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Biomedical subjects

I Walter

Publications and source records attributed to I Walter.

At least 19 recordsLinked to original sources
PubMed2006

In vitro effects of meloxicam with or without doxorubicin on canine osteosarcoma cells.

Cyclooxygenase (COX) inhibitors, already widely used to reduce fever, inflammation and pain, are under increasing consideration as potential agents for the prevention and treatment of neoplasia. As COX-2 was detected in human and canine osteosarcomas, we have evaluated the effect of the preferential COX-2 inhibitor meloxicam on an established D-17 canine osteosarcoma cell line, which expressed, as well as COX-1 and COX-2 also COX-3 (as demonstrated by Western blot). An XTT proliferation kit was used to assess surviving cells after drug treatment. At low concentrations (1, 2, 4 and 10 microm) meloxicam caused an increase in cell numbers while a marked anti-proliferative effect was observed at higher concentrations (100, 200 microm) after 3 days and also 3 weeks of incubation. The chemotherapeutic drug doxorubicin showed a cytotoxic effect at all concentrations (60-1920 nm). Exposure of tumour cells to combinations of meloxicam and doxorubicin revealed synergistic effects (with 240 nm doxorubicin), as well as sub-additive and antagonistic results, especially if combined with concentrations of meloxicam typically found in serum. Care should be taken in concluding, on the basis of one in vitro study, that meloxicam does not have a role in the treatment of canine osteosarcomas given that the results from in vivo studies may differ.

Animals↗
PubMed2006

Histological aspects of the syrinx of the male mallard (Anas platyrhynchos).

The syrinx of the duck is characterized by a conspicious sexual dimorphism. In the male mallard, a large osseous bulla is present on the left syringeal side. The present work describes the structures of the male syrinx, which were studied by means of histochemistry, immunohistochemistry and electron microscope. In the right distal tympanum a caudally oriented, protruding structure was observed, which was identified as the valvula syringealis. The syringeal structures like valvula, tympanum, bulla, pessulus and the bronchi were in general covered by a respiratory epithelium, however, local modifications in cellular height and numbers of ciliated and goblet cells were observed. The presence of intrinsic musculature was confirmed by means of immunohistochemistry. Smooth muscle cells reaching from the lateral parts of the inter-bronchial ligament to the medial line and cranially to the inner tympaniform membranes were demonstrated. We suppose that these muscle cells play a role in syringeal sound generation by influencing the tension of the medial tympaniform membranes.

Animals↗
PubMed2006

Interleukin-1alpha protein secretion in breast cancer is associated with poor differentiation and estrogen receptor alpha negativity.

While interleukins (IL)-1alpha and beta are thought to play an important role in malignant disease, little is still known about their expression in breast cancer. We have used reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry (IHC) to analyze the expression of IL-1alpha and beta in breast cancer tissues, and compared their expression to estrogen receptor (ER) status and grading. In breast cancer cell lines, we found an inverse correlation between IL-1alpha and beta gene expression and differentiation, and only one highly invasive tumor cell line expressed IL-1alpha protein, while IL-beta was not detectable. Breast cancer tissue expressed variable amounts of IL-1alpha and beta messenger RNA, but consistently high levels of IL-1 type I receptor. IL-1alpha protein was detectable in malignant epithelium and adjacent stroma in 88% of cases. IL-1alpha expression was correlated with poor differentiation (P= 0.002; r= 0.469) and decreasing ERalpha expression (P= 0.004; r=-0.387). Stromal IL-1alpha was confined to areas with low or absent ERalpha protein expression in adjacent tumor epithelium (P= 0.001; r=-0.457). Taken together, we have demonstrated a functional IL-1 system in breast cancer and observed an inverse correlation between IL-1alpha and sex steroid receptor expression. We suggest that the expression of IL-1alpha in poorly differentiated, ERalpha-negative tumors contributes to their malignant phenotype.

Breast Neoplasms↗
PubMed2005

Heavy metal speciation and phytotoxic effects of three representative sewage sludges for agricultural uses.

