julilili42/papers huggingface dataset:
Symposia
2004-01-01

Goal: The goal of this symposium is to identify 'state-of-the-art' strategies for the use of antipsychotic medications in the management of children and adolescents with major psychiatric disorders. Learning objectives: 1. Define pediatric populations for whom second-generation antipsychotics are indicated 2. Identify the role of second-generation antipsychotics in the management of major psychiatric disorders in children and adolescents 3. Describe the level of evidence for the effectiveness of second-generation anti-psychotic use in youth 4. Discuss risk-benefit ratios of individual second-generation antipsychotics in pediatric populations 5. Use treatment algorithms and practice guidelines for the safe and effective use of second-generation antipsychotics in children and adolescents Background: Second-generation antipsychotics are increasingly prescribed to children and adolescents targeting a variety of psychotic and non-psychotic disorders. This is mainly due to lower rates of neuromotor side effects compared to conventional antipsychotics. In addition, second generation antipsychotics may also have superior and broader effectiveness than traditional antipsychotics. Content: This symposium will focus on the evaluation of the evidence base for the safety and effectiveness of second generation antipsychotics in the treatment of children and adolescents with major psychiatric disorders. Furthermore, treatment guidelines and algorithms will be presented to help guide clinician's treatment decisions.
Poster
2004-01-01

Objective: One of the most powerful medications that have very broad aspects of clinical application are the selective serotonin reuptake inhibitors (SSRI). We use SSRI as a first choice agents in treatment of depression, obsessive-compulsive disorders and some anxiety disordes. Objective: To analyze the outcome of treatment of adolescent depresion with SSRI's, considering the age group, disorder categories, response to treatment and side effects. Methods: A retrospective epidemiological investigation was conducted by means of medical records for all adolescent treated with sertraline during six months period at the Department of Child and Adolescent Psychiatry in Belgrade. The clinical response to treatment was rated by Beck Depression Inventory and Hamilton Depression Rating Scale. Results: 5 boys and 10 girls (mean age 15.7) were treated with sertraline during the first episode of depression; administred doses were 50–75 mg per day. 86% of patients improved, 10% droped out because of economic reasons, and 4% experienced side affects (nausea, vomiting, headache). Conclusion: Sertraline is potent, safe and effective in the treatment of young people with first episode of depression.
Abstracts: pp 362–385
2004-01-01

effect of cisplatin and its analogue oxaliplatin is related to basolateral organic cation tansport in MDCK cells (Ludwig et al, Kidney Int, in press).In humans and laboratory animals, cisplatin induced nephrotoxic damage is predominantly located in the S3 segment of the proximal tubule.The aim of this study was to investigate whether cisplatin and its less nephrotoxic derivative oxaliplatin specifically interact with human renal organic cation transporters.Methods: The human renal (hOCT2) or liver (hOCT1) transporters were stably transfected in HEK293 cells and their function was examined fluorimetrically with the cation 4-(4-(dimethyl-amino) styril)-methylpyridinium iodide (ASP, 1 M) as substrate.Acute interaction of cisplatin and oxaliplatin with ASP-uptake has been measured in these expression systems and also in freshly isolated human proximal tubules.All values are given as mean Ϯ SEM.Results: At a concentration of 100 M only cisplatin caused a significant inhibition of ASP-uptake in hOCT2-HEK293 cells (Ϫ29 Ϯ 4%, n ϭ 10), while oxaliplatin showed no significant effect (Ϫ2 Ϯ 6%, n ϭ 8).The same cisplatin concentration had no effect on the ASP-uptake in hOCT1-HEK293 cells (ϩ16 Ϯ 18%, n ϭ 11).The EC50 value for the inhibition of ASP-uptake in hOCT2-HEK293 cells was 1.6 M, maximal inhibition of ASP-uptake with the higher cisplatin concentration used (1 mM) was 40%.In freshly isolated human proximal tubules cisplatin was also able to significantly compete with ASP (Ϫ36 Ϯ 6%, n ϭ 3), while oxaliplatin showed no significant effect (Ϫ22 Ϯ 12%, n ϭ 3).Conclusions: These findings suggest that the uptake of cisplatin in renal proximal tubules is mediated by hOCT2.This transport is kidney-specific because hOCT1, the typical organic cation transport system of the liver showed no significant interaction of cisplatin with ASP-uptake.Combination of cisplatin with other substrates competing for OCT2 could decrease its nephrotoxicity.
Gene expression patterns of epithelial cells modulated by pathogenicity factors ofYersinia enterocolitica
2004-01-05

