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S Wagner

Publications and source records attributed to S Wagner.

At least 19 recordsLinked to original sources
PubMed2007

Lactate down-regulates cellular poly(ADP-ribose) formation in cultured human skin fibroblasts.

BACKGROUND: Polyadenosine diphosphate-ribose (poly(ADP-ribose)) is a nuclear polymer which is derived from nicotinamide adenine dinucleotide (NAD(+)) catalysed by poly(ADP-ribose) polymerase 1 (PARP-1). Aside from the well known role of poly(ADP-ribosyl)ation (pADPR) in DNA repair, pADPR is also involved in other cellular processes such as apoptosis and gene expression. However, the factors that regulate the level of pADPR are not fully elucidated. In view of the fact that healing wounds contain high concentrations of lactate (10-15 mM) and exogenous lactate reduce the NAD(+) pool in cultured fibroblasts, we propose that high lactate lowers the level of nuclear pADPR. MATERIALS AND METHODS: Neonatal human dermal fibroblasts (NHDF) were plated to subconfluence and allowed to adhere. Cells were treated with 15 mM l-lactate and pADPR production was assessed by immunofluorescence analysis using 10H antibody. Difference in pADPR production was determined by calculation of positively stained cells compared to total cell numbers. Inhibition of PARP activity was tested by treatment with 100 microM 3-aminobenzamide (3-AB). Specificity of the lactate effect on pADPR synthesis was verified by using the analogue d-lactate. The contents of nicotinamide adenine dinucleotide (NAD(+)) and its reduced form (NADH) in lactated and non-lactated cell cultures were quantified by the enzymatic cyclic assay. RESULTS: We found that exogenous l-lactate (15 mM) can significantly depress pADPR content in cultured fibroblasts. PARP-1 activity was inhibited by 3-AB and analogue d-lactate showed no effect on pADPR synthesis. NAD(+)/NADH ratio was significantly lowered in lactated compared to non-lactated cell culture. CONCLUSIONS: Exogenous l-lactate (15 mM) can depress pADPR content in cultured fibroblasts. In view of the fact that healing wounds contain such high concentrations of lactate, we propose that down regulation of pADPR is associated with elevated tissue repair via pADPR dependent gene expression. This observation is important in understanding the stimulation of lactate-mediated protein expression during wound healing.

Cells, Cultured↗
PubMed2006

LACE-conditioned autologous stem cell transplantation for relapsed or refractory Hodgkin's lymphoma: treatment outcome and risk factor analysis in 67 patients from a single centre.

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a recognized treatment option for patients with relapsed Hodgkin's lymphoma. We have analysed 67 patients who underwent ASCT after LACE (lomustine (CCNU), cytarabine (Ara-C), cyclophosphamide, etoposide) conditioning for relapsed (n=61) or primary refractory (n=6) Hodgkin's lymphoma. The 100-day treatment-related mortality was 3%. With a median follow-up of 67 months (range 3.3-161.0) the probabilities of overall survival (OS) and progression-free survival (PFS) at 5 years were 68 and 64%, respectively. Probabilities for OS and PFS at 5 years for patients with chemosensitive relapse (n=40) were 81 and 78% versus 50 and 35%, respectively, for patients (n=27) with chemoresistant relapse (P=0.012 for OS, P=0.002 for PFS). In multivariate analysis mixed cellularity classical or lymphocyte-depleted classical histology subtype and haemoglobin level of 10 g/dl or less at the time of ASCT were identified as risk factors for worse OS, whereas stage III or IV disease at diagnosis and disease status at ASCT other than complete or partial remission predicted inferior PFS. LACE followed by ASCT is an effective treatment for the majority of patients with chemosensitive relapsed Hodgkin's lymphoma and a proportion of chemorefractory patients also benefit.

Adolescent↗
PubMed2006

Secondary dissemination in children with high-grade malignant gliomas and diffuse intrinsic pontine gliomas.

