A prosodic approach to filler syllables.
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Child Language↗
Biomedical subjects
K Demuth
Publications and source records attributed to K Demuth.
Homocysteine-induced decrease in endothelin-1 production is initiated at the extracellular level and involves oxidative products.
The increased cardiovascular risk associated with hyperhomocysteinemia has been partly related to homocysteine (Hcy)-induced endothelial cell dysfunction. However, the intra or extracellular starting point of the interaction between Hcy and endothelial cells, leading to cellular dysfunction, has not yet been identified. We investigated the effects of both intracellular and extracellular Hcy accumulation on endothelin-1 (ET-1) synthesis by cultured human endothelial cells. Incubation of cultures with methionine (1.0 mmol x L(-1)) for 2 h induced a slight increase in cellular Hcy content but no change in ET-1 production. Incubation of cells with Hcy (0.2 mmol x L(-1)) led to a significant fall in ET-1 generation, accompanied by a significant increase in cellular Hcy content. Addition of the amino-acid transport system L substrate 2-amino-2-norbornane carboxylic acid had no effect on the Hcy-induced decrease in ET-1 production but significantly inhibited the Hcy-induced increase in the cellular Hcy content. Incubation of cells with a lower Hcy concentration (0.05 mmol x L(-1)) also reduced ET-1 production without increasing the cellular Hcy content. Co-incubation with extracellular free-radical inhibitors (superoxide dismutase, catalase and mannitol) markedly reduced the effect of Hcy on ET-1 production. Thus, it is extracellular Hcy accumulation that triggers the decrease in ET-1 production by endothelial cells through oxidative products.
Antioxidants↗
Homocysteine decreases endothelin-1 production by cultured human endothelial cells.
Hyperhomocysteinemia is believed to be responsible for the development of vascular disease via several mechanisms, including the impairment of endothelial-cell functionality. In-vitro studies have demonstrated that homocysteine decreases the production or bioavailability of vasodilator autacoids, such as prostacyclin and NO. Here, we show that the treatment of human endothelial cells with noncytotoxic homocysteine concentrations leads to a dose-dependent decrease in both the secretion of the vasoconstrictor agent endothelin-1 (ET-1) and the level of its mRNA. Homocysteine had an inhibitory effect at pathophysiological (0.1 and 0.5 mmol.L(-1)) and pharmacological noncytotoxic (1.0 and 2.0 mmol.L(-1)) concentrations. Mean percentage variation from control for ET-1 production was -36. 2 +/- 18.9% for 0.5 mmol.L(-1) homocysteine and -41.5 +/- 26.8% for 1.0 mmol.L(-1) homocysteine, after incubation for 8 h. Mean percentage variation from control for steady-state mRNA was -17.3 +/- 7.1% for 0.5 mmol.L(-1) homocysteine and -46.0 +/- 10.1 for 1.0 mmol.L(-1) homocysteine, after an incubation time of 2 h. ET-1 production was also reduced by incubation with various other thiol compounds containing free thiol groups, but not by incubation with thiol compounds with no free thiol group. Co-incubation of cells with homocysteine and the sulfhydryl inhibitor N-ethylmaleimide prevented the effect of homocysteine on ET-1 production, confirming a sulfhydryl-dependent mechanism. Based on the reciprocal feedback mechanism controlling the synthesis of vasoactive mediators, these preliminary data suggest a mechanism by which homocysteine may selectively impair endothelium-dependent vasodilation by primary inhibition of ET-1 production.
Arteriosclerosis↗
Diagnostic impact of cerebral transit time in the identification of microangiopathy in dementia: A transcranial ultrasound study.
