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At least 1,765 records · Page 98Linked to original sources
PubMed2001

Noninvasive estimation of the aorta input function for measurement of tumor blood flow with.

Quantitative measurement of tumor blood flow with [15O]water can be used to evaluate the effects of tumor treatment over time. Since quantitative flow measurements require an input function, we developed the profile fitting method (PFM) to measure the input function from positron emission tomography images of the aorta. First, a [11C]CO scan was acquired and the aorta region was analyzed. The aorta diameter was determined by fitting the image data with a model that includes scanner resolution, the measured venous blood radioactivity concentration, and the spillover of counts from the background. The diameter was used in subsequent fitting of [15O]water dynamic images to estimate the aorta and background radioactivity concentrations. Phantom experiments were performed to test the model. Image quantification biases (up to 15%) were found for small objects, particularly for those in a large elliptical phantom. However, the bias in the PFM concentration estimates was much smaller (2%-6%). A simulation study showed that PFM had less bias and/or variability in flow parameter estimates than an ROI method. PFM was applied to human [11C]CO and [15O]water dynamic studies with left ventricle input functions used as the gold standard. PFM parameter estimates had higher variability than found in the simulation but with minimal bias. These studies suggest that PFM is a promising technique for the noninvasive measurement of the aorta [15O]water input function.

Aorta↗
PubMed2005

Sterol parameters as markers of liver function in primary biliary cirrhosis before and after liver transplantation.

Serum cholesterol reflects poorly cholesterol metabolism. From serum noncholesterol sterols cholestanol, campesterol, and sitosterol are surrogate markers of cholesterol absorption, but reflect also cholestasis, while those of lathosterol reflect cholesterol synthesis and hepatic parenchymal function. We investigated these sterols at end-stage of primary biliary cirrhosis (PBC) - prior to liver transplantation and shortly after transplantation in 67 patients to show their role as index of cholestasis and parenchymal liver function. Median preoperative values of cholestanol were increased 7.6 times, those of plant sterols 1.6-3.7 times above and the campesterol/sitosterol ratio was decreased twice below our control values, respective lathosterol levels being mainly subnormal. After transplantation, the proportions to cholesterol of the absorption markers decreased, and those of synthesis markers and the ratios of campesterol/sitosterol increased significantly. Thus, surrogate sterol markers of cholesterol absorption and synthesis in serum are also good clinical markers of chronic cholestasis and degree of hepatic parenchymal cell function in PBC. Postoperative improvement of serum sterol profile indicate clinically good function of the liver graft.

Adult↗
PubMed2005

The male seahorse synthesizes and secretes a novel C-type lectin into the brood pouch during early pregnancy.

The male seahorse incubates its young in a manner resembling that of a mammalian pregnancy. After the female deposits her eggs into the male's brood pouch they are fertilized and the embryos develop and grow for several weeks until they are able to withstand the external environmental conditions independently, at which point they are irreversibly released. Although the precise function of the brood pouch is not clear, it is probably related to providing a suitable protective and osmotic environment for the young. The aim of this project was to construct and characterize a cDNA library made from the tissue lining the pouch, in order to help understand the molecular mechanisms regulating its development and function. The library profile indicates expression of genes encoding proteins involved in metabolism and transport, as well as structural proteins, gene regulatory proteins, and other proteins whose function is unknown. However, a large portion of the library contained genes encoding C-type lectins (CTLs), of which three full-length proteins were identified and found to contain a signal peptide and a single C-lectin domain, possessing all the conserved structural elements. We have produced recombinant protein for one of these and raised antisera; we have shown, using Western analysis and 2D electrophoresis, that this protein is secreted in significant quantities into the pouch fluid specifically during early pregnancy. Preliminary functional studies indicate that this CTL causes erythrocyte agglutination and may help to repress bacterial growth.

Allosteric Site↗
PubMed2006

Role of thiazolidinediones in the management of type 2 diabetes: focus on ethnic minority populations.