The environmental impact of sewage sludges depends on the availability and phytotoxicity of their heavy metal. The influence of representative sludges (dewatered anaerobic, pelletization, and composted sludge) on the availability of heavy metals, and their effects on seed germination were compared. The total heavy metal concentrations were below the maximum permitted for land-applied waste and the differences among them were small. The DTPA-extracted metal concentrations were rather different. The sequential extraction of the compost showed a slight increase in Cd and Cu availability, and a decrease in the availability of Fe, Mn, Ni and Zn. Pelletization increased the availability of Ni and slightly reduced that of Cr. The dewatering sludge led to greater availability of Cr and Mn but reduced the concentration of Cd. The three different sludges also affected seed germination and root elongation in different ways. The most serious adverse effects were caused by the dewatered sludge extract.

Agriculture↗
PubMed2005

Localization of matrix metalloproteinases, (MMPs) their tissue inhibitors, and vascular endothelial growth factor (VEGF) in growth plates of children and adolescents indicates a role for MMPs in human postnatal growth and skeletal maturation.

Numerous studies have focused on the expression, regulation, and biological significance of matrix metalloproteinases (MMPs) in the growth plate. Findings in mouse knockout models and in vitro data from various species indicate that MMPs not only degrade extracellular matrix components but may regulate the activity of local growth factors. In this study we investigated the presence, distribution, and activity of various MMPs and inhibitors, tissue transglutaminase (tTG or TG2) and vascular endothelial growth factor (VEGF) in the human child and adolescent growth plates by means of immunohistochemistry and gelatin zymography. Tissue was derived during orthopedic surgery (epiphysiodesis) in two prepubertal and four pubertal patients.MMP-2 and MMP-14 were present in reserve cell chondrocytes. MMP-14 was the most prominent MMP within all zones of the growth plate including proliferating chondrocytes. MMP-1 and MMP-13 (collagenases 1 and 3), MMP-9 (gelatinases B), MMP-10, and MMP-11 (stromelysins) and VEGF were positive in hypertrophic chondrocytes and osteoblasts. MMP-2 showed the same expression pattern but was negative in osteoblasts. Osteoclasts stained positive for MMP-9, MMP-2, and TG2. Tissue inhibitor of MMP (TIMP)-1 was present in all zones of the growth plate, osteoblasts, and osteoclasts; TIMP-2 was found in hypertrophic chondrocytes and osteoblasts. In summary, the presence of MMPs, TIMPs, TG2, and VEGF in our study indicated that the MMPs are relevant in growth plate physiology during the postnatal period in humans. The specific location of MMP expression within the growth plate may be the basis for further studies on the role of MMPs in the local regulation of chondrocyte differentiation, proliferation, and ossification at the chondroosseus junction.

Adolescent↗
PubMed2005

Extracellular matrix components and matrix degrading enzymes in the feline placenta during gestation.

In the endotheliochorial placenta of the cat, the maternal surface epithelium and parts of the connective tissue have to be removed to bring the fetal blood vessels in close contact to the maternal capillaries. The composition of the extracellular matrix (ECM) in the feline uterus is not known and it is still not clear if and which parts of the maternal ECM persist during gestation in the placental labyrinth. We demonstrated various extracellular matrix components (collagen types I, III, IV, and laminin) and matrix metalloproteinases (MMP-1, -2, -13) using immunohistochemistry and studied the distribution of intermediate filaments (vimentin, cytokeratin) and alpha-smooth muscle actin (SMA) in the placental girdle on specimens of different stages of gestation. Collagen types I and III were mainly present in the fetal chorionic lamellae whereas diminished in the maternal placental labyrinth part. Collagen IV and laminin were expressed in fetal basement membranes and mesenchyme. Maternal endothelial cells and stromal cells showed a positive immunoreaction for anti-collagen type IV and laminin. MMP-2 was identified in the maternal stroma, including decidual cells. Endothelia of maternal blood vessels within the labyrinth contained MMP-1, -2 and -13, probably associated with angiogenesis. In the trophoblast MMP-1 and -13 were demonstrated. Maternal stem vessels were accompanied by a thick layer of syncytiotrophoblast. Around these vessels, collagen type I and SMA were present in a periendothelial region between the endothelium and the trophoblast. These findings indicate that a strictly regulated balance between ECM deposition and ECM degradation in the feline placental labyrinth is necessary for proper placental development and function.

