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Biomedical subjects

Thomas Becker

Publications and source records attributed to Thomas Becker.

At least 73 records · Page 4Linked to original sources
PubMed2004

The personal impact of schizophrenia in Europe.

The personal impact of schizophrenia is poorly described in the scientific literature. The European Psychiatric Services: Inputs Linked to Outcome Domains and Needs (EPSILON) study compared representative treated prevalence cohorts of patients with schizophrenia in five European countries, to assess unmet needs, impact on caregivers, quality of life, satisfaction with services, symptoms and disability. Of the 404 patients, 79% undertook no work of any kind, and 65% were single. Low quality of life was associated with: anxiety, depression, psychotic symptoms, more previous psychiatric admissions, alcohol abuse, having no reliable friends nor daily contact with family, being unemployed, and having few leisure activities. The most frequently occurring unmet needs among the patients were: daytime activities, company and intimate relationships, psychotic symptoms, psychological distress, and information. The most common worries of relatives were about the patient's health, and their own future, safety and financial position. Psychiatric services were therefore largely ineffective in managing the personal impact of schizophrenia, especially upon work, home and family life. Research, clinical practice and disability policy developments need to address a wider range of consequences of the disorder than symptoms alone.

Activities of Daily Living↗
PubMed2004

The protein translocon of the plastid envelopes.

The Toc and Tic translocon facilitate import of preproteins into chloroplasts. In the past, it was speculated that several translocon subunits act specifically for different types of precursor proteins or in different tissues. To generate a comprehensive picture of the expression and tissue-specific localization of the translocon subunits, their transcript levels were analyzed in roots and leaves. Certain Tocs and Tics were found to be tissue-specific. The protein composition of the transloci in the envelope membranes of chloroplasts was analyzed to describe the function and possible stoichiometry. In contrast to Tic subunits, several Toc subunits seem to have a high turnover.

Arabidopsis↗
PubMed2004

Structure of the signal recognition particle interacting with the elongation-arrested ribosome.

Cotranslational translocation of proteins across or into membranes is a vital process in all kingdoms of life. It requires that the translating ribosome be targeted to the membrane by the signal recognition particle (SRP), an evolutionarily conserved ribonucleoprotein particle. SRP recognizes signal sequences of nascent protein chains emerging from the ribosome. Subsequent binding of SRP leads to a pause in peptide elongation and to the ribosome docking to the membrane-bound SRP receptor. Here we present the structure of a targeting complex consisting of mammalian SRP bound to an active 80S ribosome carrying a signal sequence. This structure, solved to 12 A by cryo-electron microscopy, enables us to generate a molecular model of SRP in its functional conformation. The model shows how the S domain of SRP contacts the large ribosomal subunit at the nascent chain exit site to bind the signal sequence, and that the Alu domain reaches into the elongation-factor-binding site of the ribosome, explaining its elongation arrest activity.

Animals↗
PubMed2004

Preprotein recognition by the Toc complex.

The Toc core complex consists of the pore-forming Toc75 and the GTPases Toc159 and Toc34. We confirm that the receptor form of Toc159 is integrated into the membrane. The association of Toc34 to Toc75/Toc159 is GTP dependent and enhanced by preprotein interaction. The N-terminal half of the pSSU transit peptide interacts with high affinity with Toc159, whereas the C-terminal part stimulates its GTP hydrolysis. The phosphorylated C-terminal peptide of pSSU interacts strongly with Toc34 and therefore inhibits binding and translocation of pSSU into Toc proteoliposomes. In contrast, Toc159 recognises only the dephosphorylated forms. The N-terminal part of the pSSU presequence does not influence binding to the Toc complex, but is able to block import into proteoliposomes through its interaction with Toc159. We developed a model of differential presequence recognition by Toc34 and Toc159.

Arabidopsis↗
PubMed2004

Needs for care of patients with schizophrenia and the consequences for their informal caregivers- results from the EPSILON multi centre study on schizophrenia.

