Biomedical subjects

Thomas Becker

Publications and source records attributed to Thomas Becker.

At least 55 records · Page 3Linked to original sources

PubMed2005

Tenascin-C is involved in motor axon outgrowth in the trunk of developing zebrafish.

Motor axons in the trunk of the developing zebrafish exit from the ventral spinal cord in one ventral root per hemisegment and grow on a common path toward the region of the horizontal myoseptum, where they select their specific pathways. Tenascin-C, a component of the extracellular matrix, is concentrated in this choice region. Adaxial cells and other myotomal cells express tenascin-C mRNA, suggesting that these cells are the source of tenascin-C protein. Overexpressing an axon repellent fragment containing the cysteine-rich region and the epidermal growth factor-like repeats of tenascin-C led to retarded growth of ventral motor nerves between their spinal exit point and the horizontal myoseptum. Injection of a protein fragment containing the same part of tenascin-C also induced slower growth of motor nerves. Conversely, knock down of tenascin-C protein resulted in abnormal lateral branching of ventral motor nerves. In the zebrafish unplugged mutant, in which axons display pathfinding defects in the region of the horizontal myoseptum, tenascin-C immunoreactivity was not detectable in this region, indicating an abnormal extracellular matrix in unplugged. We conclude that tenascin-C is part of a specialized extracellular matrix in the region of the horizontal myoseptum that influences the growth of motor axons.

Amino Acid Sequence↗

PubMed2005

Blood transfers infectious immunologic tolerance in MHC-incompatible heart transplantation in rats.

"Infectious tolerance" or inducing immunologic tolerance of infection in allografts is still poorly understood. We investigated whether transfusing blood from LEW.1A rats tolerant of LEW.1W hearts could transmit tolerance to naive LEW.1A rats. In 4 of 6 cases, transfusing blood from tolerant animals was followed by immunologic tolerance of heart transplants from LEW.1W donor rats in LEW.1A recipient animals, whereas transplanting heart grafts that were tolerated in previous transplantations across MHC barriers did not transfer tolerance in major histocompatibility complex (MHC)-incompatible animals. We conclude that in rat heart transplantation, the transfer of immunologic tolerance can be enhanced by transfusing blood from tolerant animals to naive animals before transplantation across MHC barriers.

Animals↗

PubMed2005

Differences in the regenerative response of neuronal cell populations and indications for plasticity in intraspinal neurons after spinal cord transection in adult zebrafish.

In zebrafish, the capacity to regenerate long axons varies among different populations of axotomized neurons after spinal cord transection. In specific brain nuclei, 84-92% of axotomized neurons upregulate expression of the growth-related genes GAP-43 and L1.1 and 32-51% of these neurons regrow their descending axons. In contrast, 16-31% of spinal neurons with axons ascending to the brainstem upregulate these genes and only 2-4% regrow their axons. Dorsal root ganglion (DRG) neurons were not observed to regrow their ascending axons or to increase expression of GAP-43 mRNA. Expression of L1.1 mRNA is high in unlesioned and axotomized DRG neurons. In the lesioned spinal cord, expression of growth-related molecules is increased in a substantial population of non-axotomized neurons, suggesting morphological plasticity in the spinal-intrinsic circuitry. We propose that locomotor recovery in spinal-transected adult zebrafish is influenced less by recovery of ascending pathways, but more by regrowth of descending tracts and rearrangement of intraspinal circuitry.

Animals↗

PubMed2005

Expression of collapsin response mediator proteins in the nervous system of embryonic zebrafish.

Collapsin response mediator proteins (CRMPs also known as TUC, Drp, Ulip, TOAD-64) are cytosolic phosphoproteins that are involved in signal transduction during axon growth and in cytoskeletal dynamics. Here we report cloning and mRNA expression patterns of CRMP-1, -2, -3, -4 and, owing to a genome duplication in teleosts, two homologs of CRMP-5 (CRMP-5a and -5b) in embryonic zebrafish at 16 and 24h post-fertilization (hpf). CRMPs are evolutionarily conserved and zebrafish CRMPs show amino acid identities of 76-90% with their homologs in humans, with the exception of CRMP-3, which shows only 67% homology. Between 16 and 24hpf, expression of CRMPs generally increased in many regions of the CNS undergoing neuronal differentiation and axonogenesis, but not in the proliferative ventricular zone. Structures that were typically labeled by most, but not all the CRMP probes were the telencephalon, the nucleus of the tract of the post-optic commissure, the epiphysis, the nucleus of the medial longitudinal fascicle, clusters of hindbrain neurons, cranial ganglia, as well as Rohon-Beard neurons. No expression of CRMP mRNAs was observed outside the nervous system. Thus, expression patterns of different CRMP family members correlate with neuronal differentiation and axonogenesis in embryonic zebrafish.

