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Biomedical subjects

U Ritter

Publications and source records attributed to U Ritter.

At least 19 recordsLinked to original sources
PubMed2006

Effect of the visible light irradiation of fullerene-containing composites on the ROS generation and the viability of tumor cells.

AIM: To study the effect of fullerene-containing composites, irradiated by visible light, on the radical oxygen species (ROS) generation in thymocytes, ascitic cells from Erlich's tumor and leukemia cells L1210; to investigate viability of these cells in the presence of fullerene-containing composites under irradiation conditions. MATERIALS AND METHODS: The viability of cells was evaluated by staining with 0.4% solution of the trypan blue; ROS were detected with the use of electron paramagnetic resonance (EPR) spectroscopy and spin traps; solutions of fullerene-containing composites were irradiated with mercury-vapor lamp. RESULTS: We demonstrated that under irradiation conditions fullerene-containing composites increase the rate of ROS generation and decrease the number of viable tumor cells. CONCLUSIONS: The obtained data allow to consider the fullerene-containing composites as potential agents for photodynamic therapy.

Animals↗
PubMed2003

Design and evaluation of chemically synthesized siRNA targeting the NPM-ALK fusion site in anaplastic large cell lymphoma (ALCL).

The NPM-ALK fusion protein is found in up to 75% of pediatric anaplastic large cell lymphomas (ALCL). The ALK kinase becomes constitutively activated and triggers malignant transformation. Molecular targeting of the tumor-specific NPM-ALK fusion by gene-silencing methods seems to be a promising approach both for the treatment of ALCL and to decipher signaling pathways used by NPM-ALK. We designed and evaluated three chemically synthesized small interfering RNAs (siRNAs) for downregulation of the NPM-ALK fusion mRNA. Compared to HeLa cells transfected with the NPM-ALK expression plasmid only and to an siRNA containing two point mutations, the most potent anti-NPM-ALK siRNA reduced NPM-ALK protein expression in HeLa cells to almost undetectable levels, and the number of cells stained positively for NPM-ALK decreased by 80%. With respect to signaling, expressing of NPM-ALK increased the activity of AKT and ERK in HeLa cells, and this effect could be blocked by the specific siRNA targeting NPM-ALK. Expression of endogenous NPM-ALK mRNA in SR786 ALCL cells decreased by 50%-60% in cells transfected with the NPM-ALK siRNA. However, the amount of NPM-ALK protein was not influenced by a single transfection of the siRNAs against NPM-ALK. Repeated transfections over 8 days led to a significant reduction in NPM-ALK protein but without induction of apoptosis. We believe that the long protein half-life of NPM-ALK, at least 48 hours, limits the application of transiently transfected siRNAs. Nevertheless, RNA interference (RNAi) offers a suitable technique to dissect signaling pathways employed by NPM-ALK and may potentially be used to develop siRNA-based gene therapeutic approaches against NPM-ALK-positive lymphomas.

Base Sequence↗
PubMed2001

Rapidly fatal leishmaniasis in resistant C57BL/6 mice lacking TNF.

The resolution of infections with the protozoan parasite Leishmania major in mice requires a Th1 response that is closely associated with the expression of IL-12, IFN-gamma, and inducible NO synthase. Previous Ab neutralization studies or the use of mice deficient for both TNF receptors suggested that TNF plays only a limited role in the control of parasite replication in vivo. In this study we demonstrate that resistant C57BL/6 (B6.WT) mice locally infected with L. major rapidly succumb to progressive visceral leishmaniasis after deletion of the TNF gene by homologous recombination. A reduction of the parasite inoculum to 3000 promastigotes did not prevent the fatal outcome of the disease. An influence of the altered morphology of secondary lymphoid organs in C57BL/6-TNF(-/-) (B6.TNF(-/-)) mice on the course of disease could be excluded by the generation of reciprocal bone marrow chimeras. Although infected B6.TNF(-/-) mice mounted an L. major-specific IFN-gamma response and expressed IL-12, the onset of the immune reaction was delayed. After in vitro stimulation, B6.TNF(-/-) inflammatory macrophages released 10-fold less NO in response to IFN-gamma than B6.WT cells. However, in the presence of a costimulus, e.g., L. major infection or LPS, the production of NO by B6.WT and B6.TNF(-/-) macrophages was comparable. In vivo, inducible NO synthase protein was readily detectable in skin lesions and draining lymph nodes of B6.TNF(-/-) mice, but its expression was more disperse and less focal in the absence of TNF. These are the first data to demonstrate that TNF is essential for the in vivo control of L. major.

