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At least 1,279 records · Page 71Linked to original sources

Effects of rHuEPO on Q-EEG and event-related potentials in chronic renal failure.

Quantitative electroencephalography is a powerful tool to evaluate brain function, and preliminary data have shown its usefulness in the evaluation of patients with chronic renal failure (CRF). In this study, baseline values of different quantitative EEG variables, as well as data from the P300 component of the visual event-related potential, in 43 patients with chronic renal failure, were compared with those of a group of healthy subjects and with the results obtained after 3, 6, 9 and 12 months of treatment of these patients with rHuEPO. Baseline total power was much lower in patients with CRF than in healthy subjects, and the distribution of power among the frequency bands was also abnormal. rHuEPO promptly normalized total power and progressively improved power distribution, although full normality was not achieved. Mean dominant frequencies in brain areas were abnormal in patients with CRF, and progressive improvement was seen along the study. The latency of P300, which was increased before treatment, decreased in all subjects, but normal values were not reached. The same applies to the hypomanic and psychopathic scores of psychological tests. Altogether, brain dysfunction of CRF seems to substantially improve by treatment of the anemia with rHuEPO.

Adult↗

Monitoring early differentiation events in human embryonic stem cells by massively parallel signature sequencing and expressed sequence tag scan.

To identify genes that may be involved in the process of human embryonic stem cell (hESC) differentiation, we profiled gene expression by expressed sequenced tag (EST) enumeration and massively parallel signature sequencing (MPSS) using RNA samples from feeder-free cultures of undifferentiated (passages 40-50) and differentiated (day 14) H1, H7, and H9 lines. MPSS and EST scan analysis showed good concordance and identified a large number of genes that changed rapidly as cultures transition from a pluripotent to a differentiated state. These included known and unknown ES cell-specific genes as well as a large number of known genes that were altered as cells differentiate. A subset of genes that were either up- or down-regulated were selected and their differential expression confirmed by a variety of independent methods, including comparison of expression after further differentiation, publicly available databases, and direct assessments by reverse transcriptase (RT)-PCR and immunocytochemistry. The analysis identified markers unique to the hESC and embryoid bodies (hEBs) stage as well as signaling pathways that likely regulate differentiation. The data generated can be used to monitor the state of hESC isolated by different laboratories using independent methods and maintained under differing culture conditions.

Cell Culture Techniques↗

Regional assignment of genetic markers using a somatic cell hybrid panel: a WWW interactive program available for the pig genome.

MOTIVATION: Quick and easy gene mapping by the use of a panel of cytogenetically characterized somatic cell hybrids is possible, even if some discordant experimental results arise. RESULTS: An interactive program is proposed and is made available on a WWW site to users of a somatic cell hybrid panel. Assignments to chromosomes and subchromosomal regions are based on likelihood calculations and Bayes' theorem, and a confidence level is provided. The method is illustrated in the case of the pig genome.

Animals↗

The use of simulated annealing in chromosome reconstruction experiments based on binary scoring.

We present a method of combinatorial optimization, simulated annealing, to order clones in a library with respect to their position along a chromosome. This ordering method relies on scoring each clone for the presence or absence of specific target sequences, thereby assigning a digital signature to each clone. Specifically, we consider the hybridization of oligonucleotide probes to a clone to constitute the signature. In that the degree of clonal overlap is reflected in the similarity of their signatures, it is possible to construct maps based on the minimization of the differences in signatures across a reconstructed chromosome. Our simulations show that with as few as 30 probes and a clonal density of 4.5 genome equivalents, it is possible to assemble a small eukaryotic chromosome into 33 contiguous blocks of clones (contigs). With higher clonal densities and more probes, this number can be reduced to less than 5 contigs per chromosome.

Algorithms↗

The use of single photon emission computed tomography in depressive disorders.

Single photon emission computed tomography (SPECT) and positron emission tomography (PET) have advanced our understanding of the biological underpinnings of depression. There is, however, considerable variability in the literature. Depression is a complex disorder with marked heterogeneity in diagnosis and treatment. There is also evidence of heterogeneity in pathophysiology. In addition, the literature is marked by inconsistencies in the use of imaging techniques and data-analytical procedures. In this review we have attempted to focus on the SPECT studies that have used more refined methodologies and more homogenous clinical sub-groups of patients. We have focused on the main diagnostic sub-types of depression and on specific issues such as treatment response, correlates of neuroimaging abnormalities in depression, and so-called 'emotional circuitry' - the connectivity of regions implicated in depression. The future of molecular imaging in depression will be determined by the pace of the development of useful ligands and the exciting opportunities emerging in the field of imaging genomics. Future studies must attend to several key confounds including clinical heterogeneity, medication and the problems surrounding recruitment of drug-naive patients. It remains the case that longitudinal studies are the design of choice if questions relating to state and trait are to be addressed. Molecular imaging will be used increasingly to quantify neuroreceptor and transporter binding, and the activity of neurtransmitters, allowing the neurochemistry of this complex condition to be explored.

Brain↗

In situ hybridization analysis of isodicentric X-chromosomes with short arm fusion.

