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Effects of steady-state and variable ozone concentration profiles on pulmonary function.

Measurements of ambient ozone (O2) concentration during daylight hours have shown a spectrum of concentration profiles, from a relatively stable to a variable pattern usually reaching a peak level in the early afternoon. Several recent studies have suggested that in estimating exposure dose (O3 concentration [C] x exposure time [T] x ventilation [V]), O3 concentration needs to be weighted more heavily than either ventilation or duration of exposure in the estimates. In this study we tested the hypothesis that regardless of concentration pattern and exposure rate the same exposure dose of O3 will induce the same spirometric response. We exposed 23 healthy male volunteers (20 to 35 yr of age) for 8 h to air, 0.12 ppm O3 (steady-state), and a triangular exposure pattern (concentration increased steadily from zero to 0.24 ppm over the first 4 h and decreased back to zero by 8 h). During the first 30 min of each hour, subjects exercised for 30 min at minute ventilation (VE) approximately 40 L/min. The order of the exposures was randomized, and the exposures were separated by at least 7 days. The response patterns over the 8-h periods for spirometric variables in both O3 exposures were statistically different from air exposure changes and from each other. For FEV1 the p values were 0.017 between air and steady-state profile, 0.002 between air and triangular profile, and 0.037 between steady-state and triangular profiles. Although in the triangular pattern of exposure the maximal O3 concentration was reached at 4 h, the maximum FEV1 decrement (10.2%) was observed at 6 h of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of arginine, L-alanyl-L-glutamine or taurine on neutrophil (PMN) free amino acid profiles and immune functions in vitro.

The objective of this study was to determine the effects of arginine, L-alanyl-L-glutamine (Ala-Gln) or taurine on polymorphonuclear leucocyte (PMN) free amino acid profiles, superoxide anion (O2-) generation, hydrogen peroxide (H2O2) formation and released myeloperoxidase activity (MPO). Arginine led to significant increases in PMN arginine, ornithine, citrulline, aspartate, glutamate and alanine concentrations as well as increased H2O2-generation and MPO activity while O(2-)-formation was decreased. Ala-Gln caused significant increases in PMN free glutamine, alanine, asparagine, aspartate, glutamate, ornithine, arginine, serine and glycine concentrations and increased PMN immune functions. Taurine significantly increased PMN free taurine profiles, reduced PMN neutral amino acid content and decreased H2O2- and O(2-)-formation while MPO was increased. Altogether, the pharmacological regimens which enhance the supply of arginine, Ala-Gln or taurine in whole blood significantly affect PMN "susceptible free amino acid pool". This may be one of the determinants in PMN nutrition considerably influencing PMN immune functions. Introduction Polymorphonuclear leucocytes (PMN) ensure an important part of non-specific cell-mediated immunity and play a crucial role in the host defense

Adult↗

Using Functional Independence Measure profiles as an index of outcome in the rehabilitation of brain-injured patients.

Rehabilitation preserves and restores everyday functions in people who have disabilities. Functional change for patients undergoing a rehabilitation program is the best measure of the effectiveness of the rehabilitation program. One tool used for measuring function is the Functional Independence Measure (FIM). However, there are problems with the psychometric properties of FIM. This article presents a method for using FIM with median patient profiles. We show the method with data from 53 patients. The results show a relationship between the pattern of recovery and the length of stay in the unit. Spearman's rank order correlation coefficients confirm this observation. Median patient profiles prove to be a useful method of displaying data as outcome measures of the effectiveness of a rehabilitation program.

Activities of Daily Living↗

Versatile gene-specific sequence tags for Arabidopsis functional genomics: transcript profiling and reverse genetics applications.

