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R Schmitz

Publications and source records attributed to R Schmitz.

At least 19 recordsLinked to original sources
PubMed1997

Identification of phosphopeptide ligands for the Src-homology 2 (SH2) domain of Grb2 by phage display.

We report here on the identification of phosphopetide ligands which interact with the Src-homology 2 (SH2) domain of the adapter protein Grb2 by screening a random peptide library established on phage. Phage were phosphorylated in vitro at an invariant tyrosine residue by a mixture of phosphotyrosine kinases c-Src, Blk and Syk. Selection of binding motifs was carried out by interaction of the library with the recombinant SH2 domain of Grb2 expressed as a glutathione S-transferase (GST) fusion protein. Several subsequent cycles of selection led to the enrichment of phage which bound to the GST-Grb2 SH2 domain only when previously phosphorylated. Sequence analysis revealed that all of the selected phage displayed peptides with the consensus motif Y*M/ENW (Y* denotes phosphotyrosine). One of these peptides, bearing the Y*ENW motif, bound the Grb2 SH2 domain with a threefold higher affinity than the peptide motif Y*VNV derived from the natural ligand Shc. Thus, phage display can be employed to rapidly identify high affinity ligands to SH2 domains.

Adaptor Proteins, Signal Transducing↗
PubMed1997

["Tension-free technique" in open inguinal hernia repair. A prospective, randomized study of postoperative pain perception ("tension-free reconstruction" vs. Shouldice technique)].

A prospective randomized study was performed on 64 patients suffering from primary inguinal hernia. Two groups were formed, each consisting of 32 patients. The patients either underwent tension-free surgical treatment or Shouldice herniorraphy. The aim of the study was to determine if the tension-free operative technique on inguinal hernia patients reduces postoperative pain intensity by 2 days in comparison to the patients receiving Shouldice repair treatment. By using the VAS was shown that at no time was there any significant difference in the pain sensation levels between the two groups. The amount of pain tablets consumed among the patients was similar in each group. The number of complications in both groups was also comparable. During the postoperative follow-up of 6 days six patients in the tension-free surgical group and four patients in the Shouldice group developed uncomplicated hematomas on the 4th day, which were traced to the heparin medication. One patient from the Shouldice group suffered from temporary swelling of the scrotum. The advantage of open tension-free repair using extraperitoneally placed polypropylene mesh is that the technique is simple, size-adapted, and can be carried out easily and at any time under local anesthesia. With regard to the lower recurrence rate of hernia as published in the American literature, this can only be verified by randomized studies.

Adolescent↗
PubMed1997

Randomized clinical trial of conventional cholecystectomy versus minicholecystectomy.

BACKGROUND: The main argument for laparoscopic cholecystectomy in preference to open cholecystectomy appears to be based on less traumatic incisions inflicted on the abdominal wall. To investigate the effects of different incision lengths on patients following elective open cholecystectomy, a randomized clinical study was conducted. METHODS: In this study 130 patients were randomly assigned to undergo either open cholecystectomy through a transverse subcostal incision of mean length 5.8 cm, so called minicholecystectomy (65 patients), or to undergo conventional cholecystectomy through a paracostal incision of mean length 13.1 cm (65 patients). The perception of pain after operation was measured by a visual analogue scale. To register late complications the mean(s.d.) hospitalization period after operation was extended to 11.5(1.2) days in the minicholecystectomy group and 15.4(2.5) days in the conventional cholecystectomy group. RESULTS: The perceived pain and analgesic requirements were found to be similar in both groups. Twelve of 65 patients in the minicholecystectomy group and four of 65 in the conventional cholecystectomy group developed wound haematoma. CONCLUSION: On the basis of this prospective randomized study, the hypothesis that a smaller incision length on the abdominal wall could lower the level of perceived pain, and therefore decrease the postoperative analgesic intake after minicholecystectomy, could not be confirmed.

Adult↗
PubMed1997

[Extraperitoneal, "tension free" inguinal hernia repair with local anesthesia--a contribution to effectiveness and economy].

In this present randomized controlled study, two groups, each consisting of 45 patients, underwent tension-free inguinal hernia repair under general versus local anesthesia. Patients in the local anesthesia group described their pain during mobilisation by using the VAS and were found to have a significant pain level decrease from the first to the fifth postoperative day. In conclusion, it could be shown that tension-free hernia repair under local anesthesia is superior to tension-free hernia repair during general anesthesia concerning perception of pain and pain management.

Adolescent↗
PubMed1996

Catalytic specificity of phosphotyrosine kinases Blk, Lyn, c-Src and Syk as assessed by phage display.

