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D Fischer

Publications and source records attributed to D Fischer.

At least 55 records · Page 3Linked to original sources
PubMed2000

Sepsis-induced muscle proteolysis is prevented by a proteasome inhibitor in vivo.

Sepsis-induced muscle proteolysis mainly reflects ubiquitin-proteasome-dependent protein degradation. The effect of in vivo administration of a proteasome inhibitor on muscle protein breakdown during sepsis is not known. We treated rats with the proteasome inhibitor N-benzyloxycarbonyl-Ile-Glu-(O-t-butyl)-Ala-leucinal (PSI) or corresponding volume of vehicle i.p. 2 h before sham-operation or induction of sepsis by cecal ligation and puncture. The sepsis-induced increase in total and myofibrillar muscle protein breakdown was inhibited in rats treated in vivo with PSI and a maximal effect was seen following 15 mg/kg of the proteasome inhibitor. Results from in vitro experiments in which incubated muscles were treated with 100 microM PSI suggest that the drug has a direct effect on muscle and that the effect is specific for the proteasome. The results are important because they suggest that it may be possible to prevent or improve the cachectic response in skeletal muscle during sepsis by treatment with a proteasome inhibitor.

Animals↗
PubMed2000

The gene expression of ubiquitin ligase E3alpha is upregulated in skeletal muscle during sepsis in rats-potential role of glucocorticoids.

Muscle protein breakdown during sepsis is associated with upregulated expression and activity of the ubiquitin-proteasome proteolytic pathway. Previous studies suggest that ubiquitination of proteins in skeletal muscle is regulated by the ubiquitin ligase E3alpha together with the 14 kDa ubiquitin-conjugating enzyme E2(14k). The E3alpha gene was cloned only recently. The influence of sepsis on the gene expression of E3alpha in skeletal muscle has not been reported. In the present study, induction of sepsis in rats by cecal ligation and puncture resulted in increased mRNA levels for E3alpha in white, fast-twitch but not in red slow-twitch muscle. Treatment with the glucocorticoid receptor antagonist RU38486 (10 mg/kg) prevented the sepsis-induced increase in E3alpha and E2(14k) mRNA levels. The present study is the first report of increased E3alpha expression in skeletal muscle during sepsis. The results lend further support to the concept that glucocorticoid-mediated upregulation of the ubiquitin-proteasome proteolytic pathway is involved in sepsis-induced muscle cachexia. Increased expression of both E3alpha and E2(14k) suggests that muscle proteins are degraded in the N-end rule pathway during sepsis.

Animals↗
PubMed2000

[Intracoronary ultrasound].

IVUS imaging provides a 2-dimensional, cross-sectional view into the lumen and vessel wall structure of coronary arteries; it is superior to angiography with regard to visualization about several aspects of coronary artery disease. IVUS has given important information on the development and progression of coronary atherosclerosis. Moreover, IVUS has improved our understanding of the mechanisms of percutaneous interventions and restenosis. IVUS-guided balloon sizing during PTCA may increase acute lumen gain as compared to conventional angiographic guidance. Optimization of stent implantation by IVUS guidance also results in larger initial lumen gain than with angiographic control; this approach, however, does not reduce restenosis rates. In summary, IVUS is an optional imaging modality that provides clinically useful information in selected patients.

Angioplasty, Balloon, Coronary↗
PubMed2000

Staurosporine-induced apoptosis in cultured chick embryonic neurons is reduced by polyethylenimine of low molecular weight used as a coating substrate.

The survival of neurons largely depends on adhesion to extracellular matrix proteins. This study investigated the influence of polycationic macromolecules of different molecular weights used as coating substrates on apoptosis in primary cultures of chick embryonic neurons. Coating of the culture flasks with positively charged polyethylenimine (PEI) of 12, 32 and 1616 kDa led to different susceptibilities of the neurons to apoptosis induced by staurosporine and serum deprivation. In cultures grown as usual on polylysine (PL)-coated flasks, we found, after 24 h of incubation in medium with serum (controls), serum-free medium and staurosporine (200 nM)-containing serum-free medium, 15, 35 and 63% apoptotic neurons, respectively as evaluated by nuclear staining with Hoechst 33258. Using 12-kDa PEI as a coating substrate, only 11, 15 and 47% apoptotic neurons could be determined in controls, serum-deprived and staurosporine-treated cultures, respectively. No change in the percentage of apoptotic neurons was found after 24 h of serum deprivation or treatment with staurosporine in cultures grown on 32-kDa PEI compared with cultures grown on PL. However, in staurosporine-treated cultures grown on 1616-kDa PEI, the percentage of apoptotic neurons was even higher than in cultures grown on PL. Immunostaining using neurofilament (NF) antibodies revealed that the reduction of staurosporine-induced apoptosis using 12-kDa PEI instead of PL as a coating substrate was accompanied by a reduced disruption and aggregation of the neurofilaments. Thus, the usage of the newly synthesized 12-kDa PEI as a coating substrate enhanced neuronal resistance to apoptosis.

