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Biomedical subjects

S Wagner

Publications and source records attributed to S Wagner.

493 records · Page 28Linked to original sources

Cytoskeleton and epithelial polarity.

The membrane surface of polarized epithelial cells can be divided in apical and basolateral domains that differ in molecular composition and function. Components of the cytoskeleton are involved in critical steps of both generation and maintenance of cell polarity. Generation of polarity is controlled by microtubules that serve as uniformly aligned and polarized cytoplasmic guiding structures for the vectorial and selective transport of Golgi-derived carrier vesicles to the apical cell surface. Targeting of membrane proteins to the basolateral cell surface does not depend on microtubules but follows the constitutive bulk flow of membranes. Once inserted into the lipid bilayer several membrane proteins such as the kidney anion exchanger 1 (AE1) and the sodium pump become immobilized at specialized microdomains of the lateral cell surface. Evidence is provided that both membrane proteins are linked via ankyrin to the spectrin-based membrane cytoskeleton that underlies the basolateral membrane domain. Linkage of these and other integral membrane proteins to the cytoskeleton may not only place them to specialized sites of the plasma membrane but may also prevent these transporters from clustering and endocytosis, thus helping them to stay at the cell surface. In search of sequence motifs involved in binding of integral membrane proteins to components of the cytoskeleton we found that the binding interface of AE1 to protein 4.1 (an actin and spectrin cross-linking protein) consists of a cluster of five amino acid residues, namely IRRRY in AE1 and LEEDY on protein 4.1. This motif may play a more general role in cytoskeleton membrane linkages.

Amino Acid Sequence↗

Invitation to rural hospitals: lead efforts to fight impaired driving.

Those working in health care have long known the human and economic costs of injuries and deaths caused by impaired driving accidents. Researchers found that Michigan traffic crashes cost more than $12 billion in hospital bills, lost wages and property damages.

Accidents, Traffic↗

[Therapy of Helicobacter pylori infection: current status].

H. pylori is closely associated with gastritis, peptic ulcer disease and gastric cancer. A causative role of H. pylori is now established in type B gastritis, its role in non ulcer dyspepsia is unresolved. Eradication of H. pylori results in a marked decrease of peptic ulcer relapse rates. Gastric cancer risk is 2- to 8-fold increased if gastric mucosa is colonized by H. pylori. Treatment of H. pylori infection is difficult although the organism is highly sensitive to several antibiotics in vitro. Monotherapy with bismuth suppresses bacterial growth, but hardly ever eradicates the organism. Combination of amoxicillin with omeprazole may eradicate H. pylori in about 60-80% of patients and is well tolerated. Triple therapy (bismuth, amoxicillin, metronidazole) is the most effective treatment modality and results in eradication rates of 80% to 90%, however, side effects are noticed in 20%-30% of patients. Eradication of H. pylori should be considered under the following conditions: relapsing peptic ulcer, resistant peptic ulcer, break-through ulcer on maintenance treatment with H2-blockers, complicated ulcer. There is no indication for eradicating treatment in patients with simple H. pylori positive gastritis and NSAID-associated ulcer.

Anti-Bacterial Agents↗

Response of the germfree rat colonic mucosa to dietary endotoxins.

Suggestive to induce an immunoreactive response in the colon mucosa of germfree rats 3 diets, autoclaved or gamma-irradiated, respectively, were administered to groups of 30 days old GF Ztm:SPRD rats. Diets and rats were studied in parallel after a feeding period of 20 days. The microbiological controls confirmed the sterility of diets and animals. The aqueous suspensions of one diet displayed obviously dead yeast and Gram positive and negative bacteria, which consistently were evident in colonic cast preparations of animals fed with this diet. These findings apparently were not related to the pathohistological alterations, observed in hematoxilin-eosin stained colon sections. However, dietary endotoxin concentrations between 0.6 and 10 micrograms LPS/g corresponded with the endotoxin concentrations in feces (0.3 to 3.1 micrograms LPS/g wet weight) and in colonic tissue (0.01 to 0.6 microgram LPS/g wet weight). These endotoxins obviously mediated a dose-dependent immunoreactive response of the colonic mucosa: in parallel to the dietary endotoxin content, the cellular infiltrations ranged from single mononuclear cells to severe, cell mediated, mucosal alteration. GF rats, used as an experimental animal model for inflammatory disorders of the intestine obviously necessitate diets with low endotoxin concentrations.

Animals↗

Adjuvant therapy of renal cell carcinoma with active-specific-immunotherapy (ASI) using autologous tumor vaccine.

116 patients with renal cell carcinoma were treated with autologous tumor vaccine after radical nephrectomy. The survival rate of these patients compared to a historical control group of 106 patients from the same hospital, which received identical surgical treatment but no adjuvant therapy was evaluated. According to defined in- and exclusion criteria there was no statistical difference between the two groups. As a consequence any significant effects resulting from the treatment with autologous tumor vaccines have to be interpreted as clinically relevant in spite of the fact that no prospective randomised design was chosen. A clear significant difference (p = 0.0007) between both groups with a benefit for the group treated with autologous tumor vaccines was observed. According to the individual Robson stages patients in Robson II (p = 0.02) and Robson III (p = 0.04) showed significantly different survival rates. Due to the short follow-up time in the group Robson I and the limited number of patients in the group Robson IV no significant difference was observed. During adjuvant treatment with autologous tumor vaccine 2 patients out of 116 showed minor side effects not exceeding WHO-grade 1.

Cancer Vaccines↗

Guanidinobenzoatase and UPA in high-grade human astrocytomas and after xenografting cell suspensions into the rat cerebral cortex: proteases for metastasis and disease progression.

BACKGROUND: Invasion and metastasis is aided by the secretion of guanidinobenzoatase, that cleaves the link peptide to fibronectin, and urokinase plasminogen activator (uPA), which initiates a molecular cascade to activate plasmin and collagenases. This process permits malignant cell migration through the extracellular matrix. MATERIALS: Original human astrocytomas were examined for guanidinobenzoatase and uPA. Suspensions of high-grade human astrocytomas were xenografted into pockets in host cerebral cortex for 1-7 days. RESULTS: A class of guanidinobenzoatase positive cells was observed in the original human astrocytomas and in tumor masses formed in the implantation pocket and around blood vessels. Secondary foci containing guanidinobenzoatase positive cells formed around blood vessels and individual positive astrocytoma cells migrated on the glia limitans along parallel and intersecting nerve fiber fascicles and the corpus callosum. uPA and GFAP were colocalized with guanidinobenzoatase. CONCLUSION: The high-grade astrocytomas reestablish themselves and maintain their characteristics as a tissue although grafted as individual cells.

Animals↗