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C Schuster

Publications and source records attributed to C Schuster.

At least 37 records · Page 2Linked to original sources

Photic regulation of mt1 melatonin receptors in the Siberian hamster pars tuberalis and suprachiasmatic nuclei: involvement of the circadian clock and intergeniculate leaflet.

In the Siberian hamster suprachiasmatic nuclei and pars tuberalis of the pituitary, high affinity mt1 melatonin receptors are present. We have previously shown that night applied light pulse induced an increase in mt1 mRNA expression in the suprachiasmatic nuclei of this species, independently of the endogenous melatonin. Here, we report the photic regulation of melatonin receptor density and mRNA expression in the suprachiasmatic nuclei and pars tuberalis of pinealectomized Siberian hamsters and the implication in this control of either the circadian clock or the intergeniculate leaflet. The results show that: (1) A 1-h light pulse, delivered during the night, induces a transitory increase in mt1 mRNA expression in the suprachiasmatic nuclei and pars tuberalis. After 3 h this increase has totally disappeared (suprachiasmatic nuclei) or is greatly reduced (pars tuberalis). (2) The melatonin receptor density, in the suprachiasmatic nuclei, is not affected by 1 or 3 h of light, while it is strongly increased in the pars tuberalis. (3) In hamsters kept in constant darkness, the mt1 mRNA rise is gated to the subjective night in the suprachiasmatic nuclei and pars tuberalis. In contrast, the light-induced increase in melatonin binding is also observed in the subjective day in the pars tuberalis. (4) intergeniculate leaflet lesion totally inhibits the mt1 mRNA expression rise in the suprachiasmatic nuclei, while it has no effect on the light-induced increase in mt1 mRNA in the pars tuberalis. However, the light-induced increase in melatonin receptor density is totally prevented by the intergeniculate leaflet lesion in the pars tuberalis. These results show that: (1) the photic regulations of mt1 mRNA expression and receptor density are independent of each other in both the suprachiasmatic nuclei and pars tuberalis; and (2) the circadian clock and the intergeniculate leaflet are implicated in the photic regulation of melatonin receptors but their level of action differs totally between the suprachiasmatic nuclei and pars tuberalis.

Animals↗

Melatonin regulates the mRNA expression of the mt(1) melatonin receptor in the rat Pars tuberalis.

The pars tuberalis (PT) of the pituitary is a major neuroendocrine target site for melatonin as it contains a large number of high-affinity melatonin receptors. We have previously shown that melatonin autoregulates the density of its own receptors in the PT. However, whether melatonin regulation includes mRNA expression in vivo is unclear. In the present study we have used quantitative in situ hybridization to (1) follow the daily profile of mt(1) mRNA expression in the rat PT and (2) investigate whether mt(1) mRNA expression could be regulated in vivo by melatonin. We found clear diurnal variations of mt(1) mRNA expression that persist in constant darkness. We also showed, on pinealectomized animals, that the rhythmic pineal melatonin secretion is necessary for the expression of these daily variations. In a second step, we studied the effect of an acute suppression of endogenous melatonin synthesis on mt(1) melatonin receptors by applying a 1-hour light pulse during the night. We found that light induced a dramatic increase in mt(1) mRNA which was totally prevented by a melatonin injection showing that the acute effect of melatonin on the receptor mRNA is strongly inhibitory. A light pulse applied to animals with a chronic absence of melatonin was ineffective showing that light only affects melatonin receptors via the light-induced plasma melatonin suppression. Altogether our results show that melatonin regulates mt(1) melatonin receptor mRNA expression. However, this regulation seems to be complex: acute changes in plasma melatonin concentration regulate negatively the gene transcription, even if the daily endogenous nocturnal melatonin peak seems a prerequisite for variations in its receptor expression.

Animals↗

[Angioedema induced by ACE inhibitors and angiotensin II-receptor antagonists: analysis of 98 cases].

