Koliwer J.,Universitatskrankenhaus Hamburg Eppendorf |
Park M.,University of California at San Francisco |
Bauch C.,Universitatskrankenhaus Hamburg Eppendorf |
Von Zastrow M.,University of California at San Francisco |
Kreienkamp H.-J.,Universitatskrankenhaus Hamburg Eppendorf
Journal of Biological Chemistry | Year: 2015
Many G-protein-coupled receptors carry C-terminal ligand motifs for PSD-95/discs large/ZO-1 (PDZ) domains; via interaction with PDZ domain-containing scaffold proteins, this allows for integration of receptors into signaling complexes. However, the presence of PDZ domain proteins attached to intracellular membranes suggests that PDZ-type interactions may also contribute to subcellular sorting of receptors. The protein interacting specifically with Tc10 (PIST; also known as GOPC) is a trans-Golgi-associated protein that interacts through its single PDZ domain with a variety of cell surface receptors. Here we show that PIST controls trafficking of the interacting β1-adrenergic receptor both in the anterograde, biosynthetic pathway and during postendocytic recycling. Overexpression and knockdown experiments show that PIST leads to retention of the receptor in the trans-Golgi network (TGN), to the effect that overexpressed PIST reduces activation of the MAPK pathway by β1-adrenergic receptor (β1AR) agonists. Receptors can be released from retention in the TGN by coexpression of the plasma membrane-associated scaffold PSD-95, which allows for transport of receptors to the plasma membrane. Stimulation of β1 receptors and activation of the cAMP pathway lead to relocation of PIST from the TGN to an endosome-like compartment. Here PIST colocalizes with SNX1 and the internalized β1AR and protects endocytosed receptors from lysosomal degradation. In agreement, β1AR levels are decreased in hippocampi of PIST-deficient mice. Our data suggest that PIST contributes to the fine-tuning of β1AR sorting both during biosynthetic and postendocytic trafficking. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A.
Children of mentally ill parents: The impact of parental psychiatric diagnosis, comorbidity, severity and chronicity on the well-being of children [Kinder psychisch kranker Eltern: Merkmale elterlicher psychiatrischer Erkrankung und Gesundheit der Kinder aus Elternsicht]
Wiegand-Grefe S.,Universitatskrankenhaus Hamburg Eppendorf |
Geers P.,University of Bremen |
Petermann F.,University of Bremen |
Plass A.,Universitatskrankenhaus Hamburg Eppendorf
Fortschritte der Neurologie Psychiatrie | Year: 2011
Objective: Children of mentally ill parents are known as a high-risk population for the development of psychological disturbances. In this study, the psychiatric diagnoses, the severity and chronicity and the comorbidity of a parental mental illness as well as the non-specific parameters were examined in terms of their influence on the children's mental health. Methods: n = 62 children of psychiatric inpatients were examined regarding their psychic symptomatology, assessed with the CBCL-Parent Report Form. The psychiatric ICD-10 diagnoses and comorbidities as well as the severity (CGI) of the mentally ill parents were collected from psychiatric assessment forms. Results: Children of parents with personality disorders (PD) are evaluated as highly affected by their parents, regardless of whether the PD is the primary or the comorbid diagnosis. Children of parents suffering from addictive disorders are seen as the least affected by their parents. Overall, children of parents with multiple diagnoses tend to be rated as more affected. Severity of illness and chronicity do not have a considerable impact on the children's development of mental health problems. Strikingly, children with a high length of exposure to a parental illness are psychologically less affected than children with shorter times of exposure. Thus, children possibly acquire effective coping mechanisms with increasing time of exposure. Conclusions: The results reveal the necessity of preventive programmes, especially in case of personality disorders. In addition the necessity for external assessment of the children becomes clear, especially in those cases where the parents exhibit a poor acceptance of their disease. © Georg Thieme Verlag KG Stuttgart · New York.
Papanikolaou I.S.,National and Kapodistrian University of Athens |
Rosch T.,Universitatskrankenhaus Hamburg Eppendorf |
Schulz H.-J.,Sana Klinikum Lichtenberg
Endoskopie heute | Year: 2012
he report on the 19th United European Gastroenterology Week (UEGW: 22.-26. October 2011, Stockholm, Sweden) presents an update of gastrointestinal endoscopy, focussing on oral presentations and selected poster presentations and aims to review them in the light of recent literature, in particular endoscopy resection and other endotherapy techniques, new endoscopy imaging methods, Barrett's esophagus, gastrointestinal bleeding, enteroscopy, colonoscopy, ERCP, EUS, NOTES, PEG. © Georg Thieme Verlag.
Hartmann M.,Universitatskrankenhaus Hamburg Eppendorf |
Krege S.,Abteilung Radiologie |
Souchon R.,Universitatsklinik Tubingen |
De Santis M.,Abteilung fur Onkologie |
And 2 more authors.
