Periodic charge-density modulations on graphite near platinum particles.
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Journal Article↗
Biomedical subjects
U Müller
Publications and source records attributed to U Müller.
Structure of the T cell antigen receptor (TCR): two CD3 epsilon subunits in a functional TCR/CD3 complex.
Transgenic mice carrying and expressing the human CD3 epsilon gene incorporate the corresponding protein product into T cell receptor (TCR)/CD3 complexes on thymocyte and T cell surfaces. The chimeric antigen receptors allow normal T cell development and selection of repertoires in vivo and are able to transduce activation signals in vitro. We have exploited the ability to distinguish mouse (m) and human (h)CD3 epsilon chains to analyze the stoichiometry of CD3 epsilon in transgenic mouse TCRs. Immunoprecipitation and fluorescence resonance energy transfer experiments demonstrate that such TCRs can contain both h- and mCD3 epsilon chains, implying that more than one CD3 epsilon subunit occurs per TCR. Antigen comodulation studies are consistent with a stochastic use of h- or mCD3 epsilon during receptor assembly, and further suggest a structure for the TCR/CD3 complex with two CD3 epsilon chains. The determination of CD3 epsilon subunit stoichiometry, together with existing biochemical data, allows the generation of a minimal model for the structure of the TCR and illustrates the potential value of the transgenic approach to the analysis of complex receptors.
Animals↗
Development of lymphocytes in interleukin 7-transgenic mice.
We have developed and established mouse transgenic lines in which the mouse interleukin 7 gene was targeted for expression in the lymphoid cell compartment. Northern blot analysis indicate that the transgene is expressed in bone marrow (BM), spleen and thymus, but not in kidney, liver, brain or heart. Both the frequency and absolute numbers of B cell precursors and mature B lymphocytes are increased in the BM and spleen of the transgenic mice. Although there is no expansion of the pro-T lymphocyte population in the BM, the number of all major subsets of thymocytes and peripheral T lymphocytes is increased in the majority of the transgenic mice analyzed. The B and T cell lymphocytes in the transgenic mice are functionally competent. In contrast, the number of granulocytes and macrophages in the BM of transgenic mice is similar to that in control non-transgenic littermates. Our results indicate that interleukin 7 plays an important role in vivo in the development of B and T lymphocytes.
Animals↗
Development of the CD4 and CD8 lineage of T cells: instruction versus selection.
T cells bearing the alpha beta T cell receptor (TCR) can be divided into CD4+8- and CD4-8+ subsets which develop in the thymus from CD4+8+ precursors. The commitment to the CD4 and CD8 lineage depends on the binding of the alpha beta TCR to thymic major histocompatibility complex (MHC) coded class II and class I molecules, respectively. In an instructive model of lineage commitment, the binding of the alpha beta TCR, for instance to class I MHC molecules, would generate a specific signal instructing the CD4+8+ precursors to switch off the expression of the CD4 gene. In a selective model, the initial commitment, i.e. switching off the expression of either the CD4 or the CD8 gene would be a stochastic event which is then followed by a selective step rescuing only CD4+ class II and CD8+ class I specific T cells while CD4+ class I and CD8+ class II specific cells would have a very short lifespan. The selective model predicts that a CD8 transgene which is expressed in all immature and mature T cells should rescue CD4+ class I MHC specific T cells from cell death. We have performed experiments in CD8 transgenic mice which fail to support a selective model and we present data which show that the binding of the alpha beta TCR to thymic class I MHC molecules results in up-regulation of the TCR in the CD4+8+ population. Therefore, these experiments are consistent with an instructive model of lineage commitment.
Animals↗
Honeybee venom allergy: results of a sting challenge 1 year after stopping successful venom immunotherapy in 86 patients.