We present here an alternative approach to the study of mosaic cell lines containing dicentric chromosomes. The approach is based on chromosome-specific non-radioactive in situ hybridization with centromere (alpha satellite DNA) probes. The hybridization analysis may be used as an alternative to the C-band analysis, while at the same time to some extent replacing the Q-band analysis as well. The advantage of using in situ hybridization is mainly that it allows the very fast screening of a large number of metaphases. We illustrate this new application of the technique by using it for the analysis of two cases of isodicentric X-chromosomes. The approach is expected to be generally applicable, so that it may be applied to the scoring of other types of chromosomal mosaicism as well.

Child↗

Threshold distributions of phenylthiocarbamide (PTC) in the Chinese population.

The ability to taste phenylthiocarbamide (PTC) is a well-documented Mendelian trait. Mapping and cloning the gene(s) responsible for the PTC tasting ability would help to delineate the molecular basis for the variations in PTC tasting ability in humans and to shed new light on taste chemosensory functions. In view of the spectacular successes in genome science, the positional cloning strategy seems to be a feasible approach to the isolation of the gene(s) underlying the PTC tasting ability. As a first step toward mapping the gene(s), we collected PTC taste threshold data on 106 individuals, most of them being university students, in Shanghai, China. Using various parametric and nonparametric statistical methods, we have found that the data set is best described by a bimodal distribution. The frequency of PTC nontasters is estimated to be 10%. This is consistent with the view that the PTC nontasting ability follows a recessive mode of inheritance. Several authors had previously reported PTC data on Chinese living outside China. Our data are, to our knowledge, the first ever collected from the Chinese population within China.

Adolescent↗

Identification of procaryotic repetitive DNA suitable for use as fingerprinting probes.

We have developed a method which enables the cloning and identification of procaryotic repetitive DNA suitable for use as DNA fingerprinting probes. The method involves shotgun cloning of restricted genomic DNA with subsequent selection of clones containing repetitive DNA by reverse-probed genomic hybridizations, in which the plasmid DNA clones are probed with labelled genomic DNA. Confirmation that the clones contained repeated sequences was by Southern hybridization, gene copy equivalence, and DNA sequencing. The sequences were used for highly specific and sensitive detection of bacteria and as target sequences for the mediation of chromosomal integration of reporter gene constructs.

Bacillus subtilis↗

Comparative gene-based in silico analysis of transcriptomes in different bovine tissues and (or) organs.

A gene-based approach was used to annotate 322,168 cattle expressed sequence tags (ESTs) based on human genes in order to census the transcriptomes, analyze their expression similarities, and identify genes preferentially expressed in different bovine tissues and (or) organs. Of the 34,157 human coding genes used in a standalone BLAST search, 14,928 could be matched with provisional orthologous sequences in a total of 230,135 bovine ESTs. The remaining 92,033 bovine ESTs were estimated to represent an additional 5970 genes in cattle. On average, approximately 8600 genes were estimated to be expressed in a single tissue and (or) organ and 13,000 in a pooled tissue library. On the basis of the estimated numbers of genes, no more than 3% of genes would be missed when approximately 34,000 ESTs were sequenced from a single tissue and (or) organ library and approximately 40,000 ESTs from a pooled source, respectively. Cluster analyses of the gene expression patterns among 12 single tissues and (or) organs in cattle revealed that their expression similarities would depend on physiological functions. In addition, a total of 1502 genes were identified as preferentially expressed genes in these 12 single tissues and (or) organs with LOD (logarithm of the odds, base 10) > or = 3.0. Therefore, our study provides some insights for further investigating the developmental and functional relations of various tissues and organs in mammals.

Animals↗

Ratiometry of transmembrane voltage-sensitive fluorescent dye emission in hearts.

Transmembrane voltage-sensitive fluorescence measurements are limited by baseline drift that can obscure changes in resting membrane potential and by motion artifacts that can obscure repolarization. Voltage-dependent shift of emission wavelengths may allow reduction of drift and motion artifacts by emission ratiometry. We have tested this for action potentials and potassium-induced changes in resting membrane potential in rabbit hearts stained with di-4-ANEPPS [Pyridinium, 4-(2-(6-(dibutylamino)-2-naphthalenyl) ethenyl)-1-(3-sulfopropyl)-, hydroxide, inner salt] using laser excitation (488 nm) and a two-photomultiplier tube system or spectrofluorometer (resolution of 500-1,000 Hz and <1 mm). Green and red emissions produced upright and inverted action potentials, respectively. Ratios of green emission to red emission followed action potential contours and exhibited larger fractional changes than either emission alone (P < 0.001). The largest changes and signal-to-noise ratio (signal/noise) were obtained with numerator wavelengths of 525-550 nm and denominator wavelengths of 650-700 nm. Ratiometry lessened drift 56-66% (P < 0.015) and indicated decreases in resting membrane potential. Ratiometry lessened motion artifacts and increased magnitudes of deflections representing phase-zero depolarizations relative to total deflections by 123-188% in intact hearts (P < 0.02). Durations of action potentials at different pacing rates, temperatures, and potassium concentrations were independent of whether they were measured ratiometrically or with microelectrodes (P > or = 0.65). The ratiometric calibration slope was 0.017/100 mV and decreased with time. Thus emission ratiometry lessens the effects of motion and drift and indicates resting membrane potential changes and repolarization.

