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Biomedical subjects

H Schild

Publications and source records attributed to H Schild.

At least 55 records · Page 3Linked to original sources
PubMed2002

[MRI in cavernous transformation of the portal vein: secondary biliary abnormalities and portoportal collaterals].

PURPOSE: Evaluation of portoportal collateral vessels and associated biliary abnormalities in patients with cavernous transformation of the portal vein by MRI. MATERIAL AND METHODS: Review of 34 MRI examinations performed on patients with angiographically or MR-angiographically proven cavernous transformation. The analysis included the pattern of the portoportal collateral circulation and the abnormalities of the biliary system, such as wall thickening, stenosis, dilations and irregularities of the extra-and intrahepatic bile ducts. RESULTS: 23 (67.6%) of 34 patients with cavernous transformation had paracholedochal portoportal collateral vessels, with 22 (64.7%) showing visible luminal channels. Epicholedochal venous collaterals could be observed in 8 (23.5%) patients. 24 (70.5%) of 34 patients demonstrated biliary abnormalities due to portoportal collaterals, leading to stenosis with dilatation of the proximal bile ducts in 8 (23.5%) patients. The ductal walls were irregular in 7 (20.5%) patients, and thickened in 11 (32.3%). The gallbladder wall was thickened in 4 (12.9%) patients. CONCLUSION: Portoportal collaterals in patients with cavernous transformation of the portal vein can be identified by MRI. These collaterals frequently alter the biliary system, which must be considered in differential diagnosis of biliary abnormalities observed in the presence of portoportal collaterals.

Adult↗
PubMed2002

Hemodynamic effects of propranolol and nitrates in cirrhotics with transjugular intrahepatic portosystemic stent-shunt.

BACKGROUND: The combination of tailored TIPS with vasoactive drugs might allow reduction of the rate of subsequent shunt-related sequelae. METHODS: We studied cirrhotic patients 8 weeks (median) after TIPS insertion (8-10 mm) for variceal bleeding. Nitrate (0.1 mg/kg) and propranolol (0.15 mg/kg) alone or combined (same dosages) were infused (I h) sequentially at 1-h intervals (n = 17). Similarly, propranolol was randomly compared to placebo (NaCl, n = 14). We measured mean arterial pressure (MAP, mmHg), heart rate (HR) and portal pressure gradient (PPG: portal minus central venous pressure) prior to and after drugs. RESULTS: Propranolol reduced PPG (mean +/- s, mmHg) significantly (14.8 +/- 3.7 versus 12.1 +/- 3.7; -21% +/- 10%; P < 0.001), while nitrates alone (14.3 +/- 3.4 versus 13.7 +/- 3.4; -11% +/- 3%; P=0.06) or nitrates plus propranolol (12.9 +/- 4 versus 12.4 +/- 4; -7% +/- 8%; P=0.2) induced only minor additive effects on portal pressure. However, nitrate reduced MAP (P < 0.001) and increased HR (P < 0.01), whereas propranolol reduced only HR (P < 0.001) with unchanged MAP, and the combination decreased MAP (P < 0.001). Compared to placebo (no effect), propranolol decreased PPG (14.4 +/- 5.6 versus 11.1 +/- 5.5; -23% +/- 11%; P < 0.001) and HR (P < 0.001). Overall, most patients (92%) responded to propranolol and 54% showed a marked PPG decrease (>20%). CONCLUSIONS: Propranolol significantly reduced portal pressure in cirrhotic patients after TIPS, whereas nitrates induced only minor benefit. TIPS-treated patients might therefore profit from additive propranolol therapy allowing limited shunts to be applied initially and/or to reduce the need for TIPS revisions in the case of shunt-dysfunction during follow-up.

Blood Pressure↗
PubMed2001

Discrete cleavage motifs of constitutive and immunoproteasomes revealed by quantitative analysis of cleavage products.

Proteasomes are the main proteases responsible for cytosolic protein degradation and the production of major histocompatibility complex class I ligands. Incorporation of the interferon gamma--inducible subunits low molecular weight protein (LMP)-2, LMP-7, and multicatalytic endopeptidase complex--like (MECL)-1 leads to the formation of immunoproteasomes which have been associated with more efficient class I antigen processing. Although differences in cleavage specificities of constitutive and immunoproteasomes have been observed frequently, cleavage motifs have not been described previously. We now report that cells expressing immunoproteasomes display a different peptide repertoire changing the overall cytotoxic T cell--specificity as indicated by the observation that LMP-7(-/-) mice react against cells of LMP-7 wild-type mice. Moreover, using the 436 amino acid protein enolase-1 as an unmodified model substrate in combination with a quantitative approach, we analyzed a large collection of peptides generated by either set of proteasomes. Inspection of the amino acids flanking proteasomal cleavage sites allowed the description of two different cleavage motifs. These motifs finally explain recent findings describing differential processing of epitopes by constitutive and immunoproteasomes and are important to the understanding of peripheral T cell tolerization/activation as well as for effective vaccine development.

