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Biomedical subjects

T Schwarz

Publications and source records attributed to T Schwarz.

At least 73 records · Page 4Linked to original sources

Aortic body chemodectoma causing pulmonary oedema in a cat.

A seven-year-old male domestic shorthaired cat was presented with persistent dyspnoea. Thoracic radiography and echocardiography revealed pulmonary oedema and a mass at the base of the heart. At necropsy the mass was found to be an aortic body chemodectoma that had metastasised to the sternal lymph node. This is a rare tumour in the cat, the third reported case where there was evidence of metastasis, and only the second reported case where there was evidence of lymphocytic infiltration of the primary tumour. Pulmonary oedema is an unusual presentation of this tumour in the cat.

Animals↗

Radiographic features of a lateral extracapsular wire suture in the canine cranial cruciate deficient stifle.

Radiographs of 74 dogs (84 stifles) presented with a cranial cruciate ligament rupture and surgically treated using a lateral extracapsular wire (LEW) were reviewed. A strand of orthopaedic wire was surgically placed caudally around the lateral fabella and through a predrilled hole in the tibial crest. At six week follow-up, the LEW was broken at least once in 26 of 33 stifles, predominantly in the area of the lateral fabella. In five stifles, the LEW had slipped off the fabella and was displaced distally along the gastrocnemius muscle. Six months after surgery, the LEW was often broken at several sites. LEW migration was rare. Osteolysis and sclerosis at the site of LEW penetration through the tibial crest occurred in about two-thirds of the stifles examined.

Animals↗

Pacemaker automaticity.

The automated measurement of the main electrical parameters of pacemakers, such as battery voltage, current drain, pacing impedance, sensing levels, and pacing thresholds enables a continuous monitoring of the adequate functioning of the implanted device. New technologies in device interrogation, data transfer, and patient alert functions will enhance therapy safety significantly by the immediate detection of all, including transient, device malfunctions. The introduction of this technology will result in major changes in follow-up of patients with pacemakers. Technically we are very close to the goal of a fully automated pacemaker, although clinical acceptance lags behind. Clinical studies are necessary to demonstrate the beneficial effects of automated device functions, with regard to the main rationales for pacemaker automatization: increased patient safety, improved quality of life, and an improvement in the cost-benefit ratio in pacemaker therapy.

Arrhythmias, Cardiac↗

Frequency of polymorphisms in the B-domain of factor V gene in APC-resistant patients.

In this study we investigated a group of patients in whom a resistance to APC (activated protein C) was found but no Leiden mutation existed in the presence of missense mutations in the first 1200 bp of the Exon 13 (B-domain) in the factor V (FV) gene. The determination of the APC response was performed using the Immunochrom(R) APC response Test Kit. The mutations were determined by temperature gradient gel electrophoresis and DNA sequencing. In the APC-resistant patients without the FV Leiden, we found 4 silent mutations (2298C>T, 2325T>C, 2379A>G, 2391A>G) and 4 missense mutations (2540A>C, 2663A>G, 2684A>G, 2863A>G), which code for the amino acids N789T (GenBank Accession # AF119360), K830R, H837R, and K897E. In all of the patients and controls, the polymorphisms at nucleotide positions 2391, 2663, 2684, and 2863 appeared to be associated. In the major allele all bases are A (A allele) and in the minor allele are G (G allele). A significantly lower G allele frequency was observable in the patient group than in the control group (0.14 vs. 0.31; p<0.05). The frequency of the 2540C allele, which is associated with the 2379G and the 4070G allele (non-Leiden!), did not differ significantly between the patient and the control groups. We suggest that the G allele, which is not associated with the FV Leiden mutation, as well as the [2379G; 2540C; 4070G] allele have no influence on the APC cofactor function itself, or only subtly as determined in the test systems used.

Activated Protein C Resistance↗

Vacuum disk and facet phenomenon in a dog with cauda equina syndrome.

A 7-year-old castrated male Rottweiler was evaluated for an 18-month history of bilateral hind limb lameness, signs of pain on rising, and mild ataxia. A gas-filled lumbosacral disk space (vacuum disk phenomenon) was revealed by use of computed tomography. Additional smaller gas bubbles were in the periphery of the disk and between the degenerated L5-L6 dorsal articular facets (vacuum facet phenomenon). Vacuum disk and facet phenomena have been described in humans with degenerative disk and vertebral articular facet joint disease; gas attracted from surrounding tissues accumulates within clefts of the degenerated disk or in unstable facet joints. Vacuum disk phenomenon has been reported in dogs and indicates degenerative disk disease. The phenomenon is more commonly observed by use of computed tomography, compared with conventional radiography, and can be elicited by hyperextension of the vertebral column.

