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Biomedical subjects

S Schüller

Publications and source records attributed to S Schüller.

17 recordsLinked to original sources
PubMed2001

Coronin is involved in uptake of Mycobacterium bovis BCG in human macrophages but not in phagosome maintenance.

By applying density gradient electrophoresis (DGE) to human macrophages infected with Mycobacterium bovis BCG, we were able to separate three different bacterial fractions representing arrested phagosomes, phagolysosomes and mycobacterial clumps. After further purification of the phagosomal population, we found that isolated phagosomes containing live BCG were arrested in maturation as they exhibited only low amounts of the lysosomal glycoprotein LAMP-1 and processing of the lysosomal hydrolase cathepsin D was blocked. In addition, low amounts of MHC class I and class II molecules and the absence of HLA-DM suggest sequestration of mycobacterial phagosomes from antigen-processing pathways. We further investigated the involvement of the actin-binding protein coronin in intracellular survival of mycobacteria and showed that human coronin, as well as F-actin, were associated with early stages of mycobacterial phagocytosis but not with phagosome maintenance. Therefore, we conclude that the unique DGE migration pattern of arrested phagosomes is not as a result of retention of coronin, but that there are other proteins or lipids responsible for the block in maturation in human macrophages.

Bacterial Proteins↗
PubMed2000

[Determination of breakpoints for veterinary medically relevant antibiotics for resistance assessment of veterinary pathogens].

This article describes the meaning of the term clinical breakpoint. This is followed by a discussion of the parameters that need to be considered when setting valid breakpoints for active substances in veterinary medicine; in doing so we closely follow equivalent regulations and guidelines on the establishment of breakpoints in human medicine. Along with pharmacokinetic data and the results of clinical efficacy tests, susceptibility data of relevant organisms play a key role in the establishment of breakpoints. Published breakpoints are currently only available for a few modern drugs in veterinary medicine.

Animals↗
PubMed1999

PEGylated DNA/transferrin-PEI complexes: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery.

We investigated the in vitro and in vivo properties of DNA/transferrin-polyethylenimine (800 kDa) complexes before and after covalent coupling of poly(ethylene glycol) (PEG). Upon incubation with plasma, the positively charged non-PEGylated DNA complexes form aggregates. Plasma proteins such as IgM, fibrinogen, fibronectin and complement C3 were found to bind to non-PEGylated DNA complexes. At DNA concentrations relevant for in vivo gene delivery a strong aggregation of erythrocytes was also observed. PEGylation of the complexes strongly reduces plasma protein binding and erythrocyte aggregation. Furthermore, PEGylated complex size was stabilized and had a reduced surface charge. Prolonged circulation in the blood of the PEGylated complexes was also observed when injected intravenously. In tumor bearing mice, application of non-PEGylated complexes through the tail vein resulted in reporter gene expression in tail and lung, but severe toxicity was observed in some mice. In contrast, PEGylated complexes mediated reporter gene transfer to the tumor without significant toxicity.

Animals↗
PubMed1999

[Ranking of 20 MHz sonography of malignant melanoma and pigmented lesions in routine diagnosis].

PURPOSE: Eleven dermatology clinics from all over Germany took part in our multicenter prospective study with the aim of evaluating 20 MHz sonography in the preoperative diagnosis of malignant melanomas and other pigmented skin tumours. It was to be assessed how effective sonographic measurement of thickness would compare to histology and the clinical palpation of tumour thickness and also the significance of differential diagnosis in sonography of malignant melanomas. METHOD: The prospective multicenter study proceed as follows. To the end of August 1997 264 patients with a primary malignant melanoma and 417 patients with benign skin tumours were examined via 20 MHz sonography. Two different examiners estimated the clinical thickness of the tumour by palpation. The tumour was then excised and examined for postoperative correlation with the histology sections. RESULTS: The final results showed good correlation between the histological and sonographic estimation of tumour thickness (r = 0.97). Estimation of tumour thickness by palpation showed no correlation with the histology (r = 0.59). Most of the benign (44%) and malignant tumours (38.7%) were spindle shaped. There was no significant difference between the benign and malignant tumour groups in relation to the sonographic presented shapes or echo signs. No different diagnosis could be made. CONCLUSION: The technique of high frequency sonography in relation to preoperative diagnosis of malignant melanomas has high priority. In contrast to clinical estimation of tumour thickness, sonography provided a good correlation to histology. The effectiveness of sonography with regard to the valence of the skin tumours is limited and there is no possibility of differentiating between malignant and benign tumours from the morphological face value. Hence, there is a demand for developing a 150 MHz apparatus which will be able to supply evidence regarding the valence of skin tumours.

Diagnostic Tests, Routine↗
PubMed1998

[Focal mucinosis of the eyelid].