In 86 patients with a history of severe systemic reactions (SRs) to honeybee stings confirmed by a positive skin test and/or RAST to honeybee venom (HBV), immunotherapy (IT) with HBV was stopped after 3 to 10 years. All patients had tolerated well a honeybee sting during IT and were resubmitted to a sting 1 year after VIT was stopped. At the latter time, 15 patients (17%) developed an SR and 71 did not. There was no difference between the two groups regarding age, sex, IT duration, severity of the SR before treatment, as well as diagnostic tests with HBV (skin tests, RAST, and specific IgG) before the challenge. Patients with a relapse of their allergy had, however, developed allergic SRs to IT injections more frequently than patients with lasting protection (p less than 0.001). SRs to the sting challenge (CH) after IT was stopped occurred more frequently in those patients in whom efficacy of IT had previously been confirmed by lacking responses to a field sting than in patients who had tolerated an intentional CH during the injection period (p less than 0.025). Indeed, the incidence of relapse after venom IT was stopped was only 9.6% in patients who had previously tolerated an intentional CH. It is concluded that well-tolerated HBV IT may be stopped after at least 3 years, provided its efficacy has been documented by a CH without SR.
Adolescent↗
Isolation of the human sex determining region from a Y-enriched yeast artificial chromosome library.
We describe the isolation and characterization of yeast artificial chromosome (YAC) clones spanning the male sex determining region on the short arm of the human Y chromosome. The clones were isolated by hybridizing probes in the interval between the genes MIC2 and ZFY to a Y chromosome-enriched YAC library. The YAC clones were consistent with the order of probes established for this interval and may be useful for functional studies of the region in male sex determination. However, many of the YAC clones from this library carried only one arm of the vector ("half-YACs"), deleted sequences from one end, and contained much smaller inserts (148 kb average) than the size of ligated fragments selected by pulsed-field gel electrophoresis (greater than 440 kb). These problems were overcome by protecting DNA with polyamines during YAC library construction and a second Y-enriched YAC library was constructed with an average insert size of 627 kb.
Cell Line↗
Deletion mapping of DNA segments from the Y chromosome long arm and their analysis in an XX male.
Twelve DNA segments have been localized to the long arm of the Y chromosome and were assigned to three intervals by deletion mapping. Of these segments, six were from distal Yq11.23, which is supposed to contain a spermatogenesis locus. The physical mapping information was used to analyze an XX male who is positive for DNA sequences both from distal Yp and from Yq. Two of the twelve sequences from Yq (Y-198 and Y-253) were detected in this patient along with two of six short-arm segments tested. Long-range physical mapping placed Y-198 and Y-253 on a common 1100-kb BssHII fragment. In this patient, the long-arm sequences were assigned to distal Xp by in situ hybridization. The data suggest that this XX male derived from an unequal interchange between an X and an inverted Y chromosome presumed to have been present in the patient's father.
Cells, Cultured↗
Characterisation of the murine Hox-3.3 gene and its promoter.
The murine Hox-3.3 homeobox containing gene and its Xenopus homologue (XlHbox 1) produce two embryonic transcripts from two distinct promoters located approximately 9 kb apart. In order to begin to characterise one of these promoter regions (PRII), we have sequenced 3 kb of DNA immediately upstream of the transcription start site of the PRII transcript and analyzed the sequence for sequences known to bind transcription factors. Within this region are located a number of sequences that match known cis-elements. We have analysed the ability of two of these sequences that match to the Drosophila hunchback and Antennapedia/fushi-tarazu consensus binding sequences to specifically bind proteins extracted from embryos and from adult tissues. Using gel retention assays with oligonucleotides derived from these sequences, we show that both sequences specifically bind proteins present in extracts of mouse embryos and some, but not all extracts of various adult tissues. Protein binding cannot, however, be correlated with the known spatial domains of Hox-3.3 expression, suggesting that binding to these sequences is not simply related to activation of Hox-3.3 expression. A two base pair change in the most conserved region of the hunchback-like binding sequence completely abolishes protein binding. The presence of these highly conserved cis-acting elements that are known to be involved in regulation of the hunchback, even-skipped and engrailed genes in Drosophila suggests that these sequences may also be involved in the regulation of expression of Hox-3.3 and furthermore that regulation may in part at least involve binding of hunchback-like proteins (i.e. zinc-finger proteins) and Antennapedia-like homeobox-containing proteins.
Amino Acid Sequence↗
The phenotype of the X-linked dystonia-parkinsonism syndrome. An assessment of 42 cases in the Philippines.