Animals↗

Mycophenolate mofetil impairs the maturation and function of murine dendritic cells.

The immunosuppressive drug, mycophenolate mofetil (MMF), has been successfully introduced in allogeneic transplantation medicine and, more recently, in the treatment of autoimmune skin disorders. MMF inhibits lymphocyte proliferation via a blockade of the enzyme inosine 5'-monophosphate dehydrogenase, an enzyme on which lymphocytes solely depend to generate the purines necessary for DNA/RNA synthesis. To investigate the effects of MMF on cutaneous immune responses, a murine model of contact hypersensitivity (CHS) was used, with oxazolone or trinitrochlorobenzene as a contact allergen. Compared with the respective vehicle, i.p. applied MMF significantly inhibited the elicitation and, surprisingly, the induction of CHS responses. This prompted further studies into the effects of MMF on Ag presentation. Bone marrow-derived dendritic cells (DC) were cultured with GM-CSF and IL-4 in the presence of MMF and were tested for their Ag-presenting capacity. Sensitization and elicitation of CHS and delayed-type hypersensitivity responses by s. c. injected haptenated DC were reduced upon preincubation of DC with MMF. CHS responses were not impaired upon resensitization, indicating that MMF does not induce hapten-specific immunotolerance. In addition, MMF decreased the ability of DC to stimulate allogeneic T cells in MLR assays. Accordingly, flow cytometric analyses revealed a dose-dependent reduction of the expression of CD40, CD80, CD86, I-A, and ICAM-1 on DC with a concurrent reduction of IL-12 production. These data suggest that MMF, in addition to affecting T lymphocytes, directly affects APC, resulting in an impairment of immune responses. They furthermore point to a possible role of inosine 5'-monophosphate dehydrogenase in the maturation of DC.

Animals↗

Evidence for functional relevance of CTLA-4 in ultraviolet-radiation-induced tolerance.

Hapten sensitization through UV-exposed skin induces hapten-specific tolerance that can be adoptively transferred by injecting T lymphocytes into naive recipients. The exact phenotype of T cells responsible for inhibiting the immune response and their mode of action remain unclear. Evidence exists that CTLA-4 negatively regulates T cell activation. We addressed whether CTLA-4 is involved in the transfer of UV-induced tolerance. Injection of lymph node cells from mice that were sensitized with dinitrofluorobenzene (DNFB) through UV-irradiated skin inhibited induction of contact hypersensitivity against DNFB in the recipient animals. When CTLA-4+ cells were depleted, transfer of suppression was lost. Likewise, significantly fewer lymphocytes enriched for CTLA-4+ cells were necessary to transfer suppression than unfractionated cells. Expression of CTLA-4 appears to be functionally relevant, since in vivo injection of a blocking anti-CTLA-4 Ab was able to break UV-induced tolerance and inhibited transfer of suppression. Upon stimulation with dendritic cells in the presence of the water-soluble DNFB analogue, DNBS, CTLA-4+ T cells from DNFB-tolerized mice secreted high levels of IL-10, TGF-beta, and IFN-gamma; low levels of IL-2; and no IL-4, resembling the cytokine pattern of T regulatory 1 cells. Ab blocking of CTLA-4 resulted in inhibition of IL-10 release. Accordingly, transfer of tolerance was not observed when recipients were treated with an anti-IL-10 Ab. Hence we propose that T cells, possibly of the T regulatory 1 type, transfer UV-mediated suppression through the release of IL-10. Activation of CTLA-4 appears to be important in this process.

Abatacept↗

Ultraviolet radiation-induced interleukin 6 release in HeLa cells is mediated via membrane events in a DNA damage-independent way.

