Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischaemic strokes and transient ischaemic attacks are commonly caused by cerebral embolism originating from formation of a platelet-rich thrombus superimposed on an atherosclerotic plaque or by atherothrombotic plaque rupture in a carotid or intracranial artery. Despite advances made through ultrasound imaging in our understanding of atherosclerotic plaque progression and regression, the issue of whether differences in plaque structure alone can distinguish between lesions that become symptomatic and others that remain clinically silent continues to be debated. Recent biochemical and imaging studies have identified characteristics that may reflect a high risk of vulnerability, such as outward, abluminal plaque remodelling, the presence of intra-plaque haemorrhage, inflammation, severe flow disturbances around the encroaching lesion, plaque cap thinning and ulceration, and abnormal plaque motion. Plaque stability may be improved through management of traditional cardiovascular risk factors or with biological or pharmacological agents that target pathways involved in plaque pathophysiology. Unstable plaques place patients at risk of unpredictable ischaemic events and in patients with such lesions, specific preventive treatment beyond long-term antiplatelet therapy can be used to prevent new or recurrent events.
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PMID:The unstable plaque. 1473 Feb 54

The term "morphea" includes a wide spectrum of clinical entities, varying from localized plaques of only cosmetic importance to deep lesions resulting in considerable morbidity for the patient. In fact, although survival rates are no different from that of the general population, localized scleroderma may be associated with development of substantial disability, as occurs in deep morphea and in pediatric patients (disabling pansclerotic morphea of children). We report a case of morphea profunda affecting a young man with severe, rapidly progressive, widespread skin involvement and focus on the eventual systemic evolution of such cases. A 40-year-old man was admitted in 2002 for progressive subcutaneous indurations, preferentially involving the right side of the trunk. His health was altogether good, with the exception of a beginning chronic obstructive bronchopneumopathy. There was no family or personal history of dysmetabolic, cardiovascular, neoplastic, or cutaneous disease. Three years earlier, the patient had noted the appearance of two infiltrated, intensely red lesions on the right laterocervical and paraumbilical regions. These had been interpreted as subcutaneous lipomatosis on the basis of an ultrasound scan. The lesions had become progressively larger, while their surface had assumed a scleroatrophic appearance. Thereafter, other lesions had developed on his chest and lower limbs, mostly distributed on the right side of the body. Clinical examination revealed well demarcated, depressed sclerotic plaques with ivory-colored centers and erythematous borders ("lilac ring") localized on the neck, chest, and lower abdomen and limbs (Figure 1). They were bound to the deeper structures and arranged in a band-like linear distribution on the right side of the chest and abdomen where they extended horizontally for more than 10 cm in diameter. These lesions were totally asymptomatic. In addition, arborizing telangiectasias were evident on the neck and upper chest (Figure 2). Laboratory investigations provided normal range of erythrocyte sedimentation rat and C reactive protein levels and other inflammation markers. Antinuclear antibody, antidouble-strand DNA, antimitochondrial, anti-extractable antigens (anti-centromere, anti-Scl-70, anti-U1RNP), and anti-Borrelia burgdorferi antibodies were negative. Circulating immunocomplexes binding C1q were substantially increased. Oesophageal x-rays and lower limb electromyography were within normal limits; ventilatory function testing revealed a mild obstruction consistent with the beginning of chronic obstructive pulmonary disease. Although nailfold capillaroscopy documented nonspecific findings of connective tissue disease (mega-capillaries, segmentary dilatation and destruction), the laser-Doppler flussimetry revealed few signs of microcirculatory abnormalities, in absence of Raynaud's phenomenon. An abdominal wall ultrasonography, performed on a sclerotic plaque, documented thinning of the subcutaneous tissue, with increase of the fibrous component and lower fascia and muscle retraction. The biopsy specimen from the abdominal region included fascia and the subcutaneous tissue (previously obtained from the lower abdomen) with epidermal atrophy, a thickening and homogenization of collagen bundles in the deep dermis and hair reduction. A perivascular lympho-monocytic and plasmacellular infiltration with a dermo-epidermal distribution was present. Moreover, septal fibrosis with a perivascular lymphoplasmacellular inflammatory infiltrate was documented within the abdominal rectus muscle. The diagnosis of morphea profunda was made on the basis of clinical and histopathological findings. A therapeutic regimen based on amino benzoic potassium (Potaba; Glenwood, LLC, Glenwood, NJ), oral prednisone, and topical clobetasol was started. After several months of follow-up, the patient had obtained only moderate improvement of the clinical findings.
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PMID:Case study: periodic follow-up is necessary in morphea profunda to identify systemic evolution. 1589 Dec 59

