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Biomedical subjects

U Günther

Publications and source records attributed to U Günther.

At least 19 recordsLinked to original sources

NMR in the SPINE Structural Proteomics project.

This paper describes the developments, role and contributions of the NMR spectroscopy groups in the Structural Proteomics In Europe (SPINE) consortium. Focusing on the development of high-throughput (HTP) pipelines for NMR structure determinations of proteins, all aspects from sample preparation, data acquisition, data processing, data analysis to structure determination have been improved with respect to sensitivity, automation, speed, robustness and validation. Specific highlights are protonless (13)C-direct detection methods and inferential structure determinations (ISD). In addition to technological improvements, these methods have been applied to deliver over 60 NMR structures of proteins, among which are five that failed to crystallize. The inclusion of NMR spectroscopy in structural proteomics pipelines improves the success rate for protein structure determinations.

Algorithms↗

Serum ferritin iron in iron overload and liver damage: correlation to body iron stores and diagnostic relevance.

The iron content of serum ferritin has been determined in groups of patients with normal or increased iron stores by using a technique of ferritin immunoprecipitation followed by iron quantitation with atomic absorption spectroscopy. The results were correlated to individual liver iron concentrations, measured non-invasively by superconducting quantum interference device (SQUID) biomagnetometry. A close correlation between serum concentrations of ferritin protein and ferritin iron was found (r = 0.92) in all groups of patients. However, the correlation between ferritin iron concentration and individual liver iron concentration was poor in patients with hemochromatosis (r = 0.63) and patients with beta-thalassemia major (r = 0.57). The degree of ferritin iron saturation was about 5% in iron-loaded patients, which contrasts with results in two recent studies but confirms older observations. In patients with liver cell damage, the ferritin iron saturation in serum was significantly higher than that found in groups with iron overload disease, probably indicating the release of intracellular iron-rich ferritin into the blood. The monitoring of patients undergoing bone marrow transplantation indicated that the release of iron-rich and iron-poor ferritin occurred during phases of hepatocellular damage and inflammation, respectively. We find the benefits of serum ferritin iron measurement to be marginal in patients with iron overload disease.

Adult↗

Fibrogenesis and fibrolysis in collagenous colitis. Patterns of procollagen types I and IV, matrix-metalloproteinase-1 and -13, and TIMP-1 gene expression.

Collagenous colitis is characterized by the deposition of a superficial subepithelial collagenous layer, the pathogenesis of which is unknown. Because the excess matrix deposition is potentially reversible, a labile imbalance between fibrogenesis and fibrolysis may be suspected. Expression of procollagen alpha1(I) and alpha1(IV), matrix-metalloproteinase (MMP)-1 and -13, and tissue inhibitor of metalloproteinase (TIMP)-1 genes was semiquantitated by in situ hybridization on serial biopsies of 12 patients with collagenous colitis and compared to controls. Collagen types I, III, IV, and VI, tenascin, undulin/collagen XIV, and alpha-actin were localized by immunohistology. The superficial collagen layer stained strongly for collagen types I, III, and VI, and particularly for tenascin, but not for undulin. Elevated procollagen alpha1(I), procollagen alpha1(IV), and TIMP-1 transcript levels were found in alpha-actin-positive cells with linear distribution underneath the superficial collagenous layer, whereas MMP-1 RNA expression was variable and restricted to cell clusters. MMP-13 expression was undetectable. The patterns of procollagen alpha1(I)- and alpha1(IV)-specific labeling, combined with an intense tenascin- but absent undulin-specific staining, indicate deposition of an immature interstitial matrix that may be susceptible to degradation. The restricted MMP-1 RNA expression, counteracted by increased TIMP-1 expression, suggests locally impaired fibrolysis as a relevant factor in the pathogenesis of collagenous colitis.

Adult↗

Suppression of T cell-mediated injury in human gut by interleukin 10: role of matrix metalloproteinases.

BACKGROUND & AIMS: Activation of lamina propria T cells with pokeweed mitogen in human fetal gut explant cultures results in severe mucosal injury. In the same system, Staphylococcus aureus enterotoxin B produces villus atrophy and crypt cell hyperplasia. The aim of this study was to examine the ability of interleukin (IL)-10 to modify these changes. METHODS: Mucosal pathology and lamina propria glycosaminoglycans were assessed histologically, and CD3(+), CD25(+) and alpha-actin smooth muscle-positive cells were determined by immunohistochemistry. Reverse plaque assays and quantitative reverse-transcriptase polymerase chain reaction were used to analyze the cytokine response. Matrix metalloproteinase production was analyzed by Western blotting, in situ hybridization, and zymography. RESULTS: Both experimental enteropathies produced mucosal damage, although injury was greater after pokeweed mitogen activation than S. aureus enterotoxin B. In both cases, the increase in cytokine-secreting cells and transcripts observed after T-cell activation was inhibited by IL-10. IL-10 also inhibited the increase in collagenase and stromelysin-1 in the explant culture supernatants and the loss of glycosaminoglycans. IL-10 decreased metalloproteinase production in control explants and increased matrix. In mesenchymal cells, IL-10 had a minor effect on metalloproteinase production. CONCLUSIONS: IL-10 down-regulates mucosal T-cell activation, metalloproteinase production, and loss of extracellular matrix and prevents mucosal damage in the gut.

