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Biomedical subjects

T Schwarz

Publications and source records attributed to T Schwarz.

At least 109 records · Page 6Linked to original sources

[Embolia cutis medicamentosa (Nicolau syndrome) after intra-articular injection].

Embolia cutis medicamentosa (Nicolau Syndrome) is a very rare complication of intramuscular injections which presents with extensive necrosis of the injected skin area. Intra-arteria and/or para-arterial injections after prior perforation of certain vessels are discussed as possible pathogenetic mechanisms. We describe the occurrence of embolia cutis medicamentosa after intra-articular injections into the knee.

Anti-Inflammatory Agents↗

Popliteal entrapment syndrome: non-invasive diagnosis and complete recovery after surgery in an 11-year-old boy.

We present an unusual case of popliteal entrapment syndrome type I in an 11-year-old boy. Presenting symptoms were exercise-related pain and pallor in his left lower leg. The diagnosis of popliteal entrapment syndrome was established by acral plethysmography, colour-coded Doppler sonography and MRI. After myotomy of the gastrocnemius muscle the symptoms resolved completely. Post-operative duplex scan showed normal blood flow, even in plantar flexion of the foot.

Arterial Occlusive Diseases↗

Mechanisms involved in ultraviolet light-induced immunosuppression.

Ultraviolet light (UV) represents one of the most relevant environmental factors influencing humans, especially with regard to its hazardous health effects, which include premature skin aging, skin cancer, and exacerbation of infectious diseases. Several of these effects are mediated by the immunosuppressive properties of UV. UV can compromise the immune system in several ways, e.g., by affecting the function of antigen-presenting cells, inducing the release of cytokines, and modulating the expression of surface molecules. Recently a link between UV-induced immunosuppression and apoptosis was recognized. In the following, the basic mechanisms underlying UV-induced immunosuppression will be discussed.

Animals↗

Bipolar atrial sensing thresholds in sinus rhythm and atrial tachyarrhythmias. A comparative analysis in patients with DDDR pacemakers.

UNLABELLED: Automatic mode switching (AMS) function in dual chamber pacemakers depends on adequate detection of atrial tachyarrhythmias. There are few data on showing how intra-operative atrial signal amplititude during sinus rhythm can predict atrial tachyarrhythmias after pacemaker implantation. In 43 patients undergoing DDDR pacemaker implantation and atrioventricular nodal ablation for the treatment of drug-refractory paroxysmal atrial fibrillation, atrial sensing thresholds during sinus rhythm and during induced atrial tachyarrhythmias (24-48 h after device implantation) were analysed. Five different DDDR pacemaker systems were implanted (Chorus 7034, Ela Medical n = 13; Meta DDDR 1254, Telectronics Pacing Systems n = 12; Vigor DR 1230, Guidant n = 6; Trilogy DR 2364, Pacesetter, n = 2; Kappa DR 401, Medtronic USA n = 10). Every patient received a steroid-eluting, screwing, bipolar atrial lead (Medtronic, Capsure-Fix 4068). The mean P wave amplitude during implantation was 3.91 +/- 1.14 mV. The mean atrial sensing threshold during sinus rhythm and during all modes of induced atrial tachyarrhythmias was 3.35 +/- 1.0 mV, and 1.52 +/- 0.92 mV, respectively (P < 0.001). Atrial fibrillation was induced in 36 patients. The mean sensing threshold during sinus rhythm in this patient group was 3.39 +/- 1.01 mV, the mean sensing threshold during atrial fibrillation was 1.27 +/- 0.56 mV, reflecting a 63% reduction of sensing threshold compared with sinus rhythm (P < 0.001). Atrial flutter was induced in seven patients. The mean sensing threshold during sinus rhythm was 2.92 +/- 1.19 mV, the mean sensing threshold during atrial flutter was 2.79 +/- 1.26 mV, reflecting a reduction of 5% (ns) compared with sinus rhythm. Atrial sensing thresholds during sinus rhythm were significantly correlated with sensing thresholds during atrial tachyarrhythmias (r = 0.44; P < 0.002), but there were significant variations in intra-individual results. The reduction of atrial sensing thresholds between sinus rhythm and induced atrial tachyarrhythmias ranged from 30% to 82%. CONCLUSION: Bipolar atrial sensing thresholds during sinus rhythm are correlated with sensing thresholds during atrial tachyarrhythmias, but there is a large degree of variance in individual patients. A 4:1 to 5:1 atrial sensing safety margin based on sensing threshold during sinus rhythm is a predictor for adequate postoperative detection of atrial tachyarrhythmias and the function of AMS devices.