In children, treatment regimen for high-grade gliomas (HGG) and diffuse intrinsic pontine gliomas (DIPG) are generally not stratified according to disease stage. The hypothesis was that secondary disseminating disease (SDD) in children with HGG is related to an even worse outcome. Description of SDD pattern was performed. In total, 270 children with newly diagnosed HGG or DIPG were eligible for retrospective analysis of SDD. Medical and computer records of these patients were reviewed for demographic characteristics, sites of dissemination, prognostic variables. Forty-six (17%) of the 270 patients had developed SDD. The median time to SDD was 8.2 months. The median overall survival (OS) after dissemination was 3.2 months. The SDD was located parenchymal in the supratentorial (34.8%), infratentorial (6.5%), supratentorial and infratentorial (19.6%), spinal (10.9%), spinal and cerebral (6.5%) regions of the CNS, or leptomeningeal (21.7%). For HGG patients, the median OS was shorter among patients with SDD than among patients without SDD (1.02 vs 1.41 years, P=0.0495). In the group of patients with SDD, patients with cerebrospinal fluid dissemination had a worse outcome compared with patients with parenchymal metastases. Summarising, SDD is a negative prognostic factor for patients with HGG outside the pons. Treatment stratification should be considered.

Adolescent↗
PubMed2006

Femtosecond laser induced associative desorption of H2 from Ru(0001): comparison of "first principles" theory with experiment.

A three dimensional model based on molecular dynamics with electronic frictions is developed to describe the femtosecond laser induced associative desorption of H2 from Ru(0001)(1 x 1)H. Two molecular coordinates (internuclear separation d and center of mass distance to surface z) and a single phonon coordinate are included in the dynamics. Both the potential energy surface and the electronic friction tensor are calculated by density functional theory so that there are no adjustable parameters in the comparison of this model with the wide range of experiments available for this system. This "first principles" dynamic model gives results in semiquantitative agreement with all experimental results; nonlinear fluence dependence of the yield, isotope effect, two pulse correlation, and energy partitioning. The good agreement of theory with experiment supports a description of this surface femtochemistry in terms of thermalized hot electron induced chemistry with coupling to nuclear coordinates through electronic frictions. By comparing the dynamics with the analytical one dimensional frictional model used previously to fit the experiments for this system, we show that the success of the one dimensional model is based on the rapid intermixing of the z and d coordinates as the H-H climbs out of the adsorption well. However, projecting the three dimensional dynamics onto one dimension introduces a fluence (adsorbate temperature) dependent "entropic" barrier in addition to the potential barrier for the chemistry. This implies that some caution must be used in interpreting activation energies obtained in fitting experiments to the one dimensional model.

Journal Article↗
PubMed2006

[Ultrasound education by simulator training high acceptance by ultrasound trainees of all qualification levels].

Ultrasound education improves by simulator training, however, the acceptance of ultrasound simulator training has not been investigated. Therefore we evaluated the participants response to simulator education during an ultrasound course of abdominal emergencies at an international ultrasound congress, at a regular ultrasound course and during courses at a regional hospital and an university hospital. Altogether, 62.3% of the participants judged the simulator image quality to be good. 84.3% considered the case selection to be good and 92.7% of the participants viewed the educational benefit to be good. 98.5% whished to have further ultrasound simulator courses to be developed and 95.3% of the participants opted for the integration of simulator training into the conventional ultrasound education.

Attitude of Health Personnel↗
PubMed2006

[Cognitive impairment, depression, and work capacity of 50-59-year-old psychosomatic inpatients].

Due to aging of the population and a possible rise in retirement age, the cognitive capacity of older people is gaining great importance. As evidenced by the increase in early retirement due to psychosomatic disease, many employees are not capable of working at a higher age. Decreasing cognitive abilities have usually been studied in subjects over 65 years based on the heterogeneous construct of mild cognitive impairment (MCI). This study investigates the prevalence of cognitive impairments in the age group from 50 to 59 years and their reflections in subjective vocational achievement and social medical evaluation. Having been assigned to inpatient rehabilitation due to decreasing work performance, these patients could be considered a risk group for developing MCI. A battery of standardized cognitive tests was conducted with patients at a psychosomatic hospital (Termine Test, CVLT, Block Design, TAP, and Tower of Hanoi). The MCI was defined by performance below the average age norm in at least two of five functional areas. Depression was assessed by the Beck Depression Inventory. Cognitive impairment was observed in 24% of participants. These patients also described vocational difficulties. Cognitive impairments of older employees could possibly be compensated for by specific training programs in order to maintain or rebuild their work capacity.

Cognition Disorders↗
PubMed2006

Late response to radiochemotherapy in pediatric glioblastoma: report on two patients treated according to HIT-GBM protocols.

High-grade gliomas in children are rare and the best treatment is undetermined. The German language group study HIT-GBM compares various induction protocols for subsequent patient cohorts. Currently, cisplatinum, etoposide, ifosfamide, and vincristine are given simultaneously with extended-field radiotherapy. Imaging is done 3 weeks after to define treatment response, followed by 6-weekly controls during consolidation with lomustine, vincristine, and prednisone. The authors report on 2 patients with incompletely resected glioblastoma multiforme in which response was lacking 3 weeks after radiochemotherapy but became evident 12 weeks later. This suggests that later time points are required to assess induction protocol response.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Allergen concentration in natural rubber latex.

