Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amyloid P (AP) component is present in all types of systemic amyloid deposits. Recently, it has been shown to be also present in cerebral amyloid lesions of Alzheimer's disease (AD). In this study, we used immunocytochemical methods to extend these findings at the electron microscope level and characterize the spectrum of AP immunoreactivity in neurofibrillary pathology (NFP) of AD and other neurodegenerative disorders including Down's syndrome (DS), Creutzfeldt-Jakob, Parkinson's, Pick's and diffuse Lewy body diseases and progressive supranuclear palsy. In AD and DS, AP immunoreaction product was evident in all the classical amyloid lesions and NFP in a large sample of all cortical areas examined. The distribution and relative intensity of immunostaining was similar to that of thioflavin S staining in serial sections. In many cases, however, plaques and vessels stained by anti-AP serum were not apparent with thioflavin S. Serial sections immunostained with antiserum to amyloid A, C-reactive protein or to other proteins involved in systemic amyloidoses and the acute phase response showed no evidence of staining in any of the cerebral lesions. Electron microscopy confirmed that AP immunoreactivity was associated with the abnormal filaments characteristic of NFP as well as amyloid fibrils found in plaques and vessels showing congophilic amyloid angiopathy. Plaques of Creutzfeldt-Jakob disease, Pick bodies of Pick's disease, tangles and Lewy bodies in Parkinson's disease and a subpopulation of Lewy bodies in the diffuse Lewy body disease coexistent with AD were also stained. With the exception of vessels in two of the five cases, AP was not detected in age-matched controls. Our observations indicate AP to be a consistent feature of cerebral NFP and amyloid deposits.
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PMID:Widespread serum amyloid P immunoreactivity in cortical amyloid deposits and the neurofibrillary pathology of Alzheimer's disease and other degenerative disorders. 189 Oct 63

Plasminogen activator inhibitor-1 (PAI-1) is an important physiological inhibitor of fibrinolysis. It circulates in blood both in free active form and in inactive form complexed with tissue type plasminogen activator (t-PA). Control mechanisms for its synthesis and release from hepatocytes and endothelial cells are important in the pathogenesis of thrombosis. Possible risk factors for myocardial infarction include high insulin and PAI-1 levels, which correlate with one another in healthy subjects, and fibrinogen, which together with PAI-1, is an acute-phase reactant. We therefore studied the interrelationships between PAI-1, plasma insulin, and acute-phase proteins in 67 patients with angina pectoris. Plasma insulin correlated strongly (r = 0.59, p less than 0.001) with PAI activity, free PAI-1 antigen (r = 0.60, p less than 0.001), and total PAI-1 antigen (r = 0.58, p less than 0.001). The acute-phase proteins, fibrinogen and C-reactive protein, correlated significantly with t-PA antigen, total PAI-1 antigen, and PAI-1/t-PA complexes but not with PAI activity or free PAI-1. The results suggest that insulin stimulates synthesis and release of free PAI-1 (probably via hepatocytes as previously shown with cell culture) and that endothelial cell synthesis and release of t-PA, together with PAI-1, reflects a nonspecific acute-phase response to chronic vascular disease. Hyperinsulinemia found in patients with angina pectoris could play a role in the development of myocardial infarction via the induction of high plasma PAI-1 activity.
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PMID:Plasma plasminogen activator inhibitor-1 in angina pectoris. Influence of plasma insulin and acute-phase response. 247 Mar 43

Factor-VIII-Related antigen (VIII R:Ag) is known to be produced by the blood vessel wall. Noxious stimuli increase endothelial release of VIII R:Ag. It might be expected that the development of vasculitis would be associated with increased levels of VIII R:Ag. To investigate this, eight different groups of subjects were studied: 25 patients with systemic sclerosis, 19 with systemic lupus erythematosus, 15 with rheumatoid arthritis (RA) plus vasculitis, 19 with systemic vasculitis and 14 with atherosclerosis. These groups were compared to 29 patients with primary Raynaud's disease, 15 with RA without vasculitis and 50 controls. Results showed that where there was evidence of vascular disease, then VIII R:Ag was elevated. VIII R:Ag appeared to be a more specific marker for vascular damage than erythrocyte sedimentation rate or C-reactive protein. Longitudinal studies in 11 patients showed good correlation between progression of vascular disease and VIII R:Ag.
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PMID:Vascular damage and factor-VIII-related antigen in the rheumatic diseases. 311 42

