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)

Early diagnosis is essential for the effective management of primary angiitis of the CNS (PACNS), but the presence of cerebrovascular amyloid angiopathy (CAA) may complicate the pathologic diagnosis since nonvasculitic inflammatory reactions can accompany CAA. We report two patients with PACNS associated with CAA in whom the progression of symptoms ceased during combined corticosteroid/cyclophosphamide therapy. One patient had prominent eosinophilic vasculitis and eosinophilic CSF pleocytosis. Based on review of reported cases, features supporting the diagnosis of symptomatic vasculitis in these patients include subacute progression of mental status changes and multifocal deficits, elevated ESR and CSF protein, and multifocal nonhemorrhagic lesions on imaging studies. We conclude that combined disease (PACNS/CAA) is similar to PACNS and probably occurs more frequently than expected by coincidence. The presence of CAA should not alter the treatment strategy in patients presenting with symptoms and laboratory studies consistent with PACNS.
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PMID:Primary angiitis of the central nervous system associated with cerebral amyloid angiopathy: report of two cases and review of the literature. 900 44

Typical cases of MELAS present a combination of clinical and neuroradiological features, lactacidaemia, and ragged red fibers (RRFs) in striated muscle. We have observed a MELAS-like syndrome in monozygotic twins. They developed seizures typically in conjunction with physical exertion, sleep deprivation or febrile episodes. Stroke-like episodes occurred usually during seizures. In twin 2 the course was fatal at age 20 years. Neuroradiological findings were typical of MELAS. Plasma lactate was normal in both. CSF lactate was normal in twin 1 and normal/elevated in twin 2. RRFs were not seen in muscle biopsies of the twins. Complex I activity was reduced in muscle in twin 1. Brain tissue removed at epilepsy surgery in twin 2 showed the presence of mitochondrial angiopathy. The commonest mitochondrial DNA mutation in MELAS, at base pair 3243, was absent. Lactacidaemia and mitochondrial myopathy with RRFs constitute part of the diagnostic criteria of MELAS. However, the absence of these features does not exclude mitochondrial disorder with the serious manifestations of MELAS (seizures and stroke-like episodes) as seen in these twins.
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PMID:Monozygotic twins with MELAS-like syndrome lacking ragged red fibers and lactacidaemia. 893 33

Human serum albumin minimally-modified by methylglyoxal (MGmin-HSA) stimulated the synthesis and secretion of macrophage-colony stimulating factor (M-CSF) by mature human monocytes in vitro. Human serum albumin minimally-modified by glucose-derived advanced glycation endproducts (AGEmin-HSA) and human serum albumin highly-modified by glucose-derived advanced glycation endproducts (AGE-HSA) stimulated much lower secretion of M-CSF from human monocytes than did MGmin-HSA. MGmin-HSA and AGE-HSA but not AGEmin-HSA also stimulated the growth of human monocytic THP-1 cells in vitro which was inhibited by polyclonal antibodies to human M-CSF. For MGmin-HSA, the median growth stimulatory concentration EC50 value was 0.24 +/- 0.07 microM and the maximal increase in cell growth was 36% of control cell growth (n = 24). Similar induction of secretion of M-CSF from monocytes in vivo may contribute to atherosclerosis in macro- and micro-angiopathy, particularly in the development of diabetic complications.
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PMID:Synthesis and secretion of macrophage colony stimulating factor by mature human monocytes and human monocytic THP-1 cells induced by human serum albumin derivatives modified with methylglyoxal and glucose-derived advanced glycation endproducts. 894 11

Some patients with familial Alzheimer's disease (FAD) have mutations in the presenilin-1 (PS-1) gene on chromosome 14. We report a Japanese family with AD and an Ala285Val substitution in exon 8 of the PS-1 gene. FAD in this family was characterized by relatively late onset (mean age, 50 years) and absence of myoclonus, seizures, or paratonia. Levels of tau were markedly elevated in CSF whereas CSF levels of amyloid beta protein were normal. MRI of the cranium showed marked linear signal abnormalities within white matter in the parieto-occipital lobes, consistent with cortical amyloid angiopathy of the type encountered in patients with the PS-1 gene mutation.
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PMID:A presenilin-1 mutation in a Japanese family with Alzheimer's disease and distinctive abnormalities on cranial MRI. 910 15

