Publications by authors named "Ullrich S"

Chronic exposure to JP-8 jet fuel induces lung toxicity, adverse neurological effects and some liver and kidney dysfunction. In addition, inhalation of JP-8 induces immune suppression. Besides the lung, the other major route of JP-8 exposure is via the skin.

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In order to protect the public against the adverse effects of sunlight, the scientific, medical, and particularly the dermatologic community has promoted "safe sun exposure." This strategy includes sun avoidance whenever possible, wearing hats and other protective clothing and/or devices, such as sunglasses, and extensive use of sunscreens. Sunscreen efficacy is determined by measuring the ability of the sunscreen to block ultraviolet (UV)-induced erythema (sun protection factor or SPF), and most sunscreen formulations on the market, if used properly, are very good at preventing erythema and sunburn.

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Because interleukin-10 (IL-10) has potent immunosuppressive and anti-inflammatory properties and is produced by some cancers, including melanoma, we hypothesized that its production by tumor cells may contribute to the escape from immune surveillance. To test this hypothesis, we transfected human A375P melanoma cells that do not express IL-10 with the murine IL-10 gene and subsequently analyzed for changes in tumor growth and metastasis in nude mice. Surprisingly, IL-10 gene transfer resulted in a loss of metastasis and significant inhibition of tumor growth.

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Exposure to sunlight can result in a number of harmful effects, including sunburn, erythema, premature aging of the skin, immune suppression and skin cancer. Studies designed to understand the underlying mechanisms often depend upon the use of artificial sources of UV radiation. Unfortunately, conclusions from different laboratories using different lamps often conflict, and it is entirely possible that the different spectra of sunlights used in each may be a source of conflict.

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We demonstrated previously that p53 mutations can be detected in ultraviolet B-irradiated mouse skin months before the gross appearance of skin tumors and that applying sun protection factor 15 sunscreens to mouse skin before each Kodacel-filtered FS40 sunlamp irradiation resulted in the reduction of such mutations. To determine whether there is an association between reduction of ultraviolet-induced p53 mutations by sunscreens and protection against skin cancer using an environmentally relevant light source, we applied sunscreens (sun protection factors 15-22) on to the shaved dorsal skin of C3H mice 30 min before each exposure to 4.54 kJ ultraviolet B (290-400 nm) radiation per m2 from a solar simulator.

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Splenic NK1.1+CD4+ T cells that express intermediate levels of TCR alpha beta molecules (TCRint) and the DX5 Ag (believed to identify an equivalent population in NK1.1 allelic negative mice) possess the ability to rapidly produce high quantities of immunomodulatory cytokines, notably IL-4 and IFN-gamma, upon primary TCR activation in vivo.

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Although acute exposure to UV radiation suppresses the induction of delayed-type (DTH) and contact (CHS) hypersensitivity in mice, it is not clear whether the photobiological mechanism(s) involved in suppressing these closely related immune reactions is the same. A careful examination of the UV dose responses and wavelength dependencies involved in suppressing CHS and DTH may provide important insights into the mechanisms involved. We compared the UV dose-response curves for suppressing four closely related immune reactions, local and systemic suppression of CHS to dinitrofluorobenzene, systemic suppression of DTH to Candida albicans and systemic suppression of DTH to alloantigen using three different UV spectra (FS40 sunlamps, Kodacel-filtered FS40 sunlamps and solar-simulated light).

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Although almost all of the energy contained within the ultraviolet (UV) wavelengths of solar radiation is absorbed within the epidermis and upper layers of the dermis, UV irradiation can suppress the immune response to antigens introduced at distant, non-irradiated body sites. The production of immune modulatory cytokines, such as interleukin-10 (IL-10), by UV-irradiated keratinocytes and its effect on T helper type 1 (Th1)/Th2-cell balance are thought to play a major role in the induction of systemic immune suppression. Because it is suggested that costimulatory molecules, such as CD80 and CD86, differentially stimulate Th1 and Th2 cells we wished to investigate the role of these costimulatory molecules in the activation of immune suppression.

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Considerable evidence suggests that ultraviolet-B (UV-B) radiation suppresses certain immune responses through the induction of cyclobutane pyrimidine dimers in DNA. To determine whether induction of other forms of DNA damage in the skin mimicked the immunosuppressive effects of UV-B radiation, we produced double-strand breaks in the DNA of epidermal cells with HindIII restriction endonuclease encapsulated in liposomes. Application of these liposomes, but not liposomes containing inactive HindIII or an irrelevant endonuclease, to the skin of C3H mice suppressed the induction of delayed-type hypersensitivity responses to Candida albicans and alloantigen and induced IL-10 production in the epidermis.

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Ultraviolet (UV) radiation is a potent human carcinogen and it induces skin cancer in experimental animals. Recent studies have shown that unique mutations in the p53 tumor suppressor gene contribute to the development of human and mouse UV-induced skin cancers. Such mutations are also found in sun-damaged skin and actinic keratosis, suggesting that p53 mutations arise early during UV skin carcinogenesis.