Animals↗
PubMed2000

Monocyte chemotactic protein-1 stimulates the killing of leishmania major by human monocytes, acts synergistically with IFN-gamma and is antagonized by IL-4.

We recently demonstrated that monocyte chemotactic protein-1 (MCP-1) is strongly expressed in lesions of patients with self-healing localized cutaneous leishmaniasis (LCL) whereas it is scarce in those of chronic diffuse cutaneous leishmaniasis (DCL). This finding indicated that MCP-1 may contribute to the healing process. In the present study, we analyzed the capacity of MCP-1 to trigger leishmanicidal activities. The results show that MCP-1 directly stimulates the elimination of intracellular Leishmania parasites by human monocytes, a potential that correlates with the induction of reactive oxygen intermediates. Release of NO was not detected. To understand the cross-talk between the chemokine and T cell-associated cytokines, we studied the influence of the Th1 cytokine IFN-gamma and the Th2 cytokine IL-4 on MCP-1-mediated activation of human monocytes. The data demonstrate that IFN-gamma and MCP-1 synergistically activate monocytes to clear intracellular parasites, whereas IL-4 abrogates the effect of MCP-1. Furthermore, IL-4 inhibits MCP-1 expression by infected monocytes, a finding that may explain the lack of MCP-1 in chronic lesions. The data suggest a novel model for macrophage activation in cutaneous leishmaniasis. In lesions of LCL, the synergistic action of MCP-1 and IFN-gamma may stimulate the killing of parasites by macrophages and promote healing, whereas the presence of IL-4 in DCL lesions may favor the suppression of MCP-1 and, together with the lack of IFN-gamma, the progression of disease.

Animals↗
PubMed1997

The chemokine repertoire of human dermal microvascular endothelial cells and its regulation by inflammatory cytokines.

Activation of endothelium is a critical event during the initiation of inflammatory processes and is associated with the induction of cell adhesion molecules and cytokines. The latter include chemotactically active cytokines (chemokines) that promote leukocyte diapedesis from the circulation to sites of evolving inflammation. In this study we evaluated the chemokine repertoire of human endothelial cells derived from the skin (HDMECs) and regulation of these chemokines by cytokines. HDMECs and an immortalized human dermal microvascular endothelial cell line, HMEC-1, were investigated for the expression of C-X-C and C-C chemokines at mRNA and protein levels. Upon stimulation with interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), both HDMECs and HMEC-1 expressed high levels of IL-8, GRO, and monocyte chemoattractant protein-1 (MCP-1). RANTES was only weakly induced; however, concomitant treatment with TNF-alpha and interferon-gamma (IFN-gamma) led to upregulation of RANTES, indicating a synergy between these two cytokines. The C-X-C chemokine IFN-inducible protein-10 was upregulated by IFN-gamma but not by other cytokines studied. Macrophage inflammatory protein-1alpha and beta, 1-309, and ENA-78 could not be induced. The chemokine repertoires of HDMECs and HMEC-1 were compared to those of human umbilical vein endothelium and found to be rather similar with the important exception that IFN-gamma and IL-4 up-regulated MCP-1 only in macrovascular endothelium. Our data indicate that HDMECs contribute to the dermal cytokine network by selective production of MCP-1, IL-8, GRO, RANTES, and IP-10, which may critically influence the site-specific recruitment of leukocyte subsets.

