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Biomedical subjects

C Busch

Publications and source records attributed to C Busch.

At least 19 recordsLinked to original sources
PubMed2006

Magnetic resonance imaging of iron-oxide labeled SK-Mel 28 human melanoma cells in the chick embryo using a clinical whole body MRI scanner.

PURPOSE: To evaluate advantages and limitations of magnetic resonance imaging (MRI) to monitor the migration of superparamagnetic iron oxide (SPIO) labeled cells in the chick embryo. MATERIALS AND METHODS: Labeled human SK-Mel 28 melanoma cells were injected into the E2 chick embryo neural tube. Embryos were examined with a clinical 3 T MRI whole body system using 3D T*(2)-weighted sequences with isotropic spatial resolutions of 0.3-1.0 mm. MR-measurements of embryos were performed 2 - 16 days after cell injection. MRI findings were verified by dissection and histology. RESULTS: After injection, melanoma cells formed aggregations that were detectable in the neural tube as signal voids in MR images from day 2 after injection. Emigrating cells later left MRI detectable tracks. Aggregates that remained in the neural tube left label that was absorbed by glia cells. In E18 chick embryos, signals of haematopoiesis interfered with signals from cell labeling. CONCLUSION: It was shown that SK-Mel 28 cells will resume the neural crest pathways after injection into the embryonic micro-environment. SPIO cell labeling allows monitoring of transplanted melanoma cells during embryonic development. MRI using the standard clinical equipment promises to be valuable for high-sensitive monitoring of ex-vivo labeled cells in the chick embryo.

Animals↗
PubMed2005

[Endothelial ion channels -- novel targets for antihypertensive therapy].

Endothelial cation channel are important regulators of vascular tone by modulating intracellular Ca(2+)-signaling and thus adequate synthesis of vasodilating factors. The overall importance of these ion channels suggests that they may represent novel pharmacotherapeutic targets in addition to the well-known voltage-gated calcium channels in vascular smooth muscle. In this short overview we summarize the current knowledge about endothelial ion channels and their roles for endothelium-dependent vasodilatation. Furthermore, we perspectively discuss the usefulness of specific openers of endothelial Ca(2+)-activated K(+)-channels and TRPV-channels as novel antihypertensive drugs.

Antihypertensive Agents↗
PubMed2005

Toroidal plasma rotation induced by the dynamic ergodic divertor in the TEXTOR tokamak.

The first results of the Dynamic Ergodic Divertor in TEXTOR, when operating in the m/n=3/1 mode configuration, are presented. The deeply penetrating external magnetic field perturbation of this configuration increases the toroidal plasma rotation. Staying below the excitation threshold for the m/n=2/1 tearing mode, this toroidal rotation is always in the direction of the plasma current, even if the toroidal projection of the rotating magnetic field perturbation is in the opposite direction. The observed toroidal rotation direction is consistent with a radial electric field, generated by an enhanced electron transport in the ergodic layers near the resonances of the perturbation. This is an effect different from theoretical predictions, which assume a direct coupling between rotating perturbation and plasma to be the dominant effect of momentum transfer.

Journal Article↗
PubMed2005

[Quality of life in multiple sclerosis. Measures, relevance, problems, and perspectives].

Measuring quality of life (QOL) has made essential contributions for the management of patients with multiple sclerosis (MS). QOL measures may be used for helping to assess the complex changes which patients with MS have to go through during the disease trajectory, and they may be used for pharmacoeconomic research. The large number of tests available includes generic ones such as Short Form SF-36 and Sickness Impact Profile, health-related ones such as MSQOL-54, FAMS, or HAQUAMS, and patient generated measures such as the Patient Generated Index and SEIQOL-DW. Depression, cognitive impairment, and fatigue are important factors influencing QOL. Since the different tests measure quite different facets of QOL, this review intends to help the reader select a tool suited to the aim and specific question. It is hoped that QOL measures may help to better understand patients, to become a more helpful medical partner, to assist patients to develop perspectives for their future, and to decide about therapies or even palliative interventions.

Cognition Disorders↗
PubMed2005

Genetic structure in a solitary rodent (Ctenomys talarum): implications for kinship and dispersal.

