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T Schwarz

Publications and source records attributed to T Schwarz.

At least 19 recordsLinked to original sources
PubMed2006

Differential effects of NF-kappaB on apoptosis induced by DNA-damaging agents: the type of DNA damage determines the final outcome.

The transcription factor nuclear factor kappa-B (NF-kappaB) is generally regarded as an antiapoptotic factor. Accordingly, NF-kappaB activation inhibits death ligand-induced apoptosis. In contrast, ultraviolet light B (UVB)-induced apoptosis is not inhibited but even enhanced upon NF-kappaB activation by interleukin-1 (IL-1). This study was performed to identify the molecular mechanisms underlying this switch of NF-kappaB. Enhancement of UVB-induced apoptosis was always associated with increased release of tumour necrosis factor-alpha (TNF-alpha), which was dependent on NF-kappaB activation. The same was observed when UVA and cisplatin were used, which like UVB induce base modifications. In contrast, apoptosis caused by DNA strand breaks was not enhanced by IL-1, indicating that the type of DNA damage is critical for switching the effect of NF-kappaB on apoptosis. Surprisingly, activated NF-kappaB induced TNF-alpha mRNA expression in the presence of all DNA damage-inducing agents. However, in the presence of DNA strand breaks, there was no release of the TNF-alpha protein, which is so crucial for enhancing apoptosis. Together, this indicates that induction of DNA damage may have a significant impact on biological effects but it is the type of DNA damage that determines the final outcome. This may have implications for the role of NF-kappaB in carcinogenesis and for the application of NF-kappaB inhibitors in anticancer therapy.

Acetylcysteine↗
PubMed2006

Assessing the potential role of photopheresis in hematopoietic stem cell transplant.

The First International Symposium on Photopheresis in Hematopoietic Stem Cell Transplantation was held in Vienna, Austria with an educational grant from Therakos Inc. from 25 May to 27 May 2005. Three general issues were addressed: (1) pathophysiology of graft-versus-host disease (GvHD), (2) induction of immune tolerance and the immunology of phototherapy and (3) current standard treatment and prevention strategies of acute and chronic GvHD and the use of extracorporeal photopheresis (ECP). The objectives of the meeting were to open a dialogue among leading researchers in photobiology, immunology, and hematopoietic stem cell transplantation; foster discussions and suggestions for future studies of the mechanism of action of ECP in acute and chronic GvHD; and promote collaboration between basic scientists and clinicians. As can be seen from the summaries of the individual presentations, important advances have been made in our understanding of GvHD, including the use of photoimmunology interventions and the development of robust model systems. It is our expectation that data from photoimmunology studies can be used to generate hypotheses in animal models that can further define the mechanism of action of ECP and help translate the findings to clinical trials of ECP for the prophylaxis and treatment of both chronic and acute GvHD.

Graft vs Host Disease↗
PubMed2005

Dysplasia of the caudal vertebral articular facets in four dogs: results of radiographic, myelographic and magnetic resonance imaging investigations.

Congenital anomalies of the vertebral column associated with aberrations of one of the primary vertebral ossification centres have been frequently described in the veterinary literature, but clinically significant abnormalities of secondary vertebral ossification centres, particularly involving the caudal articular processes, are much less frequently reported. This paper describes three dogs with aplasia and one dog with hypoplasia of the caudal vertebral articular processes. Thoracolumbar spinal cord compression and ataxia was evident in the three dogs with aplasia but no clinical signs were evident in the dog with hypoplasia. The radiographic appearance was similar in all four cases, with aplasia or hypoplasia of the caudal articular facets at one or more intervertebral joints in the thoracolumbar region. Bone proliferation was evident secondary to an associated degenerative joint disease. Compensatory hyperplasia of the adjacent cranial articular facets and ligamentum flavum protruded into the vertebral canal, resulting in a compressive myelopathy observed by myelography and magnetic resonance imaging.

Animals↗
PubMed2005

Bacterial transfer of large functional genomic DNA into human cells.

Efficient transfer of chromosome-based vectors into mammalian cells is difficult, mostly due to their large size. Using a genetically engineered invasive Escherichia coli vector, alpha satellite DNA cloned in P1-based artificial chromosome was stably delivered into the HT1080 cell line and efficiently generated human artificial chromosomes de novo. Similarly, a large genomic cystic fibrosis transmembrane conductance regulator (CFTR) construct of 160 kb containing a portion of the CFTR gene was stably propagated in the bacterial vector and transferred into HT1080 cells where it was transcribed, and correctly spliced, indicating transfer of an intact and functional locus of at least 80 kb. These results demonstrate that bacteria allow the cloning, propagation and transfer of large intact and functional genomic DNA fragments and their subsequent direct delivery into cells for functional analysis. Such an approach opens new perspectives for gene therapy.