Amino Acid Sequence↗

PubMed2005

ERj1p uses a universal ribosomal adaptor site to coordinate the 80S ribosome at the membrane.

Ribosomes translating secretory and membrane proteins are targeted to the endoplasmic reticulum membrane and attach to the protein-conducting channel and ribosome-associated membrane proteins (RAMPs). Recently, a new RAMP, ERj1p, has been identified that recruits BiP to ribosomes and regulates translational activity. Here we present the cryo-EM structure of a ribosome-ERj1p complex, revealing how ERj1p coordinates the ribosome at the membrane and how allosteric effects may mediate ERj1p's regulatory activity.

Animals↗

PubMed2005

[Effects of interventions to improve compliance with antipsychotic medication in people suffering from schizophrenia-results of recent reviews].

BACKGROUND: Non-compliance (or non-adherence) with antipsychotic pharmacotherapy occurs frequently. In addition, there is overwhelming evidence that it constitutes a major risk factor for psychotic relapse. Compliance substantially affects course and treatment of schizophrenia. During the last decades, a large body of research on compliance with antipsychotic medication has been accumulated. METHOD: The authors provide an overview of meta-analyses. Reviews published since 1990 on effects of interventions aiming at increasing compliance with medication in people suffering from schizophrenia are summarized. RESULTS: We found eight reviews which reported empirical findings on the efficacy and effectiveness of interventions with the goal of improving compliance. Interventions have shown limited (psychoeducation) to moderate (cognitive-behavioral and combined interventions) effects. Other relevant findings are summarized and discussed.

Antipsychotic Agents↗

PubMed2005

[Compliance in the treatment of schizophrenia -- results of an expert survey in Saxony and Saxony-Anhalt].

OBJECTIVE: To report attitudes of psychiatrists and neurologists towards compliance with regard to medication-taking behaviour of patients suffering from schizophrenia. METHOD: A questionnaire was sent to psychiatrists and neurologists practising in Saxony and Saxony-Anhalt. Out of a total of 120, 54 completed questionnaires were returned. RESULTS: Most of the experts defined compliance as the degree of fidelity to treatment recommendations and patient cooperation. In the experts' view, a positive attitude towards treatment, insight into illness, and accurate perception of the symptoms correlate strongly with compliance, whereas the association between sociodemographic characteristics and compliance was seen as moderate. A majority of experts considered there were changes in compliance over time. DISCUSSION: With regard to the improvement of compliance, the importance of the doctor-patient-relationship is supported by the results of our study. As ratings of doctors suggest, compliance is a broadly determined behaviour which is variable over time. Future research on medication-related compliance in patients suffering from schizophrenia should take into account these findings.

Adult↗

PubMed2005

Sex differences in the subjective tolerability of antipsychotic drugs.

In recent years, research efforts have been directed to better characterize the subjective experience of taking psychotropic drugs. This study investigated the sex difference in the subjective tolerability of antipsychotic drugs. Participants were recruited from patients under the care of psychiatric services serving geographical catchment areas in Croydon (UK), Verona (Italy), Amsterdam (Netherlands), and Leipzig (Germany). Clinically unstable patients with a clinical diagnosis of schizophrenia and a research diagnosis of schizophrenia, established using the Item Group Checklist of the Schedule for Clinical Assessment in Neuropsychiatry, were enrolled. Antipsychotic subjective tolerability was rated by means of the Liverpool University Neuroleptic Side Effect Rating Scale. During the recruitment period, 245 men and 164 women with schizophrenia were recruited. In both sexes, the most frequently reported side effects were difficulty in concentrating, tiredness, and weight gain; these side effects occurred in approximately 50% of men and in up to 70% of women. Extrapyramidal and anticholinergic reactions were reported more often by women, whereas men reported sexual problems more often. After background group differences were controlled for, sex was the strongest determinant of the subjective tolerability of antipsychotic drugs. We therefore conclude that sex differences in the subjective tolerability of antipsychotic drugs should be taken into account in the pharmacological management of patients with schizophrenia. Studies should no longer consider men and women as a homogeneous group, given that the subjective tolerability of antipsychotic drugs substantially differs between sexes.

