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At least 217 records · Page 12Linked to original sources
PubMed2004

Changes in connectivity profiles define functionally distinct regions in human medial frontal cortex.

A fundamental issue in neuroscience is the relation between structure and function. However, gross landmarks do not correspond well to microstructural borders and cytoarchitecture cannot be visualized in a living brain used for functional studies. Here, we used diffusion-weighted and functional MRI to test structure-function relations directly. Distinct neocortical regions were defined as volumes having similar connectivity profiles and borders identified where connectivity changed. Without using prior information, we found an abrupt profile change where the border between supplementary motor area (SMA) and pre-SMA is expected. Consistent with this anatomical assignment, putative SMA and pre-SMA connected to motor and prefrontal regions, respectively. Excellent spatial correlations were found between volumes defined by using connectivity alone and volumes activated during tasks designed to involve SMA or pre-SMA selectively. This finding demonstrates a strong relationship between structure and function in medial frontal cortex and offers a strategy for testing such correspondences elsewhere in the brain.

Adult↗
PubMed2006

Anatomical and functional significance of urogenital hiatus in primary urodynamic stress incontinence.

OBJECTIVES: To explore the correlations of anatomical and functional sonographic parameters of urogenital hiatus in primary urodynamic stress incontinence. METHODS: We reviewed retrospectively our urodynamic database from July 1996 to June 2003 and identified subjects with primary urodynamic stress incontinence who had had anatomical assessment of the lower urinary tract and the central part of the pelvic floor by ultrasound. The morphological changes that had occurred in the central pelvic floor were determined by the measurement of genitohiatal angle, genitohiatal distance and anorectal angle. RESULTS: A total of 396 women with a mean age of 48.8 +/- 10.7 (range, 26-82) years were included in the study. One hundred and eighteen subjects (29.8%) were postmenopausal. Stage I pelvic organ prolapse was found in 345 (87.1%) of the women, stage II in 19 (4.8%) and stage III in 32 (8.1%). The genitohiatal angle and genitohiatal distance were significantly and positively associated with resting and straining bladder neck angles. The genitohiatal angle was associated with bladder neck funneling and dependent cystocele during stress (r = 0.144, P = 0.016 and r = 0.140, P = 0.02, respectively), and it was negatively associated with functional profile length (r = -0.157, P = 0.012). The genitohiatal distance was negatively associated with functional profile length and maximum urethral closure pressure (r = -0.148, P = 0.018 and r = -0.227, P = 0.009, respectively). Increased genitohiatal distance was also related to a low Valsalva leak-point pressure (r = -0.199, P = 0.02). Multivariate analysis revealed that resting bladder neck angle was the independent factor for genitohiatal angle and genitohiatal distance. CONCLUSIONS: In primary urodynamic stress incontinence, an increased resting genitohiatal distance or genitohiatal angle on sonographic imaging implies anterior vaginal wall prolapse. In addition, an increased genitohiatal distance is associated with functional impairment of urethral closure.

Adult↗
PubMed1997

Studies on ulnar nerve compression neuropathies with a new computerised instrument--the intrins-o-meter.

From 1900-1995, 48 patients with ulnar nerve compression neuropathies were studied. Pinching grip, palmar adduction of the thumb, radical abduction of the index finger, and ulnar abduction of the little finger, were measured before and after operation with the new computerised intrins-o-meter. The data were processed, assessed statistically, and printed out. From the results of the four parameters mentioned above, a special Ulnar Nerve Function Profile (UNFP) was constructed. The series was subdivided in three groups A, B, C of which group A (n = 30) comprised pure ulnar nerve compression neuropathies. The results were categorized by analysing the Ulnar Nerve Function Profile, assessing the academical and functional recovery, and recording the presence or absence of Wartenberg's and Froment's signs before and after operation.

Case-Control Studies↗
PubMed2006

Single muscle fiber adaptations with marathon training.