Cells, Cultured↗
PubMed1996

Cutaneous leishmaniasis: a model for analysis of the immunoregulation by accessory cells.

In the mammalian host, Leishmania are obligate intracellular parasites and invade macrophages and Langerhans cells. The accessory functions of both types of host cells are important for regulation of the specific cellular immune response and involve the following activities: infiltration into the site of infection, initiation of a T cell response, maintenance of immunity and the effector mechanisms that control intracellular parasite replication.

Animals↗
PubMed1996

Leishmania major infection in major histocompatibility complex class II-deficient mice: CD8+ T cells do not mediate a protective immune response.

In order to evaluate the role of CD8+ T cells in cutaneous leishmaniasis, major histocompatibility complex (MHC) class II-deficient mice of C57BL/6 background lacking functional CD4+ T cells were infected with Leishmania major. In contrast to C57BL/6 wild-type mice which are resistant to infection with L. major, these mice developed severe skin lesions that did not heal. In comparison to susceptible BALB/c mice, however, lesion development in MHC class II-deficient mice was very much retarded, even though the increase in the parasite load in lymphoid organs was only slightly delayed. Lymph node cells from L. major-infected MHC class II-deficient mice produced very low levels of interferon-gamma upon stimulation with L. major antigen, whereas the response to the mitogen concanavalin A was not impaired. Interestingly, they did not release lymphokines associated with disease exacerbation (interleukin 4 and interleukin 10) either, suggesting that the delayed lesion development is caused by the lack of disease-promoting CD4+ cells rather than by the presence of protective CD8+ cells. The lack of L. major-reactive immunoglobulins in the serum of infected MHC class II-deficient mice indicates that B cells also cannot respond to parasite antigens in the absence of MHC class II-mediated helper signals. The data demonstrate that MHC class II-deficient mice are unable to restrict the spreading of L. major, although they contain highly increased proportions of CD8+ T cells. Thus, MHC class II-restricted immune responses, most likely mediated by functional CD4+ T cells, are essential for the control of primary infections with L. major.

Animals↗
PubMed1996

Differential expression of chemokines in patients with localized and diffuse cutaneous American leishmaniasis.

The abundance of macrophages in localized cutaneous leishmaniasis (LCL) and diffuse cutaneous leishmaniasis (DCL) lesions and differences in the composition of T cell subsets indicate involvement of cell-specific chemotaxis processes. The expression of macrophage chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1 alpha and -1 beta, RANTES (regulated on activation, normal T cell expressed and secreted), I-309, and interleukin-8 were investigated in lesions of patients with LCL or DCL. In LCL, high levels of MCP-1 and moderate levels of MIP-1 alpha were detected. In DCL, MCP-1 expression was significantly lower and MIP-1 alpha expression was predominant. All other chemokines investigated were minimally expressed or absent. These findings suggest that MCP-1 and MIP-alpha are responsible for the recruitment of macrophages and T cells in cutaneous leishmaniasis. The results show that self-healing LCL is associated with higher levels of MCP-1, which may stimulate macrophage microbicidal mechanisms, and nonhealing DCL is associated with higher levels of MIP-alpha.

Animals↗
PubMed1996

Differential expression of GRO-alpha and IL-8 mRNA in psoriasis: a model for neutrophil migration and accumulation in vivo.

