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Biomedical subjects

M Wagner

Publications and source records attributed to M Wagner.

At least 289 records · Page 16Linked to original sources
PubMed1999

Identification of some of the major groups of bacteria in efficient and nonefficient biological phosphorus removal activated sludge systems.

To investigate the bacteria that are important to phosphorus (P) removal in activated sludge, microbial populations were analyzed during the operation of a laboratory-scale reactor with various P removal performances. The bacterial population structure, analyzed by fluorescence in situ hybridization (FISH) with oligonucleotides probes complementary to regions of the 16S and 23S rRNAs, was associated with the P removal performance of the reactor. At one stage of the reactor operation, chemical characterization revealed that extremely poor P removal was occurring. However, like in typical P-removing sludges, complete anaerobic uptake of the carbon substrate occurred. Bacteria inhibiting P removal overwhelmed the reactor, and according to FISH, bacteria of the beta subclass of the class Proteobacteria other than beta-1 or beta-2 were dominant in the sludge (58% of the population). Changes made to the operation of the reactor led to the development of a biomass population with an extremely good P removal capacity. The biochemical transformations observed in this sludge were characteristic of typical P-removing activated sludge. The microbial population analysis of the P-removing sludge indicated that bacteria of the beta-2 subclass of the class Proteobacteria and actinobacteria were dominant (55 and 35%, respectively), therefore implicating bacteria from these groups in high-performance P removal. The changes in operation that led to the improved performance of the reactor included allowing the pH to rise during the anaerobic period, which promoted anaerobic phosphate release and possibly caused selection against non-phosphate-removing bacteria.

Bacteria↗
PubMed1999

On the occurrence of anoxic microniches, denitrification, and sulfate reduction in aerated activated sludge.

A combination of different methods was applied to investigate the occurrence of anaerobic processes in aerated activated sludge. Microsensor measurements (O(2), NO(2)(-), NO(3)(-), and H(2)S) were performed on single sludge flocs to detect anoxic niches, nitrate reduction, or sulfate reduction on a microscale. Incubations of activated sludge with (15)NO(3)(-) and (35)SO(4)(2-) were used to determine denitrification and sulfate reduction rates on a batch scale. In four of six investigated sludges, no anoxic zones developed during aeration, and consequently denitrification rates were very low. However, in two sludges anoxia in flocs coincided with significant denitrification rates. Sulfate reduction could not be detected in any sludge in either the microsensor or the batch investigation, not even under short-term anoxic conditions. In contrast, the presence of sulfate-reducing bacteria was shown by fluorescence in situ hybridization with 16S rRNA-targeted oligonucleotide probes and by PCR-based detection of genes coding for the dissimilatory sulfite reductase. A possible explanation for the absence of anoxia even in most of the larger flocs might be that oxygen transport is not only diffusional but enhanced by advection, i.e., facilitated by flow through pores and channels. This possibility is suggested by the irregularity of some oxygen profiles and by confocal laser scanning microscopy of the three-dimensional floc structures, which showed that flocs from the two sludges in which anoxic zones were found were apparently denser than flocs from the other sludges.

Anaerobiosis↗
PubMed1999

Systematic excision of vector sequences from the BAC-cloned herpesvirus genome during virus reconstitution.

Recently the mouse cytomegalovirus (MCMV) genome was cloned as an infectious bacterial artificial chromosome (BAC) (M. Messerle, I. Crnkovic, W. Hammerschmidt, H. Ziegler, and U. H. Koszinowski, Proc. Natl. Acad. Sci. USA 94:14759-14763, 1997). The virus obtained from this construct is attenuated in vivo due to deletion of viral sequences and insertion of the BAC vector. We reconstituted the full-length MCMV genome and flanked the BAC vector with identical viral sequences. This new construct represents a versatile basis for construction of MCMV mutants since virus generated from the construct loses the bacterial sequences and acquires wild-type properties.

Animals↗
PubMed1999

Induction of TFF1 gene expression in pancreas overexpressing transforming growth factor alpha.