Epithelial cells express genes whose products signal the presence of pathogenic microorganisms to the immune system. Pathogenicity factors of enteric bacteria modulate host cell gene expression. Using microarray technology we have profiled epithelial cell gene expression upon interaction with Yersinia enterocolitica. Yersinia enterocolitica wild-type and isogenic mutant strains were used to identify host genes modulated by invasin protein (Inv), which is involved in enteroinvasion, and Yersinia outer protein P (YopP) which inhibits innate immune responses. Among 22 283 probesets (14,239 unique genes), we found 193 probesets (165 genes) to be regulated by Yersinia infection. The majority of these genes were induced by Inv, whose recognition leads to expression of NF-kappa B-regulated factors such as cytokines and adhesion molecules. Yersinia virulence plasmid (pYV)-encoded factors counter regulated Inv-induced gene expression. Thus, YopP repressed Inv-induced NF-kappa B regulated genes at 2 h post infection whereas other pYV-encoded factors repressed host cell genes at 4 and 8 h post infection. Chromosomally encoded factors of Yersinia, other than Inv, induced expression of genes known to be induced by TGF-beta receptor signalling. These genes were also repressed by pYV-encoded factors. Only a few host genes were exclusively induced by pYV-encoded factors. We hypothesize that some of these genes may contribute to pYV-mediated silencing of host cells. In conclusion, the data demonstrates that epithelial cells express a limited number of genes upon interaction with enteric Yersinia. Both Inv and YopP appear to modulate gene expression in order to subvert epithelial cell functions involved in innate immunity.
Cloning of a human antibody directed against human neuroblastoma cells and specific for human translation elongation factor 1α
2004-01-06

Abstract: Human sera have shown antitumor effects mediated by tumor‐specific immunoglobulin M (IgM) antibodies. Most people who have cytotoxic serum are in good health and show no evidence of exposure to tumor antigens. We characterized the serum of a healthy female adult that was highly lytic to a neuroblastoma cell line via IgM‐activated complement (&gt;60% of malignant cells were killed during the 60‐min assay). Complement‐dependent lysis was not mediated by other classes of serum antibodies (data not shown) which is consistent with the findings of Ollert et al. To identify the target antigen on neuroblastoma cells, we fractionated neuroblastoma cell lysates by ion‐exchange chromatography. In the fraction that showed maximal IgM binding, the dominant protein was identified as the 47‐kDa translational elongation factor 1α (eEF1α). We used the donor's B‐cells to create hybridomas producing the antibody (B12.6.22) that bound to neuroblastoma cells and mediated cytotoxicity. This antibody recognized eEF1α in a specific manner. Sequence analysis of the heavy chain of B12.6.22 showed usage of VH3‐23 and JH6 gene segments, with no somatic mutation. The structural similarity of B12.6.22 to antibodies of the innate immune system supports the assumption that natural antibodies are a potential source of therapeutic antibodies.
Sex-specific recombination rates in Parus major and P. caeruleus, an exception to Huxley's rule
2004-01-06

Huxley's rule predicts lower recombination rates in the heterogametic sex than in the homogametic one. The genotyping of Parus major and P. caeruleus families at 8 microsatellite and 4 enzyme loci yielded contradicting data. Significant genotypic disequilibrium was observed between esterase-1, esterase-2 and esterase-3 in adults of P. major and between esterase-2/esterase-3 and esterase-2/microsatellite PK-12 in P. caeruleus. Support comes from linkage analyses of nuclear families. In P. major, the recombination rate of esterase-2/esterase -3 in males is significantly lower than in females (theta(male) = 0.076, theta(female) = 0.145). The opposite is found for the recombination rates of esterase-1/esterase-2 and esterase-2/esterase-3 in P. caeruleus (EST-1/EST-2: theta(female) = 0.218, theta(male) = 0.5, EST-2/EST-3: theta(female) = 0.109, theta(male) = 0.194). We conclude that the basis of differences in recombination rates cannot be heterogamety, per se, but must have multiple genetic causes including chromosomal rearrangments that have evolved after the cladogenesis of the two species.
The transillumination possibility of imidazole‐osmium postfixed muscle tissue and its consequences for the handling of muscle tissue samples
2004-01-06

