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K Schmidt

Publications and source records attributed to K Schmidt.

At least 73 records · Page 4Linked to original sources
PubMed2001

[Application of a context-oriented model for the planning of psychotherapy].

Since clinical experience has shown that creating a therapeutic setting with borderline or psychotic patients is extremely difficult the Department of Psychoanalysis and Psychotherapy at Vienna University Hospital has developed a method of treatment designed to increase the possibilities to work with this group of patients. This procedure is conceptualised as "context oriented model exploration in psychotherapy planning" COMEPP. Initially the context is explored in which the psychotherapeutic model should be implemented which has so far failed for different reasons. Following this a setting is created in which the therapeutic team and the patient(s) can constructively and creatively reflect on alternative therapeutic models. A clinical case illustrates the problems and the basic structure of COMEPP in a schematic and condensed form.

Austria↗
PubMed2001

Non-linear changes of electrocortical activity after antenatal betamethasone treatment in fetal sheep.

We determined the effects of betamethasone on the fetal sheep electrocorticogram (ECoG) using linear (power spectral) and non-linear analysis. For non-linear analysis we used an algorithm based on the Wolf algorithm for the estimation of the leading Lyapunov exponent which calculates a prediction error based on the course of the time series in the phase space. A high prediction error stands for low predictibility or low regularity and vice versa. After 48 h of baseline recordings, vehicle (n = 6) or betamethasone (n = 7) at 10 microg h(-1) was infused over 48 h to the sheep fetus at 128 days gestational age (0.87 of gestation). ECoG spectral analysis revealed no difference in power spectrum between vehicle- and betamethasone-treated fetuses. The prediction error of the ECoG during REM sleep was higher than during non-REM or quiet sleep in both groups (P < 0.0001) revealing lower causality of brain activity during REM sleep. During REM sleep, prediction error significantly decreased 18-24 h after onset of betamethasone treatment (P < 0.05) and returned to baseline values within the following 24 h of continued betamethasone treatment. No ECoG changes were found during quiet sleep. Non-linear ECoG changes during metabolically active REM sleep accompanied the previously described decrease in cerebral blood flow. These results suggest that betamethasone in doses used in perinatal medicine acutely alters complex neuronal activity.

Algorithms↗
PubMed2001

Regulated apical secretion of zymogens in rat pancreas. Involvement of the glycosylphosphatidylinositol-anchored glycoprotein GP-2, the lectin ZG16p, and cholesterol-glycosphingolipid-enriched microdomains.

We examined the role of glycosphingolipid- and cholesterol-enriched microdomains, or rafts, in the sorting of digestive enzymes into zymogen granules destined for apical secretion and in granule formation. Isolated membranes of zymogen granules from pancreatic acinar cells showed an enrichment in cholesterol and sphingomyelin and formed detergent-insoluble glycolipid-enriched complexes. These complexes floated to the lighter fractions of sucrose density gradients and contained the glycosylphosphatidylinositol (GPI)-anchored glycoprotein GP-2, the lectin ZG16p, and sulfated matrix proteoglycans. Morphological and pulse-chase studies with isolated pancreatic lobules revealed that after inhibition of GPI-anchor biosynthesis by mannosamine or the fungal metabolite YW 3548, granule formation was impaired leading to an accumulation of newly synthesized proteins in the Golgi apparatus and the rough endoplasmic reticulum. Furthermore, the membrane attachment of matrix proteoglycans was diminished. After cholesterol depletion or inhibition of glycosphingolipid synthesis by fumonisin B1, the formation of zymogen granules as well as the formation of detergent-insoluble complexes was reduced. In addition, cholesterol depletion led to constitutive secretion of newly synthesized proteins, e.g. amylase, indicating that zymogens were missorted. Together, these data provide first evidence that in polarized acinar cells of the exocrine pancreas GPI-anchored proteins, e.g. GP-2, and cholesterol-sphingolipid-enriched microdomains are required for granule formation as well as for regulated secretion of zymogens and may function as sorting platforms for secretory proteins destined for apical delivery.