Persons from ethnic minority populations in the United States suffer disproportionately more from type 2 diabetes and its complications than do Caucasians. Genetic and acquired factors likely contribute to the ethnic disparities of type 2 diabetes. The pathophysiologic hallmarks consist of insulin resistance, progressive pancreatic beta-cell dysfunction, and excessive hepatic glucose production. The ideal treatment for type 2 diabetes should correct insulin resistance and beta-cell dysfunction; and normalize hepatic glucose output; and prevent, delay, or reverse diabetic complications. The discovery of a new class of drugs, thiazolidinediones, has provided an effective tool to correct key underlying defects in type 2 diabetes. Thiazolidinediones improve insulin sensitivity and have beneficial effects on pancreatic beta-cell function and hepatic glucose production. Furthermore, their potent insulin-sensitization effect predicts that treatment with thiazolidinediones will improve cardiovascular risk factors, including lipid profile, fibrinolysis, endothelial function, and atheroinflammatory markers. These benefits are expected to be particularly important among ethnic minority patients who tend to have greater insulin resistance than do Caucasians.

Blood Glucose↗
PubMedDate not supplied

Early orthopedic treatment for Class III skeletal pattern.

An eight-year-old female, Class III due to maxillary retrusion with brachyfacial growth pattern was treated with a functional regulator appliance (FR-3). By initiating treatment at an early age, developing skeletal imbalances were corrected. At postretention six years she had balanced profile and stable functional occlusion.

Cephalometry↗
PubMed2004

The promise of genomics to identify novel therapeutic targets.

The cataloguing of the human genome has provided an unprecedented prospectus for target identification and drug discovery. A current analysis indicates that slightly more than 3000 unique protein encoding loci are potentially amenable to pharmacological intervention (the 'druggable genome', which can be queried at http://function.gnf.org/druggable). However, the assessment of genome sequence data has not resulted in the anticipated acceleration of novel therapeutic developments. The basis for this shortfall lies in the significant attrition rates endemic to preclinical/clinical development, as well as the often underestimated complexity of gene function in higher order biological systems. To address the latter issue, a number of strategies have emerged to facilitate genomics-driven target identification and validation, including cellular profiling of gene function, in silico modelling of gene networks, and systematic analyses of protein complexes. The expectation is that the integration of these and other systems-based technologies may enable the conversion of potential genomic targets into functionally validated molecules, and result in practicable gene-based drug discovery pipelines.

Animals↗
PubMed2005

Multi-spectral image analysis and classification of melanoma using fuzzy membership based partitions.

The sensitivity and specificity of melanoma diagnosis can be improved by adding the lesion depth and structure information obtained from the multi-spectral, trans-illumination images to the surface characteristic information obtained from the epi-illumination images. Wavelet transform based bi-modal channel energy features obtained from the images are used in the analysis. Methods using both crisp and fuzzy membership based partitioning of the feature space are evaluated. For this purpose, the ADWAT classification method that uses crisp partitioning is extended to handle multi-spectral image data. Also, multi-dimensional fuzzy membership functions with Gaussian and Bell profiles are proposed for classification. Results show that the fuzzy membership functions with Bell profile are more effective than the extended ADWAT method in discriminating melanoma from dysplastic nevus.

Diagnosis, Differential↗
PubMed2001

A comparison of the neuropsychological profiles of the DSM-IV subtypes of ADHD.

Recent research on the DSM-IV subtypes of attention-deficit/hyperactivity disorder (ADHD) has demonstrated that the subtypes differ in demographic characteristics, types of functional impairment, and profiles of comorbidity with other childhood disorders. However, little research has tested whether the subtypes differ in underlying neuropsychological deficits. This study compared the neuropsychological profiles of children without ADHD (n = 82) and children who met symptom criteria for DSM-IV Predominantly Inattentive subtype (ADHD-IA; n = 67), Predominantly Hyperactive Impulsive subtype (ADHD-HI; n = 14), and Combined subtype (ADHD-C; n = 33) in the areas of processing speed, vigilance, and inhibition. We hypothesized that children with elevations of inattention symptoms (ADHD-IA and ADHD-C) would be impaired on measures of vigilance and processing speed, whereas children with significant hyperactivity/impulsivity (ADHD-HI and ADHD-C) would be impaired on measures of inhibition. Contrary to prediction, symptoms of inattention best predicted performance on all dependent measures, and ADHD-IA and ADHD-C children had similar profiles of impairment. In contrast, children with ADHD-HI were not significantly impaired on any dependent measures once subclinical symptoms of inattention were controlled. Our results do not support distinct neuropsychological deficits in ADHD-IA and ADHD-C children, and suggest that symptoms of inattention, rather than symptoms of hyperactivity/impulsivity, are associated with neuropsychological impairment.

Adolescent↗
PubMed2004

A functional genomic study on NCI's anticancer drug screen.