Animals↗
PubMed2000

Coronary collateral development during chronic ischemia: serial assessment using harmonic myocardial contrast echocardiography.

OBJECTIVES: We sought to characterize collateral development in an experimental model of chronic myocardial ischemia by using myocardial contrast echocardiography (MCE). BACKGROUND: Coronary collaterals maintain myocyte viability during myocardial ischemia. The natural history and determinants of collateral development are difficult to study serially in vivo. METHODS: The left anterior descending coronary artery (LAD) in nine dogs was encircled (day 0) with a hydraulic occluder and ameroid constrictor to enable reversible and gradual total LAD occlusion, respectively. Myocardial contrast echocardiography was performed using intravenous injection of perfluorocarbon gas-containing microbubbles during two-dimensional harmonic echocardiographic imaging. Myocardial contrast echocardiography images and radiolabeled microsphere flow measurements were obtained during transient LAD occlusion on day 0. Over the ensuing six weeks, MCE imaging was performed during LAD occlusion at 10-day intervals. RESULTS: Myocardial contrast echocardiography risk area size (expressed as a percent of the left ventricular short axis slice) decreased over the course of six weeks (32%+/-3% on day 0, 21% +/-3% at day 10, 5+/-3% at day 20, 1%+/-1% at day 30 and 1%+/-1% at day 42, p< or =0.001 vs. day 0). Radiolabeled microsphere-derived LAD flow, normalized to left circumflex flow, correspondingly increased between day 0 and day 42 (0.14+/-0.02 to 0.90+/-0.07, p<0.02). CONCLUSIONS: Collateral development occurs relatively early and rapidly in this chronic canine model. Myocardial contrast echocardiography using harmonic imaging and intravenous injection of microbubbles can uniquely track the spatial and temporal course of collateral growth, and may be a powerful tool for noninvasively mapping the efficacy of therapeutic angiogenic strategies in vivo.

Animals↗
PubMed2000

Orbital infection arising from a primary tooth: a case report.

Odontogenic infections may spread to the orbit by one or more of several paths. Such extension is potentially dangerous and may lead to loss of vision. A case of infection from a primary tooth, which extended to the retrobulbar area is presented in this report. Treatment included surgical drainage of the resulting subperiosteal orbital abscess through a Caldwell-Luc approach as well as aggressive antibiotic therapy. The importance of early suspicion of this entity and its potential sequelae are discussed.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2000

[Computer-supported tissue characterization in musculoskeletal ultrasonography].

A new diagnostic system combining conventional gray-scale ultrasonography (US) and computer-assisted texture analysis of sonograms makes it possible to differentiate more easily between specific neuromuscular diseases. The first step involves myosonography with strictly standardized US. In a group of 72 patients with histologically and molecular-genetically confirmed diagnosis 63 patients (88%) were diagnosed by conventional US as having Duchenne's muscular dystrophy, spinal muscular atrophy, hereditary sensomotor neuropathy or inflammatory myopathy. Secondly, in a double blind setting computer-assisted texture analysis was used on the same sample of subjects. Tissue Texture can be characterized by the brightness as well as the micro- and macro-structure of the tissue. The use of these parameters leads to a sensitivity of 77 to 94% and a specificity of 81 to 98%. In conclusion, the combination of both techniques allows us to avoid invasive diagnostic procedures in a substantial group of patients.

Diagnosis, Computer-Assisted↗
PubMed2000

MaxSub: an automated measure for the assessment of protein structure prediction quality.

