| 1. |
- Gustafson, Lars, et al.
(författare)
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A 50-year perspective of a family with chromosome 14-linked Alzheimer’s disease
- 1998
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 1432-1203 .- 0340-6717. ; 102:3, s. 253-257
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Tidskriftsartikel (refereegranskat)abstract
- A Swedish family with two generations suffering from presenile dementia with an unusually severe Alzheimer encephalopathy was first reported in 1946. The hypothesis that the disease was inherited through a dominant gene is strongly supported by the follow-up 50years later of three additional generations and molecular genetic findings of a novel presenilin-1 gene mutation in the family. The pedigree contains six cases with well-documented dementia in four consecutive generations. The Alzheimer encephalopathy was unusually severe in the three cases studied post-mortem, with a pronounced involvement of the central grey structures, such as the claustrum, the nuclei around the third ventricle, the central thalamic nuclei and the brain stem. There were no vascular lesions and little amyloid angiopathy. All six affected cases showed the typical temporoparietal symptom pattern and other core symptoms of Alzheimer’s disease, such as logoclonia, myoclonic twitchings and major motor seizures. Other predominant features were psychomotor slowness, increased muscular tension, a stiff stooped gait and a rapid loss of weight. The symptom pattern is convincingly explained by the consistent and severe involvement of cortical and central grey structures and is probably linked to the presenilin-1 gene mutation.
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| 2. |
- Norlund, Lena, et al.
(författare)
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A common thrombomodulin amino acid dimorphism is associated with myocardial infarction
- 1997
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 77:2, s. 51-248
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Tidskriftsartikel (refereegranskat)abstract
- Endothelial dysfunction and haemostatic imbalance are believed to be important aetiological factors in the development of acute coronary syndromes. Thrombomodulin (TM) is an integral membrane protein crucial for normal endothelial function and activation of the protein C anticoagulant pathway. We have investigated the importance of a common C/T dimorphism in the TM gene (nucleotide 1418) for development of premature myocardial infarction (MI). The C/T dimorphism predicts an Ala455 to Val replacement in the sixth EGF-like domain of TM. The dimorphism was investigated in 97 MI survivors and 159 healthy controls. The C allele was significantly more frequent among patients than controls (p = 0.035). The allele frequency for the C allele was 0.82 in the patients and 0.72 in the control group. The plasma concentration of TM was investigated among healthy controls but was not related to the C/T dimorphism. In conclusion, the association of the C allele with premature MI, suggests that the TM gene and the C/T dimorphism may be aetiological factors involved in the pathogenesis of MI. Possibly, the Ala455 to Val replacement may affect the function of the TM molecule and the activation of the protein C anticoagulant pathway.
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| 3. |
- Norlund, Lena, et al.
(författare)
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A novel thrombomodulin gene mutation in a patient suffering from sagittal sinus thrombosis
- 1997
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 78:4, s. 1164-1166
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Tidskriftsartikel (refereegranskat)abstract
- Thrombomodulin is an endothelial cell membrane glycoprotein that promotes protein C activation. It has been clearly demonstrated that the anticoagulant functions of the protein C system are important in the prevention of thromboembolic disease. Patients with protein C or protein S deficiency and/or resistance to activated protein C (APC resistance) are at higher risk for developing thromboembolic disease. The first mutation in the thrombomodulin gene was discovered in an American patient suffering from pulmonary embolism at the age of 45 (Ohlin and Marlar 1995). Here we report a case of sagittal sinus thrombosis in a 42-year-old Swedish woman. She was found to carry a heterozygous point mutation changing G127 to A, predicting an Ala25 to a Thr change in the mature thrombomodulin protein. This mutation was also found in her 16-year-old daughter, who so far has not suffered from any thrombotic events. The patient had no other detectable prothrombotic genetic defects associated with the coagulation system. This case supports the hypothesis of an association between mutations in the thrombomodulin gene and venous thrombosis.
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| 5. |
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| 6. |
- Xu, Ning, et al.
(författare)
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Role of platelet factor Xa in chylomicron-prothrombin complexes induced platelet activation
- 1995
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 208:2, s. 765-772
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Tidskriftsartikel (refereegranskat)abstract
- The effects of chylomicron-prothrombin complexes on platelet activation, including platelet aggregation, serotonin release, arachidonic acid release and increases of platelet cytosolic [Ca2+]i were examined. Furthermore the role of platelet factor Xa on the conversion of chylomicron bound prothrombin to thrombin was studied by using a synthetic inhibitor of factor Xa, TenStop. The chylomicron-prothrombin complexes could induce platelet aggregation and enhance the platelet serotonin release and arachidonic acid release in contrast to native chyle chylomicrons. An increase of platelet [Ca2+]i was observed during incubation with chylomicron-prothrombin complexes. TenStop inhibited platelet aggregation and serotonin release that were induced by chylomicron-prothrombin complexes in a dose-dependent manner, whereas the TenStop itself did not inhibit the platelet aggregation induced by thrombin and collagen. It is concluded that platelet activation induced by chylomicron-prothrombin complexes is related to the platelet factor Xa that could be the key factor in the conversion of chylomicron bound prothrombin to thrombin.
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