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Biomedical subjects

Robert Hoffmann

Publications and source records attributed to Robert Hoffmann.

15 recordsLinked to original sources

Sleep microarchitecture in childhood and adolescent depression: temporal coherence.

Previous work has indicated that low temporal coherence of ultradian sleep EEG rhythms is characteristic of depressed patients and women in particular. It may also be evident in depressed children and adolescents, although most published studies are limited in sample size. The present study evaluated temporal coherence of sleep EEG rhythms in 173 children and adolescents 8-17 years of age, including 97 who met criteria for major depressive disorder (MDD) and were symptomatic but unmedicated at the time of study and 76 healthy controls. Temporal coherence of all-night sleep EEG rhythms was evaluated on the second of two nights in the laboratory. Data were coded for diagnostic group, gender and age and subjected to MANOVAs. Temporal coherence was significantly lower in adolescents with MDD, compared to healthy controls. Findings were most robust for coherence between left and right beta and between delta and beta in both hemispheres. Both gender and age strongly influenced between-group differences, with the lowest temporal coherence among MDD girls, even in those under 13 years of age. In conclusion, early onset depression is associated with a reduction in synchronization of sleep EEG rhythms that shows a differential maturational course in boys and girls.

Adolescent↗

HomoMINT: an inferred human network based on orthology mapping of protein interactions discovered in model organisms.

BACKGROUND: The application of high throughput approaches to the identification of protein interactions has offered for the first time a glimpse of the global interactome of some model organisms. Until now, however, such genome-wide approaches have not been applied to the human proteome. RESULTS: In order to fill this gap we have assembled an inferred human protein interaction network where interactions discovered in model organisms are mapped onto the corresponding human orthologs. In addition to a stringent assignment to orthology classes based on the InParanoid algorithm, we have implemented a string matching algorithm to filter out orthology assignments of proteins whose global domain organization is not conserved. Finally, we have assessed the accuracy of our own, and related, inferred networks by benchmarking them against i) an assembled experimental interactome, ii) a network derived by mining of the scientific literature and iii) by measuring the enrichment of interacting protein pairs sharing common Gene Ontology annotation. CONCLUSION: The resulting networks are named HomoMINT and HomoMINT_filtered, the latter being based on the orthology table filtered by the domain architecture matching algorithm. They contains 9749 and 5203 interactions respectively and can be analyzed and viewed in the context of the experimentally verified interactions between human proteins stored in the MINT database. HomoMINT is constantly updated to take into account the growing information in the MINT database.

Algorithms↗

Implementing the iHOP concept for navigation of biomedical literature.

MOTIVATION: The World Wide Web has profoundly changed the way in which we access information. Searching the internet is easy and fast, but more importantly, the interconnection of related contents makes it intuitive and closer to the associative organization of human memory. However, the information retrieval tools currently available to researchers in biology and medicine lag far behind the possibilities that the layman has come to expect from the internet. RESULTS: By using genes and proteins as hyperlinks between sentences and abstracts, the information in PubMed can be converted into one navigable resource. iHOP (Information Hyperlinked over Proteins) is an online service that provides this gene-guided network as a natural way of accessing millions of PubMed abstracts and brings all the advantages of the internet to scientific literature research. Navigating across interrelated sentences within this network is closer to human intuition than the use of conventional keyword searches and allows for stepwise and controlled acquisition of information. Moreover, this literature network can be superimposed upon experimental interaction data to facilitate the simultaneous analysis of novel and existing knowledge. The network presented in iHOP currently contains5 million sentences and 40 000 genes from Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Danio rerio, Arabidopsis thaliana, Saccharomyces cerevisiae and Escherichia coli. AVAILABILITY: iHOP is freely accessible at http://www.pdg.cnb.uam.es/UniPub/iHOP/

Biomedical Engineering↗

Text mining for metabolic pathways, signaling cascades, and protein networks.

The complexity of the information stored in databases and publications on metabolic and signaling pathways, the high throughput of experimental data, and the growing number of publications make it imperative to provide systems to help the researcher navigate through these interrelated information resources. Text-mining methods have started to play a key role in the creation and maintenance of links between the information stored in biological databases and its original sources in the literature. These links will be extremely useful for database updating and curation, especially if a number of technical problems can be solved satisfactorily, including the identification of protein and gene names (entities in general) and the characterization of their types of interactions. The first generation of openly accessible text-mining systems, such as iHOP (Information Hyperlinked over Proteins), provides additional functions to facilitate the reconstruction of protein interaction networks, combine database and text information, and support the scientist in the formulation of novel hypotheses. The next challenge is the generation of comprehensive information regarding the general function of signaling pathways and protein interaction networks.