Cell Line, Tumor↗
PubMed2005

Pharmacokinetics of BAY 59-7939--an oral, direct Factor Xa inhibitor--in rats and dogs.

The pharmacokinetics of BAY 59-7939 - a novel, oral, direct Factor Xa inhibitor - were investigated in rats and dogs in support of preclinical safety studies and clinical development. BAY 59-7939 was rapidly absorbed after oral dosing, with an absolute bioavailability of 57-66% in rats, and 60-86% in dogs. Plasma pharmacokinetics of BAY 59-7939 were linear across the investigated dose range (1-10 mg kg(-1) in rats, 0.3-3 mg kg(-1) in dogs). Plasma clearance was low: 0.4 l kg(-1) h(-1) in rats and 0.3 l kg(-1) h(-1) in dogs; volume of distribution (V(ss)) was moderate: 0.3 l kg(-1) in rats, and 0.4 l kg(-1) in dogs. The elimination half-life after oral administration was short in both species (0.9-2.3 h). Whole-body autoradiography showed moderate tissue affinity. No retention or small volume enrichments of BAY 59-7939-related radioactivity were observed. The plasma-protein binding of BAY 59-7939 was high, species dependent and fully reversible. BAY 59-7939 was rapidly excreted in rats and dogs, and was not irreversibly retained. A dual mode of excretion (biliary/faecal and renal) was observed. In summary, BAY 59-7939 had a favourable, predictable pharmacokinetic profile, with high oral bioavailability and a dual route of excretion.

Administration, Oral↗
PubMed2005

Thoracic high-resolution computed tomographic findings in dogs with canine idiopathic pulmonary fibrosis.

OBJECTIVES: To identify features of canine idiopathic pulmonary fibrosis (CIPF) using high-resolution computed tomography (HRCT), and to correlate these features with clinical stages of the disease. METHODS: Ten dogs with signalment, history and clinical signs highly suggestive of CIPF were investigated. Thoracic radiography, haematology and biochemistry profiles, bronchoscopy and bronchoalveolar lavage and HRCT were performed in each case. The dogs were classified as having mild, moderate or severe stages of the disease based on their clinical presentation and radiographic signs. Features identified by HRCT were correlated with these disease stages. RESULTS: HRCT showed a spectrum of pulmonary changes and it was possible to match some of these to the stage of CIPF. CLINICAL SIGNIFICANCE: HRCT is used extensively in humans in the diagnosis and treatment planning of idiopathic pulmonary fibrosis. This preliminary study identifies the high-resolution computed tomographic features of CIPF in a small group of dogs. With further work it may be possible to use HRCT as a non-invasive tool for diagnosing, staging and therapeutically monitoring CIPF.

Animals↗
PubMed2004

Bone scintigraphy in the investigation of occult lameness in the dog.

99mTechnetium methylene diphosphonate (99mTc-MDP) scintigraphy was performed in 14 dogs of different breeds after clinical lameness examination, radiography and synovial fluid analysis failed to localise lameness to a specific area of pain. The scintigraphic protocol included an intravenous injection of 17 MBq 99mTc-MDP/kg bodyweight and vascular, soft tissue and bone phase scans in standardised positions with a low-energy all-purpose collimator. Confirmation of diagnosis was achieved in nine dogs by arthroscopy, repeated lesion-orientated radiography, computed tomography and response to treatment. In seven cases, bone phase scans showed single elbow uptakes, in two cases unilateral limb uptake, and in one case each a single shoulder and tibia uptake; in three cases there was no increased uptake. Vascular and soft tissue phase images did not reveal additional information. Diagnosis of humeral condyle fissures, a fragmented medial coronoid process, panosteitis and arthropathy was possible in nine cases. Skeletal pathology was ruled out in three normal scintigrams. In two dogs with unilateral uptake of multiple joints, no diagnostic benefit was gained from scintigraphy. The highly sensitive and relatively specific uptake allowed localisation and characterisation or exclusion of skeletal lesions in most dogs.

Animals↗
PubMed2004

Suitability of a CMV/EGFP cassette to monitor stable expression from human artificial chromosomes but not transient transfer in the cells forming viable clones.