Animals↗
PubMed2001

Alternative splice variants of hTrp4 differentially interact with the C-terminal portion of the inositol 1,4,5-trisphosphate receptors.

The molecular basis of capacitative (or store-operated) Ca2+ entry is still subject to debate. The transient receptor potential proteins have been hypothesized to be structural components of store-operated Ca2+ channels and recent evidence suggests that Trp3 and its closely related homolog Trp6 are gated by the N-terminal region of the inositol 1,4,5-triphosphate receptors (InsP3R). In this study, we report the existence of two isoforms of the human Trp4 protein, referred to as alpha-hTrp4 and beta-hTrp4. The shorter variant beta-hTrp4 is generated through alternative splicing and lacks the C-terminal amino acids G785-S868. Using a yeast two-hybrid assay and glutathione-S-transferase-pulldown experiments, we found that the C-terminus of alpha-hTrp4, but not of beta-hTrp4, associates in vitro with the C-terminal domain of the InsP(3) receptors type 1, 2 and 3. Thus, we describe a novel interaction between Trp proteins and InsP3R and we provide evidence suggesting that the formation of hTrp4-InsP3R complexes may be regulated by alternative splicing.

Alternative Splicing↗
PubMed2001

Synthesis, conformational studies, and investigations on the estrogen receptor binding of [R/S-1-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]platinum(II) complexes.

The syntheses, conformational studies, and investigations on the estrogen receptor binding of [R/S-1-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]platinum(II) complexes (1-PtL2, 2L = leaving groups) are described. A Strecker synthesis using the 2,6-dichloro-4-methoxybenzaldehyde, NaCN, and NH4Cl afforded the cyanoamine 1b, which was subsequently reduced with LiAlH4 to give the R/S-1-(2,6-dichloro-4-methoxyphenyl)ethylenediamine 1a. Ether cleavage with BBr3 yielded R/S-1-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine 1 which was coordinated to platinum(II) by use of K2PtCl4 (1-PtCl2) and K2PtI4 (1-PtI2), respectively. Reaction of 1-PtI2 with Ag2SO4 and coordination of tartronic acid led to the [R/S-1-(2,6-dichloro-4- hydroxyphenyl)ethylenediamine][hydroxymalonato]platinum(II) complex (1-Pt(MalOH)). The spatial structure of 1 and its complexes was evaluated by spectroscopic and molecular modeling methods. In solution the complexes adopt a structure very similar to estradiol. However, the in vitro and in vivo tests for the compounds indicated neither affinity to the estrogen receptor nor estrogenic properties.

Cell Line↗
PubMed2001

The relationship of depression and stressors to immunological assays: a meta-analytic review.

This is a broad meta-analysis of the relations of both depression and stressors to immunological assays. The number of study samples (greater than 180) and measures (greater than 40) is much more extensive than any so far. Analyses are done by both fixed and random effects. By a fixed-effects analysis, both major depression and naturally occurring acute stressors are associated with (1) an overall leukocytosis, (2) mild reductions in absolute NK-cell counts and relative T-cell proportions, (3) marginal increases in CD4/CD8 ratios, and (4) moderate decreases in T- and NK-cell function. However, the degree of heterogeneity of the studies' results raises questions about their robustness. Therefore, we also did the first random effects analysis to estimate what is likely to appear in future studies. For depression, the analysis showed the immunological correlates included (1) an overall leukocytosis, manifesting as a relative neutrophilia and lymphoenia; (2) increased CD4/CD8 ratios; (3) increased circulating haptoglobin, PGE(2), and IL-6 levels; (4) reduced NK-cell cytotoxicity; and (5) reduced lymphocyte proliferative response to mitogen. For stressors, the random effects analysis showed that future studies are likely to find the following effects: (1) an overall leukocytosis, manifesting as an absolute lymphocytosis; (2) alterations in cytotoxic lymphocyte levels, CD4/CD8 ratios, and natural killer cell cytotoxicity with the direction of change depending on the chronicity of the stressor; (3) a relative reduction of T-cell levels; (3) increased EBV antibody titers; (4) reduced lymphocyte proliferative response and proportion of IL-2r bearing cells following mitogenic stimulation; and (5) increased leukocyte adhesiveness. The random-effects analysis revealed that for both major depression and naturally occurring stressors the following effects are shared: leukocytosis, increased CD4/CD8 ratios, reduced proliferative response to mitogen, and reduced NK cell cytotoxicity. The implications for these findings for disease susceptibility and the pathophysiology of these conditions is discussed.