Microarray transcript profiling and RNA interference are two new technologies crucial for large-scale gene function studies in multicellular eukaryotes. Both rely on sequence-specific hybridization between complementary nucleic acid strands, inciting us to create a collection of gene-specific sequence tags (GSTs) representing at least 21,500 Arabidopsis genes and which are compatible with both approaches. The GSTs were carefully selected to ensure that each of them shared no significant similarity with any other region in the Arabidopsis genome. They were synthesized by PCR amplification from genomic DNA. Spotted microarrays fabricated from the GSTs show good dynamic range, specificity, and sensitivity in transcript profiling experiments. The GSTs have also been transferred to bacterial plasmid vectors via recombinational cloning protocols. These cloned GSTs constitute the ideal starting point for a variety of functional approaches, including reverse genetics. We have subcloned GSTs on a large scale into vectors designed for gene silencing in plant cells. We show that in planta expression of GST hairpin RNA results in the expected phenotypes in silenced Arabidopsis lines. These versatile GST resources provide novel and powerful tools for functional genomics.

Arabidopsis↗

Integrative machine learning models to unravel gut microbial dysbiosis and functional disruption in polycystic ovary syndrome.

OBJECTIVE: To study gut microbial diversity and metabolic pathway disruptions in women with PolyCystic Ovary Syndrome (PCOS) compared with healthy controls, and to evaluate the diagnostic potential of microbiome-driven machine learning models. DESIGN: Case-controlled metagenomic data analysis SUBJECTS: Gut metagenomic data from women diagnosed with PCOS and age-matched healthy female controls EXPOSURE: Presence of PCOS MAIN OUTCOME MEASURES: The primary outcome measures will include gut microbial alpha and beta diversity indices, microbial taxon abundance, functional pathway profiles, predicted metabolite levels, microbe-functional pathway-metabolite interaction networks, and the diagnostic accuracy of microbiome-based machine learning models. RESULTS: Alpha and beta diversity analyses revealed marked gut microbial dysbiosis in women with PCOS, despite comparable species richness to healthy controls. Differential abundance analysis identified 41 significantly altered microbial species, including enrichment of proinflammatory taxa, such as Bacteroides vulgatus and Ruminococcus gnavus, and depletion of beneficial commensals, including Roseburia hominis and Prevotella copri. These compositional shifts indicate a proinflammatory microbial community structure in PCOS. Functional profiling demonstrated the upregulation of pathways involved in nucleotide turnover, lipid and carbohydrate metabolism, and neurotransmitter synthesis, potentially contributing to metabolic and neuroendocrine disruption. Network analysis revealed fragmented and unstable microbial-metabolite associations in PCOS compared with cohesive networks in controls. Microbiome-based machine learning models achieved a diagnostic accuracy of 84.25% (area under the curve 0.93), underscoring their predictive potential. CONCLUSION: The gut microbiome in PCOS is characterized by a proinflammatory community structure and disrupted metabolic pathways. These findings demonstrate the diagnostic potential of microbiome-based models and underscore the gut microbiome as a promising target for therapeutic interventions in the management of PCOS.

Polycystic Ovary Syndrome↗

[Significance of the estriol profile as an endogenous function test of the fetoplacental unit].

Oestriol profile represents a functional parameter of the foetal placental unit. Basing on the fact that maternal cortisol regulates oestriol production via a negative feedback action on foetal hypothalamus, relative low serum oestriol concentrations in the morning are compared with increasing oestriol concentrations in the evening, spaced out at short-time intervals, pointing to a dynamic oestriol production of the foetal placental unit. The mean oestriol concentration in the morning and maximum peak values in the evening were determined as criteria of the oestriol profile. In normal pregnancies (n = 74) the oestriol concentration in the morning increases from an average value of 8.0 ng/ml in the 32nd/33rd week to 11.6 ng/ml in the 40th/41st week of gestation. During the same period the peak values in the evening rise from 8.8 to 15.9 ng/ml. The mean cortisol concentrations in normal pregnancies (n = 49) from 32nd to 41st week are in the range of 333 +/- 88 ng/ml in the morning and 205 +/- 66 ng/ml in the evening. There is no significant difference between individual weeks. The predictive value of the oestriol profile was assessed regarding the foetal outcome of 55 high-risk pregnancies. 32 newborn infants exhibited intrauterine growth retardation with birth weights below the 10th and 5th percentile, respectively. In this group 6 patients exhibited low oestriol values in the morning, whereas 12 demonstrated a pathological profile in the evening. In 11 of 12 high-risk pregnancies exhibiting pathological oestriol profile growth, retardation of the newborn was found to be below the 5th percentile. Cortisol concentrations do not significantly differ between normal and high-risk pregnancies.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian Rhythm↗

The profile of memory function in children with autism.