In a 64-year-old man heart transplantation had been performed for ischaemic heart disease. 7 months later severe vascular disease in the transplant necessitated a second transplantation. Both procedures had been performed under immunosuppression (cyclosporine, azathioprine, prednisolone, antithymocyte globulin), with a subsequent prednisolone maintenance dose of 10 mg daily. At first there were no complications, but 31 days after the re-transplantation atrial flutter developed. Although this was quickly terminated by drugs, circulatory failure set in. Because of signs of infection (white blood cell count 29,800/microliters, 17% stab cells, C-reactive protein 24 mg/l) broad-spectrum antibiotics were administered, but without response. As a trial anti-rejection treatment was started (prednisolone 250 mg daily: antithymocyte globulin 100 mg daily for 4 days). When cytomegalovirus (CMV) infection was demonstrated, ganciclovir and CMV hyperimmunoglobulin were administered and slow improvement was noted. The finding of Aspergillus in tracheal secretion was interpreted as apathogenic colonization. The patient died from cardiorespiratory failure 57 days after the second transplantation. Autopsy revealed Aspergillus sepsis.
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PMID:[Fatal Aspergillus sepsis following orthotopic heart transplantation]. 760 Sep 27

Amyloid P component is a normal serum protein that is highly conserved across phylogeny. Although it resembles the classic acute-phase reactant C-reactive protein, and is considered to be a normal extracellular matrix component, its physiologic role in humans is unknown. Amyloid P component is also colocalized with accumulations of all recognized forms of amyloid. The present study uses light and electron microscopy to compare the cerebral localization of amyloid P component in cases with (n = 19) and without (n = 15) Alzheimer's disease (AD). In non-AD cases, amyloid P component was predominantly localized to the cerebrovasculature. Perivascular staining was observed in most cases, more so in the white than in the gray matter. In AD cases, amyloid P component was localized to all three characteristics histopathologic lesions, namely, neurofibrillary tangles, senile plaques, and amyloid angiopathy. Furthermore, in cases with prominent staining of gray matter parenchymal lesions, intravascular staining was decreased. Given the fixation and processing methods used, amyloid P component was never seen to be localized to the cerebrovascular basement membrane. These data argue against amyloid P component's postulated role as the anchor for vascular beta-amyloid deposition. Because there is no evidence for intrinsic amyloid P component production in brain, its perivascular and parenchymal distributions suggest either compromise of the blood-brain barrier or transport across vascular endothelium.
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PMID:Localization of amyloid P component in human brain: vascular staining patterns and association with Alzheimer's disease lesions. 771 41

The association of cigarette smoking with the development of occlusive vascular disease is firmly established. Unfavourable changes in a series of variables held independent risk factors for the development of vascular lesions (HDL-cholesterol, haematocrit, white blood cell count, fibrinogen and plasminogen activator inhibitor-1 (PAI-1)) are thought to be directly influenced by cigarette smoking. However, the role played by the genotype in the effect of smoking on the above parameters has not been investigated. To control the genotype, we studied the relationship between cigarette smoking and a series of cardiovascular risk factors in 27 monozygotic twin pairs (7 male and 20 female pairs, mean age +/- SD: 47.4 +/- 12.9 yrs) with a life-long discordance for smoking. Smoking twins had a life-long dose of smoking (Brickman index) of 287.3 +/- 241.5. Body mass index, blood pressure, haematocrit, haemoglobin and red blood cell counts, total cholesterol levels and the acute phase reactants alpha 1-acid glycoprotein and C-reactive protein were similar in smokers and non-smokers. Triglyceride was higher by 12.6% (9.5-35%, 95% confidence interval, p = 0.02) and HDL-cholesterol lower by 7.5% (0.2-15%, p = 0.04) in the smoking co-twins, who also had 8.4% (-0.2-17%, p = 0.06) higher white blood cell counts and 4.1% (1.2-7%, p < 0.01) larger mean platelet volume. There was no significant difference in clottable fibrinogen (by two methods) or in the activity of plasminogen activator inhibitor-1 between the two groups, nor was the within-pair difference in these parameters related to the smoking dose. Echo-doppler examination of the carotid arteries of 24 twin pairs showed mostly minor atherosclerotic lesions in 46% and 42% of the smoking and non-smoking co-twins. After adjustment for age, systolic blood pressure and platelet count and volume were the only variables significantly associated to the presence of vascular lesions. Cigarette smoking is associated with an atherogenic lipid profile and with changes in platelets and white cells potentially reflecting endothelial cell damage. When controlling the genotype, fibrinogen and PAI-1 activity levels did not seem directly influenced by cigarette smoking.
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PMID:The effect of cigarette-smoking on cardiovascular risk factors: a study of monozygotic twins discordant for smoking. 871 73