The genetic structure of a population provides critical insights into patterns of kinship and dispersal. Although genetic evidence of kin structure has been obtained for multiple species of social vertebrates, this aspect of population biology has received considerably less attention among solitary taxa in which spatial and social relationships are unlikely to be influenced by kin selection. Nevertheless, significant kin structure may occur in solitary species, particularly if ecological or life history traits limit individual vagility. To explore relationships between genetic structure, kinship, and dispersal in a solitary vertebrate, we compared patterns of genetic variation in two demographically distinct populations of the talar tuco-tuco (Ctenomys talarum), a solitary species of subterranean rodent from Buenos Aires Province, Argentina. Based on previous field studies of C. talarum at Mar de Cobo (MC) and Necochea (NC), we predicted that natal dispersal in these populations is male biased, with dispersal distances for males and females being greater at NC. Analyses of 12 microsatellite loci revealed that in both populations, kin structure was more apparent among females than among males. Between populations, kinship and genetic substructure were more pronounced at MC. Thus, our findings were consistent with predicted patterns of dispersal for these animals. Collectively, these results indicate that populations of this solitary species are characterized by significant kin structure, suggesting that, even in the absence of sociality and kin selection, the spatial distributions and movements of individuals may significantly impact patterns of genetic diversity among conspecifics.

Animals↗
PubMed2005

Significant expression of IGFBP2 in breast cancer compared with benign lesions.

BACKGROUND/AIM: Insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) play a role in the normal development of breast tissue, and possibly in breast cancer aetiology. IGFBP2, one of six members of the IGFBP superfamily, acts as regulator of the IGFs and has pleiotropic effects in normal and neoplastic tissues. Because IGFs have mitogenic effects on mammary epithelia, this study investigated IGFBP2 expression in mammary tissues of different benign and malignant entities. METHODS: Immunohistochemistry was used to study correlations between the presence and intensity of IGFBP2 staining and tumour type and grade, in addition to steroid hormone receptor status, in 120 breast specimens. Expression was measured by quantitative colour video image analysis and semiquantitative evaluation, and the measurements correlated well (r = 0.92; p<0.05). RESULTS: Both methods found no significant expression of IGFBP2 in normal glandular cells and hyperplasia (group I). Atypical hyperplasia showed a slightly increased cytoplasmic expression of IGFBP2, and carcinoma in situ showed a distinctive, membrane associated and cytoplasmic expression (group II). Infiltrating carcinomas strongly expressed cytoplasmic IGFBP2 (group III). There were significant differences between group I and II, and between group II and III. There were no significant differences between invasive lobular and invasive ductal carcinoma, or between grades I, II, and III within these entities. There was no significant correlation between IGFBP2 immunostaining and oestrogen or progesterone receptor positivity within the malignant group. CONCLUSIONS: IGFBP2 mitogenic signals of autocrine/paracrine regulatory mechanisms may be responsible for the growth of breast carcinomas and IGFBP2 may be an independent indicator of malignancy.

Adult↗
PubMed2002

[Intussusception after Billroth II procedure--an uncommon cause of an upper gastrointestinal ileus].

We present a case of a 73-year-old male patient with Korsakow's disease who was admitted with upper gastrointestinal bleeding and recurrent vomiting. He had received partial gastric resection with Billroth II reconstruction 39 years before for recurrent ulcer disease. At gastroscopy erosive gastritis with no active bleeding and a structure-resembling necrotic mucosa suspicious for intussuscepted small bowel was seen. At exploratory laparotomy jejunogastric intussusception of 50 cm of small bowel through Braun's enteroanastomosis into the gastric remnant was found. After reposition the bowel recovered well and resection was unnecessary. As prophylaxis the bowel was partially attached by sutures in terms of a partial Noble's Operation. The patient's recovery was uneventful after surgery. Jejunogastric intussusception is a rare cause of upper gastrointestinal bleeding and ileus.

Aged↗
PubMed2001

[The route of reconstruction following esophagectomy].

The route of reconstruction following esophagectomy.Retrosternal reconstruction shows an increased rate of postoperative non-surgical complications and a slightly increased mortality compared to posterior mediastinal reconstruction. Radionuclid transit through the gastric tube is significantly longer in either way of reconstruction compared to normal controls. Tracerretention is significantly increased after retrosternal reconstruction. This however has no impact on the patients' quality of life. We therefore recommend posterior mediastinal reconstruction provided that curative resection is definitely achieved in order to avoid possible complications by local recurrence. In the palliative situation we would rather choose the retrosternal route of reconstruction as the functional disadvantages had no negative effect on quality of life and the general disadvantages seem to be neglectable in this situation. The same is true if adjuvant radiation of the tumorbed is planned. Pyloroplasty in our opinion is unnecessary. The presternal route of reconstruction is underrepresented in the literature. In our experience it has no indication.