Biomarkers↗
PubMed2001

Estimation of the number of "true" null hypotheses in multivariate analysis of neuroimaging data.

The repeated testing of a null univariate hypothesis in each of many sites (either regions of interest or voxels) is a common approach to the statistical analysis of brain functional images. Procedures, such as the Bonferroni, are available to maintain the Type I error of the set of tests at a specified level. An initial assumption of these methods is a "global null hypothesis," i.e., the statistics computed on each site are assumed to be generated by null distributions. This framework may be too conservative when a significant proportion of the sites is affected by the experimental manipulation. This report presents the development of a rigorous statistical procedure for use with a previously reported graphical method, the P plot, for estimation of the number of "true" null hypotheses in the set. This estimate can then be used to sharpen existing multiple comparison procedures. Performance of the P plot method in the multiple comparison problem is investigated in simulation studies and in the analysis of autoradiographic data.

Anesthesia, General↗
PubMed2001

Electrochemistry of pterin cofactors and inhibitors of nitric oxide synthase.

Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase (NOS), but its function is not fully understood. Specifically, it is unclear whether BH4 participates directly in electron transfer. We investigated the redox properties of BH4 and several other pteridines with cyclic voltammetry and Osteryoung square wave voltammetry. BH4 was oxidized at a potential of +0.27 V vs normal hydrogen electrode (NHE); the corresponding reductive signal after the reversal of the scan direction was very small. Instead, reduction occurred at a potential of -0.16 V vs NHE; there was no corresponding oxidative signal. These two transitions were interdependent, indicating that the reductive wave at -0.16 V represented the regeneration of BH4 from its product of oxidation at +0.27 V. Similar voltammograms were obtained with tetrahydroneopterin and 6,7-dimethyltetrahydropterin, both of which can substitute for BH4 in NOS catalysis. Completely different voltammograms were obtained with 7,8-dihydrobiopterin, sepiapterin, 2'-deoxysepiapterin, and autoxidized BH4. These 7,8-dihydropterins, which do not sustain NOS catalysis, were oxidized at much higher potentials (+0.82-1.04 V vs NHE), and appreciable reduction did not occur between +1.2 and -0.8 V, in line with the concept of a redox role for BH4 in NOS catalysis. However, the electrochemical properties of the potent pterin-site NOS inhibitor 4-amino-BH4 resembled those of BH4, whereas the active pterin cofactor 5-methyl-BH4 was not re-reduced after oxidation. We conclude that the 2-electron redox cycling of the pterin cofactor between BH4 and quinonoid dihydrobiopterin is not essential for NO synthesis. The data are consistent with 1-electron redox cycling between BH4 and the trihydrobiopterin radical BH3(*).

Antioxidants↗
PubMed2001

Cost-effective and uniform (13)C- and (15)N-labeling of the 24-kDa N-terminal domain of the Escherichia coli gyrase B by overexpression in the photoautotrophic cyanobacterium Anabaena sp. PCC 7120.

