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PubMed1989

Profile of in vitro binding affinities of neuroleptics at different rat brain receptors: cluster analysis comparison with pharmacological and clinical profiles.

A series of 21 neuroleptics with different chemical structures (phenothiazines, thioxanthenes, dibenzodiazepines, butyrophenones, benzamides, etc.) was examined for their in vitro interactions with 12 neurotransmitter binding sites in the rat brain (alpha- and beta-noradrenergic, dopaminergic, muscarinic, serotoninergic, histaminic, and opioid receptors, calcium channels, and serotonin uptake binding sites). The biochemical profile obtained from the binding data was compared with reported pharmacological and clinical profiles for this class of compounds by cluster analysis. Cluster analysis on binding data classified the compounds in three main subgroups: benzamides, compounds with an affinity mainly for DA2 and 5-HT2 receptors and inactive at muscarinic receptors, and compounds with a high affinity for alpha 1-adrenergic receptors and muscarinic receptors. The main subgroups resulting from cluster analysis of previously published pharmacological and clinical data for neuroleptics contain compounds common to the present study, with some correlations. The results extend previous observations that a complete binding profile corresponds to the pharmacological and clinical profile of this class of compounds.

Animals↗

PubMed2000

Personality coherence: moderating self--other profile agreement and profile consensus.

Traditional research on moderator variables in personality has focused on measures of relative consistency. In contrast, using Goldberg's (1992) adjectives representing the Big Five personality traits, the authors examined the applicability of moderator variables to measures of personality coherence. The authors considered 3 traditional moderator variables (interitem variability, construct similarity, and scalability) and one new moderator variable: the temporal stability of response patterns. Across 2 studies, individuals with temporally stable response patterns had higher levels of personality coherence, as measured by self-other profile agreement and informant profile consensus, than did individuals with less temporally stable patterns. By comparison, the normatively based moderator variables did not moderate self-other profile agreement and informant profile consensus. The implications for personality structure and coherence are discussed.

Adolescent↗

PubMed1994

Mycosis fungoides exhibits a Th1-type cell-mediated cytokine profile whereas Sezary syndrome expresses a Th2-type profile.

We determined T-cell cytokine profiles in the epidermis, dermis, and blood of cutaneous T-cell lymphoma to differentiate whether unique cytokine profiles were associated with mycosis fungoides (MF) versus Sezary syndrome. Punch biopsy specimens from plaque stage MF (n = 7) were compared to Sezary skin (n = 3) after undergoing rapid heat-saline separation of epidermis from dermis. Normal adult skin (n = 11), neonatal foreskin (n = 4), untreated psoriatic plaques (n = 6), and normal donor peripheral blood leukocytes (n = 3) were studied as controls. Total RNA was extracted from all skin specimens, as well as peripheral blood leukocytes from MF (n = 3) and Sezary patients (n = 7), and was converted to cDNA by reverse transcriptase. Polymerase chain reaction amplification of cDNAs using interleukin 2 (IL-2), IL-4, IL-5, IL-10, and interferon gamma-specific primers was used to differentiate Th1-type responses (IL-2+ and interferon gamma +) from Th2-type responses (IL-4+, IL-5+, and IL-10+). beta-actin specific primers were included as a positive control for mRNA integrity. All MF specimens contained mRNAs for IL-2 and interferon gamma limited to epidermis but not IL-4, IL-5, or IL-10. In contrast, Sezary skin and blood showed a cytokine mRNA pattern dominated by IL-4, IL-5, and IL-10. MF blood showed a pattern similar to normal peripheral blood T cells with mixed detection of all T-helper cell cytokine mRNAs. All psoriasis samples contained mRNAs for IL-2 and interferon gamma in both epidermis and dermis with no IL-4 or IL-10 in either compartment. These findings demonstrate that the cutaneous lesions of MF are characterized by an epidermal Th1-type cytokine profile, whereas both the blood and skin of patients with Sezary syndrome is characterized by a Th2-type profile. This work suggests that differences in cytokine production may be related to the pathophysiology and clinical presentation in cutaneous T-cell lymphoma.

