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Biomedical subjects

M Schaller

Publications and source records attributed to M Schaller.

At least 37 records · Page 2Linked to original sources

Comparative therapeutic and toxic effects of different povidone iodine (PVP-I) formulations in a model of oral candidosis based on in vitro reconstituted epithelium.

In vitro models of oral candidosis based on reconstituted epithelium have been successfully used for virulence studies. In the present study we examined the effects of two povidone iodine (PVP-I) formulations (conventional PVP-I ointment, PVP-I liposome hydrogel) on reconstituted human mucosa and on a model of oral candidosis. The morphological alterations of the reconstituted mucosa caused by infection with C. albicans and by treatment were analyzed with light and electron microscopy. Specific alterations of the epithelium (vacuoles, spongiosis, oedema, detachment of keratinocytes) and invasion of the mucosa by fungal cells were reduced by treatment with the liposomal preparation, but not by the conventional ointment. However, a single application of the liposomal hydrogel to the uninfected mucosa demonstrated some structural irritations in the deeper tissue layers which were not seen with the ointment. Light microscopical studies demonstrated multiple globular structures in all samples treated with the liposomal PVP-I preparation. At the ultrastructural level these globular structures were classified as liposomes. The great majority of liposomal particles filled with dark contrasted active substance could be observed in contact with the cell wall of C. albicans and within the fungal cells. Targeting to the fungal surface resulted in a strong amount of the active ingredient next to the pathogens but not to the host cells. In conclusion the liposomal PVP-I formulation appeared superior to the conventional ointment formulation because of both less toxicity and better therapeutical effects.

Anti-Infective Agents, Local↗

[Lipoma of the forehead].

BACKGROUND AND OBJECTIVE: Lipomas should be included in the differential diagnosis of tumors located on the forehead. They require a different operative plan. PATIENTS/METHODS: Lipomas of the forehead were extirpated in ten patients. Dermatohistopathologic investigations confirmed the diagnosis lipoma in each case and exactly identified the anatomic layers surrounding the tumor. RESULTS: Histologic investigations revealed the localization of the lipoma in the submuscular layer in eight patients and in the subgaleal layer in two patients. CONCLUSIONS: Lipomas of the forehead should be differentiated into submuscular and subgaleal lipomas depending on the exact anatomic localization below the frontalis muscle or underneath the galea aponeurotica. This classification is simple and aids in operative planning.

Adult↗

Cowpox virus infection in an 11-year-old girl.

We describe an 11-year-old girl with a cowpox virus infection, who presented with a 14-day-old crusted, ulcerated nodule on the chin/neck and a 6-day-old eroded blister on the left leg. The girl lived in a rural environment, had close contact to several cats from the neighborhood, and had an atopic predisposition. The presence of orthopox virus in the lesion on the left leg was demonstrated by electron microscopy (negative staining, transmission electron microscopy) and virus isolation. Classification as a cowpox virus was determined by polymerase chain reaction (PCR), followed by restriction enzyme digestion of the PCR product.

Animals↗

Filtered platelet concentrates from pooled buffy coats show comparable storage lesions when stored for 9 d at 20-24 degrees C or when supplemented with thromboSol at 2-6 degrees C.

The present study investigated the quality of platelet concentrates from pooled buffy coat (PCBC) along different production steps and during storage to characterize storage lesions reflected by platelet activation, changing metabolic and cell turnover status (pH, LDH activity). These criteria were compared in conventionally stored PCBCs (20-24 degrees C, n = 8, Group I) to cold stored PCBCs (2-6 degrees C, n = 8, Group II) when supplemented with ThromboSol. Platelet activation was measured on days 1, 3, 7 and 9 by flow cytometry using fluoresceinisothiocyanate-labeled monoclonal antibodies (mAbs) against glycoprotein IIb/IIIa (CD41a, PAC-1 and LIBS-1), P-selectin (CD62P) or CD40 ligand receptor (CD40L) in combination with a phycoerythrin-labeled panspecific platelet marker against GPIb (CD42b). The platelet activation assessed with mAbs PAC-1, CD41a, LIBS-1 and CD40L showed an overall activation of 98 +/- 4% (mean value +/- 1 SD) at day 7 in both groups, except for CD62P, which was significantly lower in Group II. A storage-dependent greater platelet loss occurred in Group II compared to Group I, 42% vs. 19% (p < 0.05 on day 9). We could demonstrate that platelets stored in ThromboSol show about the same in-vitro activation as conventionally stored PCBCs, but their clinical usefulness needs to be investigated.

Adult↗

Interaction of Bartonella henselae with endothelial cells results in rapid bacterial rRNA synthesis and replication.

Bartonella henselae is a slow-growing microorganism and the causative pathogen of bacillary angiomatosis in man. Here, we analysed how interaction of B. henselae with endothelial cells might affect bacterial growth. For this purpose, bacterial rRNA production and ribosome content was determined by fluorescence in situ hybridization (FISH) using rRNA-targeted fluorescence-labelled oligonucleotide probes. B. henselae grown on agar plates showed no detectable rRNA content by means of FISH, whereas B. henselae co-cultured with endothelial cells showed a rapid increase of rRNA production within the first 18 h after inoculation. The increased rRNA synthesis was paralleled by a approximately 1000-fold intracellular bacterial replication, whereas bacteria grown on agar base showed only a approximately 10-fold replication within the first 48 h of culture. Pretreatment of host cells with paraformaldehyde prevented adhesion, invasion, intracellular replication and bacterial rRNA synthesis of B. henselae. In contrast, inhibition of host cell protein synthesis by cycloheximide did not affect bacterial adhesion and invasion, but prevented intracellular replication although bacterial rRNA content was increased. Inhibition of actin polymerization by cytochalasin D did not affect adhesion, invasion, increased rRNA content or intracellular replication of B. henselae. These results demonstrate that rRNA synthesis and replication of B. henselae is promoted by viable host cells with intact de novo protein synthesis.

Anti-Bacterial Agents↗

Invasion of Candida albicans correlates with expression of secreted aspartic proteinases during experimental infection of human epidermis.

Secreted aspartic proteinases (Saps) encoded by 10 genes of Candida albicans are important virulence factors for different types of candidiasis. Distinct SAP genes have previously been shown to contribute to tissue damage in a model of oral candidiasis. In this study a progressive SAP expression in the order SAP1 and SAP2 > SAP8 > SAP6 > SAP3 was observed in an in vitro model of cutaneous candidiasis based on reconstituted human epidermis. Transcripts of SAP1 and SAP2 were detected during initial invasion of the stratum corneum by C. albicans. Deeper, extensive penetration of the corneal layer was accompanied by additional SAP8 mRNA. SAP6 expression occurred concomitantly with germ tube formation and extensive hyphal growth in the strata granulosum, spinosum, and basale. Ultrastructural studies using specific polyclonal antibodies directed against the gene products of SAP1-3 and SAP4-6 revealed predominant expression of Sap1-3. The protective effect of the aspartic proteinase inhibitor pepstatin A during infection of the epidermis and an attenuated virulence phenotype of SAP-deficient mutants suggest that the observed SAP expression correlates with tissue damage in the skin.

Aspartic Acid Endopeptidases↗

Yersinia enterocolitica invasin protein triggers IL-8 production in epithelial cells via activation of Rel p65-p65 homodimers.

Enteropathogenic Yersinia bacteria trigger the production of the proinflammatory chemokine IL-8, an important chemokine for the recruitment of polymorphonuclear leukocytes (PMN). Yersinia is resistant to phagocytosis by PMN, and the recruitment of these cells is thought to be part of a pathogenic strategy of Yersinia to establish infection by allowing the pathogen to gain access to, and disseminate within, host tissue. We report here that Yersinia expressing the outer membrane protein invasin triggers IL-8 production in epithelial cells. The 195 carboxyl-terminal amino acids of invasin when linked to latex beads are sufficient to trigger IL-8 production. By means of IL-8 promoter reporter gene assays and electrophoretic mobility shift assay experiments, the minimal optimal region of the IL-8 promoter responsive to invasin was identified and invasin-responsive control elements were characterized. Invasin-induced activation of the IL-8 promoter was found to be mediated through a previously identified NF-kappaB element. This NF-kappaB binding site preferentially binds Rel p65-p65 homodimers as well as some p50-p65 heterodimers in response to stimulation by invasin. Invasin-induced NF-kappaB activation correlated with degradation of IkappaBalpha and the inhibition of NF-kappaB by specific inhibitors of IkappaB activation blocked invasin-induced IL-8 secretion. Invasin-triggered IL-8 production does not depend on invasin-triggered uptake of bacteria, and is independent of a functional PI3-kinase. This report is the first to demonstrate the molecular basis of IL-8 production triggered by enteropathogenic bacteria. Together, these data elucidate the possible early pathomechanisms operating in Yersinia infection and may have implications for the design of novel therapeutics directed against this enteropathogen.

Adhesins, Bacterial↗

Late cutaneous schistosomiasis representing an isolated skin manifestation of schistosoma mansoni infection.

Ectopic late cutaneous schistosomiasis is usually preceded or accompanied by visceral schistosomiasis infection. Our patient presented the very rare case of late cutaneous schistosomiasis as an isolated skin manifestation. Perigenital lesions occurred 1 year after contact with infested water. Identification of the few eggs remaining in the late lesion among the dense cellular infiltrate was difficult. Electron-microscopic studies clearly demonstrated the characteristic eggshell ultrastructure.

Adult↗

Social categorization and stereotyping: 'You mean I'm one of "them"?'.