Protein tyrosine kinases (PTKs) are implicated in cell proliferation, differentiation, and receptor-mediated signalling events. Recruitment of intracellular PTKs into the signalling complex, often localized at the inner surface of the cell membrane, involves SH2 and SH3 domains attached to the catalytic kinase domain. While the interaction of SH2 and SH3 domains with their target sequences is well documented in a number of cases, the contribution of the catalytic domain itself in conferring specificity to a given signal cascade is not fully understood. We addressed this question and employed the phage display technique to assess the substrate requirements for the highly related Src-like PTKs c-Src, Blk, Lyn and the distantly related Syk. A diverse peptide library on phage was established, and after multiple rounds of phosphorylation and selection of phage displaying phosphotyrosine-containing peptides, canonical substrate sequences for each of the PTKs were enriched. The PTKs Blk and Lyn implicated in B cell signalling were found to prefer peptide substrates of the structure I/L-Y-D/E-X-L which resemble critical features of the ITAM motifs found in, e.g. the intracellular components Ig-alpha and Ig-beta of the beta cell receptor. All Src-like PTKs had a requirement for isoleucine or leucine in the position -1 with respect to the phosphorylated tyrosine residue in position 0. While Blk and Lyn had a strong preference for a negatively charged amino acid in position +1, c-Src preferred tryptophan or glycine in this position. Syk, not belonging to the Src-like PTK family, revealed a distinct substrate requirement for aspartic acid in position -1 and glutamic acid in position +1. In general, all PTKs we have tested had a strong preference for a particular amino acid in the positions -1 and +1 adjacent to the tyrosine residue.

Amino Acid Sequence↗
PubMed1995

Estimating increases in outpatient dialysis costs resulting from scientific and technological advancement.

The Medicare program's base payment rate for outpatient dialysis services has never been adjusted for the effects of inflation, productivity changes, or scientific and technological advancement on the costs of treating patients with end-stage renal disease. In recognition of this, Congress asked the Prospective Payment Assessment Commission to annually recommend an adjustment to Medicare's base payment rate to dialysis facilities. One component of this adjustment addresses the cost-increasing effects of technological change--the scientific and technological advances (S&TA) component. The S&TA component is intended to encourage dialysis facilities to adopt technologies that, when applied appropriately, enhance the quality of patient care, even though they may also increase costs. We found the appropriate increase to the composite payment rate for Medicare outpatient dialysis services in fiscal year 1995 to vary from 0.18% to 2.18%. These estimates depend on whether one accounts for the lack of previous adjustments to the composite rate. Mathematically, the S&TA adjustment also depends on whether one considers the likelihood of missing some dialysis sessions because of illness or hospitalization. The S&TA estimates also allow for differences in the incremental costs of technological change that are based on the varying advice of experts in the dialysis industry. The major contributors to the cost of technological change in dialysis services are the use of twin-bag disconnect peritoneal dialysis systems, automated peritoneal dialysis cyclers, and the new generation of hemodialysis machines currently on the market. Factors beyond the control of dialysis facility personnel that influence the cost of patient care should be considered when payment rates are set, and those rates should be updated as market conditions change. The S&TA adjustment is one example of how the composite rate payment system for outpatient dialysis services can be modified to provide appropriate incentives for producing high-quality care efficiently.

Health Care Costs↗
PubMed1995

Generation of rabbit monoclonal antibody fragments from a combinatorial phage display library and their production in the yeast Pichia pastoris.

We have applied the combinatorial immunoglobulin library and phage display technologies to generate monoclonal rabbit single-chain Fv (scFv) antibody fragments specific for recombinant human leukemia inhibitory factor (rhLIF). The B cell immunoglobulin repertoire of an immunized rabbit was immortalized by the combinatorial cloning of the rearranged variable domains of light (VL) and heavy (VH) chains. Affinity selection of the library displaying the rabbit antibody domains on the phage surface resulted in the isolation of phage encoding scFv antibodies which specifically bind to the antigen. We utilized the methylotrophic yeast Pichia pastoris for high level secretion of soluble and functional scFv antibody fragment. More than 100 mg/L of pure and functional rabbit anti-rhLIF scFv antibody was obtained directly from the P. pastoris culture supernatant by one-step affinity chromatography.

Amino Acid Sequence↗
PubMed1994

Human cyclophilin C: primary structure, tissue distribution, and determination of binding specificity for cyclosporins.

