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Biomedical subjects

S Wagner

Publications and source records attributed to S Wagner.

At least 127 records · Page 7Linked to original sources

Photobiological properties of positively charged methylene violet analogs.

O-Methyl methylene violet (OMeMV), O-methyl bromomethylene violet (OMeBrMV) and O-methyl iodomethylene violet (OMeIMV) have been prepared in order to test their potential utility as anti-viral and anti-tumor phototoxic dyes. Rates of photosensitized toxicity of KB cells with 633 nm irradiation are (x 10(-19) photon-1): 2.4, 2.2, 1.9 and 0.17 for OMeIMV, OMeBrMV, methylene violet (MV) and OMeMV, respectively. Rates of photosensitized inactivation of Sindbis virus in phosphate-buffered saline with 633 nm irradiation are (x 10(-18) photon-1): 3.3, 1.8, 0.99, 0.15 for MV, OMeIMV, OMeBrMV and OMeMV, respectively. Quantum efficiencies for singlet oxygen formation were determined as OMeIMV, 0.64; OMeBrMV, 0.40; OMeMV, 0.054. Titration of the dyes with double-stranded (ds)DNA resulted in bathochromic shifts and hypochromic effects in the visible absorption spectra. Association constants for interaction of the methylated dyes with dsDNA of approximately 1 x 10(5) M-1 were determined by Scatchard analysis of equilibrium dialysis and UV absorption titration data. Photolysis of the halogenated dyes with DNA under argon led to covalent bond formation with the nucleic acid; there was no evidence of covalent binding in the dark.

Antiviral Agents↗

Helicobacter pylori causes DNA damage in gastric epithelial cells.

Helicobacter pylori infection has been considered as a risk factor for gastric carcinoma. Strong evidence exists that reactive oxygen species (ROS) play an important role in carcinogenesis, and in vivo investigations have shown increased synthesis of ROS in the gastric mucosa of H.pylori-infected patients. In the present study the direct effects of H.pylori on ROS and DNA synthesis, induction of apoptosis and DNA repair were investigated in the gastric epithelial cell lines AGS and HM02. Incubation of gastric cells with H.pylori extract induced the synthesis of ROS, diminished the levels of reduced glutathione (GSH), induced DNA fragmentation and increased DNA synthesis in gastric cells. Poly(ADP-ribose) formation was increased in gastric cells exposed to H.pylori extract. FACS analysis of gastric cells exposed to H.pylori extract did not reveal any change in the percentage of cells in the G(2)/M phase of the cell cycle. The radical scavengers MnTBAP (a cell permeable superoxide dismutase mimic), ebselen (a GSH peroxidase mimic) and high doses of catalase completely blocked H.pylori extract-induced elevation in DNA synthesis. Our results indicate that H.pylori extract directly induces the synthesis of ROS in gastric epithelial cells and causes DNA damage.

Cell Cycle↗

[Possibilities of demonstration of growth factors in chronic wounds. Demonstration of RNA and protein in wound tissue].

Growth factors are important modulators of wound healing. So far, there is little clinical data showing that healing defects in chronic wounds are attribute to deficiency of growth factor expression. Characterization of growth factor expression is necessary to provide new directions toward developing therapies in treating wounds. Present available molecular and immunological techniques allow the analysis of mRNA and protein expression in small amounts of wound material. We analyzed growth factor expression in wound tissue and wound fluid from acute and secondary healing wounds. Wound tissue of secondary healing wounds reveals a higher mRNA growth factor expression compared to acute wound tissue. Secondary healing wounds from our studies demonstrated no deficiency of growth factor expression however, functional analysis may be necessary to determine their activity.

Endothelial Growth Factors↗

The Le Fort I downsliding osteotomy: a study of long-term hard tissue stability.

Surgical maxillary repositioning in individuals with vertical maxillary deficiency may be accompanied by skeletal instability. Long-term skeletal changes in 13 patients who underwent a Le Fort I downsliding osteotomy were studied retrospectively. Nine patients underwent a single-jaw procedure, and 4 patients underwent a bimaxillary procedure. Rigid fixation was used in 10 patients, and wire osteosynthesis was used in 3. Descriptive statistics, Pearson moment correlation, and significance testing were performed at the 5% level. The maxilla was stable horizontally over the long term, but it underwent a mean 26.7% superior relapse anteriorly. The results were variable, however. Rigid internal fixation appeared to enhance the horizontal stability of the maxilla in patients who underwent single-jaw surgery. The maxilla was more stable vertically in patients who underwent bimaxillary surgery with rigid internal fixation, compared to isolated maxillary surgery and rigid internal fixation. The results indicate that a 2-mm relapse value may be useful in planning the vertical amount of maxillary incisor exposure.