Animals↗

Acute hepatitis induced by an Aloe vera preparation: a case report.

AIM: Aloe vera, plant extracts of Aloe barbadensis miller, is widely used in phytomedicine. The first case of acute hepatitis due to this compound was described. METHODS: Description of a clinical case. RESULTS: Hepatitis in a 57-year old female could be linked to the ingestion of Aloe barbadensis miller compounds. The patient's hepatitis resolved completely after discontinuing this medication. CONCLUSION: The case emphasizes the importance of considering phytopharmaceutical over-the-counter drugs as causative agents of hepatitis.

Alanine Transaminase↗

HCAD, closing the gap between breakpoints and genes.

Recurrent chromosome aberrations are an important resource when associating human pathologies to specific genes. However, for technical reasons a large number of chromosome breakpoints are defined only at the level of cytobands and many of the genes involved remain unidentified. We developed a web-based information system that mines the scientific literature and generates textual and comprehensive information on all human breakpoints. We show that the statistical analysis of this textual information and its combination with genomic data can identify genes directly involved in DNA rearrangements. The Human Chromosome Aberration Database (HCAD) is publicly accessible at http://www.pdg.cnb.uam.es/UniPub/HCAD/.

Chromosome Breakage↗

High frequency EEG activity during sleep: characteristics in schizophrenia and depression.

Previous studies indicate that high frequency power (>20Hz) in the electroencephalogram (EEG) are associated with feature binding and attention. It has been hypothesized that hallucinations and perceptual abnormalities might be linked to irregularities in fast frequency activity. This study examines the power and distribution of high frequency activity (HFA) during sleep in healthy control subjects and unmedicated patients with schizophrenia and depression. This is a post-hoc analysis of an archival database collected under identical conditions. Groups were compared using multivariate analyses of covariance (MANCOVA) using group frequency by stage analysis. A multiple regression analyzed the association between HFA power and clinical symptoms. Schizophrenic (SZ) and major depressive disorder (MDD) patients showed significantly greater high frequency (HF) power than healthy controls (HC) in all sleep stages (p<0.0001). SZs also exhibited significantly greater HF power than MDD patients in all sleep stages except wakefulness (W) (p<0.05). In all groups, gamma (35-45Hz) power was greater in W, decreased during slow wave sleep (SWS) and decreased further during rapid eye movement (REM). Beta 2 (20-35 Hz) power was greater in W and REM than in SWS. Only positive symptoms exhibited an association with HF power. Elevated HFA during sleep in unmedicated patients with SZ and MDD is associated with positive symptoms of illness. It is not clear how HFA would change in relation to clinical improvement, and further study is needed to clarify the association of HFA to the state/trait characteristics of SZ and MDD.

Adult↗

Rest-activity cycles in childhood and adolescent depression.

OBJECTIVE: To quantify circadian rhythms in rest-activity cycles in depressed children and adolescents. METHOD: Rest-activity cycles were evaluated by actigraphy over five consecutive 24-hour periods in 100 children and adolescents, including 59 outpatients with major depressive disorder (MDD) and 41 healthy normal controls. Total activity, total light exposure, and time spent in light at more than 1,000 lux were averaged over the recording period for each participant. Time series analysis was used to determine the amplitude and period length of circadian rhythms in rest-activity. RESULTS: Overall, adolescents with MDD had lower activity levels, damped circadian amplitude, and lower light exposure and spent less time in bright light than healthy controls. Among children, those with MDD showed lower light exposure and spent less time in bright light, but only depressed girls showed damped circadian amplitude. The sex differences were substantially greater in the MDD group than in the normal control group. CONCLUSIONS: These results confirm damped circadian rhythms in children and adolescents with MDD and highlight the influence of gender and age on these measures.

Activity Cycles↗

The effects of vagus nerve stimulation on sleep EEG in depression: a preliminary report.

OBJECTIVE: The present study evaluated the effects of vagus nerve stimulation (VNS) on sleep in seven treatment-resistant depressed outpatients. METHODS: Sleep studies were conducted in the laboratory at baseline and 10-12 weeks after VNS implantation while the concomitant psychotropic medication regimen was unchanged. Standard sleep macroarchitecture based on visual stage and assessment of ultradian sleep electroencephalographic (EEG) rhythms were measured on all nights. RESULTS: An overall significant treatment effect on sleep macroarchitecture was obtained by MANOVA. Decreased awake time, decreased Stage 1 sleep and increased Stage 2 sleep were evident post-VNS, although univariate analyses did not reach significance. In addition, the strength or amplitude of ultradian sleep EEG rhythms more than doubled on VNS and was restored to within normal range. CONCLUSION: VNS improved the clinical symptoms of depression and sleep architecture. Results suggest that treatment-resistant depressed patients have dampened sleep EEG rhythms that are restored to near-normal amplitudes with VNS treatment.

