patients. The human leukocyte antigen (HLA)-DR2 was present in 45 (52%). Clinically definite multiple sclerosis (MS) was established in 33 patients. Actuarial analysis showed that the cumulative probability of developing MS within 15 years was 45%. Three risk factors were identified: low age and abnormal CSF at onset, and early recurrence of optic neuritis. Female gender, onset in the winter season, and the presence of HLA-DR2 antigen increased the risk for MS, but not significantly. Magnetic resonance imaging detected bilateral discrete white matter lesions, similar to those in MS, in 11 of 25 patients, 7 to 18 years after the isolated attack of optic neuritis. Nine were among the 13 with abnormal CSF and only 2 belonged to the group of 12 with normal CSF (p = 0.01). Normal CSF at the onset of optic neuritis conferred better prognosis but did not preclude the development of MS.
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| 4. |
- Hultberg, Björn, et al.
(författare)
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Poor metabolic control, early age at onset, and marginal folate deficiency are associated with increasing levels of plasma homocysteine in insulin-dependent diabetes mellitus. A five-year follow-up study
- 1997
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - 1502-7686. ; 57:7, s. 595-600
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Tidskriftsartikel (refereegranskat)abstract
- In a previous study, we showed that diabetic patients exhibited significantly increased concentrations of total plasma homocysteine (tHcy), but not until the onset of nephropathy. It was suggested that the hyperhomocysteinaemia might contribute to the accelerated atherosclerotic process in diabetic patients. In the present study, we have analysed the main determinants of plasma homocysteine (i.e. serum cobalamin, blood folate and serum creatinine), and also some other parameters related to diabetes mellitus, such as medical history, metabolic and renal quantities, on two occasions with a 5-year interval in 50 patients with insulin-dependent diabetes mellitus, in order to further elucidate the relation between plasma tHcy and diabetes mellitus. The result of the present study shows that diabetic patients with the lowest age at onset and with the poorest metabolic control are those most prone to a rapid increase in plasma tHcy concentration. The increment in plasma tHcy concentration in this group of patients may at least partly be explained by a marginal deficiency of blood folate concentrations.
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| 5. |
- Bengtsson, Boel
(författare)
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Improved computerized perimetric threshold strategies
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Perimetric threshold examination is the most important method for diagnosing and monitoring patients with glaucoma. Such examination, however, is time-consuming and often difficult for the elderly patients in whom glaucoma is prevalent. Shorter test strategies have been proposed, but unfortunately also with lower test quality. By using new computer-intense techniques for acquisition and processing of test data it was possible to reduce test time of perimetric threshold tests without decreasing quality in test results. The new SITA strategies were developed using such techniques to yield the same accuracy in test results as today’s traditional test strategies, the Humphrey Full Threshold and Fastpac strategies, while considerably reducing test time. Most development was performed using computer simulations. The SITA strategies were evaluated in comparison with traditional strategies in real-time measurements in both normal subjects and glaucoma patients. Test time was reduced by nearly 50% and reproducibility was at least as good as with the conventional strategies. Age normal sensitivity values were higher, and normal limits were narrower, i.e., in SITA fields shallower defects are needed to be recognized as significant loss. Both SITA strategies showed at least as good sensitivity and specificity as the Humphrey Full Threshold strategy when interpreting test results relative to age normal values and normal limits.
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| 6. |
- Ghosh, Fredrik
(författare)
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Experimental Neuroretinal Transplantation
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Embryonic full-thickness rabbit neuroretinal sheets were transplanted to the subretinal space of adult hosts. This was accomplished by using a new transplantation technique involving vitrectomy and retinotomy. The grafts were followed from 10 to 306 days after surgery, and were then examined by different histological techniques. In the light microscope, the transplants were seen to develop the normal retinal lamination and fused with the host retina, especially after long survival times. Ultrastructurally, normal photoreceptor outer segments, well integrated with the host retinal pigment epithelium were found. Growth cones were present in the zone of fusion between graft and host retina. Immunohistochemical labeling revealed many of the normal retinal components not previously found in retinal transplants, and graft-host connections between neurons in the rod pathway were seen. The morphology of vibratome sectioned neuroretinal sheets as well as adult full-thickness grafts was also examined. These transplantation types showed less of the normal morphology compared with embryonic full-thickness grafts. The immunogenicity of embryonic full-thickness and fragmented grafts was compared using Major Histocompatibility Complex (MHC) immunolabeling. Fragmented grafts elicited a response from the host immune system similar to a chronic transplant rejection. This reaction was absent in the full-thickness grafts which is in accordance with their good long-term survival.
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| 7. |
- 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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| 8. |
- Henricsson, Marianne
(författare)
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Hyperglycaemia and diabetic eye complications - a clinical and epidemiological study
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: To study the relationship between hyperglycaemia and the onset/progression of retinopathy, blindness/moderate visual impairment or death, as well as the impact of improved glycaemic control on retinopathy in patients with non-insulin-dependent diabetes mellitus (NIDDM). Methods: Between January 1990 and October 1995 a total of 3,220 diabetic patients were enrolled in a programme for control and screening for retinopathy. Of them 483 (15%) were below 30 years of age, and 2,737 (85%) 30 years or more at diagnosis and were considered representative of patients with insulin-dependent diabetes mellitus (IDDM) and NIDDM, respectively. Retinopathy was graded on fundus photographs using the Wisconsin scale. The time points for detection of blindness (visual acuity 0.1 or less)/ moderate visual impairment (visual acuity 0.2-0.4), progression of retinopathy or death were recorded. The average HbA1c for each patient was used to estimate long-term glycaemic control. Results: Prevalence, development and progression of retinopathy were significantly associated with poor glycaemic control in all diabetic patients. The presence of retinopathy at baseline predicted progression in the NIDDM group. A non-linear relationship was found in NIDDM between mean HbA1c and progression of retinopathy 3 levels or more with a threshold value of about 8.0 %. Patients who changed treatment from oral agents to insulin therapy had an increased risk for progression of retinopathy, which most likely was due to rapid lowering of blood glucose. Poor glycaemic control, severe retinopathy, and blindness were predictors of mortality. Conclusions: Poor glycaemic control and intensified treatment with insulin are risk factors for progression of retinopathy in patients with NIDDM.
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| 9. |
- Juliusson, Bengt
(författare)
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Photoreceptors in experimental retinal cell transplants
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main objective of this thesis was to investigate the fate of photoreceptor cells when using different strategies for retinal cell transplantation. Comparing transplantation of fragments of embryonic retina with cell suspensions of the same tissue we found that transplantation of fragments of embryonic retina result in mature transplants with a higher degree of cellular organization than transplantation of cell suspensions of embryonic retina. However, photoreceptor cells appeared to develop outer segments only when using the fragment method. In transplanted fragments of embryonic retina, four components of the extracellular matrix surrounding photoreceptor cells were studied. Chondroitin-6-sulfate and F22 antigen appeared with a normal distribution, whereas immunoreactivity for interphotoreceptor retinoid binding protein was absent and peanut agglutinin binding appeared increased, indicating that the interphotoreceptor matrix of these retinal transplants is not entirely normal. In the same type of transplants we also found an unexpectedly high proportion of shortwave sensitive cones. The shortwave-/middlewave-sensitive cone ratio was found to be reversed in the transplants compared to normal retina. We also developed a new technique with which it is possible to transplant a coherent sheet of both photoreceptor cells and retinal pigment epithelium to the subretinal space in rats. With this method, photoreceptor cell organization can be preserved. Previous preliminary results by others have shown a rescue effect on host cones in the rd mouse by transplantation. This could not be confirmed. The survival rate of the transplants was low and host cone survival could have been affected by the large amount of retinal detachment in the transplanted eyes. As a basis for our transplantation studies, the distribution of the different cone types were studied in mouse and rabbit retinas. Unexpectedly we found that both have areas containing exclusively shortwave sensitive cones in the ventral part of the retina.
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| 10. |
- Larsson, Jörgen
(författare)
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Central retinal vein occlusion: Cetrain risk factors, electroretinography and an experimental treatment model.
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The presence of activated protein C resistance, plasma hyperhomocysteinemia and the MTHFR C677T mutation in patients with central retinal vein occlusion were investigated and compared to a control group. Activated protein C resistance was overrepresented in the group of patients less than 50 years of age whereas this was not the case in patients more than 50 years of age. Neither hyperhomocysteinemia nor the MTHFR C677T mutation were more frequently seen in the patients independent of their age compared to the controls. Electroretinography was performed early in the course of central retinal vein occlusion, and was shown to have a good predictability concerning the development of rubeosis. We have also shown that full-field ERG, and especially the b-wave implicit time in the 30 Hz flicker ERG is a better predictor for prognosis than fluorescein angiography in patients with recent central retinal vein occlusion. An experimental model of retinal vein occlusion in the rabbit was developed to investigate if it was possible to lower the dose of streptokinase and retain a good thrombolytic effect by adding pulsed ultrasound. These results show that it is possible to halve the dose of streptokinase and still retain a good thrombolytic effect by adding pulsed ultrasound.
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