Arrhythmia, Sinus↗

Clinical evaluation of a prototype passive fixation dual chamber single pass lead for dual chamber ICD systems.

UNLABELLED: Dual chamber ICD systems use two separate leads for sensing. We developed and tested a new prototype of a single pass dual chamber passive fixation lead for dual chamber ICDs. METHODS AND RESULTS: The prototype was a modification of the Guidant CPI Endotak DSP lead. The additional sensing electrode for the right atrium consisted of a side-mounted porous atrial ring electrode (AR). Atrial signals were recorded from the lead in patients during normal sinus rhythm (NSR), atrial fibrillation (AFib), and/or atrial flutter (AFl) with the AR in stable contact with the atrial wall or floating. During NSR, with the AR in contact with the atrial wall, an average P wave amplitude of 7.2 +/- 1.5 mV (mean +/- SD, n = 12) was measured. After induction of Afib/AFl, the single amplitude decreased to 3.6 +/- 1.5 mV (n = 8) during AFib and 3.4 +/- 1.7 mV (n = 9) during AFl. Amplitudes dropped between 53% and 75% when the AR lost atrial wall contact. The atrial pacing threshold was 1.0 +/- 0.4 V (n = 16) when the AR was in contact with the atrial wall. CONCLUSIONS: In future dual chamber ICDs the signals from a passive fixation single pass lead could be used for atrial sensing and pacing as long as the sensing electrode for the right atrium remains in contact with the atrial wall. This system might lead to a simpler, less invasive implantation of dual chamber ICD systems.

Atrial Fibrillation↗

Subdural injection of contrast medium as a complication of myelography.

In a retrospective evaluation of 654 canine and feline myelograms, 58 were found to have been complicated by injection of the contrast medium into the subdural space. The medium was present predominantly dorsal to the spinal cord, with a sharp dorsal border and an undulating ventral border. Confirmation that this myelographic appearance was due to subdural localisation was achieved using fresh cadavers injected with contrast medium labelled with Indian ink. It was further showed that the dorsal accumulation of contrast medium was due to the denticulate ligaments which restricted the ventral extension of the contrast medium.

Animals↗

Phenol degradation by an enterobacterium: a Klebsiella strain carries a TOL-like plasmid and a gene encoding a novel phenol hydroxylase.

Although phenol catabolism is described for many different microorganisms, there is no example for such a pathway in an enterobacterial strain. Here we characterize a Klebsiella oxytoca strain that grows on phenol as the only source of carbon and energy. As the key enzyme of phenol degradation, phenol hydroxylase was purified to apparent homogeneity. Compared with other phenol hydroxylases, the Klebsiella enzyme differs with respect to several properties: (i) SDS-PAGE and gel-filtration analysis of the purified protein revealed that the enzyme is a monomer with a molecular mass of 156 kDa; (ii) steady-state kinetic measurements resulted in a K(m) value of 0.22 mM for phenol; and (iii) the enzyme is both dependent on NADPH/FAD and sensitive to EDTA. Further degradation of catechol, the reaction product of phenol hydroxylase, may occur via the effective meta-fission pathway often located on TOL or TOL-like plasmids. Such a plasmid was prepared from the Klebsiella strain and further characterized. The given data demonstrate that the isolated strain exhibits all characteristics of an efficient phenol-degrading microorganism.

Biodegradation, Environmental↗

[Value of mistletoe lectin standardized mistletoe extract for evaluating antitumor properties].

It could be shown from several experiments that carbohydrate-binding mistletoe lectins represent the pharmacologically active constituents of mistletoe extracts. On the basis of these findings, it was possible to develop an extract preparation standardized with respect to the mistletoe lectin concentration. This drug is the first mistletoe preparation that fulfills the criteria of the guidelines for the development of drugs (1) regarding its quality and stability of the active ingredients under certain storage conditions. The quality of this preparation has also been shown in several animal models to demonstrate antitumoral potencies.

Adjuvants, Immunologic↗

Bed rest in deep vein thrombosis and the incidence of scintigraphic pulmonary embolism.

