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PubMed1983

The effect of serum vitamin D-binding protein on polymerization and depolymerization of actin is similar to the effect of profilin on actin.

The mechanism of the interaction between two genetically determined serum vitamin D-binding protein forms and the muscle skeletal actin was investigated. Vitamin D-binding protein was isolated in a good yield from human serum, using immunoaffinity chromatography. 16 mg of pure vitamin D-binding protein were obtained from 100 ml of serum. The interaction between purified vitamin D-binding protein and skeletal muscle actin was studied by viscosity, delta A (232 nm) measurements and by electron microscopy. The effect of vitamin D-binding protein on actin polymerization is characterized by the decrease of the nucleation and elongation rates and by the decrease of the final concentration of polymerized actin in the steady state. The depolymerizing effect is not the result of direct action on vitamin D-binding protein on F-actin but rather of an increased concentration of the complex of the former protein with G-actin. The characteristics of the vitamin D-binding protein and profilin interactions with actin are similar. Both proteins seem to react only with G-actin.

Actins↗
PubMed1985

Results of radiation treatment of medulloblastoma in adults.

From 1961 to 1982, 20 adults (greater than 16 years of age) were treated with radiation therapy following surgery for medulloblastoma. All patients received neuro-axis irradiation. Five patients received adjuvant chemotherapy. A 5- and 10-year survival rate of 78 and 55%, respectively, were achieved. Treatment failures were mainly a result of local recurrences, but also of metastases. One patient died of acute myeloid leukemia. One patient developed paraplegia. The survival rate was better in males (2 deaths out of 14) than in females (5 deaths out of 6). All the survivors are free of deficit or sequelae, except the patient with paraplegia.

Adolescent↗
PubMed1995

The application of physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling for exploring risk assessment approaches of chemical mixtures.

When dealing with health impacts of environmental or occupational exposure such as groundwater contamination from or remediation effort associated with hazardous waste sites, we are obviously not facing individual, single chemicals. Thus, we are immediately confronted with the following questions: (1) Is single chemical risk assessment approach applicable to the multiple chemicals in hazardous waste sites? (2) How do we handle risk assessment of chemical mixtures? Although there were pioneering and commendable efforts from the USEPA to formulate guidelines for risk assessment of chemical mixtures, these guidelines were principally based on additivity concept. As new scientific advances are made, improvement and refinement of risk assessment methodology will be anticipated. At Colorado State University (CSU), our research effort is devoted to the challenges and potential applications of physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling in the risk assessment of chemical mixtures. With the ultimate goal of Predictive Toxicology, 3 specific research projects are described: (1) PBPK/PD modeling of toxicologic interactions between trichloroethylene (TCE) and 1,1-dichloroethylene (1,1-DCE) and the investigation and defining of an 'Interaction Threshold'; (2) PBPK/PD modeling of toxicologic interactions between Kepone and carbon tetrachloride (CCl4) and the coupling of Monte Carlo simulation for the prediction of acute toxicity; (3) PBPK modeling of the inhibition of pharmacokinetics and enzyme kinetics of TCE caused by low-level, repeated dosing of a chemical mixture of 7 groundwater contaminants. Since this paper is meant to be a commentary and the emphasis is on approaches for dealing with chemical mixtures, detailed presentation of data is avoided. These examples illustrate partially our ongoing research activities and the related ideas with respect to possible novel risk assessment applications to chemical mixtures.

Animals↗
PubMed1995

The use of physiologically-based pharmacokinetic/pharmacodynamic dosimetry models for chemical mixtures.

Human exposure to chemicals is rarely, if ever, limited to a single chemical. Therefore, it is essential that we consider multiple chemical effects and interactions in our risk assessment process. However, with the almost infinitely large number of chemical mixtures in the environment, systematic studies of the toxicology of these chemical mixtures with conventional methodologies and approaches are impossible because of the immense resources and unrealistically long durations required. Thus, the development of 'Predictive and Alternative Toxicology' is imperative. At Colorado State University (CSU), our research effort is entirely devoted to this challenge. In order to have a reasonable chance to deal with the complex issue of toxicology of chemical mixtures, we believe that the following concepts must be considered: (1) the utilization of computer, (2) the exploitation of mathematical/statistical methodologies; (3) developing very focused, mechanistically based, and short-term toxicology studies; (4) coupling computer/mathematical modeling with mechanistically-based toxicology. Our strategy therefore the utilization of physiologically-based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling, coupled with very focused, model-directed toxicology experiments as well as other statistical/mathematical methodologies such as Monte Carlo simulation, isobolographic analysis, and response surface methodology. We believe that 'Predictive and Alternative Toxicology' in terms of tissue dosimetry at the pharmacokinetic and pharmacodynamic levels is achievable with simple and complex but chemically defined mixtures. In this presentation, we describe two ongoing research projects as an illustration of our 'Bottom-Up' and 'Top-Down' approaches for handling the chemical mixtures: (1) PBPK/PD modeling of toxicologic interactions between Kepone and carbon tetrachloride (CCl4) and the coupling of Monte Carlo simulation for the prediction of acute toxicity; (2) the conceptual development of PBPK/PD modeling for a more complex chemical mixture of seven groundwater contaminants from hazardous waste sites and the consideration of subfractionation of this chemical mixture.

