Search

Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

The Protein Ontology (PRO; http://proconsortium.org) formally defines protein entities and explicitly represents their major forms and interrelations. Protein entities represented in PRO corresponding to single amino acid chains are categorized by level of specificity into family, gene, sequence and modification metaclasses, and there is a separate metaclass for protein complexes. All metaclasses also have organism-specific derivatives. PRO complements established sequence databases such as UniProtKB, and interoperates with other biomedical and biological ontologies such as the Gene Ontology (GO). PRO relates to UniProtKB in that PRO's organism-specific classes of proteins encoded by a specific gene correspond to entities documented in UniProtKB entries. PRO relates to the GO in that PRO's representations of organism-specific protein complexes are subclasses of the organism-agnostic protein complex terms in the GO Cellular Component Ontology. The past few years have seen growth and changes to the PRO, as well as new points of access to the data and new applications of PRO in immunology and proteomics. Here we describe some of these developments.

The Cell Ontology (CL) aims for the representation of in vivo and in vitro cell types from all of biology. The CL is a candidate reference ontology of the OBO Foundry and requires extensive revision to bring it up to current standards for biomedical ontologies, both in its structure and its coverage of various subfields of biology. We have now addressed the specific content of one area of the CL, the section of the ontology dealing with hematopoietic cells. This section has been extensively revised to improve its content and eliminate multiple inheritance in the asserted hierarchy, and the groundwork has been laid for structuring the hematopoietic cell type terms as cross-products incorporating logical definitions built from relationships to external ontologies, such as the Protein Ontology and the Gene Ontology. The methods and improvements to the CL in this area represent a paradigm for improvement of the entire ontology over time., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: In the general hospital setting, alcohol-use disorders very commonly remain undetected., Objective: The authors hypothesized that including a consultation-liaison (C-L) psychiatrist in primary-care rounds would improve detection rates of alcohol-use-disorders., Method: Patients (N=165) on two medical wards were screened by means of the Alcohol Use Disorders Identification Test. Diagnoses were confirmed with the International Diagnostic Checklists and compared with physicians' detection rates. C-L intervention included demonstrations of standardized diagnostic procedures in order to change primary-care physicians' behavior., Results: Primary-care-physicians' detection rates of alcohol-use disorders increased significantly after implementation of the C-L service, whereas no significant differences were observed on the control ward., Conclusion: Tentative data thus underscore the efficacy of C-L psychiatry for detection and intervention in alcohol-use disorders.

Objective: Based on the Obsessive Compulsive Drinking Scale (OCDS) we developed and validated the Mannheimer Craving Scale (MaCS) for quantitative measurements of craving across different substances and suitable for multiple substance abuse., Methods: The MaCS questionnaire measures obsessive-compulsive symptoms in the context of substance abuse and dependence similar to the OCDS. The MaCS consists of 12 items and 4 additional items. Validation of the instrument was performed by means of 3 assessments of each subject within a project for the evaluation of a detox treatment on n = 292 alcohol and drug-dependent patients with multiple substance abuse., Results: The MaCS showed a very high measurement reliability (0.87 < alpha < 0.93). The MaCS total score correlated highly significant with the mean intensity of craving (0.47 < r (tc ) < 0.64, p < 0.0001), with the maximum of craving (0.52 < r (tc) < 0.69, p < 0.0001), and with the frequency of craving (0.43 < r (tc) < 0.65, p < 0.0001) measured by means of analogue scales., Conclusions: The MaCS for overall measurements of craving across multiple substances showed very good reliability and validity. In combination with a simple and universal feasibility of the MaCS these results indicate the applicability in everyday clinical settings as well as scientific settings.

Since the application of the Obsessive Compulsive Drinking Scale (OCDS) has been reported to be problematic when used to measure alcohol craving in longitudinal studies, we examined the following questions: (1) Is it possible to skip problematic quantity items? (2) Is the score calculation rule using the higher value of item pairs necessary? (3) Can the shortened version of the OCDS be applied alternatively? We examined two samples including a total of 355 alcohol-dependent patients: a multi center study sample (n=149) and a validation control sample (n=206). Neither an advantage of the score calculation rule nor the necessity of including items regarding alcohol consumption could be demonstrated. The exclusion of consumption items lead to a clear, stable 2-factor structure with a maximum stability (.81-.91). Retest-reliability ranged from r(tt)=.73 to r(tt)=.76 at an average time interval of 5 weeks. Concerning stability (.68-.81) and reliability (r(tt)=.76), the short version turned out to be equivalent. The short version of the OCDS seems to be sufficient. If different effects on cognitive and behavioral levels are expected, the 12-item version without the quantity items should be applied.