Abstract The osmium postfixation of tissue leads to good results for transmission electron microscopy, but also produces completely blackened tissue samples that do not allow the recognition of internal structures. With imidazole‐osmium postfixation, one achieves comparable results in high electron microscopic resolution as with routine osmium postfixation. But the tissue samples are not blackened and can, therefore, be transilluminated with point light sources. The new postfixation technique makes it possible to recognize histological details such as vessels, nerve fibers, and the cross‐banding pattern in an untrimmed block. This makes it possible to screen‐embedded tissue samples for appropriate ultrastructural processing. Microsc. Res. Tech. 63:129–132, 2004. © 2004 Wiley‐Liss, Inc.
Yeast Lacking theSRO7/SOP1-encoded Tumor Suppressor Homologue Show Increased Susceptibility to Apoptosis-like Cell Death on Exposure to NaCl Stress
2004-01-13

Yeast cells deleted for the SRO7/SOP1 encoded tumor suppressor homologue show increased sensitivity to NaCl stress. On exposure to growth-inhibiting NaCl concentrations, sro7Δ mutants display a rapid loss in viability that is associated with markers of apoptosis: accumulation of reactive oxygen species, DNA breakage, and nuclear fragmentation. Additional deletion of the yeast metacaspase gene YCA1 prevents the primary fast drop in viability and diminishes nuclear fragmentation and DNA breakage. We also observed that NaCl induced loss in viability of wild-type cells is Yca1p dependent. However, a yeast strain deleted for both SRO7 and its homologue SRO77 exhibits NaCl-induced cell death that is independent on YCA1. Likewise, sro77Δ single mutants do not survive better after additional deletion of the YCA1 gene, and both sro77Δ and sro77Δyca1Δ mutants display apoptotic characteristics when exposed to growth-inhibiting salinity, suggesting that yeast possesses Yca1p-independent pathway(s) for apoptosis-like cell death. The activity of Yca1p increases with increasing NaCl stress and sro7Δ mutants achieve levels that are higher than in wild-type cells. However, mutants lacking SRO77 do not enhance caspase activity when subject to NaCl stress, suggesting that Sro7p and Sro77p exert opposing effects on the cellular activity of Yca1p.
Improvement and Decline in Tactile Discrimination Behavior after Cortical Plasticity Induced by Passive Tactile Coactivation
2004-01-14

Perceptual learning can be induced by passive tactile coactivation without attention or reinforcement. We used functional MRI (fMRI) and psychophysics to investigate in detail the specificity of this type of learning for different tactile discrimination tasks and the underlying cortical reorganization. We found that a few hours of Hebbian coactivation evoked a significant increase of primary (SI) and secondary (SII) somatosensory cortical areas representing the stimulated body parts. The amount of plastic changes was strongly correlated with improvement in spatial discrimination performance. However, in the same subjects, frequency discrimination was impaired after coactivation, indicating that even maladaptive processes can be induced by intense passive sensory stimulation.
Protracted postnatal natural histories in childhood leukemia
2004-01-14

Abstract Studies of monozygotic twins with concordant leukemia and scrutiny of archived neonatal blood by polymerase chain reaction (PCR) indicated that many pediatric leukemias are initiated prenatally by chromosomal translocation followed by a variable postnatal period before diagnosis of disease. The latter is thought to reflect a persistent preleukemic stage and a requirement for secondary genetic events. We sought to examine this further by examination of blood spots in rare cases of MLL fusion‐positive or ETV6/RUNX1 ( TEL‐AML1 ) fusion gene–positive acute leukemia that were diagnosed at ages beyond the normal age range. We present evidence that the duration of the postnatal preleukemic state can occasionally be very protracted in these biological subtypes of pediatric leukemia, and we discuss its biological significance. © 2004 Wiley‐Liss, Inc.
Using SPM normalization for lesion analysis in spatial neglect
2004-01-14

