Giant cell arteritis of the cervical radicular vessels presenting with diaphragmatic weakness.
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The clinical and histopathological details of a patient who succumbed to giant cell arteritis (GCA) of the cervical radicular vessels are described. The initial clinical presentation, with diaphragmatic weakness, has not previously been reported. Normal inflammatory indices and the unusual presentation prevented diagnosis during life, but GCA should be considered in the differential diagnosis of any unexplained neuropathic or radiculopathic syndrome, as corticosteroid therapy may lead to recovery. This is the first account of the pathological findings in cervical radiculopathy associated with GCA. (+info)
EVE and beyond, retro and prospective insights.
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Our work has focused on the discovery that an endogenous vascular elastase (EVE) plays a pivotal role in the vascular changes associated with the development and progression of pulmonary hypertension. Recent studies have identified serum factors that stimulate transcription of this enzyme and have elucidated a signal transduction process involving activation of the mitogen-activated protein kinase pathway and nuclear expression of the transcription factor AML1. Proteases release and activate growth factors that are bound to the extracellular matrix and also induce, in a beta(3)-integrin-dependent manner, the transcription of the gene for the matrix glycoprotein tenascin. Tenascin alters smooth muscle cell shape and facilitates the proliferative response to growth factors by clustering and activating growth factor receptors. In addition, breakdown products of elastin, elastin peptides, can upregulate the production of fibronectin, a glycoprotein that is critical to smooth muscle cell migration. The mechanisms regulating enhanced fibronectin production have recently been successfully targeted to prevent the development of intimal lesions. (+info)
Control of cutaneous blood vessels in psoriatic plaques.
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The aim of this study was to compare local blood flow in psoriatic plaques before and after provocations known to alter cutaneous vascular resistance, in order to determine whether plaque hyperemia is caused by a failure of normal vascular control mechanisms. Cutaneous blood flow was recorded using a laser Doppler flowmeter over plaque skin (plaque site) and clinically normal skin (nonplaque site) on the opposite arm, at least 5 cm away from the nearest plaque. It is important to note that most of the laser Doppler signal comes from the subpapillary plexus of the skin and only a small portion (2%-10%) is produced by capillary blood flow. In the psoriatic plaques the basal flux was between nine and 13 times greater than nonplaque skin. The biologic zero (a signal independent of perfusion, which also persists after complete proximal arterial occlusion) was also significantly greater at plaque sites compared with nonplaque sites. Sympathetic and local vasoconstriction in psoriatic skin was shown to be intact and responses to vasodilator tests were likewise intact, i.e., there was no failure of response to normal vascular control mechanisms, albeit some quantitative differences. Tests of vasodilatation indicated that, although basal flux is high in plaque compared with nonplaque skin, arterioles supplying plaque skin can dilate further, i.e., lesional arterioles are not normally maximally dilated but have a basal constrictor tone. Interestingly, the red cell flux at maximum dilatation in nonplaque skin is less than even the basal flux in plaque skin. This means that in plaque skin either there are more arterioles than in nonplaque skin, or there is chronic, structural widening of the existing arterioles in plaque skin. (+info)
Effects of oral folic acid supplementation on endothelial function in familial hypercholesterolemia. A randomized placebo-controlled trial.
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BACKGROUND: Folates have been suggested to be of benefit in reducing cardiovascular risk. The present study was designed to examine whether oral folic acid supplementation could improve endothelial function as an intermediate end point for cardiovascular risk in patients with increased risk of atherosclerosis due to familial hypercholesterolemia (FH). METHODS AND RESULTS: In a prospective, randomized, double-blind, placebo-controlled study with crossover design, we evaluated the effects of 4 weeks of treatment with oral folic acid (5 mg PO) on endothelial function in FH. In 20 FH patients, forearm vascular function was assessed at baseline, after 4 weeks of folic acid treatment, and after 4 weeks of placebo treatment by venous occlusion plethysmography, with serotonin and sodium nitroprusside used as endothelium-dependent and -independent vasodilators. In addition, we examined the vasoconstrictor response to the NO synthase inhibitor N(G)-monomethyl-L-arginine to assess basal NO activity. In FH patients, folic acid supplementation restored the impaired endothelium-dependent vasodilation, whereas it did not significantly influence endothelium-independent vasodilation or basal forearm vasomotion. There was a trend toward improvement in basal NO activity. CONCLUSIONS: These data demonstrate that oral supplementation of folic acid can improve endothelial function in patients with increased risk of atherosclerotic disease due to hypercholesterolemia, without changes in plasma lipids. (+info)
Molecular angiogenesis.
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New insights into the mechanisms by which blood vessels develop (angiogenesis) have been gained recently, primarily by the identification of factors that inhibit and promote this process. Angiogenesis-stimulating factors are being used to promote growth of new blood vessels in ischemic disease. In contrast, anti-angiogenesis factors are being used as inhibitors of neovascularization to control tumor growth and metastasis. (+info)
Monocyte chemotactic protein-1 expression in human corpus luteum.
