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Biomedical subjects

T Schwarz

Publications and source records attributed to T Schwarz.

At least 37 records · Page 2Linked to original sources

[Diagnosis of metastasis of malignant melanoma in the thyroid gland with f18-FDG PET scan].

Metastases in the thyroid gland are very rare. When they occur, long-term survival is dismal; thus an early diagnosis is critical. Malignant melanoma is one of the tumors which may metastasize to the thyroid gland. Therefore we wanted to demonstrate F18-Fluorodeoxyglucose-Positron emission tomography (F18-FDG-PET) is a sensitive and reliable method to identify such metastases. We report about a 51-year-old man, who had an inguinal lymph node metastasis of a malignant melanoma with unknown primary tumor site. He came to us for an a follow-up F18-FDG-PET investigation. In the PET there was a pathologic FDG-uptake in the left lobe of the thyroid gland. The nodule was removed and showed a malignant melanoma metastasis. This unusual scenario underscores the value of the PET in the oncologic follow-up of patients with malignant melanoma.

Diagnosis, Differential↗

Recurrent isolated calf muscle thrombosis due to a venous aneurysm of the soleal muscle veins.

A rare case of venous aneurysm involving the soleal muscle vein in an 18-year-old woman is presented. The patients showed three episodes of ultrasonographically proven calf muscle thrombosis within 2 years. After a short course of low-molecular-weight heparin at a therapeutic dosage, complete thrombus recanalization was achieved. To prevent further thrombotic episodes, surgery including ligation and resection of the aneurysm was performed. At the 3-month follow-up study the patient had completely recovered.

Adolescent↗

Photoimmunosuppression.

Ultraviolet (UV) radiation can exert a variety of biological effects, including induction of skin cancer, premature skin ageing and inhibition of the immune system. The immunosuppressive properties of UV radiation are of major biological relevance since suppression of the immune system by UV radiation is not only responsible for the exacerbation of infectious diseases following UV exposure, but also contributes to the induction of skin cancer. Hence, understanding of the mechanisms by which UV radiation compromises the immune system is of primary importance. UV radiation suppresses the immune system in multiple ways. It inhibits antigen presentation, stimulates the release of immunosuppressive cytokines and induces the generation of lymphocytes of the suppressor subtype. In the following, some of the basic mechanisms underlying UV-induced immunosuppression will be discussed.

Antigen Presentation↗

Apoptosis induced by disruption of the actin cytoskeleton is mediated via activation of CD95 (Fas/APO-1).

Activation of the death receptor CD95 by its ligand or by UV radiation is associated with receptor clustering. The mechanism underlying this clustering is mostly unclear. Here we show that although disruption of the actin cytoskeleton by cytochalasin B (CyB) itself induces moderate apoptosis, it enhances apoptosis in HeLa cells induced either by UV radiation or an agonistic anti-CD95 antibody. CyB augments UV-induced apoptosis independently of UV-mediated DNA damage, since induction of DNA repair by exogenous DNA repair enzymes did not alter its enhancing effect. Inhibition of caspase-8, the most upstream caspase in CD95 signaling, blocked the apoptotic effect of CyB and the enhancing effect on UV- and CD95-induced apoptosis. Confocal laser scanning microscopy revealed that (i) CyB induces CD95 clustering, (ii) enhances UV-induced CD95 clustering, and (iii) CD95 clusters colocalize with disrupted actin filaments, suggesting a link between receptor clustering and actin rearrangement. Disruption of CD95 signaling by a dominant negative mutant of the signaling protein FADD protected from CyB-induced apoptosis and prevented the UV-enhancing effect. Accordingly, both the apoptotic and the enhancing effect of CyB was reduced in epidermal cells obtained from CD95 deficient mice (lpr) when compared to wild-type mice. These data suggest that disruption of the cytoskeleton causes apoptosis via activation of CD95 and enhances UV-induced apoptosis, possibly via aiding receptor clustering.

Actins↗

[Malignant melanoma: diagnostic value of F-18 FDG positron emission tomography].

