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Biomedical subjects

M Kuhn

Publications and source records attributed to M Kuhn.

264 records · Page 15Linked to original sources
PubMedDate not supplied

Molecular analysis of bacterial cytolysins.

Results of molecular and pathogenic studies of three different bacterial hemolysins (cytolysins) are presented. These exoproteins derive from the two gram-negative bacteria Escherichia coli and Aeromonas hydrophila and from the gram-positive pathogen Listeria monocytogenes. The hemolysin of E. coli is determined by an 8-kilobase (kb) region that includes four clustered genes (hlyC, hlyA, hlyB, and hlyD). This hemolysin determinant is part either of large transmissible plasmids or of the chromosome. The genes located chromosomally are found predominantly in E. coli strains that can cause pyelonephritis and/or other extraintestinal infections. A detailed analysis of the chromosomal hyl determinants of one nephropathogenic E. coli strain revealed the existence of specific, large chromosomal insertions 75 kb and 100 kb in size that carry the hly genes but that also influence the expression of other virulence properties, i.e., adhesion and serum resistance. The direct involvement of E. coli hemolysin in virulence could be demonstrated in several model systems. The genetic determinants for hemolysin (cytolysin) formation in A. hydrophila (aerolysin) and L. monocytogenes (listeriolysin) are less complex. Both cytolysins seem to be encoded by single genes, although two loci (aerB and aerC) that affect the expression and activity of aerolysin have been identified distal and proximal to the structural gene for aerolysin (aerA). Cytolysin-negative mutants of both bacteria were obtained by site-specific deletion and/or transposon mutagenesis. These mutants show a drastic reduction in the virulence of the respective bacteria.

Aeromonas↗
PubMedDate not supplied

Acidification of endosomes is not important for the entry of rotavirus into the cell.

Rotavirus causes enteritis in both man and animals. The mechanism by which this protein-enveloped virus enters the cell to initiate infection is not known. Many viruses depend on the acidification of endosomes for entry into the cell. We studied the importance of the acidification of endosomes for the initiation of two early phases of rotavirus infection, virus RNA and peptide synthesis. Monensin, nigericin, chloroquine and ammonium chloride at a variety of concentrations caused no specific inhibition of virus RNA or peptide synthesis. We conclude that the acidification of endosomes is not important for the entry of rotavirus into the cell.

Animals↗
PubMedDate not supplied

Cytokeratin expression patterns in the rat respiratory tract as markers of epithelial differentiation in inhalation toxicology. I. Determination of normal cytokeratin expression patterns in nose, larynx, trachea, and lung.

Cytokeratin (CK) polypeptides constitute the intermediate filament cytoskeleton of epithelial cells. The patterns of CK expression can be regarded as specific markers for the epithelial differentiation status. Our objective was to map the cell type-specific CK expression patterns at all representative sites of the respiratory tract of untreated rats to use as a base for the detection of inhalation exposure-related differentiation changes. Using routine paraffin-embedded sections and a panel of well-characterized monoclonal antibodies for immunohistochemistry, we obtained CK staining patterns as follows. Nasal cavity: respiratory epithelium CK18, CK19 (basal, ciliated, nonciliated cells), CK14, and/or CK15 (basal and nonciliated cells); olfactory epithelium CK18 (basal, mid, apical zones and Bowman's glands), CK14, and CK15 (basal zone); squamous epithelium of ventral meatus CK14, CK15 (basal and suprabasal cells), CK1, 10/11, and CK13 (suprabasal cells); glands and columnar epithelia of vomeronasal organ and nasolacrimal duct CK7 and CK13 in addition to respiratory epithelial CK pattern. Trachea: similar to nasal respiratory epithelium with pronounced CK15 and additional CK7. Larynx: CK14, CK15 (basal, ciliated, nonciliated cells), CK8, CK18, CK19 (not in basal cells), CK4, and CK13 (cuboidal and squamoid cells of ventral half). Lung: bronchial epithelium CK14 and CK15 (basal cells only); bronchial and alveolar epithelium CK7, CK8, CK18, and CK19; bronchiolar epithelium similar but less CK8 and no CK7; pleural mesothelium CK7, CK8, and CK19. This inventory of complex CK expression patterns provides the basis for investigating test substance-related effects in inhalation toxicology, e.g., cigarette smoke-induced changes.