Immune cells play an important role in atheromatous plaque formation and progression and in the phase of "active plaque" and of the consequent clinical manifestations. Endothelial dysfunction is the first determinant step in atherogenesis by inducing the alteration of vasodilating and antithrombotic properties of the endothelium and of its permeability to lipoproteins. Circulating monocytes are recruited and internalized and lipoproteins are stored in the subendothelial area where they undergo oxidation (oxidized LDL) and are removed by macrophages by means of non-autoregulated scavenger receptors (foam cells). Foam cells are able to express surface receptors and to produce soluble mediators (interleukin-1, tumor necrosis factor-alpha, monocyte chemotactic protein 1) which attract other monocytes, activate endothelial cells and smooth muscle cells. Lymphocytes too are present in these first stages of atherogenesis. If the injurious agents are not removed or nullified by the inflammatory response and the inflammation progresses, the response changes from a protective to an injurious response. Recruitment of monocytes and lymphocytes occurs as a result of the up-regulation of adhesion molecules on both the endothelium and the leukocytes and the plaque progresses to an advanced lesion. Finally the activation of monocytes and T cells induces the plaque activation and rupture in presence of inducing agents such as oxidized LDL. CD4 lymphocytes are common components of atheroma and are mainly localized at the sites of rupture in strict contact with macrophages and smooth muscle cells which express activation surface molecules and which are able to process and to present the antigen to T cells. Activated lymphocytes produce proinflammatory cytokines as interferon-gamma which is able to amplify the inflammatory response but also interleukin-10 which seems to possess a regulatory effect. Activated macrophages release metalloproteinases and other proteolytic enzymes which cause degradation of the matrix, thinning of fibrous cap and plaque destabilization. Both T cells and macrophages produce cytotoxic factors which contribute to the apoptosis. The process may be potentiated by the activation of platelets, tissue factor, coagulation-fibrinolytic system which can contribute to thrombus formation, plaque rupture and artery occlusion.
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PMID:[Immune factors in atherosclerosis]. 1605 40

There is a combination of inflammation inside unstable atherosclerotic plaque and reparation of its fibrous cover. Increase of the inflammation activity with production of various proteases results in thinning of fibrous cover and loss of normal intercellular and matrix-cell interactions. Later rupture of the plaque takes place with development of a variant of ACS.
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PMID:[Morphogenesis of unstable atherosclerotic plaque and its role in development of acute coronary syndrome (ACS)]. 1607 16

Apart from the degree of stenosis, plaque morphology has emerged in recent years as an important contributory factor in stroke risk. Ultrasound studies have shown that hypo- or anechogenic plaques carry a higher risk of cerebrovascular events than echogenic ones. Similarly, heterogeneous plaques presenting a complex pattern of echogenicity in ultrasound have also been more frequently associated with the occurrence of neurological symptoms than homogeneous lesions. Further, most studies determining the surface characteristics in ultrasound have found that ulceration also predicted increased risk of subsequent stroke. These studies are, however, based on visual evaluation using different classification systems and presenting a high variability of intra- and interobserver agreement. A quantitative method using a computerised image analysis of the plaque based on a grey-scale median (GSM) value has recently been developed which allows a more objective and reproducible evaluation of plaque echogenicity. Several studies have also shown that low GSM values are associated with an increased stroke incidence. A stratified GSM analysis determining the GSM in each one millimeter-thick stratum of the plaque may represent an additional method of determining different components of unstable plaques, such as thinning of the fibrous cap and the position of the necrotic core near the surface. This article reviews the ultrasonic morphology of the carotid plaque, its clinical prognostic value and correlations with histopathological studies. Recent ultrasound developments in the assessment of plaque echogenicity are also discussed.
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PMID:Ultrasonographic assessment of the morphological characteristics of the carotid plaque. 1638 Aug 50

Dysfunctional vascular smooth muscle cell (VSMC) behaviour contributes to the pathogenesis of atherosclerosis and restenosis. Increased rates of VSMC apoptosis are thought to lead to thinning of the fibrous atherosclerotic plaque and thereby instability, while migration of VSMCs to the intima, and inappropriate VSMC proliferation, contribute to intimal thickening that occurs in atherosclerosis and restenosis. Studies, mainly in cancer and neuronal cells, have demonstrated that cell-cell adhesion by the cadherin:catenin complex modulates apoptosis, migration and proliferation. In contrast, until recently the involvement of this complex in the regulation of VSMC behaviour was relatively unstudied. In this review, evidence for the regulation of VSMC apoptosis, migration and proliferation by the cadherin:catenin complex will be discussed.
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PMID:Cadherin:catenin complex: a novel regulator of vascular smooth muscle cell behaviour. 1643 74

