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P Weber

Publications and source records attributed to P Weber.

At least 91 records · Page 5Linked to original sources
PubMed1998

Molecular modeling of hen egg lysozyme HEL[52-61] peptide binding to I-Ak MHC class II molecule.

A bound conformation of the antigenic decapeptide hen egg lysozyme HEL[52-61] associated to the mouse MHC class II (MHC II) I-Ak was modeled by homology with the three-dimensional structure of hemagglutinin HA[306-318]-HLA-DR1 complex. HEL peptide Tyr53 could not be aligned with the HA peptide Tyr308 because this resulted in a buried Tyr53 side chain within the I-Ak peptide-binding groove and this conflicted with this side chain being recognized by T cells. Therefore, Asp52 of HEL was fixed as the P1 anchor and aligned on Tyr308 of HA. After molecular dynamics, the modeled complex was stable even in the absence of any constraint. The peptide backbone adopted a polyproline II-like conformation with canonical hydrogen bonding between the peptide backbone and MHC II molecule. Asp52, IIe55, Gin57 and Ser60 were predicted to be deeply buried into P1, P4, P6 and P9 MHC II pockets, and Tyr53, Leu56, Asn59 and Arg61 as TCR contacting residues. The modeling of 15 complexes associating I-Ak with peptides derived from HEL[52-61] by single amino acid substitution proved stable with conserved hydrogen bonds and side chain orientation compatible with their recognition by two T cell hybridomas. Moreover, comparison with the recently solved crystal structure of the related HEL[50-62]-I-Ak complex revealed striking similarities.

Amino Acid Sequence↗
PubMed1998

Targeting of gliadin peptides, CD8, alpha/beta-TCR, and gamma/delta-TCR to Golgi complexes and vacuoles within celiac disease enterocytes.

Celiac disease (CD) is characterized by autodestruction of enterocytes after exposure of genetically susceptible individuals to dietary gluten. To define the transport pathways of proteins involved in the celiac immune response, we wished to determine the subcellular compartments of the intestinal mucosa where wheat gliadin peptides colocalize with receptors of T lymphocytes, including alpha/beta-TCR, gamma/delta-TCR, and CD8. Semithin and ultrathin frozen section of jejunal biopsies from CD patients and controls were used to perform immunofluorescence and immunogold labeling as well as in situ hybridization experiments. In patients with active CD, we detected gliadin peptides in vacuoles and Golgi complexes of enterocytes. CD8, alpha/beta-TCR, and gamma/delta-TCR were found in vacuoles and Golgi complexes within these gliadin-containing enterocytes in addition to the surface of intraepithelial and mucosal T lymphocytes. In contrast, we observed that the localization of CD4, CD3, T cell-restricted intracellular antigen (TIA), and leukocyte common antigen (LCA) was restricted to lymphocytes in CD patients. We further detected labeling signals for gliadin peptides, CD8, alpha/beta-TCR, and gamma/delta-TCR at the basal membrane of enterocytes that were interdigitated by extensions of lymphocytes. In situ hybridization experiments revealed that CD8 and gamma/delta-TCR were not expressed by CD enterocytes. We conclude that CD8, alpha/beta-TCR, and gamma/delta-TCR are targeted to Golgi complexes and vacuoles of small intestinal enterocytes in active CD. The observed process may be involved in the pathogenesis of CD enterocytes. We propose a mechanism for the uptake of CD8, alpha/beta-TCR, and gamma/delta-TCR by the basolateral membrane of small intestinal enterocytes.

Antibodies, Monoclonal↗
PubMed1998

Neutrophil activation after skeletal muscle ischemia in humans.

The aim of the study was to investigate the time course of neutrophil activation after skeletal muscle ischemia in humans and to assess the effect of xanthine oxidase inhibitor allopurinol or cyclooxygenase inhibitor indomethacin. In patients undergoing tourniquet ischemia of the upper limb, polymorphonuclear neutrophils (PMN) were simultaneously isolated from antecubital vein blood of both the contralateral control arm and the tourniquet arm. PMN-superoxide production (PMN-SOP) was determined by a cytochrome C reduction assay, PMN-myeloperoxidase activity (PMN-MPO) by guaiacol oxidation and serum PMN-elastase concentration by an enzyme immunoassay. At 60 min after release of the tourniquet, significant increases of PMN-SOP, PMN-MPO, and serum elastase concentrations were observed in tourniquet arms as compared with control arms (p < .05). Allopurinol (300 mg orally, 12 and 2 h before ischemia) significantly inhibited the increase of PMN-SOP, PMN-MPO, and serum elastase (p < .05). Indomethacin (50 mg orally, 2 h before ischemia) prevented increased PMN-MPO and serum elastase, but prevented increased PMN-SOP only when neutrophils were incubated in the presence of their autologous plasma. These findings suggest that ischemia/reperfusion of human skeletal muscle involves both xanthine oxidase-dependent oxygen free radicals and cyclooxygenase metabolites. These pathways could activate circulating neutrophils which potentially inflict local and remote endothelial injury.

