Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the clinical and pathologic features of a patient with peripheral neuropathy that was the first clinical expression of cholesterol emboli syndrome (CES). Biopsy of skeletal muscle and peripheral nerve revealed cholesterol clefts in lumens of small arteries, necrotizing arteritis, and severe degeneration of peripheral and intramuscular nerves. At autopsy, the peripheral nervous system was extensively affected by similar changes. We conclude that (1) peripheral neuropathy may be the initial manifestation of CES. Presumably, deposition of cholesterol leads to arteritis. (2) The underlying pathology of CES neuropathy is chronic axonal degeneration, possibly due to chronic ischemia of epineurial arteries. (3) Muscle biopsy is important in the antemortem diagnosis of CES. Nerve biopsy may show involvement of epineurial vessels. (4) CES may resemble polyarteritis nodosa clinically and pathologically. (5) CES may be under-recognized and should be included in the differential diagnosis of any neuropathy of uncertain cause, particularly when there is a history of vascular catheterization, or severe aortic atherosclerosis.
 ...
PMID:Cholesterol emboli neuropathy. 131 May 30

There is no literature report of a detailed morphologic study of the aortic depressor nerve. The aim of this study was to describe the general morphological aspects and to obtain morphometric parameters for the aortic depressor nerve of normotensive Wistar rats (n=12). Before the morphologic studies, nerves were isolated and pressure-nerve activity curves were obtained. Basal mean arterial pressure was 117+/-5 mm Hg, the systolic pressure threshold was 100+/-7 mm Hg, and mean arterial pressure at 50% of maximal activity was 115+/-5 mm Hg and the baroreceptor gain 1.99+/-0.09%/mm Hg. Semithin and thin sections of proximal and distal nerve segments were then examined by light and electron microscopy, respectively. The main nerve components were (1) unmyelinated and myelinated axons; (2) Schwann cells; (3) capillary wall endothelial cells and pericytes; (4) collagen fibers in the epineurium and endoneurium and between perineurial cell layers; and (5) fibroblasts and mast cells. The depressor nerves were found to contain 204-996 axons per nerve, 80% of which, on average, were unmyelinated, with a 4:1 unmyelinated/myelinated axon ratio. The unmyelinated axon histogram was unimodal, with a mean diameter of 0.5+/-0.02 microm. Myelinated fibers had axons averaging 1.3+/-0.06 microm in diameter and representing 53% of the total fiber diameter. The ratio between axonal and total fiber diameter of myelinated fiber ranged from 0.4 to 0.8 and tended to increase with axon size. Proximal and distal segments were morphologically similar. In conclusion, the morphologic description of the depressor nerve provides important data for further investigations of the structural basis of altered baroreflex responses in conditions such as arterial hypertension, aging, atherosclerosis, and peripheral neuropathies.
 ...
PMID:A descriptive and quantitative light and electron microscopy study of the aortic depressor nerve in normotensive rats. 932 7

According to recent knowledge, apolipoprotein E (apo E) plays a significant role in the homeostasis of intracellular cholesterol level in various tissues. Apo E deficient mice develop hyperlipidemia, and suffer from atherosclerosis in extracerebral blood vessels and neurodegeneration in the central nervous system. Furthermore, Walker et al. (Am. J. Path., 1997;151:1371-1377) demonstrated cerebral xanthomas of various sizes in the brain of apo E deficient mice. In the present study, it is illustrated that in the homozygous apo E deficient mice of advancing age, a great number of foamy macrophages extravasate from microvessels in thalamus and fimbria hippocampi, and scatter in the perivascular regions and migrate toward the ependyma, fimbria hippocampi, hippocampus, and thalamus. Here, it must be pointed out that under hyperlipidemia, although foamy macrophages made clusters in the perivascular region, the cerebral microvessels did not develop atherosclerosis. On the other hand, in the other cerebral regions such as cerebral cortex, caudoputamen, globus pallidus, and substantia nigra, macrophages did not appear and microvessels retained normal shapes, but the fluorescent granular perithelial (in short, FGP) cells accompanied by these vessels contained a certain amount of lipids. That is, in the cerebral cortex and caudoputamen, lipid components are detected in FGP cells and microglia, while in the globus pallidus and substantia nigra, they are mainly localized in astrocytes. The reason why the astrocytes in such defined regions contain, specifically, a high quantity of lipid components remains unsettled. Axonal degenerations are often represented in thalamus, globus pallidus, and substantia nigra. On the other hand, in the specimens of Wild-type mice, lipid components were observed only in FGP cells, and the vascular architecture took a normal profile. Any lipid laden macrophages and the axonal degenerations could not be detected through the cerebral parenchyma. Furthermore, it is also a noticeable finding that immunohistochemically, the FGP cells express a positive reaction against the antibody of apo E in the Wild-type mice, but those of homozygous apo E deficient mice are immunonegative. FGP cells are not only provided with the scavenger receptor, but also contribute to the lipid metabolism in the brain.
 ...
PMID:Regional difference of lipid distribution in brain of apolipoprotein E deficient mice. 1048 14