What happens when people discover that they are members of a group about which they have previously formed some stereotype? To address this question, procedures previously shown to induce negative stereotypes of minority groups were combined with a social categorization manipulation. Participants in a distinctiveness-based illusory correlation paradigm (Hamilton & Gifford, 1976) either knew nothing about their group membership, or learned that they were a member of the minority group or the majority group either before or after being presented the stereotype-engendering stimulus materials. Results revealed that social categorization into the minority group before stimulus presentation eliminated the perceived stereotype and reversed the evaluative bias, whereas social categorization into the minority group after stimulus presentation had no effect on the perceived stereotype and only a weak effect in reducing the evaluative bias. Social categorization into the majority group either before or after stimulus presentation had little effect on the perceived stereotype and evaluative bias. These results clarify the process underlying the influence of social categorization on stereotype formation, underscore the distinction between affective and cognitive influences on stereotype formation and stereotype change, and offer insights into 'autostereotyping' among members of minority groups.

Humans↗

[Extracellular hydrolytic enzymes and their relevance during Candida albicans infections].

Candida albicans cannot only infect skin and mucosa, but can also cause life threatening systemic candidosis. While natural barriers and the immune system of healthy individuals normally prevent such infections, virulence factors exist that enable C. albicans to survive on surfaces and the permit the fungus to invade tissues and organs in immunocompromised patients. Adhesions factors, morphological flexibility and hydrolytic enzymes belong to this group of virulence factors.C.albicans appears to be able to use these specific virulence attributes at distinct stages of an infection or in different types of candidosis. For example, distinct adhension factors are important for the persistence of C. albicans on mucosal epithelial cells, while other factors are necessary for the adhesion to endothelial tissue. The differential expression of specific virulence factors at different stages of an infection could be the reason why C. albicans not only has single genes for extracellular hydrolytic enzymes, but gene families. Both secreted aspartate proteinases (Saps) and secreted lipases (Lips) from C. albicans are encoded by at least 10 different genes. This high number of similar genes might empower C. albicans with the ability to secrete a specific and appropriate enzymatic response at distinct stages of an infection. For both gene families differential expression has been shown in vitro and in vivo, which would be reasonable for such an adaptation. Expression studies revealed that distinct SAP and LIP genes were expressed under conditions when potential subtrates ( proteins or lipids) were not present in the growth medium. Such expression patterns would imply that these genes may have functions other than simply providing nutrients for the fungus. The specific transcription of single SAP genes during the course of an infection suggests that these genes may have specific functions during different stages of an infection. In fact, inhibition studies and the use of mutants with targeted gene disruptions showed that distinct SAP genes (SAP1-3) are important durning infections of skin and mucosa, while others (SAP4-6) are most relevant for systemic infections.

Candida albicans↗

Side-controlled intradermal injection of botulinum toxin A in recalcitrant axillary hyperhidrosis.

BACKGROUND: Although topical application of aluminium chloride is the most common measure against axillary sweating, severely affected patients often undergo surgical procedures that are expensive and may have considerable side effects. Recently botulinum toxin A (BT-A) has been reported as a potentially effective antihyperhidrotic agent. OBJECTIVE: Our purpose was to determine the therapeutic strength, safety, and mode of application of BT-A in severe axillary hyperhidrosis. METHODS: Intradermal injection of BT-A (Dysport) was given in an open left-versus-right side trial with each patient being his own control for initial efficacy, followed by treatment of the contralateral side. RESULTS: Seven days after initial treatment sweat production fell to below 10% of the untreated contralateral axilla as determined by gravimetry. Satisfaction was rated unanimously as "very good," the highest of 5 rankings. No side effects such as skin irritation or muscle weakness were noted in any patient. CONCLUSION: Intradermal injection of BT-A is a potent and well-accepted therapeutic option in patients with recalcitrant axillary hyperhidrosis.

Adult↗

Quality assurance in thrombapheresis.

The advent of comprehensive quality systems in blood banks and laboratory environment forces apheresis units to adherence to cGMP and cGLP. These constraints have brought apheresis centers to write standard operation procedures (SOPs) and operation flow charts, to train operators using training guides and to thoroughly document their work. An example of an SOP and an operation flow chart is given. We tested systematically the performance of three cell-separators (CS-3000 plus, Fenwal/Baxter; AS-104, Fresenius; Spectra with LRS, Cobe) employing 10 platelet apheresis (PCA) under daily working conditions and according to the SOP. We found few significant differences between the three apheresis systems, mainly caused by a greater processed blood volume in the CS-3000 group. Interestingly, we found no significant difference in the residual white blood cell (WBC) content per bag. With the AS-104 and the Spectra all products contained less than 1 x 10(6) WBC per bag. With the CS-3000 only 1 out of 10 contained WBC > 1 x 10(6) per bag. With each PCA a questionnaire was sent to the clinic asking for side effects. We observed no transfusion related side effects. The record keeping of different process parameters of platelet apheresis assures a constant quality of the product that is given by the national guidelines. Additionally, the present evaluation fostered operators' motivation into their work.

Humans↗