Animals↗
PubMed2005

Interleukin 1alpha and tissue-lytic matrix metalloproteinase-1 are elevated in ectopic endometrium of patients with endometriosis.

BACKGROUND: Matrix metalloproteinases (MMP) play an essential role in tissue remodelling and menstruation and appear to be regulated by cytokines such as interleukin-1alpha (IL-1alpha). In order to investigate their role in the pathogenesis of endometriosis, the aim of the present study was to compare the protein localization of matrix metalloproteinase-1 (MMP-1) and of its main stimulatory cytokine IL-1alpha in eutopic and dystopic endometrium of patients with endometriosis. METHODS: MMP-1 and IL-1alpha protein localization was analysed retrospectively in paired paraffin-embedded tissue biopsies obtained simultaneously from the endometrial cavity and from endometrial lesions of 37 patients with peritoneal or ovarian endometriosis and in cycling endometria from 37 women without endometriosis. Protein localization was demonstrated by immunohistochemistry; antibody specificity was confirmed by western blot analysis. RESULTS: MMP-1 and IL-1alpha protein staining in women suffering from endometriosis was significantly more pronounced in endometriotic lesions than in eutopic endometrium. This held true for both epithelial MMP-1 and IL-1alpha staining (P < 0.006 and P < 0.001), and for stromal MMP-1 and IL-1alpha staining (P < 0.001 and P < 0.001). Furthermore, stromal MMP-1 and IL-1alpha were significantly co-expressed in dystopic endometriotic tissue (P = 0.045). Endometrial MMP-1 and IL-1alpha protein expression pattern in eutopic endometrium from women suffering from endometriosis, however, did not differ significantly from the pattern seen in healthy women. CONCLUSIONS: The increased expression of both matrix-degrading MMP-1 and its major stimulatory cytokine IL-1alpha in endometriotic lesions and the selective co-expression in the stroma of endometriotic foci clearly suggests their involvement in the pathogenic mechanisms leading to local invasion and tissue destruction.

Adult↗
PubMed2005

Ligula intestinalis infection as a potential source of bias in the bioindication of endocrine disruption in the European chub Leuciscus cephalus.

European chub Leuciscus cephalus collected from five localities in the lowland and subalpine regions of Austria were analysed for oestrogenic effects of endocrine-disrupting chemicals and the presence of the plerocercoid of the tapeworm Ligula intestinalis. Of 1494 chub analysed, only seven (six males, one female) were found to be infected with single, but large plerocercoids up to 15 cm in length. Ligula-infected fish showed comparatively immature gonads, as demonstrated by the gonadosomatic index and gamete developmental stages. Plasma levels of the egg precursor protein vitellogenin also showed concentrations ranging below the detection limit. The present results indicate that chub infected with L. intestinalis and exposed to exogenous oestrogenic compounds can result in reduced gonadal maturation and produce false oestrogen-positive diagnoses in male fish. For plasma vitellogenin levels, L. intestinalis infections can result in false oestrogen-negative diagnoses in male and female fish.

Animals↗
PubMed2005

Matrix metalloproteinase 2 (MMP-2) and tissue transglutaminase (TG 2) are expressed in periglandular fibrosis in horse mares with endometrosis.

Periglandular arrangement of myofibroblasts, associated with the deposition of extracellular matrix (ECM), is a cardinal feature of endometrosis in mares. We hypothesized that a disturbance in the expression of matrix degrading enzymes such as matrix metalloproteinases (MMP's) and matrix cross-linking proteins might lead to an imbalance in deposition and degradation of extracellular matrix components and thereby accentuate degeneration. Therefore, distributions of MMP-2, capable of collagen IV and laminin degradation, and tissue transglutaminase (TG2), a cross-linker of extracellular matrix proteins, were investigated by means of immunohistochemistry on uterine biopsies of healthy mares and animals with endometrosis. It was illustrated that both proteins were present in fibrotic regions of affected endometria, and that they were in most cases colocalized. Periglandular MMP-2 expression was significantly associated with dilated and fibrotic uterine glands. Furthermore, MMP-2 and TG 2 were demonstrated in the stratum compactum of healthy and endometrotic endometria. Gelatin zymography proved that active and inactive pro-form of MMP-2 were present in all examined samples with significantly higher amounts of total and active MMP-2 in affected endometria. TG 2-activity, determined by an in situ assay, was found in cases of severe periglandular fibrosis. We suggest that both enzymes play a major role in changes that occur in ECM homeostasis in endometrial fibrotic regions.