Adult↗

Life cycles of successful genes.

By exploring time-series data from MEDLINE abstracts, we observe that only a few genes have been quoted with increasing frequency during the past 25 years. This is probably the result of selective pressure by the scientific community. Over the years, this selection has produced an extreme power law distribution of the information available for individual genes. Interestingly, those genes that are successfully selected are not necessarily the most important genes to the cell. To stress the implication of this finding we show that there is no correlation between a gene's impact in the scientific literature and its centrality in protein-interaction networks.

Cell Cycle↗

The neurobiology of depression: perspectives from animal and human sleep studies.

This article reviews human and animal studies in the neurobiology of depression. The etiology of the illness, associated neurotransmitter dysregulation, sex steroids, the role of stress, and sleep regulation are discussed. It is suggested that the genesis of depression is related to homeostatic maladaptation that is sexually dimorphic. The authors propose that depressed females are hyperresponsive to stress, whereas depressed males are hyporesponsive to stress. This divergence reflects the exaggeration of naturally occurring differences between males and females, which are most obvious under challenge conditions. The authors conclude that future work in this area should fully evaluate sexual dimorphism, neural plasticity, critical periods, and individual differences in vulnerability.

Acetylcholine↗

Short note: oral contraceptives and sleep in depressed and healthy women.

STUDY OBJECTIVES: To evaluate the effects of oral contraceptives (OCs) on sleep EEG in healthy women and in those with major depressive disorders (MDD). DESIGN: This archival study selected participants who had sleep EEG measured over two consecutive nights, following a five-day regularized sleep-wake routine. Between-groups multivariate analysis of variance (MANOVA) contrasted group and OC main effects and interactions on sleep architecture. SETTING: N/A PARTICIPANTS: Sixty-eight women (ages 14-46 years) diagnosed with major depressive disorder (MDD), 13 of whom were on OCs and 55 were not. Patients were symptomatic and untreated at the time of study. Thirty-seven healthy control women (ages 12-46 years), nine of whom were on OCs and 28 were not. INTERVENTIONS: N/A Measurements and Results: OC main effects were found for %SW and for REM latency. Significant OC x Group interactions were found for sleep latency and %REM. Sleep latency was significantly shorter on OCs, but only in healthy women. Women on OCs showed a shorter REM latency, more total REM time, and less slow-wave sleep than women who were not on OCs. CONCLUSIONS: The effects of OCs were generally larger in healthy women than in those with MDD. Moreover, OC use was associated with more disturbed sleep in healthy women. These findings imply that OC use may compromise sleep EEG differences between healthy and depressed women and may be more difficult to differentiate between depressed patients and healthy controls when sleep studies include women on OCs. These findings may also have implications for evaluating gender differences in sleep architecture.

Adolescent↗

Hepatitis C virus eradication associated with hepatitis B virus superinfection and development of a hepatitis B virus specific T cell response.

BACKGROUND/AIMS: Specific T cell responses during acute hepatitis B and during chronic hepatitis C have been described in detail. However, the T cell responses during the rare setting of acute hepatitis B virus (HBV) infection in the course of chronic hepatitis C that eventually lead to clearance of both viruses are completely unknown. METHODS: We analyzed the virus specific CD4+ and CD8+ T cell response during an acute HBV superinfection in a patient with chronic hepatitis C. RESULTS: The patient eliminated hepatitis C virus (HCV)-RNA and HBV-DNA from serum soon after the clinical onset of acute hepatitis B. The HBV specific T cell response found in this patient corresponds to the typical response that has been described in acute hepatitis B without chronic HCV infection. In contrast the hepatitis C specific immune response was similar to that generally found in chronic hepatitis C despite the fact that the patient also eliminated HCV-RNA. CONCLUSIONS: We hypothesize that the acute HBV infection induced a HBV specific T cell response which was associated with elimination HBV DNA and HCV-RNA, the latter possibly by bystander mechanisms, e.g. via secretion of cytokines. If such a non-specific bystander mechanism which has proven to be effective in the experimental setting and which is formally described here for a single patient can be shown to be a more general phenomenon, it may support the approach with new antiviral strategies, e.g. the induction of non-specific defense mechanisms against HCV.

Acute Disease↗