Adenocarcinoma↗
PubMed2001

[Gastric substitute following gastrectomy].

Gastric substitute following gastrectomy. Following gastrectomy a variety of different reconstructive alternatives with different advantages and disadvantages have been proposed. Direct termino-lateral esophagojejunostomy with preservation of the duodenal passage or roux-en-Y jejuno-jejunostomy may be considered as current standard route of reconstruction. With current knowledge formation of a jejunal reservoir with a pouch length of 15 cm seems to be advantageous over simple roux-en-Y reconstruction. Preservation of the duodenal passage offers objective biochemical advantages, while its clinical implications have yet to be confirmed. True long term results of randomised studies are still pending. Thus, the technically easier pouch formation using the roux-en-Y reconstruction may currently be favored. Jejunoplicatio as an antirefluxive component of reconstruction is optional. Its value may well lie in the securement of a critical esophagojejunal anastomosis.

Anastomosis, Roux-en-Y↗
PubMed2001

Attenuation of sepsis-related immunoparalysis by continuous veno-venous hemofiltration in experimental porcine pancreatitis.

OBJECTIVES: In light of evidence suggesting that hemofiltration favorably influences septic diseases by removing sepsis mediators, the impact of different modalities of continuous veno-venous hemofiltration (CVVH) on outcome and immunologic derangements in porcine pancreatogenic sepsis was evaluated. DESIGN: Randomized, controlled intervention trial. SUBJECTS: Forty-eight minipigs of either sex. INTERVENTIONS: Pancreatitis was induced by intraductal injection of sodium taurocholate (4%, 1 mL/kg body weight [BW]) and enterokinase (2 U/kg BW). Animals were allocated either to untreated controls-group 1-or to one of three treatment groups-group 2: low-volume CVVH (20 mL/kg BW), no change of hemofilters; group 3: low-volume CVVH, filters changed every 12 hrs; and group 4: high-volume CVVH (100 mL/kg BW), filters changed every 12 hrs. Survival represented the major parameter of the study. Serum cytokine levels, sepsis-related down-regulation of major histocompatibility complex II and CD14 expression on leukocytes, bacterial translocation, and endotoxemia were further parameters evaluated in the study. MEASUREMENTS AND MAIN RESULTS: High-volume CVVH combined with periodic filter change was significantly superior compared with less intensive treatment modalities (low-volume CVVH, no filter change) in sepsis protection. Long-term survival (>60 hrs) was found in 67% of group 4 and 33% of group 3 animals (p <.05), whereas in controls and group 2 no animal survived. CVVH ameliorated the initial serum tumor necrosis factor-alpha response and prevented sepsis-induced in vitro endotoxin hyporesponsiveness. Down-regulation of major histocompatibility complex II and CD14 expression on monocytes was significantly improved by CVVH. Improved oxidative burst and phagocytosis capacity in polymorphonuclear leukocytes suggested that leukocyte function was stabilized by CVVH. Also, CVVH significantly reduced bacterial translocation and endotoxemia. CONCLUSIONS: Hemofiltration reversed sepsis-induced immunoparalysis in a porcine model of bile acid-induced pancreatitis. Implications for human pancreatitis must be validated in prospective, clinical protocols.

Acute Disease↗
PubMed2001

Biological activity of a C-terminal fragment of Pasteurella multocida toxin.

The protein toxin of Pasteurella multocida PMT is a potent mitogen and activator of phospholipase Cbeta. In this study different toxin fragments were investigated. A C-terminal fragment encompassing amino acids 581 through 1285 (PMT581C) was constructed, which was inactive toward intact embryonic bovine lung (EBL) cells after addition to culture medium but caused reorganization of the actin cytoskeleton and rounding up of cells when introduced into the cells by electroporation. As the holotoxin, the toxin fragment PMT581C induced an increase in total inositol phosphate levels after introduction into the cell by electroporation. A C-terminal fragment shorter than PMT581C as well as N-terminal fragments were inactive. Exchange of cysteine-1165 for serine in the holotoxin resulted in a complete loss of the ability to increase inositol phosphate levels. Correspondingly, the mutated toxin fragment PMT581C.C1165S was inactive after cell introduction by electroporation, suggesting an essential role of Cys-1165 in the biological activity of the toxin.

Actins↗
PubMed2001

An experimental inter-expert telepathology network using static imaging.