Evidence exists that ultraviolet radiation (UV) affects molecular targets in the nucleus or at the cell membrane. UV-induced apoptosis was found to be mediated via DNA damage and activation of death receptors, suggesting that nuclear and membrane effects are not mutually exclusive. To determine whether participation of nuclear and membrane components is also essential for other UV responses, we studied the induction of interleukin-6 (IL-6) by UV. Exposing HeLa cells to UV at 4 degrees C, which inhibits activation of surface receptors, almost completely prevented IL-6 release. Enhanced repair of UV-mediated DNA damage by addition of the DNA repair enzyme photolyase did not affect UV-induced IL-6 production, suggesting that in this case membrane events predominant over nuclear effects. UV-induced IL-6 release is mediated via NFkappaB since the NFkappaB inhibitor MG132 or transfection of cells with a super-repressor form of the NFkappaB inhibitor IkappaB reduced IL-6 release. Transfection with a dominant negative mutant of the signaling protein TRAF-2 reduced IL-6 release upon exposure to UV, indicating that UV-induced IL-6 release is mediated by activation of the tumor necrosis factor receptor-1. These data demonstrate that UV can exert biological effects mainly by affecting cell surface receptors and that this is independent of its ability to induce nuclear DNA damage.

Antigens, CD↗

[Market hyperpigmentation in psoriatic plaque as a sequelae of combination therapy with UVB-311 and calcipotriol].

The combination of UVB phototherapy with topical application of vitamin D analogs is frequently used for treating psoriasis. This regimen is not only very effective but also has only minimal side effects. Pronounced, persistent hyperpigmentation developed in the psoriatic plaques in a patient who was treated with combined UVB (311 nm) radiation and topical calcipotriol.

Aged↗

Photopatch testing: the 12-year experience of the German, Austrian, and Swiss photopatch test group.

BACKGROUND: In 1984, the German, Austrian, and Swiss Photopatch Test Group was founded to standardize the photopatch test procedure and to investigate photoallergic reactions, as well as the epidemiology of photoallergy, in central Europe. Therefore in a first test period from 1985-1990, 32 test substances were applied on the backs of patients suspected to be photosensitive. After evaluation of these data, some substances were dismissed, and others were additionally integrated into the test tray. Thus a modified test tray comprising 26 test substances was used for the second test period (1991-1997). OBJECTIVE: According to the standard photopatch test procedure defined in the first test period, the aim of this multicenter study was to apply compounds from the modified second test tray to a large group of photosensitive patients. After evaluation of the second test period (1991-1997), the outcome was compared with the results of the first period. On the basis of these results and influenced by concurrently published case reports, a third modified photopatch test tray has been established. METHODS: After the application of a duplicate test tray for 24 hours, one test site was irradiated with 10 J/cm(2) UVA, and the other test site served as the control area. Readings were performed immediately and 24, 48, and 72 hours after irradiation. Test reactions were qualitatively graded according to a 4-point scale and classified by the investigators of the participating centers. In 49 participating clinics 1261 photopatch tests were performed. All data were subjected to computer-assisted analysis by using a specially developed software to classify all positive test reactions as plain contact or photoinduced reactions (nonspecific, toxic, or allergic photoreactions) and to define substance-specific reaction patterns. RESULTS: In test period 1 data of 1129 patients were evaluated. From 2859 positive test reactions, 28.6% were excluded as plain contact reactions, 71.4% were found to be photoinduced reactions, and 3.8% were classified as photoallergic. In test period 2 data of 1261 patients were evaluated. One thousand four hundred fifteen positive test reactions were observed, and of these, 28.7% were excluded as plain contact reactions, 71.3% were classified as photoinduced reactions, and 8.1% were classified as photoallergic reactions. In both test periods nonsteroidal anti-inflammatory drugs, disinfectants, and phenothiazines represented the leading photoallergens in the evaluated central European region. By using computer-assisted reaction pattern analysis, substance-specific reaction patterns could be distinguished. These substance-specific reaction patterns comprised 4 main categories: the well-known decrescendo (phototoxic) and crescendo (photoallergic) reaction patterns, as well as a combined and a plateau pattern. CONCLUSION: The test modification after the first test period led to a notably reduced number of positive (mainly nonphotoallergic and thus nonrelevant) test reactions per patient in the second test period (from 2.6 to 1.1). In contrast, the percentage of photoallergic reactions increased significantly from 3.8% to 8.1% of all positive test reactions. Test modifications after the first test period led to a remarkably improved specificity of the photopatch test. Furthermore, substance-specific reaction patterns observed in test period 1 were confirmed in test period 2.

Adult↗

UVA rush hardening for the treatment of solar urticaria.

Induction of tolerance by subsequent UV exposures is the most effective therapy for solar urticaria; however, it is time-consuming and takes a long time until protection is achieved. Three patients with solar urticaria were exposed to multiple UVA irradiations at 1-hour intervals per day. With this rush hardening regimen, protection was achieved within 3 days.

