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Thomas Schwarz

Publications and source records attributed to Thomas Schwarz.

70 records · Page 4Linked to original sources
PubMed2002

Molecular determinants of UV-induced immunosuppression.

It is almost three decades ago that it was discovered that ultraviolet radiation (UV) can compromise the immune system. UV suppresses immune responses in several ways. It inhibits the function of antigen-presenting cells, induces T cells with suppressor activity and induces the release of immunosuppressive cytokines. The latter phenomenon is mainly responsible for systemic immunosuppression. Although UV can also target cytoplasmic and cell membrane components, UV-induced DNA damage has been recognized as the most important molecular structure in mediating UV-induced immunosuppression. Recently, it was observed that interleukin-12 (IL-12), which antagonizes UV-induced immunosuppression, can accelerate the removal of UV-induced DNA lesions, probably via inducing DNA repair. Hence, it is tempting to speculate that the activity of IL-12 to reduce UV-induced immunosuppression may be due at least partially to this new biological activity of IL-12.

Animals↗
PubMed2002

Interleukin-12 suppresses ultraviolet radiation-induced apoptosis by inducing DNA repair.

Induction of apoptosis of keratinocytes by ultraviolet (UV) radiation is a protective phenomenon relevant in limiting the survival of cells with irreparable DNA damage. Changes in UV-induced apoptosis may therefore have significant impact on photocarcinogenesis. We have found that the immunomodulatory cytokine IL-12 suppresses UV-mediated apoptosis of keratinocytes both in vitro and in vivo. IL-12 caused a remarkable reduction in UV-specific DNA lesions which was due to induction of DNA repair. In accordance with this, IL-12 induced the expression of particular components of the nucleotide-excision repair complex. Our results show that cytokines can protect cells from apoptosis induced by DNA-damaging UV radiation by inducing DNA repair, and that nucleotide-excision repair can be manipulated by cytokines.

Adjuvants, Immunologic↗
PubMed2002

20 years after--milestones in molecular photobiology.

Ultraviolet radiation represents one of the most relevant environmental factors because of its hazardous health effects, which include induction of skin cancer, premature skin aging, and exacerbation of infectious diseases. The biologic effects exerted by ultraviolet radiation have been well characterized by a variety of in vitro and in vivo studies. The events taking place inside the cell during the ultraviolet response, however, remained unclear for quite a long time. Molecular photobiology has increased our knowledge about ultraviolet-induced signal transduction enormously within the last 10 years. For a long time, nuclear DNA has been regarded as the only chromophore for ultraviolet radiation. Today we know that ultraviolet radiation can affect also other molecular targets located in the cytoplasm and at the cell membrane. These targets include cell surface receptors, kinases, phosphatases, and transcription factors. Detailed knowledge about ultraviolet-induced signal transduction will certainly increase our understanding of how ultraviolet radiation exerts its biologic effects and furthermore will provide us with tools to interfere with these pathways, thereby reducing the adverse effects of ultraviolet radiation.

Animals↗
PubMed2002

Finding meaning.

Explore the source record for details and available documents.

Disaster Planning↗
PubMed2002

Mechanisms of UV-induced signal transduction.

Ultraviolet radiation (UV) causes a variety of biological effects that can be either beneficial or harmful for human health. To exert these effects on a cellular basis, UV uses a variety of signaling pathways. DNA is the major chromophore for UVB. Thus, nuclear DNA damage has been detected to be a major mediator of numerous UVB effects, and experimental reduction of DNA damage is associated with a loss of these effects. On the other hand, UV has been found to utilize molecular components within the cytoplasm or at the cell membrane for signaling. UV can directly activate cell surface receptors, kinases, and transcription factors. The nuclear and extranuclear signaling pathways are generated independently and have been recently recognized to be not mutually exclusive but to contribute to various UV effects in an independent and additive way. Further knowledge of how these signaling pathways relate to each other will certainly increase our understanding of how UV acts as a pathogen. The following review will briefly discuss current aspects of the mechanisms involved in UV-induced signal transduction.

Apoptosis↗
PubMed2002

Beta2 integrins are required for skin homing of primed T cells but not for priming naive T cells.

Beta2 integrins are of critical importance for leukocyte extravasation through vascular endothelia and for T cell activation. To elucidate the role of beta2 integrins in T cell-mediated immune responses, allergic contact dermatitis (ACD), irritant dermatitis, and delayed-type hypersensitivity (DTH) were assessed in mice lacking the beta2 integrin subunit, CD18. ACD and DTH responses, but not edema formation, were severely suppressed in CD18(-/-) mice. Extravasation of CD18(-/-) T cells into eczematous skin lesions was greatly impaired, whereas migration of Langerhans cell precursors and dendritic cells was normal in CD18(-/-) mice. CD18(-/-)lymph nodes (LNs) contained an abnormal population of CD3(-)CD44(high) lymphocytes and showed evidence of widespread T cell activation. T cells from regional LNs of sensitized CD18(-/-) mice proliferated in response to hapten challenge, and subcutaneous injection of sensitized syngeneic LN cells directly into ears of hapten-challenged naive recipients restored the defective ACD in CD18(-/-) mice, suggesting that CD18 is not required for priming of naive T cells but is indispensable for T cell extravasation. Thus, a dysfunction of T cells, in addition to granulocytes, may contribute to the pathophysiology of leukocyte adhesion deficiency type I, which arises from mutations in the human CD18 gene.

Animals↗
PubMed2002

Interobserver agreement of complete compression ultrasound for clinically suspected deep vein thrombosis.