In several countries of central Europe, patients with acute proximal deep vein thrombosis (DVT) are treated not only by anticoagulation and compression therapy but additionally by strict bed rest for 6-8 days. Until now the theoretical assumption that bed rest substantially reduces the incidence of pulmonary embolism has not been subjected to empirical verification. Patients with acute proximal DVT proven by ultrasonography were randomly assigned to strict bed rest for 8 days (treatment group) or to stay mobilised (control group). In both groups, basic treatment consisted in anticoagulation by subcutaneous low molecular weight heparin/vitamin-K-antagonist and compression therapy. The incidence of pulmonary embolism was assessed by serial ventilation/perfusion SPECT on day 1 and days 8-10. Of the 309 patients with proximal DVT considered for inclusion, 180 were excluded according to the study protocol, and 3 did not give informed consent. One hundred and twenty-six patients were randomly assigned to observe bed rest (n = 62) or to keep mobilised (n = 64). Four patients refused follow-up lung scan. A new lung perfusion defect was detected in 10/59 patients in the treatment group compared to 14/63 patients in the control group (one-sided p-value = 0.25; power 0.8). Bed rest as an additional measure in the treatment of DVT is not able to substantially reduce the incidence of scintigraphically detectable pulmonary embolism. The discomfort and costs associated with the prescription of bed rest in DVT are obviously inappropriate.

Adult↗

Impaired cutaneous immune responses in Thy-1-deficient mice.

Thy-1 is a cell surface glycoprotein expressed mainly on brain and lymphoid tissue. Although the functions of Thy-1 are incompletely understood, evidence exists that Thy-1 participates in T cell activation. To examine the functional role of Thy-1 in cutaneous immune responses in vivo, Thy-1 gene-targeted mice (Thy-1-/-) and wild-type mice (Thy-1+/+) were immunized with the hapten oxazolone. After challenge with oxazolone, contact hypersensitivity responses in Thy-1-/- mice were reduced by 25% compared with Thy-1+/+ mice. Likewise, irritant dermatitis induced by croton oil was also decreased. In addition, Thy-1-/- mice showed a significantly reduced delayed-type hypersensitivity response after injection of allogeneic spleen cells into the hind footpads of allosensitized animals when compared with Thy-1+/+ mice. Moreover, proliferative responses to immobilized anti-CD3 were decreased in peripheral Thy-1-/- lymphocytes; this decrease was associated with a significantly reduced intracellular Ca2+ influx and protein tyrosine phosphorylation, indicating impairment of early lymphocyte activation. In contrast, the T cell proliferation induced by mitogens was normal, suggesting that Thy-1 expression weakly contributes to TCR-mediated T cell activation. Epidermal Langerhans cells and bone marrow-derived dendritic cells from Thy-1-/- mice exhibited a normal expression of costimulatory surface molecules as well as an unaltered ability to stimulate allogeneic T cells. Taken together, these findings demonstrate that a lack of Thy-1 expression does not generally compromise the immune system; however, Thy-1 expression may be involved in the fine-tuning of T cell-mediated immune responses.

Animals↗

Interleukin-1 protects transformed keratinocytes from tumor necrosis factor-related apoptosis-inducing ligand.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor family. It induces apoptosis primarily of transformed but not of normal cells and may therefore be a promising anti-cancer drug. Studying the role of TRAIL in apoptosis of keratinocytes, we detected TRAIL transcripts and protein in both normal human keratinocytes and transformed keratinocyte cell lines HaCaT and KB. Although normal keratinocytes were resistant to TRAIL, HaCaT and KB cells underwent apoptosis following TRAIL exposure. When HaCaT and KB cells were pretreated with the pro-inflammatory cytokine interleukin-1 (IL-1), cells became resistant to TRAIL-induced apoptosis. IL-1 significantly induced activation of the transcription factor NFkappaB in transformed keratinocytes. Moreover, the proteasome inhibitor MG132, which inhibits IL-1-induced NFkappaB activation, completely prevented the protective effect of IL-1. Thus, IL-1 appears to protect transformed keratinocytes from the cytotoxic effect of TRAIL via activation of NFkappaB. These data suggest that NFkappaB activation may protect cells from TRAIL-induced apoptosis and indicate a TRAIL receptor-independent pathway, which allows cells to escape the cytotoxic effect of TRAIL. Because IL-1 is secreted by a variety of tumor cells and is also released by inflammatory cells participating in the tumor-host immune response, tumors under these conditions could become resistant to TRAIL.

Apoptosis↗

Short-term regulation of insulin gene transcription by glucose.

Whereas short-term regulation of insulin biosynthesis at the level of translation is well accepted, glucose-dependent transcriptional control is still believed to be a long-term effect occurring after more than 2 hr of glucose stimulation. Because pancreatic beta cells are exposed to elevated glucose levels for minutes rather than hours after food uptake, we hypothesized the existence of a short-term transcriptional control. By studying the dynamics of newly synthesized (prepro)insulin RNA and by employing on-line monitoring of gene expression in single, insulin-producing cells, we were able to provide convincing evidence that insulin gene transcription indeed is affected by glucose within minutes. Exposure of insulinoma cells and isolated pancreatic islets to elevated glucose for only 15 min resulted in a 2- to 5-fold elevation in (prepro)insulin mRNA levels within 60-90 min. Similarly, insulin promoter-driven green fluorescent protein expression in single insulin-producing cells was significantly enhanced after transient glucose stimulation. Thus, short-term signaling, such as that involved in insulin secretion, also may regulate insulin gene transcription.