BACKGROUND AND PURPOSE: The diagnosis and quantification of microangiopathy in dementia is difficult. The assessment of small-vessel disease requires expensive and sophisticated nuclear medicine techniques. This study was performed to identify microangiopathy related to the integrity of cerebral microcirculation by sonographic measurements (arteriovenous cerebral transit time [cTT]). METHODS: We performed transcranial color-coded duplex sonography in 40 patients with vascular dementia, 20 patients with Alzheimer's disease or Lewy body disease, and 25 age-matched controls. The clinical diagnosis was established by history of dementia and neuroimaging findings. Cognitive impairment was assessed by the Mini-Mental State Examination and Alzheimer's Disease Assessment Scale. cTT is defined as the time required by an ultrasound contrast agent to pass from a cerebral artery to a vein. This was measured by recording the power-Doppler intensity curves in the P2 segment of the posterior cerebral artery and the vein of Galen. Previous studies have shown a prolongation of cTT in patients with cerebral microangiopathy. RESULTS: cTT was substantially prolonged in patients with vascular dementia (5.8 seconds; 25th percentile 4.5; 75th percentile 7.5; U test, P<0.001) compared with controls (3.1 seconds; 2.3; 3.4) but not in patients with degenerative dementia (3.7 seconds; 3.7; 4.2). In patients with vascular dementia, cTT was significantly correlated with cognitive impairment. CONCLUSIONS: cTT may be useful tool to disclose small-vessel disease in demented patients. Examination is noninvasive and quickly performed. It may be also useful in follow-up examinations in patients undergoing therapy.
Aged↗
The effect of high density lipoprotein subfractions on endothelial eicosanoid secretion.
Epidemiological, clinical, and experimental studies have demonstrated that high density lipoproteins (HDL) are protective against atherosclerosis. However, the respective influence of two main HDL subfractions (HDL2 and HDL3) on atherosclerosis process is not yet clear. The present study was designed to determine, which HDL subfraction was antiatherogenic in terms of eicosanoid release by human umbilical vein endothelial cells (HUVEC). Endothelial cells were incubated for 4 hours with HDL2 or HDL3 and prostaglandins 6-keto-PGF1alpha, thromboxane B2 and prostaglandin E2 were measured by RIA in culture supernatant. HDL2 has a dose dependent stimulatory effect on 6-keto-PGF1alpha release without stimulatory effect on thromboxane B2 secretion. The 6-keto-PGF1alpha/thromboxane B2 ratio increased progressively from 1.65 to 4.65 for 0.39 to 6.25 mg HDL protein/ml. The pattern of prostanoid secretion under influence of HDL3 showed a predominant response in 6-keto-PGF1alpha and TxB2 release. As regards PGE2, both HDL subfractions stimulated considerably secretion of this prostanoid in a dose dependent manner. In terms of PGI2/TxA2 balance the better antiatherogenic effect was observed with HDL2 subfraction.
Cells, Cultured↗
Endothelin and cardiovascular remodelling in end-stage renal disease.
