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C Busch

Publications and source records attributed to C Busch.

At least 19 recordsLinked to original sources
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

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↗
PubMed2000

Systemic lobar shunting induces advanced pulmonary vasculopathy.

OBJECTIVES: We characterized the morphology and vasomotor responses of a localized, high-flow model of pulmonary hypertension. METHODS: An end-to-side anastomosis was created between the left lower lobe pulmonary artery and the aorta in 23 piglets. Control animals had a thoracotomy alone or did not have an operation. Eight weeks later, hemodynamic measurements were made. Then shunted and/or nonshunted lobes were removed for determination of vascular resistance and compliance by occlusion techniques under conditions of normoxia, hypoxia (FIO (2) = 0.03), and inspired nitric oxide administration. Quantitative histologic studies of vessel morphology were performed. RESULTS: Eighty-three percent of animals having a shunt survived to final study. Aortic pressure, main pulmonary artery and wedge pressures, cardiac output, blood gases, and weight gain were not different between control pigs and those receiving a shunt. Six of 9 shunted lobes demonstrated systemic levels of pulmonary hypertension in vivo. Arterial resistance was higher (24.3 +/- 12.0 vs 1.3 +/- 0. 2 mm Hg. mL(-1). s(-1), P =.04) and arterial compliance was lower (0. 05 +/- 0.01 vs 0.16 +/- 0.03 mL/mm Hg, P =.02) in shunted compared with nonshunted lobes. Hypoxic vasoconstriction was blunted in shunted lobes compared with nonshunted lobes (31% +/- 13% vs 452% +/- 107% change in arterial resistance, during hypoxia, P <.001). Vasodilation to inspired nitric oxide was evident only in shunted lobes (34% +/- 6% vs 1.8% +/- 8.2% change in arterial resistance during administration of inspired nitric oxide, P =.008). Neointimal and medial proliferation was found in shunted lobes with approximately a 10-fold increase in wall/luminal area ratio. CONCLUSIONS: An aorta-lobar pulmonary artery shunt produces striking vasculopathy. The development of severe pulmonary hypertension within a short time frame, low mortality, and localized nature of the vasculopathy make this model highly attractive for investigation of mechanisms that underlie pulmonary hypertension.

Anastomosis, Surgical↗
PubMed2000

Characterization of the catalytic domain of Clostridium novyi alpha-toxin.

Clostridium novyi alpha-toxin belongs to the family of large clostridial cytotoxins which act on cells through the modification of small GTP-binding proteins. We present here an analysis of the catalytic domain of alpha-toxin. A NH(2)-terminal 551-amino-acid fragment, alpha 551, was found to contain the full enzyme activity of the holotoxin, whereas a slightly shortened fragment encompassing 509 amino acids showed no detectable enzyme activity. Further characterization of the enzymatically active fragment alpha 551 revealed a substrate specificity for both UDP-N-acetylglucosamine and UDP-glucose. A Michaelis-Menten constant of 17 microM was determined for the substrate UDP-N-acetylglucosamine, while that for UDP-glucose was about 20 times higher, indicating a weaker affinity of the toxin for the latter substrate. Mutation of the aspartic acids of a conserved motif DXD within alpha 551 reduced enzyme activity >700-fold and inhibited cytotoxicity after microinjection in cells. Inhibition of enzyme activity of the DXD mutant could be partially overcome by increased concentrations of manganese ions, suggesting the involvement of these aspartic acids in Mn(2+) binding. By construction of chimeras of enzymatically active fragments of C. sordellii lethal toxin and C. novyi alpha-toxin, we located the region involved in nucleotide-sugar specificity to amino acids 133 through 517.

Bacterial Toxins↗
PubMed2000

New method to generate enzymatically deficient Clostridium difficile toxin B as an antigen for immunization.

The family of the large clostridial cytotoxins, encompassing Clostridium difficile toxins A and B as well as the lethal and hemorrhagic toxins from Clostridium sordellii, monoglucosylate the Rho GTPases by transferring a glucose moiety from the cosubstrate UDP-glucose. Here we present a new detoxification procedure to block the enzyme activity by treatment with the reactive UDP-2', 3'-dialdehyde to result in alkylation of toxin A and B. Alkylation is likely to occur in the catalytic domain, because the native cosubstrate UDP-glucose completely protected the toxins from inactivation and the alkylated toxin competes with the native toxin at the cell receptor. Alkylated toxins are good antigens resulting in antibodies recognizing only the C-terminally located receptor binding domain, whereas formaldehyde treatment resulted in antibodies recognizing both the receptor binding domain and the catalytic domain, indicating that the catalytic domain is concealed under native conditions. Antibodies against the native catalytic domain (amino acids 1 through 546) and those holotoxin antibodies recognizing the catalytic domain inhibited enzyme activity. However, only antibodies against the receptor binding domain protected intact cells from the cytotoxic activity of toxin B, whereas antibodies against the catalytic domain were protective only when inside the cell.