Based on histopathology, electron microscopic corrosion cast studies, optic nerve blood flow studies, and clinical data, the pathogenesis of idiopathic nonarteritic ischemic optic neuropathy includes the following features: (1) structurally crowded optic discs are predisposed; (2) laminar and retrolaminar regions are the most common locations for infarction; (3) there is flow impairment in the prelaminar optic disc during the acute phase; (4) lack of consistent choroidal flow impairment and the retrolaminar location of infarcts suggest vasculopathy within or distal to the paraoptic branches of the posterior choroidal arteries; (5) diabetes is the most consistently identified vasculopathic risk factor; (6) impaired autoregulation of the disc circulation by atherosclerosis, with a possible contribution from serotonin and endothelin-mediated vasospasm, may play a role; and (7) progression may be caused by secondary cell death after the initial ischemic insult or compression from cavernous degeneration and mechanical axonal distortion.
 ...
PMID:Pathogenesis of nonarteritic anterior ischemic optic neuropathy. 1278 32

Cells can sense changes in their mechanical environment and promote alterations and adaptations in tissue structure and function. Mechanical stimuli regulate such fundamental processes as cell division and differentiation and determine tissue form. The current editorial outlines the general scope of a subject area we have called 'mechanical morphogenesis'. We are promoting it as an area of special interest for future issues of the European Journal of Morphology. Clearly, mechanical loading is of pivotal importance to the development, function and repair of all tissues in the musculoskeletal system, including bone, ligament, tendon, skeletal muscle, intervertebral disc and meniscus. Bone in particular has attracted special interest and mechanical strain is central to both Wolff 's law and Frost's 'mechanostat' model of bone behaviour. But it is skeletal muscle that shows the most obvious and rapid response to altered load, with striated muscle fibres hypertrophing with strength-training programmes, and atrophing in the absence of adequate mechanical stimulation. Articular cartilage, together with tendons and ligaments is also responsive to changing exercise levels, and either abnormally high or low loads are detrimental. However, the influence of mechanical forces extends to many other organ systems, including the respiratory, cardiovascular, nervous and integumentary systems. The bronchial mucosa and the alveoli are subject to tensile and compressive loading during the volume changes that occur in respiration, and surface tension is also of paramount importance. The whole form of the cardiovascular system is driven by the haemodynamic influences of blood, and atherosclerosis has an underlying mechanical basis. The characteristic plaques tend to occur at sites of obvious mechanical significance - regions of arterial branching and curvature, where shear stress on the vessel wall may be low, but tensile stress high. Sensory perception by the nervous system has a well known mechanical basis and the cochlea is perhaps the most elaborate example of a site where sensory cells transduce mechanical forces and relay information to the brain. Mechanical force has also been proposed as a regulating factor in controlling axonal growth. Finally, the integumentary system has several structural adaptations that obviously relate to the influence of mechanical forces. The thickened layer of keratinised squames in the palms and soles is directly related to the high levels of shear at these locations.
 ...
PMID:Mechanical influences on cells, tissues and organs - 'Mechanical Morphogenesis'. 1512 43

