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R König

Publications and source records attributed to R König.

At least 37 records · Page 2Linked to original sources
PubMed1999

Improving genetic algorithms for protein folding simulations by systematic crossover.

To improve protein folding simulations, we investigated a new search strategy in combination with the simple genetic algorithm on a two-dimensional lattice model. This search strategy, we called systematic crossover, couples the best individuals, tests every possible crossover point, and takes the two best individuals for the next generation. We compared the standard genetic algorithm with and without this new implementation for various chain lengths and showed that this strategy finds local minima with better energy values and is significantly faster in identifying the global minimum than the standard genetic algorithm.

Algorithms↗
PubMed1999

[Variants of the hepatic artery: detection with color--coded sonography pre and post levovist injection].

PURPOSE: Detection of hepatic artery variants is of great clinical importance, for instance, pre liver transplantation, pre intraarterial chemotherapy or for measurement of the Doppler perfusion index. We therefore investigated how accurate variants of the hepatic artery can be detected using color-coded sonography pre and post Levovist injection. MATERIALS AND METHODS: 52 patients (21-78 years) were examined using color-coded sonography pre and post Levovist injection. After the sonographic examination, intraarterial digital subtraction angiography was performed and the results were compared. RESULTS: Using angiography 14 variants of the hepatic artery were detected in 13 patients. The most common variant in 10 patients were hepatic arteries originating from the superior mesenteric artery. This could be detected with unenhanced color-coded sonography in 8 and with enhanced sonography in 9 patients. In one patient in addition, a hepatogastric trunk was noted by angiography, this was not recognized by sonography. In 2 patients with a hepatogastric trunk, this variant was sonographically seen after Levovist injection in both but with unenhanced sonography in only 1 patient. CONCLUSION: Most variants of the arterial hepatic blood supply can be diagnosed using conventional color-coded sonography. In some cases enhanced sonography provides additional information, but even with these techniques all variations cannot be detected.

Adult↗
PubMed1999

[MR whole-spine recording: computer-assisted simulation of the conventional x-ray technic].

PURPOSE: Development of an MR-based imaging technique for the spine allowing reduction of frequency of conventional Nadiographs in the monitoring of juvenile scoliosis. PATIENTS AND METHODS: 25 patients between the ages of 6 to 36 years were examined in supine position. Two examinations of the cervical and upper thoracic spine and of the lower thoracic and lumbar spine were performed with a 1.5 T Gyroscan ACS-NT Powertrak 6000 system with body coil employing 3D EPI-sequence (TR 17 ms, TE 9 ms, flip angle 20 degrees, field of view 450 mm) or 3D FFE sequences (TR 9 ms, TE 4.5 ms, flip angle 20 degrees, field of view 450 mm) and pulse-oximetry gating. 64 coronal slices were acquired with reconstructed slice thickness of 2 mm. Image processing was performed with an algorithm merging acquisition results into two single images in the coronal and sagittal orientations allowing measurement of the Cobb angle. RESULTS: Mean examination time was 14 minutes per patient. Mean data processing time was seven minutes. Interobserver variance of determination of the Cobb angle was 1.8 degrees. CONCLUSIONS: It is to be hoped that MR whole spine projection will allow a reduction of the frequency of conventional projection in the monitoring of juvenile scoliosis.

Adolescent↗
PubMed1999

Point mutations throughout the GLI3 gene cause Greig cephalopolysyndactyly syndrome.