A clinical memory test was administered to 38 high-functioning children with autism and 38 individually matched normal controls, 8-16 years of age. The resulting profile of memory abilities in the children with autism was characterized by relatively poor memory for complex visual and verbal information and spatial working memory with relatively intact associative learning ability, verbal working memory, and recognition memory. A stepwise discriminant function analysis of the subtests found that the Finger Windows subtest, a measure of spatial working memory, discriminated most accurately between the autism and normal control groups. A principal components analysis indicated that the factor structure of the subtests differed substantially between the children with autism and controls, suggesting differing organizations of memory ability.

Adolescent↗

Stability of the Iceberg Profile as a function of perceived difficulty in defeating an opponent.

9 starters and 8 nonstarters of a university women's softball team completed the Profile of Mood States prior to playing the team perceived to be the most and least difficult to defeat in their conference. A significant interaction indicated that nonstarters displayed higher fatigue prior to playing the opponent perceived as most difficult to defeat. In addition, significant mean differences were found between starters and nonstarters on constructs of Anger, Confusion, Tension, and Depression, suggesting that nonstarters may not share same psychological profile as their peers who start.

Adult↗

Profiles of cognitive functioning in chronic spinal cord injury and the role of moderating variables.

A traumatic spinal cord injury (SCI) is accompanied by a documented moderate to severe head injury in significant numbers of SCI patients. In a previous study (Dowler et al., 1995), cognitive deficits were found in 41% of the SCI individuals who were studied with a chronic injury from a traumatic event. The present study investigated whether clinically useful subtypes of normal and impaired cognition could be identified in a chronic (M = 17 years postinjury) SCI sample using a cluster analysis of neuropsychological test performance. A battery of 16 neuropsychological tests was administered to 91 SCI patients and 75 control participants. Composite scores, reflecting performance in different cognitive domains, were derived from a factor analysis of the battery, and these scores were then used in the cluster analysis. A six-cluster solution generated the most distinct and clinically relevant SCI group profiles. Two of the cognitive profiles were characterized by normal functioning in all cognitive domains, but they were distinguished by differences in performance levels. The remaining four SCI groups (60% of the sample) showed clinically significant deficits in one or more cognitive domains, with different groups showing moderate attention and processing speed deficits, mild deficits in processing speed, executive processing difficulties, or moderate memory impairments. Though age and premorbid intellectual ability were strong predictors of the cognitive profiles of some SCI groups, when these factors were controlled, the findings suggested that the patterns of cognitive impairment were likely due to a potential concomitant head injury.

Adult↗

Assessment of cellular profile and lung function with repeated bronchoalveolar lavage in individual mice.

In this study, we sought to develop procedures that would enable repeated bronchoalveolar lavage (BAL) in individual mice on multiple occasions. To achieve this objective, we first developed the procedures that would allow individual mice to survive a whole lung lavage, and then tested whether, on subsequent days, there was an effect of this initial BAL on the cell profile, lung permeability, and baseline respiratory function. Our results demonstrate that the repeated lavage procedure can be readily carried out in individual mice of different strains on multiple occasions. The lavage procedure itself results in immediate increases in respiratory system resistance and concomitant decreases in compliance, but these parameters return to prelavage values by the 2nd or 3rd day postlavage. Lavage also induces variable increases in inflammatory cells depending on the strain used. However, in all three strains examined here (A/J, BALB/c, and C3H/HeJ), inflammatory cell numbers returned to baseline values within 3 days after an initial lavage procedure. The ability to perform repeated BAL in individual mice should prove to be an extremely useful tool in a variety of functional genomic studies in the lung.

Airway Resistance↗

Effects of ornithine on neutrophil (PMN) free amino acid and alpha-keto acid profiles and immune functions in vitro.