Animals↗

Novel combinations based on epidermal growth factor receptor inhibition.

In spite of recent advances in molecular biology leading to the introduction of clinically active novel agents, such as imatinib, erlotinib, and bevacizumab, therapy of the most common epithelial tumors, such as lung cancer, remains unsuccessful. The diversity of molecular abnormalities in these tumors is felt to partly contribute to their resistance to therapy. It is, therefore, widely accepted that one approach to improving the efficacy of cancer therapy is the development of rational, hypothesis-based combinations of anticancer agents that may exhibit synergistic cytotoxic interactions. A number of empirical combination studies with the epidermal growth factor receptor and classic cytotoxic agents were undertaken in clinical trials, with disappointing results. It is, therefore, felt that preclinical combinations of epidermal growth factor receptor inhibitors and other novel agents, based on sound knowledge of complementary signaling pathways whose concerted inhibition would be hypothesized to inhibit growth, is the reasonable approach in the future. A brief overview of some of these pathways (mammalian target of rapamycin, vascular endothelial growth factor receptor, and ras/mitogen-activated protein kinase signaling) is provided in this review.

Antineoplastic Combined Chemotherapy Protocols↗

Improved tumor targeting by combined use of two antitenascin antibodies.

PURPOSE: In the pretargeted antibody-guided radioimmunotherapy (PAGRIT) system, the combined use of two different antibodies directed against the same tumor antigen could represent a valid approach for improving tumor targeting and therapeutic efficacy. We developed a novel monoclonal antitenascin antibody, ST2485, and studied its biochemical and functional properties by in vitro and in vivo assays. We then investigated the first of the three-step therapy combining ST2485 with another antitenascin antibody, ST2146, previously described, to increase accumulation of biotinylated antibodies at the tumor site. EXPERIMENTAL DESIGN: Studies of immunoreactivity, affinity, immunohistochemistry, and biodistribution in xenograft model were carried out on ST2485. Analysis of the ST2485 and ST2146 combination was preliminary carried out by ELISA and BiaCore tests and then by in vivo distribution studies after administration of the radiolabeled biotinylated antibodies, followed by a chase with avidin as clearing agent. RESULTS: ST2485 was found to be a suitable antibody for therapeutic applications. Indeed, for its behavior in all tests, it was comparable with ST2146 and better than BC2, an antibody already used for clinical trials. The additivity of ST2146 and ST2485 in tenascin C binding, shown by in vitro tests, was confirmed by biodistribution studies in a xenograft model where tumor localization of the antibodies was near the sum of each antibody alone, with a tumor-to-blood ratio higher than 24. CONCLUSION: The results reported in this study suggest that a monoclonal antitenascin antibody mixture can improve tumor targeting. This strategy could represent progress for therapeutic approaches such as PAGRIT.

Amino Acid Sequence↗

Psychotropic drug profiles: comparisons by topographic maps of absolute power.

In a double-blind fourfold crossover design, 11 subjects were randomly assigned to placebo, 10 mg diazepam, 75 mg amitriptyline, and 75 mg chlorpromazine. During a simple vigilance task, 12 midline and left hemisphere leads were recorded before and 3 h after drug administration. The EEG was quantified by spectrum analysis, the topographic structure displayed by brain mapping techniques, and the results compared with earlier studies which used the same design and drugs. Diazepam showed the expected increase in beta; however, fast beta was increased as much as slow beta. Amitriptyline showed an increase of slow wave power and a reduction of alpha. In contrast to earlier studies, a decrease of fast beta was found. In addition, the spatial pattern of alpha changed from an occipital to a parietal maximum. Chlorpromazine showed an increase in the theta band. In occipital regions, there was a small decrease of fast beta; however, centrally there was an increase of both slow and fast beta. These results were confirmed by a multivariate analysis of variance.

Adult↗

From ecology to base pairs: nursing and genetic science.

With the mapping of the human genome has come the opportunity for nursing research to explore topics of concern to the maintenance, restoration, and attainment of genetic-related health. Initially, nursing research on genetic topics originated primarily from physical anthropology and from a clinical, disease-focused perspective. Nursing research subsequently focused on psychosocial aspects of genetic conditions for individuals and their family members. As findings emerge from current human genome discovery, new programs of genetic nursing research are originating from a biobehavioral interface, ranging from the investigations of the influence of specific molecular changes on gene function to social/ethical issues of human health and disease. These initiatives reflect nursing's response to discoveries of gene mutations related to phenotypic expression in both clinical and community-based populations. Genetic research programs are needed that integrate or adapt theoretical and methodological advances in epidemiology, family systems, anthropology, and ethics with those from nursing. Research programs must address not only populations with a specific disease but also community-based genetic health care issues. As genetic health care practice evolves, so will opportunities for research by nurses who can apply genetic concepts and interventions to improve the health of the public. This article presents an analysis of the evolution of genetic nursing research and challengesfor the future.

Base Pairing↗