The purpose of this investigation was to characterize the effects of marathon training on single muscle fiber contractile function in a group of recreational runners. Muscle biopsies were obtained from the gastrocnemius muscle of seven individuals (22 +/- 1 yr, 177 +/- 3 cm, and 68 +/- 2 kg) before, after 13 wk of run training, and after 3 wk of taper. Slow-twitch myosin heavy chain [(MHC) I] and fast-twitch (MHC IIa) muscle fibers were analyzed for size, strength (P(o)), speed (V(o)), and power. The run training program led to the successful completion of a marathon (range 3 h 56 min to 5 h 35 min). Oxygen uptake during submaximal running and citrate synthase activity were improved (P < 0.05) with the training program. Muscle fiber size declined (P < 0.05) by approximately 20% in both fiber types after training. P(o) was maintained in both fiber types with training and increased (P < 0.05) by 18% in the MHC IIa fibers after taper. This resulted in >60% increase (P < 0.05) in force per cross-sectional area in both fiber types. Fiber V(o) increased (P < 0.05) by 28% in MHC I fibers with training and was unchanged in MHC IIa fibers. Peak power increased (P < 0.05) in MHC I and IIa fibers after training with a further increase (P < 0.05) in MHC IIa fiber power after taper. These data show that marathon training decreased slow-twitch and fast-twitch muscle fiber size but that it maintained or improved the functional profile of these fibers. A taper period before the marathon further improved the functional profile of the muscle, which was targeted to the fast-twitch muscle fibers.

Adaptation, Physiological↗
PubMed1987

Selective IgM deficiency in adults: phenotypically and functionally altered profiles of peripheral blood lymphocytes.

Peripheral blood lymphocytes from four patients with selective IgM deficiency were examined phenotypically and functionally. Although B cell subpopulations determined by surface immunoglobulins were within normal or nearly normal range, T8+ cells were significantly increased and T4/T8 ratios were inverted in three patients. IgM specific hyporesponsiveness in the PWM-driven immunoglobulin production system was observed in all four patients. Ia-like antigen positive T cells were increased in two patients; both had increased Leu2a+ Leu15+ suppressor-effector cells. In addition, Leu3a+ Leu8+ suppressor-inducer cells were increased in one of these two patients. Excessive (either IgM-specific or isotype non-specific) suppressor activity of T cells and IgM specific hyporesponsiveness of non-T cells were observed in these two patients in the recombination plaque assay. Although these results showed the complexity of the pathogenesis of this syndrome, they suggested that suppressor-associated T cells may play a role in some patients with selective IgM deficiency.

Adult↗
PubMed1994

Stroke risk profile: adjustment for antihypertensive medication. The Framingham Study.

BACKGROUND AND PURPOSE: We sought to modify existing sex-specific health risk appraisal functions (profile functions) for the prediction of first stroke that better assess the effects of the use of antihypertensive medication. METHODS: Health risk appraisal functions were previously developed from the Framingham Study cohort. These functions were Cox proportional hazards regression models relating age, systolic blood pressure, diabetes mellitus, cigarette smoking, prior cardiovascular disease, atrial fibrillation, left ventricular hypertrophy by electrocardiogram, and the use of antihypertensive medication to the occurrence of stroke. Closer examination of the data indicated that antihypertensive therapy effect is present only for systolic blood pressures between 110 and 200 mm Hg. Adjustments to the regressions to better fit the observed data were developed and tested for statistical significance and goodness-of-fit of the model residuals. RESULTS: Modified functions more consistent with the data were developed, and, from these, tables to evaluate 10-year risk of first stroke were computed. CONCLUSIONS: The stroke profile can be used for evaluation of the risk of stroke and suggestion of risk factor modification to reduce risk. The effect of antihypertensive therapy in the evaluation of stroke risk can now be better evaluated.

Aged↗
PubMed1990

Lymphokine mRNA profile and functional analysis of a human CD4+ clone with unique antitumor specificity isolated from renal cell carcinoma ascitic fluid.