Base Sequence↗

PubMedDate not supplied

Geometrical aspects of computed tomography: sensitivity profile and exposure profile.

A simple model has been developed for the generation of theoretical sensitivity and exposure profiles perpendicular to the tomographic plane in computed x-ray tomography. The model incorporates the functional dependence on scanner geometry, focal spot size and shape, and detector sensitivity. The sensitivity and exposure profiles are best depicted as the convolution of functions, when appropriately scaled, describing the focal spot intensity distribution and the transmittance of the pre- and postpatient collimators. Predictions of the model agree well with experimental results on both sensitivity and exposure profiles for small and large nominal slice thicknesses from five different computed tomography (CT) x-ray systems. The CT x-ray systems selected represent both state of the art and older scanner models. Comparisons are also made on the degree of matching of the sensitivity and exposure profiles for each scanner which can be used as a measure of geometrical efficiency in the direction perpendicular to the tomographic plane.

Humans↗

PubMed2006

The use of in vitro peptide binding profiles and in silico ligand-receptor interaction profiles to describe ligand-induced conformations of the retinoid X receptor alpha ligand-binding domain.

It is hypothesized that different ligand-induced conformational changes can explain the different interactions of nuclear receptors with regulatory proteins, resulting in specific biological activities. Understanding the mechanism of how ligands regulate cofactor interaction facilitates drug design. To investigate these ligand-induced conformational changes at the surface of proteins, we performed a time-resolved fluorescence resonance energy transfer assay with 52 different cofactor peptides measuring the ligand-induced cofactor recruitment to the retinoid X receptor-alpha (RXRalpha) in the presence of 11 compounds. Simultaneously we analyzed the binding modes of these compounds by molecular docking. An automated method converted the complex three-dimensional data of ligand-protein interactions into two-dimensional fingerprints, the so-called ligand-receptor interaction profiles. For a subset of compounds the conformational changes at the surface, as measured by peptide recruitment, correlate well with the calculated binding modes, suggesting that clustering of ligand-receptor interaction profiles is a very useful tool to discriminate compounds that may induce different conformations and possibly different effects in a cellular environment. In addition, we successfully combined ligand-receptor interaction profiles and peptide recruitment data to reveal structural elements that are possibly involved in the ligand-induced conformations. Interestingly, we could predict a possible binding mode of LG100754, a homodimer antagonist that showed no effect on peptide recruitment. Finally, the extensive analysis of the peptide recruitment profiles provided novel insight in the potential cellular effect of the compound; for the first time, we showed that in addition to the induction of coactivator peptide binding, all well-known RXRalpha agonists also induce binding of corepressor peptides to RXRalpha.

Amino Acid Sequence↗

PubMed2000

Facial growth in a cleft palate patient treated with the Herbst appliance: a long-term profile roentgenographic and roentgen stereometric analysis of profile changes and displacement of the jaws.

OBJECTIVE: To monitor facial development in a patient with cleft palate who was treated with the Herbst appliance. Monitoring was in terms of changes in the skeletal profile and growth in the circummaxillary sutures and temporomandibular joints (TMJs). DESIGN: Prospective profile roentgenography (between the ages of 6 and 20 years) and roentgen stereometric analysis (between the ages of 8 and 19 years). SETTING: Center for Craniofacial Anomalies and Department of Plastic and Reconstructive Surgery, Malmö University Hospital, Malmö, Sweden. PATIENT: Boy with cleft of the soft and posterior part of the hard palate and marked facial convexity. INTERVENTIONS: Surgical repair of the soft palate at age 9 months, velopharyngeal flap at age 8 years, and insertion of implants under general anesthesia and treatment with the Herbst appliance at age 11 years. Roentgen examinations were performed in connection with continued clinical evaluations and treatment. MAIN OUTCOME MEASURES: Profile roentgenograms were traced and measured by one of the authors using conventional point-based analysis. Stereo roentgenograms were digitized by the Department of Orthopedic Surgery, Malmö University Hospital. RESULTS: The direction of profile changes was partly discordant with the direction of articular growth in the circummaxillary sutures and TMJs. The successful treatment result was accomplished by a temporary influence on sagittal growth direction in the circummaxillary sutures and on rotational growth direction in the TMJs, combined with a favorable natural remodeling and articular growth pattern. CONCLUSIONS: The mode of growth by which treatment aims were reached was partly unexpected, i.e., discordant with the generally accepted principal concept that treatment with the Herbst appliance positions the mandible forward.