Animals↗
PubMed2004

Endocrine disrupters in the aquatic environment: the Austrian approach--ARCEM.

A consortium of Austrian scientists (ARCEM) carried out a multidisciplinary environmental study on Austrian surface and ground waters including chemical monitoring, bioindication, risk assessment and risk management for selected endocrine disrupters: 17beta-estradiol, estriol, estrone, 17alpha-ethinylestradiol, 4-nonylphenol, 4-nonylphenol ethoxylates (4-NP1EO, 4-NP2EO) and their degradation products, ocytlphenol, ocytlphenol ethoxylates (OP1EO, OP2EO) as well as bisphenol A. To obtain data representative for Austria, a material flow analysis served to select relevant compounds and water samples were collected monthly over one year at those sites routinely used in Austrian water quality control. The following results were obtained and conclusions drawn: 1. Chemical monitoring: As compared to other countries, relatively low levels of pollution with endocrine disrupters were detected. 2. Bioindication: In the surface waters under study, male fish showed significant signs of feminization and demasculinization (increased production of the egg-yolk protein and histological changes of the gonads. 3. Risk assessment: For humans, exposure via either drinking water abstraction (ground water) or fish consumption was considered. The exposure levels of the compounds under study were below those considered to result in human health risks. Likewise, for bisphenol A and octylphenols, there was no indication for risk posed upon the aquatic environment (fish). However, nonylphenol or 17alpha-ethinylestradiol exposure along with results of bioindication (2) suggest a borderline estrogenic activity in a considerable number of surface waters. Consequently the emissions of these substances into the surface waters affected have to be reduced. 4. Risk management: Waste water treatment experiments revealed a positive correlation between the removal rate of endocrine disrupters from the waste water and the sludge retention time in the treatment plants. These substances are removed to a higher extend at low loaded plants designed for nutrient removal than at plants that remove carbon and/or employ nitrification only. As to drinking water treatment, chlorine dioxide and ozone were found to eliminate all investigated substances, except nonylphenol ethoxylates. (For the complete study see: www.arcem.at)

Animals↗
PubMed2003

Mineralised deposits in the uterine glands of mares with chronic endometrial degeneration.

Chronic degenerative disease of the mare's endometrium is characterised by changes in the uterine glands, including cystic dilation, hyperplasia and periglandular fibrosis. Endometrial biopsies were taken from 23 mares with different grades of endometrial degeneration. Solid structures were identified within the lumina of the uterine glands and shown to be calcified by histochemical staining. Most of them were not homogenous but composed of a mixture of mineral and organic substances. Further examinations of these mineralised structures by immunohistochemical methods revealed the presence of the non-collagenous matrix proteins osteopontin, osteonectin and bone sialoprotein, which are known to be involved in calcification processes such as urolithiosis. Osteopontin and bone sialoprotein were identified within the calculi, frequently arranged in concentric layers. Osteonectin was the only matrix protein that was also present in the glandular epithelium. Osteocalcin was not found in either the calculi or the glandular epithelial cells.

Animals↗
PubMed2003

Modulation of DNA repair processes by arsenic and selenium compounds.