Adolescent↗

Naive and memory T lymphocytes migrate in comparable numbers through normal rat liver: activated T cells accumulate in the periportal field.

Although the liver is known to contain a significant number of lymphocytes, migration of these through the compartments of the liver, parenchyma and periportal field, has not been studied. The periportal field, in particular, is affected in several immunological disorders of the liver. Populations of labeled naive, activated, and memory T cells were injected into congenic rats. The recipient livers and draining lymph nodes were removed at various time points, and cryostat sections were analyzed for the presence of donor cells using quantitative immunohistology. Donor cell proliferation and apoptosis were examined in vivo by BrdU (5 microM 5-bromo-2-deoxyuridine) incorporation and the TUNEL technique, respectively. Early after injection (0.5-1 h), naive, activated, and memory T cells were localized to the parenchyma and periportal field in comparable numbers. With time, all T cell subsets left the parenchyma but remained or, in the case of activated T cells, significantly accumulated in the periportal field. Furthermore, 12% of activated donor T cells proliferated in vivo within the periportal field, and 0.5% showed evidence of apoptosis. Taken together, not only activated and memory, but also naive T cells continuously migrate through the liver, showing a preference for the periportal field, and activated T cells mainly proliferate there. This may explain why many immunological liver diseases predominantly affect the periportal field.

Animals↗

Microglial/macrophage expression of interleukin 10 in human glioblastomas.

Interleukin 10 (IL-10) expression has been found to be correlated with the extent of malignancy in gliomas. In vitro, IL-10 increases proliferation and migratory capacity in human glioma cell lines. In this study, we localized the site of IL-10 synthesis in gliomas to cells of microglial origin. Biopsy specimens from 11 patients with malignant glioma were processed on native tissues and at early cell culture passages (0-4). IL-10 mRNA was analyzed by RT-PCR and in situ hybridization. Protein was quantitatively assessed by ELISA in cell culture supernatants, and cells expressing IL-10 were determined by a combination of immunohistochemistry for CD68 (specific for microglia/macrophage lineage) and IL-10 in situ hybridization. IL-10 mRNA decreased from passage 0 to 4 in all samples and was undetectable beyond passage 5. Such downregulation of mRNA leads to a steep decrease of IL-10 protein in culture supernatants (below detection level, 0.05 ng/ml, beyond passage 1). The combination of in situ hybridization for IL-10 and CD68 immunostaining revealed that only cells of the microglia/macrophage lineage produced IL-10 mRNA. Our results identify microglia/macrophage cells as the major source of IL-10 expression in gliomas which decreases markedly during early passages of primary cultures of human gliomas due to a progressive reduction of microglia/macrophages present.

Adult↗

Effect of synthetic matrix-metalloproteinase inhibitors on invasive capacity and proliferation of human malignant gliomas in vitro.

Glioma invasion into the surrounding brain tissue is still a major obstacle for any therapeutical approach. As in other solid tumors, matrix-metalloproteases (MMPs) have been suggested as being involved. The aim of this study was to evaluate whether the use of MMP inhibitors to target the protease-mediated invasion process could be a feasible approach. Two human cell lines (U251 and GaMG) and surgical specimens of 6 patients with malignant gliomas were grown as monolayers and spheroid cultures respectively. MMP- and u-PA-mRNA expression was investigated by semi-quantitative RT-PCR. Invasion was studied in Matrigel-coated Boyden chamber transwell assays for monolayers and in confrontation cultures of tumor spheroids with fetal rat brain aggregates in the presence of the synthetic MMP inhibitors batimastat (BB-94) and marimastat (BB-2516). Cytotoxicity/cytostatic effects of high concentrations of both compounds were assessed by growth curves, MTT assays and flow cytometry in human glioma cell lines. Batimastat and marimastat revealed a cytostatic effect at high concentrations (above 1 microM) without cytotoxicity. Both MMP inhibitors effectively reduced glioma invasion in Boyden-chamber assays at low concentrations of 0.3 microM. In confrontation cultures, concentrations of 10 microM and above were necessary to reduce invasion. This effect was observable with inter-individual heterogeneity in the patient's tumor material. MMP inhibitors effectively reduce glioma invasion, although high concentrations were required in 3-dimensional culture systems. At these concentrations, both compounds revealed a cytostatic, but no cytotoxic effect. Thus, high local concentrations of MMP inhibitors could offer a new therapeutic strategy for the treatment of gliomas.

