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Biomedical subjects

Thomas Schwarz

Publications and source records attributed to Thomas Schwarz.

At least 19 recordsLinked to original sources
PubMed2003

Coagulation factor V G allele and HR2 haplotype: factor V activity, activated protein C resistance and risk of venous thrombosis.

Factor V Leiden is a well-known risk factor for venous thrombosis. The dual role of factor V as a coagulatory and anticoagulatory cofactor permits the assumption that further mutations in the factor V gene are of importance in the study of the risk of thrombosis. Relevant studies to date have given rise to a controversy over this risk for the HR2 haplotype. For the G allele, defined in our work group as a G at the nucleotide positions 2391, 2663, 2684 and 2863, there have been to date no other investigations of thrombotic risk. In a case-control study on 347 patients with deep venous thrombosis (DVT) and 282 controls, we investigated the association of the HR2 haplotype and the G allele with DVT. We found no association between HR2 haplotype and DVT [odds ratio (OR) 0.87; 95% confidence interval (CI) 0.58-1.30; P = 0.537]. The frequency of the G allele was, on the contrary, higher in the control group than among the patients (OR 0.68, 95% CI: 0.53 to 0.89; P = 0.005). The factor V activity of the HR2 carriers was lower than that of the wild type and G allele carriers. The HR2 haplotype exhibited a moderate influence on activated protein C response. This study presented no evidence of thrombotic risk for the HR2 haplotype alone. The results here permit the assumption of a protective effect of the G allele. The source of a possible protective influence of the G allele on thrombotic risk is at present unclear.

Activated Protein C Resistance↗
PubMed2003

Complete compression ultrasonography of the leg veins as a single test for the diagnosis of deep vein thrombosis.

Noninvasive diagnosis of deep vein thrombosis (DVT) is based on ultrasound examination of the leg veins, usually restricted to only compression of the proximal veins (CUS). Patients with negative CUS findings require a second examination or a combination with other tests, which impairs clinical efficiency. In this prospective outcome study, 1646 consecutive patients with clinically suspected DVT were examined once by a standardized protocol of complete compression ultrasound comprising all proximal and distal veins (CCUS) as the only diagnostic test. The examination was equivocal in 15 patients (1% technical failure rate). Another 366 patients (22%) were tested positive for proximal DVT, distal DVT, muscle vein thrombosis, or phlebitis. Of 1265 patients in whom CCUS findings were negative, 242 met exclusion criteria for follow-up (age <18, life expectancy <3 months, other reasons for anticoagulation, postthrombotic lesions of the leg veins, or lack of informed consent). During the 3 months of follow-up, three of 1023 patients with negative CCUS findings experienced a symptomatic venous thromboembolic event (0.3% [95% CI 0.1%-0.8%]). We conclude that the CCUS protocol has a low technical failure rate and is safe with respect to excluding DVT, thereby reducing the diagnostic workup of patients with suspected DVT to a single ultrasound examination.

Adult↗
PubMed2002

DNA damage, death receptor activation and reactive oxygen species contribute to ultraviolet radiation-induced apoptosis in an essential and independent way.

Nuclear DNA damage and death receptor (CD95) activation by ultraviolet-B radiation (UVB) play a major role in UVB-induced apoptosis. Removal of DNA damage combined with inhibition of death receptor activation resulted in pronounced but not complete suppression of apoptosis, indicating that a third independent pathway is involved. Since reactive oxygen species (ROS) cause apoptosis and are induced by UVB, the radical scavenger pyrrolidene-dithiocarbamate (PDTC) was used. PDTC prevented UVB-induced apoptosis partially, H(2)O(2)-induced cell death largely, but not CD95-mediated apoptosis. The same was observed for cytochrome c release from mitochondria, another important event during apoptosis. The proapoptotic protein Bid was cleaved upon exposure to UVB or to agonistic anti-CD95-antibodies, but not to H(2)O(2), indicating that H(2)O(2) uses a different pathway. The fact that PDTC neither inhibited CD95-mediated apoptosis nor affected UV-induced DNA damage indicated that ROS generated during UVB irradiation may directly trigger mitochondrial cytochrome c release, thereby contributing to apoptosis. Accordingly, complete inhibition of apoptosis was observed when in addition to DNA damage removal via photoreactivation and blockade of CD95 signaling by caspase-8 inhibitor zIETD, PDTC was added before UVB exposure. This indicates that DNA damage, death receptor activation and ROS formation contribute to UVB-induced apoptosis in an essential and independent way.

Apoptosis↗
PubMed2002

[SAPHO syndrome: case report of an 18-year-old man and review of the literature].

We report about an 18-year-old man, suffering from acne on his face and trunk and complaining about indefinite bone pains--without any trauma. SAPHO-syndrome was diagnosed which consists of synovitis, acne, pustulosis, hyperostosis and osteitis. Five types of this syndrome can be differentiated: spondarthritis hyperostotica pustulo-psoriatica, chronic recurrent multifocal osteomyelitis, inflammatory chest wall syndrome, isolated sternocostoclavicular hyperostosis, and the combined form of acne-associated spondarthritis and chronic recurrent osteomyelitis. Although the sapho-syndrome is very rare, it should be considered a possible diagnosis in the case of indefinite bone pains in combination with acne, pustulosis and hyperostosis.

Acne Vulgaris↗
PubMed2002

Independent contribution of three different pathways to ultraviolet-B-induced apoptosis.

Ultraviolet-B radiation (UVB) causes a variety of biological effects which include the induction of apoptosis. UVB-induced apoptosis provides a well controlled scavenging mechanism protecting cells from malignant transformation. To induce programmed cell death, UVB uses a variety of cellular signaling pathways. In this context induction of nuclear DNA damage seems to be the predominant pathway, since experimental reduction of DNA damage was associated with a strong suppression of apoptosis. Additionally, UVB has been shown to target cytoplasmatically located or membrane bound components to induce signal transduction. UVB was found to directly activate cell surface death receptors, thereby triggering the apoptotic machinery. Furthermore, UVB-induced intracellular formation of reactive oxygen species (ROS) accompanied by mitochondrial dysfunction and cytochrome c release was demonstrated to be additionally involved in the apoptotic program. The following review will briefly discuss current aspects of the interplay between the different signaling pathways involved in UVB-induced apoptosis.

Animals↗
PubMed2002

Role of immunomodulation in diseases responsive to phototherapy.

Within the last two decades phototherapy has turned out to be a major therapeutic strategy in dermatology and thus has significantly influenced the treatment of many dermatoses. The goals of therapeutic photomedicine are the suppression of ongoing disease processes and, more importantly, the prevention, modulation, or abrogation of pathogenic mechanisms causing the disease. Therapeutic photomedicine has been largely empirical and most of it is still empirical today. However, parts of it are already based on the advances in photoimmunology and molecular biology. Although, we are far from a detailed understanding of the mechanisms underlying phototherapy, there is increasing evidence that phototherapy acts via modulation of the immune system. Most of the effects of both ambient and therapeutic ultraviolet radiation are immunosuppressive in nature.

Animals↗
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↗