Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a 36-year-old man with familial protein S deficiency and homozygosity to the methylene tetrahydrofolate reductase (MTHFR) thermolabile variant who had a stroke followed by an episode of idiopathic osteonecrosis that was successfully managed by surgical core decompression. The patient's symptomatic thrombophilia, as well as that of several of his first-degree relatives who also had thrombotic events, raises the possibility that the thrombophilia was a contributing factor to the development of his osteonecrosis.
 ...
PMID:Idiopathic osteonecrosis in an adult with familial protein S deficiency and hyperhomocysteinemia. 1168 42

The discovery of the resistance to activated protein C (APCR) has provoked a new insight into the etiopathogenesis of venous and arterial thrombosis. APCR is determined in 95% genetically by point mutation in the gene for factor V resulting in substitution of arginine in the position 506 by glutamine. This change makes the activated form of factor V (factor Va) resistant to the cleavage by protein C in the place, where the cleavage takes place most quickly under normal conditions. The mutant factor V is known as factor V Leiden. Factor V Leiden preserves its procoagulation activity for a longer period, resulting thus into thrombophilia with all its negative consequences. The inherited deficiencies of antithrombin III, protein C and protein S occur in 10% of patients suffering from venous thrombosis, whereas factor V Leiden is present in as many as 20 to 60%. Thus, it seems that factor V Leiden is the most important inherited risk factor of venous thrombosis. The results of several trials did not indicate the participation of APCR in the development of myocardial infarction. On the other hand, APCR seems to be a risk factor of cerebrovascular accidents, especially of stroke and transitory brain ischemia. Factor V Leiden is an important risk factor of abortions, especially those occurring in the second trimester of pregnancy. According to recent results, factor V Leiden is considered to play a role in the pathogenesis of venous and arterial thromboses in children. The significant risk potential of factor V Leiden with respect to venous thrombosis development and relatively simple diagnosis of this mutation predispose the investigation of this disorder to become the screening method in indicated groups of patients. The investigation of APCR is recommended in all patients with either first or reoccurring attacks of venous thrombosis or thromboembolism, in patients with positive family history of thrombosis and thromboembolism and in women with repeated abortions, particularly in the second trimester of pregnancy. The investigation of APCR in selected groups of patients and early prophylactic anticoagulation therapy may be important in thrombosis prevention in situations with an increased thrombotic potential. (Tab. 1, Ref. 78.)
 ...
PMID:Resistance to activated protein C--frequent etiologic factor for venous thrombosis. 1172 76

From the information presented in this article, it can be concluded that clinical suspicion of VTE should be increased in patients with a history of VTE, recent surgery, spinal cord injury, trauma, or malignancy. A variety of medical illnesses also increase the risk of venous thrombosis, including congestive heart failure, myocardial infarction, stroke with paresis, nephrotic syndrome, cigarette smoking, and obesity. Hypercoagulable states, such as antithrombin III deficiency, protein C deficiency, protein S deficiency, or factor V Leiden mutation should be considered in those patients who develop VTE in the absence of known risk factors. Additionally, the presence of vena caval filters does not exclude the possibility of PE or recurrent DVT. With a careful assessment of risk, physicians can hope to increase the diagnostic yield of VTE and decrease the significant morbidity and mortality of caused by this disease.
 ...
PMID:Epidemiology of venous thromboembolic disease. 1176 74

A 10-year-old Turkish boy was admitted with mild right spastic hermiplegia. First, he experienced sudden numbness and weakness in the right extremities at the age of 2 years and was diagnosed with right hemiparesis. His parents were generally healthy and non-consanguineous. His mother suffered from deep vein thrombosis of the left lower extremity during pregnancy and had recurrent fetal loss. At the age of 10 years, a thrombophilia marker examination revealed that plasma-free protein S was 49.3% (normal range = 70-123%), and factor VIII level was found to be 470 IU/dL (normal = 150 IU/dL). The patient and his two siblings were found to be heterozygous for factor V Leiden mutation. His mother was also heterozygous for factor V Leiden mutation and had protein S deficiency. A combination of protein S deficiency, factor V Leiden mutation, and a high level of factor VIII was detected in our patient. After his first attack at the age of 2 years, in spite of no prophylaxis, he did not experience any other ischemic insult. To our knowledge, this is the first patient with these combinations of genetic defects and ischemic stroke to be reported in the literature.
 ...
PMID:Combined genetic defects in a child with ischemic stroke: case report. 1226 33