BACKGROUND: Plasma endothelin (ET) is elevated in end-stage renal disease (ESRD), but the origin and consequences of this increase remain unclear. In the present study we analysed the relationships between plasma ET levels and cardiovascular alterations in ESRD. METHODS AND RESULTS: Common carotid artery (CCA) intima-media thickness (IMT) and diameter, atherosclerotic plaque occurrence, and left ventricular (LV) geometry and function were determined by ultrasound imaging in 76 haemodialysis patients and in 57 age-, sex-, and blood pressure-matched controls. Arterial stiffness was evaluated via carotid-femoral pulse wave velocity (CF-PWV), forearm post-ischaemic vasodilation was measured by venous plethysmography, and plasma ET levels were determined using a specific immunoenzymoassay. Compared with controls, ESRD patients had elevated plasma ET levels (1.6 +/- 1.4 vs 4.6 +/- 3.8 pg/ml; P < 0.001), increased LV mass (P < 0.001), increased CCA-IMT (P < 0.001), a higher prevalence of atherosclerotic plaques (P < 0.001) and increased CF-PWV (P < 0.01). Plasma ET levels correlated positively with LV outflow velocity integral (r = 0.57; P < 0.0001), stroke index (P < 0.01), and baseline forearm blood flow (P < 0.001) which were all significantly higher in ESRD patients than in controls (P < 0.01). After adjustment for age, blood pressure, haemoglobin levels, gender and body dimensions, plasma ET levels were significantly correlated to LV mass (r = 0.46; P < 0.001), CCA-IMT and CCA intima-media cross-sectional area (r = 0.41; P < 0.001), and CF-PWV (P < 0.05). Post-ischaemic forearm vasodilation was decreased in ESRD (85 +/- 31 vs 119 +/- 28%; P < 0.001) and there was a negative correlation between post-ischaemic flow recovery and ET levels (r = -0.49; P < 0.001). In ESRD patients, plasma ET levels were positively and independently correlated with the prevalence of CCA atherosclerotic plaque (P < 0.01). CONCLUSIONS: These results indicate that the increased plasma ET levels in ESRD patients are associated with left ventricular hypertrophy and arterial intima-media thickening, suggesting that increased ET concentrations in ESRD patients may be of pathophysiological significance in the process of cardiovascular remodelling.
Adaptation, Physiological↗
Opposite effects of plasma homocysteine and the methylenetetrahydrofolate reductase C677T mutation on carotid artery geometry in asymptomatic adults.
Studies of symptomatic patients have identified hyperhomocysteinemia as an independent risk factor for vascular disease. In case-control studies, a point mutation (C677T) in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) has also been linked to an increased risk of vascular disease through its effect on homocysteinemia. Our aim was to extend these observations to asymptomatic subjects by studying the influence of both homocysteinemia and its mutation on carotid artery geometry. We examined 144 subjects free of atherosclerotic lesions. Fasting homocysteinemia was measured by high-performance liquid chromatography with fluorometric detection. MTHFR genotype was analyzed by polymerase chain reaction followed by HinfI digestion. Carotid artery geometry was characterized by internal diameter and intima-media thickness, as assessed by a high-resolution echo-tracking system. Subjects in the upper homocysteine tertile had a greater carotid internal diameter than did subjects in the middle and lower tertiles (6516+/-770 versus 6206+/-641 and 5985+/-558 microm, respectively; P<0.001). Subjects homozygous for the mutation had a smaller carotid artery internal diameter than did subjects heterozygous or homozygous for the wild-type allele (5846+/-785 versus 6345+/-673 and 6199+/-671 microm, respectively; P<0.05). Homocysteinemia was not significantly increased in subjects homozygous for the mutation. In multivariate regression analysis, homocysteinemia was independently and positively associated with lumen diameter (P=0.0008) and wall thickness (P=0.020). Conversely, homozygosity for the mutation was negatively associated with internal diameter (P=0.009). These preliminary data suggest that mildly elevated homocysteinemia and homozygosity for the MTHFR C677T mutation are associated with opposite preclinical modifications of carotid artery geometry. If confirmed, these results may have important implications for new treatment strategies for vascular disease before the onset of clinical manifestations.
Adult↗
Influence of biochemical alterations on arterial stiffness in patients with end-stage renal disease.