PURPOSE: To present a case of focal mucinosis of the eyelid. PATIENT: A male patient of Turkish origin born in 1982 desired therapy in 1995 for an asymptomatic tumour of the left medial upper lid which had been present probably since birth. The tumour was reduced with argon laser photocoagulation. Fourteen months later, in 1997, the tumour had enlarged so that a surgical excision was performed which histologically was interpreted as an unspecific inflammation. In 1998, the tumour had grown again at the original site, and there were additional three pedunculated tumours nearby at the lid margin. All tumours were surgically excised. Histology showed empty spaces in the upper dermis which contained some connective fibers, benign appearing fibroblasts and some leukocytes. The PAS-reaction and S100-immunohistology were negative while the lesion stained positive for alcianblue. The epidermis was intact. A diagnosis of a focal mucinosis of the eyelid was established. CONCLUSIONS: Focal mucinosis of the eyelid seems to be exceedingly rare. It is probably caused by a local overproduction of hyaluronic acid of unknown etiology. Our patient demonstrates that focal mucinosis might perhaps be congenital. Moreover it may recur if excision is not complete. Focal mucinosis should be included in the differential diagnosis of long-lasting, asymptomatic lid tumours.

Adolescent↗
PubMed1998

Suppression of major histocompatibility complex class I and class II gene expression in Listeria monocytogenes-infected murine macrophages.

Macrophage cells play a central role during infection with Listeria monocytogenes by both providing a major habitat for bacterial multiplication and presenting bacterial antigens to the immune system. In this study, we investigated the influence of L. monocytogenes infection on the expression of MHC class I and class II genes in two murine macrophage cell lines. Steady-state levels of I-Abeta chain mRNA were decreased in both resting J774A.1 and P388D1 macrophages infected with L. monocytogenes whereas reduction of H-2K mRNA was only observed in P388D1 cells. In addition, L. monocytogenes suppressed induction of MHC class I and class II mRNAs in response to gamma-interferon as well as the maintenance of the induced state in activated P388D1 macrophages. Exposure to the non-pathogenic species L. innocua or a deletion mutant of L. monocytogenes, which lacks the lecithinase operon, did not cause a reduction in H-2K and I-Abeta mRNA levels nor suppress expression of Ia antigens. Inhibition of MHC gene expression may represent an important part of the cross-talk between L. monocytogenes and the macrophage that probably influences the efficiency of a T cell-mediated immune response and thus the outcome of a listerial infection.

Animals↗
PubMed1997

Involvement of MAP-kinases and -phosphatases in uptake and intracellular replication of Listeria monocytogenes in J774 macrophage cells.

In this study we show that protein tyrosine kinases and also protein tyrosine phosphatases are involved in the uptake of Listeria monocytogenes by J774 macrophages to a different extent than in the uptake of inert latex beads. In addition, protein tyrosine kinases are necessary for the intracellular growth and survival of L. monocytogenes. The expression of the MAP kinase phosphatase MKP-1, a protein tyrosine phosphatase, is induced upon infection, and phagocytosis of L. monocytogenes by J774 cells overexpressing the MKP-1 protein is reduced compared to control cells. The decreased phagocytosis of L. monocytogenes as a result of the MKP-1 overexpression in J774 macrophages suggests that the activation of the MAP kinase(s) ERK-1 and/or ERK-2 is an essential requirement for the uptake of L. monocytogenes by J774 macrophages.

Animals↗
PubMed1996

Detection and characterization by differential PCR of host eukaryotic cell genes differentially transcribed following uptake of intracellular bacteria.

Host eukaryotic cell genes that are differentially transcribed after phagocytosis of various pathogenic and nonpathogenic bacterial cells were identified by a differential PCR (DPCR) system. This DPCR procedure favors detection and isolation of host genes affected at the transcriptional level by selecting for poly(A) tails but differs substantially from reverse transcription-PCR. Several unidentified macrophage gene fragments from genes that were either transcriptionally activated or downregulated following uptake of Listeria monocytogenes into J774 mouse macrophage cells were initially defined by this DPCR procedure. Because of the sensitivity of the DPCR technique, all of the genes exhibited less than a 10-fold difference in transcription compared with noninfected cells as measured by limiting-dilution PCR. One of the gene fragments has a very high level of homology with a mitogen-activated protein kinase phosphatase (MKP-1), whereas the other affected fragments showed no homologies to known gene sequences. In addition, one of the gene fragments (WS30-B2/1) was specifically downregulated after L. monocytogenes uptake and another gene was repressed by uptake of either Shigella flexneri or L. monocytogenes, while transcription of the genes represented by fragment WS13-B9/9, and to some extent MKP-1, was activated following general phagocytosis (i.e., following uptake of any species of bacterium tested). Further characterization of the affected genes was conducted by using mutants of L. monocytogenes. A hemolysin-negative mutant of L. monocytogenes failed to elicit transcriptional regulation of gene fragment WS10-B4/14 or WS30-B2/1, and it elicited only minimal regulation of MKP-1, suggesting that escape from the phagosome may be required to initiate these responses. Furthermore, mutants with mutations in mpl and actA, two genes whose gene products are involved in actin polymerization and intrahost spread, also did not induce regulation of WS10-B4/14. These results demonstrate that (i) DPCR can identify specific host cell genes which are differentially transcribed after infection with certain microorganisms and (ii) some of these genes may be new or may never before have been linked to interactions between hosts and pathogens.