Pharmacogenomics requires massive computer exploration on heterogeneous databases. COMPARE, the gateway to the NCI's anticancer drug screen database, allows users to correlate drug-sensitivity profiles with a functional genomic database. However, most drugs of known molecular mechanism turn out to be uncorrelated with their molecular-target gene expression. Based on a novel statistical concept, liquid association, we develop an on-line system to identify candidate genes that intervene, confound and weaken the drug-gene correlation. The system takes queries and returns button-clickable tables of functionally associated genes for rerouting to knowledgebases such as Locus Link, OMIM and PubMed. We report results that link methotrexate resistance to DNA component biosynthesis, and taxol sensitivity to genes associated with human immunodeficiency virus infection. The drug-sensitivity database can be synergistically coanalyzed with gene expression data to study proteins of poorly understood physiological roles. When applied to the human prion, a cellular context embroidered with the gene expression network of Alzheimer disease is revealed.

Databases, Nucleic Acid↗
PubMed2002

Functional interleukin-7 receptors (IL-7Rs) are expressed by marrow stromal cells: binding of IL-7 increases levels of IL-6 mRNA and secreted protein.

DNA spotted microarrays were used to compare gene expression profiles from 2 functionally distinct human marrow stromal cell lines: HS-27a, which supports cobblestone area formation by early hematopoietic progenitors, and HS-5, which secretes multiple cytokines that support the proliferation of committed progenitors. One unexpected result was the high level of interleukin-7 receptor (IL-7R) gene expression in HS-27a stromal cells. Northern blot analysis confirmed the IL-7R RNA expression, and Western blots for the IL-7R protein detected both a full-length (90-kd) IL-7R and a smaller 30-kd fragment in both HS-27a cells and primary stromal cell cultures, whereas only the 90-kd receptor protein was detected in peripheral blood mononuclear cells. Biotinylated IL-7 was shown to bind to HS-27a cells under physiologic conditions, and this binding was inhibited by blocking anti-IL-7 antibodies. Tyrosine phosphorylation of several proteins (55 kd, 30 kd, and 24 kd) in HS-27a cells was rapidly increased after incubation with recombinant IL-7. One of the phosphorylated proteins proved to be the 30-kd IL-7R fragment. Exposure of HS-27a cells to IL-7 resulted in a 10-fold increase in secretion of IL-6 into culture supernatants but no increase in the cytokines stromal cell-derived factor 1, macrophage inflammatory protein 1 alpha, or IL-1 beta. The up-regulation of IL-6 secretion is associated with a rapid but transient increase in detectable levels of IL-6 messenger RNA. These data suggest that IL-7 may function to regulate the milieu of the microenvironment by modulating IL-6 secretion by the IL-7R-expressing stromal elements.

Antibodies↗
PubMed2001

Photoreceptor rescue after low-dose intravitreal IL-1beta injection in the RCS rat.

Photoreceptor survival in the dystrophic rat was evaluated following administration of IL-1beta at dosages much lower than those used previously for this purpose. Royal College of Surgeons rats (pink-eyed, pigmented, or non-dystrophic) received 1 microl intravitreal injections of murine recombinant IL-1beta (0.5, 2, or 5 microg ml(-1); at 3 or 4 weeks of age). Eyes were harvested 4 weeks later and outer nuclear layer profiles counted. Additional animals received intravitreal basic fibroblast growth factor (1000 microg ml(-1)), or vehicle alone. Others were treated with IL-1beta to evaluate the inflammatory response (CD45+ profiles) or visual function via opto-kinetic response. IL-1beta was associated with photoreceptor rescue that was both dose-dependent and comparable to that seen following high-dose basic fibroblast growth factor. Significant anatomical rescue relative to controls was seen in both pink-eyed and pigmented strains, although the degree and distribution varied between strains. Functional rescue was confirmed by opto-kinetic response using the pigmented strain. At 5 microg ml(-1), IL-1beta resulted in numerous CD45+ profiles within the retina and vitreous. Infiltration peaked at 48 hr and was minimal at 4 weeks, without dysplastic sequelae. IL-1beta therefore induces visually significant photoreceptor rescue in a potent, dose-dependent manner that need not entail cytoarchitectural disruption. This is consistent with the known association between injury and rescue in the rat retina. Neuroprotection may be a general, if under-appreciated, consequence of inflammatory cascade activation.

Animals↗
PubMed2005

Density-functional theory and Monte Carlo simulation for the surface structure and correlation functions of freely jointed Lennard-Jones polymeric fluids.