Urologe - Ausgabe A | Year: 2011
Background: Clear treatment recommendations for patients with testicular cancer exist and their stringent application has led to significant improvements in remission and survival rates. Moreover, active surveillance has become a cornerstone in the management of clinical stage I seminomatous and nonseminomatous germ cell tumors. On the other hand, the existing recommendations for the follow-up of testis cancer patients differ widely and have been changed frequently in recent years. Material and methods: Follow-up recommendations in this young patient population have to be as evidence-based as possible, feasible in order to ensure adherence, and should not be harmful. Primarily, attention has to be paid to the negative impact of unnecessary radiation exposure. Results: Recently, new evidence has become available regarding the relapse pattern of different disease stages of testicular cancer, the use of imaging at follow-up, and the risks of excessive radiation due to imaging, in particular that of CT scans. An interdisciplinary multinational working group consisting of urologists, medical oncologists, and radiation oncologists has reviewed and discussed the current evidence and on this basis formulated new recommendations for patients with germ cell tumors of the testis. © 2011 Springer-Verlag.
Beutel M.E.,Universitatsmedizin Mainz |
Schulz H.,Universitatskrankenhaus Hamburg Eppendorf
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz | Year: 2011
Based on the literature, the assessment of psychological comorbidity in epidemiological studies is reviewed along with prevalence rates of psychological comorbidity and the effect of mental diseases on the development and course of chronic disease as exemplified by coronary heart disease. Psychological comorbidity is associated with reduced quality of life, disease progression, and increased mortality, as numerous studies in coronary heart disease and other chronic diseases have shown. In spite of available valid screening measures which enable large population surveys, diagnostic problems remain, especially with respect to separating mental and somatic symptoms and diagnosing somatic diseases reliably. Psychological comorbidity is frequently overlooked in medical care and poses a high risk for the future somatic and mental course of disease, associated with individual suffering and serious health economic consequences. There is a need for research on suitable interventions for patients with chronic disorders and psychological comorbidity in order to improve their care. © 2010 Springer Medizin Verlag.
Meister K.,Universitatskrankenhaus Hamburg Eppendorf |
Rietschel L.,Universitatskrankenhaus Hamburg Eppendorf |
Burlon M.,Universitatskrankenhaus Hamburg Eppendorf |
Gouzoulis-Mayfrank E.,Universitatsklinik Cologne |
And 2 more authors.
Fortschritte der Neurologie Psychiatrie | Year: 2010
Despite the high prevalence of comorbid substance use disorders (SUD) in young schizophrenic patients and the association of persisting SUD and poor outcome, there are only few randomized controlled psychological treatment studies in this special dual diagnosis group available. According to therapeutic recommendations, efficient treatment models need to integrate traditional psychiatric therapy and therapy of addiction offered in one setting. Short-term interventions have adapted Motivational interviewing (MI) for dual diagnosis, which has been shown to be effective among other substance abuse disorders. However a recent Cochrane review showed that insufficient evidence exists to show that any psychosocial treatment method for dual diagnosis is superior to others. The aim of this review was to assess the current evidence for the efficacy of psychosocial interventions for reducing substance in young patients with psychosis. Five randomized-controlled studies were identified. This review did not find any specific psychosocial intervention that had been replicated and consistently showed clear advantages over comparison condition for substance-related and other psychiatric outcomes. © Georg Thieme Verlag KG Stuttgart · New York.
Gouveia R.,New University of Lisbon |
Schaffer L.,Scripps Research Institute |
Papp S.,Scripps Research Institute |
Grammel N.,GlycoThera GmbH |
And 6 more authors.
Biochimica et Biophysica Acta - General Subjects | Year: 2012
Background: Several glycan structures are functionally relevant in biological events associated with differentiation and regeneration which occur in the central nervous system. Here we have analysed the glycogene expression and glycosylation patterns during human NT2N neuron differentiation. We have further studied the impact of downregulating fucosyltransferase 9 (FUT9) on neurite outgrowth. Methods: The expression of glycogenes in human NT2N neurons differentiating from teratocarcinoma NTERA-2/cl.D1 cells has been analysed using the GlycoV4 GeneChip expression microarray. Changes in glycosylation have been monitored by immunoblot, immunofluorescence microscopy, HPLC and MALDI-TOF MS. Peptide mass fingerprinting and immunoprecipitation have been used for protein identification. FUT9 was downregulated using silencing RNA. Results and conclusions: One hundred twelve mRNA transcripts showed statistically significant up-regulation, including the genes coding for proteins involved in the synthesis of the Lewisx motif (FUT9), polysialic acid (ST8SIA2 and ST8SIA4) and HNK-1 (B3GAT2). Accordingly, increased levels of the corresponding carbohydrate epitopes have been observed. The Lewisx structure was found in a carrier glycoprotein that was identified as the CRA-a isoform of human neural cell adhesion molecule 1. Downregulation of FUT9 caused significant decreases in the levels of Lewisx, as well as GAP-43, a marker of neurite outgrowth. Concomitantly, a reduction in neurite formation and outgrowth has been observed that was reversed by FUT9 overexpression. General Significance: These results provided information about the regulation of glycogenes during neuron differentiation and they showed that the Lewis x motif plays a functional role in neurite outgrowth from human neurons. © 2012 Elsevier B.V.