Antigens, CD↗

Influence of different types of recovery positions on perfusion indices of the forearm.

BACKGROUND: Basic life support guidelines of the European Resuscitation Council (ERC) suggest a modified type of recovery position compared to that recommended by the American Heart Association (AHA). However, anecdotal reports and the results of a small study by Fulstow and Smith (Resuscitation 1993; 26: 89-91) gave evidence that the new ERC position may cause an impairment of perfusion of the lower forearm. The aim of our study was to evaluate the effects of different recovery positions on arterial perfusion and venous drainage of the forearm. METHODS: We placed 20 young healthy volunteers randomly in either ERC or AHA position for 15 min first, and in the other position thereafter. Before and between volunteers were positioned supine. In a second series 10 volunteers were positioned according to the same protocol in semiprone positions as described by Morrison, Mirkhur and Craig (MMC), and Rautek's position, respectively. Forearm perfusion indices of the dependent arm were continuously assessed by photoplethysmographic pulsatility change, photoplethysmographic volume change, invasive peripheral venous pressure and non-invasive blood pressure amplitude. Subjective discomfort was assessed non-qualitatively. RESULTS: All indices of arterial perfusion demonstrated an impairment of arterial inflow in ERC, MMC and Rautek's position as well as venous congestion in these three positions. On the contrary, AHA position was associated with no significant changes of arterial flow and only moderate, insignificant signs of venous congestion. CONCLUSION: The results of this study suggest that AHA position causes less circulatory disturbances than the ERC, MMC and Rautek's positions.

Adult↗

Benzodiazepine-insensitive mice generated by targeted disruption of the gamma 2 subunit gene of gamma-aminobutyric acid type A receptors.

Vigilance, anxiety, epileptic activity, and muscle tone can be modulated by drugs acting at the benzodiazepine (BZ) site of gamma-aminobutyric acid type A (GABAA) receptors. In vivo, BZ sites are potential targets for endogenous ligands regulating the corresponding central nervous system states. To assess the physiological relevance of BZ sites, mice were generated containing GABAA receptors devoid of BZ sites. Following targeted disruption of the gamma 2 subunit gene, 94% of the BZ sites were absent in brain of neonatal mice, while the number of GABA sites was only slightly reduced. Except for the gamma 2 subunit, the level of expression and the regional and cellular distribution of the major GABAA receptor subunits were unaltered. The single channel main conductance level and the Hill coefficient were reduced to values consistent with recombinant GABAA receptors composed of alpha and beta subunits. The GABA response was potentiated by pentobarbital but not by flunitrazepam. Diazepam was inactive behaviorally. Thus, the gamma 2 subunit is dispensable for the assembly of functional GABAA receptors but is required for normal channel conductance and the formation of BZ sites in vivo. BZ sites are not essential for embryonic development, as suggested by the normal body weight and histology of newborn mice. Postnatally, however, the reduced GABAA receptor function is associated with retarded growth, sensorimotor dysfunction, and drastically reduced life-span. The lack of postnatal GABAA receptor regulation by endogenous ligands of BZ sites might contribute to this phenotype.

Animals↗

13C NMR investigation of synovial fluids.

13C NMR spectra of synovial fluids from 20 patients suffering from rheumatic diseases have been recorded. Structural changes in hyaluronic acid, the main carrier of the viscoelastic properties of synovial fluid, could be observed in the NMR spectra of the native biological fluid. By comparing these spectra with those of purified hyaluronic acid, a rough estimation of the degree of depolymerization of synovial hyaluronic acid was possible. The patients with rheumatoid arthritis appeared to have a lower degree of polymerization compared to patients with osteoarthrosis. Thus, 13C NMR spectroscopy provides useful information about biophysical properties of synovial fluid.

Arthritis, Rheumatoid↗

19F nuclear magnetic resonance spectroscopy of neuroleptics: the first in vivo pharmacokinetics of trifluoperazine in the rat brain and the first in vivo spectrum of fluphenazine in the human brain.