Greig cephalopolysyndactyly syndrome, characterized by craniofacial and limb anomalies (GCPS; MIM 175700), previously has been demonstrated to be associated with translocations as well as point mutations affecting one allele of the zinc finger gene GLI3. In addition to GCPS, Pallister-Hall syndrome (PHS; MIM 146510) and post-axial polydactyly type A (PAP-A; MIM 174200), two other disorders of human development, are caused by GLI3 mutations. In order to gain more insight into the mutational spectrum associated with a single phenotype, we report here the extension of the GLI3 mutation analysis to 24 new GCPS cases. We report the identification of 15 novel mutations present in one of the patient's GLI3 alleles. The mutations map throughout the coding gene regions. The majority are truncating mutations (nine of 15) that engender prematurely terminated protein products mostly but not exclusively N-terminally to or within the central region encoding the DNA-binding domain. Two missense and two splicing mutations mapping within the zinc finger motifs presumably also interfere with DNA binding. The five mutations identified within the protein regions C-terminal to the zinc fingers putatively affect additional functional properties of GLI3. In cell transfection experiments using fusions of the DNA-binding domain of yeast GAL4 to different segments of GLI3, transactivating capacity was assigned to two adjacent independent domains (TA(1)and TA(2)) in the C-terminal third of GLI3. Since these are the only functional domains affected by three C-terminally truncating mutations, we postulate that GCPS may be due either to haploinsufficiency resulting from the complete loss of one gene copy or to functional haploinsufficiency related to compromised properties of this transcription factor such as DNA binding and transactivation.

Animals↗
PubMed1999

A new technique for oral endotracheal airway access in rabbits under fluoroscopic control: An easy way for drug administration in chronic experiments.

Endotracheal drug administration plays an important role in rabbit models of pulmonary injury and lung disease. However, anatomical features of the oral fissure and pharynx of rabbits make orotracheal intubation a difficult task with a high failure rate. We developed a new technique for airway access in rabbits under fluoroscopic control using a balloon catheter. The procedure consists of four major steps: (1) a shortened 5-french vertebralis catheter is placed into the mesopharynx just above the epiglottic valve, (2) through the catheter lumen a guidewire is carefully moved across the epiglottis and inserted into the trachea, (3) the vertebralis catheter is replaced by a balloon catheter that subsequently is introduced into the tracheal tree over the guidewire, and (4) with the balloon catheter in the right position the guidewire is removed and the balloon is inflated so that finally the drug can be delivered. This procedure was performed in 55 New Zealand White rabbits under general anesthesia with ketamine/xylazine. In all 55 cases the procedure was performed successfully without any major complications and within a reasonably short time period. Removal of the catheter and awakening of the animals were uneventful. The described technique is a simple and safe method for airway access in rabbits and can be useful in chronic experiments for endotracheal drug administration.

Animals↗
PubMed1998

Selection and function of CD4+ T lymphocytes in transgenic mice expressing mutant MHC class II molecules deficient in their interaction with CD4.

Interactions of the T cell coreceptors, CD4 and CD8, with MHC molecules participate in regulating thymocyte development and T lymphocyte activation and differentiation to memory T cells. However, the exact roles of these interactions in normal T cell development and function remain unclear. CD4 interacts with class II MHC7 molecules via several noncontiguous regions in both the class II MHC alpha- and beta-chains. We have introduced a double mutation that disrupts interaction with CD4 into the I-A(beta)k gene and used this construct to generate transgenic mice expressing only mutant class II MHC. Although CD4+ thymocytes matured to the single-positive stage in these mice, their frequency was reduced by threefold compared with that of wild-type transgenics. Positive selection of CD4+ T cells in the mutant transgenic mice may have been mediated by TCRs with a higher than usual affinity for class II MHC/Ag complexes. In A(beta)k mutant transgenics, peripheral CD4+ lymphocytes promoted B cell differentiation to plasma cells. These CD4+ T cells also secreted IFN-gamma in response to various stimuli (e.g., protein Ag, bacterial superantigen, and alloantigen), but were deficient in IL-2 secretion. Interactions between CD4 and class II MHC molecules appeared to regulate lymphokine production, with a strong bias toward IFN-gamma and against IL-2 in the absence of these interactions. Our results have implications for the manipulation of T cell-dependent immune responses.

Amino Acid Substitution↗
PubMed1998

Sibs affected with both Ehlers-Danlos syndrome type IV and cystic fibrosis.