Until relatively recently, depression has been considered a purely "mental" disorder and therefore in the natural domain of psychologists and psychiatrists. However, recent epidemiological studies have revealed that aging, physical and psychological stress, chronic pain, several metabolic disorders such as insulin resistance and established diabetes, alcoholism, inflammatory conditions, and vascular disorders such as arterial hypertension all may be associated with depression. The present review examines some of these depression-associated factors and the mechanisms by which they might give rise to vascular disorders such as atherosclerosis, microcirculation endothelial dysfunction, and interstitial disturbances leading to organ damage. A number of disorders involving the circulation can lead progressively and insidiously to large artery rigidity, remodeling of peripheral arteries, and alterations of the microcirculation of large blood vessels. Perturbations in vasa vasorum blood flow may contribute to atherogenesis, in addition to the influence of numerous cellular events involved in inflammation (tumor necrosis factor alpha, interleukin 1 beta, etc). Since Hans Selye first described the neuroendocrine cascade generated by experimentally induced stress half a century ago, phenomena such as the axonal release of neurotransmitters (including serotonin), accumulation of metabolites such as homocysteine, platelet-activating factor, and nitric oxide also have been implicated in the pathogenesis of depression. Moreover, vascular consequences of depression such as heart rate and pulse pressure variations may lead to endothelial dysfunction in critical microcirculation networks (cerebral, myocardial, and renal) and initiate physicochemical alterations in interstitial compartments adjacent to vital organs. The appropriate use of ambulatory monitoring of vascular parameters, such as heart rate and pulse pressure, and eventually, early identification of genetic and metabolic markers may prove helpful in the early detection of events preceding and predicting the clinical manifestations of depression.
 ...
PMID:Depression and cardiovascular disease: a reciprocal relationship. 1587 13

Abnormalities of cerebral white matter are present in a majority of patients with Alzheimer's disease (AD) and probably contribute to motor dysfunction and cognitive impairment. The white matter abnormalities are usually attributed to degenerative vascular disease and cerebral amyloid angiopathy (CAA) but the evidence is scanty or inconclusive. In the present study we examined sections of frontal lobe from 125 autopsy-confirmed cases of AD and assessed the relationship of degenerative large and small vessel disease, CAA, parenchymal Abeta load and APOE genotype, to several objective measures of white matter damage: extent of immunolabelling for glial fibrillary acidic protein (GFAP), axonal accumulation of amyloid precursor protein (APP), axon density in superficial and deep white matter, and intensity of staining for myelin. We found no association between atherosclerosis, arteriolosclerosis, CAA or APOE genotype and white matter damage. However, labelling of white matter for GFAP correlated strongly with the parenchymal Abeta load (P = 0.0003) and with APP accumulation (P = 0.008). Our findings suggest that severity of frontal white matter damage in AD is closely related to parenchymal Abeta load and that in most cases the contribution of degenerative vascular disease, CAA and APOE is relatively minor.
 ...
PMID:Contributors to white matter damage in the frontal lobe in Alzheimer's disease. 1628 11

Cockayne syndrome and xeroderma pigmentosum-Cockayne syndrome complex are rare autosomal recessive disorders with poorly understood biology. They are characterized by profound postnatal brain and somatic growth failure and by degeneration of multiple tissues resulting in cachexia, dementia, and premature aging. They result in premature death, usually in childhood, exceptionally in adults. This study compares the clinical course and pathology of a man with Cockayne syndrome group A who died at age 31(1/2) years with 15 adequately documented other adults with Cockayne syndrome and 5 with xeroderma pigmentosum-Cockayne syndrome complex. Slowing of head and somatic growth was apparent before age 2 years, mental retardation and slowly progressive spasticity at 4 years, ataxia and hearing loss at 9 years, visual impairment at 14 years, typical Cockayne facies at 17 years, and cachexia and dementia in his twenties, with a retained outgoing personality. He experienced several transient right and left hemipareses and two episodes of status epilepticus following falls. Neuropathology disclosed profound microencephaly, bilateral old subdural hematomas, white-matter atrophy, tigroid leukodystrophy with string vessels, oligodendrocyte proliferation, bizarre reactive astrocytes, multifocal dystrophic calcification that was most marked in the basal ganglia, advanced atherosclerosis, mixed demyelinating and axonal neuropathy, and neurogenic muscular atrophy. Cellular degeneration of the organ of Corti, spiral and vestibular ganglia, and all chambers of the eye was severe. Rarely, and for unexplained reasons, in some patients with Cockayne syndrome the course is slower than usual, resulting in survival into adulthood. The profound dwarfing, failure of brain growth, cachexia, selectivity of tissue degeneration, and poor correlation between genotypes and phenotypes are not understood. Deficient repair of DNA can increase vulnerability to oxidative stress and play a role in the premature aging, but why patients with mutations in xeroderma pigmentosum genes present with the Cockayne syndrome phenotype is still not known.
 ...
PMID:Cockayne syndrome in adults: review with clinical and pathologic study of a new case. 1709 72