Angiooedema has been reported as a rare but in most cases serious adverse effect of ACE inhibitors. Recent reports have indicated that angiotensin II-receptor antagonists may also induce angiooedema. As part of the spontaneous reporting scheme in Switzerland the Swiss Drug Monitoring Centre (SANZ) has received reports on 94 cases of ACE inhibitor-induced and 4 cases of angiotension II-receptor antagonist-induced angiooedema. These 98 spontaneously reported cases were analysed in detail. 28 cases were classified as serious and in three patients intubation was even required. In 35% of cases angiooedema was induced within the first week of therapy and in 64% within the first year. In one case the angio-oedema displayed latency of 8 years. Latency of this duration shows that this adverse drug reaction (ADR) may be hard to detect. In 45 of the 98 cases the oedema persisted for more than one day (maximum 2 months), although in some instances the patients continued ACE-inhibitor therapy. In 25 cases the oedema recurred, in one instance as many as 20 times. In rare cases angiooedema may also be induced by angiotensin II-receptor antagonists, although in such instances the course of the oedema was usually milder. In two of the four reported cases angiooedema recurred after switching from an ACE inhibitor to an angiotensin II-receptor antagonists. The four reported cases from Switzerland showed a similar profile when compared with 25 internationally documented cases. Our data indicate that angiooedema is a specific ACE inhibitor ADR. A protracted latency period may be observed and recurrence of oedema is frequent. Angiotensin II-receptor antagonist-induced angiooedema may also occur in rare instances.

Adult↗

[Community emergency medical service. Epidemiology and quality of treatment in a rural district].

OBJECTIVES: Rapid aid provided by lay witnesses and emergency services can improve the outcome in medical emergencies arising in the community. We attempted to study the quality of first aid rendered by lay persons, paramedical personnel, and community medical practitioners attending out-of-hospital emergencies. We also evaluated the frequency of first aid provided before the arrival of specialised emergency physicians. METHODS: Over a period of six months all emergencies in a rural district of Germany leading to the pre-hospital medical service being dispatched were studied. Specialised community emergency physicians arriving at the site of the event recorded demographic, clinical, and process data using a standardised instrument. They also assessed the performance of lay persons, paramedical personnel, and community physicians providing immediate care. Implicit and explicit criteria were used. RESULTS: In 97% of cases analysed (n = 1150) members of the above mentioned groups were present before the arrival of the dedicated medical service. Lay persons were judged to provide inadequate care especially with regard to airway management and immobilisation of suspected fractures. For paramedical personnel, the administration of medication, venous lines and immobilisation turned out to be problematic areas. Medical practitioners fell below the defined standards especially in airway management, immobilisation and venous lines. CONCLUSION: Our project has shown how important the evaluated groups are for community emergency care. Despite methodological problems in this area of study, the shortcomings demonstrated may be targeted by future training at different levels.

Emergency Medical Services↗

Cloning experiments and developmental expression of both melatonin receptor Mel1A mRNA and melatonin binding sites in the Syrian hamster suprachiasmatic nuclei.

The suprachiasmatic nuclei (SCN) are implicated in the control of circadian biological rhythms, and especially the melatonin nocturnal synthesis. In numerous rodents, melatonin has been shown to feed back on the SCN activity through high affinity receptors. In contrast, Syrian hamster SCN activity is unresponsive to melatonin injections. As this lack of effect could be linked to a developmental loss of SCN melatonin receptors, the goals of the present study were 1) to report in Syrian hamster SCN, and pars tuberalis (PT) as a control, a complete pattern of the postnatal (PN) development of the melatonin receptor density and 2) to investigate whether the regulation of the Mel1a mRNA expression could be implicated in the post natal variations of the melatonin binding capacities. We first subcloned by PCR a partial cDNA encoding the Mel1a receptor from Syrian hamster SCN. Subsequent quantification of Mel1a mRNA expression and melatonin receptor density revealed that in the PT and SCN, both Mel1a mRNA expression and melatonin binding capacities declined abruptly between PN 0 and PN 8. Afterwards, in the PT, both parameters went up until they got stabilized in adulthood. Therefore, in the PT, post natal melatonin receptor density variations were highly correlated with post natal variations of the Mel1a mRNA expression. In the SCN, after PN 8, the melatonin receptor density followed its drop and then declined by more than 92% between post natal day 0 (PN 0) and PN 60 (12.11+/-0. 27 vs. 0.94+/-0.08 fmol/mg protein at PN 0 and PN 60 respectively). In contrast, Mel1a mRNA expression only slightly went down after PN 8 and got stabilized in adult age at 42% of the birth day expression level. These results show that Syrian hamster SCN undergo a dramatic post natal loss of their melatonin receptors that could explain the lack of effect of melatonin injections on SCN circadian activity. Furthermore, this SCN binding capacities decline could not be attributed to an inhibition of the mRNA expression, but rather to a post transcriptional blockade of the Mel1a receptor expression.

