Search PubMed⌕ Search

Biomedical subjects

K B Pedersen

Publications and source records attributed to K B Pedersen.

At least 19 recordsLinked to original sources

Interferon-gamma suppresses S100A4 transcription independently of apoptosis or cell cycle arrest.

The S100A4 protein has been associated with increased metastatic capacity of cancer cells, and recent studies have suggested a correlation between the expression level of S100A4 and the prognostic outcome for patients with various types of cancer. The knowledge about the mechanisms underlying the metastasis-promoting effects is still limited, and the aim of the present study was to elucidate signal transduction pathways involved in the regulation of S100A4. After treatment of human carcinoma cells with interferon-gamma (IFN-gamma), we observed downregulation of S100A4 both at mRNA and protein levels. The effect was not dependent on IFN-gamma-induced apoptosis or IFN-gamma-mediated cell cycle arrest. Moreover, IFN-gamma-mediated decrease in mRNA stability could not account for the observed decrease in S100A4 transcript level. Finally, microarray analysis suggests ISGF3G, ETV5, ZNF133 and CEBPG as possible candidate genes involved in IFN-gamma-mediated repression of S100A4.

Apoptosis↗

Expression of S100A4, E-cadherin, alpha- and beta-catenin in breast cancer biopsies.

In 66 breast cancer biopsies, the expression of the Ca(2+)-binding protein S100A4, E-cadherin, alpha- and beta-catenin was examined by immunohistochemistry, and the results were related to clinical and pathological parameters. High levels of S100A4 were found to significantly correlate with histological grade (P=0.030) and loss of oestrogen receptor (P=0.046), but not to the time interval between surgery and development of distant metastasis (P=0.51) or to patient survival (P=0.89). Loss of E-cadherin expression, associated with altered cell-cell adhesion, showed a highly significant association to overall survival (P=0.020) and metastasis-free period (P=0.0052). In multivariate analysis, only lymph node involvement was a more significant predictor of patient demise. No association was found between expression of S100A4 and any single member of the cadherin-catenin complex, but a trend (P=0.053) towards reduced expression of one or several of these proteins and S100A4 immunoreactivity was observed. In conclusion, although our results suggest an association between S100A4 expression and an aggressive tumour phenotype, no relationship to overall survival was found. Deregulation of E-cadherin expression, however, was of high prognostic significance.

Adult↗

The need for a veterinary antibiotic policy.

The international recognition of the 'stable to table' approach to food safety emphasises the need for appropriate and safe use of antibiotics in animal production. An appropriate use of antibiotics for food animals will preserve the long-term efficacy of existing antibiotics, support animal health and welfare and limit the risk of transfer of antibiotic resistance to humans. Furthermore, it may promote consumer confidence in the veterinary use of antibiotics. In advancing these arguments, the authors of this article argue that there is a need for a visible and operational policy for veterinary use of antibiotics, paying particular attention to the policies that are being developed in Denmark.

Animal Husbandry↗

Regulation of tissue-degrading factors and in vitro invasiveness in progression of breast cancer cells.

Hormone-independent growth and invasiveness represent phenotypic properties acquired during early progression of breast cancer. We compared human mammary adenocarcinoma cells, MCF-7, which are estrogen-dependent and poorly metastatic, with the estrogen-independent and highly metastatic subline, MCF7/LCC1, with regard to expression of tissue-degrading factors of the matrix metalloproteinase (MMP)-and urokinase (uPA)-dependent degradative pathways, as well as for their in vitro invasive properties. Both cell lines showed low constitutive mRNA expression of the MMP inhibitor TIMP-1. Baseline expression of TIMP-2 mRNA was also very low in MCF-7 cells, whereas the MCF7/LCC1 level was much higher (approximately 10-fold). Furthermore, both cell lines revealed low constitutive capacity to migrate in an in vitro invasion assay. Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 nM) induced the mRNAs for TIMP-1 as well as for MMP-1, MMP-9, the uPA receptor, and the uPA inhibitor PAI-1, amongst which only the responses of MMP-9 and PAI-1 were cell-specific. The mRNA levels of MMP-9 and PAI-1 were approximately 10-fold and approximately 15-fold higher in MCF7/LCC1 cells compared to MCF-7 cells. The secretion of immunoreactive PAI-1 was considerably elevated (> 20-fold) in TPA-treated MCF7/LCC1 cells, whereas the TPA-dependent level of 92-kDa MMP-9 was only approximately 2-fold higher in MCF7/LCC1 cells than in MCF-7 cells. In both cell lines treatment with TPA was associated with an increase (approximately 10-fold) in in vitro migration, which in the MCF7/LCC1 cells was significantly attenuated by a reconstituted basement membrane extract (Matrigel). These data suggest that TPA-responsive in vitro invasive properties that are probably associated with PAI-1 expression may co-vary with progression from hormone-dependent to -independent breast cancer.

Breast Neoplasms↗

Characterization of the dermal lesions induced by a purified protein from toxigenic Pasteurella multocida.