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Cutaneous exposure to ultraviolet radiation suppresses the induction of T cell mediated responses such as contact and delayed type hypersensitivity (DTH) by altering the function of immune cells in the skin and causing the release of immunoregulatory cytokines. Extracts of crude Aloe barbadensis gel prevent this photosuppression. Because the regulation of contact hypersensitivity and DTH responses differ, we investigated whether protection was afforded by a single or multiple agents in Aloe and the mechanism by which this material prevents suppression of DTH immunity.

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Even though all of the energy contained with the UV wavelengths of solar radiation is absorbed within the epidermis and upper layers of the dermis, UV irradiation can suppress immune responses to Ag introduced at distant nonirradiated sites. In addition, data from a number of laboratories have suggested that one consequence of UV exposure is suppressed Th1 cell activation with normal or enhanced Th2 cell activation, resulting in a shift to a Th2-like phenotype. Cytokines secreted by UV-irradiated keratinoctyes, particularly IL-10, have been shown to play a major role in the induction of systemic immune suppression and differential activation of T helper cell subsets.

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In this study, we investigated whether the spectrum of p53 mutations in skin tumors induced in hairless SKH-hr1 mice by a solar simulator (290-400 nm) are similar to those found in skin tumors induced in C3H mice by UV radiation from unfiltered (250-400 nm) and Kodacel-filtered (290-400 nm) FS40 sunlamps. Analysis of tumor DNA for p53 mutations revealed that 14 of 16 (87.5%) SkH-hr1 skin tumors induced by the solar simulator contained mutations.

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Cell capacitance (Cm), cell conductance (Gm), access conductance (Ga) and membrane voltage (Vm) were measured simultaneously in insulin secreting cells using the dual frequency method. Depolarization and stimulation of the cells with secretagogues increased Cm. EGTA abolished the increase in [Ca2+]i and prevented the rise of Cm.

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TIMP-4, a novel human tissue inhibitor of metalloproteinase, was identified and cloned (Greene, J., Wang, M., Raymond, L.

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Photocarcinogenesis represents the sum of a complex of simultaneous and sequential biochemical events that ultimately lead to the occurrence of skin cancer. These events, initiated by UV radiation of appropriate wavelength, include the formation of DNA photoproducts: DNA repair; mutation of proto-oncogenes and tumor suppressor genes; UV-production of radical species with subsequent effects on mutation and extra-nuclear function; and other epigenetic events that influence the course of carcinogenesis. The epigenetic influences may include immunological responses, antioxidant defenses, and dietary factors.

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STRL22 is a human seven transmembrane domain orphan receptor related to known chemokine receptors and expressed in peripheral blood lymphocytes, tumor infiltrating lymphocytes and lymphoid tissues. MIP-3alpha/LARC/Exodus is a CC chemokine that is chemotactic for lymphocytes and that is expressed in activated cells, including monocytes, T cells, endothelial cells, and fibroblasts, and in liver, lung, and some lymphoid tissues. We report here that STRL22-transfected human embryonic kidney 293 cells demonstrated specific binding for MIP-3alpha and that MIP-3alpha, but no other chemokines, produced a calcium flux in the STRL22-transfected cells.

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Recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) has been successfully used in different clinical settings. We evaluated the tolerability of rhGM-CSF treatment in addition to its efficacy in preventing myelosuppression and reducing infectious complications after standard-dose chemotherapy of various tumors. Of the patient group analyzed (n = 308), 75% had solid tumors and 25% had hematological malignancies.

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Information presented at this symposium indicates that modulation of Th cell responses is one means by which xenobiotics may cause immunotoxicity. A shift from Th1 to Th2 responses can enhance both infectious and allergic disease. Hence, in some cases, a common mechanism may be responsible for effects that are generally considered to be very different.

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Exposing skin to UVB (280-320 nm) radiation suppresses contact hypersensitivity by a mechanism that involves an alteration in the activity of cutaneous antigen-presenting cells (APC). UV-induced DNA damage appears to be an important molecular trigger for this effect. The specific target cells in the skin that sustain DNA damage relevant to the immunosuppressive effect have yet to be identified.

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UV-induced mutations in the p53 tumor suppressor gene play an essential role in skin cancer development. We report here that such mutations can be detected in UV-irradiated mouse skin months before the gross appearance of skin tumors. Application of SPF-15 sunscreens to mouse skin before each UV irradiation nearly abolished the frequency of p53 mutations.

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Forebrain overgrowth, fog, is a spontaneous autosomal recessive mutation in the mouse producing forebrain, lumbo-sacral, and facial defects. The defects appear to result from excessive growth or cellular proliferation leading to abnormalities in neural tube closure. Three unique features of the mutant are: (1) the growth of telencephalon cells into the surrounding mesenchyme, (2) presence of an encephalocele through the midline cleft in some mutants, and (3) dissociation of the tail defect from the caudal neural tube defect.

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The NADPH-dependent HC-toxin reductase (HCTR), encoded by Hm1 in maize, inactivates HC-toxin produced by the fungus Cochliobolus carbonum, and thus confers resistance to the pathogen. The fact that C. carbonum only infects maize (Zea mays) and is the only species known to produce HC-toxin raises the question: What are the biological functions of HCTR in other plant species? An HCTR-like enzyme may function to detoxify toxins produced by pathogens which infect other plant species (R.

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