The incremental elastic modulus of the common carotid and radial arteries is increased in patients with end-stage renal disease (ESRD), independently of blood pressure, wall stress, and the presence of atherosclerotic alterations. Whether biochemical factors may be involved in the arterial changes and related to renal dysfunction remain largely ignored. To assess this question, we measured aortic (carotid-femoral), upper-limb (carotid-radial), and lower-limb (femoral-tibial) pulse wave velocity (PWV) in 74 ESRD patients undergoing hemodialysis in comparison with 57 control subjects similar in age, sex ratio, and mean blood pressure. We evaluated arterial blood pressure by sphygmomanometry, aortic calcifications and cardiac mass by echography, and routine biochemical parameters, total plasma homocysteine, and plasma endothelin levels by standard techniques. In the population of patients with ESRD, on the basis of multiple stepwise regression analysis, aortic PWV was positively and independently correlated with systolic blood pressure (P<.0001), age (P<.0001), prevalence of aortic calcification (P=.0004), and the prevalence of diabetes mellitus (P=.0043). Upper-limb PWV was influenced exclusively by mean blood pressure (P<.0001). Lower-limb PWV was positively and independently correlated with plasma total homocysteine (P=.0004) and plasma endothelin (P=.0187) only. At any vascular site, PWV was not independently correlated with tobacco consumption; plasma levels of cholesterol, triglyceride, fibrinogen, or hemoglobin; body mass index; or the presence of bilateral nephrectomy. Finally, plasma homocysteine was independently correlated with cardiac mass (P=.0022). This study provides evidence that in ESRD patients, the stiffness of the arterial wall and cardiac mass are strongly influenced by biochemical factors related to the kidney alterations and are independent of age and blood pressure level. Increased plasma endothelin and homocysteine may be specifically involved in the vascular damage of lower limbs.
Adult↗
[The effect of plasma lipoproteins on the secretion of prostanoids in endothelial cells in vitro].
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Endothelium, Vascular↗
[Atherogenic and anti-atherogenic plasma lipoproteins modulate secretion of prostanoids by endothelial cells in vitro].
The authors present the evidence of atherogenic properties of VLDL and LDL potentiation on the model of endothelial cells-human umbilical vein endothelial cells, by preferable stimulation of the endothelial cell to thromboxane A1 production at in vitro conditions by atherogenic lipoproteins. The vasoconstrictive, thrombogenic and atherogenic effects of TXA2 are exerted on the vessel in this way. The ratio prostacycline/thromboxane, decisive for the maintenance of vascular homeostasis, is less than 1, this means the beneficial effect of prostacycline can not be applied. Protective, antiatherogenic effect of HDL and its subfractions HDL2 and HDL3/predominantly through their function in the reverse cholesterol transport from the periphery to the liver, antioxidative influence on LDL, as far as antiaggregation and fibrinolytic effects of HDL/is multiplied by the fact that HDL preferably stimulates the secretion of prostacycline by the endothelial cell. The ratio prostacycline/thromboxane A2 is higher than 1, that means beneficial vasodilative, antiaggregation and antiatherogenic effect of prostacycline on the vessel wall predominate. Quantitative evaluation of antiatherogenic effects of HDL subfractions (HDL2 and HDL3) revealed more significant antiatherogenic effect in HDL2 subfraction-in the sense of prostacycline secretion stimulation and exertion of its beneficial effects on the vessel. (Fig. 5, Ref. 33.)
Arteriosclerosis↗
A cytotoxic electronegative LDL subfraction is present in human plasma.
By using fast protein liquid chromatography, we isolated from human plasma a minor electronegative LDL subfraction designated LDL(-). After immunoaffinity chromatography against apolipoprotein (apo)(a) and apo A-I, LDL(-) represented 6.7 +/- 0.9% (mean +/- SD; n = 18) of total LDL. Compared with the major LDL subfraction, designated LDL(+), LDL(-) contained similar amounts of thiobarbituric acid-reactive substances, conjugated dienes, and vitamin E and had a similar lipid/protein ratio and mean density. Moreover, the apo B of LDL(-) was not aggregated and its LDL receptor-binding activity was slightly increased. These results were consistent with the nonoxidized nature of LDL(-). LDL(-) showed increased contents of sialic acid (38.1 +/- 5.2 versus 28.9 +/- 3.3 nmol/mg protein; n = 7; P < .01), apo C-III (1.43 +/- 0.21% versus 0.14 +/- 0.04%; n = 7; P < .01), and apo E (1.64 +/- 0.26% versus 0.10 +/- 0.05%; n = 7; P < .0005). Compared with LDL(+), LDL(-) displayed enhanced cytotoxic effects on cultured human umbilical vein endothelial cells, as shown by lactate dehydrogenase assay (P < .003; n = 6), neutral red uptake (P < .02; n = 6), and morphological studies. We also studied the relationship of LDL(-) to age and plasma lipid levels in 133 subjects. The percentage of contribution of LDL(-) to total plasma LDL correlated with age (P < .05), total cholesterol (P < .05), and LDL cholesterol (P < .003). In conclusion, this study shows that LDL(-), a circulating human plasma LDL, is an electronegative native LDL subfraction with cytotoxic effects on endothelial cells. This subfraction, which correlates positively with common atherosclerotic risk factors, might induce atherogenesis by actively contributing to alteration of the vascular endothelium.