Extracellular deposition of amyloid beta protein (A beta) as senile plaques and cerebral amyloid angiopathy (CAA) is one of the essential pathological characteristics of Alzheimer's disease (AD). Several A beta species with different carboxyl termini, including A beta 42 (43) and A beta 40 ending at residue 42 (43) and 40, respectively, have been identified in CAA and in senile plaque cores. Because A beta 42 (43), the major component of diffuse plaque which is the earliest pathological change in AD brains, forms insoluble amyloid fibrils more rapidly than does A beta 40, it has been hypothesized that A beta 42 (43) plays a role in amyloid seeding and A beta 40, in the elongation of amyloid fibrils on a seed of A beta 42 (43). We used enzyme-linked immunosorbent assay (ELISA) with site-specific monoclonal antibodies to differentiate A beta 42 (43) from A beta 40. First, we measured the amounts of different A beta species in plasma from patients with sporadic probable AD, age-matched patients with neurologic diseases but without dementia, and age-matched normal controls. Concentrations of A beta 1-40 and A beta 1-42 (43) in plasma did not differ significantly among the three groups. Second, CSF levels of A beta species (CSF-A beta) with different carboxy termini, i.e., A beta X-40 and A beta X-42 (43) as well as A beta 1-40 and A beta 1-42 (43), were measured in patients with AD and in age-matched controls without dementia using ELISA. Levels of both CSF-A beta X-42 (43) and A beta 1-42 (43) were significantly lower in the patients with AD that in the controls, but neither the levels of CSF-A beta X-40 nor those of CSF-A beta 1-40 differed between the two groups, which suggest that increased adsorption of A beta 42 (43) to A beta deposition in AD brains, decreased secretion of A beta 42 (43) in CSF, or increased clearance of A beta 42 (43) from CSF might explain the low levels of A beta 42 (43) in the CSF of patients with AD. Third, we measured the concentrations of various A beta species post-mortem in the cerebral cortex of patients with PS-1 mutations and beta amyloid precursor protein (APP) 717 mutation linked to familial AD or Down syndrome. The results indicate that one effect of PS-1 mutations, APP717 mutation and Down syndrome is to cause dramatic and accelerated accumulation of A beta 42 (43) in the brain as compared with sporadic AD. In particular, the increases in A beta 1-42 (43) showed a crude inverse correlation with the age of onset in each subtype of AD. Thus, quantitative studies differentiating A beta 42 (43) from A beta 40 have established the fundamental importance of A beta 42 (43) in AD.
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PMID:[Characterization of amyloid beta protein species in the plasma, cerebrospinal fluid and brains of patients with Alzheimer's disease]. 964 8

The diagnosis of MS is based exclusively on clinical examination disclosing at least two focal lesions, repeatedly occurring recurrences and ruling out of other causes. This is the generally accepted principle based on the diagnostic criteria of Poser. The presence of the lesions can be demonstrated in clinical examinations by magnetic resonance imaging /MRI/ or the study of evoked potentials /EP/ which detect these changes in about 90% of cases of clinically certain MS. In 10% of cases the results are negative--but can this exclude MS? It happens also that MRI or EP carried out for another reason demonstrate the presence of such lesions--is it MS in such cases? The diagnosis of SM is supported by age below 40 years and the presence of at least four focal lesions in the white matter of the hemispheres. After the age of 50 years such lesions can be the consequences of vascular disease. Contrast administration makes possible the detection of new foci and their differentiation from the old ones. In 65-85% of cases the initial phase is marked by remitting course with more or less evident worsening after each exacerbation. Out of them, in 40-70% of cases the remitting course changes to secondary progressing course. In only 10% of cases the course is progressing from the beginning. The prognosis is better if the disease begins with optic nerve involvement and is worse if pyramidal or cerebellar signs appear first. CSF examination is less important than MRI or EP. In biochemical tests no sure markers of the disease are found. In the treatment of acute exacerbations steroids are still most effective. In clinically confirmed MS interferon beta given in the first 2 years is effective in 30% of cases.
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PMID:[Multiple sclerosis--certain clinical and diagnostic problems]. 1110 65