High plasma fibrinogen levels are associated with vascular complications in the general population. Fibrin, the structural element in a clot, is derived from fibrinogen by activation of thrombin. An abnormal fibrin gel structure has been demonstrated in patients with myocardial infarction and in diabetic patients during poor metabolic control. In the present study the properties of fibrin gel structure were investigated in 20 patients with insulin-dependent diabetes mellitus (IDDM): 10 patients without (age: 30 +/- 8; diabetes duration: 7 +/- 6 years), and 10 patients (age: 44 +/- 7; diabetes duration: 27 +/- 9 years) with microangiopathy. Fifteen healthy subjects served as controls (age: 40 +/- 8 years). The glycosylated haemoglobin level (HbA1c) was elevated (p < 0.001) in the patients: 6.5 +/- 1.5% in diabetic patients without, and 7.1 +/- 1.0% in diabetic patients with microangiopathy. C-reactive protein and plasma fibrinogen were similar as compared to healthy control subjects. The properties of the fibrin gel structure; i.e. the permeability coefficient (Ks) and the fibre mass length ratio (mu) formed in recalcified plasma on addition of thrombin were investigated. Ks was decreased in the diabetic patients, with (6.5 +/- 2.0 cm2; p < 0.01) and without microangiopathy (6.5 +/- 2.7 cm2; p < 0.05), as compared to healthy subjects (10.0 +/- 3.4 cm2), while mu was not significantly (p = 0.14) altered. The results indicate a lower fibrin gel porosity in patients with IDDM, despite normal plasma fibrinogen and irrespective of microangiopathy. The abnormal fibrin gel structure may be due to an increased glycosylation of the fibrin (-ogen) molecule caused by long-term hyperglycaemia and may be of importance for the development of angiopathy in diabetic patients.
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PMID:Altered properties of the fibrin gel structure in patients with IDDM. 924 13

The present study evaluated the clinical significance of hepatocyte growth factor (HGF) in patients with pulmonary fibrosis. Twenty-one patients with a diagnosis of pulmonary fibrosis [14 with idiopathic pulmonary fibrosis (IPF) and seven with pulmonary fibrosis associated with a collagen vascular disorder (PF-CVD]) and 21 normal subjects as control were studied. HGF levels in sera of patients with pulmonary fibrosis (0.34 +/- 0.02 ng ml-1) were elevated significantly as compared with normal subjects (0.21 +/- 0.01 ng ml-1) (P < 0.0001). HGF/albumin levels in broncho-alveolar lavage fluid (BALF) of patients with pulmonary fibrosis (72 +/- 17 ng g-1 albumin) were also significantly elevated as compared with normal subjects (under the detection limit) (P < 0.01). HGF levels in sera correlated significantly with elastase levels in sera and C-reactive protein, and correlated negatively with PaO2. HGF levels in sera were significantly higher in smokers with pulmonary fibrosis (0.42 +/- 0.03 ng ml-1) as compared with non-smokers with pulmonary fibrosis (0.29 +/- 0.03 ng ml-1) (P < 0.005). HGF/albumin levels in BALF correlated significantly with elastase/albumin levels in BALF, lactate dehydrogenase/albumin in BALF, Immunoglobulin A/albumin in BALF, total cell count/albumin in BALF, total number of alveolar macrophage/albumin in BALF, total number of neutrophil/albumin in BALF, CEA/albumin in BALF, CA19-9/albumin in BALF, and SCC/albumin in BALF. These results suggest that following lung injury, HGF may be a mediator involved in the repair which leads to pulmonary fibrosis.
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PMID:Measurement of hepatocyte growth factor in serum and bronchoalveolar lavage fluid in patients with pulmonary fibrosis. 961 25