Adult↗
Enhanced modifications of low-density lipoproteins (LDL) by endothelial cells from smokers: a possible mechanism of smoking-related atherosclerosis.
OBJECTIVE: The aim of the study was to investigate LDL modifications by cultured human umbilical vein endothelial cells (HUVEC) from women smokers and non-smokers. METHODS: Modifications of LDL by HUVEC were studied by determining the values of thiobarbituric acid-reactive substances (TBARS) and the percentage of the most electronegative oxidized LDL fraction (fraction C) by using an ion-exchange chromatographic method based on fast protein liquid chromatography (FPLC). We also studied the cellular production of superoxide anion, the effect of various inhibitors and cysteine, and determined total intracellular glutathione content and cell growth. RESULTS: LDL exposed to HUVEC from smokers for 48 h showed significantly greater modifications than LDL exposed to HUVEC from non-smokers, as assessed by TBARS determination (19.4 +/- 1.2, mean +/- s.e.m., n = 20 versus 15.4 +/- 0.7 nmol/mg LDL, n = 19; P < 0.01) and by FPLC (percentage of fraction C: 39 +/- 7, n = 29 versus 14 +/- 3, n = 34; P < 0.001). Moreover, HUVEC from smokers produced significantly more superoxide anion than those from non-smokers (0.46 +/- 0.13 nmol/10(5) cell/min, n = 9 versus 0.22 +/- 0.05, n = 10; P < 0.05). Superoxide production, like cell-induced modification of LDL, was strongly dependent on the presence of cysteine in the medium. Furthermore, HUVEC from smokers had a significantly (P < 0.05) higher total intracellular glutathione content than those from non-smokers (39.9 +/- 3.1 nmol/mg, n = 9 versus 31.8 +/- 2.2, n = 7). Finally, HUVEC from smokers and non-smokers showed similar growth at 48 h. CONCLUSION: HUVEC from smokers converted significantly more LDL into an atherogenic form than HUVEC from non-smokers, a phenomenon that was not due to altered cell growth. HUVEC-mediated LDL modifications were strongly thiol-dependent, as both LDL modifications and superoxide anion production were inhibited in cysteine-free medium. Stimulation of cystine uptake by HUVEC, reflected by the enhanced total glutathione content, could account for the enhanced superoxide anion production. All these observations may be relevant to the pathophysiology of smoking-related cardiovascular disease.
Adult↗
[Charge heterogeneity of low density lipoproteins].
Traditionally, low-density lipoprotein (LDL) are separated with respect to their size, density and apolipoprotein composition. Fractionation of LDL according to their electrical charge is also interesting as modified LDL have been implicated in the onset of atherosclerosis. This review discusses possible mechanisms underlying charge heterogeneity of human plasma LDL, such as oxidation, glycation, conjugation with aldehydes, carbamylation and changes in sialic acid content and protein composition.
Aldehydes↗
Susceptibility to copper oxidation of neuraminidase-treated LDL.
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Copper↗
[Biology of the endothelial cell and atherogenesis].
