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Biomedical subjects

H Schild

Publications and source records attributed to H Schild.

At least 127 records · Page 7Linked to original sources
PubMed1998

[Radiologic changes following cement-free implantation of hip prostheses. 5-year follow-up and clinical experience with the cement-free hip prosthesis Autophor-900-S].

PURPOSE: To evaluate early reliable radiographic signs of loosening in cementless total hip arthroplasty compared to clinical follow-up. METHODS: Within a time interval of 5 years 89 patients with 101 hips underwent total hip arthroplasty using the Autophor 900 S-prosthesis. Clinical and radiographic follow-up were first performed retrospectively followed by a prospective investigation. RESULTS: Radiographic evaluation showed prosthesis fixation in 93%. Loosening of the prosthesis was identified in 4 cases of the acetabular component and in 4 cases of the femoral stem. Pain was associated with radiographically detectable loosening of the cementless arthroplastic components in only two cases. CONCLUSION: Within a follow-up period of up to five years, loosening of cementless total hip arthroplasty occurs in about 7%. The most reliable radiographic signs of loosening are complete radiolucent zones wider than 2 mm at the bone-component interface, progressive subsidence, migration, or tilt of the component. Pain and movement disorders are not specific symptoms and do not necessarily indicate a loosening of the prosthesis.

Adult↗
PubMed1997

Substrate specificity of cathepsins D and E determined by N-terminal and C-terminal sequencing of peptide pools.

Degradation of protein antigens by cellular proteases is a crucial step in the initiation of a T-cell-mediated immune response. But still little is known about the enzymes responsible for the processing of antigens, including their specificity. In this paper, we show that the combination of automated N-terminal sequencing with a newly developed method for C-terminal sequencing of peptide pools generated by the aspartic proteases cathepsins D and E is a fast and easy method to obtain detailed information of the substrate specificity of these endopeptidases. Using a 15-residue synthetic peptide library and a native protein as substrates, we confirm and extend the knowledge about the cleavage motif of cathepsin E where positions P1 and P1' of the substrate must be occupied exclusively by hydrophobic amino acids with aromatic or aliphatic side chains. However, Val and Ile residues are not allowed at position P1. Position P2' accepts a broad range of amino acids, including charged and polar ones. Additional requirements concerning the substrate positions P3' and P4' were also defined by pool sequencing. Furthermore, pool sequencing analysis of melittin digests with the aspartic proteases cathepsin D and E provided evidence that both enzymes share the same cleavage motif, identical to the one derived from the peptide library and the native protein. Therefore, pool sequencing analysis is a valuable and fast tool to determine the substrate specificity of any endopeptidase.

Amino Acid Sequence↗
PubMed1997

Influences of transporter associated with antigen processing (TAP) on the repertoire of peptides associated with the endoplasmic reticulum-resident stress protein gp96.

The endoplasmic reticulum (ER)-resident stress protein gp96 induces protective immunity and specific cytotoxic T lymphocyte (CTL) responses against antigens expressed in those cells it has been isolated from. This ability is based on peptides associated with gp96. Because gp96 is located inside the ER, our experiments address the question whether or not the repertoire of peptides associated with gp96 is influenced by the transporter associated with antigen processing (TAP). For this purpose, gp96 was isolated from cells with and without a TAP defect and used for immunization of mice. We found that for some antigens the association of peptides with gp96 required functional TAP molecules, whereas the association of peptides from other antigens was TAP independent. In the case of a TAP-dependent association of peptides with gp96, our results prove that peptide binding by gp96 in vivo occurs inside the ER and is not an artifact induced by cell lysis during the gp96 purification. The finding that some antigens can also associate with gp96 in the absence of functional TAP molecules indicates that the repertoire of peptides bound by gp96 truly reflects the entire repertoire of peptides present inside the ER and not only those peptides transported by TAP. These results, together with the earlier finding that the gp96 peptide repertoire is independent of the major histocompatibility complex molecules expressed by the cell gp96 is isolated from, give the theoretical foundation for the ability of gp96 to induce CTL responses against all kinds of intracellular antigens.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Human histocompatibility leukocyte antigen (HLA)-G molecules inhibit NKAT3 expressing natural killer cells.