Malignant melanoma is one of those malignancies with worldwide increasing incidence. The prognosis of malignant melanoma is bad because of its early hematogenous and lymphogenous metastases. Earliest possible diagnosis and sensitive follow-up of disease are important parameters to improve prognosis. In the literature a sensitivity of 92% and a specificity of 77% is found for blinded reading of F-18-FDG-PET of the whole body, and a specificity of 100% when clinical information was provided.

Fluorodeoxyglucose F18↗

Deep vein and isolated calf muscle vein thrombosis following long-haul flights: pilot study.

The risk of venous thromboembolism associated with long-haul flights is the subject of controversy. In a prospective, controlled study, we examined 160 passengers before and after return from a long-haul flight and 160 age-matched and sex-matched, non-travelling volunteers using venous compression ultrasound. Deep vein thrombosis was not observed in either group. Isolated calf muscle vein thrombosis (ICMVT) was present in 4/160 (2.5%) flight passengers and in 1/160 (0.6%) controls. All subjects with ICMVT were clinically asymptomatic, and ICMVT was located in the soleal muscle veins in all four subjects. Three of the four passengers with ICMVT had other risk factors for thrombosis.

Adult↗

Influence of oviductal fluid on ovine embryo viability.

The severe loss of developmental competence affecting fertilized ova when removed from the oviductal environment suggests that this organ plays a functional role in early embryonic development. The purpose of this study was to determine the effect of sheep heat-inactivated OF on the mortality rate of ovine embryos produced in vitro and transferred into recipients. As control groups we used embryos fertilized and cultured in media supplemented with different kinds of proteins (FCS, BSA). Transfer of embryos in the two pronuclei stage to the oviducts of synchronized recipients resulted in 60% of successfully termed pregnancies after incubation of embryos in OF, 40% in BSA and only 10% after FCS. All ewes were further assessed for pregnancy by ultrasonography 33, 53 and 80 days after embryo transfer. The highest embryo mortality appeared between day 33 and 52. We concluded that incubation of ovine oocytes in OF during the final period of the maturation process may play a functional role at the time of fertilization and early embryonic development.

Animals↗

IL-12 prevents the inhibitory effects of cis-urocanic acid on tumor antigen presentation by Langerhans cells: implications for photocarcinogenesis.

UV radiation induces skin cancer primarily by its DNA-damaging properties, but also by its capacity to suppress the immune system. The photoisomer of urocanic acid (UCA), cis-UCA, is an important mediator of UV-induced immunosuppression and is involved in the inhibition of tumor immunity. The immunomodulatory cytokine IL-12 is known to counteract many of the immunosuppressive effects of UV radiation, including UV-induced immune tolerance. In this study, we addressed whether IL-12 also reverts the immunosuppressive activities of cis-UCA. Cis-UCA inhibits the ability of Langerhans cells to present tumor Ags for primary and secondary tumor immune responses. IL-12 treatment completely prevented the suppression by cis-UCA. IL-12 also protected mice from cis-UCA-induced suppression of contact hypersensitivity responses. To study the effects of cis-UCA on Ag-processing and Ag-presenting function in vitro, Langerhans cells were treated with UCA isomers and incubated with OVA or OVA peptide(323-339) before exposure to OVA-specific transgenic T cells. Cis-, but not trans-UCA suppressed Ag presentation, which was completely reversed upon addition of IL-12. Since these findings suggest that cis-UCA may play an important role in photocarcinogenesis by inhibiting a tumor immune response, mice were chronically UVB irradiated to induce skin cancer. Whereas all mice in the control groups developed tumors, mice treated with a mAb with specificity for cis-UCA showed a significantly reduced tumor incidence. These data strongly indicate the importance of cis-UCA during photocarcinogenesis and support the concept of counteracting cis-UCA as an alternative strategy to prevent UV-induced skin cancer, possibly via the application of IL-12.

Animals↗

Overexpression of CD40 ligand in murine epidermis results in chronic skin inflammation and systemic autoimmunity.