Adolescent↗

PubMed2000

Nondestructive Angle-resolved X-ray Depth Profiling: Interpretation of Angle-resolved Profiles Using a Monte Carlo Approach.

A technique has been developed for the interpretation of composition-depth profiles from angle-resolved X-ray data using a Monte Carlo electron scattering simulation. This is a nondestructive depth profiling procedure. Software has been developed that uses a Monte Carlo scattering simulation to generate the signal intensity from a multilayer sample for any combination of primary beam angle of incidence and take-off angle to the X-ray detector. An interactive C++ application uses this simulation to interpret measured angle-resolved depth profiles. The method has been tested using a custom-made Ag/Al "staircase" sample containing two layers each of Ag and Al. Using the technique, it is possible to quantify the composition-depth profile for the two- and three-layer "steps" of the sample. Qualitative information may be gained about the four-layer area of the sample.

Journal Article↗

PubMed2003

Profile-profile alignment: a powerful tool for protein structure prediction.

The problem of computing the tertiary structure of a protein from a given amino acid sequence has been a major subject of bioinformatics research during the last decade. Many different approaches have been taken to tackle the problem, the most successful of which are based on searching databases to identify a similar amino acid sequence in the PDB and using the corresponding structure as a template for modeling the structure of the query sequence. An important advance for the evaluation of sequence similarity in this context has been the use of a frequency profile that represents a part of the protein sequence space close to the query sequence instead of the query sequence itself. In this paper, we present a further extension of this principle by using profiles instead of the template sequences, also. We show that, by using our newly developed scoring model, the profile-profile alignment approach is able to significantly outperform current state of the art methods like PSI-BLAST, HMMs, or threading methods in a fold recognition setup. This is especially interesting since we show that it holds for closely related sequences as well as for very distantly related ones.

Algorithms↗

PubMed1998

A simple mathematical model applied to selection of the sodium profile during profiled haemodialysis.

BACKGROUND: Among dialysis patients in the last 10 years the incidence of intradialytic dysequilibrium syndrome and symptomatic hypotension has increased significantly. Profiled haemodialysis (PHD), a new dialysis technique based on intradialytic modulation of the dialysate sodium concentration according to pre-elaborated individual profiles, has been set up to reduce intradialytic imbalances and the incidence of dysequilibrium syndrome and symptomatic hypotension. The present paper illustrates a new mathematical model for solute kinetics, single-compartment for sodium and two-compartment for urea, aimed at improving the use of PHD. The model allows the sodium profile to be elaborated a priori, before each dialysis session, according to the patient's clinical needs and respecting the individual sodium mass removal and weight gain. METHOD: The mathematical model was first derived and then applied to determining a rational dialysate sodium profile. A procedure which allows the method to be tuned to individual clinical needs on the basis of routine measurements performed before each session is also presented. The proposed method was validated in vivo during seven dialysis sessions, each performed on a different patient. RESULTS: The comparison between data predicted by the model and those obtained in vivo shows a good correspondence in particular concerning the time pattern of blood urea and sodium. The comparison between the model prediction and in vivo determined sodium and urea plasma curves showed standard deviations (2.25 mEq/l for sodium and 0.87 mmol/l for urea) only slightly higher than those attributable to laboratory measurement errors. Moreover, in vivo implementation of PHD by our model enables one to remove an amount of sodium mass comparable with the a priori quantity predicted by the model.

Aged↗

PubMed2005

Chemostat culture characterization of Escherichia coli mutant strains metabolically engineered for aerobic succinate production: a study of the modified metabolic network based on metabolite profile, enzyme activity, and gene expression profile.

