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Results for “functional profiling”

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PubMed2002

Hyperhomocysteinemia in children with renal transplants.

Many studies have demonstrated a strong association between elevated plasma total homocysteine (tHcys) levels and vascular disease. The aim of the present study was to determine the plasma levels of tHcys in pediatric recipients of renal transplants, to establish possible correlations with renal function, lipid profile, and folate and vitamin B12 status, and to assess whether the C677T and A1298C polymorphisms in the 5, l0-methylenetetrahydrofolate reductase (MTHFR) gene were associated with a particular risk. A total of 26 transplanted children and adolescents were investigated. tHcys levels were elevated in transplanted patients (12.9+/-4.8 micro mol/l) and 73% of these displayed values above the 97th percentile of healthy children. Plasma tHcys correlated negatively with creatinine clearance ( r=-0.58, P<0.001) and plasma vitamin B(12) ( r=-0.40, P<0.05) and positively with plasma triglycerides ( r=0.53, P<0.005). No significant correlations were found between plasma tHcys level and age, gender, time elapsed after transplantation and plasma values of glucose, insulin, folic acid, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, apolipoprotein B, and apolipoprotein A-1. Plasma tHcys level was clearly increased in 3 patients with a MTHFR 677TT/1298AA genotype. In a multiple stepwise regression model plasma creatinine and triglyceride levels and MTHFR 677TT/1298 AA genotype accounted for 60% of the observed plasma tHcys variability. The MTHFR 677CT/1298 AC genotype was not a significant predictor of tHcys plasma levels. We conclude that a moderate degree of hyperhomocysteinemia is often present in renal transplant children and that folate supplementation must be considered in this population.

Adolescent↗
PubMed2006

Executive functioning in children with an Autism Spectrum Disorder: can we differentiate within the spectrum?

The aim of this study was to investigate whether children with high-functioning autism (HFA), Asperger's syndrome (AS), and pervasive developmental disorder not otherwise specified (PDDNOS) can be differentiated from each other and from normal controls on their neurocognitive executive functioning (EF) profile. Children with HFA and AS showed the most EF deficits. The EF profile of the PDDNOS group was more disturbed that the normal control group, but was less disturbed than the profile of the HFA and AS groups. Little difference was found between the three PDD subtypes with respect to EF. This study supports the view that executive dysfunctioning plays an important role in autism. The usefulness of a distinction between different PDD subtypes was not demonstrated.

Adolescent↗
PubMed2006

Starch-based microspheres produced by emulsion crosslinking with a potential media dependent responsive behavior to be used as drug delivery carriers.

This paper describes the development and characterization of starch microspheres for being used as drug delivery carriers in tissue engineering applications. The developed starch microspheres can be further loaded with specific growth factors and immobilized in scaffolds, or administrated separately with scaffolds. Furthermore and due to the processing conditions used, it is expected that these microspheres can be also used to encapsulate living cells. The aim of this study was to evaluate the efficacy of this methodology for further studies with biologically active agents or living cells. The starch microspheres were prepared using an emulsion crosslinking technique at room temperature to allow for the loading of biologically active agents. A preliminary study was performed to evaluate the incorporation of a model drug (nonsteroidal anti-inflammatory drug-NSAID) and investigate its release profile as function of changes in the medium parameters, such as ionic strength and pH. The developed starch-based drug delivery system has shown to be dependent on the ionic strength of the release medium. From preliminary results, the release seems to be pH-dependent due to the drug solubility. It was found that the developed microspheres and the respective processing route are appropriate for further studies. In fact, and based in the processing conditions and characterization, the developed system present a potential for the loading of different growth factors or even living cells on future studies with these systems for improving bone regeneration in tissue engineering, especially because the crosslinking reaction of the microspheres takes place at room temperature.

Absorption↗
PubMed2005

Simultaneous modelling of survival and longitudinal data with an application to repeated quality of life measures.