The interobserver variability of compression ultrasound of proximal and distal veins in clinically suspected deep vein thrombosis was assessed. One hundred one symptomatic legs of all patients referred for clinically suspected deep vein thrombosis on 21 consecutive workdays were examined by two investigators independently according to a standardized protocol of complete compression ultrasound (CCUS) with 28 predefined venous segments between groin and ankle. Incompressible vein segments were defined as thrombotic. Cohen's kappa coefficient was used to calculate interobserver variability regarding diagnosis of deep vein thrombosis. Kappa for entire lower extremity was 0.94 (95% CI, 0.87-1). Kappa for proximal veins was 1; for calf veins 0.9 (95% CI, 0.79-1). For the posterior tibial veins and peroneal veins, kappa was 0.84 (95% CI, 0.66-1) and 0.77 (95% CI, 0.59-0.94), respectively. The results show that almost complete interobserver agreement can be achieved in compression ultrasound of both proximal and distal deep veins conducted according to a standardized examination protocol in clinically suspected deep vein thrombosis.

Adolescent↗
PubMedDate not supplied

Venous thrombosis after long-haul flights.

BACKGROUND: The risk for venous thromboembolism after long-haul flights represents a controversial issue. The aim of our study was to assess the incidence of venous thrombosis associated with long-haul flights in a prospective, controlled cohort study. METHODS: We included 964 passengers returning from long-haul flights (flight duration, > or =8 hours) and 1213 nontraveling control subjects. We excluded participants who were being treated with anticoagulant drugs or who used compression stockings. Main outcome measures were the incidence of ultrasonographically diagnosed thrombosis in the calf muscle and deep veins, symptomatic pulmonary embolism, and death. RESULTS: We diagnosed venous thrombotic events in 27 passengers (2.8%) and 12 controls (1.0%) (risk ratio [RR], 2.83; 95% confidence interval [CI], 1.46-5.49). Of these, 20 passengers (2.1%) and 10 controls (0.8%) presented with isolated calf muscle venous thrombosis (RR, 2.52; 95% CI, 1.20-5.26), whereas 7 passengers (0.7%) and 2 controls (0.2%) presented with deep venous thrombosis (RR, 4.40; 95% CI, 1.04-18.62). Symptomatic pulmonary embolism was diagnosed in 1 passenger with deep venous thrombosis (P =.44). All of these individuals had normal findings at baseline ultrasonography. Passengers with isolated calf muscle venous thrombosis or deep venous thrombosis had at least 1 risk factor for venous thrombosis (>45 years of age or elevated body mass index in 21 of 27 passengers). The follow-up after 4 weeks revealed no further venous thromboembolic event. CONCLUSIONS: Long-haul flights of 8 hours and longer double the risk for isolated calf muscle venous thrombosis. This translates into an increased risk for deep venous thrombosis as well. In our study, flight-associated thrombosis occurred exclusively in passengers with well-established risk factors for venous thrombosis.

Adolescent↗
PubMedDate not supplied

Preoperative image fusion of fluoro-2-deoxy-D-glucose-positron emission tomography and computed tomography data sets in oral maxillofacial carcinoma: potential clinical value.

OBJECTIVE: The aim was to evaluate the clinical and therapeutic value of digital image fusion of 2-[18]-fluoro-2-deoxy-D-glucose (F18-FDG) positron emission tomography (PET) and computed tomography (CT) in patients suffering from an oral maxillofacial carcinoma. METHODS: Seventeen patients (11 male, 6 female; age range: 45-89 years) suffering from an oral maxillofacial carcinoma underwent CT and F18-FDG-PET (333-370 MBq). The data of the 2 imaging modalities were fused on an image workstation. This image fusion was then visualized in the axial, coronal, and sagittal planes. RESULTS: PET showed a high pathologic FDG uptake in the tumor in 17 of 17 patients. CT detected the tumor in 12 of 17 patients. The image fusion of FDG-PET and CT showed the tumor in 17 of 17 patients. The final diagnosis was carcinoma of the mandible in 9 of 17 patients, carcinoma of the mouth floor in 3 of 17 patients, carcinoma of the tongue in 3 of 17 patients, carcinoma of the roof of the mouth in 1 of 17 patients, and carcinoma of the parotis gland in 1 of 17 patients. CONCLUSIONS: Preoperative image fusion of FDG-PET and CT data sets in oral maxillofacial carcinoma is possible in the clinical routine. Combined morphologic (CT) and functional (PET) imaging improves tumor localization even if the tumor is hardly visible on CT because of the artefacts of dental metallic implants (3/17 patients) or because of the small size of the tumor (2/17 patients). Image fusion is helpful for planning possible surgery (visual models) or radiotherapy (exact region of interest).

Aged↗
PubMedDate not supplied

Molecular mechanisms involved in UV-induced apoptotic cell death.

Ultraviolet radiation (UV) induces a variety of biological effects which include the induction of programmed cell death. UV-induced apoptosis seems to represent a controlled scavenging mechanism which protects cells from malignant transformation in human skin. To exert these effects on a cellular base, UV uses a variety of signaling pathways, involving nuclear DNA damage as a predominant pathway, since experimental reduction of DNA damage is associated with a loss of these effects. On the other hand, UV has been found to utilize extranuclear components located in the cytoplasm or at the cell membrane for signaling. UV can directly activate cell surface death receptors, thereby triggering the apoptotic machinery. Oxidative stress accompanied by mitochondrial changes and cytochrome c release are further involved in UV-mediated apoptosis. The following review will briefly discuss current aspects of the interplay between the different signaling pathways involved in UV-induced apoptosis.

Animals↗