Traditionally, the neglect syndrome has been associated with damage to the right inferior parietal lobule (IPL) and the right temporoparietal junction (Heilman et al ., 1983; Vallar and Perani, 1986). Thus, it was surprising when a recent study found that the centre of lesion overlap covered the right superior temporal gyrus and planum temporale, suggesting that the superior temporal cortex rather than the inferior parietal lobule is the critical substrate for spatial neglect in humans (Karnath et al ., 2001). In that study, the authors used a new tool for lesion analysis (MRIcro; www.mricro.com), which allows more precise lesion localization than ever before. Lesions are mapped manually on a T1‐weighted template MRI that is aligned with stereotaxic space (Rorden and Brett, 2000). The template scan provides various anatomical landmarks for precisely plotting the size and localization of the lesion. Moreover, automatic three‐dimensional rendering of the lesion data derived from the transverse slices is available (Rorden and Brett, 2000). This reduces significantly the uncertainty brought in by the paper‐and‐pencil procedures used in previous anatomical studies on spatial neglect (Heilman et al ., 1983; Vallar and Perani, 1986). In a recent article by Mort et al . (2003), the authors noted that the lesions in the study of Karnath et al . (2001) were still demarcated by hand onto standard template images. To overcome this limitation, Mort et al . (2003) used a lesion analysis method that did not rely on the manual transfer of lesions to standard template slices, employing a technique in which the location of the lesion is drawn directly onto the patient’s own MRI scan, and both the scan and the lesion shape are then mapped into stereotaxic space using an automated normalization process (Brett et al ., 2001). This procedure avoids the need for ...
Novel Polymer and Linker Reagents for the Preparation of Protease‐Inhibitor Libraries
2004-01-14

This chapter contains sections titled: A Concept for Advanced Polymer Reagents Protease-inhibitor Synthesis — A Demanding Test Case for Polymer Reagents The Development of Advanced Oxidizing Polymers Polymer-supported Heavy-metal Oxides Oxidation with Immobilized Oxoammonium Salts Oxidations with Immobilized Periodinanes Preparation of Peptide Aldehyde Collections Polymer-supported Acylanion Equivalents Conclusions References Polymer-supported Synthetic Methods — Solid-phase Synthesis (SPS) and Polymer-assisted Solution-phase (PASP) Synthesis Inhibition of Proteases
Immunomagnetic Enrichment, Genomic Characterization, and Prognostic Impact of Circulating Melanoma Cells
2004-01-15

Abstract Purpose: The finding of melanoma cells in the peripheral blood, thus far mainly inferred from the PCR-based demonstration of tyrosinase mRNA, has been associated with metastatic melanoma. Neither the malignant nature nor the prognostic significance of circulating cells could be established. To address this question, we analyzed immunomagnetically isolated circulating melanoma cells for chromosomal aberrations and performed a clinical follow-up study of the enrolled patients. Experimental Design: In a prospective study, blood samples were taken from 164 melanoma patients and 50 donors without malignant disease. Circulating melanoma cells were enriched by immunomagnetic cell sorting using a murine monoclonal antibody against the melanoma-associated chondroitin sulfate proteoglycan. To prove the malignant origin of the positive cells and to define their chromosomal aberrations, we analyzed the genomes of 15 individually isolated cells from seven patients by single-cell comparative genomic hybridization (SCOMP). Results: Absolute and relative frequencies of circulating melanoma cells were associated with stage and with the presence or absence of detectable tumor. The detection of two or more cells correlated significantly with a reduced survival of patients with metastatic melanoma. All of the cells that were analyzed by SCOMP displayed multiple chromosomal changes and carried aberrations typical for melanoma. Conclusions: Immunomagnetic enrichment enables isolation and genomic characterization of circulating melanoma cells. The prognostic impact on survival of metastatic patients apparently reflects the aggressiveness of an ongoing tumor spread. Direct genomic analysis of the enriched and isolated cells will help to clarify the molecular-genetic basis of the establishment of generalized melanoma.
Quantitative Analysis of Prion-Protein Degradation by Constitutive and Immuno-20S Proteasomes Indicates Differences Correlated with Disease Susceptibility
2004-01-15