The objective of this study was to determine the effects of ornithine on polymorphonuclear leucocyte (PMN) free amino- and alpha-keto acid profiles, superoxide anion (O2-) generation, hydrogen peroxide (H2O2) formation and released myeloperoxidase activity (MPO). Exogenous ornithine significantly increased PMN asparagine, glutamine, aspartate, glutamate, arginine, citrulline, alanine, alpha-ketoglutarate and pyruvate as intracellular ornithine increased. Concerning PMN immune function markers ornithine increased H2O2-generation and MPO activity while O2- -formation was decreased. We believe therefore that ornithine is important for affecting PMN "susceptible free amino- and alpha-keto acid pool" although the mechanisms are not yet clear. This may be one of the determinants in PMN nutrition considerably influencing and modulating PMN host defense capability.

Adult↗

Lipid profiles and endothelial function with low-dose hormone replacement therapy in postmenopausal women at risk for coronary artery disease: a randomized trial.

AIMS: To compare the effect of low (0.3 mg) and commonly prescribed (0.625 mg) doses of conjugated equine estrogens (CEE) on brachial artery flow-mediated dilation and lipid profiles. METHODS AND RESULTS: Twenty-five postmenopausal women (mean age, 65+/-6 years) at risk for coronary artery disease (CAD) (> or =2 established risk factors) entered a double-blind crossover study. Brachial artery endothelial function was evaluated by means of high-resolution vascular echography. Both CEE doses significantly decreased total cholesterol (-13%, 0.3 mg; -15%, 0.625 mg), low-density lipoprotein-cholesterol (LDL-C) (-15%, 0.3 mg; -16%, 0.625 mg), and lipoprotein(a) (-28%, 0.3 mg; -39%, 0.625 mg) values from baseline levels. Both treatments increased high-density lipoprotein-cholesterol (HDL-C) (5%, 0.3 mg; 7%, 0.625 mg) and triglycerides (3%, 0.3 mg; 8%, 0.625 mg). There was no dose effect for changes in the LDL-C/HDL-C ratio (-21%, 0.3 mg; -23%, 0.625 mg). Both doses improved brachial artery dilation during reactive hyperemia by 63% over baseline. CONCLUSION: In women at risk for CAD, low-dose hormone replacement treatment (HRT) improves lipid profiles and brachial artery endothelial function comparably to the most commonly prescribed dose. The benefit:risk ratio of low-dose HRT provides an attractive option for postmenopausal women at risk for CAD.

Aged↗

Alterations in neutrophil (PMN) free intracellular alpha-keto acid profiles and immune functions induced by L-alanyl-L-glutamine, arginine or taurine.

The objective of this study was to determine the dose as well as duration of exposure-dependent effects of L-alanyl-L-glutamine, arginine or taurine on polymorphonuclear neutrophil (PMN) free alpha-keto acid profiles and, in a parallel study, on PMN immune functions. Exogenous L-alanyl-L-glutamine significantly increased PMN alpha-ketoglutarate, pyruvate PMN superoxide anion (O2-) generation, hydrogen peroxide (H2O2) formation and released myeloperoxidase (MPO) activity. Arginine also led to significant increases in alpha-ketoglutarate, pyruvate, MPO release and H2O2 generation. Formation of O2- on the other hand was decreased by arginine. Incubation with taurine resulted in lower intracellular pyruvate and alpha-ketobutyrate levels, decreased O2- and H2O2 formation and a concomitant significantly increased MPO activity. We therefore believe that considerable changes in PMN free-alpha-keto-acid profiles, induced for example by L-alanyl-L-glutamine, arginine or taurine, may be one of the determinants in cell nutrition that considerably modulates the immunological competence of PMN.

Adult↗

Locally defined protein phylogenetic profiles reveal previously missed protein interactions and functional relationships.

Phylogenetic profiles encode patterns of presence or absence of genes across genomes, and these profiles can be used to assign functional relationships to nonhomologous pairs of proteins (Pellegrini et al., Proc Natl Acad Sci USA 1999;96:4284-4288). Although it is well known that many proteins were created from combinations of domains, most of the existing implementations of phylogenetic profiles do not consider this fact. Here, we introduce an extension that considers the multidomain nature of proteins and test the method against the known interaction data sets. Whereas earlier implementations associated one entire sequence with one protein phylogenetic profile (Single-Profile), our method instead breaks the sequence into a set of segments of predetermined size and constructs a separate profile for each segment (Multiple-Profile). The results show that the Multiple-Profile method performs as well as the Single-Profile method. However, the two methods share, surprisingly, a small fraction of their predictions, indicating that the Multiple-Profile method can detect known interactions missed by the Single-Profile method. Thus, the Multiple-Profile method can be used with other methods to determine functional relationships on a genome scale with wider coverage.