Nickel, cadmium, cobalt and arsenic compounds are well known carcinogens to humans and experimental animals. In addition to the induction of mainly oxidative DNA damage, they interfere with nucleotide and base excision repair (BER) at low, non-cytotoxic concentrations. In case of arsenic, an inactivation of DNA repair has also been observed for the trivalent and pentavalent methylated metabolites, with the strongest effects exerted by MMA(III) and DMA(III). As potential molecular targets, interactions with so-called zinc finger proteins involved in DNA repair and/or DNA damage signaling have been identified. For example, arsenite suppresses poly(ADP-ribosyl)ation at extremely low, environmentally relevant concentrations. Also, Fpg and XPA involved in BER and NER, respectively, are inactivated by arsenite, MMA(III) and DMA(III). Nevertheless, an interaction with the zinc finger structures of DNA repair proteins may also occur by essential trace elements such as certain selenium compounds, which appear to exert anticarcinogenic properties at low concentrations but may compromise genetic stability at higher concentrations.

Animals↗
PubMed2003

Morphological changes of the endometrial epithelium in the bitch during metoestrus and anoestrus.

Although cyclic changes of the endometrium in dogs involving both stromal and glandular compartments have been described, the fate of the surface epithelium after progressive growth and secretion is still unclear. In the present study, uteri of 43 healthy bitches in metoestrus and anoestrus were examined macroscopically and histologically. Tissue biopsies were taken from three different locations (cranial and middle parts of uterine horns and bifurcation). The stage of the oestrous cycle was determined by evaluation of progesterone and oestradiol levels in plasma hormone and was also confirmed clinically. Crypts formed in the luteal phase were covered with a columnar epithelium which gradually underwent fatty degeneration. In addition, the stromal part of the crypts disappeared and finally, in early anoestrus, epithelial sheaths desquamated and shed off into the uterine lumen. The surface epithelium was replaced by new cuboidal cells proliferating and migrating from the glandular openings. These findings were confirmed by oil red O staining and immunohistochemical detection of proliferation with Ki-67 marker.

Anestrus↗
PubMed2003

Lectin binding patterns in normal canine endometrium and in bitches with pyometra and cystic endometrial hyperplasia.

Cystic endometrial hyperplasia (CEH) and pyometra in the bitch are dioestral syndromes, supposed to be caused by hormonal disturbances and changes in endometrial steroid hormone receptor levels. Histologically, the endometria show cystic dilated glands and, if bacteria succeed in invading the uterus, pyometra may develop in the following metoestrus. In this study, lectin histochemistry was performed on paraffin sections to compare carbohydrate expression of uterine glands and surface epithelium in healthy dogs and in dogs with CEH and pyometra. Lectin binding is a useful tool to identify glycoconjugates, especially of the glycocalyx, which has essential functions in the endometrium during reproduction. Uterine tissue was obtained from 18 healthy bitches in metoestrus or anoestrus and 18 bitches with a clinical diagnosis of CEH or pyometra. Normal endometria showed cycle-dependent changes in SBA, PNA, HPA and UEA binding during metoestrus and anoestrus. LCA did not show cycle-dependent changes and WGA bound to Golgi regions in the apical parts of surface epithelial cells only in metoestrous. Endometria with inflammatory alterations lost cycle-specific lectin binding patterns and, with increasing severity of pathological changes, showed a marked decrease in binding intensity to the glandular and surface epithelial glycocalyx and secretions. In dogs with CEH, unaltered glands with generally strong lectin binding to the glycocoalyx and Golgi regions were found adjacent to altered glands. The decrease of lectin binding in pyometra cases is supposed to be a result of glandular exhaustion after cystic hyperplasia. In addition, bacterial adhesion to sugar residues on the uterine surface epithelium might impede lectin binding.

Animals↗
PubMed2002

Interleukin-1 system and sex steroid receptor gene expression in human endometrial cancer.