Amino Acid Sequence↗
PubMed2001

A role for a novel luminal endoplasmic reticulum aminopeptidase in final trimming of 26 S proteasome-generated major histocompatability complex class I antigenic peptides.

Peptides presented to cytotoxic T lymphocytes by the class I major histocompatability complex are 8-11 residues long. Although proteasomal activity generates the precise C termini of antigenic epitopes, the mechanism(s) involved in generation of the precise N termini is largely unknown. To investigate the mechanism of N-terminal peptide processing, we used a cell-free system in which two recombinant ornithine decarboxylase (ODC) constructs, one expressing the native H2-K(b)-restricted ovalbumin (ova)-derived epitope SIINFEKL (ODC-ova) and the other expressing the extended epitope LESIINFEKL (ODC-LEova), were targeted to degradation by 26 S proteasomes followed by import into microsomes. We found that the cleavage specificity of the 26 S proteasome was influenced by the N-terminal flanking amino acids leading to significantly different yields of the final epitope SIINFEKL. Following incubation in the presence of purified 26 S proteasome, ODC-LEova generated largely ESIINFEKL that was efficiently converted to the final epitope SIINFEKL following translocation into microsomes. The conversion of ESIINFEKL to SIINFEKL was strictly dependent on the presence of H2-K(b) and was completely inhibited by the metalloaminopeptidase inhibitor 1,10-phenanthroline. Importantly, the converting activity was resistant to a stringent salt/EDTA wash of the microsomes and was only apparent when transport of TAP, the transporter associated with antigen processing, was facilitated. These results strongly suggest a crucial role for a luminal endoplasmic reticulum-resident metalloaminopeptidase in the N-terminal trimming of major histocompatability complex class I-associated peptides.

Amino Acids↗
PubMed2001

Hoffa's recess: incidence, morphology and differential diagnosis of the globular-shaped cleft in the infrapatellar fat pad of the knee on MRI and cadaver dissections.

We frequently observed a fluid-like indentation at the inferior posterior margin of Hoffa's fat pad of the knee and sought to establish the incidence and differential diagnostic criteria of this cleft. In total, 133 MRI studies and 35 cadaver specimens were analyzed for the location, size, and shape of clefts at the inferior posterior margin of Hoffa's fat pad. The incidence of a fluid-like ovoid cleft on MR images was 13.5% and in cadavers 14.3%. The cleft was located just below the insertion of the infrapatellar synovial fold (plica synovialis infrapatellaris, ligamentum mucosum). More linear-shaped indentations at the posterior margin were visible in all patients and cadavers due to the horizontal course of the alar folds. A fluid-filled indentation within the inferior posterior margin of Hoffa's fat pad has to be expected in more than 10% of knee studies and should not be confused with tumors like ganglion cysts. We term this cleft the infrahoffatic recess. One hypothesis of its origin concerns the embryological regression process of the infrapatellar membrane into the infrapatellar synovial fold. It should not be confused with linear clefts due to the alar folds.

Adult↗
PubMed2001

Proton magnetic resonance spectroscopy of the motor cortex in 70 patients with amyotrophic lateral sclerosis.

OBJECTIVE: To evaluate proton magnetic resonance spectroscopy for detection and monitoring of upper motoneuron degeneration in patients with amyotrophic lateral sclerosis. METHODS: Seventy patients with amyotrophic lateral sclerosis according to the El Escorial criteria were compared with 48 healthy control subjects. Single-volume proton magnetic resonance spectroscopy (echo time, 272 milliseconds; repetition time, 2000 milliseconds) was performed in both motor cortices for detection of N-acetylaspartate (NAA), phosphocreatine + creatine ([P]Cr), and choline-containing compounds (Cho) to calculate the metabolite ratios NAA/Cho, NAA/(P)Cr, and Cho/(P)Cr. In addition, absolute metabolite concentrations of NAA, (P)Cr, and Cho were obtained in 30 patients and 15 controls with the unsuppressed water signal used as an internal reference. RESULTS: Absolute concentrations of NAA (P<.001) and (P)Cr (P<.05) were reduced in motor cortices of patients, whereas Cho concentrations remained unchanged. The NAA/Cho and NAA/(P)Cr ratios were reduced in all El Escorial subgroups (P<.001). The Cho/(P)Cr ratio was elevated in patients with definite amyotrophic lateral sclerosis (P<.05). Metabolite ratio changes corresponded to the lateralization of clinical symptoms and were weakly correlated with disease duration and disease severity. In follow-up observations of 16 patients during a mean (+/-SD) of 12.1 +/- 8.7 months, NAA/Cho dropped by 9.1% (P<.01), and Cho/(P)Cr increased by 7.0% (P<.01). Changes of metabolite ratios were significantly correlated with progression of disease severity. CONCLUSIONS: Measurement of NAA concentrations and NAA/Cho ratios appear to be most suitable for detection of motor cortex degeneration by single-volume proton magnetic resonance spectroscopy. Reduced NAA/Cho ratios correspond to aspects of the clinical presentation and reflect disease progression in follow-up measurements.