Adolescent↗

PubMed2005

Neuromuscular blocking properties of atracurium during sevoflurane or propofol anaesthesia in dogs.

OBJECTIVE: To quantify the neuromuscular blockade (NMB) produced by atracurium in either sevoflurane or propofol-anaesthetized dogs. ANIMALS: Twelve healthy, female adult mixed-breed dogs weighing 13 +/- 3 kg (range 10-22 kg). MATERIALS AND METHODS: Three doses of atracurium (0.1, 0.2 and 0.3 mg kg(-1)) were tested at 1-week intervals. Anaesthesia was induced with inhaled sevoflurane or intravenous propofol and maintained with end-tidal sevoflurane concentrations of 1.95% (1.25 x MAC) or propofol 0.6 mg kg(-1) minute(-1) respectively. Acceleromyography and train-of-four stimulation of the fibular nerve were used for the assessment of NMB. The percentage depression of the first twitch (T1) and the fourth to the first twitch ratio (T4/T1), the maximum degree of neuromuscular block achieved and surgical muscle relaxation were recorded. Before and during neuro muscular blockade (at 10 minute intervals) body temperature, ECG, arterial blood pressure, inspired and expired CO2 concentrations and SpO2 were recorded. RESULTS: Atracurium produced a dose-dependent duration of NMB in both propofol and sevoflurane-anaesthetized dogs. Duration of block was longer in dogs anaesthetized with sevoflurane. All studied doses of atracurium caused twitch depression > or =95% with little or no cardiovascular changes. CONCLUSIONS: Sevoflurane produces a clinically relevant potentiation of atracurium-induced NMB in dogs compared with propofol. CLINICAL RELEVANCE: Significant differences in the potentiation of NMB drugs are encountered with commonly used anaesthetics in the dog.

Anesthesia, General↗

PubMed2005

Biliary atresia research is crossing national and interdisciplinary borderlines by the European Biliary Atresia Registry (EBAR).

The European Biliary Atresia Registry (EBAR) was founded in 2001 in order to raise awareness of the rare disease biliary atresia and to reinforce international and interdisciplinary cooperation. The number of participating centres and registered patients increases continuously. EBAR activities can be found at the website www.biliary-atresia.com. A first evaluation of the EBAR data is scheduled for 2006, when the registry will alter its infrastructure. This meeting will be organized together with the European Federation for Biliary Atresia Research (EFBAR), a scientific committee, which was founded in 2003. The objectives of this association are to create clinical and basic research studies, which are based on existing registries in Europe.

Biliary Atresia↗

PubMed2005

Structural and functional evidence for a singular repertoire of BMP receptor signal transducing proteins in the lophotrochozoan Crassostrea gigas suggests a shared ancestral BMP/activin pathway.

The transforming growth factor beta (TGF-beta) superfamily includes bone morphogenetic proteins, activins and TGF-betasensu stricto (s.s). These ligands, which transduce their signal through a heteromeric complex of type I and type II receptors, have been shown to play a key role in numerous biological processes including early embryonic development in both deuterostomes and ecdyzozoans. Lophochotrozoans, the third major group of bilaterian animals, have remained in the background of the molecular survey of metazoan development. We report the cloning and functional study of the central part of the BMP pathway machinery in the bivalve mollusc Crassostrea gigas (Cg-BMPR1 type I receptor and Cg-TGFbetasfR2 type II receptor), showing an unusual functional mode of signal transduction for this superfamily. The use of the zebrafish embryo as a reporter organism revealed that Cg-BMPR1, Cg-TGFbetasfR2, Cg-ALR I, an activin Type I receptor or their dominant negative acting truncated forms, when overexpressed during gastrulation, resulted in a range of phenotypes displaying severe disturbance of anterioposterior patterning, due to strong modulations of ventrolateral mesoderm patterning. The results suggest that Cg-BMPR1, and to a certain degree Cg-TGFbetasfR2 proteins, function in C. gigas in a similar way to their zebrafish orthologues. Finally, based on phylogenetic analyses, we propose an evolutionary model within the complete TGF-beta superfamily. Thus, evidence provided by this study argues for a possible conserved endomesoderm/ectomesoderm inductive mechanism in spiralians through an ancestral BMP/activin pathway in which the singular, promiscuous and probably unique Cg-TGFbetasfR2 would be the shared type II receptor interface for both BMP and activin ligands.

