Neurons of the claustrum projecting to the motor and somatosensory cortex in the rabbit--assessment with the method of retrograde transport of fluorescent tracers.
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Insulin deficiency due to autoimmune destruction of pancreatic beta cells (insulin is an autoantigen) is responsible for insulin-dependent diabetes mellitus. Since 1923, substitutive administration of insulin has been used to treat the disease. Surprisingly, initial usage of insulin is associated with partial resumption of insulin secretion in most patients. This phenomenon is intensified by aggressive insulin therapy. When observed at a late phase of destruction, it has been interpreted as an immunomodulatory effect of insulin which is presumed to act either by masking the target of effector cells in the autoimmune reaction (beta cells at rest because of glycaemic normalisation would expose fewer antigens) or by direct action on autoreactive T lymphocytes (which are rich in insulin receptors). There could also be a direct beneficial effect on anti-apoptotic or pro-regenerative beta cells. Efficient prevention of diabetes has been achieved by administration of parenteral insulin to non-obese diabetic (NOD) mice. Certain sequences of the B chain appear to be responsible for this effect, which seems to be immunomediated. Some preliminary data from the groups of G. Eisenbarth and N. MacLaren have suggested that this effect could be obtained in man by administering small doses of subcutaneous insulin to prediabetic patients. Two trials have been under way since 1994: DPT1 (a non-randomised trial concerning children and adults at high risk) in the United States, and EPP-SCIT (a randomised trial concerning children at very high risk) in Europe. Another approach has also been attempted in diabetes as well as other diseases with an organ-specific autoimmune reaction (SEP, PR) i.e. oral administration of an antigen present at the reaction site. A positive effect has been shown by the group of H. Weiner in the NOD mouse in which islet infiltration was reduced and diabetes prevented by "oral tolerisation" with insulin. Oral insulin is easy to use in therapeutic studies and is currently being administered in two trials: DPT1 (prediabetic children and adults at moderate risk) in the United States, and DIOR (recently diabetic children and adults) in France. However, recent experimental data suggest that oral administration of an antigen in certain artificial circumstances can trigger an autoimmune reaction in the animal, which would indicate that due caution should be exercised in trials involving prediabetic patients.
TOPIC: Using the Nursing Interventions Classifications (NIC) as a standard to classify interventions identified in a hospital intervention system. SOURCES: Literature and the authors experience with standardized data systems for nursing. PURPOSE: To describe the processes used and the issues that arose as interventions from a hospital nursing information system were mapped to interventions in the NIC. CONCLUSIONS: The NIC provided a standard for the classification of nursing interventions from a hospital information system resulting in data that could be compared across sites. Ongoing testing of nursing intervention classifications is recommended.
Construction of population atlases is a key issue in medical image analysis, and particularly in brain mapping. Large sets of images are mapped into a common coordinate system to study intra-population variability and inter-population differences, to provide voxel-wise mapping of functional sites, and help tissue and object segmentation via registration of anatomical labels. Common techniques often include the choice of a template image, which inherently introduces a bias. This paper describes a new method for unbiased construction of atlases in the large deformation diffeomorphic setting. A child neuroimaging autism study serves as a driving application. There is lack of normative data that explains average brain shape and variability at this early stage of development. We present work in progress toward constructing an unbiased MRI atlas of 2 years of children and the building of a probabilistic atlas of anatomical structures, here the caudate nucleus. Further, we demonstrate the segmentation of new subjects via atlas mapping. Validation of the methodology is performed by comparing the deformed probabilistic atlas with existing manual segmentations.
13-(S)-Hydroxyoctadecadienoic acid (13-HODE), the lipoxygenase metabolite of linoleic acid, has been shown to reverse the epidermal hyperproliferation induced by topical application of docosahexaenoic acid (DNA, 22:6 n-3) on guinea pig skin. Our initial studies demonstrated that 13-HODE exerts a selective inhibition of the membrane-bound PKC-beta activity in the hyperproliferative skin. To delineate the antiproliferative effects of 13-HODE, we investigated the nuclear events associated with this process. Our data demonstrated that the major PKC isozymes in the epidermal nuclear fraction are alpha and zeta. Epidermal hyperproliferation induced by DHA caused an increase in nuclear total PKC and atypical PKC activities, and this was accompanied by an increase in the two nuclear isozymes, alpha and zeta (P < 0.05). This increase was reversed after topical application of 13-HODE. Similarly, 13-HODE suppressed elevated nuclear MAP-kinase. Taken together, these data suggest that nuclear signalling events in the epidermis involve PKC-MAP-kinase pathway.