The crucial immunological function of the classical human major histocompatibility complex (MHC) class I molecules, human histocompatibility leukocyte antigen (HLA)-A, -B, and -C, is the presentation of peptides to T cells. A secondary function is the inhibition of natural killer (NK) cells, mediated by binding of class I molecules to NK receptors. In contrast, the function of the nonclassical human MHC class I molecules, HLA-E, -F, and -G, is still a mystery. The specific expression of HLA-G in placental trophoblast suggests an important role for this molecule in the immunological interaction between mother and child. The fetus, semiallograft by its genotype, escapes maternal allorecognition by downregulation of HLA-A and HLA-B molecules at this interface. It has been suggested that the maternal NK recognition of this downregulation is balanced by the expression of HLA-G, thus preventing damage to the placenta. Here, we describe the partial inhibition of NK lysis of the MHC class I negative cell line LCL721.221 upon HLA-G transfection. We present three NK lines that are inhibited via the interaction of their NKAT3 receptor with HLA-G and with HLA-Bw4 molecules. Inhibition can be blocked by the anti-NKAT3 antibody 5.133. In conclusion, NK inhibition by HLA-G via NKAT3 may contribute to the survival of the fetal semiallograft in the mother during pregnancy.

Cells, Cultured↗
PubMed1997

The endoplasmic reticulum-resident stress protein gp96 binds peptides translocated by TAP.

The endoplasmic reticulum (ER)-resident stress protein gp96 induces a major histocompatibility complex class I-restricted cytotoxic T lymphocyte (CTL) response against antigens present in the cells from which it has been prepared. In this study, photoreactive peptides were translocated into the ER by the transporter associated with antigen processing (TAP). These peptides can be cross-linked specifically to gp96. Thus, we provide the first evidence that gp96 binds TAP-translocated peptides which have been implicated in the induction of specific CTL responses after immunization with gp96 (Srivastava, P. K. et al., Immunogenetics 1994. 39: 93).

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Protein disulfide isomerase is the dominant acceptor for peptides translocated into the endoplasmic reticulum.

Peptides derived from cytosolic protein degradation are translocated into the lumen of the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP). In the ER, class I molecules bind the peptides fitting to their respective motifs and present them on the cell surface to CD8+ T lymphocytes. However, most TAP-translocated peptides are not expected to bind to the class I molecules present in a particular cell. Recently, we have demonstrated that TAP-translocated peptides containing a photoreactive phenylalanine analogue can be cross-linked to two luminal ER-resident proteins: with low efficiency to the stress protein gp96 and with high efficiency to a 60-kDa protein (Lammert, E. et al., Eur. J. Immunol. 1997. 27: 923). Both proteins have also been labeled specifically by TAP-translocated peptides conjugated to a different photoreactive group (Marusina, K. et al., Biochemistry 1997. 36: 856). Here, we show that the 60-kDa peptide-binding protein is identical to the multifunctional protein disulfide isomerase (PDI). Since PDI is the only luminal ER-resident protein that is labeled by the photoreactive peptides with high efficiency, it might represent the dominant acceptor for TAP-translocated peptides.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

[Carbon dioxide (CO2) as contrast medium for the new installation and follow-up of a TIPS].

PURPOSE: To determine the efficacy of CO2 as negative contrast medium compared with iodinated contrast medium in creation and control of TIPS. MATERIAL AND METHODS: CO2 was used during TIPS procedures in 33 patients. In 21 patients a wedged hepatic venography was obtained for planning the shunt tract. Additional TIPS-control DSA was performed in 42 cases by direct portal venography to verify the TIPS function and patency. In all cases CO2 gas was used in addition to iodinated contrast medium. RESULTS: CO2 produced excellent wedged hepatic venographies in all patients. Visualisation of the portal veins and collaterals was superior to iodinated contrast medium. The TIPS-control DSA performed with CO2 were comparable to those performed with iodinated contrast medium. Complications were not observed in our study. CONCLUSION: CO2 is an effective contrast medium for TIPS procedures. In particular the visualisation of portal veins performed by CO2-wedged hepatic venography is superior to iodinated contrast medium.