Multiple sclerosis (MS) is a common autoimmune neurodegenerative disease of unknown cause, which results in inflammation and plaques of demyelination in brain and eventual axonal degeneration. We report the novel presence of oxidized phosphatidylcholine [1-palmitoyl-2-(5'-oxo)valeryl-sn-glycero-3-phosphorylcholine (POVPC)], a lipid associated with inflammatory diseases such as atherosclerosis and lung disease, in the brain of MS patients. The OxPC epitope was detected by Western blotting with the E06 monoclonal antibody. E06-positive lipid was present in the highest amounts in MS plaques, which also showed evidence of low-molecular-weight (15-kDa) OxPC-modified protein. E06 reactivity did not change with post-mortem interval, and E06-positive lipids were largely absent from control tissue. We then used a second monoclonal antibody (AB1-2, which recognizes the E06/T15 idiotype and therefore detects the presence of antibody to OxPC) to show that MS brain samples were strongly positive for the 50-kDa antibody heavy chain. We also showed that isoelectric focussing of the oligoclonal IgG characteristic of MS revealed some immunoglobulin bands that Western blotted with the AB1-2 antibody. Spinal cords from mice induced to undergo experimental allergic encephalomyelitis (EAE) also showed strong AB1-2 reactivity by both immunocytochemistry and Western blot analysis. We therefore conclude that we can detect both OxPC and 15-kDa protein modified by OxPC and the antibody to the antibody to OxPC (antiidiotype) in pathological tissue and suggest that this could play a role in the progression of MS.
 ...
PMID:Oxidized phosphatidylcholine is a marker for neuroinflammation in multiple sclerosis brain. 1730 73

An autopsy case of diffuse axonopathic leukoencephalopathy induced by drug treatment is reported. A 70-year-old woman with multiple myeloma developed encephalopathy several days after completing a course of intravenous human immunoglobulin (IVIg) and granulocyte-colony stimulating factor (G-CSF), and died within I month. T2-weighted MRI demonstrated multifocal high-signal areas in the bilateral cerebral white matter, especially in the right frontal lobe. Neuropathologically, multifocal hydropic axonal swelling with a poor glial reaction was recognized diffusely in the bilateral deep cerebral white matter, being especially marked in the frontal lobe. The cortex, subcortical U-fibers, corpus callosum, and anterior commissure were spared. The cerebellar white matter also showed similar changes, albeit less marked, but the brainstem was spared. Microscopically, the myeloma involvement of the CNS was limited to the dura, and the cerebral arteries showed slight atherosclerosis, but neither thrombi nor angitis. This case, although ultimately fatal, neurologically and neuroradiologically resembled reversible posterior leukoencephalopathy syndrome (RPLS) induced by IVIg and/or G-CSF, and the nature and selective distribution of the neuropathological changes suggested that the pathogenesis involved vasospasm of the bilateral internal carotid artery and the main trunks of the cerebral arteries, due to unknown cause, inducing ischemia in the deep white matter, which is supplied by long nutrient arteries.
 ...
PMID:An autopsy case of drug-induced diffuse cerebral axonopathic leukoencephalopathy: the pathogenesis in relation to reversible posterior leukoencephalopathy syndrome. 1789 90


1 2 Next >>