Animals↗
PubMed1996

Differences in virulence and in expression of PrfA and PrfA-regulated virulence genes of Listeria monocytogenes strains belonging to serogroup 4.

Listeria monocytogenes isolates belonging to serogroup 4 (subtypes 4a, 4ab, 4b, 4c, 4d, and 4e) exhibit different levels of virulence in mice. Molecular studies indicate that in comparison with the control strain EGD (serotype 1/2a), these strains differ in the expression of the PrfA-regulated virulence genes, including prfA itself. Strains of serotypes 4c, 4d, 4e, and especially 4a show a low level of invasiveness in Caco-2 cells, which correlates in part with the low level of expression of the inlA gene. All serotypes reach the cytoplasm, at the latest, 2 h postinfection and become surrounded by polymerized actin within the next hour, but actin tail formation by serotype 4a, 4c, 4d, and 4e strains is drastically reduced. The actA genes in these serogroup 4 strains are expressed in minimum essential medium and within the phagocytic cell line J774. However, the amounts and (in part) the sizes of the ActA proteins in these strains differ under these conditions. The reduced actin tail formation by serotype 4a, 4c, 4d, and 4e strains may be due to the low level of in vivo expression of ActA. In addition, the loss of one repeat unit in the ActA proteins of serotype 4a and 4e strains may also contribute to the less efficient actin tail formation observed with these strains.

Animals↗
PubMed1996

Lacrimal secretion of human epidermal growth factor in perforating keratoplasty.

Human epidermal growth factor (hEGF) plays a key role in the regulation of corneal epithelial regeneration. As the lacrimal concentration of EGF is known to decrease following corneal injury, therapeutic application of exogenic EGF to support corneal wound healing is currently being investigated. To evaluate the role of topical EGF substitution in perforating keratoplasty, the lacrimal secretion of EGF was determined in 12 patients prior to keratoplasty and on the 1st and 7th days postoperatively using a newly developed modular immunofluorometric assay. EGF secretion and tear-flow rates in the tear samples of the keratoplasty patients were compared with those of 39 patients with corneal epithelial defects of other origin and those of 21 healthy controls. Levels of EGF secretion and tear flow reflectorily increased both in the post-operative samples of keratoplasty patients (secretion 0.77 +/- 0.56 pg/s, tear flow 18.7 +/- 14.9 microliter/min) and in the samples of patients with corneal epithelial defects (0.6 +/- 0.4 pg/s, 19.6 +/- 19.2 microliter/min) in comparison with preoperative values and healthy controls (0.3 +/- 0.2 pg/s, 4.0 +/- 5.4 microliter/min). Men showed higher average levels of basal and reflectory EGF secretion (0.4 and 0.8 pg/s), respectively than did women (0.25 and 0.55 pg/s, respectively). The results indicate a physiological feedback mechanism that reflectorily adjusts the lacrimal EGF secretion following corneal irritation. Topical therapy with recombinant EGF should therefore be restricted to patients with persistent corneal epithelial defects and proven deficiency of EGF secretion.

Adult↗
PubMed1993

Latent Marek's disease virus can be activated from its chromosomally integrated state in herpesvirus-transformed lymphoma cells.

Marek's disease virus (MDV), a lymphotropic herpesvirus, induces T-cell lymphomas in chicken, its natural host. The lymphoma cells are latently infected with MDV but the viral contribution to the transformed phenotype is not understood. To investigate the virus-cell interaction, we focused on the status of MDV in the transformed cells. By the use of highly sensitive fluorescent in situ hybridization with metaphase chromosomes, we found (i) MDV DNA to be randomly integrated at multiple sites in the chromosomes of primary lymphoma cells from chicken tissues; (ii) extrachromosomal, circular MDV genomes were absent and linear virion DNA was usually not detectable in the latently infected lymphoma cells; (iii) the pattern of integration sites revealed the clonal origin of the tumour cells; which (iv) was retained in in vitro established cell lines derived from primary lymphomas; (v) activation of the lytic phase of MDV's life cycle occurred in vitro suggesting that MDV can escape from its integrated status by an unknown mechanism.