AIMS: To set up a network for remote consultation using static imaging telepathology via Internet connection between pathologists in different European countries, and to collect some numerical and subjective impressions on the usefulness of this form of telepathology. METHODS: A static image remote consultation network between 11 pathologists in nine European countries was set up; all pathologists were equipped with the same telepathology system. The pathologists formed three subject oriented subgroups concerned with prostate, melanoma, and soft tissue sarcoma pathology. Each pathologist sent and received a small number of cases, and data on each case were collected and analysed. The whole experiment was controlled through a World Wide Web site. RESULTS: A total of 56 case consultations on 34 different cases were exchanged. The average case document contained seven images, and contained 1.97 Mbytes of data. For cases in which data were recorded, average case preparation and remote consultation time was 55 minutes and 9.2 minutes, respectively. Transmission times averaged 3.9 minutes. In subjective impressions, reservations were expressed in several cases regarding the confidence that could be given to the diagnosis from the images presented. CONCLUSIONS: Remote consultation by telepathology via the Internet is now technically feasible and reasonably user friendly, but is only suitable as a method of disease diagnosis in some cases.

Diagnostic Imaging↗
PubMed2001

Automatic registration and error detection of multiple slices using landmarks.

OBJECTIVES: When analysing the 3D structure of tissue, serial sectioning and staining of the resulting slices is sometimes the preferred option. This leads to severe registration problems. In this paper, a method for automatic registration and error detection of slices using landmark needles has been developed. A cost function takes some parameters from the current state of the problem to be solved as input and gives a quality of the current solution as output. The cost function used in this paper, is based on a model of the slices and the landmark needles. The method has been used to register slices of prostates in order to create 3D computer models. Manual registration of the same prostates has been undertaken and compared with the results from the algorithm. METHODS: Prostates from sixteen men who underwent radical prostatectomy were formalin fixed with landmark needles, sliced and the slices were computer reconstructed. The cost function takes rotation and translation for each prostate slice, as well as slope and offset for each landmark needle as input. The current quality of fit of the model, using the input parameters given, is returned. The function takes the built-in instability of the model into account. The method uses a standard algorithm to optimize the prostate slice positions. To verify the result, s standard method in statistics was used. RESULTS: The methods were evaluated for 16 prostates. When testing blindly, a physician could not determine whether the registration shown to him were created by the automated method described in this paper, or manually by an expert, except in one out of 16 cases. Visual inspection and analysis of the outlier confirmed that the input data had been deformed. The automatic detection of erroneous slices marked a few slices, including the outlier, as suspicious. CONCLUSIONS: The model based registration performs better than traditional simple slice-wise registration. In the case of prostate slice registration, other aspects, such as the physical slicing method used, may be more important to the final result than the selection of registration method to use.

Algorithms↗
PubMed2001

Stage progression in Ta papillary urothelial tumors: relationship to grade, immunohistochemical expression of tumor markers, mitotic frequency and DNA ploidy.

PURPOSE: We studied 363 patients with stage Ta bladder tumors during long-term followup who were classified according to the 1998 WHO and International Society of Urological Pathology consensus classifications. We determine whether various immunohistochemical and molecular markers could predict tumor progression. MATERIALS AND METHODS: A total of 680 patients in western Sweden with a first diagnosis of bladder carcinoma in 1987 and 1988 were registered and followed for at least 5 years. There were 363 (53%) tumors that were papillary stage pTa. The tumors were classified as papillary urothelial neoplasm of low malignant potential in 95 patients, low grade papillary urothelial carcinoma in 160 and high grade carcinoma in 108. Of the patients in the latter group 95 were subdivided into WHO grade 2 and 13 into WHO grade 3. Tissue from the primary tumors that progressed in stage during followup was further analyzed with immunohistochemical methods (p21, p53, Ki67 and pRb), DNA ploidy and mitotic frequency. The results were compared with those in matched controls (nonprogressors). RESULTS: Recurrence developed in 35% of patients with papillary urothelial neoplasm of low malignant potential compared to 71% with low grade urothelial carcinoma and 73% with high grade carcinoma (p <0.0001). No papillary urothelial neoplasm of low malignant potential progressed in stage. Disease progressed in 4% of patients with low grade compared to 23% with high grade carcinoma (p <0.0001). Of the patients with WHO grade 3 disease progressed in 45% compared to grade 2 in 20% (p <0.0011). At first diagnosis p53 score was significantly higher (p <0.0022) among patients with WHO grade 2 carcinoma which later progressed compared to that in matched controls but there was no significant difference regarding the other markers. In contrast to grade 2 most grade 3 carcinoma was aneuploid, had high mitosis frequency, high p53 and Ki67 scores as well as loss of retinoblastoma gene expression. CONCLUSIONS: The 1988 WHO and International Society of Urological Pathology consensus classifications divide noninvasive papillary bladder tumors into 3 subgroups with different clinical behavior, which seems to be an advantage compared with the 1973 WHO classification. A disadvantage is that the high grade carcinoma group contains 2 subgroups with different progression rates and immunohistochemical marker profiles, corresponding to the 1999 WHO grades 2 and 3. Grade 2 tumors in patients that progressed in stage years later seem to have different immunohistochemical and molecular marker profiles compared to those in matched controls.