Adolescent↗
PubMed1998

False-positive gliadin and endomysium antibodies and exocrine pancreatic insufficiency as pitfalls in the differential diagnosis of duodenal Crohn's versus celiac disease.

We report a 13-yr-old boy with Crohn's disease in the upper gastrointestinal tract presenting with abdominal pain, failure to thrive, recurrent fever, iron-deficient anemia, and exocrine pancreatic insufficiency. Initially, latent celiac disease was suggested because of normal endoscopic findings, the finding of non-specific inflammation on histological evaluation of duodenal biopsies, positive IgA and IgG gliadin, as well as endomysium antibodies and exocrine pancreatic insufficiency. There was no response to a gluten-free diet. A reevaluation revealed Crohn's disease.

Abdominal Pain↗
PubMed1998

Factor V Leiden and genetic defects of thrombophilia in childhood porencephaly.

AIMS: To determine to what extent the Arg506 to Gln point mutation in the factor V gene and further genetic factors of thrombophilia affect the risk of porencephaly in neonates and infants. METHODS: The Arg506 to Gln mutation, factor V, protein C, protein S, antithrombin, antiphospholipid antibodies and lipoprotein (a) (Lp(a)) were retrospectively measured in neonates and children with porencephaly (n = 24). RESULTS: Genetic risk factors for thrombophilia were diagnosed in 16 of these 24 patients: heterozygous factor V Leiden (n = 3); protein C deficiency type I (n = 6); increased Lp (a) (n = 3); and protein S type I deficiency (n = 1). Three of the 16 infants had two genetic risk factors of thrombophilia: factor V Leiden mutation combined with increased familial Lp (a) was found in two, and factor V Leiden mutation with protein S deficiency type I in one. CONCLUSIONS: The findings indicate that deficiencies in the protein C anticoagulant pathway have an important role in the aetiology of congenital porencephaly.

Adolescent↗
PubMed1998

The critical role of social work in risk management.

If they are included in cases early enough, social workers can help agencies manage risk, protect patients, and avoid litigation. These professionals offer unique skills that agencies should tap into more consistently to reap the benefits of better risk management.

Case Management↗
PubMed1998

Zebrafish tenascin-W, a new member of the tenascin family.

A cDNA clone encoding tenascin-W, a novel member of the tenascin family, was isolated from a 20- to 28-h postfertilization (hpf) zebrafish cDNA library on the basis of the conserved epidermal growth factor-like domains represented in all tenascin molecules. An open reading frame of 2796 base pairs encodes a mature protein consisting of heptad repeats, a cysteine-rich amino terminal region, 3.5 epidermal growth factor-like repeats, five fibronectin type III homologous repeats, and a domain homologous to fibrinogen. These domains are the typical modular elements of molecules of the tenascin family. Sequence comparison demonstrated that TN-W shares homologies with the members of the tenascin family but is not a species homolog of any identified tenascin. The expression pattern of tn-w was analyzed by in situ hybridization in 1-day-old embryos, in 3-day-old larvae, and in juvenile zebrafish. At 24-25 hpf, tn-w mRNA was expressed in the lateral plate mesoderm, most conspicuously in the presumptive sclerotome. Migrating cells of sclerotomal and neural crest origins also showed high levels of expression. At 3 days, expression by sclerotomal and neural crest cells continued to be observed while expression in the somitic mesoderm was decreased. In juvenile fish, tn-w was expressed weakly by cells in the myosepta and, more strongly, by presumably nonneuronal cells in the dorsal root ganglia. In these tissues and at the same developmental stages, the expression of tn-w partially overlapped with the distribution of tn-c mRNA. In addition, tn-c was expressed in the central nervous system (CNS) and in the axial mesoderm, neither of which expressed tn-w at any of the age stages examined. The expression pattern of tn-w suggests an involvement in neural crest and sclerotome cell migration and in the formation of the skeleton. Similar and possibly overlapping functions could also be performed by tn-c, which appears to have additional functions during the development of the CNS.