BACKGROUND/AIMS: Chronic pancreatitis is an inflammatory disease of the exocrine pancreas associated with extensive fibrosis, enlarged pancreatic ducts, acinar cell degeneration, and the formation of tubular complexes. The molecular and biochemical alterations associated with these histological changes are not kown. Generally, the new family of TFF peptides (formerly known as P-domain peptides or trefoil factors) is aberrantly expressed during chronic inflammatory diseases of the gastrointestinal tract. METHODS: Using human pancreatic tissues obtained from patients with chronic pancreatitis and murine pancreatic tissues obtained from transgenic mice overexpressing transforming growth factor alpha (TGF-alpha), the expression and cellular distribution of TFF1 was analysed using northern blot analysis, polymerase chain reaction (PCR), and immunohistochemistry. RESULTS: In the normal human pancreas, TFF1 was scarce, with only a few ducts exhibiting cytoplasmic TFF1 immunoreactivity. In contrast, human chronic pancreatitis tissue specimens exhibited strong TFF1 immunoreactivity in ductal cells, areas of ductal hyperplasia, and tubular complexes. Semiquantitative PCR analysis of TFF1 mRNA levels showed enhanced expression of TFF1 in the pancreas of patients with chronic pancreatitis. Furthermore, TFF1 mRNA levels were detectable in the pancreas in four of five transgenic mice overexpressing TGF-alpha. In contrast, four of five wild type mice did not exhibit a TFF1 mRNA transcript. In addition, while no specific TFF1 immunoreactivity was present in the pancreas of the wild type mice, ductal epithelial cells and duct-like tubular complexes in the pancreas of the transgenic mice overexpressing TGF-alpha exhibited pronounced TFF1 immunoreactivity. CONCLUSIONS: Ductal cells and tubular complexes in pancreatic fibrosis express TFF1. As the 5'-flanking region of TFF1 contains an epidermal growth factor responsive enhancer region and the expression of epidermal growth factor and TGF-alpha is enhanced in pancreatic fibrosis, the enhanced expression of TFF1 in pancreatic fibrosis may be mediated by TGF-alpha.

Adolescent↗
PubMed1999

Caerulein-induced NF-kappaB/Rel activation requires both Ca2+ and protein kinase C as messengers.

The eukaryotic transcription factor NF-kappaB/Rel is activated by a large variety of stimuli. We have recently shown that NF-kappaB/Rel is induced during the course of caerulein pancreatitis. Here, we show that activation of NF-kappaB/Rel by caerulein, a CCK analog, requires increasing intracellular Ca2+ levels and protein kinase C activation. Caerulein induces a dose-dependent increase of nuclear NF-kappaB/Rel binding activity in pancreatic lobules, which is paralleled by degradation of IkappaBalpha. IkappaBbeta was only slightly affected by caerulein treatment. Consistent with an involvement of Ca2+, the endoplasmic reticulum-resident Ca2+-ATPase inhibitor thapsigargin activated NF-kappaB/Rel in pancreatic lobules. The intracellular Ca2+ chelator TMB-8 prevented IkappaBalpha degradation and subsequent nuclear translocation of NF-kappaB/Rel induced by caerulein. BAPTA-AM was less effective. Cyclosporin A, a Ca2+/calmodulin-dependent protein phosphatase (PP2B) inhibitor, decreased caerulein-induced NF-kappaB/Rel activation and IkappaBalpha degradation. The inhibitory effect of bisindolylmaleimide suggests that protein kinase C activity is also required for caerulein-induced NF-kappaB/Rel activation. These data suggest that Ca2+- as well as protein kinase C-dependent mechanisms are required for caerulein-induced NF-kappaB/Rel activation.

Animals↗
PubMed1999

Induction of stress proteins in human endothelial cells by heavy metal ions and heat shock.

In the present study, we compared the induction of heat shock proteins (HSPs) by heat and heavy metal ions in three different endothelial cell types, namely, human umbilical vein endothelial cells, human pulmonary microvascular endothelial cells, and the cell line EA.hy 926. Our results show that especially Zn(2+) and Cd(2+) are inducers of 70-kDa (HSP70), 60-kDa (HSP60), 32-kDa (HSP32), and 27-kDa (HSP27) HSPs. The strength of inducibility is specific for each HSP. Ni(2+) and Co(2+) only show an inducible effect at very high concentrations, that is, in the clearly cytotoxic range. Furthermore, we investigated the time course of HSP expression and the involvement of heat shock factor-1. Our study demonstrates that the three endothelial cell types that were under investigation show comparable stress protein expression when treated with heavy metal ions or heat shock. The expression of stress proteins may be used as an early marker for the toxic damage of cells. This damage can be an inducer of acute respiratory distress syndrome in which microvascular endothelial lesions occur early. Our study provides evidence that human umbilical vein endothelial cells or EA.hy 926 cells, which are much more easily isolated and/or cultivated than pulmonary microvascular endothelial cells, could be used as alternative cell culture systems for studies on cellular dysfunction in the lung caused by toxic substances, certainly with respect to the expression of HSPs.

Blotting, Western↗
PubMed1999

Technical aspects of left-sided pancreatic resection for cancer.

Adenocarcinoma of the pancreas that originates to the left of the portal vein, i.e. in the body or tail of the pancreas, is seen in approximately one third of all cases with exocrine pancreatic cancer. Except for symptoms of pain and weight loss, these patients usually appear normal upon physical examination. In 5-10% of cases, the tumor is resectable by standard surgical procedures. Unresectability is due to local spread (30-40%) or distant metastases (50-65%). The technique of distal pancreatic resection was outlined by Mayo in 1913. The intimate relationship of the splenic artery and vein to the body of the pancreas makes en bloc mobilization of the spleen and pancreatic tail a safe option; the splenic artery and vein being ligated near their origin and termination. Although the spleen can frequently be preserved when performing a distal pancreatectomy for benign disease, splenic artery preservation is hazardous for oncologic radicality when resection is performed for cancer. Therefore, splenectomy is routine in distal pancreatectomy - in Mayo's and all subsequent descriptions - with the splenic artery being ligated early in the procedure. Recent reports from specialized centers indicate that the procedure is associated with a decrease in mortality rate, often zero or less than a few percent.

Adenocarcinoma↗
PubMed1999

Intrapancreatic accessory spleen. A rare cause of a pancreatic mass.

CONCLUSION: The clinical significance of intrapancreatic accessory spleens resides in the mimicry of pancreatic cancer. Radionuclide tests (Octreotide scan and Tc99m sulfur colloid scan) should be undertaken to distinguish these lesions from neuroendocrine tumors, hypervascular metastases and pancreatic carcinoma. If the tests are equivocal, diagnostic laparotomy or laparoscopy is recommended. BACKGROUND: Despite its relatively common occurrence, intrapancreatic ectopic splenic tissue is rarely detected owing to its asymptomatic nature. METHODS: We report a case of a clinically asymptomatic patient in which abdominal computed tomography (CT) scans revealed a mass of 1.5 cm in diameter in the distal pancreas. The tumor markers CA 19-9 and carcinoembryonic antigen (CEA) were slightly elevated, and pancreatic neoplasm was suspected. RESULTS: Left pancreatic resection and splenectomy were performed. The removed specimen disclosed the presence of an accessory spleen within the pancreatic tail.

Aged↗
PubMed1999

Event-related potential correlates of proactive interference in schizophrenic patients and controls.

Performance and event-related potentials (ERPs) were examined in a proactive interference (PI) task with 15 male schizophrenic patients and 15 matched healthy controls. Within a paired-associate task, 30 pairs of semantically unrelated words (A-B) were presented twice, followed by cued recall, in which the paired-associate B had to be named upon cue A. Subsequently, 50% of the A-words were paired with new words (A-C) and presented in random order together with 15 novel pairings (D-E). Slower responses and poorer recall of C- than of E-words in the final recall indicated PI in both groups. During acquisition, the paired-associates (C/E) evoked larger P3 and positive slow wave in controls than in patients. During recall, cues (A/D) evoked a slow wave with predominating anterior negativity in controls and posterior positivity in patients. The group-specific ERP pattern suggests deviant encoding and retrieval processes in schizophrenic individuals.