OBJECTIVES: The interleukin-1 system is known to play a pivotal role in human physiology and reproduction. In the cycling endometrium, interleukin-1alpha activity is controlled by sex steroids and is confined to the perimenstrual phase, where it is involved in the events leading to tissue lysis and menstruation. Since local tissue degradation is also a feature of malignant tumors, our goal was to analyze the gene expression of interleukin-1alpha and other interleukin-1 family members and compare it with estrogen receptor alpha, estrogen receptor beta, and progesterone receptor mRNA expression in 27 endometrial carcinomas and 13 normal endometria. METHODS: Endometrial tumor tissues were obtained during hysterectomy for endometrial cancer, and normal endometrium was sampled in women undergoing surgical procedures for nonendometrial pathologies. Gene expression was analyzed by reverse transcription polymerase chain reaction. Protein expression was detected and localized by immunohistochemical staining. RESULTS: A strong gene expression of interleukin-1 type I receptor, estrogen recptor alpha, and progesterone receptor was detected in all tumor tissues and in the majority of benign endometrial tissues. However, in contrast to nonmalignant endometria, variable amounts of interleukin-1beta and interleukin-1 receptor antagonist mRNA were also detected in most of the tumor samples. Gene expression of interleukin-1alpha and estrogen receptor beta was considerably less frequent, with interleukin-1alpha being absent in all peri- and postmenopausal endometria and in all but one of the well-differentiated tumors. With decreasing differentiation interleukin-1alpha gene expression became more frequent. In these cases, interleukin-1alpha protein was detected predominantly in epithelial tumor cells of lower-grade tumors. CONCLUSION: We have demonstrated the presence of the interleukin-1 system in endometrial malignancies, and found a negative correlation between interleukin-1alpha and tumor differentiation. We hypothesize that the nonphysiological expression of interleukin-1alpha in less differentiated tumors might contribute to their invasiveness and malignant behavior.

Carcinoma, Endometrioid↗
PubMed2002

Composting of fish offal and biosolids in northwestern Patagonia.

Composting of fish processing wastes and biosolids with wood by-products and yard trimmings was conducted during the summer of 1996 and winter of 1997 in NW Patagonia using: (i) static piles for fish offal and (ii) turning piles for biosolids. Fish offal was mixed with sawdust + wood shavings (FOC) at 3:1 ratio by weight and biosolids with wood shavings (BCw) and yard trimmings (BCt) at 1:1 ratio by volume. Samples were taken at six dates during the composting period and analyzed to determine the factors that predict compost maturity. Composting of biosolids was affected by the type of bulking agent during winter. Thermophilic temperatures > or = 55 degrees C were sustained long enough to satisfy the USEPA requirements for processes to further reduce pathogens (PFRP) in FOC and BCt, and for processes to significantly reduce pathogens (PSRP) in summer BCw, while in winter BCw temperatures were lower than those recommended for effective pathogen reduction. However, coliform fecal content in all BC treatments was less than 10 most probable number (MPN) g(-1) dry sample at the end of the process. The ratio of water soluble carbon (WSC) to total nitrogen (TN) appeared to be a more adequate index to predict compost maturity than the ratio of total organic carbon to nitrogen.

Animals↗
PubMed2001

Cetaben-induced changes on the morphology and peroxisomal enzymes in MH1C1 rat hepatoma cells and HepG2 human hepatoblastoma cells.

Human HepG2 and rat MH1C1 hepatoma cell lines were examined for their response to cetaben, an exceptional type of peroxisome proliferator. Shape change and proliferation of peroxisomes as well as induction of selected peroxisomal enzymes catalase, acyl-CoA oxidase, and peroxisomal bifunctional enzyme, were assessed in response to cetaben. In MH1C1 cells, peroxisomes were seen in clusters displaying typical features of microperoxisomes. Cetaben caused little but reversible proliferation and morphological heterogeneity with the occurrence of dumbbell-shaped and cup-shaped peroxisomal profiles. Peroxisomes in HepG2 cells showed marked variation in size and shape. Cetaben treatment of HepG2 cells caused disintegration of Golgi regions and augmented mitochondrial matrix. Interestingly, MH1C1 cells showed different subunit composition of acyl-CoA oxidase in immunoblot analysis: only subunit A at 72 kDa was detected but not the cleavage products. In situ hybridization underlined the marked morphological heterogeneity observed, and both cell lines revealed different stages of gene expression. Our results indicate that cetaben represents an extraordinary type of peroxisomal proliferator with pleiotropic effects on human and rat hepatoma cells, and, at least in the human hepatoma cell line HepG2, these effects are not restricted to peroxisome proliferation.

4-Aminobenzoic Acid↗