| 41. |
- Ekström, Ulf, et al.
(författare)
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Detection of alterations in all three exons of the peripherin/RDS gene in Swedish patients with retinitis pigmentosa using an efficient DGGE system
- 1998
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Ingår i: Molecular Pathology. - 1366-8714. ; 51:5, s. 287-291
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To develop a sensitive mutation screening procedure suitable for routine analysis of the peripherin/RDS gene, and to estimate the nature and prevalence of peripherin/RDS gene mutations in Swedish patients with autosomal dominant retinitis pigmentosa. METHODS: To make the method as sensitive as possible, as many as eight segments, covering the three exons and the flanking intron sequences of the peripherin/RDS gene, were analysed by denaturing gradient gel electrophoresis. A group of 38 Swedish patients with a clinical diagnosis of autosomal dominant retinitis pigmentosa were screened for mutations in the peripherin/RDS gene. RESULTS: Three point mutations were found in four of the patients and five polymorphisms were defined. One mutation in exon 1, R172W, has been described previously in other ethnic groups as causing a macular degeneration. Another mutation, in exon 2 and causing the substitution F211L, was found in two unrelated patients. A third mutation, resulting in the likely non-pathogenic substitution S289L, as well as a polymorphism not reported previously, was found in exon 3. CONCLUSIONS: The screening procedure described allows detection of mutations in all of the exons, including the polymorphic 5' and 3' ends of the gene, and is therefore suitable for routine screening of peripherin/RDS gene defects in patients with autosomal dominant retinitis pigmentosa. The frequency of mutations found in the Swedish patient group indicates that defects in the peripherin/RDS gene might be a more common cause of autosomal dominant retinitis pigmentosa than was thought previously.
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| 42. |
- Ekström, Ulf, et al.
(författare)
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Mutations in the low-density lipoprotein receptor gene in Swedish familial hypercholesterolaemia patients: clinical expression and treatment response
- 1998
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972. ; 28:9, s. 740-747
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Familial hypercholesterolaemia, an autosomal co-dominant disorder caused by defects in the low-density lipoprotein receptor gene, is strongly associated with premature development of cardiovascular disease. METHODS: In this study, we have applied a gene screening method in a population of familial hypercholesterolaemia patients in order to describe the genetic background of the disease in southern Sweden. These patients were studied with the aim of relating the presence of the different mutations to the clinical expression of the disease and to the response to pharmacological treatment. RESULTS: In 16 out of 21 patients, potentially disease-causing low-density lipoprotein receptor gene defects were found, including five not previously described alterations (C240-->F, C122-->stop, C356-->Y, 785insG, 165delG). No defects in apolipoprotein B were found. One group of patients (n = 4) carried the mutation C122-->stop and another group of patients (n = 4) a mutation causing the substitution W66-->G. Patients in the two genotype subgroups were very similar with respect to lipid levels before treatment. CONCLUSION: A tendency towards differential susceptibility to treatment with statins was observed for the patient groups, encouraging further comparative studies of heterozygous FH patients.
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| 43. |
- Ekström, Ulf, et al.
(författare)
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Phenotypic expression of autosomal dominant retinitis pigmentosa in a Swedish family expressing a Phe-211-Leu variant of peripherin/RDS
- 1998
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Ingår i: Ophthalmic Genetics. - : Swets & Zeitlinger Publishers. - 1744-5094 .- 1381-6810. ; 19:1, s. 27-37
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To characterize the clinical phenotype, with emphasis on electrophysiology, of members of a Swedish family with autosomal dominant retinitis pigmentosa due to a novel mutation, F211L, in the peripherin/RDS gene. METHODS: Nine patients with autosomal dominant retinitis pigmentosa and two healthy family members underwent a full clinical evaluation including kinetic visual field testing, measurement of dark adaptation threshold, and full-field electroretinography. Blood samples were collected and DNA analysis was performed using denaturing gradient gel electrophoresis (DGGE). RESULTS: The grandfather, six of seven siblings from the middle generation, and two young boys carried the mutation F211L in the peripherin/RDS gene. The mutation segregated with the clinical presentation of disease. Fundus examination revealed mainly macular atrophy. All assessed parameters of retinal function (visual acuity, dark adaptation threshold, visual fields, and full-field electroretinograms) demonstrated a successive reduction with increasing age. Full-field electroretinograms showed a diminished rod response in all affected individuals and a reduction of the cone b-wave amplitudes with increasing age, indicating retinitis pigmentosa. In the affected family members, the disease seems to progress at a similar rate with increasing age. CONCLUSIONS: The peripherin/RDS gene mutation F211L is associated with a clinical phenotype and includes early loss of rod function and successive reduction of cone function with increasing age, but impressively well-preserved visual acuity and visual fields in young and middle-aged patients and moderately reduced vision in the old patient. Compared to previously described phenotypes segregating with mutations in the peripherin/RDS gene, the present family demonstrates a more benign clinical phenotype, which is concordant within the family.
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| 44. |
- Flodmark, Carl-Erik, et al.