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Invasion of the corpus luteum by macrophages is a characteristic of luteal regression. Monocyte chemotactic protein-1 (MCP-1), a chemokine that recruits macrophages, is expressed in the rat corpus luteum where it increases in amount during luteolysis. In this study we examined the temporal and spatial expression of MCP-1 and changes in macrophage concentration in the human corpus luteum. Corpora lutea (n = 39) were grouped according to menstrual cycle phase and were examined by immunohistochemistry for MCP-1 and macrophages, and by Northern blot for MCP-1 mRNA. We found increasing amounts of macrophages with progressing luteolysis (P < 0.001). Staining for MCP-1 was stronger in the regressing corpora lutea compared with the staining in corpora lutea of early luteal phase (P < 0.05). MCP-1 was more prominent in blood vessel walls surrounding the corpus luteum than in vessels located far from it. The mean MCP-1 mRNA expression in regressing corpora lutea was higher than that observed in corpora lutea of the early and mid-luteal phase (P = 0.003). In conclusion, we found that MCP-1 expression and the number of macrophages increase with regression of the corpus luteum. MCP-1 is mostly expressed in blood vessel walls surrounding the corpus luteum and may play a role in the recruitment of macrophages to the corpus luteum during its regression. (+info)
Myocardialization of the cardiac outflow tract.
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During development, the single-circuited cardiac tube transforms into a double-circuited four-chambered heart by a complex process of remodeling, differential growth, and septation. In this process the endocardial cushion tissues of the atrioventricular junction and outflow tract (OFT) play a crucial role as they contribute to the mesenchymal components of the developing septa and valves in the developing heart. After fusion, the endocardial ridges in the proximal portion of the OFT initially form a mesenchymal outlet septum. In the adult heart, however, this outlet septum is basically a muscular structure. Hence, the mesenchyme of the proximal outlet septum has to be replaced by cardiomyocytes. We have dubbed this process "myocardialization." Our immunohistochemical analysis of staged chicken hearts demonstrates that myocardialization takes place by ingrowth of existing myocardium into the mesenchymal outlet septum. Compared to other events in cardiac septation, it is a relatively late process, being initialized around stage H/H28 and being basically completed around stage H/H38. To unravel the molecular mechanisms that are responsible for the induction and regulation of myocardialization, an in vitro culture system in which myocardialization could be mimicked and manipulated was developed. Using this in vitro myocardialization assay it was observed that under the standard culture conditions (i) whole OFT explants from stage H/H20 and younger did not spontaneously myocardialize the collagen matrix, (ii) explants from stage H/H21 and older spontaneously formed extensive myocardial networks, (iii) the myocardium of the OFT could be induced to myocardialize and was therefore "myocardialization-competent" at all stages tested (H/H16-30), (iv) myocardialization was induced by factors produced by, most likely, the nonmyocardial component of the outflow tract, (v) at none of the embryonic stages analyzed was ventricular myocardium myocardialization-competent, and finally, (vi) ventricular myocardium did not produce factors capable of supporting myocardialization. (+info)
Oestrogen and progesterone receptor immunoreactivity and c-fos expression in the ovine cervix.
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Immunocytochemistry was used to detect the presence of oestrogen and progesterone receptors in the cervices of prepubertal lambs, seasonally anoestrous ewes, cyclic ewes, and pregnant ewes of known gestational stages, to define the roles of gonadal steroids in cervical function. The presence of the immediate early gene product, c-Fos, a marker for cellular activation, was also investigated using immunocytochemistry and in situ hybridization. Oestrogen receptor immunoreactivity was restricted to the endometrium on days 0-3 of the oestrous cycle (day 0 = oestrus). In immature animals, very few scattered nuclei in the endometrium were immunoreactive. Oestrogen receptor immunoreactivity was not apparent in the endometrium during the remainder of the oestrous cycle or in this region in anoestrous animals. In pregnant ewes, oestrogen receptor immunostaining appeared as relatively few isolated nuclei in the connective tissue stroma. Progesterone receptor immunoreactivity was found in the endometrium at days 0-3 of the oestrous cycle and also in the luminal epithelium, the myometrium and the blood vessels. Progesterone receptor immunoreactivity was also found in these regions, with the exception of the endometrium, at all other stages examined. Immunostaining for c-Fos was present in the endometrium at days 0-3 of the oestrous cycle, and some scattered immunopositive nuclei were present in prepubertal animals. c-Fos immunoreactivity was also found in the myometrium and in blood vessels at all other stages examined. Visualization of c-fos gene expression by in situ hybridization showed that it occurred in the luminal epithelium and blood vessels at oestrus, but was restricted to the blood vessels in all other samples examined. (+info)