In biomedical studies, interest often focuses on the relationship between patient's characteristics or some risk factors and both quality of life and survival time of subjects under study. In this paper, we propose a simultaneous modelling of both quality of life and survival time using the observed covariates. Moreover, random effects are introduced into the simultaneous models to account for dependence between quality of life and survival time due to unobserved factors. EM algorithms are used to derive the point estimates for the parameters in the proposed model and profile likelihood function is used to estimate their variances. The asymptotic properties are established for our proposed estimators. Finally, simulation studies are conducted to examine the finite-sample properties of the proposed estimators and a liver transplantation data set is analyzed to illustrate our approaches.

Algorithms↗
PubMed1996

Immune regulation by cannabinoid compounds through the inhibition of the cyclic AMP signaling cascade and altered gene expression.

Immune modulation by cannabinoid compounds, although established for several decades, has remained up until recently mechanistically obscure. The identification of a novel class of G-protein coupled receptors that negatively regulate the cyclic adenosine 3':5'-monophosphate (cAMP) cascade, bind cannabinoids, and are expressed on cells within the immune system has provided new insights into the mechanism for their biologic activity. Although the role of the cAMP cascade in the regulation of immune responses is itself highly controversial, a number of laboratories recently demonstrated that aberrant regulation of this signaling pathway leads to alterations in the expression of critical immunoregulatory genes, cell cycle arrest, and decreased immune function. This profile of effects is strikingly similar to that which is induced in leukocytes in the presence of cannabinoid compounds. In the present commentary, a putative mechanism of immune regulation by cannabinoids is proposed. This mechanism is discussed in the context of decreased cAMP signaling, the transcription factors that are consequently adversely regulated, and immunologically relevant genes that ultimately exhibit altered expression.

Adjuvants, Immunologic↗
PubMed1989

Enhanced phosphoinositol hydrolysis in response to vasopressin in the septum of the homozygous Brattleboro rat.

Arginine8-vasopressin (AVP) receptors in the septum of the Long-Evans rat have been shown to be both pharmacologically (displacement profiles) and functionally (ability to stimulate phosphoinositide hydrolysis) similar to the peripheral V1-type receptor for AVP. Previous binding studies of AVP receptors in the septum of heterozygous (HE) and homozygous (vasopressin-deficient, HO) Brattleboro (BB) rats revealed an increased number of receptors with a lower affinity for AVP in the HO-BB rat when compared to the HE-BB rat. To determine the effect of these receptor changes in the HO-BB rat septum on the postreceptor response of the tissue to AVP, concentration-response relationships for AVP-stimulated phosphoinositide hydrolysis were examined in septal slices from age-matched, adult male HE- and HO-BB rats. AVP-stimulated accumulation of [3H]inositol-1-phosphate (IP1) was significantly greater in the HO-BB (43.7%) than in the HE-BB (13.7%) at AVP concentrations of 10(-08) to 10(-05) M. The two groups did not, however, differ in their ability to stimulate [3H]IP1 accumulation in response to 2.0 mM carbachol. When the AVP-stimulated phosphoinositide response in both genotypes was compared to that obtained for the Long-Evans (LE) rat (the parent strain of the Brattleboro rat) septum under the same assay condition, it was found that the response in the HE-BB was much lower than in the LE. AVP receptor binding capacity (Bmax) correlated (r = 0.975) with release of IP1 ([3H]IP1 accumulation) for all 3 groups studied (LE, HE, HO).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Response of Earth's atmosphere to increases in solar flux and implications for loss of water from Venus.

A one-dimensional radiative-convective model is used to compute temperature and water vapor profiles as functions of solar flux for an Earth-like atmosphere. The troposphere is assumed to be fully saturated, with a moist adiabatic lapse rate, and changes in cloudiness are neglected. Predicted surface temperatures increase monotonically from -1 to 111 degrees C as the solar flux is increased from 0.81 to 1.45 times its present value. Surface temperatures corresponding to high solar fluxes may be underestimated, however, owing to neglect of H2O continuum absorption outside of the 8- to 12-micrometers window region. These results imply that the surface temperature of a primitive water-rich Venus should have been at least 80-100 degrees C and may have been much higher. The existence of liquid water at the surface depends on poorly known aspects of H2O continuum absorption and on uncertainties concerning relative humidity and cloudiness. In any case, water vapor should have been a major atmospheric constituent at all altitudes, leading to the rapid hydrodynamic escape of hydrogen. The oxygen left behind by this process was presumably consumed by reactions with reduced minerals in the crust. Both the loss of oxygen and the presently observed enrichment of the deuterium-to-hydrogen ratio are most easily explained if oceans of liquid water were initially present.