We present a nonlocal density-functional theory of polymeric fluids consisting of freely jointed Lennard-Jones chains with explicit consideration of the segment size, van der Waals attraction, and structural correlations due to chain connectivity. The excess Helmholtz energy functional is derived from a modified fundamental measure theory for the short-ranged repulsion and the first-order thermodynamic perturbation theory for chain connectivity. The contribution of the long-ranged attraction to the Helmholtz energy functional is taken into account using a quadratic density expansion with the direct correlation function obtained from the first-order mean-spherical approximation. The numerical performance of the density-functional theory is compared well with the simulation results from this work as well as those from the literature for the segment-level density profiles and correlation functions of Lennard-Jones chains in slit pores, near isolated nanoparticles, or in bulk.

Journal Article↗
PubMed2005

Functional dysconnectivity in schizophrenia associated with attentional modulation of motor function.

It is not known whether there is a core abnormality that occurs in all cases of schizophrenia. The cognitive dysmetria hypothesis proposes that there is such an abnormality which is characterized cognitively by a disruption in control and coordination processes, and functionally by abnormal inter-regional connectivity within the cortico-cerebellar-thalamo-cortical circuit (CCTCC). In the current study, we used functional MRI (fMRI) to investigate these two key aspects of the hypothesis. Since patients with schizophrenia show deficits in attention which have been characterized extensively using the continuous performance task (CPT) and since functional imaging studies have also demonstrated that this task engages the CCTCC, we used this task to investigate whether two patient groups with distinct symptom profiles would show functional dysconnectivity within this network. Three groups of subjects participated in the study: healthy volunteers (n = 12), schizophrenia patients with both negative and positive symptoms (n = 11) and schizophrenia patients with primarily positive symptoms (n = 11). Patient groups were matched for age of illness onset and medication, and to the control group for age, gender and handedness. Subjects were scanned using fMRI whilst they performed a modified version of the CPT, involving both degraded and non-degraded stimuli. Stimulus degradation has been shown to produce decrements in sensitivity, which is thought to reflect increased demands on the limited capacity of visual attention. Between-group comparisons revealed that patients with schizophrenia, irrespective of symptomatology, showed attenuation of the anterior cingulate and cerebellar response to stimulus degradation in comparison with control subjects. We also observed disruptions of inter-regional brain integration in schizophrenia. A task-specific relationship between the medial superior frontal gyrus and both anterior cingulate and the cerebellum was disrupted in both patient groups in comparison with controls. In addition, patients with negative symptoms showed impaired behavioural performance, and abnormal task-related connectivity between anterior cingulate and supplementary motor area. These findings are consistent with theoretical accounts of schizophrenia as a disorder of functional integration, and with the cognitive dysmetria hypothesis, which posits a disconnection within the CCTCC as a fundamental abnormality in schizophrenia, independent of diagnostic subtype. Furthermore, these data show evidence of additional functional deficits in patients with negative symptoms, deficits which may explain the accompanying attentional impairment.

Adult↗
PubMed2002

[Microgravity and weightlessness: experimental model accelerates nutritional pathology].

Short space flights affect nutritional intakes, body composition and functional parameters. Prolonged space flights (SF) over weeks or months further worsen these alterations and result in acute or chronic physical deterioration at earth return. Current planning of SF to Mars, with microgravity conditions for more than 2 years, stresses the need for developing and optimising a nutritional program and physical countermeasures to prevent body mass atrophy and functional body alterations. This review presents the models of microgravity simulation on earth and the main effects of weightlessness on body composition, protein metabolism, hormonal profile and muscle function. It summarizes contradictory findings related to the oxidative stress related to SF. It discusses potential countermeasures (nutrition, physical activity) to the negative effects of microgravity on human body. Future research possibilities in ground and space medicine are evoked.

Aerospace Medicine↗
PubMed2006

Location and spatial profile of category-specific regions in human extrastriate cortex.