Adult↗
PubMed2001

Improving the detectability of focal liver lesions on T2-weighted MR images: ultrafast breath-hold or respiratory-triggered thin-section MRI?

The purpose of this study was to determine whether a respiratory-triggered (RT) T2-weighted turbo spin-echo (TSE) sequence with thin section can improve the detectability of focal liver lesions compared to a breath-hold (BH) T2-weighted TSE sequence. In 25 patients an RT TSE with 8-mm sections (8-TSE RT) and 5-mm sections (5-TSE RT) and a BH TSE sequence with 8-mm sections (8-TSE BH) were performed. Forty-one focal liver lesions (mean: 1.8 +/- 1.2 cm; 14 lesions < or =1 cm; 27 lesions >1 cm) were evaluated. The 5-TSE RT was significantly better in lesion detection compared to the 8-TSE BH sequence for all sizes of lesions (40/41 vs. 33/41; P = 0.014). For lesions >1 cm no relevant differences in the detection rate of the sequences were found (8-TSE RT, 26/27; 5-TSE RT, 26/27; 8-TSE BH, 25/27), for lesions < or =1 cm the 5-TSE RT provided significantly better sensitivity than the 8-TSE BH (14/14 vs. 8/14, P = 0.015). The results of this study suggest that lesion detection could be significantly improved by using an RT TSE sequence with thin sections compared with a BH TSE sequence.

Female↗
PubMed2001

PAProC: a prediction algorithm for proteasomal cleavages available on the WWW.

The first version of PAProC (Prediction Algorithm for Proteasomal Cleavages) is now available to the general public. PAProC is a prediction tool for cleavages by human and yeast proteasomes, based on experimental cleavage data. It will be particularly useful for immunologists working on antigen processing and the prediction of major histocompatibility complex class I molecule (MHC I) ligands and cytotoxic T-lymphocyte (CTL) epitopes. Likewise, in cases in which proteasomal protein degradation has been indicated in disease, PAProC can be used to assess the general cleavability of disease-linked proteins. On its web site (http://www.paproc.de), background information and hyperlinks are provided for the user (e.g., to SYFPEITHI, the database for the prediction of MHC I ligands).

Algorithms↗
PubMed2001

Phenotype assignment in symptomatic female carriers of X-linked adrenoleukodystrophy.

However, only very few studies have systematically investigated the extent and distribution of nervous and endocrine system involvement in female carriers of X-ALD. To define the phenotype in symptomatic female carriers of X-ALD we performed a prospective study including eight symptomatic women who were followed for a mean period of 3.4+/-1.8 years (range 1-6) using standardized clinical examination protocols, magnetic resonance imaging and spectroscopy, evoked potential studies including visual, brainstem auditory, somatosensory and magnetic evoked potentials, neurographic recordings and endocrine studies. Spastic paraparesis and decreased vibration sense in the lower extremities were the most frequent clinical findings. Slightly hyperintense symmetric parieto-occipital white matter lesions on magnetic resonance imaging were detectable in two of seven cases, and the N-acetylaspartate/choline ratios on magnetic resonance spectroscopy were decreased in three of seven patients. P40 latencies were abnormal in all patients, and central motor conduction times to the lower extremities in seven of eight patients. Prolonged latencies of brainstem auditory evoked potential waves III-V or interpeak latencies of waves I-III, I-V and III-V were detectable in all patients. The degree of walking impairment was positively correlated with the duration of clinical disease (r=0.58, P < 0.05) and inversely correlated with the N-acetylaspartate/choline ratios (r=0.85; P < 0.05). Neurographic recordings revealed only subtle abnormalities, suggesting that nervous system involvement in symptomatic female carriers of X-ALD is confined mainly to the central nervous system. No evidence of adrenal insufficiency was detected in any of the patients.

Adrenal Insufficiency↗
PubMed2001

[MRI of the lung parenchyma].