Animals↗

UV light affects cell membrane and cytoplasmic targets.

For a long time DNA has been regarded as the only molecular cellular target for UVB and UVC. However, evidence is accumulating that ultraviolet light (UV) can also affect cytoplasmic and membrane structures. It has been shown that UV can directly affect cytoplasmatically located transcription factors, kinases closely located to the cellular membrane and even membrane receptors. The identification of additional cellular UV targets and the mechanisms by which these targets transduce the UV signal will increase the understanding of the biological effects of UV. Recently, we observed that UV can interfere with cytokine signalling and induce apoptosis via direct activation of apoptosis-related surface receptors. These findings will be briefly reviewed in the paper.

Animals↗

Ultraviolet light-induced immune tolerance is mediated via the Fas/Fas-ligand system.

Hapten sensitization through UV-exposed skin induces tolerance that is mediated via the induction of hapten-specific T suppressor cells. However, the detailed mechanisms underlying tolerance induction remain unclear to date. We show here that the apoptosis-related surface Ag Fas (APO-1, CD95) and its ligand, Fas ligand (FasL) are critically involved, since Fas-deficient lpr mice and FasL-deficient gld mice do not develop UV-induced tolerance. Adoptive transfer experiments revealed that the mediation of tolerance does not require the expression of Fas or FasL by the T suppressor cells but does require the expression of both molecules by the cells of mice receiving the T suppressor cells. To identify the mechanisms involved, the effect of suppressor cells on Ag-presenting dendritic cells (DC) was studied. Coincubation of hapten-pulsed DC with T cells that were obtained from UV-tolerized mice resulted in an enhanced death rate of DC, and this cell death was dependent upon Fas expression. The addition of IL-12, which recently was found to break established tolerance in vivo, prevented DC death. Moreover, IL-12 did not only rescue DC from T suppressor cell-induced death but also from apoptosis induced by rFasL, suggesting that IL-12 may interfere with the Fas/FasL system. Together, these data indicate a crucial role for the Fas/FasL system in UV-induced tolerance, and suggest that UV-induced T suppressor cells may act by inducing the cell death of APCs via the Fas pathway. The ability of IL-12 to break established tolerance may be due to the prevention of DC death induced by T suppressor cells.

Animals↗

Ultraviolet light induces apoptosis via direct activation of CD95 (Fas/APO-1) independently of its ligand CD95L.

Induction of apoptosis in keratinocytes by UV light is a critical event in photocarcinogenesis. Although p53 is of importance in this process, evidence exists that other pathways play a role as well. Therefore, we studied whether the apoptosis-related surface molecule CD95 (Fas/APO-1) is involved. The human keratinocyte cell line HaCaT expresses CD95 and undergoes apoptosis after treatment with UV light or with the ligand of CD95 (CD95L). Incubation with a neutralizing CD95 antibody completely prevented CD95L-induced apoptosis but not UV-induced apoptosis, initially suggesting that the CD95 pathway may not be involved. However, the protease CPP32, a downstream molecule of the CD95 pathway, was activated in UV-exposed HaCaT cells, and UV-induced apoptosis was blocked by the ICE protease inhibitor zVAD, implying that at least similar downstream events are involved in CD95- and UV-induced apoptosis. Activation of CD95 results in recruitment of the Fas-associated protein with death domain (FADD) that activates ICE proteases. Immunoprecipitation of UV-exposed HaCaT cells revealed that UV light also induces recruitment of FADD to CD95. Since neutralizing anti-CD95 antibodies failed to prevent UV-induced apoptosis, this suggested that UV light directly activates CD95 independently of the ligand CD95L. Confocal laser scanning microscopy showed that UV light induced clustering of CD95 in the same fashion as CD95L. Prevention of UV-induced CD95 clustering by irradiating cells at 10 degrees C was associated with a significantly reduced death rate. Together, these data indicate that UV light directly stimulates CD95 and thereby activates the CD95 pathway to induce apoptosis independently of the natural ligand CD95L. These findings further support the concept that UV light can affect targets at the plasma membrane, thereby even inducing apoptosis.

Antibodies↗