Animals↗

[Cardiopulmonary parameters in hyperthyroidism].

BACKGROUND: Hyperthyroid patients often suffer from impaired exercise capacity with dyspnoea. Two well established, non-invasive methods were used to evaluate the influence of hyperthyroidism on cardiopulmonary function. PATIENTS AND METHODS: In 42 patients with hyperthyroidism we performed spirometry and cardiopulmonary exercise testing before and after 7 days of propranolol therapy as well as in euthyroidism. RESULTS: In hyperthyroidism reduced vital capacity and 1-second capacity were observed (95.5 +/- 2.4% vs 102.6 +/- 1.5%; p = 0.0087; 89.4 +/- 2.3% vs 95.2 +/- 2.2%; p = 0.0179). No changes showed during beta-blockade. At the anaerobic threshold reduced tidal volume and enhanced respiratory frequency were noted (1119.8 +/- 48.9 ml vs 1289.3 +/- 62.7 ml; p = 0.0227; 28.3 +/- 0.8 vs 25.4 +/- 0.9; p = 0.0012). A significant tachycardia could be shown. Impaired response to exercise in pulse and respiratory frequency were observed. Work at the anaerobic threshold was impaired in hyperthyroidism (70 +/- 5 watts vs 86.9 +/- 5.7 watts; p = 0.016) and did not change during propranolol therapy. Oxygen pulse at the anaeorbic threshold was reduced in hyperthyroidism (7.7 +/- 0.4 ml O2/beat vs 9.1 +/- 0.4 ml O2/beat; p = 0.0012) and increased with propranolol (8.9 +/- 0.4 ml O2/beat; p = 0.0001). CONCLUSION: In hyperthyroidism significant changes in cardiopulmonary function were noted at rest and exercise. High resting function and impaired response to exercise suggest a cardiopulmonary work with low efficiency. Propranolol leads to economization and lowers patients complaints.

Adrenergic beta-Antagonists↗

Successful treatment of a saphenous vein graft perforation with an autologous vein-covered stent.

A 52-year-old man with a history of prior coronary bypass surgery suffered recurrent angina and underwent percutaneous placement of a stent within the midportion of the saphenous vein graft to the marginal branch of the left circumflex coronary artery, which was complicated by a significant perforation. The perforation was successfully closed using an NIR stent covered with a segment of autologous antecubital vein. Subsequent surgical exploration confirmed successful closure of the perforation. Cathet. Cardiovasc. Intervent. 48:382-386, 1999.

Angioplasty, Balloon, Coronary↗

Synovial Epstein-Barr virus infection increases the risk of rheumatoid arthritis in individuals with the shared HLA-DR4 epitope.

OBJECTIVE: To investigate the presence of the Epstein-Barr virus (EBV) in rheumatoid arthritis (RA) synovium and its correlation with the HLA genotype in an attempt to elucidate the role of EBV in the pathogenesis of RA. METHODS: EBV DNA/RNA was investigated by polymerase chain reaction (PCR) analysis of synovial tissue from 84 patients with RA and from 81 patients with non-RA arthritis (controls) and was correlated with the patients' HLA genotype. RESULTS: EBV DNA and EBV-encoded RNA 1 transcripts were significantly more frequently present in synovial tissue from the RA patients (29 of 84) than in that from the non-RA patient controls (8 of 81). EBV DNA-positive individuals had a 5.47 times higher risk of presenting with RA than did EBV DNA-negative individuals. In HLA-DRB1*0401,0404,0405,0408-positive or shared epitope-positive patients, the risk was further increased (odds ratio for EBV and HLA-DR4 approximately 41, for EBV and the shared epitope approximately 15) compared with those who lacked both EBV DNA and RA-linked HLA genotypes. CONCLUSION: EBV seems to function as an environmental risk factor for RA, particularly in patients with the RA-linked HLA-DRB1 alleles.

Adult↗

High-resolution magnetic relaxation dispersion measurements of solute spin probes using a dual-magnet system.