Various Escherichia coli mutant strains designed for succinate production under aerobic conditions were characterized in chemostat. The metabolite profiles, enzyme activities, and gene expression profiles were studied to better understand the metabolic network operating in these mutant strains. The most efficient succinate producing mutant strain HL27659k was able to achieve a succinate yield of 0.91 mol/mol glucose at a dilution rate of 0.1/h. This strain has the five following mutations: sdhAB, (ackA-pta), poxB, iclR, and ptsG. Four other strains involved in this study were HL2765k, HL276k, HL2761k, and HL51276k. Strain HL2765k has mutations in sdhAB, (ackA-pta), poxB and iclR, strain HL276k has mutations in sdhAB, (ackA-pta) and poxB, strain HL2761k has mutations in sdhAB, (ackA-pta), poxB and icd, and strain HL51276k has mutations in iclR, icd, sdhAB, (ackA-pta) and poxB. Enzyme activity data showed strain HL27659k has substantially higher citrate synthase and malate dehydrogenase activities than the other four strains. The data also showed that only iclR mutation strains exhibited isocitrate lyase and malate synthase activities. Gene expression profiles also complemented the studies of enzyme activity and metabolites from chemostat cultures. The results showed that the succinate synthesis pathways engineered in strain HL27659k were highly efficient, yielding succinate as the only major product produced under aerobic conditions. Strain HL27659k was the only strain without pyruvate accumulation, and its acetate production was the least among all the mutant strains examined.

Aerobiosis↗

PubMed1999

p75NTR immunoreactivity in the rat dentate gyrus is mostly within presynaptic profiles but is also found in some astrocytic and postsynaptic profiles.

To localize neurotrophin binding sites within the rat dentate gyrus, the distribution of low-affinity p75 neurotrophin receptor (p75NTR) immunoreactivity (IR) was examined by using antiserum raised against the cytoplasmic domain of the receptor. Semiquantitative electron microscopic examination of p75NTR-labeled sections showed that most p75NTR-labeled profiles were axons and axon terminals (72% from a total of 3,975); p75NTR-IR was observed throughout the extent of these structures and was not limited to the plasmalemmal surface. Axons and axon terminals containing p75NTR-IR were distributed in approximately equal proportions across the hilus, infragranular zone, and the inner, middle, and outer molecular layers; significantly fewer p75NTR-labeled profiles were observed in the granule cell layer. Axon terminals containing p75NTR-IR, which made synapses (296 of 552), formed equal proportions of symmetric and asymmetric synapses, primarily with the shafts and spines of dendrites. The remainder of the p75NTR-labeled terminals apposed unlabeled somata and dendrites without forming synapses in the single sections analyzed. In addition, p75NTR-IR was contained within some astrocytes (17.5% of 3,975) and dendritic shafts (3%) and spines (5%). Within dendritic spines, p75NTR-IR was most often associated with the plasmalemmal surface near postsynaptic densities; in dendritic shafts, p75NTR labeling was associated with microfilaments distant from the plasmalemma. Most p75NTR-labeled dendritic profiles were located in the molecular layer, and some originated from granule cells. Moreover, in some granule cell somata (<1% of 3,975), p75NTR-IR was associated with endosomes. The primary localization of p75NTR-IR to presynaptic structures in the dentate gyrus, presumably arising from medial septal/diagonal band neurons, agrees with previous reports. However, p75NTR-IR within some astrocytes, somata, and dendritic structures suggests that this receptor may also be involved in controlling local neurotrophin levels and possibly modulating the viability of local hippocampal cell populations.

Animals↗

PubMed2006

Cocaine profiling for strategic intelligence purposes, a cross-border project between France and Switzerland. Part I. Optimisation and harmonisation of the profiling method.

Optimisation and harmonisation of analytical and statistical methodology have been carried out between two forensic laboratories (Lausanne, CH and Lyon, F) in order to provide drug intelligence for cross-border cocaine seizures. The aim was to improve the gas chromatographic analysis of cocaine samples for profiling. Some important validation parameters were tested to verify the developed method and demonstrate its profiling capacity: the selectivity of the method with retention time reproducibility, the choice of a derivatisation agent improving the chromatography (MSTFA, BSA, TMSI and BSTFA+TMCS 1%), the cutting agents influence (matrix effect), the influence of the sample storage conditions and the sample quantity to weigh for analyses. Eight main alkaloids, which represent the sample signature, have been selected: ecgonine methyl ester, ecgonine, tropacocaine, benzoylecgonine, norcocaine, cis- and trans-cinnamoylcocaine and 3,4,5-trimethoxycocaine. Their stability in the solvent used (CHCl(3)/pyridine) was demonstrated. In order to reach the final objective, which is the comparison of samples seized and analyzed in two different laboratories, the harmonisation of the profiling method between the two laboratories had to be ensured and is the subject of ongoing research.

Journal Article↗

PubMed1998

Comparison of the modified biophysical profile to a "new" biophysical profile incorporating the middle cerebral artery to umbilical artery velocity flow systolic/diastolic ratio.

OBJECTIVES: The objective of this study was to determine whether the addition of the middle cerebral to umbilical artery systolic/diastolic velocity waveform ratio to the modified biophysical profile would improve perinatal outcome in patients at high risk. STUDY DESIGN: A prospective, randomized outcome study of patients referred to the perinatal laboratory for antenatal surveillance was undertaken. Six hundred sixty-five patients were randomized to two antenatal surveillance protocols: group 1, modified biophysical profile; and group 2, modified biophysical profile plus evaluation of the middle cerebral artery to umbilical artery systolic/diastolic ratio. Patients were followed up serially and neonatal outcome data including gestational age at delivery, birth weight, incidence of cesarean section delivery for fetal distress, admission to the neonatal intensive care unit, days in the neonatal intensive care unit, and the presence of significant neonatal morbidity were tabulated. RESULTS: The total population showed no statistical difference in outcome parameters between groups 1 and 2. However, a subgroup of patients evaluated for suspected uteroplacental insufficiency did show a significant reduction in caesarean section for fetal distress in group 2 patients. CONCLUSIONS: In a subgroup of patients at risk for uteroplacental insufficiency, the addition of the middle cerebral/umbilical artery ratio to an antenatal surveillance protocol should be expected to improve perinatal outcome.

Adult↗

PubMed1980

Micturitional static urethral pressure profile: a method of recording urethral pressure profile during voiding and the implications.

Using a tri-lumen graduated 10F catheter we attempted to record static (lateral) pressures at successive points in the urethra, synchronous with intravesical pressure recorded during voiding. Based on our understanding of the essential physical principles described by many earlier investigators we attempted numerous studies in a predominantly male population, which included normal male and female subjects, and male subjects with bladder outlet obstruction of varied etiology. We also attempted to evaluate the effects of the Valsalva maneuver, augmenting the detrusor contraction and artificial distal obstruction (penile compression) on the micturitional static urethral pressure profiles. Studies also were performed to compare the static urethral pressure profiles obtained with the anterograde (catheter withdrawal) and with the retrograde (catheter insertion during voiding) techniques. All of these studies have helped in understanding the various factors, such as double obstructions, artifactual catheter obstructions and incompetent distal sphincter mechanisms, in the interpretation of the micturitional static urethral pressure profile.

Adult↗

PubMed1990

Disposition and metabolic profiling of the penetration enhancer Azone. I. In vitro studies: urinary profiles of hamster, rat, monkey, and man.

Chain-labeled 14C-Azone was intravenously administered to hamster, monkey, and rat, to compare its metabolic profile with that obtained previously in humans after dermal application. Azone-derived radioactivity was excreted predominantly in the urine for both hamster and monkey, which is similar to the disposition in humans. Metabolic profiling in urine revealed extensive systemic metabolism to occur in all species studied. The main fraction of the metabolites was most polar in man, followed by rat, monkey, and hamster. Traces of the parent compound were detectable only in hamster urine. Although some of the polar major human metabolites were also present in rat urine, the animals were unsuitable for collecting metabolites of Azone observed in humans. In rats, complete cleavage of the dodecyl side chain was ruled out by administering Azone that had been labeled at two distinct positions of the molecule. Additionally, oral administration of Azone to rats resulted in the same metabolic profile as intravenous administration, indicating that gastrointestinal metabolism does not occur or is similar to systemic metabolism.

