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PubMed1998

Increased apolipoprotein E mRNA in the hippocampus in Alzheimer disease and in rats after entorhinal cortex lesioning.

The distribution of apolipoprotein E (ApoE) mRNA was characterized in the hippocampus of humans with Alzheimer disease (AD) and in rats with experimental lesions (unilateral ablation of the entorhinal cortex) that model selected features of AD. In both AD and the lesion model, we observed a shift in the location of astrocytes containing prevalent ApoE mRNA from the neuropil to regions with densely packed neurons. The increased abundance of ApoE mRNA in astrocytes close to neuron cell bodies could be indicative of lipid uptake in regions where neurons are degenerating or where synaptic remodeling is taking place.

Alzheimer Disease↗

PubMed2000

Modular bacterial artificial chromosome vectors for transfer of large inserts into mammalian cells.

To facilitate the use of large-insert bacterial clones for functional analysis, we have constructed new bacterial artificial chromosome vectors, pPAC4 and pBACe4. These vectors contain two genetic elements that enable stable maintenance of the clones in mammalian cells: (1) The Epstein-Barr virus replicon, oriP, is included to ensure stable episomal propagation of the large insert clones upon transfection into mammalian cells. (2) The blasticidin deaminase gene is placed in a eukaryotic expression cassette to enable selection for the desired mammalian clones by using the nucleoside antibiotic blasticidin. Sequences important to select for loxP-specific genome targeting in mammalian chromosomes are also present. In addition, we demonstrate that the attTn7 sequence present on the vectors permits specific addition of selected features to the library clones. Unique sites have also been included in the vector to enable linearization of the large-insert clones, e. g., for optical mapping studies. The pPAC4 vector has been used to generate libraries from the human, mouse, and rat genomes. We believe that clones from these libraries would serve as an important reagent in functional experiments, including the identification or validation of candidate disease genes, by transferring a particular clone containing the relevant wildtype gene into mutant cells or transgenic or knock-out animals.

Animals↗

PubMed1995

Vasopressin gene related products are markers of human breast cancer.

Immunohistochemical analysis for products of vasopressin and oxytocin gene expression was performed on acetone-fixed tissues from 19 breast cancers representing a variety of tumor sub-types. Studies employed the avidin-biotin complex (ABC) immunohistochemical procedure and utilized rabbit polyclonal antibodies to arginine vasopressin (VP), provasopressin (ProVP), vasopressin-associated human glycopeptide (VAG), oxytocin (OT), oxytocin-associated human neurophysin (OT-HNP), and a mouse monoclonal antibody to vasopressin-associated human neurophysin (VP-HNP). Western Blot analysis was performed on protein extracts of fresh-frozen tissues from 12 additional breast tumors. While VP gene related proteins were not detected in normal breast tissue, immunohistochemistry revealed the presence of VP, ProVP, and VAG in all neoplastic cells for all of the tumor tissues examined. Vasopressin-associated human neurophysin was evident in only one of 19 acetone-fixed tumor preparations. However, Western blot analysis for all 12 fresh-frozen tumor samples showed the presence of two proteins, 42,000 and 20,000 daltons, that were immunoreactive with antibodies to VP, VP-HNP, and VAG. Oxytocin and OT-HNP, by immunohistochemistry, were found to be common to cells of normal breast tissues. For tumors, positive staining for OT was observed in 8 of 18 tumors, while OT-HNP was not detected in any of the tumors examined. These findings indicate that VP gene expression is a selective feature of all breast cancers, and that products of this expression might therefore be useful as markers for early detection of this disease and as possible targets for immunotherapy.

Antibodies, Monoclonal↗

PubMed1995

A study of the histological criteria for ulcerative colitis: retrospective evaluation of multiple colonic biopsies.

It is clinically important to distinguish idiopathic inflammatory bowel disease (IBD) from other colitides, and ulcerative colitis (UC) from Crohn's disease (CD); however only a few histological criteria based on colonic biopsies have been established. We investigated 209 consecutive series of biopsies taken from 38 patients with UC, 12 with CD, and 105 with other colitides, to evaluate whether combinations of histological features, selected on the basis of our experience, and listed below, could be useful criteria for the differential diagnosis of IBD, and, more specifically, of UC: (A) chronic inflammation with a predominant increase of plasma cells, (B) crypt distortion, (C) crypt atrophy, (D) diffuse chronic inflammation within a biopsy and between biopsies, and (E) diffuse mucin depletion within a biopsy and between biopsies. Findings that fulfilled all or two of A-C distinguished IBD from the other colitides with high sensitivity (94.3%) and specificity (95.8%). When the findings fulfilled the additional criteria of D and/or E, UC was differentiated from CD or the other colitides with high sensitivity (86.4%) and specificity (99.3%).