Aging↗

TcDJ1, a putative mitochondrial DnaJ protein in Trypanosoma cruzi.

A full length cDNA encoding a novel Trypanosoma cruzi DnaJ protein was cloned and characterized. The 324 amino acid protein encoded by the cDNA (TcDJ1) displays a characteristics J-domain, but lacks the Gly-Phe and zinc finger regions present in some other DnaJ proteins. Relative to four other T. cruzi DnaJ proteins, TcDJ1 has an amino terminal extension containing basic and hydroxylated resides characteristic of mitochondrial import peptides. A T. cruzi transfectant expressing epitope-tagged TcDJ1 was generated and subcellular fractions were produced. Western blot analysis revealed that the protein has a molecular mass of 29 kDa and is found in the mitochondrial fraction. The expression of TcDJ1 is developmentally regulated since the levels of both mRNA and protein are much higher in epimastigotes (replicative form) than in metacyclic trypomastigotes (infective form). Thus it may participate in mitochondrial biosynthetic processes in this organism.

Amino Acid Sequence↗

Small cryptic plasmids of Streptococcus pneumoniae belong to the pC194/pUB110 family of rolling circle plasmids.

The DNA sequences of two related plasmids pPR1 and pPR3 described previously in Streptococcus pneumoniae isolates from Germany and Spain were now determined. Both plasmids belong to a family of rolling circle (RC) plasmids found in a variety of bacteria. Their GC content with 32% is lower than that of the S. pneumoniae chromosomal DNA. The plasmid pPR3 has a molecular size of 3160 bp with four putative open reading frames, whereas pPR1 contained a deletion of 313 bp that included the 5'-part of ORF2 and upstream regions and differed by three bp from pPR3. The predicted protein of ORF1 showed high similarity to replication proteins of RC plasmids with 74% identical amino acids to RepA of Streptococcus thermophilus plasmids. Sequences similar to the plus origin of replication of ssDNA plasmids were present in both plasmids. They also contained a 152-bp region with over 83% identity to the minus origin of replication of the Streptococcus agalacticae plasmid pMV158.

Base Sequence↗

Evaluation of the age-dependent development of lymphocyte surface receptors in children.

Components and functions of the immune system change during postnatal development, not only in the first years of life, but well through adolescence and even into adult life. These age-dependent changes within the immune system greatly complicate any attempt to assess pathological alterations of immunologic variables in children. The need for studies on possible substance-induced changes, including risk assessment of environmental chemicals, has increased the necessity to establish reference ranges for certain immunologic variables against which an abnormal developmental status can be evaluated. In the present study age-related changes of surface receptors on peripheral white blood cells were studied in 82 children, aged between 2 months and 17 years. The blood samples were triple labeled with monoclonal antibodies followed by a whole blood lysis technique and were subsequently analyzed by flow cytometry. Complex statistical analyses were performed in order to determine probability ranges for some immunological variables. In this paper we describe the age-dependent development of components involved in major maturational processes, including the appearance and varying expression of adhesion receptors (CD11a, CD18, CD28, CD29, CD44, CD49d and CD54) on CD4+ "helper" cells and CD8+ "suppressor and cytotoxic" cells. A clear-cut increase of high epitope density expression of the integrins on both CD4+ and CD8+ cells was noted. These results suggest that the components of immune T cells for performing adhesion by interacting with other cells and many matrix components are largely acquired during postnatal development. Maximal levels of adhesion receptor expression are reached at different ages depending on the specific T cell subpopulation.

Adolescent↗

Daily and photoperiodic 2-125I-melatonin binding changes in the pars tuberalis of the Syrian hamster (Mesocricetus auratus): effect of constant light exposure and pinealectomy.

Using quantitative autoradiography, 2-125I-melatonin binding was investigated throughout the light/dark cycle in the pars tuberalis (PT) of the pituitary of adult Syrian hamsters kept for 8 weeks either in long or short photoperiod (LP or SP, respectively). Melatonin receptor density in the PT displayed photoperiod dependent daily variations (maximal values in LP). Indeed, in LP, melatonin receptor density underwent strong daily variations with maximal values during the first half of the light period and minimal values at the end of the night. These variations depended on changes in the maximal binding (Bmax) without differences in the dissociation constant (Kd). In contrast, PT melatonin receptor density was constant and at a very low level throughout the light:dark cycle in SP exposed animals. Daily PT melatonin receptor density variations of LP exposed animals were abolished by pinealectomy or continuous light exposure. These results show clearly that both at the daily and at the seasonal level the regulation of PT melatonin receptors is strongly dependent on circulating melatonin concentrations in the Syrian hamster, but that other regulatory factors, yet unclarified, might also play a role.