UNLABELLED: The importance of accurate attenuation correction, especially for imaging of the thorax region, is widely acknowledged. Appropriate compensation methods have been developed and introduced into clinical practice. Most of these methods use attenuation maps obtained using various transmission scanning systems. However, when maps are inaccurate, the correction procedure may introduce artifacts into the final images that can be difficult to identify and might inadvertently alter diagnosis and study outcome. As a result, attenuation correction is often avoided in clinical practice. Our objective was to examine issues related to the quality of attenuation maps and the effects that map artifacts may have on attenuation-corrected emission images. METHODS: The topics that are investigated include the problem of low transmission counts, cross-talk contributions from the emission isotope, truncation of the transmission data, and methods of map reconstruction and segmentation. Examples of patient studies displaying specific problems guided our investigations, but, because truth in these studies is seldom known, analytic and Monte Carlo-simulated data were used in the analysis. Attenuation maps and final emission images were visually checked for artifacts and for the presence of perfusion defects. In addition, quantitative evaluation of map uniformity, defect visibility, and size variation was performed. RESULTS: The statistical paired-sample t test showed significant (P < 0.05) improvement of relative SD for attenuation maps reconstructed with iterative methods as compared with filtered backprojection and for maps created with higher photon fluxes. When maps with artifacts were used to correct emission data, an increase in myocardial infarct size and creation of false heart defects were observed. CONCLUSION: Our study strongly recommends that at least a visual inspection of the quality of attenuation maps be performed before their use in compensation procedures. To improve image quality, remove artifacts, and increase diagnostic confidence, attenuation maps used in the correction procedure must be accurate and free of artifacts.
PURPOSE: An alternative approach to anal Bowen's disease was investigated. The use of topical 5 percent 5-fluorouracil for large lesions and surgical excision of small lesions were evaluated. METHODS: A prospective study was undertaken for anal Bowen's disease in 11 patients over a six-year period. Before therapy all patients underwent anal mapping biopsy and colonoscopy. For one-half circumferential disease or greater, patients underwent topical 5 percent 5-fluorouacil therapy for 16 weeks. For smaller involvement, wide surgical excision was performed. All patients underwent anal mapping biopsy one year after completion of therapy. RESULTS: Of 11 patients, 8 (5 male) received 16 weeks of topical 5 percent 5-fluorouacil therapy. Three patients (3 female) underwent surgical excision for localized disease. All but one patient, who was HIV positive, were free of Bowen's disease one year after completion of therapy. One patient underwent total excision of a residual microinvasive squamous carcinoma after circumferential Bowen's disease had resolved. One patient received eight additional weeks of topical 5-fluorouacil therapy for incomplete resolution. All patients were followed yearly, with a mean follow-up of 39 months and a range of 12 to 74 months. There have been no recurrences. There were no long-term side effects or morbidity from topical 5-fluorouacil or local excision. All colonoscopies were normal. CONCLUSION: Topical 5 percent 5-fluorouacil therapy is a safe and effective method to treat anal Bowen's disease. Wide local excision is appropriate for smaller, isolated areas of disease. Anal Bowen's disease was not associated with colonic or other neoplasms.
This paper describes two interactive templates for representing spatially indexed estimates. Both templates use a matrix layout of small panels. The first template, called linked micromap plots, can represent multivariate estimates associated with each spatially indexed study unit. The second template, called conditioned choropleth maps, shows the connection between a dependent variable, as represented in a classed choropleth map, and two explanatory variables. The paper describes the cognitive considerations that motivate the layouts and representation details. The discussion also addresses topics of data quality and access, hypothesis generation, and interactive features such as pan and zoom and dynamic conditioning via sliders. The examples show epidemiological (mortality rates) and environmental (toxic concentrations) applications.
The mapping resolution of the physical map for chicken Chromosome 4 (GGA4) was improved by a combination of radiation hybrid (RH) mapping and bacterial artificial chromosome (BAC) mapping. The ChickRH6 hybrid panel was used to construct an RH map of GGA4. Eleven microsatellites known to be located on GGA4 were included as anchors to the genetic linkage map for this chromosome. Based on the known conserved synteny between GGA4 and human Chromosomes 4 and X, sequences were identified for the orthologous chicken genes from these human chromosomes by BLAST analysis. These sequences were subsequently used for the development of STS markers to be typed on the RH panel. Using a logarithm of the odds (LOD) threshold of 5.0, nine linkage groups could be constructed which were aligned with the genetic linkage map of this chromosome. The resulting RH map consisted of the 11 microsatellite markers and 50 genes. To further increase the number of genes on the map and to provide additional anchor points for the physical BAC map of this chromosome, BAC clones were identified for 22 microsatellites and 99 genes. The combined RH and BAC mapping approach resulted in the mapping of 61 genes on GGA4 increasing the resolution of the chicken-human comparative map for this chromosome. This enhanced comparative mapping resolution enabled the identification of multiple rearrangements between GGA4 and human Chromosomes 4q and Xp.