Animals↗
PubMed2005

Anxiety-related differences in affective categorizations of lexical stimuli.

Effects of emotional valence on attention have been shown to occur even when stimuli are presented outside awareness. The impact of negative valence on stimulus processing has been demonstrated to be particularly salient in anxiety. Therefore, it has been hypothesized that compared to nonanxious individuals, anxious individuals have an enhanced ability to detect the valence of negative stimuli. However, it remains unclear whether anxious individuals are better at identifying the valence of threatening stimuli or, rather, more likely to label ambiguous stimuli as threatening. To investigate these hypotheses, high and low anxious participants categorized lexical stimuli as "safe" or "dangerous." Stimuli were presented at durations that allowed for both conscious (unmasked) and nonconscious (masked) processing. Results show that on masked trials, anxious individuals evidenced an enhanced ability to correctly classify threatening information, whereas nonanxious participants demonstrated an enhanced ability to correctly classify neutral or positive information. Signal detection analyses indicated results were explained by a response bias, whereby anxious individuals were more likely than nonanxious individuals to categorize masked words as threatening and nonanxious individuals were more likely to categorize masked words as nonthreatening. No group differences for nonword stimuli emerged, suggesting that anxiety-related response bias tendencies are activated only after detection of a weak semantic signal.

Adult↗
PubMed2006

Circulating markers of endothelial function in cardiovascular disease.

Endothelial dysfunction is a key event in cardiovascular disease. Measurement of endothelial dysfunction in vivo presents a major challenge, but has important implications since it may identify the clinical need for therapeutic intervention, specifically in primary prevention. Several biological markers have been used as indicators of endothelial dysfunction. The soluble adhesion molecules sICAM-1 and sVCAM-1 lack specificity and are increased in inflammatory processes. Both markers are increased in coronary artery disease. sICAM-1 level predicts the risk for cardiovascular disease or diabetes mellitus in healthy individuals. sE-selectin is specific for the endothelium and is increased in coronary artery disease and diabetes mellitus. sE-selectin is also associated with diabetic risk. The endothelium-specific marker, soluble thrombomodulin, is associated with severity of coronary artery disease, stroke or peripheral occlusive arterial disease and is not increased in healthy or asymptomatic subjects. Interestingly, thrombomodulin decreases during treatment of hypercholesterolemia or hyperhomocysteinemia. In contrast, von Willebrand factor is the best endothelial biomarker and predicts risk for ischemic heart disease or stroke.

Animals↗
PubMed2006

Reduced thalamic and cerebellar rest metabolism in relapsing-remitting multiple sclerosis, a positron emission tomography study: correlations to lesion load.

Magnetic resonance imaging (MRI) is the main tool for detecting central nervous system lesions in MS. However, classical anatomical MRI is unable to assess exactly disease related injury in normal-appearing brain tissue and to give information about the functional consequences of the disease, explaining weak correlation frequently observed between lesion load and clinical data. Recently, functional brain imaging techniques have provided new insights concerning pathophysiological processes of the disease. Among them Positron Emission Tomography (PET), a sensitive technique to evaluate functional consequences of tissue injury in other neurological diseases, has rarely been used in MS. Seventeen Relapsing-Remitting (RR-) MS patients with low disability at the early stage of the disease underwent measurements of cerebral metabolic rate of glucose (rCMRglu) in resting state by PET using [(18)F] fluorodeoxyglucose (FDG) and assessment of regional cortical and white matter lesion volume (LV), using an in-house-developed semi-automatic method, was done at the same time on MRI. rCMRglu of MS patients was compared with rCMRglu of 18 normal control subjects using univariate SPM99 analysis through Matlab 5 and correlations between rCMRglu and LV were tested using multivariate linear regression using SPM99. Statistical threshold was set at p<0.05 corrected for multiple comparisons and correlations. Compared to controls, reduced rCMRglu was found in the right thalamus (p<0.001), in bilateral cerebellum (p<0.05 for right and p<0.01 for left) and the posterior part of left inferior parietal cortex (p<0.05). In addition, higher rCMRglu in patients compared to controls was observed in left inferior frontal cortex, left (anterior part) and right inferior parietal cortex (p<0.001). rCMRglu in right thalamus correlates negatively with different LV: total LV, total juxtacortical and/or overlapping cortico-subcortical LV, total and frontal deep white matter LV. rCMRglu of the right superior frontal cortex negatively correlated with total and parieto-occipital deep white matter LV. The results of this study, performed in a group of recent RR-MS patients with low disability, suggest that demyelinating lesions in MS mainly have a remote effect on cortical, basal ganglia and cerebellum metabolism and that regional cortical compensatory mechanisms may be observed concurrently.