The cerebral cortex undergoes changes during normal ageing with increasing effect on cognition. Disruption of minicolumnar organization of neurons is found with increased cognitive impairment in primates. We measured the minicolumn spacing and organization of cells in Heschl's gyrus (primary auditory cortex, A1), the Planum Temporale (Tpt, BA22), and middle temporal gyrus (MTG, BA21) of 17 normally aged human adults. Age-associated minicolumn thinning was found in temporal lobe association cortex (Tpt and MTG) but not primary auditory cortex (HG). Minicolumn thinning was also associated with greater plaque load, although this effect was present in all areas. The regional variability of age-associated minicolumn thinning reflects the regionally selective progression of tangle pathology in Alzheimer's Disease (AD). The generalized effect of plaque load persists when controlling for age. Therefore plaque load combines with age to increase minicolumn thinning, which may reflect increasing risk of AD. Since old age is the greatest risk factor for dementia, the transition to dementia may involve an extension of normal ageing processes.
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PMID:Minicolumn thinning in temporal lobe association cortex but not primary auditory cortex in normal human ageing. 1649 64

Acute coronary syndrome is a clinical state induced by the thrombosis following the rupture of unstable atherosclerotic plaque. Atherosclerotic plaque increases its vulnerability by the accumulation of foam cells, inflammation, oxidative stress, and apoptosis of vascular wall cells including macrophage. Inflammation and oxidative stress stimulates macrophages to produce matrix metalloproteinase (MMP), which degrades extracellular matric proteins and causes thinning of the fibrous cap. When the fibrous cap of the plaque tears, thrombogenic lipid core is exposed to blood, and platelets accumulate at the site, resulting in the significant reduction of coronary blood flow. Treatment of acute coronary syndrome patients should be focused on the stabilization of the plaque as well as vasodilatation, oxygen supply, or control of hemodynamics.
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PMID:[Definition and pathophysiology of acute coronary syndrome]. 1661 76

Vascular smooth muscle cell (VSMC) apoptosis occurs in many arterial diseases, including aneurysm formation, angioplasty restenosis and atherosclerosis. Although VSMC apoptosis promotes vessel remodeling, coagulation and inflammation, its precise contribution to these diseases is unknown, given that apoptosis frequently accompanies vessel injury or alterations to flow. To study the direct consequences of VSMC apoptosis, we generated transgenic mice expressing the human diphtheria toxin receptor (hDTR, encoded by HBEGF) from a minimal Tagln (also known as SM22alpha) promoter. Despite apoptosis inducing loss of 50-70% of VSMCs, normal arteries showed no inflammation, reactive proliferation, thrombosis, remodeling or aneurysm formation. In contrast, VSMC apoptosis in atherosclerotic plaques of SM22alpha-hDTR Apoe-/- mice induced marked thinning of fibrous cap, loss of collagen and matrix, accumulation of cell debris and intense intimal inflammation. We conclude that VSMC apoptosis is 'silent' in normal arteries, which have a large capacity to withstand cell loss. In contrast, VSMC apoptosis alone is sufficient to induce features of plaque vulnerability in atherosclerosis. SM22alpha-hDTR Apoe-/- mice may represent an important new model to test agents proposed to stabilize atherosclerotic plaques.
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PMID:Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis. 1689 61

Non-contiguous local recurrence of posterior uveal melanoma occurs rarely after plaque therapy. A 50-year-old white first presented with choroidal melanoma. He underwent therapy with episcleral iodine-125 radioactive plaque therapy. Nine years later fundus evaluation revealed a new pigmented lesion in the inferotemporal equatorial area. Patient was considered to have a non-contiguous recurrent melanoma and the eye was enucleated. Histologic microscopic examination disclosed a 3 x 1.8 mm densely pigmented tumour internal to the choroid at the equator. The tumour was composed of large round cells with round nuclei, prominent nucleoli, abundant cytoplasm and spindle-shaped cells with spindle-shaped nuclei and prominent nucleoli. The tumour extended through the retina. The superior nasal area of plaque therapy had extensive chorioretinal atrophy with loss of retinal pigment epithelium, thinning of the retina and thinning and depigmentation of the choroids. Within this area of atrophy, there was a pigmented lesion composed by densely packed, spindle-shaped cells with spindle-shaped nuclei. Our patient illustrated non-contiguous recurrence of choroidal melanoma, such finding raises concerns about physiopathology and treatment of choroidal melanoma.
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PMID:Non-contiguous recurrence or secondary choroidal melanoma following plaque radiotherapy. 1789 87


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