Ogura cytoplasmic male sterility (CMS) in radish (Raphanus sativus) is caused by an aberrant mitochondrial gene, Orf138, that prevents the production of functional pollen without affecting female fertility. Rfo, a nuclear gene that restores male fertility, alters the expression of Orf138 at the post-transcriptional level. The Ogura CMS/Rfo two-component system is a useful model for investigating nuclear-cytoplasmic interactions, as well as the physiological basis of fertility restoration. Using a combination of positional cloning and microsynteny analysis of Arabidopsis thaliana and radish, we genetically and physically delimited the Rfo locus to a 15-kb DNA segment. Analysis of this segment shows that Rfo is a member of the pentatricopeptide repeat (PPR) family. In Arabidopsis, this family contains more than 450 members of unknown function, although most of them are predicted to be targeted to mitochondria and chloroplasts and are thought to have roles in organellar gene expression.
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Single nucleotide polymorphisms in the human genome have become an increasingly popular topic in that their analyses promise to be a key step toward personalized medicine. We investigate two related questions, how much the haplotype information contributes to linkage disequilibrium (LD) mapping and whether an in silico haplotype construction preceding the LD analysis can help. For disease gene mapping, using both simulated and real data sets on cystic fibrosis and the Alzheimer disease, we reached the following conclusions: (1) for simple Mendelian diseases, in which case a tractable full statistical model can be developed, the loss of haplotype information for either control or disease data do not have a great impact on LD fine mapping, and haplotype inference should be carried out jointly with LD mapping; (2) for complex diseases, inferring haplotype phases for individuals prior to LD mapping helps achieve a better accuracy. An improved version of the linkage disequilibrium mapping program, BLADE v2, is available at http://www.fas.harvard.edu/junliu/TechRept/03folder/bladev2.tgz.
The modeling of nonlinear descriptor-target relationships is a topic of considerable interest in drug discovery. We, herein, continue reporting the use of the self-organizing map-a nonlinear, topology-preserving pattern recognition technique that exhibits considerable promise in modeling and decoding these relationships. Since simulated annealing is an efficient tool for solving optimization problems, we combined the supervised self-organizing map with simulated annealing to build high-quality, highly predictive quantitative structure-activity/property relationship models. This technique was applied to six data sets representing a variety of biological endpoints. Since a high statistical correlation in the training set does not indicate a highly predictive model, the quality of all the models was confirmed by withholding a portion of each data set for external validation. Finally, we introduce new cross-validation and dynamic partitioning techniques to address model overfitting and assessment.
The management of the febrile infant is truly a complex and evolving topic in pediatrics. The clinical practice guideline provides a map for physician decision making in this important clinical issue. An individual physician may alter the course of action based on his or her treatment threshold but must recognize the limitations of that approach. Documentation of management decisions that deviate from published guidelines are important for patient care. The medical record must carefully represent the appearance of the patient, the actions taken, and the discussion with the family regarding management. Close follow-up includes phone contact with documentation and reexamination of the patient in a reasonable period of time. All who deal with the common problem of fever in infants should follow this subject closely and be ready to adopt new management strategies when evidence from outcomes-based research emerges. In the mean time, the current practice guideline offers an excellent starting point in the management of this common and vexing clinical problem.
We outline a theory of metaphor interpretation. The theory posits varying levels of semantic processing and formalizes them in terms of kinds of semantic-mapping operators that transform properties of the metaphoric vehicle (i.e., predicate) into properties of the metaphoric topic (i.e., subject). We used cognitive-developmental theory to estimate the mental-processing complexity of the various mapping operators, and thereby to predict the timing of their emergence in childhood, and to construct a measure of the metaphoric-processing levels. Metaphor interpretations collected from children (aged 6-12 years) and adults were coded and scored according to the processing levels. In two separate developmental studies, processing score increased with age in a predictable way. Growth in a mental-attentional resource accounted for much of the developmental variance in metaphor interpretation. Possible moderating effects of knowledge and context are discussed.