Abstract The main part of cytosolic protein degradation depends on the ubiquitin-proteasome system. Proteasomes degrade their substrates into small peptide fragments, some of which are translocated into the endoplasmatic reticulum and loaded onto MHC class I molecules, which are then transported to the cell surface for inspection by CTL. A reliable prediction of proteasomal cleavages in a given protein for the identification of CTL epitopes would benefit immensely from additional cleavage data for the training of prediction algorithms. To increase the knowledge about proteasomal specificity and to gain more insight into the relation of proteasomal activity and susceptibility to prion disease, we digested sheep prion protein with human constitutive and immuno-20S proteasomes. All fragments generated in the digest were quantified. Our results underline the different cleavage specificities of constitutive and immunoproteasomes and provide data for the training of prediction programs for proteasomal cleavages. Furthermore, the kinetic analysis of proteasomal digestion of two different alleles of prion protein shows that even small changes in a protein sequence can affect the overall efficiency of proteasomal processing and thus provides more insight into the possible molecular background of allelic variations and the pathogenicity of prion proteins.
A Glutamate Receptor–Interacting Protein homolog organizes muscle guidance in Drosophila
2004-01-15

During Drosophila embryogenesis, developing muscles extend growth-cone–like structures to navigate toward specific epidermal attachment sites. Here, we show that the homolog of Glutamate Receptor–Interacting Proteins (DGrip) acts as a key component of proper muscle guidance. Mutations in dgrip impair patterning of ventral longitudinal muscles (VLMs), whereas lateral transverse muscles (LTMs) that attach to intrasegmental attachment sites develop normally. Myoblast fusion, stabilization of muscle contacts, and general muscle function are not impaired in the absence of DGrip. Instead, the proper formation of cellular extensions during guidance fails in dgrip mutant VLMs. DGrip protein concentrates at the ends of VLMs while these muscles guide toward segment border attachment sites. Conversely, LTMs overexpressing DGrip form ectopic cellular extensions that can cause attachment of these muscles to other muscles at segment borders. Our data suggest that DGrip participates in the reception of an attractive signal that emanates from the epidermal attachment sites to direct the motility of developing muscles. This dgrip phenotype should be valuable to study mechanistic principles of Grip function.
Evolution of planetary systems in resonance
2004-01-19

We study the time evolution of two protoplanets still embedded in a protoplanetary disk. The results of two different numerical approaches are presented and compared. In the first approach, the motion of the disk material is computed with viscous hydrodynamical simulations, and the planetary motion is determined by N-body calculations including exactly the gravitational forces exerted by the disk material. In the second approach, only the N-body integration is performed but with additional dissipative forces included such as to mimic the effect of the disk torques acting on the disk. This type of modeling is much faster than the full hydrodynamical simulations, and gives comparative results provided that parameters are adjusted properly. Resonant capture of the planets is seen in both approaches, where the order of the resonance depends on the properties of the disk and the planets. Resonant capture leads to a rise in the eccentricity and to an alignment of the spatial orientation of orbits. The numerical results are compared with the observed planetary systems in mean motion resonance (Gl 867, HD 82943, and 55 Cnc). We find that the forcing together of two planets by their parent disk produces resonant configurations similar to those observed, but that eccentricity damping greater than that obtained in our hydrodynamic simulations is required to match the GJ 876 observations.
Evolution of planetary systems in resonance
2004-01-19

We study the time evolution of two protoplanets still embedded in a protoplanetary disk. The results of two different numerical approaches are presented and compared. In the first approach, the motion of the disk material is computed with viscous hydrodynamical simulations, and the planetary motion is determined by N-body calculations including exactly the gravitational forces exerted by the disk material. In the second approach, only the N-body integration is performed but with additional dissipative forces included such as to mimic the effect of the disk torques acting on the disk. This type of modeling is much faster than the full hydrodynamical simulations, and gives comparative results provided that parameters are adjusted properly. Resonant capture of the planets is seen in both approaches, where the order of the resonance depends on the properties of the disk and the planets. Resonant capture leads to a rise in the eccentricity and to an alignment of the spatial orientation of orbits. The numerical results are compared with the observed planetary systems in mean motion resonance (GJ 876, HD 82943, and 55 Cnc). We find that the forcing together of two planets by their parent disk produces resonant configurations similar to those observed, but that eccentricity damping greater than that obtained in our hydrodynamic simulations is required to match the GJ 876 observations.