Animals↗
PubMed2000

Boerhaave-mimicking esophageal perforation with subsequent esophagobronchial fistula formation as the primary manifestation of Crohn's disease.

BACKGROUND: Spontaneous ruptures of the esophagus are rare, but may lead to deleterious courses, even if diagnosed early. CASE REPORT: We report a case of Boerhaave's syndrome-mimicking esophageal perforation due to a stricture of the distal esophagus as the primary manifestation of Crohn's disease. Diagnosis was delayed resulting in a complicated clinical course. The presented patient is the first case in the literature with esophageal perforation related to a previously undiagnosed Crohn's disease that lead to stenosis of the distal esophagus before becoming clinically apparent. CONCLUSION: Difficulties in differential diagnosis, problems related to initial misdiagnosis and consecutive mismanagment of spontaneous esophageal perforation, and treatment options including nonsurgical approaches are discussed.

Aged↗
PubMed2000

Paraffin section storage and immunohistochemistry. Effects of time, temperature, fixation, and retrieval protocol with emphasis on p53 protein and MIB1 antigen.

It has been observed that immunoreactivity in paraffin sections decreased during storage. In this study, stored paraffin sections from both biopsy material and cultured cells were assessed for changes in immunoreactivity, using color-based image analysis to quantitate extent and intensity of the stainings. For seven of the 11 antibodies studied, storage at 20 degrees C for 16 weeks reduced the extent of immunostaining compared with that of freshly cut sections. Furthermore, increased storage temperatures resulted in a progressive loss of immunoreactivity. After 2 weeks of storage, at both 4 degrees C and 20 degrees C, p53 protein- and MIB1-antigen expression was significantly reduced regarding extent and intensity. The extent of the immunoreactivity reduced more for p53 protein than for MIB1 antigen, but the intensity did not. Boric acid was used for antigen retrieval on sections stored for 12 weeks at 20 degrees C. For both p53 protein and MIB1 antigen, this resulted in an extent and intensity of immunostaining equal to or higher than (MIB1) that obtained in freshly cut sections, using citrate buffer. Staining of cultured cells confirmed the results from biopsy material on the influence of storage temperature. Fixation time only marginally influenced the storage-related decrease in immunoreactivity. In conclusion, storage of paraffin sections leads to a varying degree of decreased immunoreactivity for several antibodies. The degree is at least partly dependent on storage time and temperature but not fixation time. However, this may be compensated for by optimizing the antigen retrieval protocol.

Antigens, Nuclear↗
PubMed2000

Intraepithelial lesions of urinary bladder: morphologic considerations.

Urological pathologists representing the World Health Organization and the International Society of Urological Pathology have reached a new consensus on the definitions of flat, non-invasive lesions of the urothelium. Lesions are classified as: (1) carcinoma in situ (CIS); (2) dysplasia; (3) atypia of unknown significance; and (4) reactive atypia. These terms are intended to describe a histological spectrum of architectural and cytological abnormalities ranging from the unequivocally malignant (CIS) through the probably neoplastic (dysplasia) to the benign (atypia). The biological potential of these lesions in individual patients cannot be accurately predicted, although the degree of risk for an adverse outcome is very likely to be proportional to the degree of architectural and cytological anaplasia. It is likely that each phenotype has two biological potentials: dynamic and effete. It should be emphasized that most of our knowledge concerning these lesions in humans has been obtained from studies of groups of patients who have already developed a papillary or nodular, invasive or non-invasive urothelial carcinoma, as descriptions of primary CIS, dysplasia, and atypia are uncommon. Future knowledge in this area might be enhanced by attention to the following: better definitions of terms and more accurate application of words such as bladder cancer, early lesion, tumor progression, precursor, and premalignant; increased understanding of the biological processes underlying phenotypic changes; development of models (probably computer-based) with the capacity to factor in the complexities of human carcinogenesis in an ongoing fashion, as new information becomes available.

Biopsy↗