The dermonecrotic effect of purified Pasteurella multocida toxin (PMT) was studied sequentially in guinea pigs and rats. The skin reaction was initially an acute inflammatory reaction, with edema and emigration of neutrophils and a few eosinophils and diapedesis of some erythrocytes. Four hours after intracutaneous injection the vessels were congested and thrombocytes were focally attached to the endothelial wall. Twenty-four h after the injection the inflammatory reaction appeared more severe and venules and arterioles were thrombosed. Necrotic changes were seen in hair follicles and in striated muscle fibers. Crude extracts from P. multocida and Clostridium perfringens injected intracutaneously into guinea pigs induced skin lesions qualitatively similar to the lesions induced by the purified PMT, indicating that dermonecrotic bacterial toxins may share similar biochemical properties.

Animals↗

Differentiation of toxigenic from nontoxigenic isolates of Pasteurella multocida by enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay (ELISA) was developed for the rapid and simple differentiation of toxigenic from nontoxigenic strains of Pasteurella multocida. The sandwich ELISA is based on two different murine monoclonal antibodies with specificity for the P. multocida toxin. The ELISA, which is now used as a routine test in Denmark, has several advantages compared with previously described biological tests.

Animals↗

Production of toxin in strains previously classified as Pasteurella multocida.

169 strains of P. multocida ssp. multocida, 24 strains of P. multocida ssp. septica, 22 strains of P. multocida ssp. gallicida, and 8 strains of P. avium and P. canis, respectively, were tested for toxin production in EBL-cell culture assay. Toxin production was only demonstrated in strains belonging to P. multocida ssp. multocida. Toxigenic strains were derived from pigs, calves, cats, dogs, rabbits and turkeys.

Animals↗

The pathogenesis of persistent turbinate atrophy induced by toxigenic Pasteurella multocida in pigs.

Six one-week-old piglets were pretreated with a 1% acetic acid solution for two days in one or both nostrils. Three piglets were not treated with acetic acid. Three days after treatment all nine piglets were inoculated in both nostrils with a toxigenic type D strain of Pasteurella multocida. Three piglets were killed seven days after inoculation; one died spontaneously 13 days after inoculation and the remaining pigs were killed at approximately 90 kg body weight, i.e., five to six months of age. All acetic acid-treated animals developed severe atrophy of the turbinates in the treated nostrils. Untreated nostrils were normal. The present results showed that toxigenic P. multocida can induce turbinate atrophy that persisted until 90 kg body weight when the lesions were similar to spontaneous atrophic rhinitis in pigs. The turbinate atrophy was not accompanied by inflammatory reaction, atrophy of other bone structures, or lesions in other organs. The experiment showed furthermore that toxigenic P. multocida may be present in the tonsils of control animals without causing turbinate atrophy. A pathogenesis for atrophic rhinitis in pigs is proposed.

Acetates↗

Characterization of Pasteurella species isolated from lungs of calves with pneumonia.

During routine bacteriological examination of pneumonic calf lungs it was experienced that many Pasteurella multocida-like isolates had a fermentation pattern different from what is generally accepted for P. multocida sensu stricto. Forty-one out of 50 strains selected for further investigation were phenotypically related and formed a group of indole-, mannitol-and sorbitol-negative P. multocida-like strains, which was tentatively designated taxon 13. Deoxyribonucleic acid/deoxyribonucleic acid hybridizations including both ornithine positive and ornithine negative strains of taxon 13 allowed the classification of the former as P. multocida biovar 6 and the latter as V factor independent strains of Haemophilus avium.

Animals↗

The pathogenesis of atrophic rhinitis in pigs induced by toxigenic Pasteurella multocida.

The pathogenesis of atrophic rhinitis was studied in an experiment in which piglets were infected with a toxigenic type D Pasteurella multocida strain in the right half of the nasal cavity. Two days before inoculation the nasal mucosa on the right side had been subjected to mild irritation by intranasal instillation of a weak solution of acetic acid. The untreated (left) half of the nasal cavity served as an intrinsic control. Macroscopically, changes in the turbinates were already appreciable at 3 days p.i., and pronounced turbinate atrophy was noted at 7 days p.i. At 14 days p.i. deviation of the snout and almost complete turbinate atrophy was observed. The turbinates in the untreated half of the nasal cavity developed normally. Histologically, the changes were initially characterized by bone resorption mediated by an increased number of osteoclasts. Later osteoclasts were sparse, and there was an apparent disruption of osteoid synthesis. Ultrastructurally, the osteoblasts showed nuclear indentations and dilatation of the endoplasmic reticulum. Since no inflammatory reaction was observed, the hypothesis is advanced that atrophic rhinitis in pigs is caused by a P. multocida-produced factor which will stimulate bone resorption and suppress osteoid synthesis.

Animals↗

The bacteriology of endocarditis in slaughter pigs.

Streptococcus suis was isolated from 11 (10 per cent) out of 107 cases of endocarditis in slaughter pigs from which bacteria of any kind were isolated. Seven of the isolates belonged to the capsular serotypes 1, 2 and 1/2. Four were non-typable owing to lack of capsule. The organism isolated most often was Erysipelothrix rhusiopathiae, which was found in 68 (64 per cent) cases.

Animals↗

Serology of capsulated streptococci pathogenic for pigs: six new serotypes of Streptococcus suis.

A total of 138 capsulated strains of streptococci were isolated from pigs with various infections, notably septicemia and bronchopneumonia. Biochemically all strains were similar, and 31 strains were serologically identical to the previously described groups R, S, and RS streptococci, provisionally designated Streptococcus suis types 1, 2, and 1/2 by Elliot. The remaining 107 strains could be divided into six new capsular serotypes of S. suis.

Animals↗