BACKGROUND: Hevea brasiliensis latex serum is commonly used as the in vivo and in vitro reference antigen for latex allergy diagnosis as it contains the full complement of latex allergens. OBJECTIVE: This study quantifies the concentrations of the significant allergens in latex serum and examines its suitability as an antigen source in latex allergy diagnosis and immunotherapy. METHODS: The serum phase was extracted from centrifuged latex that was repeatedly freeze-thawed or glycerinated. Quantitation of latex allergens was performed by two-site immunoenzymetric assays. The abundance of RNA transcripts of the latex allergens was estimated from the number of their clones in an Expressed Sequence Tags library. RESULTS: The latex allergens, Hev b 1, 2, 3, 4, 5, 6, 7 and 13, were detected in freeze-thawed and glycerinated latex serum at levels ranging from 75 (Hev b 6) to 0.06 nmol/mg total proteins (Hev b 4). Hev b 6 content in the latex was up to a thousand times higher than the other seven latex allergens, depending on source and/or preparation procedure. Allergen concentration was reflected in the abundance of mRNA transcripts. When used as the antigen, latex serum may bias the outcome of latex allergy diagnostic tests towards sensitization to Hev b 6. Tests that make use of latex serum may fail to detect latex-specific IgE reactivity in subjects who are sensitized only to allergens that are present at low concentrations. CONCLUSION: Latex allergy diagnostics and immunotherapy that use whole latex serum as the antigen source may not be optimal because of the marked imbalance of its constituent allergens.

Allergens↗
PubMed2006

Genetic analysis of brain circuits underlying pheromone signaling.

Molecular approaches and genetic manipulations have provided novel insights into the processing of pheromone-mediated information by the olfactory and vomeronasal systems of mammals. We will review and discuss the specific contribution of each of the two chemosensory systems that ensure specific behavioral responses to conspecific animals.

Animals↗
PubMed2006

Molecular imaging of matrix metalloproteinases in vivo using small molecule inhibitors for SPECT and PET.

Matrix metalloproteinases (MMPs) are a family of zinc- and calcium-dependent secreted or membrane anchored endopeptidases. MMPs are involved in many physiological processes but also take part in the pathophysiological mechanisms responsible for a wide range of diseases. Pathological expression and activation of MMPs are associated with cancer, atherosclerosis, stroke, arthritis, periodontal disease, multiple sclerosis and liver fibrosis. Thus, noninvasive visualisation and quantification of MMP activity in vivo are of great interest in basic research and clinical application. This can be achieved by scintigraphic molecular imaging techniques such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) provided suitable radiolabelled tracers exist, e.g. radioactive inhibitors of matrix metalloproteinases (MMPIs). The approach to monitor MMP activity in vivo using radiolabelled small molecule inhibitors suitable for SPECT and PET is summarised in this review. Briefly, latest advances in scintigraphic imaging are introduced and followed by a report about the enzyme class of MMPs. The involvement of MMPs in cancer and atherosclerosis is exemplified and small molecule MMPIs are classified. Subsequently, the development of radiolabelled small molecule MMPIs, their synthesis and in vitro and in vivo evaluation is reviewed. Finally, an outlook on the clinical potential of labelled MMPIs in diagnostic algorithms is given.

Animals↗
PubMed2005

Subcutaneous nephrovesical and nephrocutaneous bypass.

OBJECTIVE: We evaluated the effectiveness of the subcutaneous bypass for ureteral obstruction in patients with advanced malignancies. Two versions of the minimally invasive technique were performed: nephrovesical and nephrocutaneous bypass. METHODS: A specially designed composite implant consisting of an inner smooth silicone-covered tube covered by a coiled e-PTFE-tube was used in 14 patients. RESULTS: 10 subcutaneous nephrovesical bypasses were inserted in 10 patients, 8 nephrocutaneous bypasses in 4 patients. During the mean follow-up period of 13.1 months complications were observed in 2 patients with nephrocutaneous bypass, one encrustation and one infection of the bypass system. CONCLUSIONS: The subcutaneous nephrovesical and nephrocutaneous bypass is a safe alternative for palliative treatment of ureteral obstruction caused by pelvic malignancy.