Objective: This study aims at evaluating the tolerability and efficacy of the antiepileptic drug oxcarbazepine in benzodiazepine detoxification in ten patients., Methods: In this case study of an inpatient withdrawal program, each of the ten patients was detoxified using oxcarbazepine and completed withdrawal successfully without the occurrence of withdrawal symptoms. The detoxification program followed an outlined dosage scheme with oxcarbazepine increase and benzodiazepine tapering., Results: The rapidity of benzodiazepine detoxification using oxcarbazepine was remarkable, benzodiazepine withdrawal being completed in as little as 11 days., Conclusions: The results support the assumption that oxcarbazepine is a valuable drug for inpatient benzodiazepine withdrawal programs.

Objective: For more than 50 years, disulfiram has been approved for the treatment of chronic alcohol dependence. In the last years there has been observed an increase in the prescription of disulfiram in germany. It acts as a psychological deterrence of a possible disulfiram-alcohol reaction. This paper describes the current clinical impact and possible future of disulfiram., Methods: Clinical trials using disulfiram for the treatment of alcohol dependence were discussed. Furthermore, the options of combining disulfiram with novel anti-craving agents were considered. Moreover, experiences and results of a cross section of the Mannheimer Disulfiram program will be presented., Results and Conclusions: Nowadays there exists consent in the matter that Disulfiram should only be adminsitered as part of a comprehensive therapy program, this means in the context of an intake under medical supervision. This paper is supposed to help estimate the value of disulfiram in recent addiction medicine.

Objectives: In the present study, we investigated whether buprenorphine as a partial mu-opioid receptor agonist is associated with less cognitive impairment than methadone., Methods: Neuropsychological functioning of opioid-dependent patients, previously assigned to methadone (MMP, n = 30) or buprenorphine (BMP, n = 26) maintenance treatment according to their own preference, was compared and dose effects were investigated., Results: MMP and BMP performed equally well on all measures of neuropsychological functioning including the trail making test, the continuous performance test, and a vigilance task. However, patients receiving a higher dose of methadone were impaired in a vigilance task., Conclusions: In a free-choice administration of methadone or buprenorphine, there seems to be no difference in cognitive functioning. Possible explanations are discussed.

Onset and course of alcohol dependence show gender related differences (telescoping effect) suggesting that women are more vulnerable to chronic alcohol consumption. This raises the question whether the differences are associated with a different treatment outcome as well. We hypothesized, that alcohol dependent women with a telescoping course show a less favourable treatment outcome compared to men. We investigated 212 alcohol dependent patients; matching 106 consecutively admitted women with 106 men drawn from a total sample of 343 male patients. The treatment program consisted of a 6 week inpatient treatment and 12 months of outpatient aftercare. We assessed milestone variables in development and course of alcoholism and carried out standardized diagnostic tests, physical and blood examinations to evaluate the course of the disease and treatment outcome. Overall, we confirm the telescoping effect, a faster progression in the course of alcoholism (developmental events and adverse consequences) in women compared to men ("telescoping effect"). However, despite the telescoping effect treatment outcome was similar in women and men. During the inpatient treatment program no alcohol relapse occurred. Throughout the 12 months outpatient treatment we found no significant differences in the survival analysis between women (283.29+/-11.26 days) and men (284.72+/-12.16 days). At the end of the 12 months both groups had an abstinence rate of approximately 50% and a drop-out rate of 33%.

Objective: There's still no effective treatment established for Tardive Dyskinesia. Aim of the study was to analyse the effect of pergolide, a D1 and D2 receptor agonist with prevalence for presynaptic auto receptors, in oro-facial tardive dyskinesia by means of a double-blind, placebo controlled cross-over study. Low-dose pergolide should activate presynaptic auto receptors, decrease dopamintransmission and reduce tardive dyskinesia., Method: Assessment of dyskinesia was performed with the computer-assisted technique Digital-Imaging-Processing in addition to the clinical scale AIMS (Abnormal-Involuntary-Movement-Scale). 10 patients with oro-facial dyskinesia were examined for alteration to dyskinesia, psychopathology, vital functions and laborchemical parameter., Results: Dyskinesia decreased 25 % for relax and 17 % for task conditions under pergolide treatment. Low-dose pergolide showed no side effects or worsening of the psychopathological state. Results of the Digital-Imaging-Processing correlated significantly with the results of clinical AIMS scale, but the computer-assisted technique gives more detailed information about degree and type of the movement disorder., Conclusion: Results suggest a therapeutic effect of pergolide in tardive dyskinesia, this has to be verified with a larger study population and longer observation. Assessment of dyskinesia is rater independent and more significant with the computer-assisted technique.