A complementary DNA (cDNA) for human cyclophilin C (Cyp-C) was isolated from a human kidney cDNA library. Northern blot experiments with several human tissues and cell lines revealed that Cyp-C is less abundant than Cyp-A. The amount of Cyp-C mRNA was 10-fold lower than that of Cyp-A in kidney. Expression of human Cyp-C in the kidney is not significantly elevated compared to pancreas, skeletal muscle, heart, lung, and liver. This argues against a previously postulated specific role for Cyp-C in the nephrotoxic effects of CsA in humans, based on the studies of its relative abundance in murine kidney. It is present in extremely low concentrations in brain and in the Jurkat T cell line. The binding of recombinant human Cyp-A, -B, and -C to cyclosporin A (CsA) was studied by immunochemical methods. The relative affinity of Cyp-C for CsA is lower by a factor of 2 than that of Cyp-A, which itself is 10-fold lower than that of Cyp-B. Cross-reactivity studies with a series of Cs derivatives showed that Cyp-C binds CsA with a fine specificity similar to that of Cyp-A and Cyp-B. Cs amino acid residues 1, 2, 10, and 11 seemed essential for the interaction with all three Cyp subtypes. However, Cyp-C tolerates a greater variety of structures on Cs at position 2 than Cyp-A does, suggesting that this residue of CsA might not be in tight contact with Cyp-C. This was confirmed by modeling of human Cyp-C on the structure of the complex formed by Cyp-A and CsA. The knowledge of the fine specificity of human Cyps for CsA and of their expression levels may provide better insights into how CsA acts on its different target proteins in vivo.

Amino Acid Isomerases↗
PubMed1994

[Quality of life after prograde jejunum interposition with and without pouch. A prospective study of stomach cancer patients on the reservoir as a reconstruction principle after total gastrectomy].

Out of 74 consecutive patients with gastric carcinoma only 39 patients fulfilled the inclusion criteria for this randomized study. These patients were divided into two groups intraoperatively, 21 were reconstructed with and 18 without performing a stapled interposed jejunal pouch. Quality of life was evaluated using Spitzer's QL index and Cuschieri's assessment for 6 months. Spitzer's QL index showed--as expected--no differences concerning the specific reconstruction in gastrointestinal complaints, whereas Cuschieri's assessment revealed an advantage in the pouch group. Cuschieri's assessment needs to be validated by larger comparable groups to prove its suitability for the determination of specific gastrointestinal complaints concerning the type of reconstruction in gastric cancer patients.

Adult↗
PubMed1992

[Benefits and risks of surgical therapy of acute lateral fibular ligament rupture of the upper ankle joint. Results of a retrospective study].

In 60 patients with an intra-operatively confirmed first-time tear of the lateral ligaments of the ankle joint an examination carried out after a period ranging from 11.6 and 35 months post-op. showed that ligament suturing coupled with immobilisation for 6 weeks was not associated with any major or persistent impairment. The important advantage of the procedure was the possibility of accurately determining the extent of the injury, together with the chance of providing suitable and immediate correction. In 91% of the patient group, a comparison of sides revealed equal or greater stability of the surgically treated ankle joint. Even when occasional temporary, varyingly pronounced, sensory disorders are taken into account, in comparison with the possibilities of conservative therapy, we consider that these results confirm a tear of the lateral ligaments of the ankle to be a justifiable indication for surgery.

Adolescent↗
PubMed1990

[Primary and metastatic liver tumors--evaluation of tumor regression and response with regional cytostatic drug therapy by sonography and fine needle puncture histology].

Primary and metastatic hepatic tumours--evaluation of tumour regression or response under regional cytostasis with sonography and fine needle puncture histology. The results obtained through the use of regional liver perfusion with a 5-FU-BCNU application on non-resectable hepatic metastases of colorectal tumours following primary curative removal of the primary tumour and primary hepatocellular carcinomas display comparable results to those specified in the literature after the use of 5-FUDR. The effectivity of the cytostasis regime is checked using histological criteria. The ultrasonically guided fine needle puncture can prove the success of the cytostasis regime on the basis of cytomorphologic criteria more reliably than has been the case up to now. Patients displaying histological signs of tumour regression have a significantly longer survival time than those displaying no signs of regression (12 +/- 9.2 vs 4.5 +/- 2.2 months; p less than 0.05).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Steady-state intravenous pharmacokinetics of pirenzepine in patients with hepatic insufficiency and combined renal- and hepatic insufficiency.

The steady-state intravenous pharmacokinetics of pirenzepine has been investigated in patients with chronic liver disease and others with combined chronic liver disease and renal insufficiency. The plasma clearance (CL) of Pirenzepine, steady-state plasma concentration Cmin(ss) and dominant half life t1/2 gamma were not significantly altered in the chronic liver disease group. In patients with renal and hepatic insufficiency, CL was reduced, t1/2 gamma was prolonged from 11.1 to 19.4 h and Cmin(ss) was elevated from 36 ng/ml to 66 ng/ml compared to healthy controls. Plasma concentrations remained in the therapeutic range and the dosage regimen was well tolerated. Adjustment of the dose of pirenzepine need be considered only in cases of severe impairment of both renal and hepatic elimination.

Adult↗