Activin Receptors, Type I↗

PubMed2005

Split liver transplantation: a reliable approach to expand donor pool.

BACKGROUND: Orthotopic liver transplantation as a successful treatment of end-stage liver disease is hampered by a persistent lack of cadaveric organs. Split liver transplantation, which was first successfully performed by Medical School of Hannover in 1988, has become a mature surgical technique to expand the donor pool. Between 1993 and 1999, split liver transplantation activities have increased in Europe from 1.2% to 10.4% in all performed liver transplantations. Current data have strongly supported that the survival rate of patients after split liver transplantation is not significantly different from that of patients after whole-size orthotopic liver transplantation. The most important step of donor graft selection is surgeon's observation judged by the experience of individual transplant center. The paper aims to provide the guideline of donor selection, hepatic graft splitting, and recipient management as well. DATA SOURCES: Medical School of Hannover has accumulated plentiful experience of split liver transplantation for more than 10 cases ever since 1998. Besides that, we also reviewed a variety of literatures from other famous European and American centers specialized in this field for many years. RESULTS: According to our experience combined with the view points of others, the donor should meet the following criteria as well: (1) age less than 50 years; (2) hemodynamics stable; (3) ICU less than 5 days; (4) Na less than 170 mmol/L or better if less than 150 mmol/L. In 1996 and 1997, the Hamburg group and the UCLA group separately introduced a breakthrough technique performing split liver transplantation in situ. Evidently, the in situ technique has been limited by prolonged time of donor organ procurement, coordination with other organ procurement teams, and even extra burden on donor hospital. Some groups, therefore, have restored the ex situ or bench splitting technique, and fortunately the transplant outcomes of the ex situ technique are equivalent to those of the in situ one. Recently some new techniques have been introduced to split the liver for two adult patients, including the split-cava technique. CONCLUSIONS: It is clear that the most important factor for determining the prognosis of the patient is the time of receiving liver transplantation, not the type of liver transplantation. We still need to pay close attention to the graft to recipient weight ratio (GRWR) and the UNOS classification or MELD score before the patient is subjected to split liver transplantation.

Health Care Rationing↗

PubMed2004

Directed forgetting in schizophrenia: prefrontal memory and inhibition deficits.

Schizophrenia is associated with cognitive deficits in the domains of working memory, strategic memory and other executive functions. In the current study we used a computerised and item-cued variant of the directed forgetting (DF) task to assess inhibitory processes in verbal memory. Twenty-five patients with schizophrenia and a group of matched controls were tested. Recognition memory was better for to-be-remembered (TBR) than for to-be-forgotten (TBF) words in both patients and controls. As compared to healthy controls the patients with schizophrenia showed overall memory deficits and difficulties to inhibit memories as indicated by a significant group by cue interaction and a smaller DF effect. The DF effect was associated with disease duration but not with symptom severity. Memory-related inhibition problems are difficult to assess in patients with schizophrenia and might be related to fronto-temporal disconnection.

Adult↗

PubMed2004

Living donor nephrectomy: flank incision versus anterior vertical mini-incision.

BACKGROUND: Currently, many centers perform laparoscopic donor nephrectomy (DN). We studied the outcome of donors and recipients following open DN using either flank incision (ODN) or mini-incision (MIDN). METHODS: Data of 196 living kidney donors were recorded prospectively. In 127 cases ODN and 69 cases MIDN were performed. RESULTS: Demographic details of donors were comparable for both groups. The left kidney was procured in 58% for ODN and in 64% for MIDN. Multiple arteries were more frequently present when MIDN (11% vs. 28%) was performed. The mean operating time was 129 min for ODN and 133 min for MIDN. Early complications occurred in 7% following ODN and in 4% following MIDN. Late complications were observed in 21% after ODN and 1% after MIDN. The mean hospital stay was significantly longer following ODN compared with MIDN (7.5 vs. 6.4 days). The primary graft function rate was 97% in both groups. One-year graft survival was 97% after ODN and 100% after MIDN. CONCLUSIONS: Results following MIDN are superior to those following ODN. Even in case of multiple renal vessels MIDN can be safely applied. In comparison with laparoscopic DN advantages of MIDN may be reduced costs, shorter operating time, and comparable cosmetic results.