We here describe the isolation, characterization, profile of lymphokine expression and T-cell-receptor gene rearrangement pattern of 444P.3, a CD3+ CD4+ CD8- 4B4+ interleukin-2 (IL-2)-dependent clone derived from the malignant ascites of a patient with renal cell cancer. The 444P.3 clone exhibited unique antitumor specificity between days 45 and 84 in culture and then lost its lytic, but not its proliferative, capacity. To our knowledge this is the first description of a specific antitumor reaction in a patient with renal cell cancer against autologous tumor. IL-2-expanded 444P.3 cells, tested on day 104 in culture, expressed mRNA for tumor necrosis factor (TNF), IL-2 and tumor growth factor beta (TGF-beta) but not for IL-1, lymphotoxin or granulocyte/macrophage-colony stimulating factor (GM-CSF). The parental noncloned population expressed mRNA for TNF, lymphotoxin, GM-CSF and TGF-beta but not for IL-1 beta or IL-2. Analysis of established human T cell clones should include profiles of lymphokine secretion in addition to growth and proliferation patterns, antitumor activity and surface phenotype. Such characterization of clones may provide a better understanding of the immunoregulatory role and functional potential of various T cell subsets involved in human antitumor reactivity.

Ascites↗
PubMed2003

Gene expression profiling and functional proteomic analysis reveal perturbed kinase-mediated signaling in genetic stroke susceptibility.

The stroke-prone spontaneously hypertensive rat (SHRSP) is a model of heritable hypertension-associated cerebrovascular injury. This study sought to compare SHRSP to the stroke-resistant SHR strain to identify genes and protein pathways whose expression and/or function was significantly altered between the strains prior to the onset of stroke. Cerebral cortex gene expression profiles from male SHRSPs and matched SHRs were examined by Affymetrix microarray analysis. mRNAs encoding the brain-derived neurotrophic factor receptor (TrkB) and multiple kinases of the MAPK/AKT signaling pathways, including JNK2, AKT2, and PI3K, were differentially expressed between SHRSP and SHR. Because these data suggest altered function in pathways involving MAP and AKT kinase activity, we performed Western blot using phosphorylation state-specific antibodies to characterize activity of MAP kinase and PI3K/AKT pathways. Changes in the levels of the phosphorylated forms of these kinases paralleled the changes in transcript levels observed between the strains. Two-dimensional gel electrophoresis and peptide fragment mass fingerprinting were used to identify altered protein substrates of these kinases. Protein profiling of kinase substrates further supported the notion of perturbed kinase-mediated signaling in SHRSP and identified adenylyl cyclase associated protein 2, TOAD-64, propionyl CoA carboxylase, APG-1, and valosin-containing protein as kinase targets whose phosphorylation state is altered between these strains. Altered gene and protein expression patterns in SHRSP are consistent with increased vulnerability of this strain to cerebrovascular injury.

Animals↗
PubMed2006

Laminar profiles of functional activity in the human brain.

Functional magnetic resonance imaging (fMRI) data were obtained in human visual cortex using sub-millimeter voxels at a field strength of 3 T. Reliable functional signals were largely confined to the gray matter and these responses measure the retinotopic organization of visual cortex. Functional signals were further characterized with respect to their laminar position within the cortical gray matter. The laminar response profiles during our visuospatial attention task, normalized for cortical thickness, had a stereotypical shape, with a peak in the superficial gray matter and declining in the deeper layers. The thickness of the sheet producing functional signals was in excellent agreement with the estimated structural thickness of the gray matter throughout early visual cortex (error < 0.5 mm). Thickness measurements were highly repeatable from session-to-session (error < 0.4 mm). Hence, it is feasible and useful to use high-resolution fMRI to measure laminar activity profiles. The ability to distinguish signals arising in different lamina has significant potential scientific and clinical applications.

Brain↗
PubMedDate not supplied

High resolution "ultra performance" liquid chromatography coupled to oa-TOF mass spectrometry as a tool for differential metabolic pathway profiling in functional genomic studies.

The combination of a new 1.7 mum reversed-phase packing material, and a chromatographic system, operating at ca. 12,000 psi, (so-called ultra performance liquid chromatography, UPLC) has enabled dramatic increases in chromatographic performance to be obtained for complex mixture separation. This increase in performance is manifested in improved peak resolution, together with increased speed and sensitivity. Here, we show that UPLC offers significant advantages over conventional reversed-phase HPLC amounting to a more than doubling of peak capacity, an almost 10-fold increase in speed and a 3- to 5-fold increase in sensitivity compared to that generated with a conventional 3.5 microm stationary phase. The first functional genomic application of UPLC-MS technology is illustrated here with respect to multivariate metabolic profiling of urines from males and females of two groups of phenotypically normal mouse strains (C57BL19J and Alpk:ApfCD) and a "nude mouse" strain. We have also compared this technology to conventional HPLC-MS under similar analytical conditions and show improved phenotypic classification capability of UPLC-MS analysis together with increased ability to probe differential pathway activities between strains as a result of improved analytical sensitivity and resolution.