Animals↗

Two distinct domains in Staf to selectively activate small nuclear RNA-type and mRNA promoters.

Staf is a transcriptional activator of prime importance for enhanced transcription of small nuclear (snRNA) and snRNA-type genes transcribed by RNA polymerases II and III (Pol II and III). In addition to this activity, it also possesses the capacity to stimulate expression from an RNA polymerase II mRNA promoter. This promiscuous activator thus provides a useful model system for studying the mechanism by which one single transcription factor can activate a large variety of promoters. Here, we report the use of in vivo assays to identify the Staf activation domains involved in promoter selectivity. Analysis of Staf mutants reveals the existence of two physically and functionally distinct regions, outside of the DNA binding domain, responsible for mediating selective transcriptional activation. While a 93-amino-acid domain, with the striking presence of four repeated units, is specialized for transcriptional activation of an mRNA promoter, a segment of only 18 amino acids, with a critical Leu-213 residue, acts specifically on Pol II and Pol III snRNA and snRNA-type promoters. In addition, this study disclosed the fundamental importance of invariant leucine and aspartic acid residues located in each repeat unit of the mRNA activation domain. Staf is therefore the first transcriptional activator described so far to harbor two physically and functionally distinct activator domains. This finding suggests that the same activator can contact different, specialized transcription complexes formed on different types of basal promoters through promoter-specific transactivation pathways.

Amino Acid Sequence↗

Effect of a light pulse on melatonin receptor density and mRNA expression in Siberian hamster suprachiasmatic nuclei.

Melatonin receptors located in the suprachiasmatic nuclei (SCN) have been cloned in mammals hypothalamus. We previously reported a SCN melatonin receptor photic regulation in the rat. The present study's aim was to investigate whether a photic regulation of both melatonin receptor density and mRNA expression takes place in the SCN of a highly photoperiodic species, the Siberian hamster. To achieve this goal, we first set up an in situ hybridization protocol without RNase treatment to allow a highly sensitive and reproducible quantitative analysis of melatonin receptor mRNA expression. Results showed that a 1 h light pulse delivered during night-time did not affect SCN melatonin binding capacities while it induced a strong increase of the melatonin receptor mRNA expression in the SCN of pinealectomized animals.

Animals↗

Staf, a promiscuous activator for enhanced transcription by RNA polymerases II and III.

Staf is a zinc finger protein that we recently identified as the transcriptional activator of the RNA polymerase III-transcribed selenocysteine tRNA gene. In this work we demonstrate that enhanced transcription of the majority of vertebrate snRNA and snRNA-type genes, transcribed by RNA polymerases II and III, also requires Staf. DNA binding assays and microinjection of mutant genes into Xenopus oocytes showed the presence of Staf-responsive elements in the genes for human U4C, U6, Y4 and 7SK, Xenopus U1b1, U2, U5 and MRP and mouse U6 RNAs. Using recombinant Staf, we established that it mediates the activating properties of Staf-responsive elements on RNA polymerase II and III snRNA promoters in vivo. Lastly a 19 bp consensus sequence for the Staf binding site, YY(A/T)CCC(A/G)N(A/C)AT(G/C)C(A/C)YY-RCR, was derived by binding site selection. It enabled us to identify 23 other snRNA and snRNA-type genes carrying potential Staf binding sites. Altogether, our results emphasize the prime importance of Staf as a novel activator for enhanced transcription of snRNA and snRNA-type genes.

Animals↗

Histochemical evaluation of placental dipeptidyl peptidase IV (CD26) in pre-eclampsia: enzyme activity in villous trophoblast indicates an enhanced likelihood of gestational hypertensive disorders.

PROBLEM: To determine whether differences in placental dipeptidyl peptidase IV (DPP IV, CD26) activities occurred in hypertensive complicated pregnancies as compared with uncomplicated pregnancies. METHOD: DPP IV activity was detected with H-Gly-Pro-4M2NA as the substrate in placental cryostat sections from 65 patients with gestational hypertension and 67 patients with uncomplicated pregnancies. The graduated intensities of the reaction product in the villous trophoblast were scored semiquantitatively by light microscopy and were related to the relative frequencies of hypertensive disorders (proportional odds model). After detection of enzyme activity, the same tissue samples were homogenized and used for kinetic fluorometric measurements. RESULTS: Enhanced villous trophoblastic DPP IV activity was significantly associated with an increased frequency of proteinuric hypertension in pregnant women (cumulative odds ratio theta1 = 1.6; P < 0.01). CONCLUSION: This study demonstrates for the first time that increased villous trophoblastic DPP IV activity indicates an increased likelihood of the presence and of the severity of hypertensive disorders in pregnancy.