Adult↗

PubMed2004

L1.1 is involved in spinal cord regeneration in adult zebrafish.

Adult zebrafish, in contrast to mammals, regrow axons descending from the brainstem after spinal cord transection. L1.1, a homolog of the mammalian recognition molecule L1, is upregulated by brainstem neurons during axon regrowth. However, its functional relevance for regeneration is unclear. Here, we show with a novel morpholino-based approach that reducing L1.1 protein expression leads to impaired locomotor recovery as well as reduced regrowth and synapse formation of axons of supraspinal origin after spinal cord transection. This indicates that L1.1 contributes to successful regrowth of axons from the brainstem and locomotor recovery after spinal cord transection in adult zebrafish.

Animals↗

PubMed2004

Liver transplantation using organs from donors older than 60 years.

At present, it is frequently accepted to expand the organ pool for liver transplantation (LTx) by including livers from critical donors. From 1990 to June 2002 a total of 1,208 LTx were performed. Of those, 67 livers from donors older than 60 years were transplanted to 66 patients, including re-LTx in eight patients. Fourteen patients had malignant diseases (21%). Ten patients had a high urgency status (15%). Median donor age was 65 years (range 61-80 years). Primary graft function was observed in 84%. Patient survival rate at 1 and 5 years was 79% and 62%, and graft survival was 68% and 53%, respectively. No difference was observed in LTx with livers from donors younger than 60 years. Fifteen graft losses occurred during the study. Surgical complications were observed in 23 patients (34%). The outcome of LTx with livers from donors older than 60 years is satisfactory and is comparable to results of LTx with livers from donors younger than 60 years. The frequency of vascular complications and cholestasis syndrome is not increased.

Adult↗

PubMed2004

Toc12, a novel subunit of the intermembrane space preprotein translocon of chloroplasts.

Translocation of proteins across membranes is essential for the biogenesis of each cell and is achieved by proteinaceous complexes. We analyzed the translocation complex of the intermembrane space from chloroplasts and identified a 12-kDa protein associated with the Toc machinery. Toc12 is an outer envelope protein exposing a soluble domain into the intermembrane space. Toc12 contains a J-domain and stimulates the ATPase activity of DnaK. The conformational stability and the ability to stimulate Hsp70 are dependent on a disulfide bridge within the loop region of the J-domain, suggesting a redox-regulated activation of the chaperone. Toc12 is associated with Toc64 and Tic22. Its J-domain recruits the Hsp70 of outer envelope membrane to the intermembrane space translocon and facilitates its interaction to the preprotein.

Adenosine Triphosphate↗

PubMed2004

Platelet P-selectin and GPIIb/IIIa expression after liver transplantation and resection.

Platelet dysfunction contributes to haemostatic defects, possibly leading to bleeding complications. We hypothesised that liver transplantation and liver resection, together with portal clamping time, might be a potential stimulus for platelet activation. Therefore, we determined the expression of platelet GPIIb/IIIa and P-selectin, representing important platelet activation markers, and the thrombopoietin (TPO) serum level after transplantation and resection. Twenty patients [ten that had undergone orthotopic liver transplantation (OLT), ten with liver resection (LRX)] were included in the study. From sequential venous blood samples, surface expression of GPIIb/IIIa and P-selectin was quantified by flow cytometry, and TPO serum levels were determined by ELISA. Baseline GPIIb/IIIa receptor expression on circulating platelets was significantly reduced in the OLT group compared to the LRX group and healthy volunteers. GPIIb/IIIa expression after activation with TRAP-6 increased significantly ( P<0.001) in the LRX group but not in the OLT group. P-selectin expression after TRAP-6 stimulation increased significantly ( P<0.001) in the LRX group, being comparable to that in healthy volunteers, whereas only a very low increase in the OLT group was found. In the OLT group, TPO serum levels were in the lower normal range and rose above the upper limit of normal values 24 h after reperfusion. These data indicate that neither liver transplantation nor liver resection influences GPIIb/IIIa and P-selectin expression on circulating platelets. There was a lack of expression in cirrhotic patients and unimpaired baseline expression and functional reserve in non-cirrhotic liver-resection patients. After liver transplantation, increasing serum TPO levels, which indicated a recovering graft function, resulted in rising peripheral platelet counts.

Adult↗