Binding Sites↗

Targeted metabolite profiling provides a functional link among eucalypt taxonomy, physiology and evolution.

Adaptation to aridity is considered a major factor in the evolution of the genus Eucalyptus. For the first time, targeted metabolite profiling has uncovered a quantitative yet discrete phytochemical link with eucalypt taxonomy. The distribution of cyclitols among Eucalyptus species, and a range of other Australian tree genera, support their proposed functions in plant tissues and provide putative links with the acclimation of trees to arid environments.

Adaptation, Physiological↗

Testosterone plasma profiles, as a function of age in young bulls from the bovine double-muscled Belgian white blue breed a preliminary report.

Plasma testosterone (T) 10 hour-profiles were determined at 10-day intervals in 29 young double-muscled bulls from the BBB-V breed between the ages 130 days and 190 days. Age at onset of T pulsatile profiles allowed to distinguish 3 groups of animals: We hypothesize that early appearance of pulsatile T profiles might mean precocity in onset of male puberty and sexual maturity. If this assumption is true, determination of T plasma profiles at a well specified age, might allow early selection of sexually precocious and capable BBB-V males.

Journal Article↗

Synthesis and antitrypanosomal profile of new functionalized 1,3,4-thiadiazole-2-arylhydrazone derivatives, designed as non-mutagenic megazol analogues.

In this work we reported the synthesis and the trypanocidal profile of new 1,3,4-thiadiazole-2-arylhydrazone derivatives of nitroimidazole series (4) or phenyl series (5), designed by exploring the molecular hybridization approach between megazol (2) and guanyl hydrazone derivative (3). The evaluation of the activity against bloodstream trypomastigote forms of Trypanosoma cruzi forms lead us to identify a new potent trypamomicide prototype, that is, brazilizone A (4k), which present an IC50/24 h=5.3 microM.

Animals↗

Gastric sensorimotor functions and hormone profile in normal weight, overweight, and obese people.

BACKGROUND & AIMS: Peptide YY (PYY) levels are reported to be decreased in obesity. The relation between gastric functions, satiation, and gut hormones in obesity is incompletely understood. The aim of this study was to compare gastric volumes, emptying, maximum tolerated volumes, postchallenge symptoms, and selected gut hormones in normal, overweight, or obese healthy volunteers. METHODS: In 73 nonbulimic normal, overweight, or obese participants weighing less than 137 kg, we measured gastric emptying of solids and liquids by scintigraphy (gastric emptying half-time [GE t(1/2)]); gastric volumes by single-photon emission computed tomography; maximum tolerated volumes and symptoms by satiation test; and plasma leptin, ghrelin, insulin, glucagon-like peptide 1, and PYY levels. Groups were compared using 1-way analysis of covariance adjusted for sex. Univariate associations among measured responses were assessed using Spearman correlations. Multiple linear regression models, adjusting for weight and sex, assessed the independent ability of gastric functions and hormones to predict satiation volume. RESULTS: Obese and overweight subjects had significantly lower postprandial gastric volumes, higher fasting and postprandial insulin and leptin levels, and lower fasting ghrelin and lower postprandial reduction in ghrelin levels. PYY levels were not different in obese or overweight subjects compared with controls. The GE t(1/2) was correlated inversely with postprandial PYY; increased body weight was associated with faster GE t(1/2) of solids (r(s) = 0.33, P = .005) and liquids (r(s) = 0.24, P = .04). Postprandial changes in gastric volume and PYY were independent predictors of satiation (both P = .01). CONCLUSIONS: Overweight or obesity are associated with lower postprandial gastric volumes and normal PYY levels. Gastric emptying influences postprandial PYY levels. Postprandial PYY and gastric volume independently predict satiation volume in nonbulimic people across a wide body mass index range.

Adolescent↗