We report the case of a 65 year old female patient with biopsy-proven cerebral amyloid angiopathy (CAA). She experienced intracerebral hemorrhages 4 times during 23 days but these serious strokes did not recur after corticosteroid therapy was started and her condition greatly improved. Since high titers of antinuclear antibodies and elevated erythrocyte sedimentation rate were found in her serum, she may have an inflammatory disorder involving amyloid-laden cerebral vessels. This is the first report showing the usefulness ofcorticosteroid for the treatment of CAA-related cerebral hemorrhages. Additionally, the concentrations of Abeta40 and Abeta42 in the CSF of this patient decreased rapidly after the use of corticosteroid, and ultimately fell far below normal values.
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PMID:Cessation of cerebral hemorrhage recurrence associated with corticosteroid treatment in a patient with cerebral amyloid angiopathy. 1113 98

Kawasaki disease (KD) is a childhood-onset vascular disease. We assessed the concentrations of macrophage-colony stimulating factor (M-CSF) and those of lipids in sera from patients with KD. The M-CSF concentration in patients with acute-phase KD was 2,914+/-159 U/ml, significantly higher than that in control subjects with Infectious diseases (1,241+/-96 U/ml). The elevated levels of this cytokine in the acute phase fell to 1,319+/-138 U/ml in the convalescent phase. Total and high-density lipoprotein cholesterol concentrations in acute phase KD (113.8+/-8.4 and 21.5+/-2.3 mg/dl, respectively) were lower than in the infectious disease controls (195.8+/-7.0 and 62.5+/-1.8 mg/dl). The elevation of M-CSF correlated with the decrease of total and high-density lipoprotein cholesterol. Overproduction of macrophage-colony stimulating factor activates macrophages and monocytes and may disturb the lipid metabolism. Both effects could contribute to vasculitis in KD.
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PMID:Inverse correlation between macrophage-colony stimulating factor, cholesterol and high density lipoprotein cholesterol in Kawasaki disease. 1169 25

In vitro experiments and animal models indicate that advanced glycation end products (AGEs) may play a crucial role in the vascular dysfunctions observed in patients with diabetes mellitus. These results prompted us to study subrogate markers of inflammation or vascular dysfunction in type II diabetic patients. Monocyte count and activation are dependent upon macrophage colony stimulating factors (M-CSF). Soluble vascular cell adhesion molecule (sVCAM-1) blood levels have been proposed as a marker for endothelium activation. To explore a possible relationship between these factors in diabetic patients, we measured a chemically defined AGE, N(carboxymethyl)lysine-protein (CML-protein) in a group of normal subjects (n = 55) and of diabetic patients (n = 40) using ELISA. Simultaneously, we determined M-CSF and sVCAM-1 blood levels. We found that CML-protein blood levels were significantly higher in patients with diabetes compared to non-diabetic subjects (40.2 +/- 4.7 and 7.9 +/- 0.7 pmol/mg protein respectively, p < 0.0001). M-CSF was increased while sVCAM-1 blood levels were normal in the group of diabetics. M-CSF blood level was correlated to CML-protein blood level (p < 0.05). In addition CML-protein, M-CSF and sVCAM-1 were increased in patients with micro-angiopathy. These results suggest that AGE may contribute to vascular dysfunction including microangiopathy.
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PMID:AGEs, macrophage colony stimulating factor and vascular adhesion molecule blood levels are increased in patients with diabetic microangiopathy. 1511 47

The three common forms of dementias in the elderly include Alzheimer's disease (AD), vascular dementia (VD) and normal pressure hydrocephalus (NPH). These disorders are distinguished by their specific pathological features. However, overlapping clinical and imaging features in a given case are not too uncommon. Based on alterations in CSF dynamics study, a unifying concept in the pathogenesis of AD and NPH has been proposed recently which may have therapeutic implications. Altered CSF dynamics by affecting the absorptive process may lead to hydrocephalic change. This may also affect clearance of amyloid protein leading to increased amyloid deposition in brain parenchyma resulting in AD pathology. Hence it is likely that a subgroup of patients may have an AD-NPH syndrome who may be benefitted by CSF drainage procedure. The present author attempts to extend this concept to hypothesise a unifying concept to explain the pathophysiology of all the three disorders which may explain overlapping features observed clinically and in neuroimaging studies. It is surmised that altered CSF dynamics and hypoperfusion from vascular disease may be interlinked. The defective clearance of amyloid may also lead to amyloid angiopathy perpetuating hypoperfusion. Hypoperfusion may also affect formation as well as absorption of CSF altering clearance of amyloid and promoting vascular and parenchymal deposition. Thus the pathologies of AD, VaD and NPH get interrelated.
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PMID:Unifying concept for Alzheimer's disease, vascular dementia and normal pressure hydrocephalus - a hypothesis. 1548 55


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