MOTIVATION: Evaluating the accuracy of predicted models is critical for assessing structure prediction methods. Because this problem is not trivial, a large number of different assessment measures have been proposed by various authors, and it has already become an active subfield of research (Moult et al. (1997,1999) and CAFASP (Fischer et al. 1999) prediction experiments have demonstrated that it has been difficult to choose one single, 'best' method to be used in the evaluation. Consequently, the CASP3 evaluation was carried out using an extensive set of especially developed numerical measures, coupled with human-expert intervention. As part of our efforts towards a higher level of automation in the structure prediction field, here we investigate the suitability of a fully automated, simple, objective, quantitative and reproducible method that can be used in the automatic assessment of models in the upcoming CAFASP2 experiment. Such a method should (a) produce one single number that measures the quality of a predicted model and (b) perform similarly to human-expert evaluations. RESULTS: MaxSub is a new and independently developed method that further builds and extends some of the evaluation methods introduced at CASP3. MaxSub aims at identifying the largest subset of C(alpha) atoms of a model that superimpose 'well' over the experimental structure, and produces a single normalized score that represents the quality of the model. Because there exists no evaluation method for assessment measures of predicted models, it is not easy to evaluate how good our new measure is. Even though an exact comparison of MaxSub and the CASP3 assessment is not straightforward, here we use a test-bed extracted from the CASP3 fold-recognition models. A rough qualitative comparison of the performance of MaxSub vis-a-vis the human-expert assessment carried out at CASP3 shows that there is a good agreement for the more accurate models and for the better predicting groups. As expected, some differences were observed among the medium to poor models and groups. Overall, the top six predicting groups ranked using the fully automated MaxSub are also the top six groups ranked at CASP3. We conclude that MaxSub is a suitable method for the automatic evaluation of models.

Algorithms↗
PubMed2000

The 2000 Olympic Games of protein structure prediction; fully automated programs are being evaluated vis-à-vis human teams in the protein structure prediction experiment CAFASP2.

In this commentary, we describe two new protein structure prediction experiments being run in parallel with the CASP experiment, which together may be regarded as the 2000 Olympic Games of structure prediction. The first new experiment is CAFASP, the Critical Assessment of Fully Automated Structure Prediction. In CAFASP, the participants are fully automated programs or Internet servers, and here the automated results of the programs are evaluated, without any human intervention. The second new experiment, named LiveBench, follows the CAFASP ideology in that it is aimed towards the evaluation of automatic servers only, while it runs on a large set of prediction targets and in a continuous fashion. Researchers will be watching the 2000 protein structure prediction Olympic Games, to be held in December, in order to learn about the advances in the classical 'human-plus-machine' CASP category, the fully automated CAFASP category, and the comparison between the two.

Amino Acid Sequence↗
PubMed2000

Subtle shifts in the ratio between pro- and antiapoptotic molecules after activation of corticosteroid receptors decide neuronal fate.

Glucocorticoid receptor (GR) activation induces apoptosis of granule cells in the hippocampus. In contrast, neuroprotection is seen after mineralocorticoid receptor (MR) activation. To date there is no in vivo evidence for direct interactions between corticosteroids and any of the key regulatory molecules of programmed cell death. In this report, we show that the opposing actions of MR and GR on neuronal survival result from their ability to differentially influence the expression of members of the bcl-2 gene family; specifically, in the rat hippocampus, activation of GR induces cell death by increasing the ratio of the proapoptotic molecule Bax relative to the antiapoptotic molecules Bcl-2 or Bcl-x(L); the opposite effect is observed after stimulation of MR. The same results were obtained in both young and aged animals; however, older subjects (which were more susceptible to GR-mediated apoptosis) tended to express the antiapoptotic genes more robustly. Using a loss-of-function mouse model, we corroborated the observations made in the rat, demonstrating Bax to be essential in the GR-mediated cell death-signaling cascade. In addition, we show that GR activation increases and MR activation decreases levels of the tumor suppressor protein p53 (a direct transcriptional regulator of bax and bcl-2 genes), thus providing new information on the early genetic events linking corticosteroid receptors with apoptosis in the nervous system.

Aging↗
PubMed2000

Left hydronephrosis caused by Crohn disease successfully treated conservatively.