Through their specific biological properties, vascular endothelial cells play a major role in maintaining the homeostasis of the cardiovascular system. The vascular endothelium participates actively in coagulation and fibrinolysis, contributes to regulating vascular tone, is involved in inflammation and immunological responses, produces several different stromal components, plays a crucial role in angiogenesis and wound-healing, and interacts with plasma lipoproteins. These physiological functions of endothelial cells are triggered by different endothelium derived mediators and are regulated by numerous environmental factors that can markedly modulate the functional state of these cells by affecting their biosynthetic capabilities, giving them different phenotypes in native, activated and injured states. Excessive endothelial activation leads to changes in endothelial cell gene expression, leading to what is referred to as a dysfunctional state. In this non-adaptative functional state, endothelial cells lose the ability to adjust, within the physiological range, some of their constitutive functions and express newly induced molecules, some of which act as proatherosclerotic factors. Activated endothelial cells thus participate actively in the pathogenesis of atherosclerosis.
Arteriosclerosis↗
Issues in the acquisition of the Sesotho tonal system.
This paper examines the acquisition of the grammatical tone system of Sesotho, a southern Bantu language where tone sandhi is rich, and where surface and underlying representations are often quite distinct. Results of the longitudinal case study show that rule-assigned tone on subject markers is generally marked appropriately by age two. In contrast, underlying tonal representations on verb roots are learned gradually over time, showing an early Default High tone pattern. The study also finds that, while some tone sandhi rules are in the process of being acquired between 2;6 and 3;0, problems in the mapping between tonal representations and segments persist. The paper raises methodological and theoretical issues not only for the acquisition of tonal systems, but for the acquisition of phonology in general.
Acoustic Stimulation↗
Transcranial color-coded real-time sonography in the evaluation of intracranial neoplasms and arteriovenous malformations.
Transcranial color-coded real-time sonography (TCCS) was performed in 57 patients with primary intracranial brain tumors (n = 49) or arteriovenous malformations (n = 8) to evaluate its diagnostic potential. In 46 patients (81%), lesions could be identified employing this technique. In 7 patients, transcranial ultrasound examination was not feasible because of bone thickness; in the remaining 4 patients, the tumor was indistinguishable from adjacent brain tissue despite sufficient insonation, suggesting that these neoplasms are isoechogenic. The sonographic features of brain tumors were very similar: a hyperechogenic matrix of the lesion was interspersed by hypoechogenic pixels. Larger hypoechogenic areas (0.5-1 cm) gave evidence of tumor necrosis. Differences between the findings of TCCS and computed tomography concerning tumor size were found in 7 patients, in whom TCCS revealed an area of smaller extension within the corresponding hypodense area on the computed tomographic scan. Perifocal brain edema could not be detected by ultrasound examination. In 13 patients, a thin, hypoechogenic peritumoral halo was disclosed that did not correlate with perifocal brain edema identified by computed tomography and that may have been due to compression of adjacent parenchyma. In patients with arteriovenous malformations, TCCS permitted the identification of the main feeders, the nidus, and the draining venous system by color-coded depiction of intravascular blood flow. In conclusion, TCCS is an additional method for initial diagnosis and highly suitable for follow-up in tumor patients and provides valuable information about tissue characteristics and blood flow.
Adult↗
Subject, topic and Sesotho passive.
Counter to findings in English, German and Hebrew, recent acquisition studies have shown that the passive is acquired early in several non-Indo-European languages. In an attempt to explain this phenomenon, this paper addresses certain typological phenomena which influence the early acquisition of passives in Sesotho, a southern Bantu language. After outlining the structure of the Sesotho passive and its syntactic and discourse functions, I examine Sesotho-speaking children's spontaneous use of passives, showing that the acquisition of passives in Sesotho is closely linked to the fact that Sesotho subjects must be discourse topics. I conclude that a detailed examination of how passive constructions interact with other components of a given linguistic system is critical for developing a coherent and universally applicable theory of how passives are acquired.
Child, Preschool↗