Structural studies of biomolecules using nuclear magnetic resonance (NMR) rely on the availability of samples enriched in (13)C and (15)N isotopes. While (13)C/(15)N-labeled proteins are generally obtained by overexpression in transformed Escherichia coli cells cultured in the presence of an expensive mixture of labeled precursors, those of the photoautotrophic cyanobacterium Anabaena sp. PCC 7120 can be uniformly labeled by growing them in medium containing Na(15)NO(3) and NaH(13)CO(3) as the sole nitrogen and carbon sources. We report here a novel vector-host system suitable for the efficient preparation of uniformly (13)C/(15)N-labeled proteins in Anabaena sp. PCC 7120. The 24-kDa N-terminal domain of the E. coli gyrase B subunit, used as a test protein, was cloned into the pRL25C shuttle vector under the control of the tac promoter. The transformed Anabaena cells were grown in the presence of the labeled mineral salts and culture conditions were optimized to obtain over 90% of (13)C and (15)N enrichment in the constitutively expressed 24-kDa polypeptide. The yield of purified 24-kDa protein after dual isotope labeling under anaerobic conditions was similar to that obtained with E. coli cells bearing a comparable expression vector and cultured in parallel in a commercially available labeling medium. Furthermore, as probed by NMR spectroscopy and mass spectrometry, the 24-kDa N-terminal domain expressed in Anabaena was identical to the E. coli sample, demonstrating that it was of sufficient quality for 3D-structure determination. Because the Anabaena system was far more advantageous taking into consideration the expense for the labels that were necessary, these results indicate that Anabaena sp. PCC 7120 is an economic alternative for the (13)C/(15)N-labeling of soluble recombinant proteins destined for structural studies.

Carbon Isotopes↗
PubMed2001

[Resection of colorectal liver metastases. What prognostic factors determine patient selection?].

AIM OF THE STUDY: Based on a consecutive series of patients undergoing liver resection for colorectal metastases, indicators of prognosis and selection criteria were evaluated. PATIENTS AND METHODS: From 1960 to 1998, a total of 654 patients underwent resection of colorectal liver metastases. In 516 patients (78.9%) this was an R0 resection for initial metastatic disease. These patients form the basis for the investigation. RESULTS: 30-day mortality in this group was 5.8%, while the total procedure-related mortality was 8.3%. Significant morbidity was observed in 16% of patients. Follow-up information until 1 January, 2000 was achieved in 99.5% of patients. Including operative mortality, the actuarial 5-, 10-, and 20-year survival is 38 +/- 5%, 27 +/- 6% und 24 +/- 24%, rising to 41 +/- 5%, 29 +/- 6% and 26 +/- 26% after excluding operative deaths. Tumor-free survival is 35 +/- 5% at 5 years. In the multivariate analysis the following factors are associated with decreased crude survival: extrahepatic tumor (P < 0.0001), intraoperative hypotension (P = 0.0001), non-anatomical procedures (P = 0.0002), a metastasis diameter > or = 5 cm (P = 0.0002), unfavourable grading of the primary tumor (P = 0.0003), satellite metastases (P = 0.0069), mesenteric lymph node involvement (P = 0.0260), use of FFP (P = 0.0307) and synchronous diagnosis of metastases (P = 0.1240). With respect to disease-free survival metastasis diameter is first, followed by extrahepatic disease (P < 0.0001 each). Satellite metastases are removed, while the primary tumor site becomes important with inferior results for rectal cancer (P = 0.0188). The other factors remain stable and in the same order. The number of independent tumor nodules as well as the width of resection margin fail to be significant in both univariate and multivariate analysis. CONCLUSION: These results underline the paramount importance of an R0 resection, but diminish the relevance of most commonly used "contraindications". For the actual decision on liver resection, beside the possibility of achieving an R0 situation, safety aspects regarding comorbidity and acceptable extent of parenchyma loss represent the prime limitation.

Adult↗
PubMed2001

[Prosthesis implantation of the rheumatoid arthritis shoulder].

Omarthritis occurs frequently during the early course of rheumatoid arthritis. Many rheumatoid patients ignore omarthritis because of the good compensation mechanism of the shoulder. Sonography and tomography enable early diagnosis of omarthritis before deterioration is radiologically visible. Arthroplasty gives better results when the musculotendinous rotator cuff is still intact. Therefore, arthroplasty should be performed before severe damage develops. Early indication for cup arthroplasty of the humeral head is justified because of better options in revision surgery. Glenoid components show a high incidence of radiolucency and loosening in rheumatoid patients. Cemented hemiarthroplasties show the lowest rate of loosening.