The clinical phenotype of X-linked recessive torsion dystonia was documented in 42 affected individuals from 21 families. In 7 families, there were 9 sibships (core families) with 2 or more affected individuals available for evaluation. The ages of the patients ranged from 29 to 79 years with a mean of 46.2 +/- 10.1 years; the mean age of onset of dystonia was 35.0 +/- 8.0 years with a range of 12 to 48 years; and the mean duration of illness was 11.1 +/- 7.9 years. First manifestations were noted in the lower extremities in 36%, the axial musculature in 29%, the upper extremities in 23%, and in the head in 12% of the cases. The majority of patients displayed gait abnormalities (90%), leg dystonia (79%), oromandibular dystonia (64%), neck dystonia (57%), blepharospasm (57%), and truncal dystonia (52%). The disease generalized in 90% of the cases within 1 to 11 years of onset (median duration, 5 years). Overall, the condition was disabling, but the Fahn-Marsden disability score did not correlate with age of onset, duration of illness, site of onset, rate of generalization, or presence of parkinsonism. Thirty-six percent of the cases displayed at least 1 of the following "parkinsonian symptoms": bradykinesia, tremor, rigidity, loss of postural reflexes and a shuffling gait. Parkinsonism was diagnosed as definite in 14%, probable in 2%, and possible in 19% of the cases. Given this high association of dystonia and parkinsonism, we propose to call the disorder X-linked dystonia-parkinsonism syndrome (XDP).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Emergency treatment of allergic reactions to Hymenoptera stings.
Allergic reactions to Hymenoptera stings are frequently observed all over Europe. Rarely they may induce long-standing morbidity or even be fatal. Several investigations have shown that the emergency treatment given to these patients is often inadequate. Cutaneous symptoms respond well to antihistamines and also to adrenaline. Adrenaline is the mainstay for outside hospital treatment of more severe reactions involving the respiratory tract (bronchial asthma, laryngeal oedema) and the cardiovascular system (anaphylactic shock). Inhaled adrenaline is especially useful in respiratory symptoms, while parenteral application of adrenaline is prefered for shock treatment. All patients with severe respiratory or cardiovascular reactions must be hospitalized, treated under intensive care conditions and observed for at least 24 hr. Emergency medications including adrenaline for inhalation or for self-injection must be given to all patients with a history of systemic allergic reactions to hymenoptera stings. These patients must also get instructions for safety measures to avoid further stings. They should be referred to an allergist in order to evaluate the indication for venom immunotherapy.
Anaphylaxis↗
Structure and expression of a gene encoding a putative GTP-binding protein identified by provirus integration in a transgenic mouse strain.
The Mov-10 mouse strain was derived by infection of preimplantation embryos with the Moloney murine leukemia virus and carries one copy of the provirus in its germ line. Here we show that the provirus has integrated into an evolutionarily conserved gene that can code for a protein of 110 kDa containing the three consensus elements characteristic for GTP-binding proteins. The Mov-10 locus was expressed in a variety of cell types, including embryonal carcinoma and embryonic stem cells. Transcription of the gene was down-regulated about 10-fold when F9 embryonal carcinoma cells are differentiated into parietal endodermlike cells and about 2-fold when they are differentiated into visceral endodermlike cells. High levels of Mov-10 transcripts were also found at different stages of embryonal development and in the testes and thymus of adult animals. Expression was cell cycle controlled, with steady-state RNA levels significantly higher in growth-arrested than in growth-stimulated cells. The results suggest that the Mov-10 locus has an important function in development and/or control of cell proliferation. The provirus was shown to have integrated into intron 1 of the gene without disrupting expression, indicating that integration into intronic sequences of a transcription unit does not necessarily affect transcription. This result together with previous results from the Mov-13 mouse strain suggested that proviruses exert their mutagenic effect only by integration in specific sites, such as cis-regulatory DNA elements.
Amino Acid Sequence↗
A cardiodepressant factor isolated from blood blocks Ca2+ current in cardiomyocytes.