Families with Mentally Ill Parents - Connections between family functioning and health-related life quality of children [Familien mit Psychisch Kranken Eltern - Zusammenhang von Familienfunktionalität und Gesundheitsbezogener Lebensqualität der Kinder]
Jeske J.,Universitatsklinik Hamburg Eppendorf |
Bullinger M.,Universitatsklinik Hamburg Eppendorf |
Bullinger M.,Universitatskrankenhaus Hamburg Eppendorf |
Wiegand-Grefe S.,Universitatsklinik Hamburg Eppendorf
Familiendynamik | Year: 2010
The article discusses connections between family functioning as an indicator of interaction quality in families with a mentally ill parent and the health-related life quality of 72 children of mentally ill parents. Family functioning was assessed (1) from the parents' viewpoint via family questionnaires (FB-A) and (2) from the physician/therapist viewpoint via the Global Assessment of Relational Functioning Scale (GARF). The children's life quality from the viewpoint of the mentally ill parents was assessed via the parents' version of the KINDL-R. We established medium-strength correlations between family functioning and the parents' assessments of the life quality of their children. Mentally ill parents tend to give an unfavourable assessment of family functioning and have a low opinion of their children's life quality in comparison with a reference population of healthy parents. The findings support hypotheses suggesting that positive family functioning is significant for the high health-related life quality of children from the parents' perspective. They also indicate that interventions aimed at improving family functioning may be operative in improving the life quality of children of mentally sick parents.
Bobsin K.,Universitatskrankenhaus Hamburg Eppendorf |
Kreienkamp H.-J.,Universitatskrankenhaus Hamburg Eppendorf
Journal of Neurochemistry | Year: 2016
Learning and memory is dependent on postsynaptic architecture and signaling processes in forebrain regions. The insulin receptor substrate protein of 53 kDa (IRSp53, also known as Baiap2) is a signaling and adapter protein in forebrain excitatory synapses. Mice deficient in IRSp53 display enhanced levels of postsynaptic N-methyl-D-aspartate receptors (NMDARs) and long-term potentiation (LTP) associated with severe learning deficits. In humans, reduced IRSp53/Baiap2 expression is associated with a variety of neurological disorders including autism, schizophrenia, and Alzheimer's disease. Here, we analyzed mice lacking one copy of the gene coding for IRSp53 using behavioral tests including contextual fear conditioning and the puzzle box. We show that a 50% reduction in IRSp53 levels strongly affects the performance in fear-evoking learning paradigms. This correlates with increased targeting of NMDARs to the postsynaptic density (PSD) in hippocampi of both heterozygous and knock out (ko) mice at the expense of extrasynaptic NMDARs. As hippocampal NMDAR-dependent LTP is enhanced in IRSp53-deficient mice, we investigated signaling cascades important for the formation of fear-evoked memories. Here, we observed a dramatic increase in cAMP response element-binding protein-dependent signaling in heterozygous and IRSp53-deficient mice, necessary for the transcriptional dependent phase of LTP. In contrast, activation of the MAPK and Akt kinase pathways required for translation-dependent phase of LTP are reduced. Our data suggest that loss or even the reduction in IRSp53 increases NMDAR-dependent cAMP responsive element-binding protein activation in the hippocampus, and interferes with the ability of mice to learn upon anxiety-related stimuli. © 2015 International Society for Neurochemistry.
PubMed | Universitatskrankenhaus Hamburg Eppendorf
Type: Journal Article | Journal: The Journal of biological chemistry | Year: 2012
CHL1 plays a dual role by either promoting or inhibiting neuritogenesis. We report here that neuritogenesis-promoting ligand-dependent cell surface clustering of CHL1 induces palmitoylation and lipid raft-dependent endocytosis of CHL1. We identify II spectrin as a binding partner of CHL1, and we show that partial disruption of the complex between CHL1 and II spectrin accompanies CHL1 endocytosis. Inhibition of the association of CHL1 with lipid rafts by pharmacological disruption of lipid rafts or by mutation of cysteine 1102 within the intracellular domain of CHL1 reduces endocytosis of CHL1. Endocytosis of CHL1 is also reduced by nifedipine, an inhibitor of the L-type voltage-dependent Ca(2+) channels. CHL1-dependent neurite outgrowth is reduced by inhibitors of lipid raft assembly, inhibitors of voltage-dependent Ca(2+) channels, and overexpression of CHL1 with mutated cysteine Cys-1102. Our results suggest that ligand-induced and lipid raft-dependent regulation of CHL1 adhesion via Ca(2+)-dependent remodeling of the CHL1-II spectrin complex and CHL1 endocytosis are required for CHL1-dependent neurite outgrowth.