We report on the unprecedented combination of two recessively inherited disorders, the kyphoscoliosis type of Ehlers-Danlos syndrome (EDS type VI) and cystic fibrosis (CF), in two sibs born to consanguineous Turkish parents. Because of failure to thrive and bronchitis CF was diagnosed in the index patient early whereas EDS VI was recognized only very late. Both patients had marked muscular hypotonia at birth, delayed gross motor development, progressive kyphoscoliosis, joint dislocations, Marfanoid habitus, hypertrophic and atrophic scars, and osteopenia. EDS VI was proven by collagen studies and the pathognomonic pattern of urinary pyridinolines. Because the genes coding for the two disorders are located on different chromosomes and a chromosomal rearrangement was excluded, we conclude that their combination is a chance association. The cardiopulmonary impairment common to both diseases makes the prognosis dismal.

Amino Acids↗
PubMed1998

Regulation of T cell immunity and tolerance in vivo by CD4.

Previous experiments showed that peptides corresponding to a major CD4-binding site on the beta2 domain of MHC class II molecules, IAbeta134-148, enhance responses by CD4+ T lymphocytes to antigen, allo-antigen and bacterial superantigen in vitro, and to soluble protein in vivo. To determine whether peptide IAbeta134-148 acted by inhibiting antigen-induced T cell tolerance, ovalbumin-specific CD4+ lymph node (LN) T cells from TCR transgenic DO.11.10 mice were adoptively transferred into H-2 syngeneic BALB/c recipients. Tolerance was then induced by injecting antigen i.v. When peptide IAbeta134-148 was used to interfere with CD4-MHC class II interactions, accumulation of clonotype-positive T lymphocytes in the LN and induction of T cell tolerance in vivo were delayed. The mechanism by which peptide IAbeta134-148 inhibited T cell tolerance included the peptide's ability to block activation-induced cell death. Further, antigen-specific splenic T lymphocytes were not tolerized in IAbeta134-148-treated mice, providing a reservoir of T cells that could respond to a secondary immunization. The results reported here suggest that participation of the T cell co-receptor, CD4, in TCR signaling differentially affected both T cell migration and the induction of antigen-specific tolerance. Therefore, in this in vivo model system, the combined strength of all signals received (e.g. via TCR, co-receptors and co-stimulators) determined whether T cell immunity or apoptosis and tolerance resulted from antigenic stimulation. These findings are potentially important for the development of reagents to enhance vaccine efficacy and tumor immunity.

Animals↗
PubMed1998

The U3 promoter and the nef gene of simian immunodeficiency virus (SIV) smmPBj1.9 do not confer acute pathogenicity upon SIVagm.

Two chimeric proviruses comprising the U3 promoter and the nef gene of simian immunodeficiency virus (SIV) smmPBj1.9 in addition to other genomic regions of SIVagm3mc from African green monkeys (Cercopithecus aethiops) were constructed. The derived chimeric viruses (SIVagm3mc/SIVsmmPBj1.9) were both able to replicate in nonstimulated peripheral blood leukocytes from pig-tailed macaques (Macaca nemestrina), a biological property often correlated with acute pathogenicity. However, only one of the chimeric viruses was acutely pathogenic, inducing a rapid depletion of the peripheral CD4+ T cells in two infected pig-tailed macaques within 10 days after infection in a manner similar to infection with SIVsmmPBj1.9 itself. The other chimeric virus actively replicated during the first 8 weeks after experimental infection of two pig-tailed macaques but induced neither acute disease nor CD4+ T-cell depletion for 113 weeks after infection. Thus, the U3 promoter and the nef gene of SIVsmmPBj1.9 alone appear to be insufficient to confer acute pathogenicity to SIVagm3mc.

Animals↗
PubMed1997

Congenital microgastria, growth hormone deficiency and diabetes insipidus.

UNLABELLED: Microgastria is a rare malformation of the stomach always associated with variable patterns of malformations of the lung, heart, aortic arch, skeleton, and central nervous system. Many cases present with asplenia and hepatic symmetry as well as intestinal malrotation. We report a first case of a 4.5-year-old girl with congenital microgastria in association with growth hormone deficiency, diabetes insipidus, brachyoesophagus, hernia of the diaphragm, gastro-oesophageal reflux, intestinal malrotation, enlarged symmetrical liver, asplenia, as well as mental and statomotor retardation. CONCLUSION: Congenital microgastria is always associated with malformations of other organs. Patients at any age presenting one of the symptoms: failure to thrive, vomiting, asplenia, midline defects and parts of the VACTERL association should be carefully examined to exclude microgastria.