Subjects were scanned in a single functional MRI (fMRI) experiment that enabled us to localize cortical regions in each subject in the occipital and temporal lobes that responded significantly in a variety of contrasts: faces>objects, body parts>objects, scenes>objects, objects>scrambled objects, and moving>stationary stimuli. The resulting activation maps were co-registered across subjects using spherical surface coordinates [Fischl et al., Hum Brain Mapp 1999;8:272-284] to produce a "percentage overlap map" indicating the percentage of subjects who showed a significant response for each contrast at each point on the surface. Prominent among the overlapping activations in these contrasts were the fusiform face area (FFA), extrastriate body area (EBA), parahippocampal place area (PPA), lateral occipital complex (LOC), and MT+/V5; only a few other areas responded consistently across subjects in these contrasts. Another analysis showed that the spatial profile of the selective response drops off quite sharply outside the standard borders of the FFA and PPA (less so for the EBA and MT+/V5), indicating that these regions are not simply peaks of very broad selectivities spanning centimeters of cortex, but fairly discrete regions of cortex with distinctive functional profiles. The data also yielded a surprise that challenges our understanding of the function of area MT+: a higher response to body parts than to objects. The anatomical consistency of each of our functionally defined regions across subjects and the spatial sharpness of their activation profiles within subjects highlight the fact that these regions constitute replicable and distinctive landmarks in the functional organization of the human brain.

Adult↗
PubMed2006

Systematic identification of microRNA functions by combining target prediction and expression profiling.

Target predictions and validations are major obstacles facing microRNA (miRNA) researchers. Animal miRNA target prediction is challenging because of limited miRNA sequence complementarity to the targets. In addition, only a small number of predicted targets have been experimentally validated and the miRNA mechanism is poorly understood. Here we present a novel algorithm for animal miRNA target prediction. The algorithm combines relevant parameters for miRNA target recognition and heuristically assigns different weights to these parameters according to their relative importance. A score calculation scheme is introduced to reflect the strength of each parameter. We also performed microarray time course experiments to identify downregulated genes due to miRNA overexpression. The computational target prediction is combined with the miRNA transfection experiment to systematically identify the gene targets of human miR-124. miR-124 overexpression led to a significant downregulation of many cell cycle related genes. This may be the result of direct suppression of a few cell growth inhibitors at the early stage of miRNA overexpression, and these targeted genes were continuously suppressed over a long period of time. Our high-throughput approach can be generalized to globally identify the targets and functions of other miRNAs.

Algorithms↗
PubMed2026

Oral and gut microbiota profiles in patients with locally advanced rectal cancer with varying responses to neoadjuvant chemoradiotherapy.

Recent research has focused on gut bacteria in colorectal cancer, but the influence of other microbiota, including oral and nonbacterial gut microbiota, on treatment efficacy remains insufficiently explored. This study aimed to investigate their relationship with the efficacy of neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). Saliva and fecal samples were collected from patients with LARC before treatment. Shotgun metagenomic sequencing was used to profile bacterial, archaeal, eukaryotic, and viral taxonomic groups and to examine oral and gut microbial functions. An artificial intelligence-based prediction model was developed by integrating oral and gut microbiome data with clinical information. Statistical analyses compared diversity and response-associated microbial features between responders and non-responders to nCRT. Response-associated differences were observed in bacterial and nonbacterial taxonomic profiles and in oral and gut microbial functional profiles. In the internal test subset, the integrated analysis yielded an observed AUC of 0.917. Given the small cohort and the exploratory comparison of candidate classifiers, this estimate requires confirmation in larger, independent cohorts. Baseline oral and gut microbiome profiles were associated with response to nCRT. Integrating microbiome and clinical features showed potential for response prediction, but the model remains exploratory and requires validation in larger, independent cohorts before clinical application. Retrospectively registered on 01/08/2026, NCT07346729.

Aged↗
PubMed1993

[EEG maturation and hemispheric functional asymmetry in 5- to 7-year-old children with general speech retardation].

EEG and a hand-eye functional asymmetry (FAS) profile have been compared in children with general speech retardation (GSR, 45 cases) and in normal children (45 cases) aged 5-7 years. The least EEG deviations have been noted in healthy full right-handed cases. Some delay in EEG maturation as well as existence of pathologic activity foci mostly in associative cortical brain areas have been noted in healthy non-right-handed and in GSR children. The most pronounced EEG disturbances have been observed in GSR children, 40% of whom were ambidextrous, left-handed and cross-lateralized children. The percentage of non-right-handed cases in the healthy group was less and decreased up to the age of 7 years. Prenatal, perinatal and 1st year postnatal pathology have been revealed in 86.6% of children in GSR group (in comparison to 11.1% in normal control group). Such pathology is suggested to be the reason of dysontogenesis and probably to be involved in brain electrical activity maturation, in FAS profile and in speech development.

Child↗