Animals↗
PubMed1994

Pulmonary function testing in the critically ill neonate, Part I: An overview.

Respiratory insufficiency, a frequent problem encountered by the critically ill neonate, has many etiologies. Pulmonary function testing can effectively diagnose, quantify, and qualify the dysfunction so as to better define a prognosis and guide appropriate therapy. Recent advances in computer-assisted technology and miniaturization of equipment now allow simple, reproducible, and rapid neonatal pulmonary function assessment at the bedside. The indications for, and benefits of, pulmonary function testing vary with gestation, age, and clinical condition of the infant. The overall description of the pulmonary function profile is discussed in this article. The general questions and approaches utilized for routine testing, the initial pulmonary function profile, and evaluation of the acutely ill infant and that of the convalescing preterm are addressed. The expertise of the intensive care nurse is invaluable in ensuring that safe, accurate, and reproducible data are obtained. The nurse can then use the data to alter the infant's care plan and to determine the necessity and timing for retesting. Specific information on methodology and examples of specific tests are given in related articles (Parts II, Vol. 13 No. 2 and III, Vol. 13 No. 4, respectively). A complete knowledge of pulmonary function assessment is important for any nurse caring for critically ill neonates.

Humans↗
PubMed1993

Anthropometric and pulmonary function test profiles of outpatients with stable chronic obstructive pulmonary disease.

PURPOSE: To determine the prevalence of abnormalities in the nutritional status, and their correlation with pulmonary function test results, in a population of outpatients with stable chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: During 1 year of study, body weight, height, triceps skinfold, arm muscle circumference, and pulmonary function parameters were assessed in 126 patients. On the basis of body mass index (BMI = weight/height2) of less than 20, 20 to 27, and greater than 27, the patients were divided into underweight (n = 29, 23%), normal weight (n = 67, 53.2%), and overweight (n = 30, 23.8%), respectively. RESULTS: Diffusing capacity for carbon monoxide (DLCO), both as absolute and percent predicted, differed significantly among the three groups, being lowest in the underweight and highest in the overweight patients. A significant and positive correlation was present between BMI as the independent variable and DLCO, forced expiratory volume in 1 second, and its ratio to forced vital capacity. A significant and negative correlation existed between BMI and residual volume and its ratio to total lung capacity. CONCLUSION: A substantial number of stable COPD patients (46.8%) have nutritional abnormalities. BMI is a simple and accurate indicator of nutritional status in these patients. BMI correlates significantly with some tests of pulmonary function.

Aged↗
PubMed2002

Transcript profiling of functionally related groups of genes during conditional differentiation of a mammalian cochlear hair cell line.

We have used Affymetrix high-density gene arrays to generate a temporal profile of gene expression during differentiation of UB/OC-1, a conditionally immortal cell line derived from the mouse cochlea. Gene expression was assessed daily for 14 days under differentiating conditions. The experiment was replicated in two separate populations of cells. Profiles for selected genes were correlated with those obtained by RT-PCR, TaqMan analysis, immunoblotting, and immunofluorescence. The results suggest that UB/OC-1 is derived from a population of nonsensory epithelial cells in the greater epithelial ridge that have the potential to differentiate into a hair-cell-like phenotype, without the intervention of Math1. Elements of the Notch signaling cascade were identified, including the receptor Notch3, with a transient up-regulation that suggests a role in hair cell differentiation. Several genes showed a profile similar to Notch3, including the transcriptional co-repressor Groucho1. UB/OC-1 also expressed Me1, a putative partner of Math1 that may confer competence to differentiate into hair cells. Cluster analysis revealed expression profiles for neural guidance genes associated with Gata3. The temporal dimension of this analysis provides a powerful tool to study genetic mechanisms that underlie the conversion of nonsensory epithelial cells into hair cells.