Animals↗
PubMedDate not supplied

Cytokeratin expression patterns in the rat respiratory tract as markers of epithelial differentiation in inhalation toxicology. II. Changes in cytokeratin expression patterns following 8-day exposure to room-aged cigarette sidestream smoke.

The expression of specific cytokeratin (CK) polypeptide patterns is a sensitive marker of the cytoskeletal differentiation of epithelial cells. We developed an immunohistochemical method to assess CK expression patterns in the rat respiratory tract using serial paraffin-embedded sections from the nasal cavity, trachea, and lung. In the present study, this method was used to detect exposure-related differences in CK expression patterns in adult Wistar rats following inhalation of room-aged sidestream smoke (11 mg total particulate matter/m3 air, 8 days, 12 hr/day, whole body). In the anterior nasal cavity level 1 (NL1), changes in CK expression patterns were observed in the respiratory epithelium of the lateral wall and the maxilloturbinate (CK14, CK15, and CK18) and in the squamous epithelium of the ventral meatus (CK13). At nasal cavity level 2 (NL2), immediately behind NL1, changes were observed in the olfactory epithelium (CK13, CK14, and CK18) and in the respiratory epithelium of the septum (CK7 and CK19), the lateral wall (CK7 and CK13), and the lateral aspect of the maxilloturbinate (CK14). Changes were also observed in the submucosal glands, nasolacrimal duct, and vomeronasal organ. In the trachea only CK7 expression changed, and in the lung expression of CK7 (bronchioli) and CK8 (bronchus) changed; the expression of other CK polypeptides did not change. The observed changes in CK expression at NL1 correlated with the histomorphological changes, whereas CK expression changes were also seen in the olfactory and respiratory epithelia at NL2 and in the trachea and lung, where no histomorphological changes were seen. These findings indicate that changes in CK expression in respiratory tract epithelial cells are a sensitive marker for cellular stress response.

Animals↗
PubMedDate not supplied

[The Swiss Centre of Pharmacovigilance].

The Swiss Drug Monitoring Center SANZ operates the spontaneous reporting system in Switzerland and is a private institution founded and funded by the societies of the Swiss health professionals and the Swiss pharmaceutical industries. The goal of SANZ is to collect and evaluate ADRs and thus to create signals. In 1991 SANZ received 792 reports. SANZ informs the health professionals periodically on drug safety problems. Reports on serious ADRs are exchanged with the regulatory authorities.

Adverse Drug Reaction Reporting Systems↗
PubMedDate not supplied

Urodilatin, a new therapy to prevent kidney failure after heart transplantation.

Kidney failure after heart transplantation still remains a crucial problem, especially when cyclosporine is used for early postoperative immunosuppressive therapy. To preserve good renal function during immunosuppression with cyclosporine, urodilatin (CDD/ANP-95-126), the kidney-born analogue to the circulating cardiac peptide hANP (CDD/ANP-99-126), was given for the first time as a long-term, low-dose infusion in addition to the usual drug therapy immediately after heart transplantation. From November 1990 to January 1992, 47 patients (44 men and three women; mean age, 51 years) were treated by a 20 ng/kg body weight/min infusion for 96 hours after heart transplantation. Renal function and hemodynamic parameters of these patients were compared with a group of 40 patients (34 male and six female; mean age, 50 years) as controls, who underwent heart transplantation from May 1990 to November 1991. Both groups did not differ significantly with respect to age, sex, indication for heart transplantation, and preoperative renal function. With urodilatin treatment, renal function was significantly improved with lower peak plasma creatinine (1.83 +/- 0.1 versus 2.47 +/- 0.19 mg/dl; p = 0.003), lower peak serum urea (118 +/- 7 versus 178.3 +/- 10.3 mg/dl; p = 0.0036) and absence of hemodialysis (0% versus 10%; p = 0.026). Additionally, adequate diuresis was maintained although furosemide was reduced by more than 50% (p = 0.005) on each day of urodilatin treatment. Mean central venous pressure was significantly lower (-2 mm Hg; p = 0.02) during application of urodilatin, despite reduction of vasodilator therapy with nitroglycerin by about 50% (p = 0.02). Because of the significantly improved renal function and beneficial hemodynamic effects, the recommendation is therefore to introduce urodilatin in the postoperative treatment protocol after heart transplantation.

Adult↗