Adult↗

RNAs mediating cotranslational insertion of selenocysteine in eukaryotic selenoproteins.

Selenocysteine, a selenium-containing analog of cysteine, is found in the prokaryotic and eukaryotic kingdoms in active sites of enzymes involved in oxidation-reduction reactions. Its biosynthesis and cotranslational insertion into selenoproteins is performed by an outstanding mechanism, implying the participation of several gene products. The tRNA(Sec) is one of these. In eukaryotes, its transcription mode by RNA polymerase III differs from that of classical tRNA genes, both at the level of the promoter elements and transcription factors involved. In addition, enhanced transcription is afforded by a newly characterized zinc finger activator. Not only transcription of the gene, but also the tRNA(Sec) itself is atypical since its 2D and 3D structures exhibit features which set it apart from classical tRNAs. Decoding of eukaryotic selenocysteine UGA codons requires a stem-loop structure in the 3'UTR of mRNAs, the selenocysteine insertion sequence (SECIS) element. Structure probing and sequence comparisons led us to propose a 2D structure model for the SECIS element, containing a novel RNA motif composed of four consecutive non-Watson-Crick base-pairs. A 3D model, rationalizing the accessibility data, was elaborated by computer modeling. It yields indicative or suggestive evidence for the role that could play some conserved residues and/or structural features in SECIS function. These might act as signals for interaction with SBP, the SECIS binding protein that we have characterized.

Animals↗

Fasciclin II controls proneural gene expression in Drosophila.

Fasciclin II (Fas II), an NCAM-like cell adhesion molecule in Drosophila, is expressed on a subset of embryonic axons and controls selective axon fasiculation. Fas II is also expressed in imaginal discs. Here we use genetic analysis to show that Fas II is required for the control of proneural gene expression. Clusters of cells in the eye-antennal imaginal disc express the achaete proneural gene and give rise to mechanosensory neurons; other clusters of cells express the atonal gene and give rise to ocellar photoreceptor neurons. In fasII loss-of-function mutants, the expression of both proneural genes is absent in certain locations, and, as a result, the corresponding sensory precursors fail to develop. In fasII gain-of-function conditions, extra sensory structures arise from this same region of the imaginal disc. Mutations in the Abelson tyrosine kinase gene show dominant interactions with fasII mutations, suggesting that Abl and Fas II function in a signaling pathway that controls proneural gene expression.

Animals↗

Staf, a novel zinc finger protein that activates the RNA polymerase III promoter of the selenocysteine tRNA gene.

The selenocysteine tRNA gene (tRNA(Sec)) is atypical. Though transcribed by RNA polymerase III like all other tRNA genes, its basal promoter elements are distinct and reside essentially upstream of the coding region. In addition, transcription from the basal promoter is activated by a 15 bp activator element. In this report we describe the cloning and functional characterization of Staf (selenocysteine tRNA gene transcription activating factor), a novel Xenopus laevis transcription factor which binds to the tRNA(Sec) activator element and mediates its activation properties. The 600 amino acid Staf protein contains seven zinc fingers and a separate acidic activation domain. Seven highly conserved regions were detected between Staf and human ZNF76, a protein of unknown function, thereby aiding in predicting the locations of the functional domains of Staf. With the use of a novel expression assay in X.laevis oocytes we succeeded in demonstrating that Staf can activate the RNA polymerase III promoter of the tRNA(Sec) gene. This constitutes the first demonstration of the capacity of a cloned factor to activate RNA polymerase III transcription in vivo.

Amino Acid Sequence↗

[Cranial sinus thrombosis in puerperium].

Sinus venous thrombosis is a rare and severe disease, clinically characterised by headache, nausea, vomiting, focal deficits and epileptical seizures. We describe a case of sinus venous thrombosis 7 days post partum in a 21-year old woman. The pathogenesis symptoms, diagnosis and therapy are discussed. Advice for obstetric and gynaecological treatment after sinus venous thrombosis is given.

Adult↗