Hereditary prothrombotic states of clinical importance include factor V Leiden, the prothrombin 20210A mutation, deficiencies of protein C, protein S, or antithrombin, sickle cell disease, and hyperhomocysteinemia. Major acquired prothrombotic states include cancer, myeloproliferative disorders, the antiphospholipid syndrome, and heparin-induced thrombocytopenia. Because most of the hereditary prothrombic states are not established risk factors for arterial thrombosis, routine laboratory testing in most patients with ischemic stroke should be limited to complete blood count, lupus anticoagulant, anticardiolipin antibodies, and plasma total homocysteine. Additional testing for factor V Leiden, prothrombin 20210A, antithrombin, protein C, and protein S may be indicated for patients under the age of 50 or those with paradoxical cerebral embolism. The treatment of acute ischemic stroke in patients with prothrombotic states is similar to that in patients without an identifiable prothrombotic condition, and may include antiplatelet agents, anticoagulants, or thrombolytic therapy in patients who otherwise meet eligibility criteria. The potential benefit of chronic anticoagulation therapy for the primary or secondary prevention of stroke in patients with prothrombotic states has not been addressed in controlled clinical trials. Specific therapeutic approaches for the prevention of stroke are established for patients with sickle cell disease, myeloproliferative disorders, and heparin-induced thrombocytopenia, and are under investigation for hyperhomocysteinemia and the antiphospholipid syndrome.
 ...
PMID:Prothrombotic States that Predispose to Stroke. 1235 68

The role of paradoxical embolism through patent foramen ovale as a mechanism of cryptogenic stroke is controversial. If a venous source of emboli is relevant, prothrombotic states should be associated with patent foramen ovale and cryptogenic stroke. We assessed the occurrence of several prothrombotic states (factor V Leiden, prothrombin G20210A, deficiencies in protein S, protein C and antithrombin, lupus anticoagulant, anticardiolipin antibodies, elevated factor VIII, resistance to activated protein C) and classical risk factors for venous thrombosis in 57 adult patients with cryptogenic stroke and patent foramen ovale and in 104 matched controls. Prothrombotic states [odds ratio (OR) 2.8; 95% confidence interval (CI), 1.2-6.5; P = 0.021], migraine with aura (OR 4.4; 95% CI 1.8-10.8; P = 0.001) and classical risk factors for venous thrombosis (OR 2.5; 95% CI 1.1-5.7; P = 0.037) were independent risk factors for cryptogenic stroke. In particular factor V Leiden or prothrombin G20210A associated with cryptogenic stroke (P = 0.022) whereas other coagulation abnormalities did not (P = 0.140). Among the patients with prothrombotic states, Valsalva manoeuvre was common at onset of stroke. Our results support the possibility of paradoxical embolism behind strokes in patients with patent foramen ovale.
 ...
PMID:Factor V Leiden and prothrombin gene mutation may predispose to paradoxical embolism in subjects with patent foramen ovale. 1269 49

Recombinant mouse protein C was cloned, expressed, purified, and activated by Protac or thrombin. The anticoagulant activities of mouse and human activated protein C (APC) were compared using mouse and human plasma and the neuroprotective properties of murine APC were studied in an ischemic stroke model. Both human APC and mouse APC prolonged the activated partial thromboplastin time in a dose-dependent manner, but mouse APC was sixfold more effective than human APC as an anticoagulant in mouse plasma. Human protein S enhanced prolongation of the APTT clotting time of human plasma by human APC, but not by mouse APC. Hydrolysis of the S-2366 chromogenic substrate by murine APC was essentially identical to human APC. Mouse plasma contains 75 nM protein C. In a murine ischemic stroke model based on middle cerebral artery occlusion, murine APC was highly neuroprotective. The results show that recombinant murine APC is functionally similar to human APC both in vitro and in vivo and that it displays significant species specificity. The results imply that murine APC is notably superior to human APC for studies of murine disease models, including thrombosis and ischemic brain injury.
 ...
PMID:Recombinant murine-activated protein C is neuroprotective in a murine ischemic stroke model. 1273 45