BACKGROUND: Schizophrenia as a chronic mental disorder not only has far-reaching consequences for patients, but also for their family members or other informal caregivers. In this study, we investigated whether needs for care of patients with schizophrenia are related to (negative) consequences for their informal caregivers. METHOD: A total of 287 patients with schizophrenia and their informal caregivers participated in the EPSILON study of schizophrenia in five European countries. Caregiver consequences were measured by the Involvement Evaluation Questionnaire (IEQ) and needs for care by the Camberwell Assessment of Need (CAN). RESULTS: Total number of needs for care as well as specific areas of needs for care of patients appeared to be only weak predictors of caregiver consequences in terms of explained variance. CONCLUSION: Subjective needs for care as measured by the CAN are not a good indicator for consequences experienced by the informal care system of patients with schizophrenia.

Adolescent↗
PubMed2004

Tenascin-R as a repellent guidance molecule for newly growing and regenerating optic axons in adult zebrafish.

In adult fish, in contrast to mammals, new optic axons are continuously added to the optic projection, and optic axons regrow after injury. Thus, pathfinding of optic axons during development, adult growth, and adult regeneration may rely on the same guidance cues. We have shown that tenascin-R, a component of the extracellular matrix, borders the optic pathway in developing zebrafish and acts as a repellent guidance molecule for optic axons. Here we analyze tenascin-R expression patterns along the unlesioned and lesioned optic pathway of adult zebrafish and test the influence of tenascin-R on growing optic axons of adult fish in vitro. Within intraretinal fascicles of optic axons and in the optic nerve, newly added optic axons grow in a tenascin-R immunonegative pathway, which is bordered by tenascin-R immunoreactivity. In the brain, tenascin-R expression domains in the ventral diencephalon, in non-retinorecipient pretectal nuclei and in some tectal layers closely border the optic pathway in unlesioned animals and during axon regrowth. We mimicked these boundary situations with a sharp substrate border of tenascin-R in vitro. Optic axons emanating from adult retinal explants were repelled by tenascin-R substrate borders. This is consistent with a function of tenascin-R as a repellent guidance molecule in boundaries for adult optic axons. Thus, tenascin-R may guide newly added and regenerating optic axons by a contact-repellent mechanism in the optic pathway of adult fish.

Animals↗
PubMed2004

Expression and mapping of duplicate neuropilin-1 and neuropilin-2 genes in developing zebrafish.

Previously, we described the isolation and characterization of the first zebrafish neuropilin gene, which we now call nrp1a, and found its protein to be a mediator of vascular endothelial growth factor (VEGF)-dependent angiogenesis [Proc. Natl Acad. Sci. USA 99 (2002) 10470]. Subsequently, we have isolated three other full-length neuropilin genes (nrp1b, nrp2a, and nrp2b) and find that they map to independent zebrafish linkage groups. The nrp1s and nrp2s had differential spatio-temporal gene expression profiles with nrp1a being most prominent in the gut, brain, retina, hypochord, motorneurons, fin bud and mandibular cartilage, nrp1b in the brain, dorsal aorta, melanophores, ventral fin, and heart, nrp2a in the brain, retina, heart, and caudal vessels, and nrp2b in the brain, retina, gut, fin bud, melanophores, heart, and caudal vessels. In addition, we have identified an alternatively-spliced transcript of the nrp1b gene (denoted as nrp1b(s)) which is predicted to encode a soluble form of Nrp1b, containing only the a, b, and c extracellular domains. Transcript expression of nrp1b(s) was different from full-length nrp1b transcript, with prominence in the brain, developing mouth, heart, and fin bud. The NRP1s were tested for VEGF-binding ability. Both 125 kDa Nrp1a and 145 kDa Nrp1b bound 125I-labelled VEGFA165. In summary, two nrp1 and two nrp2 genes, with expression patterns similar to higher vertebrates, have been isolated from zebrafish.

Alternative Splicing↗
PubMed2004

[Psychiatric inpatient care and sexuality].