Adult↗
PubMed1997

[Indirect MR arthrography in the diagnosis of lesions of the labrum glenoidale].

PURPOSE: It has been shown that intravenous administration of contrast media produces an MR arthrographic effect without the need for intraarticular injection. This is the first study evaluating this new technique of indirect MR arthrography in the diagnosis of glenoid labrum tears. METHODS: 28 patients with clinically suspected labral injuries were prospectively investigated (1.5 Tesla, flexible surface coil). A plain MR examination of the shoulder (transverse and oblique-coronal orientation, T1-weighted spin- [TE/TR 15/675], proton density- and T2*-weighted gradient echo [TE/TR/Flip 14,32/600/30 degrees] sequences) and indirect MR arthrography (transverse and oblique-coronal orientation, fat-suppressed T1-weighted spin-echo sequences [TE/TR 15/675], intravenous injection of gadopentetate dimeglumine [0.1 mmol/kg], followed by 10-15 min of joint movement) were performed. Results were confirmed by arthroscopy and/or open surgery. RESULTS: Indirect MR arthrography significantly improved delineation of the glenoid labrum and hyaline cartilage (p < 0.05). Sensitivity and specificity of indirect MR arthrography in the diagnosis of labral injuries were 90% and 89%, compared to 79% and 67% of the native MR examination. CONCLUSION: Indirect MR arthrography is a promising non-invasive technique in the evaluation of the glenoid labrum.

Adult↗
PubMed1997

[MRI dacryocystography after applying gadolinium-containing eyedrops].

PURPOSE: To determine the efficacy of MRI for the lacrimal drainage system after conjunctival application of gadolinium-DTPA solution. MATERIAL AND METHODS: MRI dacryocystography of 32 nasolacrimal duct systems was performed in 16 patients additional to digital subtraction dacryocystography. The gadolinium solution was prepared by diluting the commercially available gadolinium-DTPA (Magnevist, Schering AG, Berlin) 1:10 in sterile saline solution. 3 x 2 drops of this contrast medium were instilled bilaterally immediately before MRI scanning. RESULTS: MRI dacryocystography provided detailed information on the nasolacrimal duct system in all 32 cases. In 16 cases localisation and functional degree of nasolacrimal duct obstruction or stenosis was determined reliably. In 15 cases normal nasolacrimal duct system showed no contrast enhancement. In one case stenosis of the canaliculus was observed. CONCLUSION: MRI dacryocystography provides detailed morphological soft tissue information of the lacrimal drainage system. Local conjunctival application of gadolinium solution allows functional tests of the lacrimal duct system in patients suffering from epiphora.

Adult↗
PubMed1997

[Stent implantation and balloon dilatation in the treatment of stenosis and obstruction of the lacrimal apparatus].

PURPOSE: To evaluate treatment of epiphora caused by obstructions of the nasolacrimal duct system with balloon dilatation and stent implantation. MATERIAL AND METHODS: 28 dacryocystoplasties were performed in 20 patients with complete (n = 7) or incomplete (n = 13) obstruction of the nasolacrimal duct system. RESULTS: Dacryocystoplasty was technically successful performed in 26 cases (93%). Recanalisation was not achieved in two patients with complete obstructions. 17 patients showed complete or partial resolution of epiphora during follow-up of up to two years (clinical success 85%). Complete reobstruction occurred only in one patient 9 months after balloon dilatation and recanalisation was not possible. CONCLUSION: With a technical success rate of 93% and a clinical success rate of 85% dacryocystoplasty is a non-operative alternative for treatment of epiphora caused by obstructions of the nasolacrimal duct system.

Adult↗
PubMed1997

[Oral contrast media in CT: improvement by addition of guar?].