Paediatric patients with systemic lupus erythematosus (SLE) and antiphospholipid antibodies (aPL), specifically lupus anticoagulants (LAC) are at high risk of developing thromboembolic events (TE). Our objectives were to determine the prevalence of TE in paediatric SLE patients with LAC and to determine if anticoagulation was effective to decrease morbidity, and prevent recurrent TE. We reviewed data on 149 paediatric SLE patients treated over 10 years. In all, 24 patients (16%) were LAC positive, and 21 TE occurred in 13 of these LAC positive patients (54% incidence of TE in LAC positive patients). The events were cerebral venous thrombosis (9), arterial stroke (3), deep venous thrombosis (4), pulmonary embolism (2), other venous event (1) and other arterial events (2). The median duration between SLE diagnosis and first TE was 15.2 months (range 0-62), and the median age at first TE was 15.1 years (range 11.4-18.4). Long-term anticoagulation was prescribed, and eight patients (62%) were transferred to adult care on lifelong oral warfarin; four (31%) remain under our care on lifelong warfarin, and one patient died of causes unrelated to her TE. No patient has been identified with deficiencies of protein C, protein S or antithrombin III. One patient is heterozygous for Factor V Leiden, and one is heterozygous for both the Prothrombin 20210A mutation and the MTHFR (methylene tetrahydrofolate reductase) mutation. Four patients had recurrent TE (31%), and three were not anticoagulated at the time of their second event. One patient had two recurrences on therapeutic anticoagulation. Thromboembolic events are prevalent in the LAC positive paediatric SLE population, and consideration for lifelong anticoagulation must occur after an initial TE.
 ...
PMID:Thromboembolism in paediatric lupus patients. 1459 22

The product of the growth arrest-specific gene 6 (GAS6), a ligand for the Axl, Sky, and Mer tyrosine kinase receptors, is a vitamin K-dependent protein, structurally related to anticoagulant protein S. Gas6-deficient mice are protected against thrombosis, demonstrating the importance of this protein in the cardiovascular system. The present study was aimed at determining the human GAS6 intron-exon structure and analyzing the gene for the presence of allelic variants that could be associated with atherothrombotic disease. Online analyses allowed us to localize 15 GAS6 exons and to determine the sequence of their intron-flanking regions, in a chromosome 13 region spanning 43.8 kb of DNA. SSCP analysis of PCR-amplified GAS6 exons with their intron-flanking regions from a minimum of 12 control DNA samples, revealed the presence of eight different variants, which were confirmed to be single nucleotide polymorphisms (SNPs). Three of them (c.1263G>C, c.1332C>T, and c.1869T>C) are localized in exons 11, 12, and 14, and appear to be neutral since they do not modify the encoded amino acid. The other SNPs (c.280+170C>G, c.712+26G>A, c.713-155C>T, c.834+7G>A, and c.1478-94C>G) are in introns 3, 7, 8, and 12. A preliminary analysis of five of these SNPs in a group of 110 healthy controls and 188 patients with atherothrombotic disease has revealed statistically significant differences between controls and stroke patients in the allelic distributions of one of these variants (c.834+7G>A in intron 8). The SNP identification in GAS6 reported here would be very useful in future association studies aimed at determining the physiologic role of GAS6 in stroke and other human diseases.
 ...
PMID:Human vitamin K-dependent GAS6: gene structure, allelic variation, and association with stroke. 1510 83

Reduced activity of naturally occurring anticoagulants (NOAC) protein C and protein S may contribute to vaso-occlusion in sickle cell disease (SCD). We studied whether protein C and S are related to clinical vaso-occlusion, hematological markers of disease severity (hemoglobin levels, leukocyte counts, and percentage of fetal hemoglobin), and inflammation in SCD. Protein C activity, protein S (free and total) antigen, endothelial activation markers (soluble vascular cell adhesion molecule-1 [sVCAM-1], von Willebrand antigen [vWF]), and high sensitive C-reactive protein (hsCRP) levels were measured in 30 HbSS and 20 HbSC patients and in race-matched HbAA controls. NOAC levels were reduced in patients, and endothelial activation markers and hsCRP were elevated (except vWF in HbSC patients). Protein C activity and vWF levels were lower in HbSC patients who experienced painful crises compared to HbSC patients who were clinically asymptomatic. No other differences were observed between patients who did and did not experience vaso-occlusive events (painful crises, stroke, acute chest syndromes) or leg ulcers. A significant positive correlation between total protein S with hemoglobin levels and a significant negative correlation between total and free protein S and sVCAM-1 were detected in HbSS patients. Except perhaps for protein C in relation to painful crises in HbSC patients, these markers were not associated with the occurrence of clinical events. The protein S, hemoglobin, and sVCAM-1 associations may suggest decreased endothelial protein S production due to the more severe endothelial perturbation in HbSS patients with lower hemoglobin levels.
 ...
PMID:Protein C and S and inflammation in sickle cell disease. 1511 93


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>