Abnormalities, Multiple↗
PubMed1997

Point mutations in human GLI3 cause Greig syndrome.

Greig cephalopolysyndactyly syndrome (GCPS, MIM 175700) is a rare autosomal dominant developmental disorder characterized by craniofacial abnormalities and post-axial and pre-axial polydactyly as well as syndactyly of hands and feet. Human GLI3, located on chromosome 7p13, is a candidate gene for the syndrome because it is interrupted by translocation breakpoints associated with GCPS. Since hemizygosity of 7p13 resulting in complete loss of one copy of GLI3 causes GCPS as well, haploinsufficiency of this gene was implicated as a mechanism to cause this developmental malformation. To determine if point mutations within GLI3 could be responsible for GCPS we describe the genomic sequences at the boundaries of the 15 exons and primer pair sequences for mutation analysis with polymerase chain reaction-based assays of the entire GLI3 coding sequences. In two GCPS cases, both of which did not exhibit obvious cytogenetic rearrangements, point mutations were identified in different domains of the protein, showing for the first time that Greig syndrome can be caused by GLI3 point mutations. In one case a nonsense mutation in exon X generates a stop codon truncating the protein in the C-H link of the first zinc finger. In the second case a missense mutation in exon XIV causes a Pro-->Ser replacement at a position that is conserved among GLI genes from several species altering a potential phosphorylation site.

Abnormalities, Multiple↗
PubMed1997

Clustering of mutations responsible for branchio-oto-renal (BOR) syndrome in the eyes absent homologous region (eyaHR) of EYA1.

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder, characterised by the association of branchial, otic and renal anomalies with variable degrees of severity. We have recently identified EYA1 , a human homologue of the Drosophila eyes absent gene, as the gene underlying this syndrome. The products of both genes share a highly conserved 271 amino acid C-terminal region (eyaHR). The eyaHR was also found in the products of two other human genes (EYA2 and EYA3), demonstrating the existence of a novel gene family. We report here on the complete genomic structure of EYA1. This gene consists of 16 coding exons and extends over 156 kb. It encodes various alternatively spliced transcripts differing only in their 5' regions. Sequence analysis of the entire EYA1 coding region was performed for 20 unrelated patients affected by BOR syndrome, and six novel mutations were identified. Among these mutations, two are missense mutations, highlighting amino acid residues essential for the function of the EYA1 protein, and one mutation comprises a de novo Alu insertion into an exon. This insertion presumably occurs by retrotransposition, and the mobile Alu element has a poly(A) tail that is unstable throughout generations. To date, 14 mutations have been detected in BOR patients, all of which are different. However, all the mutations are located within or in the immediate vicinity of the eyaHR; the significance of this clustering is discussed.

Amino Acid Sequence↗
PubMed1997

Surgical and neurological complications in a series of 708 epilepsy surgery procedures.