Aged↗
PubMed2001

[Outcome measurement in musculoskeletal diseases: recommendation for a core set of scales for use in rehabilitation].

By application of a standardized core set of outcome measurement instruments, comparison between studies as well as meta-analyses in rehabilitation research can be facilitated. The German Society for Rheumatology has commissioned its working group on rehabilitation with the development of a proposal for such a core set of outcome measurement instruments. In a first step, dimensions for outcome measurement in rehabilitation were defined by a group of experts which represented rehabilitation hospitals, acute care hospitals, and research groups specialized in outcome measurement. The Delphi method was used in a multiple step consensus process. In a second step, instruments and procedures to operationalize the relevant dimensions were chosen. Reliability, validity, sensitivity to change, and practicability were used as criteria for selecting measurement instruments. The main intention of the proposed core set of outcome measurement instruments is to facilitate the processes of planning and carrying out rehabilitation research studies. Furthermore, the proposed instruments can be used for clinical documentation systems as well as for internal or external quality assurance programs.

Arthritis, Rheumatoid↗
PubMed2001

A novel proliferation-associated variant of CFR-1 defined by a human monoclonal antibody.

The germline coded human monoclonal IgM antibody 103/51 was isolated from a gastric carcinoma patient. This antibody binds to a 130-kd membrane molecule and has a mitotic effect on tumor cells in vitro. To characterize the target, we sequenced the protein and showed that the antibody binds to the cysteine-rich fibroblast growth factor receptor (CFR)-1, which is highly homologous to MG-160 and the E-selectin-ligand (ESL)-1. The epitope was determined by glycosidase-digestion experiments to be an N-linked carbohydrate side chain. Immunohistochemistry was used to investigate the tissue distribution of CFR-1. Different healthy tissues were tested and only the collecting tubes of the kidney, the Golgi apparatus, and the glomerular and fascicular zones of the adrenal gland stained positive. However, on malignant tissue the receptor is overexpressed in nearly all tested stomach cancers (12 of 15) and other tested carcinomas (13 of 15). Most interestingly, the receptor is also present in Helicobacter pylori gastritis and gastric dysplasia, but absent on uninflamed stomach mucosa. This restricted tissue pattern indicates that antibody 103/51 reacts with a membrane-bound variant of CFR-1, which is mainly expressed on transformed cells and precursor lesions and is essential for proliferation processes. The possible activity of antibody 103/51 as an activating ligand in these proliferative changes of gastric epithelial mucosa is discussed.

Adenocarcinoma↗
PubMed2001

Rat inositol 1,4,5-trisphosphate receptor isoform 2 interacts with itself in its C-terminal portion and upstream of the first transmembrane domain.

In response to stimulation at the plasma membrane, hepatocellular Ca(2+) signals are fast and precise and lead to rapid local changes in cytoplasmic free Ca(2+) concentration. These changes result from the opening of the inositol 1,4,5-trisphosphate receptor (InsP(3)R), which is a four-subunit intracellular InsP(3)-gated channel that releases Ca(2+) from the stores. To investigate the molecular mechanism underlying interactions between the InsP(3)R subunits, we cloned the predominant hepatocellular isoform, InsP(3)R isoform 2 (InsP(3)R2), and screened for interactions using the yeast two-hybrid assay. We found that the C-terminal domain of rat InsP(3)R2 interacts with itself, and that the cytoplasmic part preceding the first transmembrane domain, a region near a Ca(2+)-binding site, also interacts with itself. These interactions were confirmed by pull-down experiments. The C-terminal domain of InsP(3)R2 is also able to interact with the C-termini of rat InsP(3)R1 and InsP(3)R3. These results advance our understanding of the molecular mechanisms that underlie the oligomerization and interactions of the InsP(3)R subunits during the opening/closing of the Ca(2+) channel.