The magnetic field dependence of the nuclear spin-lattice relaxation rate provides a detailed report of the spectral density functions that characterize the intra- and intermolecular fluctuations that drive magnetic relaxation. We have addressed the difficult sensitivity and resolution problems associated with low magnetic field strengths by using two magnets in close proximity and shielded from each other. The sample is stored in the high magnetic field, pneumatically driven to the variable satellite field, then returned to the high field for detection at high resolution. A magnetic shield effectively decouples the two magnets so that varying the satellite field strength has minimal effect on the field strength and shim of the high field magnet. The disadvantage of the sample-shuttle magnet-pair system is the restriction imposed on the relaxation times by the finite shuttle times. Experiments not described here have shown this rate maximum to be about 20 s(-1) for most practical solutions. However, we demonstrate here that the sensitivity gains over switched-current magnet systems permit characterization of solute inter- and intramolecular dynamics over the time scale range from tens of microseconds to less than a picosecond. This range permits investigation of a number of crucial chemical dynamics questions, while high sensitivity permits examination of a variety of solute spins. Representative data are presented for (1)H, (111)Cd, and (7)Li.

Cadmium↗

[Ultrasound therapy for nonunions. Three case reports].

Despite of the good results of operative treatment disorders of fracture healing are still a challenge for surgeons. In some cases all endeavours are frustrating and bone does not heal. Low intensity pulsed ultrasound (frequency: 1.5 MHz, pulsed by 1 KHz, signal burst width: 200 musec, intensity: 30 mW/cm2) offers the opportunity of an alternative treatment. In contrast to magnetic field therapy, electric stimulation or use of extracorporal shock waves this therapy is judged positively all over the literature. Within an own series of 76 cases at present time we can show a 86% healing rate under defined conditions. Within this paper we present three case reports, which clearly show the efficiency of low intensity pulsed ultrasound.

Female↗

[Late results after fracture of the femoral head].

The dislocation fracture of the femoral head is the result of high speed trauma. Most of the patients have additional injuries. The prognosis of this kind of fracture of the femoral head depends on the type of fracture, the additional injuries and the age of the patients. The diagnosis and the specific treatment are most important, since most of the patients with this injury are of a younger age. The reposition of the fracture has to be performed within 6 hours. In our opinion, this should be done by surgery if possible. For the operation some routine pelvic X-rays and a CT of the pelvis should be prepared. The therapy depends on the type of fracture. In patients with Type I and II fractures the broken head fragments should be refixed by only taking out small parts of bone which are not elementary for the pressure zone of the femoral head. Younger patients with Type III fractures should always receive the possibility of a screw fixation of the neck of femur, whereas total hip replacement should generally be achieved in the older patient. An exact reconstruction of the dorsal acetabulum must be performed in Pipkin Type IV fractures. The usual approach for Type I-III fractures is the ventrolateral Smith-Peterson and lateral Watson-Jones, for Type IV fractures, the dorsal Kocher-Langenbeck approach. We suggest indometacine as a prophylaxis for ossifications due to high tissue damage. Several scores for the evaluation and documentation of the outcome of this kind of fracture are useful: the clinical results according to Merle d'Aubigne, social status scored by the Karnofsky Index and X-ray results using Brooker and Helfet to classify the heterotopic ossification and post traumatic joint changes.

Adolescent↗

[Surgical treatment of injuries of the thoracolumbar transition. 1: Epidemiology].

The authors report on a prospective multicenter study with regard to the operative treatment of fractures and dislocations of the thoracolumbar spine. 18 traumatologic centers in Germany and Austria, forming the working group "spine" of the German Society of Trauma Surgery, are participating in this continuing study. Between September 1994 and December 1996 682 patients (64% male) with an average age of 39 1/2 (7-83) years were entered. The entry criteria included all patients with acute and operatively treated (within 3 weeks after trauma) fractures and dislocations of the thoracolumbar spine (Th 10-L 2). Part 1 of this publication outlines the protocol and epidemiologic data. The incidence of fractures and dislocations of the thoracolumbar spine and associated injuries were recorded according to a standardized protocol, as well as the different operative methods and complications, duration of hospital stay, rehabilitation and incapacity. The analysis of the clinical social and radiological course was a second focus. The most frequent mechanism of injury was a fall (50%) or traffic accident (22%). Most of the fractures occurred at the L 1 level (49%). All injuries were classified according to the ASIF (AO) classification. 65% sustained an A-type fracture (compression fracture). Associated injuries were observed in 35% and 6% were polytraumatized. