Welcome to Wordpublish.org Body!
Dendritic cells are professional antigen-presenting cells with a key role in both immunity induction and tolerance maintenance. Dendritic cells are highly specialized in antigen capture, processing and presentation, and express co-stimulation signals which activate T lymphocytes and NK cells. Dendritic cells generated in culture and loaded with an antigen efficiently induce antigen-specific immunity after injection. More recently, methods have been developed that target antigens to dendritic cells in vivo, bypassing the need for ex vivo cell manipulations. Numerous ongoing studies aim to evaluate the effectiveness of dendritic cell vaccines in preventing tumor relapses and extending patients’ survival. Further implementation of this form of immunotherapy is expected following the identification of the mechanisms controlling dendritic cell immunogenicity, and from a better understanding of the cell dynamics whereby immune responses are orchestrated. Here, we discuss these new insights together with an overview of the dendritic cell-based clinical studies carried out to date.
Alberto Ballestreroa Davide Boya Eva Morana Gabriella Cirmenaa Peter Brossartb Alessio NencioniaEmail:A.Nencioni@gmx.net
[a]Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy;[b]Department of Hematology, Oncology and Immunology, University of Tübingen, D-72076 Tübingen, Germany
Progress in gene therapy has produced promising results that translate experimental research into clinical treatment. Gene modification has been extensively employed in cell transplantation. The main barrier is an effective gene delivery system. Several viral vectors were utilized in end-stage differentiated cells. Recently, successful applications were described with adenovirus-associated vectors. As an alternative, embryonic stem cell- and stem cell-like systems were established for generation of tissue-specified gene-modified cells. Owing to the feasibility for genetic manipulations and the self-renewing potency of these cells they can be used in a way enabling large-scale in vitro production. This approach offers the establishment of in vitro cell culture systems that will deliver sufficient amounts of highly purified, immunoautologous cells suitable for application in regenerative medicine. In this review, the current technology of gene delivery systems to cells is recapitulated and the latest developments for cell transplantation are discussed.
Yi Laia Irina Drobinskayab Eugen Kolossovc Chunguang Chend Thomas LinndEmail:Thomas.linn@innere.med.uni-giessen.de
[a]Department of Molecular Microbiology & Immunology, University of Missouri-Columbia, USA;[b]Institute for Neurophysiology, University of Cologne, Germany;[c]Axiogenesis AG, Cologne, Germany;[d]Medical Clinic and Policlinic 3, Justus Liebig University, Rodthohl 6, 35392 Giessen, Germany
Among the family of the so-called cell-penetrating peptides (CPP) sequences derived from the native peptide hormone human calcitonin (hCT) have recently proven to translocate different bioactive molecules across cellular membranes. Herein, we give an extensive summary of the development of hCT-derived carrier peptides, beginning with the therapeutic nasal administration of full-length hCT. Hence, N-terminally truncated hCT fragments were investigated and subsequently optimised to extend their field of application. The latest generation of hCT-derived carrier peptides are highly effective, branched peptides. The current state of the art is reviewed concerning the structural requirements, mechanistic assumptions and metabolic features of these peptides as well as experiments proving their excellent carrier potential.
Robert Rennerta Ines Neundorfa Annette G. Beck-SickingeraEmail:beck-sickinger@uni-leipzig.de
[a]Institute of Biochemistry, Faculty of Bioscience, Pharmacy and Psychology, Leipzig University, Brüderstr. 34, D-04103 Leipzig, Germany
Aims Trials in Switzerland, the Netherlands and Spain have found that heroin-assisted treatment (HAT) as maintenance treatment for opioid-dependent patients reduces illicit drug use. A German trial also found diamorphine treatment to be superior to methadone treatment. The present study describes the association between 2 years of heroin treatment and improvements in health and social stabilization, as well as illicit drug use. Design A prospective cohort study design. Participants A total of 515 patients were assigned to diamorphine treatment; 278 patients remained in the study treatment for the entire period of 24 months (54.8%). Measurements The results on physical (Opiate Treatment Index Health Symptoms Scale) and mental (Symptom Checklist 90-Revised Global Severity Index) health and illicit drug use (number of days with drug use within the last month-European Addiction Severity Index) were examined by repeated-measures analyses. Findings Symptoms of physical (Pillai’s trace = 0.837, df = 4, P < 0.001) and mental health (Pillai’s trace = 0.450, df = 4, P < 0.001) improved during treatment. Street heroin use declined rapidly (Pillai’s trace = 0.836, df 4, P < 0.001), as did cocaine use (Pillai’s trace Conclusions HAT is associated with improvements in mental and physical health in the long term.