A cardiodepressant factor (CDF) was isolated (salt free) from the plasma of dogs after hypovolemic-traumatic shock by column chromatography. CDF was found to exert a concentration-dependent negative inotropic effect in guinea pig papillary muscle; it reduced the amplitude of cell wall motion, the contraction and relaxation velocity, and the frequency of spontaneously beating rat cardiomyocytes in culture, effects that were rapidly reversible upon washout. By means of electrophysiological methods (whole cell recording with patch electrodes and voltage clamp) we tested the effect of CDF on adult guinea pig cardiomyocytes: application of CDF initially decreased the plateau by 7 mV (150 ms after peak of action potential) and reduced the action potential duration by 93 ms (76% of control action potential duration) at 50% and 88 ms (79%) at 90% of repolarization. The plateau was further reduced by 13 mV and the action potential duration was prolonged by 25 ms (106%) at 50% and was prolonged drastically by 156 ms (137%) at 90% of repolarization compared with control. Voltage-clamp experiments have shown that the most prominent effect of CDF is a strong reduction of ICa accompanied by inhibition of IK and subsequent repolarization. Similar results have been obtained with neonatal rat cardiomyocytes. Blockage of the calcium inward current can explain the negative inotropic and chronotropic effect of CDF in cardiomyocytes.
Action Potentials↗
Pseudomonas immunoglobulin therapy in patients with Pseudomonas sepsis and septic shock.
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Adult↗
[Intraoperative cholangioscopy].
There are the best diagnostic results by endoscopic examination of the common bile duct. Both rigid and flexible instruments can be used for the examination. The advantages and disadvantages will be discussed. The stump of the cystic dust will be useful to clarify pathological finding by x-ray in the distal bile duct. Usually, however, the instrument is introduced by means of a choledochotomy. In the last 16 years in 1023 cases the bile duct were examined endoscopically, 330 via the cystic duct, 693 via a choledochotomy. Stones were detected in 541 cases (52.9%), in 16 cases (2.9%) a stone was overlooked. Severe complications by operative choledochoscopy were not seen.
Cholangiography↗
Risk factors for adverse drug reactions communication of the CHDM.
In the CHDM (Comprehensive Hospital Drug Monitoring for Adverse Drug Reactions, Bern/St. Gallen), the data of the 34,838 computer registered patient admissions 1974-1988 were available for evaluation. We summarize the results of three different studies: 1. A multivariate analysis of the risk factors to developed an ADR during hospital stay, mainly the number of drugs, age, sex and renal function. 2. The occurrence rate of hyperkalemia under the treatment with diurectics, mainly potassium (K+)-losing with K+ substitution compared to the combination of K(+)-sparing with K(+)-losing preparations. 3. The occurrence-rate of exanthema in relation to amino-penicillin preparations an allopurinol. The results are presented in the communication. (Tab 7, Fig. 1, Ref. 15). Ref. 15.).
Adverse Drug Reaction Reporting Systems↗
No evidence of mutations in four candidate genes for male sex determination/differentiation in sex-reversed XY females with campomelic dysplasia.
Campomelic dysplasia (Cd) occurs combined with sex reversal resulting in XY females. The recent identification of candidate genes for sex determination/differentiation and of a sex determining region on the human Y chromosome prompted the authors to study these genes for mutations in patients with Cd and sex reversal. In a total of five cases, no evidence for a mutation in the genes SRY, ZFY, ZFX, MEA and some anonymous Y-linked sequences was found. In addition to Southern analysis, gene expression of ZFY, ZFX and MEA was found to be normal as well. It is concluded that sex reversal in this condition is due to mutation in a so far unidentified gene which may act secondary to the testis-determining factor (TDF).
Base Sequence↗
[Bronchial asthma in high-performance athletes].
Bronchial asthma is as frequent among high performance athletes as in the general population. We requested information from 2961 athletes of national or international level about these matters and received 2060 answers. From these, we identified 146 athletes (7.1%) with exercise-related deep respiratory airways symptoms. Athletes subject to hay fever (42%) suffer significantly more often (p less than 0.001) from such symptoms during exercise. 80% of these 146 cases had an insufficient diagnostic investigation and/or were treated with medicines unsuited to their needs or even not treated at all. Of particular interest, athletes who additionally had hay fever also received inadequate treatment, even though it is well known that they are subject to enhanced bronchial irritability during the pollen season. As a rule, athletes with exercise-related respiratory problems should be advised to abstain from smoking, especially if they suffer from an atopy-like illness, such as hay fever.
Adult↗
[A school for patients in long-term hospital care in Ulm].
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Child↗