Adolescent↗

PubMed1993

Comparison of spectral techniques for computer-assisted classification of spectra of heart sounds in patients with porcine bioprosthetic valves.

The diagnostic performance of two spectral techniques (the fast Fourier transform, FFT, and autoregressive modelling, ARM) combined with four windowing functions (rectangular, Hanning, Hamming, and sine-cosine) and two classifiers (Bayes and nearest neighbour) to detect valvular degeneration was evaluated in a group of 95 patients. Forty-seven patients had a porcine bioprosthetic valve inserted in the aortic position and 48 patients had a porcine bioprosthetic valve inserted in the mitral position. Among the aortic valves, 24 were normal and 23 were degenerated whereas among the mitral valves, 19 were normal and 29 were degenerated. The aortic and mitral valves were analysed separately. For each type of valve, 21 features were extracted from the spectra of the valve closure sounds to train and test the performance of four pattern recognition systems by using the leave-one-out method. The discriminant properties of all feature combinations between two and five among the 21 features selected were evaluated. Results show that the FFT combined to the nearest neighbour classifier provided the best performances: 87 per cent of correct classifications (CCs) for aortic valves when using the Hanning or the Hamming window and 94 per cent of CCs for mitral valves when using the rectangular window. The best performances obtained with the ARM were 81 per cent of CCs for the aortic valves (nearest neighbour classifier and the Hanning or the Hamming window) and 92 per cent of CCs for the mitral valves (nearest neighbour classifier and the Hamming window or the Bayes classifier and the Hanning or the Hamming window).

Aortic Valve↗

PubMedDate not supplied

Serum extravasation and cytoskeletal alterations following traumatic brain injury in rats. Comparison of lateral fluid percussion and cortical impact models.

Disruption of the blood-brain barrier (BBB) and neuronal cytoskeletal damage were evaluated in two commonly used rat models of traumatic brain injury. Adult rats received a lateral cortical impact (CI) or lateral fluid percussion (FP) injury of mild or moderate severity or a sham procedure. Six hours after trauma, the brains were removed and analyzed with immunocytochemical techniques for alterations in the serum protein, IgG, and the cytoskeletal protein, microtubule-associated protein 2 (MAP2). Both models induced profound alterations in these proteins in the ipsilateral cortex and hippocampus compared to sham-injured controls. Following an injury of moderate severity, the CI injury resulted in greater IgG extravasation in the cortex and hippocampus than the FP injury. Conversely, after a mild injury, IgG extravasation in the hippocampus was greater for FP than CI. All of the animals in the CI group and most of the FP group showed a loss of MAP2 in the hippocampus. The specific subregions within the cortex and hippocampus that were affected by the injury varied between models, despite having identical impact sites. These data demonstrate that there are both similarities and differences between a CI and FP injury on vascular and neuronal cystoskeletal integrity, which should be considered when utilizing these animal models to study selected features of human head injury.

Animals↗

PubMed2000

Personality in frontal lobe disorders.

Personality changes in frontal lobe disorders are easy to recognize, but their evolution can be hard to predict. Both focal lesions and diffuse neurodegenerative processes may produce personality change based on interruption of prefrontal cortex or subcortical structures that comprise the frontal-subcortical circuits. Observed changes in personality have been classified by behavioral neurologists into three frontal-subcortical circuit syndromes, yet a given patient may defy this classification system by manifesting only selective features of one or more syndromes simultaneously, based on the neuroanatomic distribution of pathology. The orbitofrontal syndrome is the most well known and consists of major antisocial behaviors such as disinhibition, emotional lability, and impulsivity. In some cases, changes are severe enough to lead to new onset of criminality. Apathy and amotivational state lie at the other end of the personality change spectrum. Many psychologic instruments can measure the degree of change in personality, but none of them can be used to extrapolate a patient's ability to function at home or at large in society. The psychopathy checklist by Hare may predict risk of violence but has been validated only for use in criminal populations.

Brain Diseases↗

PubMed2025

Digital Immunophenotyping of Lung Atypical Carcinoids and Large Cell Neuroendocrine Carcinomas Identifies Three Subtypes With Specific Tumor-Immune Microenvironment Features.