Verthein,U Bonorden-Kleij,K Degkwitz,P Dilg,C Kohler,WK Passie,T Soyka,M Tanger,S Vogel,M Haasen,C
Centre for Interdisciplinary Addiction Research of Hamburg University, CIAR, Hamburg, Germany.
Aims Addiction is a frequent comorbid disorder in schizophrenia and associated with poor outcome. The present study sought to determine whether addicted and non-addicted schizophrenic patients are impaired differentially on the executive abilities of working memory and multi-tasking which are relevant for maintaining abstinence. Design Comparisons of executive performance in clinical and control groups. Setting In-patient setting. Participants The cognitive profile of schizophrenic patients with and without comorbid substance abuse disorder was compared with that of patients suffering from major depression or alcoholism and healthy participants. Measurements A range of cognitive tasks was used to assess: (i) the ability to update continuously context information in working memory and to use it for action selection; and (ii) the capacity to divide attention between different sensory input channels and to coordinate verbal and manual responses. Findings Single-diagnosis schizophrenic patients showed pronounced impairments on measures of online maintenance and use of context information. Their ability to coordinate different sensory input channels (divided attention) was also impaired. Addicted schizophrenics showed evidence of impaired sensory input management and of reduced context sensitivity, when age differences were controlled. Conclusions The present study indicates severe working memory and multi-tasking deficits in schizophrenia which are, however, not exacerbated by comorbid addiction.
Thoma,P Daum,I
Institute of Cognitive Neuroscience, Department of Neuropsychology, Ruhr-University of Bochum, Germany.
Aims Alcoholism is associated with a range of cognitive deficits. These deficits might be explained by the ‘frontal lobe hypothesis’ which suggests a specific vulnerability of the prefrontal cortex (PFC) to the neurotoxic effects of alcohol. Social cognition is thought to be processed in the PFC, but so far only few studies have addressed the issue of social cognition deficits in alcoholism. This review aims to evaluate the deficits in social cognition in alcoholic patients. In addition an outline for future perspectives is given. Methods Medline and Psyclit searches were performed for a 30-year period (1977-2007). Results Alcoholism is associated clearly with social cognition impairments which include emotional face and prosody perception problems, theory of mind deficits and humour processing difficulties. Conclusions In summary, the social cognition impairments are consistent with the frontal lobe hypothesis of alcoholism. Future studies should focus on (i) the delineation of the basic cognitive processes which underlie social cognition deficits; and (ii) their relevance as predictors of treatment outcome in alcoholism.
Uekermann,J Daum,I
Institute of Cognitive Neuroscience, Ruhr-University of Bochum, Bochum, Germany.
The incidence of renal cell carcinoma (RCC) is increasing worldwide; diagnosis is made in an earlier stage due to increasing use of CT; ultrasound. Patients with a history of RCC have a high risk to develop another RCC within their remaining kidney. Especially, patients after tumor nephrectomy have to undergo follow-up examinations regularly allowing an early detection of new RCCs. Especially in patients with solitary kidney gold standard therapy (nephron-sparing surgery) can often account for consecutive renal failure with the need for hemodialysis. Percutaneous radiofrequency ablation (RFA) gained worldwide acceptance for the treatment of liver tumors in patients unable to undergo surgery. Furthermore, during the past few years, there is an increasing amount of publications dealing with the effectiveness of minimally invasive therapies like RFA in patients with renal masses. However, in the subgroup of patients with solitary kidney suffering from RCC, there are only case reports regarding safety; midterm outcome available so far. Therefore, the aim of this article is to briefly describe the basic technical principles of RFA; then focus on indications, technique, safety; the midterm outcome after treatment in terms of renal function; relapse.