PURPOSE: To evaluate the additional effect of guar with iotrolan as an oral contrast medium. METHOD: In a clinical double-blind randomised study a viscous iotrolan (11.2 mg iodine/ml)/guar (4 g/l)-suspension was compared with aqueous solutions of pure iotrolan (11.2 mg iodine/ml) and meglumine ioxithalamate (12 mg iodine/ml). The contrast media were evaluated according to filling, distribution, transit time, artifacts, radiodensity, patient acceptance and side effects. RESULTS: The addition of guar delayed the transit time of the contrast media. Consequently a more homogeneous filling of the bowel with fewer artifacts was observed in comparison to the aqueous contrast media. The results of the pure iotrolan solution were comparable to meglumine ioxithalamate, except for a higher radiodensity in the distal small intestine. The colon showed a better filling with non-viscous contrast media in the given time frame. Pure iotrolan had the best patient acceptance. Two patients considered the iotrolan/guar-solution impossible to drink, the other 18 patients found taste and consistency just about acceptable. CONCLUSION: In spite of the discussed advantages, due to a less subjective acceptance the guar/iotrolan solution is not suitable in routine-diagnosis, unless taste and consistency are greatly improved. Individual use is recommended in selected cases and long-term examinations.

Administration, Oral↗
PubMed1997

[MR relaxation time measurements with and without selective fat suppression (SPIR) in endocrine orbitopathy].

PURPOSE: To determine the value and utility of relaxation time measurements with magnetic resonance (MR) imaging in patients with Graves' ophthalmopathy (G.O.). MATERIALS AND METHODS: 20 orbits were studied in control subjects and 58 orbits in patients with G.O. T2 relaxation times of extraocular muscles and retrobulbar fat tissue were calculated. The thickness of the eye muscles was correlated with the calculated T2 times. 18 orbits were measured before and after retro-orbital radiation therapy. RESULTS: Upper limits of determined normal T2 values were 60 ms in extraocular eye muscles and 40 ms in retrobulbar fat tissue. 89% (17/19) of the patients with G.O. had prolonged T2 times in extraocular eye muscles. The retrobulbar fat tissue in 5 of 38 orbits revealed minimal edema with the use of fat saturated sequences. T2 relaxation times decreased significantly (p < 10(-4)) after 10 Gy radiation therapy. No correlation was found between enlargement and T2 relaxation times in extraocular eye muscles (r = 0.44 in patients before radiation therapy). CONCLUSION: In patients with G.O. the determination of the enlargement of extraocular eye muscles in computed tomography is not a sufficient parameter for an antiinflammatory therapy, since CT cannot visualise eye muscle edema. T2 relaxation time measurements with MR imaging allow differentiation between edematous and fibrotic changes. This is the diagnostic method of choice in patients with Graves' ophthalmopathy.

Adipose Tissue↗
PubMed1997

Evolutionary conserved cathepsin E substrate specificity as defined by N-terminal and C-terminal sequencing of peptide pools.

The substrate specificity of the non-lysosomal aspartic protease cathepsin E from three different species has been studied using the method of automated N-terminal sequencing and a newly developed method for C-terminal sequencing of peptides and peptide pools. The combination of N-terminal and C-terminal sequencing of peptide pools is a fast and easy method to identify and compare the substrate specificity of endopeptidases. Our analysis shows a conserved hydrolytic specificity between human, mouse and bovine cathepsin E, with only small differences in fine specificity. Furthermore, our results confirm and extend the rules governing the interactions of the substrate with the amino acid (aa) side chains of the various pockets within the enzyme's active cleft. We found that the positions flanking the scissile peptide bond P1-P1' are occupied exclusively by hydrophobic aa with both aliphatic or aromatic side chains; Val and Ile, however, are not allowed in the S1 binding site. The S2 and S2' subsites accept hydrophilic aa. Additional requirements concerning the S3' to S5' subsites were also revealed. Finally, the sequences of single peptides generated by cathepsin E from the three different species can be easily aligned to the determined cleavage motif, showing the reliability of our pool sequencing methods.