CD40-CD40 ligand (L) interactions play a pivotal role in immune-mediated inflammatory responses via the activation of antigen-presenting cells (APCs). To investigate the effects of continuous activation of resident tissue APCs, in this case the Langerhans cells (LCs) of the skin, CD40L expression was targeted to the basal keratinocytes of the epidermis of mice using the keratin-14 promoter. Approximately 80% of the transgenic (Tg) mice spontaneously developed dermatitis on the ears, face, tail, and/or paws. Compared with littermates, Tgs had a >90% decrease in epidermal LCs yet increased numbers within the dermis suggestive of enhanced emigration of CD40-activated LCs. Tgs also displayed massive regional lymphadenopathy with increased numbers of dendritic cells and B cells. Moreover, a decrease in IgM and an increase in IgG1/IgG2a/IgG2b/IgE serum concentrations was detectable. Screening for autoantibodies revealed the presence of antinuclear antibodies and anti-dsDNA antibodies implicative of systemic autoimmunity. Accordingly, renal Ig deposits, proteinuria, and lung fibrosis were observed. Adoptive transfer of T cells from Tgs to nonTg recipients evoked the development of skin lesions similar to those found in the Tgs. Dermatitis also developed in B cell-deficient CD40L Tg mice. These findings suggest that in situ activation of LCs by CD40L in the skin not only leads to chronic inflammatory dermatitis but also to systemic mixed-connective-tissue-like autoimmune disorders, possibly by breaking immune tolerance against the skin.

Animals↗

Osteodystrophia fibrosa in two guinea pigs.

Two adult guinea pigs were examined because they were lethargic and reluctant to walk. Additionally, I guinea pig had otitis media, and the other had dental malocclusion. Both guinea pigs had been fed a commercially available diet of cereals and pellets enriched with vitamin C and formulated for this species. Radiographically, the guinea pigs had coarse trabecular bone patterns, skeletal deformations, pathologic fractures, and polyarthritic degenerative joint disease. A double cortical line was also evident on several long bones, the pelvis, and the vertebrae. A diagnosis of osteopenia was confirmed by use of dual-energy x-ray absorptiometry. Analysis of a food sample fed to 1 guinea pig revealed calcium and phosphorus contents of 0.524 and 0.425%, respectively (Ca:P ratio, 1.23:1). Microscopic examination of bone tissue from both guinea pigs revealed severe fibrous osteodystrophy. Nutritional secondary hyperparathyroidism caused by calcium-phosphorus imbalance was considered to be the underlying cause of osteodystrophia fibrosa in both guinea pigs.

Animal Feed↗

Intracellular persistence of Staphylococcus aureus small-colony variants within keratinocytes: a cause for antibiotic treatment failure in a patient with darier's disease.

Intracellular persistence assays were performed with small-colony variants (SCVs) derived from a patient with Darier's disease from whom different phenotypes and genotypes of Staphylococcus aureus were isolated over a 28-month period; the assays revealed that >100-fold more SCV cells persisted intracellularly relative to the normal phenotype. The presence of intracellular S. aureus SCVs may protect against host defenses and antibiotic therapy and thus may have contributed to this patient's very prolonged skin infection.

DNA, Bacterial↗

Ultraviolet radiation inhibits interleukin-2-induced tyrosine phosphorylation and the activation of STAT5 in T lymphocytes.

UV radiation was recently found to hinder interferon-gamma from exerting its biological effects by inhibiting the phosphorylation of signal transducer and activator of transcription (STAT)-1, a crucial signal transducing protein in the interferon-gamma pathway. Because this activity by UV may contribute to its immunosuppressive properties we studied whether this is specific for STAT1 or whether UV also affects other members of the STAT family. STAT5 is crucially involved in signaling of interleukin (IL)-2, enabling up-regulation of the IL-2 receptor alpha chain, an essential component of the high affinity IL-2 receptor. Exposure of the murine T cell line CTLL to IL-2 caused tyrosine phosphorylation of STAT5 that was remarkably reduced when cells were exposed to UV. Accordingly, STAT5 binding activity was significantly impaired in UV-exposed cells. In contrast, IL-2-induced tyrosine phosphorylation of the kinases Jak1 and Jak3 located upstream of STAT5 was not affected by UV. The effect of UV on STAT5 phosphorylation was antagonized by orthovanadate, implying involvement of a phosphatase in this process. Accordingly, up-regulation of the IL-2 receptor alpha chain was reduced in cells that were treated with IL-2 plus UV. Because STAT5-mediated IL-2 effects are vital for normal immune functions, inhibition of STAT5 signaling by UV may contribute to its well known immunosuppressive properties.