Aged↗
PubMed2005

[Is a blockade of the lateral cutaneous nerve of the thigh an alternative to the classical femoral nerve blockade for knee joint arthroscopy? A randomised controlled study].

BACKGROUND: Gaps in the distribution area of the lateral femoral cutaneous nerve (LFCN) are assumed to be the reason for pain caused by a thigh tourniquet when performing a femoral nerve (FN) block according to Winnie. The aim of the study was to evaluate if a direct single blockade of the LFCN in patients undergoing knee surgery resulted in a better tolerance to the tourniquet with equally good analgesic quality during surgery. METHODS: A total of 40 patients undergoing knee arthroscopy received a proximal blockade of the sciatic nerve and randomly either an FN or an LFCN block. Practicability, onset time, quality of sensory and motor block, and clinical effectiveness during tourniquet and surgery were assessed. RESULTS: Stimulation time was significantly longer in the LFCN than in the FN group. Quality of sensory and motor block was worse in the LFCN than the NF group. Of the LFCN patients 65% indicated troublesome paraesthesia or pain when a tourniquet was placed, compared to 35% of the FN patients. Of the LFCN patients 50% had pain during cutaneous incision, compared to none of the FN group. During the course of surgery, 70% of the LFCN patients needed supplemental systemic analgesia, but this was required by only 30% of the FN group. CONCLUSION: An LFCN block is not a suitable alternative to an FN block for regional anaesthesia. For patients with contraindications for an FN block according to Winnie (e.g. vessel surgery in the groin) other more effective methods are available.

Adult↗
PubMed2005

Multiple in vivo passages enhance the ability of a clinical Helicobacter pylori isolate to colonize the stomach of Mongolian gerbils and to induce gastritis.

The Mongolian gerbil is an excellent animal model for Helicobacter pylori-induced gastritis in humans. In this study, initially low colonization rates of the H. pylori strains ATCC 43504, SS1, or HP87 inoculated into gerbils caused difficulties in establishing this model. In order to increase the colonization ability and pathogenicity, the clinical HP87 isolate was selected for adaptation to the gerbil stomach by multiple in vivo passages through gerbils. Development of gastritis was examined histologically at 4-52 weeks after infection. The proportion of gerbils which tested positive for H. pylori by culture at four weeks after inoculation gradually increased from 11.1% of gerbils inoculated with HP87 without prior in vivo passage (P0) to 100% of gerbils inoculated with HP87 with seven in vivo passages (P7). In addition, adaptation of HP87 resulted in more severe histopathological changes. Gerbils infected with adapted HP87 (P7) exhibited severe infiltration by monomorphonuclear and polymorphonuclear leukocytes in the mucosa, submucosa, and subserosa of the gastric antrum, as well as epithelial changes consisting of hyperplasia, erosion, and ulceration. Histopathological changes increased in severity from four to 52 weeks after infection. Adaptation of HP87 during its passages through gerbils could be due to genetic changes in bacterial colonization factors. Identification of these changes might be useful to understand the underlying mechanism of gastric adaptation and pathogenesis of H. pylori.

Animals↗
PubMed2005

Non-invasive molecular imaging of beta-adrenoceptors in vivo: perspectives for PET-radioligands.

Recently, the spectrum of molecular imaging devices such as positron emission tomography (PET) was further expanded by the now clinically available combined imaging modalities such as PET-CT and the preclinically used small animal PET scanners. These are powerful tools that can bridge the gap between preclinical and clinical evaluation studies of new radiotracers for molecular imaging of healthy and diseased states in vivo. The beta-adrenoceptor (beta-AR) radioligands discussed in this review represent a class of molecular probes for the non-invasive in vivo assessment of beta-AR density eg. in the heart with PET. The beta-AR radioligands (S)-[11C]CGP 12177 (1) or (S)-[11C]CGP 12388 (2) are currently investigated in clinical studies with PET. Additionally, subtype-selective beta1-AR radioligands are used in preclinical research which show potential for the diagnostics of the "beta1-AR organ" as such the heart can be defined. Non-invasive quantification of beta-ARs could facilitate the accurate choice and control of therapeutic interventions. Here we summarize the state-of-the-art of the radiochemistry of radioactive beta-AR radioligands.

Adrenergic beta-Agonists↗
PubMed2004

Role of the receptor-mediated apoptosis in Helicobacter pylori in gastric epithelial cells.