Atypical carcinoids (ACs) and large cell neuroendocrine carcinomas (LCNECs) are defined by the WHO as intermediate- and high-grade lung neuroendocrine neoplasms, respectively, based on morphological criteria; however, treatment strategies remain debated. Given the emerging role of the tumor microenvironment (TME) and tumor-infiltrating lymphocytes (TILs) in cancer prognosis and therapy response, this study aimed to characterize the immune landscape of ACs and LCNECs comprehensively. Immunohistochemistry for T-cell markers (CD3, CD8), immune checkpoints (PD-1, PD-L1), HLA molecules (HLA-DR, HLA-I), and fibroblasts (α-SMA) was performed on a re-evaluated cohort of 56 ACs and 104 LCNECs. Digital image analysis quantified intra-tumor (iTILs) and stromal (sTILs) CD3 and CD8 TILs in the whole slide and in specific tumor regions (invasive margin [IM] and central tumor [CT]). LCNECs exhibited significantly higher stromal T-cell infiltration, immune checkpoint expression, and HLA compared to ACs (p < 0.001), while α-SMA was more prominent in ACs. No ACs showed PD-L1 tumor expression. Digital quantification confirmed greater iTILs and sTILs in LCNECs across all regions, with moderate concordance to manual counts. Interestingly, TIL parameters were higher at the IM than in the CT (p < 0.001). Using Boruta feature selection algorithm, Principal Component Analysis and Hierarchical Clustering, three patient clusters were identified: Cluster 1 (mainly ACs, low TILs, favorable prognosis), Cluster 2 (mixed histology, intermediate TILs, moderate prognosis), and Cluster 3 (mostly LCNECs, high TILs, poor prognosis), with distinct TME marker profiles. PD-L1 tumor expression was strongly linked to Cluster 3. These findings suggest that ACs and LCNECs may be stratified into three distinct immune clusters, highlighting the heterogeneity of their tumor microenvironment and providing a rationale for further translational studies.

Humans↗

PubMed1992

On AR modelling for MEG spectral estimation, data compression and classification.

The use of the autoregressive (AR) model for magnetoencephalogram (MEG) processing is examined and compared to other methods. Spectral estimation, classification and data compression of MEG signals are studied. In application to spectral estimation the AR model is compared to the classical modified periodogram method. Also, AR modelling appears to perform very successfully when used for the classification of normal and epileptic MEG signals. Finally, the 17:1 to 23:1 data compression achieved by AR modelling, along with the above-mentioned advantages, render it suitable for storage applications. For comparison, the method of feature selection via orthogonal expansion is used as a tool to achieve data reduction. It is seen that while effective, this is less drastic than the compression of data volume achieved by AR modelling.

Brain Mapping↗

PubMed1976

Dynamic decision models for clinical diagnosis.

A unified approach to clinical decision-making is presented. This combines partially observable Markovian decision processes (Markov or semi-Markov) with cause-effect models as a probabilistic representation of the diagnostic process. Pattern recognition techniques are used in a first stage of system state identification. This new class of dynamic models has a direct application to medical diagnosis and treatment and specific physiological examples are emphasised. The methodology is given for combining the patient state of health, the clinician's state of knowledge of the cause-effect representation from the observation space (measurements), feature selection using pattern recognition techniques and, finally, the treatment decisions with which to restore the patient to a more desirable state of health. A cost functional for the decision process has then to be optimised according to some pre-assigned objective function (social return from the patient state of health or treatment cost for the patient), when the process has an infinite time horizon.

Computers↗

PubMed1985

Becoming a nurse: the ethical perspective.

This paper examines selected features of neophyte nursing students' approach to the moral dimension of their future practice. It argues that rapid changes in medical technology and in social perceptions of morality necessitate a critical examination of the content, sequence and methods of introductory ethics education in nursing. It suggests that greater emphasis should be placed upon individual moral development; and that Codes of Ethics and Bills of Rights should be presented as ideal statements, to serve as guides in assessing the ethical situation of the client. Some reactions of students are reported.

Curriculum↗

PubMed1988

Evoked potential estimates of the time course of adaptation and recovery to counterphase gratings.

Scalp-recorded evoked potentials (VEP) were sequentially sampled in humans during adaptation to and recovery from prolonged viewing of counterphase sinusoidal grating targets. The sum of the power at the first and second harmonics of the Fourier-transformed VEP components was found to decrease during adaptation and increase during recovery. Time constants (T) for the adaptation and recovery processes as estimated from exponential functions ranged from 2.9 to 19 sec, varying non-monotonically with the spatial frequency and contrast of the stimulus. The observed T values are shorter than those reported in psychophysical studies of adaptation but overlap estimates derived from single cell studies. An unexpected finding was the occurrence of a 3-6 sec delay in the appearance of the maximum VEP response after the onset of the adaptation stimulus. The delay occurred in all subjects and at all spatial frequencies when moderate to high adapting contrasts (e.g. greater than 0.2) were used. The data support a feature-selective, multi-channel lateral inhibitory model of spatial vision and suggest the presence of tonic inhibition between the channels.

Adaptation, Ocular↗

PubMed1993

Post-reactivation cocaine administration facilitates later acquisition of an avoidance response in rats.

We previously demonstrated that cocaine administered immediately prior to a reactivation episode comprised of re-exposure to selected features of the original fear-conditioning session alters subsequent memory retrieval or reconsolidation. In the present study we determined that, similar to pre-reactivation administration, post-reactivation administration of cocaine also alters memory retrieval or reorganization, as measured by subsequent conditioned performance. The dose-response function for this effect of cocaine was U-shaped; maximal enhancement of subsequent avoidance performance was produced by a 7.5 mg/kg i.p. dose of cocaine. Because a dose of lidocaine equimolar to the effective cocaine dose was found not to alter subsequent conditioned performance, the effect of cocaine on memory processing most likely is not attributable to its local anesthetic properties.