We report the case of a 35-year-old man who presented with fever, diarrhea, and a left abdominal mass. Diagnostic studies confirmed Crohn disease and revealed an abdominal mass obstructing the left ureter with hydroureter and hydronephrosis. The patient was successfully treated conservatively, with corticosteroids and mesalamine, A review of the literature indicates a predominance of right ureteral involvement in Crohn disease, associated with a high incidence of ileocecal disease. Most of these patients were treated surgically, with resection of ileocecal lesion and/or ureterolysis. Ureteral obstruction as a complication of Crohn disease is discussed, with emphasis on conservative treatment.

Adult↗
PubMed2000

Significance of saliva for the denture-wearing population.

UNLABELLED: This paper summarises a series of studies already published in German and presents new data related to the aetiology of the 'dry mouth' and its associated problems. AIMS: To study factors affecting mucous and serous salivary gland secretion, the aetiology of the 'dry mouth' and its associated problems, causative factors for hyposalivation and it's treatment. SETTING: Two university dental hospitals. SUBJECTS: 587 denture wearers and 521 control subjects, and autopsy material. INTERVENTIONS: Exercise, chewing, water, oestrogen, pilocarpine, and anetholtrithion therapy, biopsy of the minor glands. MAIN OUTCOME MEASURES: Palatal secretion (PAL, microL/cm2/min) and parotid salivary flow (PAR), subjective complaints and clinical findings. RESULTS: Resting flow rates for PAL between 0 and 65 microliters/cm2/min were seen in every age group. The flow rates of PAR (0 to 3.7 ml/10 min) were not correlated with PAL. Most patients with a resting flow rate of PAL < or = 6.0 microliters/cm2 suffer from a 'dry mouth' and Burning Mouth Syndrome (BMS) or oral dysaesthesia (OD) with or without chronic lesions of the oral mucosa. Etiological factors for the incidence of reduced PAL and associated problems include xerostomic drugs, oestrogen deficiency, radiotherapy, thyroid dysfunction, smoking or continuous wearing of complete upper dentures. PAL also correlated with the retention of upper complete dentures. PAL was correlated with the water content of epithelial tissues. PAL and PAR were both increased by drinking ample fluid, improving their circulation by physical exercises, chewing intensively, or taking oestrogens, pilocarpine, anetholtrithion. CONCLUSIONS: Variation in palatal salivary secretion occurs and is clinically important.

Adult↗
PubMed2000

Photoreceptor degeneration in the RCS rat attenuates dendritic transport and axonal regeneration of ganglion cells.

PURPOSE: Photoreceptor loss in the Royal College of Surgeons (RCS) rat deprives the retinal ganglion cells (RGCs) of sensory input, which could interfere with RGC physiology. Whether axonal and dendritic transport is altered, and whether RGCs retain their capacity to regenerate their axons, both in vivo and in culture, was ascertained. METHODS: The study was conducted at postnatal days (P) 30 (while most photoreceptors are still intact), P90 (photoreceptors being almost completely absent), and P180 (approximately 3 months after photoreceptor disappearance). RGCs were studied with retrograde transport of the fluorescent dye 4Di-10ASP. Dendritic transport was also studied with 4Di-10ASP that is transported from the cell bodies into the RGC dendrites. Regeneration of RGC axons in vivo was monitored in the grafting paradigm of replacing the cut optic nerve (ON) with a sciatic nerve (SN) piece. Cell counts were performed in retinal wholemounts. Axonal regrowth in vitro was assessed in organotypic cultures of retinal stripes. RESULTS: Photoreceptor dystrophy did not adversely affect retrograde axonal transport but attenuated dendritic transport compared with the wild-type control rats. Axons of RGCs were able to regenerate if provided with a SN graft, and regeneration was observed to be similar between RCS and wild-type rats at P30 but differed significantly at P90 and P180. In addition to an age-dependent decline in the regenerative ability, seen also in control animals, the number of RCS RGCs able to regenerate declined drastically beginning at 3 months. It is plausible that the intraretinal reorganization, as a consequence of photoreceptor disappearance, interferes with the regenerative ability of the RGCs. CONCLUSIONS: The findings suggest for the first time that diminution of photoreceptor sensory input does not induce detectable death of RGCs until P180, but that it attenuates certain ganglion cell functions like intraretinal dendritic transport and propensity for axonal regeneration.