Animals↗
PubMed1993

Identification of genomic regions of the herpesvirus of turkeys (HVT) with helper activity for avian adeno-associated virus (AAAV).

Herpesvirus of turkeys (HVT) is a potent helper for the defective parvovirus avian adeno-associated virus (AAAV). To study the helper mechanism at the molecular level, we established a complete cosmid library of HVT DNA in a set of seven overlapping clones and transiently cotransfected secondary chicken embryo fibroblast (CEF) cells with AAAV DNA and recombinant cosmids (cBL) (individual as well as in different combinations). Using an AAAV-specific indirect immunofluorescence assay, we identified four regions on the HVT genome, represented by cBL267, cBL27, cBL33, and cBL34, which express helper functions for AAAV. As demonstrated by infection studies with extracts from cotransfected CEF cells, cBL267 promotes productive AAAV growth, while the helper effect induced by cBL27, cBL33, and cBL34 is limited to the synthesis of noninfectious AAAV antigen. In view of the data presented, possible HVT-specific helper mechanisms for AAAV are discussed.

Animals↗
PubMed1992

[EGF in therapy of corneal diseases. Principles and possible uses].

Numerous recent research results stress the importance of the epidermal growth factor (EGF) for the growth and differentiation of corneal tissues. EGF, a physiological ingredient in the tears, plays a predominant role in the regeneration of corneal epithelium. Furthermore, EGF has been shown to increase the proliferation and differentiation of corneal keratocytes and endothelial cells. Topically applied EGF significantly enhances both the re-epithelialization of denuded areas and the tear strength of stromal cicatrices. These results may lead to interesting pharmacological management procedures for numerous corneal disorders. Thus, the clinical feasibility of EGF therapy is currently the subject of intensive evaluation. A better understanding of its mode of action, both on the molecular and cellular level, and increasing knowledge of the pharmacokinetics, together with the development of suitable application media, may all make EGF an integral part of the next generation of ophthalmic drugs. This survey reviews basic molecular-pharmacological and biochemical findings on EGF and evaluates its possible value for therapeutical use.

Animals↗
PubMedDate not supplied

Polycation-based DNA complexes for tumor-targeted gene delivery in vivo.

BACKGROUND: Efficient and target-specific in vivo gene delivery is a major challenge in gene therapy. Compared to cell culture application, in vivo gene delivery faces a variety of additional obstacles such as anatomical size constraints, interactions with biological fluids and extracellular matrix, and binding to a broad variety of non-target cell types. METHODS: Polycation-based vectors, including adenovirus-enhanced transferrinfection (AVET) and transferrin-polyethylenimine (Tf-PEI), were tested for gene delivery into subcutaneously growing tumors after local and systemic application. DNA biodistribution and reporter gene expression was measured in the major organs and in the tumor. RESULTS: Gene transfer after intratumoral application was 10-100 fold more efficient with Tf-PEI/DNA or AVET complexes in comparison to naked DNA. Targeted gene delivery into subcutaneously growing tumors after systemic application was achieved using electroneutral AVET complexes and sterically stabilized PEGylated Tf-PEI/DNA complexes, whereas application of positively charged polycation/DNA complexes resulted in predominant gene expression in the lungs and was associated by considerable toxicity. CONCLUSION: For systemic application, the physical and colloidal parameters of the transfection complexes, such as particle size, stability, and surface charge, determine DNA biodistribution, toxicity, and transfection efficacy. By controlling these parameters, DNA biodistribution and gene expression can be targeted to different organs.

Adenoviridae↗
PubMedDate not supplied

Liquid crystalline DNA in fowl adenovirus.

Fowl adenovirus particles were studied using negative stain electron microscopy. Upon preparation, some particles collapsed and showed their internal structure. The DNA could be observed as thin parallel lines with a spacing of 25 A, very similar to images of the liquid crystalline DNA in bacteriophage heads and in herpes virus.

Aviadenovirus↗
PubMedDate not supplied

[Heart involvement in progressive systemic sclerosis (generalized scleroderma)].

17 patients with progressive systemic sclerosis were examined for cardiac involvement using standard ECG, chest X-ray, 24-h Holter ECG, and echocardiography. The control groups consisted of 7 patients with mixed connective tissue disease, 10 patients with systemic lupus erythematosus, and 10 patients with rheumatoid arthritis. The results disclosed a cardiac involvement of 70% using all 4 methods, which is more than is reported in the literature. The data also show that all 4 methods are necessary to diagnose the cardiac involvement. Conduction and rhythm disorders especially are more frequent than in other collagen vascular diseases. The use of calcium channel blockers is discussed as a new therapeutic possibility.

Electrocardiography↗