BACKGROUND: Although sexuality has implications for psychiatric services, there is little research about ,,psychiatric in-patient care and sexuality". METHOD: Pertinent psychiatric literature published since 1970 was reviewed comprehensively. Recurring themes were identified, and were discussed in terms of historical trends and conceptual contradictions. RESULTS: Papers discussing sexuality and its relevance to psychiatric services can be summarised under three conceptual headings: (1) sexuality as taboo, (2) normalisation/empowerment, and (3) problematisation. The three clusters of papers focusing on these aspects were consecutive in time. DISCUSSION: During the 1970s and 1980s patients' equal rights to sexuality were weighed against moralistic concerns. Currently, patients' sexuality is discussed against the background of potentially negative consequences for the individual patient. A discussion is needed that encompasses this dilemma in order to find ways towards adequate practical handling of the issue of patients' sexuality in psychiatric services.

Hospitalization↗
PubMed2003

Nanofluidics: viscous dissipation in layered liquid films.

We studied the layer-by-layer collapse of molecularly thin films of a model lubricant confined between two atomically smooth substrates. The dynamics of the consecutive expulsion of four molecular layers were found to slow down with decreasing film thickness but showed no evidence for confinement-induced solidification. Using a hydrodynamic model, we show that the sliding friction of liquid layers on top of the solid substrates is approximately 18 times higher than the mutual friction between adjacent liquid layers. The latter was independent of film thickness and in close agreement with the bulk viscosity.

Journal Article↗
PubMed2003

Tenascin-R as a repellent guidance molecule for developing optic axons in zebrafish.

To investigate the role of tenascin-R in nervous system development, we studied axon pathfinding in the developing optic system of zebrafish. Zebrafish tenascin-R has the same domain structure as tenascin-R in amniotes. Amino acid sequence identity with human tenascin-R is 60%. In 3-d-old larvae, tenascin-R mRNA is expressed in scattered cells throughout the periventricular cell layer of the diencephalon and tectum. Tenascin-R immunoreactivity is not detectable in the optic nerve, optic tract, or tectal optic neuropil but immediately borders the optic tract caudally. Reducing expression of tenascin-R in 3-d-old larvae in vivo by injecting morpholinos into fertilized eggs led to excessive branching of the optic tract in 86% of all injected larvae compared with 20-37% in controls. Branches were almost exclusively caudal, where tenascin-R immunoreactivity normally borders the optic tract, suggesting a role for tenascin-R in guiding optic axons in the ventral diencephalon by a contact-repellent mechanism.

Animals↗
PubMed2003

Expression of protein zero is increased in lesioned axon pathways in the central nervous system of adult zebrafish.

The immunoglobulin superfamily molecule protein zero (P0) is important for myelin formation and may also play a role in adult axon regeneration, since it promotes neurite outgrowth in vitro. Moreover, it is expressed in the regenerating central nervous system (CNS) of fish, but not in the nonregenerating CNS of mammals. We identified a P0 homolog in zebrafish. Cell type-specific expression of P0 begins in the ventromedial hindbrain and the optic chiasm at 3-5 days of development. Later (at 4 weeks) expression has spread throughout the optic system and spinal cord. This is consistent with a role for P0 in CNS myelination during development. In the adult CNS, glial cells constitutively express P0 mRNA. After an optic nerve crush, expression is increased within 2 days in the entire optic pathway. Expression peaks at 1 to 2 months and remains elevated for at least 6 months postlesion. After enucleation, P0 mRNA expression is also upregulated but fails to reach the high levels observed in crush-lesioned animals at 4 weeks postlesion. Spinal cord transection leads to increased expression of P0 mRNA in the spinal cord caudal to the lesion site. The glial upregulation of P0 mRNA expression after a lesion of the adult zebrafish CNS suggests roles for P0 in promoting axon regeneration and remyelination after injury.

Age Factors↗
PubMed2003

Integrin antagonists affect growth and pathfinding of ventral motor nerves in the trunk of embryonic zebrafish.