Animals↗

PubMed2006

Improvement of cardiovascular risk profile in an elderly population of low social level: the ICON (Improving Cardiovascular risk profile in Older Neapolitans) study.

Older age and low socio-economic conditions are associated with poor control of cardiovascular risk factors (RFs). We assessed the prevalence and awareness of cardiovascular RFs in 503 elderly outpatients of low social status attending two public Internal Medicine clinics in Naples, and studied the interaction of education and employment level with risk profile. The therapeutic intervention was oriented to improve patients' motivation through a positive patient-physician relationship, in keeping with the current guidelines for hypertension. The effect of treatment was evaluated by comparing retrospectively the level of cardiovascular RFs at baseline and at the last follow-up examination performed within 31 October 2005. Only 33.3% of patients (age=68+/-6 years) had attended primary school. Overall (current or previous) employment level was also low. Obesity, hypertension and dyslipidaemia were present in most patients, diabetes in 17.3% of them. In all 8.0% of hypertensives, 16.1% of diabetics and 24.7% of dyslipidaemiacs were unaware of their diseases. Cardiovascular risk profile was worse at lower educational and employment levels. Odds ratios for the metabolic syndrome were 0.28 (95% confidence interval (CI)=0.15-0.52) and 0.35 (0.20-0.62) in the most qualified of three education and employment groups, respectively, compared to the lowest ones. The level of all cardiovascular RFs was effectively reduced during treatment. Control rate of most RFs improved significantly (for hypertension, from 12.8 to 36.5%, P<0.001). These patients had a high prevalence of cardiovascular RFs, which correlated with their educational and work activity levels. Awareness of their health status was unsatisfactory. Treatment, specifically addressing patient-physician relationship, favourably affected cardiovascular risk profile.

Aged↗

PubMed1993

A comparison of human and bovine Escherichia coli O157:H7 isolates by toxin genotype, plasmid profile, and bacteriophage lambda-restriction fragment length polymorphism profile.

Foods of bovine origin have been linked to human disease outbreaks caused by Escherichia coli O157:H7 and may be linked to the more common sporadic cases as well. In this study, E. coli O157:H7 from the bovine reservoir (22 isolates: 12 from dairy and 10 from beef breed cows) and from human patients (50 isolates from sporadic human infections) were compared using Shiga-like toxin genotypes, plasmid profiles, and DNA restriction fragment length polymorphisms identified with a bacteriophage lambda probe (lambda-RFLP). Twenty-three lambda-RFLP profiles, 4 Shiga-like toxin genotypes, and 8 plasmid profiles were identified among the isolates tested. Together the typing methods distinguished 43 strains, of which 3 were isolated from both humans (5 isolates) and cattle (6 isolates; 5 from dairy herds). These data demonstrate the value of lambda-RFLP as a means of strain identification for E. coli O157:H7.

Animals↗

PubMed1996

Physician profiling: applications for the Robert Wood Johnson Profiling Project database.

An overview of the applications and limitations of the Center for Research in Ambulatory Health Care Administration (CRAHCA) Profiling Project database funded by The Robert Wood Johnson Foundation is presented. The Profiling Project collects data from 77 practices and links organizational, provider, and patient demographics to administrative data. The Project's database has the capacity (1) to profile physicians based on the Resource Based Relative Value Scale (RBRVS) relative value units as a measure of work and (2) to identify practice patterns as defined by procedures used by physicians with the same diagnosis. The Project will further explore variations between physicians and specialties based on systems of care, physician specialty, and patient differences. The comparative reports generated from these data provide comparisons on selected indicators for participating practices.

Ambulatory Care↗