Atmosphere↗
PubMed1990

Intraventricular conduction defect (IVCD), real or fancied, QRS duration in 1,254 normal adult white males by a multilead automated algorithm.

The QRS duration (QRSD) on a digital 12 simultaneous lead ECG was measured by a commercially available recording cart (Marquette MACII 12SL) in 1,254 white male safety workers (ages 19-65, mean 34). All had a negative history (including drugs known to affect the cardiovascular or pulmonary systems), a negative family history (in immediate family members before age 55), no physical findings suggestive of heart disease, a normal blood chemistry profile, pulmonary function tests, and symptom limited bicycle exercise test. The frontal QRS axis was between -30 and -65 in 22 of 1,254 (1.8%). Twenty-seven of 1,254 (2.1%) had QRSD greater than or equal to 120 ms-14 of these had normal morphology; 2 had RBB; 3 had atypical RBB; 5 had R' in V1, V2; 2 had WPW; and 1 had Superior Fascicular Block. Sixty-three (5%) had a QRSD greater than or equal to 112 and less than or equal to 116 ms-36 of this group had normal morphology; 1 had typical RBBB; and 26 had R' V1, V2 (considered a normal variant as it occurred in 360 of 1,164 remaining with QRSD less than or equal to 108). In 1,224 white men with normal QRS morphologies and frontal axis (-25 to 100), the 98% upper and lower bounds of QRSD with the 12SL algorithm, like that seen in BSMs, was 80-116 ms, peak 96 ms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Characterization of cytosolic phospholipases C from porcine aortic endothelial cells.

Phospholipases C (PLCs) are ubiquitous enzymes which play key roles in the response of cells to extracellular agonists. Endothelial cells are involved in myriad normal and pathophysiologic functions. Although it is known that agonists activate PLCs in endothelial cells, second messengers form, and cellular responses ensue, more knowledge is needed about the specific types of PLCs in these cells. To this end, cytosolic PLCs from porcine aortic endothelial cells were partially purified by ammonium sulfate fractionation and column chromatography on DEAE-Sepharose CL-6B and heparin-agarose. Three PLC isozymes immunologically similar to bovine brain PLC-beta, PLC-gamma, and PLC-delta were identified. The relative levels of PLC activities in the cytosol were: PLC-beta, 50%; PLC-gamma, 44%; PLC-delta, 6%. The level of PLC-beta activity in porcine endothelial cells appeared higher than the levels reported for several established cell lines, suggesting that this enzyme may play a specific role in endothelial cell function. Elution profiles of PLC activity with phosphatidylinositol 4,5-bisphosphate (Ptdlns(4,5)P2) as substrate were similar to those with phosphatidylinositol (Ptdlns) as substrate, indicating that cytosolic PLCs hydrolyze both Ptdlns and Ptdlns(4,5)P2 and no Ptdlns(4,5)P2-specific PLC was present in the cytosol. The catalytic properties of the partially purified PLC isozymes from porcine endothelial cells were similar to their counterparts from bovine brain. These include the dependence of hydrolysis of Ptdlns on Ca2+, the optimal Ca2+ concentrations for the hydrolysis of Ptdlns and Ptdlns(4,5)P2, the pH optima, and the stimulatory effects of deoxycholate.

Animals↗
PubMed1985

MMPI, personality dysfunction and the dexamethasone suppression test in major depression.