Aging↗
PubMed1998

[Computer assisted training of attention and concentration with healthy children].

The intention of this study was to analyze in how far a computer assisted training for brain damaged adults can be used for the practice with children. Healthy children of different ages were trained with this attention and concentration programme. The results should help to adapt the training programme for the use in brain damaged children. Age-groups differed significantly in level of performance. Data showed that in comparison to Kindergarten-children, first-grade children showed a higher benefit from the training. Implications for modifications of the training-programme are discussed. Other parameter of performance (reaction-time, errors) in relation to school age provide clues to the distribution of structure of difficulty in the programmes. A questionnaire assessing motivation before and during the training, intelligibility of the task, feasibility of the computer and adequacy of the test in children showed that sustained motivation can be achieved provided the training is used in an adaptive way. Thereby demotivating with too easy tasks as well as frustration caused by difficult tasks can be avoided. In general, there was good acceptance of the computerised cognitive training. The presence of a therapist during every training session proved to be necessary in children under the age of 6 years.

Attention↗
PubMed1997

Pregnancy complicated by vesical calculus and vesicocutaneous fistula.

Bladder stones are a rare complication of pregnancy, with only 10 cases reported this century. This patient required a cesarean section for obstructed labor resulting from a 7 cm stone. Cystotomy with removal of the stone was performed with subsequent development of a vesicocutaneous fistula.

Adult↗
PubMed1997

Hepatic retinopathia. Changes in retinal function.

In patients suffering from hepatic failure, the brain is subject to defined morphological and functional changes known as hepatic encephalopathia (HE). The morphological changes are dominated by glial cells (Alzheimer-type II astrocytes). It has recently been possible to demonstrate, that the retinal glia (Müller) cells undergo similar morphological changes. The present study was carried out in order to reveal if these Müller cell changes cause any characteristic functional deficits. We examined 11 patients with different stages of HE due to liver cirrhosis. Six patients were at stage 0 or 1 (group I) and five at stage 2 or 3 (group II). They underwent ophthalmological routine examination, colour vision testing and standard ERG recording. None of the patients reported impaired vision, in daylight or at night. There were no fundus abnormalities except very mild changes of the pigment epithelium and abnormal reflexes of the inner limiting membrane, especially in the higher HE stages. The number of confusions in the colour arrangement test increased with the higher stages of HE, preferably in the tritan axis. The scotopic a- and b-waves of the electroretinogram (ERG) were almost unchanged in group I and significantly decreased and delayed in group II. The photopic ERG b-wave amplitudes were changed in a similar fashion. Oscillatory potentials proved to be most sensitive to hepatotoxic changes. Their latencies were significantly delayed even in group I. Amplitudes were decreased significantly only in group II. Patients suffering from hepatic failure and accompanying HE display functional abnormalities of the retina. These are best demonstrated by the ERG, and correlate well with the degree of HE. A hypothesis is presented that relates the observed functional changes to altered neurotransmitter levels and impaired retinal glial-neuronal interaction, due to Müller cell damage caused by elevated ammonia levels.

Adult↗
PubMed1997

Vitamin E and human health: rationale for determining recommended intake levels.

The recent literature provides strong evidence that vitamin E intakes much higher than the current recommendations can contribute to and/or improve human health. In fact, the available data indicate that at higher-than-current recommended intake levels, vitamin E affects several functions related to human health. For example, Vitamin E is required to protect polyunsaturated fatty acids (PUFAs) against auto-oxidation. The amount of vitamin E needed to protect PUFAs against oxidative damage is at least 0.4-0.8 mg vitamin E per gram PUFAs and may be in excess of 1.5 mg/g when diets contain higher-than-average levels of long-chain PUFAs. Based upon studies of vitamin E kinetics and metabolism, a daily vitamin E intake of 135-150 IU is suggested. Important functions such as protection against oxidative damage, immune response, and the propensity of platelets to adhere to the vessel wall are related to vitamin E intakes. Vitamin E intake of 40 IU/d was the least amount demonstrated to inhibit low-density lipoprotein oxidation; a dose-dependent effect was seen up to 800 IU/d. Vitamin E intakes of at least 60 IU/d enhanced immune responses and intakes of 200 IU-400 IU/d decreased platelet adhesion to the vessel wall. Based upon the effects of modulating these functions, it is hypothesized that vitamin E plays a pivotal role in the prevention of cardiovascular diseases. Indeed, many observational studies have reported vitamin E to reduce the risk of cardiovascular disease. Recent intervention studies corroborate these findings. Of equal importance, there is a solid body of literature that demonstrates that these and much higher vitamin E intakes are safe.