In vivo 19F nuclear magnetic resonance (19F-NMR) spectroscopy measurements of trifluorinated neuroleptics (fluphenazine--FL and trifluoperazine--TFP) were made in rat brain as well as in human brain. Animal studies were performed at 4.7 Tesla. Using rats that have been treated with FL over a period of 3 weeks, a NMR signal could be detected within 8-15 min. Following a single intravenous injection of TFP, brain levels could be monitored with a time resolution of 30 min. The first 19F-NMR examination of a patient was made at 3.0 Tesla 1 day after injection of FL decanoate (37.5 mg) in the course of which a signal could be detected within 30 min. It is expected that 19F-NMR will become an important tool in psychopharmacological research.

Adult↗

[The incidence of fatal lung emboli with special reference to the underlying disease and the effect of weather].

The frequency of the fatal pulmonary embolism in the autopsy material of Rostock University undergoes greater variations. After an increase of the incidence in connection with hyperalimentation and increase of age to the twofold to threefold between 1922 and 1974 as possible sequel of a prophylaxis of thrombosis a decrease of maximally 12.4 to 8.2% is to be established. The average age is 67.8 years, females are more affected to the relation of 1:1.6. Clinically the diagnosis of causes of death was exactly made in 25.9%. In the relation of causes dominate basic diseases of the cardiovascular and respiratory system with disturbances of the haemodynamics, malignant tumours without significant preference of certain organ carcinomas and infectious-toxic complications. A conspicuous accumulation concerned the chronic respiratory syndrome, often a polypathia existed. In the region of the coast of the Baltic Sea pulmonary embolisms appeared statistically significantly more frequently in fine weather phases and at beginning fine weather, respectively, with indifferent or tendencially rising global radiation on the day of the event and particularly in winter season. An influence of passages of weather fronts could not be established.

Aged↗

[Meteoropathologic effects on the development of fatal lung embolism].

The metoropathological analysis of 958 fatal lung embolisms in the territory of Rostock does not make notice of special relation of the summer, preparing the material acc. to the both main seasons. In winter the fine weather phases 1-4 and normal radiation conditions result in a significant increase of the rate of mortality. A special endangering seams to occur after a period of dark weather at the transition to a period of light weather (weather phase 1).

Cause of Death↗

[Serum carotene and serum retinol in psoriasis].

The serum carotene and retinol levels were determined in 25 male psoriatic patients and 25 healthy male controls. No difference was observed in carotene level, however, retinol level was found lower in psoriatic patients as compared to controls.

Adult↗

[Sulfides in acne].

Fifty-three patients suffering from acne vulgaris or acne conglobata have been treated with natural sulphides over a period of 4 weeks. All cases showed improvement; normalization of the skin could be achieved in 36 patients (67.9%).

Acne Vulgaris↗

[Psoriasis vulgaris--sulfur brine therapy in 140 patients].

140 patients suffering from generalized chronic psoriasis were treated with the help of the natural sulphur resources of St. Peter-Ording over a period of 4 to 6 weeks. In 135 of these cases (96.4%), the skin became well improved. In 4 patients (2.9%) the skin lesions remained unchanged, while in only one case (0.7%) the lesions worsened.

Adolescent↗

Schizophrenic patients' attitudes toward their former illness.

This study deals with the question what schizophrenic patients think about their psychosis after remission. Literature is reviewed and the results of a standard study of 40 remitted patients are presented. Integrating ways of assimilation are separated from isolating ones. The way of assimilation is rather independent of the duration of illness, hospitalization, treatment, and their particular social situation. The method of psychotherapeutic treatment to be applied in a certain case has to take the individual way of assimilation into account. Possibilities of refined indication will have to be considered.

Adaptation, Psychological↗

Controlled clinical studies with an antidote against the urotoxicity of oxazaphosphorines: preliminary results.

A randomized study in 20 patients with cancer was carried out to test the clinical efficacy of sodium-2-mercaptoethane sulfonate (ASTA D-7093; mesnum) as an agent to prevent urotoxic side effects (in particular, hemorrhagic cystitis) during cytostatic therapy with the oxazaphosphorines cyclophosphamide and ifosfamide. Eleven patients received mesnum iv and nine patients received a standard prophylaxis. The frequency of microhematuria was significantly lower in the patients receiving mesnum. A slight microhematuria was observed in one patient. With the standard prophylaxis, all nine patients receiving single-agent therapy with ifosfamide or cyclophosphamide had hematuria and three of these had macrohematuria. According to the available results, a daily mesnum dose of 60% (wt/wt) of the ifosfamide or cyclophosphamide dose is recommended. This dose should be divided into three equal fractions. The first administration should be given concurrently with the cytostatic agent and the subsequent two administrations at 4 and 8 hours after administration of the cytostatic agent. Significantly higher doses of mesnum (eg, 133% of the cyclophosphamide or ifosfamide doses) lead to gastrointestinal disorders, which are easily reversible.

Clinical Trials as Topic↗