OBJECTIVE: There are few modern data on the complications of surgery for epilepsy from the neurosurgeon's point of view. A survey of complications observed in a large current epilepsy surgery series is presented to facilitate the assessment of a risk:benefit ratio, which must be known when planning for epilepsy surgery and counseling patients. METHODS: A series of 429 consecutive patients operated on during 6.5 years in the newly established University of Bonn epilepsy surgery program was, in part, retrospectively, and, in larger part, prospectively analyzed for complications originating from 279 invasive diagnostic procedures and 429 therapeutic procedures. Neuropsychological and psychiatric complications as well as the rate of failure to control seizures are not addressed in this article. RESULTS: Two hundred and seventy-nine temporal operations, 59 frontal operations, 22 other extratemporal operations, 33 callosotomies, 3 multilobectomies, and 33 hemispherectomies were performed. Complications were grouped into general surgical and neurological complications. No mortality resulted from 708 invasive procedures. Two hundred and seventy-nine invasive diagnostic procedures (various combinations of strip, grid, and depth electrode insertions) resulted in 3.6% transient morbidity (2.9% surgical complications, 0.7% neurological complications) and 0.7% permanent morbidity (dysphasia). During 429 therapeutic procedures, 33 surgical complications were encountered. None of these resulted in permanent morbidity, except for the necessity for permanent shunt insertion in three patients. Wound infection was the most frequent surgical complication, but we were able to demonstrate a steady decrease during the 6.5-year observation period. The total rate of neurological complications in 429 therapeutic procedures was 5.4%, with 3.03% causing transient morbidity and 2.33% causing permanent morbidity. CONCLUSION: Our data indicate that epilepsy surgery can be performed with an acceptable rate of resultant morbidity. The indications for epilepsy surgery, the learning curve determined, and the results from other series are discussed in the light of these figures.

Adolescent↗
PubMed1996

Minimal definition of the imprinting center and fixation of chromosome 15q11-q13 epigenotype by imprinting mutations.

Patients with disorders involving imprinted genes such as Angelman syndrome (AS) and Prader-Willi syndrome (PWS) can have a mutation in the imprinting mechanism. Previously, we identified an imprinting center (IC) within chromosome 15q11-ql3 and proposed that IC mutations block resetting of the imprint, fixing on that chromosome the parental imprint (epigenotype) on which the mutation arose. We now describe four new microdeletions of the IC, the smallest (6 kb) of which currently defines the minimal region sufficient to confer an AS imprinting mutation. The AS deletions all overlap this minimal region, centromeric to the PWS microdeletions, which include the first exon of the SNRPN gene. None of five genes or transcripts in the 1.0 Mb vicinity of the IC (ZNF127, SNRPN, PAR-5, IPW, and PAR-1), each normally expressed only from the paternal allele, was expressed in cells from PWS imprinting mutation patients. In contrast, AS imprinting mutation patients show biparental expression of SNRPN and IPW but must lack expression of the putative AS gene 250-1000 kb distal of the IC. These data strongly support a model in which the paternal chromosome of these PWS patients carries an ancestral maternal epigenotype, and the maternal chromosome of these AS patients carries an ancestral paternal epigenotype. The IC therefore functions to reset the maternal and paternal imprints throughout a 2-Mb imprinted domain within human chromosome 15q11-q13 during gametogenesis.

Angelman Syndrome↗
PubMed1996

Peptides corresponding to CD4-interacting regions of murine MHC class II molecules modulate immune responses of CD4+ T lymphocytes in vitro and in vivo.

Immune responses mediated by CD4+ T cells depend on Ag-specific alpha beta TCRs that recognize the specific antigenic peptide presented by MHC class II molecules. Interactions between CD4 coreceptors and monomorphic regions of MHC class II molecules contribute to these responses. To examine whether immune reactions could be modulated by specifically interfering with CD4-MHC class II interactions, we have used, in various in vitro and in vivo assays, peptides that correspond to a region of MHC class II molecules previously shown to control interaction with CD4. Depending on the chemical nature and concentration of these peptides, they modulated Ag-specific responses of CD4+ T cells. At high concentrations, these peptides inhibited T cell responses in vitro. However, under conditions that can cause Ag-induced unresponsiveness, the peptides enhanced T cell responses. Also, primary in vivo immune responses to systemically administered soluble protein Ag, keyhole limpet hemocyanin, were enhanced when mice were treated with peptides corresponding to the CD4-interacting region of MHC class II molecules but not when treated with control peptides. Lymphokine profiles suggested that the peptides may favor the differentiation of Th1 cells, because lymphocytes from peptide-treated mice secreted more IL-2 and IFN-gamma than lymphocytes from nontreated or control-peptide-treated mice upon restimulation with Ag in vitro. These results demonstrate that MHC class II-derived peptides can directly interfere with interactions with CD4 and modulate T cell responses in vitro and in vivo.

Adjuvants, Immunologic↗