Coagulation factor levels predict arterial thrombosis in epidemiological studies, but studies of older persons are needed. We studied 3 plasma antigenic markers of fibrinolysis, viz, plasminogen activator inhibitor-1 (PAI-1), fibrin fragment D-dimer, and plasmin-antiplasmin complex (PAP) for the prediction of arterial thrombosis in healthy elderly persons over age 65. The study was a nested case-control study in the Cardiovascular Health Study cohort of 5201 men and women >/=65 years of age who were enrolled from 1989 to 1990. Cases were 146 participants without baseline clinical vascular disease who developed myocardial infarction, angina, or coronary death during a follow-up of 2.4 years. Controls remained free of cardiovascular events and were matched 1:1 to cases with respect to sex, duration of follow-up, and baseline subclinical vascular disease status. With increasing quartile of D-dimer and PAP levels but not of PAI-1, there was an independent increased risk of myocardial infarction or coronary death, but not of angina. The relative risk for D-dimer above versus below the median value (>/=120 microg/L) was 2.5 (95% confidence interval, 1.1 to 5.9) and for PAP above the median (>/=5.25 nmol/L), 3.1 (1.3 to 7.7). Risks were independent of C-reactive protein and fibrinogen concentrations. There were no differences in risk by sex or presence of baseline subclinical disease. D-dimer and PAP, but not PAI-1, predicted future myocardial infarction in men and women over age 65. Relationships were independent of other risk factors, including inflammation markers. Results indicate a major role for these markers in identifying a high risk of arterial disease in this age group.
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PMID:Fibrinolytic activation markers predict myocardial infarction in the elderly. The Cardiovascular Health Study. 1007 48

Lipid-lowering by postmenopausal hormone therapy (HRT) explains only partly the assumed coronary risk reduction associated with therapy. To explore other possible mechanisms, we studied associations of HRT use with inflammation and hemostasis risk markers in women >/=65 years of age. Subjects were selected from 3393 participants in the fourth year examination of the Cardiovascular Health Study, an observational study of vascular disease risk factors. After excluding women with vascular disease, we compared levels of inflammation and hemostasis variables in the 230 women using unopposed estrogen and 60 using estrogen/progestin, with those of 196 nonusers selected as controls. Compared with nonusers, unopposed estrogen use was associated with 59% higher mean C-reactive protein (P<0.001), but with modestly lower levels of other inflammation indicators, fibrinogen, and alpha-1 acid glycoprotein (P<0.001). Factor VIIc was 16% higher among estrogen users (P<0.001), but this was not associated with higher thrombin production (prothrombin fragment 1-2), or increased fibrin breakdown (D-dimer). Concentration of plasminogen activator inhibitor-1 was 50% lower in both using groups (P<0.001) compared with nonusers, and this was associated with higher plasmin-antiplasmin complex: 8% higher in estrogen and 18% higher in estrogen/progestin users (P<0. 05). Relationships between the markers and hormone use were less pronounced in estrogen/progestin users, with no association for C-reactive protein except in women in upper 2 tertiles of body mass index (P for interaction, 0.02). The direction and strength of the associations of HRT use with inflammation markers differed depending on the protein, so it is not clear whether HRT confers coronary risk reduction through an inflammation-sensitive mechanism. Associations with hemostasis markers indicated no association with evidence of procoagulation and a possible association with increased fibrinolytic activity.
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PMID:Hormone replacement therapy, inflammation, and hemostasis in elderly women. 1019 15


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