(författare)
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Waist measurement correlates to a potentially atherogenic lipoprotein profile in obese 12-14-year-old children
- 1994
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Ingår i: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 83:9, s. 941-945
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological studies have indicated a relationship between overweight and cardiovascular disease. The present investigation was undertaken to identify anthropometric variables in childhood which may reflect the risk of cardiovascular disease in terms of unfavourable changes in apolipoprotein and lipid concentrations. Twenty-nine obese 14-year-olds and 32 obese 12-year-olds were recruited from a school screening programme and anthropometric data reflecting overweight and fat distribution were subjected to analysis of covariance, with blood pressure, apolipoprotein and lipid concentrations as dependent variables. Results from the two groups were adjusted for puberty, gender and screening group, allowing pooling of data. After such an adjustment, waist circumference was significantly correlated (r = partial correlation coefficient) to high density lipoprotein (HDL) cholesterol (r = -0.08, p < 0.05) and triglycerides (r = +0.24, p < 0.01). The waist:hip ratio was significantly correlated to HDL-cholesterol (r = -0.10, p < 0.01) and triglycerides (r = +0.22, p < 0.01). BMI was significantly correlated to triglycerides (r = +0.25, p < 0.001), and diastolic blood pressure (r = +0.08, p < 0.05). The partial regression coefficients for waist circumference versus apolipoprotein B (r = +0.07) and the apolipoprotein B:A-I ratio (r = +0.06) were as strong as those for waist:hip ratio (r = +0.03 and r = +0.05, respectively). Our results demonstrate that abdominal obesity is associated with an unfavourable lipid profile in obese 12-14-year-old children. This may be related to an increased cardiovascular risk later in life. The waist measurement appears to be a convenient and informative anthropometric indicator of such metabolic alterations.
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Hansen, Ole, et al.
(författare)
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Effects of carvedilol on the metabolic, hemodynamic, and electrocardiographic responses to increased plasma epinephrine in normal subjects
- 1994
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Ingår i: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 24:6, s. 853-859
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Tidskriftsartikel (refereegranskat)abstract
- To study the effects of the new vasodilating beta-blocking agent carvedilol on a variety of metabolic, hemodynamic, and ECG parameters of importance for the clinical outcome of acute myocardial infarction (AMI), we infused epinephrine (EPI) in healthy male volunteers on two separate occasions to serum concentrations of the same level reached in AMI. Before the EPI infusions, the volunteers were pretreated for 2 weeks with either carvedilol or placebo in randomized order. EPI caused significant decreases in serum levels: S-potassium (0.62 mM), S-magnesium (0.07 mM), S-calcium (0.12 mM), and S-phosphate (0.26 mM). After pretreatment with carvedilol, the decreases in S-calcium and S-phosphate were partly prevented and those in S-potassium and S-magnesium were completely inhibited. Short-term treatment with carvedilol significantly decreased S-insulin and serum C-peptide and significantly attenuated the EPI-induced increase in B-glucose observed after placebo. The EPI infusion significantly increased serum concentrations of free fatty acids and glycerol. These increases were significantly attenuated by carvedilol, whereas carvedilol had no significant affects of a variety of other lipid variables. EPI infusion caused a significant (p < 0.01) increase in systolic blood pressure (SBP) from 124.8 +/- 8.1 to 135.8 +/- 12.5 mm Hg and an increase in heart rate (HR) from 71.0 +/- 11.5 to 77.2 +/- 12.2, resulting in a significant increase in rate-pressure product (RPP). This estimate of cardiac work was significantly (p < 0.05) reduced by pretreatment with carvedilol.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 49. |
- Hemani, Ahmed, et al.
(författare)
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Lowering power consumption in clock by using globally asynchronous locally synchronous design style
- 1999
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Ingår i: Design Automation Conference, 1999. Proceedings. 36th. ; , s. 873-878
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Konferensbidrag (refereegranskat)abstract
- Power consumption in clock of large high performance VLSIs can be reduced by adopting globally asynchronous, locally synchronous design style (GALS). GALS has small overheads for the global asynchronous communication and local clock generation. We propose methods to (a) evaluate the benefits of GALS and account for its overheads, which can be used as the basis for partitioning the system into optimal number/size of synchronous blocks, and (b) automate the synthesis of the global asynchronous communication. Three realistic ASICs, ranging in complexity from 1 to 3 million gates, were used to evaluate GALS benefits and overheads. The results show an average power saving of about 70% in clock with negligible overheads
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| 50. |
- Hemani, Ahmed, et al.
(författare)
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Lowering Power Consumption in Clock by Using Globally Asynchronous Locally Synchronous Design Style
- 1999
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Ingår i: Proceedings of the 36th ACM/IEEE conference on Design automation. - New York, NY, USA : ACM. ; , s. 873-878
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Konferensbidrag (refereegranskat)abstract
- Power consumption in clock of large high performance VLSIs can be reduced by adopting Globally Asynchronous, Locally Synchronous design style (GALS). GALS has small overheads for the global asynchronous communication and local clock generation. We propose methods to a) evaluate the benefits of GALS and account for its overheads, which can be used as the basis for partitioning the system into optimal number/size of synchronous blocks, and b) automate the synthesis of the global asynchronous communication. Three realistic ASICs, ranging in complexity from 1 to 3 million gates, were used to evaluate GALS benefits and overheads. The results show an average power saving of about 70% in clock with negligible overheads.
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