Up to now the role of lung imaging in routine diagnostic work-up of pulmonary diseases has remained rather limited. However, the well-known technical problems of lung MRI (low spatial resolution, motion artifacts, low signal-to-noise ratio of the lung parenchyma) have been reduced by recent technical advances, thus leading to a significantly improved image quality in MRI of the lungs. Compared to helical CT good results have been demonstrated using a cardiac and respiratory triggered T2 weighted turbo spin echo sequence which should be included in every imaging protocol. Recent studies have proven that MRI is comparable or even better than the gold-standard helical CT regarding the staging of bronchogenic cancer and follow-up examinations of pneumonia and lung metastases. For other indications like the assessment of pulmonary nodules and the early diagnosis of pneumonia MRI has shown promising results; however these results need to be confirmed in larger patient groups. In patients with chronic infiltrative lung disease, CT scanning remains the superior imaging modality due to the inferior spatial resolution of MRI. In conclusion MRI is a reliable alternative imaging method to helical CT for many indications; in some cases it may be a promising additional examination method.

Diagnosis, Differential↗
PubMed2001

[Value of selective MIP reconstructions in respiratory triggered 3D TSE MR-cholangiography on a workstation in comparison with MIP standard projections and single-shot MRCP].

PURPOSE: Comparison of anatomical visualisation and diagnostic value of selective MIP reconstructions of respiratory triggered 3D-TSE-MRCP versus standard MIP reconstructions and single-shot MRCP. MATERIAL AND METHODS: 50 patients with pancreaticobiliary disease were examined at 1.5 Tesla (ACS NT II, Philips Medical Systems) using a breath-hold single-shot (SS) and a respiratory triggered 3D-TSE-MRCP technique in 12 standard MIP projections. Additional selective MIP reconstructions with different slice thickness (2, 4, 10 cm) and projections were performed on a workstation. Visualization of the pancreaticobiliary system and the diagnostic value of the examinations were analysed. RESULTS: Single-shot and 3D-TSE in standard projections showed comparable anatomical visualisation. On selective MIP reconstructions the biliary system (SS p < 0.002; 3D-TSE p < 0.000) and the periampullary region (SS p < 0.000; 3D-TSE p < 0.003) were more clearly seen than on SS and standard MIP reconstructions. Furthermore, superior visualisation of the pancreatic duct could be achieved with additional selective MIP reconstructions in contrast to standard MIP (p < 0.003). Sensitivity and diagnostic accuracy showed superior results for selective and standard MIP reconstructions, but no significant differences between the three techniques were found. CONCLUSION: SS and standard MIP reconstructions showed comparable anatomical visualisation. Selective MIP postprocessing on a workstation offers a better visualisation of the pancreaticobiliary system and is useful for detecting pathological alterations.

Artifacts↗
PubMed2001

[Obstruction of surgical portosystemic shunts in the early postoperative phase: interventional treatment by angioplasty with stent implantation].

PURPOSE: Recurrent variceal bleeding in patients treated with surgical porto-systemic shunting is most often due to shunt stenoses or occlusion. Radiological interventional procedures are a possible method of therapy and our experience herein is described in this report. PATIENTS AND METHODS: From 1997 to 1999 54 patients with recurrent variceal bleeding were treated with a surgical porto-systemic shunt procedure. Of these early shunt occlusion occurred in 5 patients, which was treated with percutaneous transcatheter techniques. RESULTS: In only one patient was PTA alone sufficient to reestablish shunt patency, in four patient stent placement was necessary in addition. In the follow-up period 1 patient died 26 month after intervention with (autopsy-proven) patent shunt, in one patient shunt reocclusion occurred after 11 months and in 3 patients the shunt is still patent. CONCLUSIONS: PTA, if necessary in combination with stent placement, is an attractive alternative method of therapy in case of an early surgical porto-systemic shunt occlusion.

Adult↗
PubMed2001

Percutaneous translymphatic thoracic duct embolization for treatment of chylothorax.

A modified technique for transabdominal, translymphatic occlusion of the thoracic duct is described. During unilateral lymphangiography an abdominal lymph vessel was punctured with a fine needle under fluoroscopic guidance, and a 4 French access to the lymph system established. The thoracic duct was successfully embolized with coils and tissue adhesive in a patient with postoperative high output chylothorax. Chylous drainage immediately decreased after the intervention, the intercostal drain could be removed after seven days. Long term follow up over a ten months period confirmed the clinical success; the patient is still free of pleural effusions.

Aged↗
PubMed2001

The role of heat shock proteins and their receptors in the activation of the immune system.