In this study we examined the relationship of psychopathology and personality dysfunction to neuroendocrine functioning. MMPI profiles were examined for 30 psychiatric inpatients with major depression who were suppressors (60%) and nonsuppressors (40%) on the dexamethasone suppression test. There were no differences between suppressors and nonsuppressors on any of the MMPI scales or on DSM-III Axis-II diagnosis. When subdivided according to T-score elevations above 70 on MMPI scales 4 and 6, or 4 and 9, 30% of the sample, however, met criteria for personality dysfunction. Furthermore, a significantly higher proportion of suppressors (50%) evidenced personality dysfunction than did the nonsuppressors (8%). This suggests that certain MMPI scales are able to identify a subgroup of depressed patients with personality disturbances who also have a hypothalamic-pituitary-adrenal dysfunction.

Adult↗
PubMed1991

Predicting relapse and recovery in alcoholism and addiction: neuropsychology, personality, and cognitive style.

Neuropsychological studies of substance abuse treatment outcome have generally found successful recoverers to show intact functioning on most measures, whereas relapsers do poorly on tests of language, abstract reasoning, planning, and cognitive flexibility. These have been related to involvement of left hemisphere and frontal lobe functions. Personality profiles of successful remitters, with or without formal treatment, include future goal-orientation, frustration-tolerance, and self-efficacy, while relapsers are characterized by impulsivity, antisocial personality, and affective disorders. It is proposed that what these neuropsychological and personality indexes are actually describing in successful recoverers is the neuropsychodynamic trait variable of ego autonomy, which is related to a reflective, nonimpulsive, goal-directed cognitive style. Implications of the neuropsychodynamic model for the evaluation and treatment of substance abusers is discussed.

Alcoholism↗
PubMed2005

Clinical characteristics and rehabilitation outcomes of patients with posterior cerebral artery stroke.

OBJECTIVES: To describe the demographics, clinical profile, and functional outcomes in posterior cerebral artery (PCA) stroke and to identify factors associated with functional change during rehabilitation and discharge disposition. DESIGN: Retrospective study of patients with PCA stroke admitted to a rehabilitation hospital over an 8-year period. SETTING: Free-standing urban rehabilitation hospital in the United States. PARTICIPANTS: Eighty-nine consecutive patients with PCA stroke (48 men, 41 women; mean age, 71.5y) met inclusion criteria. INTERVENTION: Inpatient multidisciplinary comprehensive rehabilitation program. MAIN OUTCOME MEASURES: Demographic, clinical, and discharge disposition information were collected. Functional status was measured using the FIM instrument, recorded at admission and discharge. The main outcome measures were the discharge total FIM score, the change in total FIM score (DeltaFIM), and the discharge disposition. Multiple and logistic regression analyses were performed to identify factors associated with the main outcome measures. RESULTS: The most common impairments were motor paresis (65%), followed by visual field defects (54%) and confusion or agitation (43%). The mean discharge total FIM score +/- standard deviation was 88.3+/-28.2. The mean DeltaFIM was 23.3+/-16.4. Fifty-five (62%) patients were discharged home. On multiple regression analysis, higher admission total FIM score, longer length of stay (LOS), and a rehabilitation stay free of interruptions were associated with higher discharge total FIM score and greater DeltaFIM. Absence of diabetes mellitus and younger age were also associated with higher discharge total FIM scores, and male sex had greater DeltaFIM. On logistic regression analysis, younger patients, higher discharge FIM scores, presence of a caregiver, and the nonnecessity for 24-hour support were associated with a discharge to home. CONCLUSIONS: Motor, visual, and cognitive impairments are common in PCA stroke, and good functional gains are achievable after comprehensive rehabilitation. Higher admission FIM scores, longer LOS, and younger and male patients were associated with better functional outcomes. Most patients were discharged home, particularly those with caregivers and those for whom 24-hour support was not required. Further research should aim at the development of functional outcome measures of greater breadth and sensitivity to visual and cognitive deficits and should compare PCA stroke outcomes with outcomes of strokes in other vascular territories.

Aged↗
PubMed2006

Delay in initiation and termination of tibialis anterior contraction in lower-limb hemiparesis: relationship to lower-limb motor impairment and mobility.