Ralf-Thorsten Hoffmann1 Email:rthoffma@med.uni-muenchen.de Tobias F. Jakobs1 Christoph Trumm1 Thomas K. Helmberger2 Maximilian F. Reiser1 Email:rthoffma@med.uni-muenchen.de
[1] Institute of Clinical Radiology, University of Munich, Marchioninistr. 15, Munich, 81377, Germany ;[2] Institute for Radiology; Nuclear Medicine, University Hospital of Schleswig—Holstein, Campus Luebeck, Luebeck, Germany
The study of allergies in creatures living together without being relatives can help us understand the impact of environmental influences. We tested the association of allergies in humans and their pets. A nested unmatched case-control study was performed in a random sample of 4261 inhabitants, aged 25-74 years, of the City of Augsburg, Germany and two adjacent counties (September 1999-August 2001). Using standardized computer-assisted face-to-face interviews, we determined and compared the prevalence of doctor-diagnosed atopic diseases (hay fever, asthma and atopic dermatitis) in the study subjects and veterinarian-diagnosed allergies in their pets. Pets were kept in 48.0% of the households (cats, 26.1%; dogs, 20.1% and rodents, 9.7%) and allergy was diagnosed in 3.9% of the animals (cats, 3.3%; dogs, 4.7% and rodents, 1.2%). Atopic diseases were diagnosed in 20.2% of the study subjects (asthma, 6.1%; hay fever, 13.7% and atopic dermatitis, 5.1%). After adjustment for age, sex, parental predisposition and social status, a significant association between hay fever in the study subjects and allergies in their pets was observed [odds ratio (OR) 1.74, 95% confidence interval (CI) 1.01-2.97]. This association was more pronounced when investigating dogs only (OR 2.76, 95% CI 1.32-5.77) where in addition, an association with the overall prevalence of atopic diseases in the study subjects reached significance (OR 2.31, 95% CI 1.16-4.58). We conclude that there is indication for a concomitant occurrence of allergies in humans and pets. Shared environmental factors are the most likely explanation.
Schafer, T. Merkl, J. Klemm, E. Wichmann, HE Ring, J.
Department of Social Medicine, Medical University Lubeck, Beckergrube 43-47, 23552 Lubeck, Germany.
BACKGROUND: The purpose of this study was to evaluate whether an electronic-colonic-cleansing (ECC) algorithm is beneficial for the diagnostic performance compared to a CT colonography (CTC) evaluation without electronic cleansing in tagged datasets. METHODS: Two blinded readers evaluated CTC datasets from 79 patients with 153 colorectal polyps confirmed by optical colonoscopy. Cases were read in a randomized order with and without the use of electronic colon-cleansing software. Per-polyp sensitivity, per-polyp/per-patient specificity and reading times (with and without ECC) have been calculated and reported. RESULTS: Per-polyp sensitivity for polyps >6 mm without using ECC was 60.4% (Reader 1: 59.7%, Reader 2: 61.1%), while polyps >10 mm were detected with a sensitivity of 58.3% (Reader 1: 66.7%, Reader 2: 50%). On electronically cleansed datasets, the sensitivity was 73.6% (Reader 1: 76.4%; Reader 2: 70.8%) for polyps >6 mm and 83.3% (Reader 1: 83.3%; Reader 2: 83.3%), respectively. Per-patient specificity was 75% without using cleansing (Reader 1: 68%, Reader 2: 82%) and 81.5% using ECC (Reader 1: 86%, Reader 2: 77%). CONCLUSION: Reading CTC cases using ECC software improves sensitivity in detecting clinically relevant colorectal polyps.
Juchems MS Ernst A Johnson P Virmani S Brambs HJ Aschoff AJ
Department for Diagnostic and Interventional Radiology, University Hospitals Ulm, Ulm, Germany, markus.juchems@uni-ulm.de.
BACKGROUND: In order to investigate whether 1-mm thin slices and multiplanar reconstructions (MPRs) of multi-detector computed tomography (CT) datasets interpreted in addition to isotropic 5-mm thick slices in one session improve the detection of peritoneal carcinomatosis. METHODS: The abdominal CT datasets of 44 patients with histologically proven tumors of the abdomen or pelvis were retrospectively evaluated for peritoneal carcinomatosis by four radiologists with variable experience (radiologist 1: >/=10 years, radiologists 2 and 3: 1.5 years, radiologist 4: 0.5 years). In three successive steps, the radiologists evaluated first the axial 5-mm slices, second the 1-mm slices, and third the MPRs and rated their diagnostic confidence. RESULTS: Specificity was nearly unchanged for all the four radiologists. Sensitivity improved for the most experienced and the least experienced radiologists and was unchanged for the two readers with intermediate skills. Except for the third step of radiologist 4, no statistically significant differences in diagnostic performance were detected. The diagnostic confidence of all the four readers benefited to variable degrees from interpretation of the 1-mm slices and MPRs. CONCLUSIONS: While 5-mm slices are sufficient for the detection of peritoneal carcinomatosis, 1-mm slices and MPRs can improve sensitivity and diagnostic confidence.
Franiel T Diederichs G Engelken F Elgeti T Rost J Rogalla P
Department of Radiology, Charite Universitatsmedizin, Campus Charite Mitte, Schumannstrasse 20-21, Berlin, 10098, Germany, tobias.franiel@charite.de.