BACKGROUND AND AIMS: Two major pathways leading to apoptosis have been described. It has been shown that Helicobacter pylori-mediated apoptosis is mainly effected through the mitochondrial pathway (type II). The role of the type I pathway, including the death receptors, has been discussed controversially. Therefore, we investigated the role of Fas ligand (FasL) and TRAIL in H. pylori-mediated apoptosis by overexpressing antiapoptotic proteins in the human gastric epithelial cell line AGS. METHODS: AGS cells overexpressing the antiapoptotic proteins dnFADD, CrmA and Bcl-2 were generated. Apoptosis induced by Fas and H. pylori was monitored by histone ELISA. To investigate the role of TRAIL-mediated apoptosis, AGS cells were transduced with antisense constructs against the proapoptotic TRAIL receptors DR4 and DR5. Protein expression of Fas, TRAIL, DR4, and DR5 was analyzed by Western blot. RESULTS: Fas and H. pylori-mediated apoptosis was significantly inhibited in all generated cell lines, mainly in cells overexpressing CrmA and Bcl-2 with equal effectiveness. In the presence of H. pylori, TRAIL ligand and DR5 receptor were continuously expressed whereas DR4 expression was increasing time dependently. TRAILDR5 antisense significantly reduced H. pylori-mediated apoptosis. CONCLUSIONS: H. pylori-mediated apoptosis is characterized by activation of either type I or type II pathway. Caspase-8 plays an important role since it triggers the Type II pathway. Fas and TRAIL play an important role in the H. pylori-mediated apoptosis.

Apoptosis↗
PubMed2004

[Prognosis of hepatocellular carcinoma according to new staging classifications].

BACKGROUND AND OBJECTIVE: We investigated prognostic factors and survival of patients with hepatocellular carcinoma (HCC) in North-Germany. Established staging systems (Child-Pugh, Okuda and UICC classification) were compared with new prognostic scores from Italy (CLIP) and Spain (BCLC). PATIENTS AND METHODS: The clinical course of 62 consecutive patients (34-82 years, 48 males, 14 females) with HCC observed in the Medical School of Hannover from October 1996 to September 1998 were retrospectively analyzed. The patients were classified according to the staging systems of Child Pugh, Okuda, UICC, CLIP and BCLC. Follow-up ended on December 31 (st) 2001. RESULTS: Overall median survival was 11,3 (1 - 59,5) months. At univariate analysis (log-rank test) Okuda, UICC, CLIP and BCLC Score were each associated with a shorter survival. In contrast Child Pugh score provided no significant prognostication. By multiple regression analysis (Cox regression analysis), only the CLIP and UICC score and chronic hepatitis B infection were shown to be independent risk factors. CONCLUSION: Our investigations indicate, that the CLIP and UICC classifications identified those patients with the best prognosis and they, as well as chronic hepatitis C, were shown to be independent risk factors.

Adult↗
PubMed2004

[Laryngeal tube versus laryngeal mask airway in anaesthetised non-paralysed patientsA comparison of handling and postoperative morbidity].

BACKGROUND: The purpose of this study was to compare the classical laryngeal mask airway (LMA) with the laryngeal tube (LT) in anaesthetised non-paralysed patients. PATIENTS AND METHODS: A total of 100 patients scheduled for minor elective surgery were included. After standardised induction and maintenance of anaesthesia with propofol and remifentanil, patients were randomly allocated to receive either a LMA or LT; muscle relaxants were not applied. Selection of the appropriate size and the initial inflation volume were chosen according to the manufacturers instructions. Ease of insertion, initial intra-cuff pressure, oropharyngeal leak pressure at an intra-cuff pressure of 60 cm H(2)O and incidence and severity of complications during and after anaesthesia were compared. RESULTS: The LT was inserted significantly quicker than the LMA (35.1+/-15.9 s vs. 56.6+/-42.5 s; mean+/-SD). Insertion of the LT was successful within 1 attempt in 90% and within 2 or 3 attempts in another 4% of patients for the LT compared with 68% and 20% of patients for the LMA, respectively. For the LT the initial cuff pressure was significantly lower (75.1+/-16.2 cm H(2)O) and the oropharyngeal leak pressure after adjustment of the intra-cuff pressure to 60 cm H(2)O was significantly higher (27.2+/-6.9 mbar) compared with the LMA (109.5+/-25.7 cm H(2)O and 19.9+/-4.0 mbar, respectively). Incidence of postoperative laryngeal complications in the LT group (31%) was lower compared with the LMA group (54%). CONCLUSION: In anaesthetised non-paralysed patients the LT compares favourably to the LMA in terms of ease of insertion and postoperative morbidity.

Adult↗