Integrins are thought to be important receptors for extracellular matrix (ECM) components on growing axons. Ventral motor axons in the trunk of embryonic zebrafish grow in a midsegmental pathway through an environment rich in ECM components. To test the role of integrins in this process, integrin antagonists (the disintegrin echistatin in native and recombinant form, as well as the Arg-Gly-Asp-Ser peptide) were injected into embryos just prior to axon outgrowth at 14-16 h postfertilization (hpf). All integrin antagonists affected growth of ventral motor nerves in a similar way and native echistatin was most effective. At 24 hpf, when only the three primary motor axons per trunk hemisegment had grown out, 80% (16 of 20) of the embryos analyzed had abnormal motor nerves after injection of native echistatin, corresponding to 19% (91 of 480) of all nerves. At 33 hpf, when secondary motor axons were present in the pathway, 100% of the embryos were affected (24 of 24), with 20% of all nerves analyzed (196 of 960) being abnormal. Phenotypes comprised abnormal branching (64% of all abnormal nerves) and truncations (36% of all abnormal nerves) of ventral motor nerves at 24 hpf and mostly branching of the nerves at 33 hpf (94% of all abnormal nerves). Caudal branches were at least twice as frequent as rostral branches. Surrounding trunk tissue and a number of other axon fascicles were apparently not affected by the injections. Thus integrin function contributes to both growth and pathfinding of axons in ventral motor nerves in the trunk of zebrafish in vivo.

Animals↗
PubMed2003

Double labeling of neurons by retrograde axonal tracing and non-radioactive in situ hybridization in the CNS of adult zebrafish.

A number of genes affecting axonal projections are currently being identified in zebrafish mutant screens. Analyzing the expression of these genes in the adult brain in relation to specific neuronal populations could yield insights into new functional contexts, such as the successful axonal regeneration in adult zebrafish. Here, we provide a relatively simple procedure for non-radioactive in situ hybridization in sections of adult zebrafish brains in combination with retrograde axonal tracing using the fluorescent neuronal tracer rhodamine dextran amine (RDA). A lesion is inflicted on the spinal cord of adult zebrafish and a crystal of RDA is then applied to the lesion site resulting in retrograde labeling of neurons in the brain through their spinal axons. Six to eighteen days later fish are perfusion-fixed, and in situ hybridization is carried out on vibratome-cut floating sections using a protocol simplified from that used for whole-mounted zebrafish embryos. This procedure leads to robust double labeling of axotomized neurons with RDA and an in situ hybridization signal for the growth-associated protein 43 (GAP-43). This method can be used to identify gene expression in specific populations of projection neurons and to detect changes in gene expression in axotomized neurons in the CNS of adult zebrafish.

Animals↗
PubMed2003

Comparing protein stabilities during zebrafish embryogenesis.

The stabilities of many key proteins are regulated, e.g. via ubiquitination and proteasomal degradation, with important biological consequences. We present a convenient method that allows the analysis and comparison of protein stabilities during embryogenesis using early zebrafish development as a model system. Basically, this method involves ectopic overexpression of epitope-tagged proteins via mRNA injections in one-to-four-cell stage embryos and subsequent protein detection after various time points. Indeed, the protein stability of the ubiquitin ligase RLIM, which is able to autoubiquitinate and target itself for proteasomal degradation, was much shorter when compared to a protein consisting of a Myc epitope-tag and a nuclear localization domain. Thus, this method may be used more widely for the study of developmental protein stability.

Animals↗
PubMed2003

Reduced P-selectin expression on circulating platelets after prolonged cold preservation in renal transplantation.