Animals↗

Pyodera gangrenosum after aortic valve replacement.

A 68-year-old male patient developed pyoderma gangrenosum after elective aortic valve replacement. Treatment with steroids and clofazimine was initiated, which resulted in rapid cessation of the necrotic process. Due to thoracic instability, stabilization of the sternum was performed followed by surgical debridement and atraumatic wound closure. Postoperatively, immunosuppression with cyclosporine A was added; the patient recovered completely. Pyoderma gangrenosum is a potential life-threatening complication that must be considered in patients with severely impaired wound healing after cardiac operation.

Aged↗

Patients with persistent APC-resistance without factor V Leiden mutation.

BACKGROUND: Activated protein C (APC) resistance and factor V Leiden mutation are major risk factors for deep venous thrombosis. Previous work has led to the view that the coagulation phenotype and the genetic defect are associated in almost all patients. It has been reported about single APC-resistant patients without associated factor V Leiden, but significance and thrombotic risk of this constellation have not yet been established. PATIENTS AND METHODS: We tested 486 consecutive patients with deep venous thrombosis, arterial disease or other than vascular disease for APC-resistance with a factor VIII based assay. RESULTS: 149 patients (31%) showed a pathological APC-ratio. Sensitivity and specificity for detection of factor V Leiden were 100% and 40%, respectively. At 6 months follow-up APC-ratio returned to normal in 55% of the patients with initial pathological APC-resistance. At 12 months follow-up 91% of the patients with persistent APC-resistance showed a pathological ratio as well. CONCLUSIONS: Patients with APC-resistance not due to factor V Leiden can be attributed to one subset with reversible APC-resistance--possibly due to a hypercoagulable state in an acute thrombotic situation, and to another with persistent APC-resistance.

Activated Protein C Resistance↗

Complete compression ultrasound for the diagnosis of proximal and distal deep venous thrombosis--a retrospective outcome study.

BACKGROUND: Compression ultrasound is considered the preferred test for the diagnosis of deep vein thrombosis of the leg (DVT). Since sensitivity for distal thrombosis is low-additional tests are required. We developed a protocol of complete compression ultrasound of all venous segments of the leg (CCUS). A retrospective outcome study was performed to get an estimate of the rate of indeterminate results necessitating repeated testing as well as for the clinical safety of CCUS in a cohort of consecutive, unselected patients. PATIENTS AND METHODS: Case records of all patients referred for clinical suspicion of deep vein thrombosis within a three months period were reviewed. Patients with negative CCUS were followed directly or via the general practitioner in order to know whether an episode of venous thromboembolism had been documented since the initial CCUS. RESULTS: 132 inpatients and 154 outpatients were identified. Clinical probability was high in 50 patients, medium in 142, and low in 94. The first CCUS was negative in 209 cases. Five patients (1.8%) had repeated CCUS within the next 7 days because of incomplete visualisation of the distal veins and turned out to be negative as well. Of all 214 patients with negative CCUS a clinical follow-up information was obtained after 168 +/- 25 days. Five patients had died, none due to pulmonary embolism. In two patients deep vein thrombosis had been documented (0.9% [95% CI: 0.1-3.3%]) 148 and 172 days after CCUS, respectively. CONCLUSION: CCUS for diagnosis of DVT needs to be repeated in very few cases only. Clinical safety seems to fall into the same range as with combined algorithms and should be tested in a prospective design. Patients with medium and high probability showed a very low incidence of DVT within three months following CCUS; therefore, they may be included in a prospective outcome study.

Adolescent↗