Adult↗
PubMed2004

Magnetic resonance imaging contrast-enhanced relaxometry of breast tumors: an MRI multicenter investigation concerning 100 patients.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using extracellular contrast agents has proved to be useful for the characterization of breast tumors. DCE-MRI has demonstrated a high sensitivity (around 95%) but a rather poor and controversial specificity, varying, according to the different studies, from 45% to 90%. In order to increase (a) the specificity and (b) the robustness of this quantitative approach in multicenter evaluation (five MRI units), a quantitative approach called dynamic relaxometry has been developed. According to the proposed method, the time-dependent longitudinal relaxation rate measured on region of interest of the lesion was calculated during the contrast uptake, after intravenous bolus injection of contrast agent. A specifically developed method was used for fast R(1) measurements. Relaxometry time curves are fitted to the Tofts model allowing the measurement of the parameters describing the enhancement curve (maximum relation rate enhancement, initial, 30-s and 60-s slopes) and the tissue parameters [transfer constant (K(trans) min(-1)) and extracellular extravascular space fraction (v(e))]. Correspondence factorial analysis followed by hierarchical ascendant classification are then performed on the different parameters. Higher K(trans) values were observed in infiltrative ductal carcinomas than in infiltrative lobular carcinomas, in agreement with data published by other groups. Specificity of DCE-MRI has been increased up to 85%, with a sensitivity of 95% with K(trans)/v(e) and enhancement index I (ratio of initial slope by maximum relaxation rate enhancement). A multiparametric data analysis of the calculated parameters opens the way to include quantitative image-based information in new nosologic approaches to breast tumors.

Adenocarcinoma, Mucinous↗
PubMed2004

Relationship between performance on the Stroop test and N-acetylaspartate in the medial prefrontal cortex in deficit and nondeficit schizophrenia: preliminary results.

The aim of this research was to investigate the relationship between performance on the Stroop test and N-acetylaspartate/creatine assessed using proton magnetic resonance spectroscopy in the medial prefrontal cortex (MPFC) of schizophrenia patients. The Schedule for the Deficit Syndrome was used to subdivide the schizophrenia patients into deficit (n=5) and nondeficit (n=17) subtypes. Twenty-one control subjects served as a comparison group. A strong correlation between right-sided N-acetylaspartate/creatine levels and Stroop scores was found in the deficit patients but not in the nondeficit patients and the controls. This result suggests a relationship between a dysfunction of the right medial prefrontal cortex and a deficit in selective attention in schizophrenia patients with the deficit syndrome.

Aspartic Acid↗
PubMed2004

[Editorial].

Explore the source record for details and available documents.

France↗
PubMed2005

[Hypodermoclysis: benefits and indications in geriatrics].

PURPOSE: Older people are at high risk of dehydration. Oral intakes are often inadequate routinely. Intravenous infusion may be difficult in these patients and harmful. Subcutaneous infusion or hypodermoclysis is a useful technique for the cure of a moderate dehydration in elderly patients and especially for its prevention. Moreover, this technique is of great interest in end-life patients. CURRENT KNOWLEDGE AND KEY POINTS: When it is used correctly and when its contraindications are respected (emergency situations), hypodermoclysis is a simple, safe, sure, effective and comfortable technique. It does not need trained supervision and can be used both in an institution and at home, thus avoiding hospitalization of older subjects and reducing health costs. This technique has considerable benefits both psychologically and financially. FUTURE PROSPECTS AND PROJECTS: The numerous advantages of hypodermoclysis should encourage its wider use in older patients at home as well as in institutions. Moreover, new indications need to be evaluated. In this way, subcutaneous infusion of therapeutics or prevention of protein-energy malnutrition by hypodermoclysis of amino acids need further investigations.

Aged↗
PubMed2005

[Painful bruising syndrome: a psychogenic disease].