Adult↗

Female mice heterozygous for IKK gamma/NEMO deficiencies develop a dermatopathy similar to the human X-linked disorder incontinentia pigmenti.

IKK gamma/NEMO is the essential regulatory subunit of the I kappa B kinase (IKK), encoded by an X-linked gene in mice and humans. It is required for NF-kappa B activation and resistance to TNF-induced apoptosis. Female mice heterozygous for Ikk gamma/Nemo deficiency develop a unique dermatopathy characterized by keratinocyte hyperproliferation, skin inflammation, hyperkeratosis, and increased apoptosis. Although Ikk gamma+/- females eventually recover, Ikk gamma- males die in utero. These symptoms and inheritance pattern are very similar to those of incontinentia pigmenti (IP), a human genodermatosis, synthenic with the IKK gamma/NEMO locus. Indeed, biopsies and cells from IP patients exhibit defective IKK gamma/NEMO expression but normal expression of IKK catalytic subunits. This unique self-limiting disease, the first to be genetically linked to the IKK signaling pathway, is dependent on X-chromosome inactivation. We propose that the IKK gamma/NEMO-deficient cells trigger an inflammatory reaction that eventually leads to their death.

Animals↗

[The concept of ambulatory therapy of proximal deep venous thrombosis].

In recent studies outpatient treatment of proximal deep venous thrombosis with low-weight-molecular heparin is shown as safe and effective as the treatment within the hospital. The incidence of recurrent thromboembolism, major bleeding and mortality is not higher in an ambulatory setting than in the hospital. The comfort of the patient is higher, the costs can be reduced. The present review discusses the different conditions for ambulatory treatment of deep venous thrombosis. The question will be addressed which patients will probably be considered for outpatient treatment of deep vein thrombosis.

Ambulatory Care↗

Molecular mechanisms of UV-induced apoptosis.

Sunburn cells, single standing cells with typical morphologic features occurring in UV-exposed skin, have been recognized as keratinocytes undergoing apoptosis following UV irradiation. Induction of apoptosis following UV exposure appears to be a protective mechanism, getting rid off severely damaged cells that bear the risk of malignant transformation. UV-mediated apoptosis is a highly complex process in which different molecular pathways are involved. These include DNA damage, activation of the tumor suppressor gene p53, triggering of cell death receptors either directly by UV or by autocrine release of death ligands, mitochondrial damage and cytochrome C release. Detailed knowledge about the interplay between these pathways will increase our understanding of photocarcinogenesis. This review briefly discusses recent findings concerning the molecular mechanisms underlying UV-induced apoptosis.

Apoptosis↗

Inhibition of growth of melanoma cells by CD95 (Fas/APO-1) gene transfer in vivo.

Interaction of CD95 ligand with its cognate receptor CD95 induces apoptotic cell death. Alterations in this pathway within tumor cells can result in escape from apoptosis and from immune surveillance. Melanoma cells recently were found to escape an immune attack via high expression of CD95 ligand, thereby inducing apoptosis of activated T lymphocytes. When screening four human melanoma cell lines for expression of CD95 and CD95 ligand, respectively, an inverse correlation was found, i.e., cells expressing high levels for CD95 ligand (CD95L(high)) were almost negative for CD95 and vice versa. Since coexpression of CD95 and CD95 ligand may lead to apoptosis by autocrine suicide or fratricide, it was tested whether overexpression of CD95 in CD95L(high) melanoma cells results in apoptotic cell death. Upon transfection with a cytomegalovirus-promoter-driven expression vector encoding the CD95 gene, CD95L(high) melanoma cells underwent apoptosis at a much higher level than CD95L(low) melanoma cells. Apoptosis appeared to be due to the activation of CD95 as cell death was inhibited by cotransfection with a dominant negative mutant for the CD95 signaling protein, Fas-associated protein with death domain. Tumor progression of CD95L(high) melanoma cells transplanted into nude mice was significantly reduced when recipient animals were injected with liposomes containing the CD95 expression vector. As demonstrated by immunohistochemistry and TUNEL staining, in vivo transfected tumor cells expressed CD95 and underwent apoptotic cell death. Hence, this study indicates that delivery of the CD95 gene inhibits tumor growth in vivo and thus might be a therapeutic strategy to treat tumor cells that express high levels of CD95 ligand. J Invest Dermatol 115:1008-1014 2000

Apoptosis↗