Human artificial chromosomes (HACs) were generated by transfer of telomerized PAC constructs containing alpha satellite DNA of various human chromosomes. To monitor which cells took up constructs and subsequently formed stable clones under blasticidin S (BS) selection, a CMV/EGFP expression cassette was inserted into a HAC construct based on chromosome 5 alpha satellite DNA (142 kb). Lipofection into HT1080 cells resulted in a small proportion of cells exhibiting bright green fluorescence on day 1. Areas containing such early green cells were marked, and plates monitored over 2 weeks. In only one out of 41 marked areas, a viable clone developed. In the remaining 40 areas, the green cells ceased division at 1-8 cells. In contrast, outside the marked areas, 16 stable clones formed which did not exhibit green fluorescence during the first cell divisions, but all cells of each became green around day 4-6. Fluorescence in situ hybridization (FISH) analysis of isolated clonal lines demonstrated low copy HAC formation without integration. We conclude that transient expression of an EGFP marker on HAC DNA is not a suitable means for the identification of the proportion of transfected cells which are capable of forming viable clones. One explanation could be that the high copy number required to consistently detect transient EGFP expression (Schindelhauer and Laner, 2002) impairs viability and clone formation.

Cell Line↗
PubMed2003

[Current controversies in the diagnosis and management of cerebral venous and dural sinus thrombosis].

Over the last few years, the results from clinical studies and innovative radiological approaches have significantly altered the management of patients with cerebral venous thrombosis. In contrast to previously held beliefs, cerebral venous thrombosis is considered to be a relatively benign disease with an overall favourable prognosis. Mortality is <10%, and the vast majority of patients recover completely. Although the efficacy of heparin has not been unequivocally proven, it is employed in most centres as the standard therapy. There are not sufficient data supporting long-term anticoagulation. In patients with a proven hypercoagulability syndrome, anticoagulation therapy is generally recommended for a period of 6 months. Whether patients with idiopathic thrombosis should also be treated remains controversial. Non-invasive MR and CT angiography techniques have largely replaced conventional angiography for initial evaluation and follow-up examinations. Both methods have a high sensitivity for cerebral venous thrombosis. Local fibrinolytic therapy or other aggressive recanalizing methods can not be generally recommended.

Anticoagulants↗
PubMed2003

Skin immunity.

As the major barrier of the body to the outside, the skin is constantly confronted with microbial, chemical and physical insults. However, the skin does not only function as a mechanical barrier but also uses the immune system for protection. Therefore, the skin is endowed with the capacity to generate immune responses of the innate as well as of the adaptive type.

Antigen-Presenting Cells↗
PubMed2003

Automatic capture verification in ICD lead systems using intracardiac ventricular evoked response and reduced coupling capacitance.

AIM: Intracardiac ventricular evoked-response (ER) signals detected by implanted cardioverter defibrillator (ICD) lead systems were investigated for automatic capture verification (AC). METHOD: ER signals were evaluated with an external pacing system equipped with a reduced coupling capacitance (CC=2.2 microF) in the pacing output circuit during ventricular step-down threshold testing at 0.4 ms pulse duration. Real-time pacing markers, surface ECG and intracardiac electrograms pre- and post-filtering were digitally recorded. RESULTS: Twenty consecutive patients, age 61+/-12 years, with leads from two different manufacturers were tested - 10 were implanted with acute leads (AL) and 10 with chronic leads (CL). The analysis was based on the ER amplitude during capture and on the ER-to-afterpotential ratio (SAR), with SAR>2 as the criterion for successful capture detection. ER amplitudes (median and range) were 8.1 mV (2.1-19.5 mV) for AL and 8.3 mV (3.7-14.2 mV) for CL. SAR values (median and range) were 48.0 (2.5-682.6) for AL and 13.2 (6.3-35.9) for CL, indicating that AC could successfully be applied in all patients. CONCLUSIONS: Reducing the pacing CC allows adequate ER detection for automatic capture verification on non-selected ICD lead systems. The effect of high-voltage shock treatment on ER signal detection requires further investigation.

Cardiac Pacing, Artificial↗
PubMed2003

Localization and diagnosis of septic endoprosthesis infection by using 99mTc-HMPAO labelled leucocytes.