Cardiovascular Diseases↗
PubMed1997

Otoacoustic emissions as indicators of neurologically based hearing loss in childhood.

One of the most frequent causes of sensorineural hearing loss in childhood is damage to outer hair cells of the cochlea. The presence of otoacoustic emissions, generated by outer hair cells, provides evidence for normal hearing. This finding, however, may give rise to false reassurance, because even severe hearing loss, localized behind the cochlea, can be associated with normal otoacoustic emissions. The coexistence of otoacoustic emissions and hearing loss calls for the prompt exclusion of neurological disease.

Child↗
PubMed1997

Cloning and characterization of a porcine protein kinase gene and relationship to a class of heat shock proteins.

We have determined the genomic sequence of a porcine protein kinase (PPK) gene, including 1,844 bp upstream of the transcription initiation site. The gene spans over 19 kb and consists of 18 exons and 17 introns. The 5' regulatory region contains a characteristic heat shock element in the first intron, a weak heat shock element 1,464 bp upstream of the transcription initiation site, an atypical TATA box, and further consensus sequences typical for eukaryotic promoters such as an SP-1 binding site. Southern blot analysis indicates that PPK exists as a single-copy gene in the porcine haploid genome. The PPK gene is transcribed in all investigated tissues as shown by Northern blotting and reverse transcriptase polymerase chain reaction. Comparison of the protein and cDNA sequences of PPK to other sequences in DNA and protein databases indicates significant homology to a class of heat shock proteins, the glucose-regulated proteins (GRP94). In addition, nucleotide sequences at the 5' terminus of the PPK gene show strong homology to the GRP94 family. Domains highly conserved with human tumor rejection antigen (GP96) or glucose-regulated protein (GRP94) genes are identified within the 5' terminus and the first intron of the PPK gene. These findings suggest that these proteins are either identical or represent a family of closely related proteins.

Animals↗
PubMed1997

Pancreatic autoantibodies in Crohn's disease: a family study.

BACKGROUND: Pancreatic antibodies occur in about one third of patients with Crohn's disease. AIMS: To evaluate the relevance of pancreatic antibodies as a genetic marker in patients with Crohn's disease and their first degree family members and spouses. To characterise further pancreatic antibodies by assessment of IgG subclasses. METHODS: Six hundred and fifty serum samples were tested for pancreatic antibodies by immunofluorescence on sections of human pancreas. Incidence of pancreatic antibodies and their subtypes were studied on 212 serum samples from patients with Crohn's disease. In the familial study, 72 patients with Crohn's disease and 196 first degree family members and 26 patients with ulcerative colitis and 90 first degree family members were included. Ten healthy families served as controls. RESULTS: Pancreatic antibodies were found in 58 (27%) of the patients with Crohn's disease and in none of the controls. Thirty patients had pancreatic antibodies of subtype I characterised by a drop-like fluorescence in the pancreatic acini, 28 patients had subtype II with a fine speckled staining in the acinar cells. Pancreatic antibodies of subtype I were both IgG1 and IgG2 antibodies by contrast with subtype II which were mainly of IgG1 subclass. Only five of 196 first degree relatives of patients with Crohn's disease had pancreatic antibodies. Four of these people had anamnestic data compatible with inflammatory bowel disease. Further investigations showed Crohn's disease in two of these people. In families with more than one member positive for pancreatic antibodies, pancreatic antibodies were of the same subtype in all cases. CONCLUSIONS: Pancreatic antibodies are a specific marker for Crohn's disease. Two subgroups of pancreatic antibodies can be distinguished by their pattern and immunoglobulin subclasses. Pancreatic antibodies rarely occur in family members of patients with Crohn's disease. These family members may also have Crohn's disease.

Autoantibodies↗