Animals↗
PubMed2000

Hybrid fold recognition: combining sequence derived properties with evolutionary information.

Recent assessments of structure prediction have demonstrated that (i) although fold recognition methods can often identify remote similarities when standard sequence search methods fail, the score of the top-ranking fold is not always significant enough to allow a confident prediction; (ii) the use of structural information such as secondary structure increases recognition accuracy; (iii) modern sequence-based methods incorporating evolutionary information from neighboring sequences can often identify very remote similarities; (iv) there is no one single method that is superior to other methods when evaluated over a wide range of targets, and (v) extensive human-expert intervention is usually required for the most difficult prediction targets. Here, I describe a new, hybrid fold recognition method that incorporates structural and evolutionary information into a single fully automated method. This work is a first attempt towards the automation of some of the processes that are often applied by human predictors. The method is tested with two cases that are often applied by human predictors. The method is tested with two fold-recognition benchmarks demonstrating a superior performance. The higher sensitivity and selectivity enable the applicability of this method at genomic scales.

Algorithms↗
PubMed2000

Clinical classification and staging.

The identification of increasingly powerful prognostic factors has led to sequential modifications of the cutaneous melanoma staging system. Changes in the staging system are anticipated as more refined prognostic factors are identified. This article provides an overview of the system, including a brief history and an introduction to recent advances in staging of patients with primary melanoma (i.e., sentinel lymphadenectomy). Practical recommendations for a stage-specific workup for the patient, which are especially important given the need for quality care in an increasingly cost-conscious environment, are provided.

Humans↗
PubMed2000

Cataractogenic lens injury prevents traumatic ganglion cell death and promotes axonal regeneration both in vivo and in culture.

PURPOSE: To examine and quantify neuroprotective and neurite-promoting activity on retinal ganglion cells (RGCs) after injury of the lens. METHODS: In adult albino rats, penetrating lens injury was performed by intraocular injection. To test for injury-induced neuroprotective effects in vivo, fluorescence-prelabeled RGCs were axotomized by subsequent crush of the optic nerve (ON) with concomitant lens injury to cause cataract. The numbers of surviving RGCs were determined in retinal wholemounts and compared between the different experimental and control groups. To examine axonal regeneration in vivo, the ON was cut and replaced with an autologous piece of sciatic nerve (SN). Retinal ganglion cells with axons that had regenerated within the SN under lens injury or control conditions were retrogradely labeled with a fluorescent dye and counted on retinal wholemounts. Neurite regeneration was also studied in adult retinal explants obtained either after lens injury or without injury. The numbers of axons were determined after 1 and 2 days in culture. Putative neurotrophins (NTs) were studied within immunohistochemistry and Western blot analysis. RESULTS: Cataractogenic lens injury performed at the same time as ON crush resulted in highly significant rescue of 746 +/- 126 RGCs/mm(2) (mean +/- SD; approximately 39% of total RGCs) 14 days after injury compared with controls without injury or with injection of buffer into the vitreous body (30 +/- 18 RGCs/mm(2)). When lens injury was performed with a delay of 3 days after ON crush, 49% of RGCs survived, whereas delay of 5 days still rescued 45% of all RGCs. In the grafting paradigm virtually all surviving RGCs after lens injury appeared to have regenerated an axon within the SN graft (763 +/- 114 RGCs/mm(2) versus 79 +/- 17 RGCs/mm(2) in controls). This rate of regeneration corresponds to approximately 40% of all RGCs. In the regeneration paradigm in vitro preceding lens injury and ON crush 5 days previous resulted in a maximum of regeneration of 273 +/- 39 fibers/explant after 1 day and 574 +/- 38 fibers/explant after 2 days in vitro. In comparison, in control retinal pieces without lens injury 28 +/- 13 fibers/explant grew out at 1 day, and 97 +/- 37 fibers/explant grew out at 2 days in culture. Immunohistochemical and Western blot analysis of potential NTs in the injured lens revealed no expression of ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF), NT-4, nerve growth factor (NGF), and basic fibroblast growth factor (bFGF). CONCLUSIONS: The findings indicate that the lens contains high neuroprotective and neuritogenic activity, which is not caused by NT. Compared with the data available in the literature, this neuroprotection is quantitatively among the highest ever reported within the adult rat visual system.

Animals↗