Animals↗
PubMedDate not supplied

[Typologic analysis of comparative effects of tobacco and Pi phenotype on the respiratory function].

Seven hundred and fourty-eight subjects from the general population were included in a transversal epidemiologic survey. The aim was the determination of a possible relationship between functional profile and Pi phenotype. Seric levels of alpha 1-antitrypsin (alpha 1 AT) and phenotypes were determined in all subjects. All underwent clinical examination, chest X-ray and functional tests (flow-volume curves and single breath nitrogen test). Distribution of the various phenotypes appeared similar to those described in other studies. No homozygote Z was found. Typologic analysis allowed identification of 7 functional profiles, among which 3 were normal and 4 had various levels of obstruction. The comparison between functional impairment and the phenotypes or smoking habits showed that smoking played the major part in the onset of obstructive disease. Mean age of the population surveyed was however rather low, which led to questions about rapidity of onset of chronic obstructive lung disease. This survey thus will lead to a longitudinal study.

Closing Volume↗
PubMed2003

Profiling the global tyrosine phosphorylation state.

Protein tyrosine kinases and protein tyrosine phosphatases play a key role in cell signaling, and the recent success of specific tyrosine kinase inhibitors in cancer treatment strongly validates the clinical relevance of basic research on tyrosine phosphorylation. Functional profiling of the tyrosine phosphoproteome is likely to lead to the identification of novel targets for drug discovery and provide a basis for novel molecular diagnostic approaches. The ultimate aim of current mass spectrometry-based phosphoproteomic approaches is the comprehensive characterization of the phosphoproteome. However, current methods are not yet sensitive enough for routine detection of a large percentage of tyrosine-phosphorylated proteins, which are generally of low abundance. In this article, we discuss alternative methods that exploit Src homology 2 (SH2) domains for profiling the tyrosine phosphoproteome. SH2 domains are small protein modules that bind specifically to tyrosine-phosphorylated peptides; there are more than 100 SH2 domains in the human genome, and different SH2 domains bind to different classes of tyrosine-phosphorylated ligands. These domains play a critical role in the propagation of signals in the cell, mediating the relocalization and complex formation of proteins in response to changes in tyrosine phosphorylation. We have developed an SH2 profiling method based on far-Western blotting, in which a battery of SH2 domains is used to probe the global state of tyrosine phosphorylation. Application to the classification of human malignancies suggests that this approach has potential as a molecular diagnostic tool. We also describe ongoing efforts to modify and improve SH2 profiling, including the development of a multiplexed assay system that will allow high-throughput functional profiling of the tyrosine phosphoproteome.

Blotting, Far-Western↗
PubMed2004

A comparison of scoring functions for protein sequence profile alignment.

MOTIVATION: In recent years, several methods have been proposed for aligning two protein sequence profiles, with reported improvements in alignment accuracy and homolog discrimination versus sequence-sequence methods (e.g. BLAST) and profile-sequence methods (e.g. PSI-BLAST). Profile-profile alignment is also the iterated step in progressive multiple sequence alignment algorithms such as CLUSTALW. However, little is known about the relative performance of different profile-profile scoring functions. In this work, we evaluate the alignment accuracy of 23 different profile-profile scoring functions by comparing alignments of 488 pairs of sequences with identity < or =30% against structural alignments. We optimize parameters for all scoring functions on the same training set and use profiles of alignments from both PSI-BLAST and SAM-T99. Structural alignments are constructed from a consensus between the FSSP database and CE structural aligner. We compare the results with sequence-sequence and sequence-profile methods, including BLAST and PSI-BLAST. RESULTS: We find that profile-profile alignment gives an average improvement over our test set of typically 2-3% over profile-sequence alignment and approximately 40% over sequence-sequence alignment. No statistically significant difference is seen in the relative performance of most of the scoring functions tested. Significantly better results are obtained with profiles constructed from SAM-T99 alignments than from PSI-BLAST alignments. AVAILABILITY: Source code, reference alignments and more detailed results are freely available at http://phylogenomics.berkeley.edu/profilealignment/

Algorithms↗