Amino Acid Sequence↗
PubMed1997

[Incidence of lesions described by magnetic resonance imaging in the clarification of focal epilepsy of frontal and temporal origin].

AIM: Today, MRI is an integral part of the presurgical evaluation of patients suffering from partial epilepsy. These patients frequently show focal morphological abnormalities with potential epileptogenic character and surgical resection of these lesions is associated with superior postsurgical outcome as to seizure frequency. Apart from easily detectable defects, such as post-traumatic lesions or cerebral infarction, as wide variety of mainly small abnormalities can be detected using MRI. METHODS: In this study, 484 patients suffering from partial epilepsy of temporal or frontal onset were evaluated for the incidence of different lesions in this population. RESULTS: All lesions found were included without evaluating their potential epileptogenicity, which remains to be proven using other procedures (EEG, SPECT, PET, etc.). Involvement of the hippocampal formation was a major finding in temporal lobe epilepsy, which could be detected as sclerosis (T2w-images), atrophy (T2w-TSE or T1w-IR-images) or both (15%). In addition and in declining frequency various tumors (14%), post-traumatic lesion (-5%), and focal cortical dysplasia or other disturbances of cortical integrity (-4%) were found. These lesions are detectable with best contrast on different sequences. As a consequence it is suggested to acquire sequences in 3 dimensions including a T1w-SE, two (coronal and axial) double-echo-SE sequences and similarly two T1w-IR-sequences. The application of contrast media can be restricted to special questions, derived either from the first imaging results or from the patients history. CONCLUSION: Using qualitative data for interpretation, the sensitivity as to the detection of any focal pathology of a recent-generation MRI in this population was 75%, with 79% for temporal lobe epilepsies and 67% for frontal lobe epilepsies. Quantitative measurements of hippocampal volume or signal seem to be able to increase the sensitivity of the method.

Atrophy↗
PubMed1996

Coordinated dual cleavages induced by the proteasome regulator PA28 lead to dominant MHC ligands.

The eukaryotic 20S proteasome is known to associate with the IFN gamma-inducible regulator PA28. We analyzed the kinetics of product generation by 20S proteasomes with and without PA28. In the absence of PA28, the 20S proteasome rapidly generates peptides that have been cleaved only once, while internal fragments accumulate only slowly. In the presence of PA28, products generated by two flanking cleavages appear immediately as main products while the generation of single-cleavage products is strongly reduced. Kinetic data support a PA28-induced, coordinated double-cleavage mechanism. In particular, degradation of peptides derived from mouse cytomegalovirus pp89 and JAK1 kinase in the presence of PA28 leads to strongly enhanced production of the respective major histocompatibility complex ligands and potential precursors. These results show that PA28 profoundly alters the cleavage mechanism of the proteasome and appears to optimize the generation of dominant T-cell epitopes.

Amino Acid Sequence↗
PubMed1996

A role for the proteasome regulator PA28alpha in antigen presentation.

Cytotoxic T cells recognize viral proteins as peptide fragments which are produced in the cytosol and transported on major histocompatibility complex (MHC) class I proteins to the cell surface. Viral peptides that meet the stringent binding characteristics of class I proteins are generated by the 20S proteasome. The interferon (IFN)-gamma-inducible activator of the 20S proteasome, PA28, strongly influences the proteasomal cleavage pattern in vitro. This led us to investigate whether changes in cellular levels of PA28 affect the efficiency of viral antigen processing. A mouse fibroblast line expressing the murine cytomegalovirus pp89 protein was transfected with either the human or murine gene encoding the PA28alpha subunit, which is sufficient to activate the peptide-hydrolysing activity of the 20S proteasome in vitro. Here we report that enhanced expression of PA28alpha at a level similar to that obtained after IFN-gamma induction resulted in a marked enhancement of recognition by pp89-specific cytotoxic T cells; the presentation of influenza nucleoprotein was also significantly improved. These results demonstrate a fundamental in vivo function for PA28alpha in antigen processing.

Amino Acid Sequence↗