Amino Acid Sequence↗
PubMed2001

Minimal renal dysfunction in inflammatory bowel disease is related to disease activity but not to 5-ASA use.

BACKGROUND: Conflicting data exist about proteinuria in inflammatory bowel diseases. It is still unclear whether the occurrence of proteinuria in inflammatory bowel disease patients is an extra-intestinal manifestation of disease or the result of adverse effects to medication, especially to aminosalicylates (ASA). METHODS: A total of 95 patients (51 with Crohn's disease and 44 with ulcerative colitis) were enrolled in the study. Disease activity was assessed by Crohn's Disease Activity Index (CDAI) or the Truelove index, respectively. Urine was collected over 24 h and protein excretion of specific marker proteins for tubular (alpha 1-microglobulin-alpha 1-MG) and glomerular (albumin-Alb, Immunoglobulin G-IgG) dysfunction was measured using a highly sensitive immunoluminometric assay. RESULTS: Out of 51 Crohn's disease patients, 20 showed elevated urinary alpha 1-MG. The amount of alpha 1-MGuria was strongly correlated to the CDAI (r=0.6, P < 0.001). Only four Crohn's disease patients showed slightly elevated values for glomerular proteins in urine. Similar results were obtained for ulcerative colitis: whereas only two ulcerative colitis patients showed albuminuria, tubular proteinuria was detected in 28 out of 44 ulcerative colitis patients. Proteinuria was strongly dependent on disease activity (P < 0.01) but was not related to ASA treatment. CONCLUSIONS: Proteinuria of tubular marker proteins occurs in the majority of inflammatory bowel disease patients and is related to disease activity rather than to ASA treatment. Tubular proteinuria seems to reflect a renal extra-intestinal manifestation of inflammatory bowel disease and may serve as a new relevant marker of disease activity.

Adolescent↗
PubMed2001

Detection of extracellular bound proteinase in EPS-producing lactic acid bacteria cultures on skim milk agar.

AIMS: Skim milk agar was developed to investigate extracellular cell-bound proteinase in yogurt cultures, Streptococcus thermophilus and Lactobacillus bulgaricus. METHODS AND RESULTS: The Lact. bulgaricus cultures produced more extracellular cell-bound proteinase than did Strep. thermophilus cultures. Strong positive correlations between the size of the exopolysaccharide (EPS) layer and extracellular cell-bound proteinase were found for both Streptococcus and Lactobacillus cultures. CONCLUSION: Strong positive linear relationships existed between the EPS size and colony size and the diameter of clear zone and colony size for Streptococcus cultures, whereas weak positive linear relationships were observed for Lactobacillus cultures. SIGNIFICANCE AND IMPACT OF THE STUDY: These data are useful to validate the relationship between extracellular proteinase and the EPS size of LAB. Also, a convenient medium to detect the presence of extracellular cell-bound proteinase of LAB is valuable for dairy industries.

Animals↗
PubMed2001

[Effects of shaft length of finger joint prostheses on tension distribution in the bone].

In order to investigate the influence of stem length in finger joint prostheses on stress in the surrounding bone area, finite element (FEM) calculations of finger bones before and after prosthetic replacement of metacarpophalangeal joints with cementless implants of different stem length were performed. CT scans of the metacarpal bone and proximal phalanx before and after implantation of a prototype of a noncemented semiconstrained implant for the MP joint, which has been developed to replace metacarpophalangeal joints destroyed by rheumatoid arthritis, were analysed. The FEM calculations showed comparatively decreased differences of the von-Mises stress after implantation of intramedullary stems reaching the middle of the diaphysis. At the metaphysis of the metacarpal head we found an increase of the von-Mises stress of 1.3 MPa (Mega Pascal = 10(6) Pa), an increase of 18.9 MPa around the shortest prosthesis and a decrease of 21.4 MPa around the prosthesis with the longest stem.

Adult↗