The uremic state in patients with terminal renal insufficiency is accompanied by a bleeding tendency connected with platelet dysfunction. Prolonged cold ischemia and inflammatory interactions between leukocytes, platelets and endothelial cells contribute to ischemia-/reperfusion (I/R) injury and may impair long-term graft survival. We evaluated the influence of the duration of cold preservation time on the expression of platelet GPIIb/IIIa and P-selectin and on the formation of leukocyte-platelet complexes after kidney transplantation. Fourteen patients undergoing kidney transplantation were divided into group I with long preservation time (26.6 +/- 1.9 h) and group II with short preservation time (8 +/- 6.1 h). Five venous blood samples (3 ml) were taken before induction of anesthesia, 12 h, 2, 7 and 14 d after transplantation. Surface expression of the GPIIb/IIIa, P-selectin and the percentage of platelet-granulocyte complexes were quantified by flow cytometry. Additionally blood from seven healthy volunteers was analyzed. GPIIb/IIIa and P-selectin expression on circulating platelets were significantly decreased in the long and the short-term graft preservation group compared with healthy volunteers. A significantly reduced P-selectin expression was found in the long-term preservation group compared with the short-term group. The percentage of platelet-granulocyte complexes also decreased in both preservation groups in the first 2 d after reperfusion and remained in this state in the long-term preservation group. Reduced expression of P-selectin on circulating platelets may be an indicator of I/R injury after prolonged kidney graft preservation.

Blood Platelets↗
PubMed2003

Successful treatment of fibrosing cholestatic hepatitis using adefovir dipivoxil in a patient with cirrhosis and renal insufficiency.

Fibrosing cholestatic hepatitis is a deleterious manifestation of hepatitis B virus infection in immunocompromised patients. Without treatment, this condition is usually fatal within weeks of onset. Liver retransplantation has not been successfully performed to date, and treatment intervention was generally unsuccessful before the advent of adefovir dipivoxil. However, concerns have been expressed about the use of this agent in patients who are renally compromised. A 40-year-old liver transplant recipient with hepatitis B virus reinfection, resistance to lamivudine, and fibrosing cholestatic hepatitis complicated by terminal renal impairment and spontaneous bacterial peritonitis was treated with adefovir dipivoxil 10 mg after every dialysis. Since initiating treatment with adefovir dipivoxil 10 mg, a dramatic virologic and clinical improvement was observed in this patient. The patient returned to work full-time within 6 months of starting adefovir dipivoxil without the need for liver retransplantation. Serum HBV DNA (Amplicor HBV; Roche Diagnostics, Basle, Switzerland) decreased by 6 log(10) copies/mL and became negative (< 400 copies/mL) within 8 weeks of treatment and remains negative at the last available assessment. The patient continues to require renal dialysis, but is generally well. Creatinine clearance improved from 8 mL/min to 16 mL/min during the course of treatment. No adverse events related to adefovir dipivoxil were observed. Adefovir dipivoxil resulted in significant clinical improvement in this patient with hepatitis B virus-induced fibrosing cholestatic hepatitis, despite the presence of renal impairment and lamivudine resistance.

Adenine↗
PubMed2003

Results of combined and sequential liver-kidney transplantation.

Experience with combined liver-kidney transplantation (L-KTx) has increased, but controversy regarding this procedure continues because the indications are not clearly defined yet. Between 1984 and 2000, 38 patients underwent simultaneous L-KTx and 9 patients underwent sequential transplantation, receiving either a liver before a kidney or a kidney before a liver. Main indications for a simultaneous procedure were polycystic liver-kidney disease with cirrhosis and coincidental renal failure. The main indications for sequential procedure were cirrhosis caused by viral infection for the liver and glomerulonephritis for the kidneys. Outcomes in these patients were evaluated retrospectively. Regarding simultaneous transplantation, 28 (73.7%) long-term survivors were followed up for 0.7 to 12.5 years. Currently, 24 (63.2%) patients are alive with good liver function. Fourteen patients died; 10 patients died in the early postoperative phase because of septic complications, and most of them were cirrhotic with a poor preoperative clinical status. Currently, 2 of the surviving patients (8%) have returned to dialysis, 4 (17%) have reduced renal function, and 18 (75%) have good renal function. Five liver and 2 kidney retransplantations were performed during the follow-up. In cases of sequential grafting, patients undergoing kidney transplantation in the presence of a previously transplanted stable liver did better than those who underwent liver transplantation after kidney transplantation. When liver transplantation was performed early and electively before substantial worsening, combined L-KTx is a safe procedure offering excellent long-term palliation.

Adolescent↗