Adult↗
PubMed1999

Standard surgical treatment in pancreatic cancer.

Pancreatic cancer is the third leading neoplasm of the gastrointestinal system and has a dismal prognosis. The majority of patients are no more suitable for resection at time of diagnosis due to early development of distant metastases or major infiltrations of adjacent structures. However, due to the resistance of pancreatic cancers against chemoradiation, curative resection represents the only therapy with a potential for cure. For the surgical treatment of pancreatic head cancer, the classical Whipple operation is still the standard procedure but during the last two decades, pylorus-preserving duodenopancreatectomy has been evolved as a more conservative procedure in order to omit the consequences of partial gastrectomy. For cancer of the pancreatic body and tail, distal pancreatectomy or total pancreatectomy represent the current standard treatment. More radical methods like regional pancreatectomy and resection with extended lymph node dissection have failed so far to demonstrate any improvements in long-term survival compared to the standard types of resection. To further improve the treatment of pancreatic cancer, prospectively randomised trials are needed to compare these extended surgical procedures with the standard types of resection.

Humans↗
PubMed1999

Mechanism-based PK/PD model for the lymphocytopenia induced by endogenous and exogenous corticosteroids.

OBJECTIVE: Lymphocytopenia is a sensitive surrogate marker for the immunological effects of corticosteroids. This pharmacokinetic/pharmacodynamic (PK/PD) study investigated whether the circadian variation of blood lymphocytes observed after placebo is secondary to the circadian rhythm of endogenous cortisol, and developed based on this relationship an improved PK/PD model for a more sensitive description of the effect of low-dose corticosteroid therapy on blood lymphocytes considering the net activity of the exogenous corticosteroid budesonide and endogenous cortisol. METHODS: In an open, parallel study design, 3 mg oral budesonide or placebo were given at 8.00 a.m., 4.00 p.m. and midnight to two groups of 12 volunteers. Lymphocyte counts and serum concentrations of budesonide and cortisol were monitored for 24 hours. A mechanism-based PK/PD model which considered the non-linear protein binding of cortisol and the budesonide-induced cortisol suppression was employed to relate changes in blood lymphocytes to free cortisol levels after placebo and to the net activity of free budesonide and free endogenous cortisol after active treatment. RESULTS: The circadian rhythm of blood lymphocytes observed after placebo could inversely be related to the circadian rhythm of serum cortisol. After budesonide administration, lymphocyte counts could accurately be linked to the net activity of budesonide and endogenous cortisol. The resulting EC50 values for the effect of budesonide on cortisol, budesonide on lymphocytes and cortisol on lymphocytes were 0.063 +/- 0.034, 0.22 +/- 0.13 and 26.3 +/- 15.0 ng/ml (placebo group 15.4 +/- 3.4 ng/ml), respectively. CONCLUSIONS: The presented mechanism-based PK/PD model suggests that blood lymphocytes are under physiological control of cortisol. It further indicates that endogenous and exogenous corticosteroids and their pharmacological interaction need to be considered for modeling the effects of low doses of exogenous corticosteroids on the immune system.

Anti-Inflammatory Agents↗
PubMed1999

The principle of toxicopy and its integration into the administrative proceedings in Austria.

Toxicopy can be understood as an analogon to placebo but within any setting. Placebo is state-of-the-art since decades with relevant consequences: Only those effects may be considered as being pharmacon-specific, that go beyond non-pharmacological ("Placebo") effects. Placebo--theory is a limitation for the applicability of Morgans Canon (4), which is/was accepted within medicine like an axiom: When searching for the causes of disease physiological causes need to be ruled out, before other especially psychological etiologies can be taken into consideration. Toxicopy principle could be confirmed in different settings all over the world, in old and young, male and female, rich and poor and in different cultures. Therefore Morgans Cannon is falsified. Toxicopy principle is accepted as state-of-the-art and part of stand court rulings of the Austrian administrative tribunal. The plant law in Austria--and in Germany--provides for the protection of citizens against health hazards caused by plants, regardless of their etiologies. Therefore, non-toxicological threats must also be considered in plant approval proceedings in future.