Heat shock proteins (HSPs) have been described as potent tumor vaccines in animal models and are currently studied in clinical trials. The underlying immune response relies on immunogenic peptides that the HSPs have acquired intracellularly by interfering with the classical antigen processing pathways. There have been numerous reports shedding light on how HSPs are able to gain this function and a number of important requirements for HSP-mediated specific immunity have been described: first, the ability of HSPs to bind immunogenic peptides. Second, the acquisition of HSPs by specialized antigen presenting cells with efficient antigen processing pathways capable of inducing cellular immune responses. Third, the existence of specific receptors on the surfaces of antigen presenting cells, allowing efficient and rapid uptake of HSP-peptide complexes from the extracellular fluid. And fourth, the ability of heat shock proteins to activate antigen presenting cells, enabling the latter to prime cytotoxic T cell responses against the peptides associated to HSPs.

Animals↗
PubMed2000

One-step single-chain Fv recombinant antibody-based purification of gp96 for vaccine development.

Heat shock proteins such as gp96 (grp94) isolated from tumor or infected cells are able to induce specific cytotoxic T-cell responses and protective immunity. To facilitate rapid and efficient isolation, we generated gp96-specific recombinant single-chain Fv (scFv) antibodies from a semisynthetic phage display library. When immobilized on Sepharose beads, these antibodies allow a high-yield, one-step purification of native gp96 molecules from both mouse and human tumor cell lysates. gp96 molecules eluted from these affinity columns under mild conditions are still capable of generating antigen-specific CTL responses in mice. Thus, scFv-purified gp96 is still associated with peptides; however, in contrast to conventionally purified gp96, scFv-isolated gp96 is free of contaminating material such as mitogenic concanavalin A and proteolytic cathepsins. With the help of these high-yield antibody columns, it is now possible to rapidly isolate immunogenic gp96-peptide complexes from small amounts of tumor material to a purity that allows their use in cancer immunotherapy protocols.

Amino Acid Sequence↗
PubMed2000

The human 26 S and 20 S proteasomes generate overlapping but different sets of peptide fragments from a model protein substrate.

Intracellular protein degradation is a major source of short antigenic peptides that can be presented on the cell surface in the context of major histocompatibility class I molecules for recognition by cytotoxic T lymphocytes. The capacity of the most important cytosolic protease, the 20 S proteasome, to generate peptide fragments with an average length of 7-8 amino acid residues has been thoroughly investigated. It has been shown that the cleavage products are not randomly generated, but originate from the commitment of the catalytically active subunits to complex recognition motifs in the primary amino acid sequence. The role of the even larger 26 S proteasome is less well defined, however. It has been demonstrated that the 26 S proteasome can bind and degrade ubiquitin-tagged proteins and minigene translation products in vivo and in vitro, but the nature of the degradation products remains elusive. In this study, we present the first analysis of cleavage products from in vitro digestion of the unmodified model substrate beta-casein with both the 26 S and 20 S proteasome. The data we obtained show that 26 S and 20 S proteasomes generate overlapping, but at the same time substantially different, sets of fragments by following very similar instructions.

Adenosine Triphosphatases↗
PubMed2000

Cross-presentation of glycoprotein 96-associated antigens on major histocompatibility complex class I molecules requires receptor-mediated endocytosis.

Heat shock proteins (HSPs) like glycoprotein (gp)96 (glucose-regulated protein 94 [grp94]) are able to induce specific cytotoxic T lymphocyte (CTL) responses against cells from which they originate. Here, we demonstrate that for CTL activation by gp96-chaperoned peptides, specific receptor-mediated uptake of gp96 by antigen-presenting cells (APCs) is required. Moreover, we show that in both humans and mice, only professional APCs like dendritic cells (DCs), macrophages, and B cells, but not T cells, are able to bind gp96. The binding is saturable and can be inhibited using unlabeled gp96 molecules. Receptor binding by APCs leads to a rapid internalization of gp96, which colocalizes with endocytosed major histocompatibility complex (MHC) class I and class II molecules in endosomal compartments. Incubation of gp96 molecules isolated from cells expressing an adenovirus type 5 E1B epitope with the DC line D1 results in the activation of E1B-specific CTLs. This CTL activation can be specifically inhibited by the addition of irrelevant gp96 molecules not associated with E1B peptides. Our results demonstrate that only receptor-mediated endocytosis of gp96 molecules leads to MHC class I-restricted re-presentation of gp96-associated peptides and CTL activation; non-receptor-mediated, nonspecific endocytosis is not able to do so. Thus, we provide evidence on the mechanisms by which gp96 is participating in the cross-presentation of antigens from cellular origin.

Adenovirus E1B Proteins↗