Dense focal accumulation of neutrophils in the upper epidermis is a hallmark of psoriasis. Because the signals for neutrophil diapedesis and migration in vivo are not fully understood, psoriatic lesions with pronounced migration of neutrophils may serve as an important model for studying neutrophil chemotaxis. In this study, we present evidence for differential expression of the neutrophil chemotactic cytokines growth-related oncogene alpha, interleukin-8, and ENA-78 (epithelial cell derived and neutrophil-activating properties, 78 amino acids) in psoriatic lesions. In situ hybridization and immunohistochemistry of serial sections were employed to identify and microanatomically localize the cells producing these chemokines. High levels of focal interleukin-8 message were found to be expressed in the upper epidermis by keratinocytes and, most importantly, neutrophils themselves. Growth-related oncogene alpha transcripts were detected in clusters of keratinocytes of the upper epidermis at the same sites where interleukin-8 mRNA was abundant. In contrast to interleukin-8, growth-related oncogene alpha was also detected in the papillary dermis produced by vessel-associated cells. Sites of interleukin-8 and growth-related oncogene alpha mRNA expression were associated with infiltration of neutrophils. Interestingly, mRNA expression of the highly homologous chemokine ENA-78 was quiescent. In conclusion, our data indicate that growth-related oncogene alpha is an important chemoattractant for neutrophil diapedesis in vivo, whereas further migration of neutrophils and formation of micropustules appears to be influenced by the cooperative action of both growth-related oncogene alpha and interleukin-8.

Cell Movement↗
PubMed1994

[The microbe colonization of the palatine tonsils of healthy school age children].

In 1988-1992 the tonsillar flora of 1799 children, six years of age and staying at certain kindergartens in Bavaria (Bayern), was examined. The microbiological investigations, directed at five indicator-germs showed the following results: 28.6% of the children were carriers of beta-haemolytic Streptococci, 17.4% of Enterobacteriaceae and 11.8% of Candida spp., Pseudomonadales and moulds could be found in 0.6% of the specimens.

Bacterial Infections↗
PubMed1990

[Simple in vitro test systems for determining the toxicity of environmental chemicals: microcultures of human lymphocytes and monoxenic ciliate cultures].

Two test methods were developed to assess (I) the cytotoxicity, (II) the environmental toxicity of chemicals. Test parameter for (I) is the growth inhibition of human T-lymphocytes stimulated by PHA (test period 6-7 days), for (II) the inhibition of cell multiplication of the ciliate Tetrahymena pyriformis grown monoxenically in a chemically defined medium which contained glucose and citrate as only carbon source (test period 13-14 days). The EC50 values (mol/l) of Pb, Cd, Hg, dichlorvos, atrazine and lindane were for (I): greater than or equal to 10(-2,5), 10(-5,4), 10(-5,6), 10(-5,0), 10(-4,75) and 10(-3,95) respectively, for (II): 10(-6,72), less than or equal to 10(-6,66), 10(-7,84), 10(-3,61), 10(-3,93) and 10(-4,75) respectively. The advantages of the described bioassays are simple handling and high sensitivity.

Animals↗
PubMed1984

[Sonographic study of the effect of hyoscin-N-butylbromide on cholecystokinin stimulated gallbladder motility].

The influence of the spasmolytic agent Hyoscine-N-butylbromide on the Cholecystokinin induced gallbladder contraction was investigated by ultrasonography in 25 volunteers. Even at a dosage of 0.15 mg/kg i.v. administered Hyoscine-N-butylbromide inhibited significantly the gallbladder emptying. In the investigated dosage range up to 0.6 mg/kg Hyoscine-N-butylbromide a strong response relationship was found. Since after the application of Hyoscine-N-butylbromide 30 min. before Cholecystokinin injection no loss of efficacy was observed, a considerably longer duration of the spasmolytic effect can be assumed. Also the oral form of the spasmolytic (dragees, mean dosage 0.6 mg/kg, application 30 min. before Cholecystokinin) showed a significant inhibition of gallbladder motility.

Adult↗
PubMed1983

[Clinical trial of febuprol, a new substance with choleretic activity. Study of efficacy and tolerability].

In a clinical trial, performed according to new criteria of the AMG (Arzneimittelgesetz) 1976, a new choleretic monosubstance 3-n-butoxy-1-phenoxy-2-propanol (code number: K 10.033, H 33, febuprol, Valbil) has been tested. The clinical investigations conducted on 712 healthy volunteers and patients within a period of 4 years showed that Valbil is an effective and safe drug. Besides the choleretic properties, febuprol has some additional spasmolytic and lipid lowering effects.

1-Propanol↗