INTRODUCTION: Painful bruising syndrome was described by Gardner and Diamond in 1955. It is marked by spontaneous bruising, without any biological abnormality, affecting young women with pathological mental context. EXEGESIS: We report three observations with painful bruising syndrome. In a patient, psychotherapy induced improvement in dermatological and articular manifestations. In other case, placebotherapy made clinical symptoms go away for a prolonged period. CONCLUSION: Some etiological hypotheses have been postulated for Gardner and Diamond syndrome. However, published cases speak in favour of psychogenic hypothesis. Somatic and psychological approach must be offered to these patients.

Adolescent↗
PubMed2001

Plasma vascular endothelial growth factor and its receptor Flt-1 in patients with hyperlipidemia and atherosclerosis and the effects of fluvastatin or fenofibrate.

Increased vascular endothelial cell growth factor (VEGF) may be important in cardiovascular pathophysiology (perhaps relating to angiogenesis and collateral vessel development) and binds target endothelium via receptors such as Flt-1. We hypothesized that there would be increased levels of plasma VEGF and Flt-1 in patients with atherosclerosis and others with hyperlipidemia compared with controls, and a reduction in these factors with 3 months of lipid-lowering therapy. Twenty patients with uncomplicated hyperlipidemia but no atherosclerosis, 20 patients with hyperlipidemia plus clear atherosclerosis, and 40 matched controls were studied. Plasma VEGF was higher in patient groups than in healthy controls (p <0.01), but Flt-1 was not significantly altered. After lipid-lowering therapy, patients with uncomplicated hyperlipidemia had significantly reduced total cholesterol and VEGF (all p <0.05) but no significant change in Flt-1. Lack of a significant correlation between the von Willebrand factor and VEGF suggests the latter is unrelated to endothelial damage. Plasma VEGF that increases in patients with uncomplicated hyperlipidemia free of major underlying atherosclerosis and in patients with hyperlipidemia plus established atherosclerosis is reduced by successful lipid-lowering treatment. These findings may have implications for the pathophysiology and treatment of hyperlipidemia and atherosclerosis, and suggest an alternative mechanism (i.e., modulation of angiogenesis) by which lipid-lowering therapy may reduce cardiovascular events beyond lipid reduction alone.

Anticholesteremic Agents↗
PubMed2003

Comparison of four clinical prediction scores for the diagnosis of lower limb deep venous thrombosis in outpatients.

PURPOSE: We compared three scores for the prediction of deep venous thrombosis with a new score designed specifically for outpatients. METHODS: Patients referred for evaluation because of suspected deep venous thrombosis were examined by ultrasonography. Sensitivity and specificity were calculated for three clinical scores (Wells [nine components], Kahn [four components], and St. André [six components]). We developed a new score by multivariate analysis, and then compared this score with the others in a new sample. RESULTS: Four hundred and forty-four outpatients were included in the first sample, of whom 126 (28%) had deep venous thrombosis. The Wells score was a better predictor of deep venous thrombosis than the Kahn and St. André scores. According to the Wells score, 73 patients had a high probability of deep venous thrombosis (of whom 51 [70%] actually had a thrombosis) and 178 had a low probability of deep venous thrombosis (of whom 19 [11%] had a thrombosis). A new score was developed as follows: male sex (+1), lower limb palsy or immobilization (+1), confinement to bed >3 days (+1), lower limb enlargement (+1), unilateral lower limb pain (+1), and other plausible diagnosis (-1). In a validation sample of 282 outpatients, this score identified 31 patients who had a high probability of deep venous thrombosis (score > or =3), of whom 18 (58%) had a thrombosis, and 70 patients who had a low probability (score < or =0), of whom 3 (4%) had a thrombosis. The Wells score and this ambulatory score had similar test operating characteristics in the validation sample. CONCLUSION: Our new six-component score had similar diagnostic utility as the nine-component Wells score among outpatients being evaluated for deep venous thrombosis.

Female↗
PubMed2004

[Is the screening of asymptomatic carotid stenosis worthwhile?].

Endarteriectomy may be of some benefit for those patients who have asymptomatic carotid stenosis above 80%. Duplex echography is a useful non-invasive diagnosis method, and the detection of asymptomatic carotid stenosis is questionable. Detection in the whole population seems inefficient since most stenosis are found in patients who experience other locations of atherosclerosis or who have several risk factors. The conditions where detection seems useful are the patients above 55 years with lower limb occlusive arterial disease or aortic aneurysm, and the subjects who have three of the four following conditions: age above 65 years, hypercholesterolemia, tobacco, and ischaemic cardiopathy.

Age Factors↗