OBJECTIVE: To assess the relationship between delays in initiation and termination of tibialis anterior contraction in the hemiplegic lower limb and clinical measures of lower-limb motor impairment and mobility. DESIGN: Cross-sectional correlational study. SETTING: Outpatient rehabilitation clinic of an academic medical center. PARTICIPANTS: Convenience sample of 22 chronic stroke survivors with lower-limb hemiparesis. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Delays in initiation and termination of tibialis anterior electromyographic activity during isometric contraction, lower-limb Fugl-Meyer Assessment (FMA), and Modified Emory Functional Ambulation Profile (mEFAP). RESULTS: The affected lower limb exhibited significantly longer delays in initiation and termination of tibialis anterior contraction relative to the unaffected limb. Delay in termination of 3-second tibialis anterior contraction of the affected limb correlated significantly with the FMA and mEFAP. However, delay in initiation of tibialis anterior contraction did not correlate with clinical measures. CONCLUSIONS: Delay in termination of muscle activity in the hemiparetic lower limb may have important clinical implications, but delay in initiation did not correlate with clinical measures. Controlled, interventional trials are needed to demonstrate a cause and effect relationship.

Adult↗
PubMed2005

Novel ketal ligands for the glucocorticoid receptor: in vitro and in vivo activity.

A novel series of selective ligands for the human glucocorticoid receptor is described. Structure-activity studies focused on variation of B-ring size, ketal ring size, and ketal substitution. These analogs were found to be potent and selective ligands for GR and have partial agonist profiles in functional assays for transactivation (TAT, GS) and transrepression (IL-6). Of these compounds, 27, 28, and 35 were evaluated further in a mouse LPS-induced TNF-alpha secretion model. Compound 28 had an ED(50) of 14.1 mg/kg compared with 0.5 mg/kg for prednisolone in the same assay.

Animals↗
PubMed2005

Down syndrome, Alzheimer's disease and seizures.

Neuropathologically, Alzheimer-type abnormalities are demonstrated in patients with Down syndrome (DS), both demented and nondemented and more than a half of patients with DS above 50 years develop Alzheimer's disease (AD). The apolipoprotein E epsilon4 allele, oestrogen deficiency, high levels of Abeta1-42 peptide, elevated expression of BACE2, and valine polymorphism of prion protein gene are associated with earlier onset of dementia in DS individuals. Advanced AD alone may be an important risk factor for new-onset seizures in older adults and age above 60 years is a recognized risk factor for poor outcome from convulsive and nonconvulsive status epilepticus. DS patients aged over 45 years are significantly more likely to develop Alzheimer's disease than those less than 45 years and up to 84% demented individuals with DS develop seizures. Late-onset epilepsy in DS is associated with AD, while early-onset epilepsy is associated with an absence of dementia. In AD patients with a younger age of dementia onset are particularly susceptible to seizures. DS adults with epilepsy score significantly higher overall on the adaptive behaviour profile. Language function declined significantly more rapidly in AD patients with seizures and there is a good correlation between the severity of EEG abnormalities and cognitive impairment whereas in DS slowing of the dominant occipital rhythm is related to AD and the frequency of the dominant occipital activity decreases at the onset of cognitive deterioration.

Adult↗
PubMed2006

Proteomic discovery of protease substrates.

Elucidation of in vivo substrate degradomes of a protease is a daunting endeavor because of the large number of proteins in a proteome and often minute and transient amounts of key substrates. Proteomic substrate screens for proteases are currently experiencing impressive progress. Mass spectrometry-based global proteome analysis, interfaced with liquid-chromatography and together with stable isotope labeling strategies, has provided increased coverage and sensitivity for quantitative proteomics. ICAT and iTRAQ labeling have been used to identify a plethora of new matrix metalloproteinase substrates. Emerging techniques focus on the quantitative analysis of proteolytically generated neo amino-termini, which we call terminopes, on a system-wide basis. In vivo SILAC pulse-chase experiments have also enabled the study of individual protein turnover and global proteome dynamics in cells and whole organisms. Together with activity-based probes for the profiling of functional proteases, there is now in place an array of complementary technologies to dissect the 'protease web' and its distortion in pathology.

Chromatography, Liquid↗