Age Factors↗
PubMed1999

Misoprostol.

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Female↗
PubMed1998

Localization and regulation of the cdk-activating kinase (Cak1p) from budding yeast.

Eukaryotic cell cycles are controlled by the activities of cyclin-dependent kinases (cdks). The major cdk in budding yeast, Saccharomyces cerevisiae, is Cdc28p. Activation of Cdc28p requires phosphorylation on threonine 169 and binding to a cyclin. Thr-169 is phosphorylated by the cdk-activating kinase (CAK), Cak1p, which was recently identified as the physiological CAK in budding yeast. Here we present our further characterization of yeast Cak1p. We have found that Cak1p is dispersed throughout the cell as shown by immunofluorescence; biochemical subcellular fractionation confirmed that most of the Cak1p is found in the cytoplasm. Cak1p is a monomeric enzyme in crude yeast lysates. Mutagenesis of potential sites of activating phosphorylation had little effect on the activity of Cak1p in vitro or in vivo. Furthermore, Cak1p contains no posttranslational modifications detectable by two-dimensional isoelectric focusing. We found that Cak1p is a stable protein during exponential growth but that its expression decreases considerably when cells enter stationary phase. In contrast, Cak1p levels oscillate dramatically during meiosis, reflecting regulation at both the transcriptional and post-translational level. The localization and regulation of Cak1p are in contrast to those of the known vertebrate CAK, p40(MO15).

Amino Acid Sequence↗
PubMed1998

Mechanisms of cell activation by heavy metal ions.

Heavy metal ions can be released by corroding metallic implants into the surrounding tissue. When they enter blood vessels some of them are carried by proteins like albumin and can be taken up by endothelial cells lining the vessels. To study their involvement in the inflammatory response we investigated heavy metal ion induced effects in cultured human vascular endothelial cells (HUVECs). NiCl2 and CoCl2 upregulate, especially in concentrations of 1 mM, the expression of adhesion molecules (e.g., E-selectin and intercellular adhesion molecule-1), as well as the cytokines IL-6 and IL-8, as shown by enzyme immunoassay and Northern blot analysis. In addition, possible signal transduction mechanisms were elucidated. The HUVECs were treated with various selective inhibitory drugs followed by the incubation of metal ions before measuring the expression of the above-mentioned endothelial factors. Two protein kinase inhibitors (H-7 and H-8) strongly repressed Ni2+ and Co2+ enhanced expression, as did the phospholipase A2 inhibitor quinacrine. Other selective inhibitors of protein kinases C or A, or cGMP-dependent protein kinases, as well as calcium antagonists like 1,2-bis(2-aminophenoxy)ethan-N,N,N',N'-tetraacetic acid and 3,4,5-trimethoxybenzosaure 8-(diethylamino)-octylester and inhibitors of receptor mediated endocytosis (primary amines), had no influence. We showed that NiCl2 and CoCl2 activate the translocation of the transcription factor nuclear factor (NF)-kappaB into the cell nucleus and enhance its binding to a NF-kappaB consensus sequence as shown by mobility shift analysis. Furthermore, we demonstrated the activation of AP-1. Despite the repression of heavy metal induced adhesion molecule synthesis, we did not detect any inhibition of NF-kappaB translocation by H-7 or H-8. Therefore, it must be concluded that heavy metal ions like Ni2+ and Co2+ activate two or more signal transduction pathways in endothelial cells. We clearly showed that there is one pathway in which H-7 and H-8 sensitive protein kinases are involved and a second pathway leading to NF-kappaB activation, which is insensitive to H-7 and H-8. Our results demonstrate that heavy metal ions induce mechanisms of gene activation in endothelial cells as do proinflammatory mediators, indicating that corroding metal ion containing biomaterials can provoke inflammatory reactions by known, as well as by yet unknown, intracellular signaling pathways.

Base Sequence↗