Aged↗
PubMed2000

Involvement of a conserved tryptophan residue in the UDP-glucose binding of large clostridial cytotoxin glycosyltransferases.

Large clostridial cytotoxins catalyze the glucosylation of Rho/Ras GTPases using UDP-glucose as a cosubstrate. By site-directed mutagenesis of Clostridium sordellii lethal toxin and Clostridium difficile toxin B fragments, we identified tryptophan 102, which is located in a conserved region within the catalytic domain of all clostridial cytotoxins, to be crucial for UDP-glucose binding. Exchange of Trp-102 with alanine decreased the glucosyltransferase activity by about 1,000-fold and blocked cytotoxic activity after microinjection. Replacement of Trp-102 by tyrosine caused a 100-fold reduction in enzyme activity, indicating a partial compensation of the tryptophan function by tyrosine. Decrease in glucosyltransferase and glycohydrolase activity was caused predominantly by an increase in the K(m) for UDP-glucose of these mutants. The data indicate that the conserved tryptophan residue is implicated in the binding of the cosubstrate UDP-glucose by large clostridial cytotoxins. Data bank searches revealed different groups of proteins sharing the recently identified DXD motif (Busch, C., Hofmann, F., Selzer, J., Munro, J., Jeckel, D., and Aktories, K. (1998) J. Biol. Chem. 273, 19566-19572) and a conserved region defined by a tryptophan residue equivalent to Trp-102 of C. sordellii lethal toxin. From our findings, we propose a novel family of glycosyltransferases which includes both prokaryotic and eukaryotic proteins.

Amino Acid Sequence↗
PubMed2000

Cultured human fibroblasts in agarose gel as a multi-functional control for immunohistochemistry. Standardization Of Ki67 (MIB1) assessment in routinely processed urinary bladder carcinoma tissue.

Immunohistochemistry (IHC) in clinical practice is hampered by lack of standardization and by subjectivity in interpretation and quantitation. This study aimed to develop a control system for IHC in routinely fixed and histoprocessed tissues. Such a system should be easy to handle in clinical practice and should reflect variations in fixation time, section thickness, section storage conditions, and staining protocols. In addition, in image analysis quantitation of immunostained tissues, when using classifiers computed on IHC-control images, the control system should be very stable. Cultured human fibroblasts were suspended in agarose, transferred into a length of tubing and stored at 4 degrees C. Three pieces of the cellgel control were separately fixed, histoprocessed, and paraffin-embedded as external controls. One piece was prepared together with each of 18 bladder carcinoma biopsies as internal controls. Slides with sections from the biopsy and all types of cellgel controls were stored at different temperatures and then stained using three different IHC protocols. The fibroblasts were homogeneously distributed in the agarose gel. Variation in section thickness did not influence immunostaining as evaluated by the MIB1 labelling index (MIB1 LI). The external controls decreased notably in MIB1 LI with increased fixation time. This was not seen in the 18 internal controls that were each fixed with a fresh biopsy. However, section storage and immunostaining conditions influenced the MIB1 expression equally in all control types and to a similar degree to the biopsies. Furthermore, colour-based image analysis quantitation of MIB1 LI in biopsies proved stable and independent of the control type used to compute the classifier.

Biopsy↗
PubMed2000

Microbial toxins and the glycosylation of rho family GTPases.

Large clostridial cytotoxins act on cells by glycosylating low molecular mass GTPases using nucleotide-sugars as the sugar donor. These toxins are important virulence factors in human and animal diseases, but are also valuable cell biology tools. Recent findings shed some light on their mode of action and provide new insights into the structure/activity relationship of these bacterial toxins.

Amino Acid Sequence↗