The aim of this study was to evaluate, retrospectively, the diagnostic value of Tc hexamethylpropylene amine oxime (99mTc-HMPAO) labelled autologous leucocytes for the preferred septic localizations of the infection of the endoprosthesis. We retrospectively reviewed 67 patients with implanted endoprostheses. Diagnosis was found in 42/67 patients. In 25/67 patients we were able to negate an acute pathological process of infection of the endoprosthesis. Our patients were divided into three groups according to the type of endoprosthesis (hip joint, knee joint, shoulder joint). The localizations of the endoprosthesis disorders are shown. The preferred localizations of the acute infection of the hip endoprosthesis are the regio intertrochanterica and the middle part of the shaft of the prosthesis. The preferred localization of the acute infection of the knee endoprosthesis is the proximal shaft of the tibia. The preferred localization of the acute infection of the shoulder endoprosthesis is the distal end of the prosthesis in the proximal humerus. It is hoped that the knowledge of these preferred localizations of infection of endoprosthesis will help patients and doctors in diagnosis and treatment in the future.

Acute Disease↗
PubMed2003

Pathology results in [18F]fluorodeoxyglucose positron emission tomography of the thyroid gland.

The aim of this retrospective study was to evaluate pathologically increased uptake of [18F]fluorodeoxyglucose (18F-FDG) in positron emission tomography (PET) results of the thyroid gland. Results of 18F-FDG PET and [99mTc]pertechnetate scintigraphy of the thyroid gland are shown, compared to each other and discussed. In a retrospective study 16 patients underwent whole-body 18F-FDG PET and [99mTc]pertechnetate scintigraphy of the thyroid gland within 3 weeks. In addition, an examination of the thyroid gland by using ultrasound and laboratory tests was carried out. The 18F-FDG PET studies were carried out on a dedicated whole-ring PET scanner. Eight patients had a pathological FDG uptake in the thyroid and a cold nodule in [99mTc]pertechnetate scintigraphy of the thyroid gland (in 7/8 cases histology showed malignancy). Five patients had an inhomogeneous FDG uptake in the thyroid gland and were suspected of thyroiditis in 18F-FDG PET (in 3/5 cases thyroiditis was confirmed). Three patients had an especially low FDG uptake compared to normal physiological FDG uptake (no malignancy). Results from studies using 18F-FDG represent a growing body of evidence showing the differentiation between malignant and benign disease: we saw many pathological results in the thyroid gland. High uptake of 18F-FDG in the thyroid gland suggests possible malignancy. Thyroiditis can only be suspected based upon the results of 18F-FDG PET. We conclude that 18F-FDG PET has a potential clinical impact for detecting possible malignant lesions of the thyroid gland, but further studies, in which a higher number of patients are evaluated, are necessary.

Adolescent↗
PubMed2003

Hohenheimer Consensus Talk. Oxidative and premature skin ageing.

To elucidate the scientific state of the art with respect to the role of nutrition in skin ageing, nine experts from different disciplines discussed the role of micronutrients on 'oxidative and premature skin ageing'. In this 25th Hohenheim Consensus Meeting, 13 questions were discussed and, based on published valid data, answered by mutual agreement. The consensus answers achieved during the meeting are justified by a scientific background text. The importance of in vitro and in vivo models regarding oxidative and premature skin ageing was critically evaluated. There was a special focus on prevention and intervention of skin ageing with nutrition. Finally, the paper summarizes the scientific background from different areas related to oxidative and premature skin ageing.

Animals↗
PubMed2003

Diagnosis of a contralateral second testicular carcinoma by F18-FDG PET.

BACKGROUND: In testicular carcinoma the early diagnosis is very important because with an early therapy there are good chances for long-term survival (50-90%). Metastases of a testicular carcinoma are at first lymphogenous, hematogenous only in late stages. CASE REPORT: This is a case report about a 28-year-old man, whose testicular carcinoma (left testis) had already been operated on (unripe teratoma with parts of an embryonic carcinoma, an endodermal sinus tumor and a chorion carcinoma). Because of the elevated tumor marker AFP an FDG PET (F18-fluorodeoxyglucose positron emission tomography) investigation was made. CT (covering thorax, abdomen and pelvis) and ultrasound of the testis showed no pathological results. In the FDG PET a significant pathological FDG uptake in the right testis was found. Histology showed an unripe teratoma with parts of an embryonic carcinoma, an endodermal sinus tumor, and a chorion carcinoma. It was a second carcinoma of the contralateral testis. CONCLUSION: F18-FDG PET was a sensitive and reliable modality for diagnosis in this patient.

Adult↗