Anesthetics, Local↗

PubMed1986

BMDP program for piecewise linear regression.

Piecewise linear regression has potentially broad applications in medical data analysis as well as other types of regression. Various kinds of algorithms have been proposed for finding optimum piecewise linear regressions. This paper presents a BMDP program for obtaining near optimum piecewise linear regression equations. An idea intrinsic to the method is that restricting parameter space to a discrete set makes the difficult problems become standard problems. Any software having the variable selection feature in the multiple linear regression can be used to apply the method.

Computers↗

PubMedDate not supplied

Beneficial effects of nicotine administered prior to a delayed matching-to-sample task in young and aged monkeys.

Our earlier studies have demonstrated that administration of low micrograms/kg doses of nicotine to young adult monkeys prior to a delayed matching-to-sample (DMTS) task resulted in a centrally mediated improvement in performance of the task, particularly when delay intervals which most greatly challenged the animal's capabilities were involved. The present study confirmed these findings using a completely computer driven and automated procedure. In addition, performance on the DMTS was observed to be enhanced when animals were again tested 24 h after the dose of nicotine. Further analysis of the data indicated that the majority of enhancement to nicotine could be accounted for by a greatly increased performance at the least preferred stimulus color. Position preference (left vs. right stimulus) was not a factor in nicotine-induced enhancement. Two aged monkeys (34 years old Macaca mulatta) were significantly more difficult to train in the DMTS task and their longest delay capabilities were significantly shorter than the young animals (Macaca fascicularis). Nevertheless, the aged animals were essentially similar in most respects in their responses to nicotine administration. These data are consistent with a role for central nicotinic systems in memory performance and with the ability of nicotine to produce enhancement of selective features of mnemonic strategy in young and old monkeys. Furthermore, it is possible that either model, the aged animal, or the young animal stressed to his mnemonic capability may provide a good model for learning and memory disorders in humans.

Aging↗

PubMed1986

Lung collagen and elastin after ozone exposure in vitamin B-6-deficient rats.

The effects of vitamin B-6 deficiency and ozone exposure on selected features of connective tissue metabolism in lung were investigated in groups of weanling male rats fed one of three diets: B-6-supplemented, fed ad lib; B-6-deficient, fed ad lib; or B-6-supplemented, restricted to the food intake of deficient rats for 5 weeks. Also, perinatal rat pups were studied that were nursed from dams fed one of the 3 diets from parturition to day 15 of lactation. During the final week of each experiment, half of the rats in each of the groups were exposed to 0.64 ppm of ozone (23.5 h per day). The collagen and elastin content, collagen synthesis rate, total protein synthesis rate, and lysyloxidase activity of lungs were measured. Perinatal pups rendered vitamin B-6-deficient were particularly sensitive to ozone exposure (65% died as compared to fewer than 5% of the ad lib or food-restricted controls). When L-proline incorporation into collagen and total protein was investigated using lung minces, food restriction and B-6-deficiency resulted in about one-half the incorporation normally observed. Total lung lysyl oxidase activity was also decreased in B-6-deficient and food-restricted rats compared to B-6-supplemented rats fed ad lib. Exposure to ozone resulted in increased lysyl oxidase activity and collagen synthesis in lungs from B-6-supplemented rats, but such responses were not observed in B-6-deficient or food-restricted (FR) rats exposed to ozone.

Aging↗

PubMedDate not supplied

Skin cancer recognition by computer vision.

Automatic detection of several features characteristic of basal cell epitheliomas is described. The features selected for this feasibility study are semitranslucency, telangiectasia, ulcer, crust, and tumor border. Image processing methods used in this study include frequency analysis of the Fourier transform of the image, the Sun-Wee texture analysis algorithm, and several other image analysis techniques suitable for skin photographs. This image analysis software is designed for use with AI/DERM, an expert system that models diagnosis of skin tumors by dermatologists.

Basal Cell Carcinoma↗

PubMed1996

Sleep classification in infants by decision tree-based neural networks.

This paper presents an AI-based approach to automatic sleep stage scoring. The system TBNN (Tree-Based Neural Network) uses a decision-tree generator to provide knowledge that defines the architecture of a backpropagation neural network, including feature selection and initialisation of the weights. The case study reports a successful application to the data from polygraphic all-night sleep of 8 babies aged 6 months. The teaching input was provided by a medical expert in accordance with the rules of Guilleminault and Souquet. The performance of TBNN is compared with 5 other methods and the results are discussed.

Artificial Intelligence↗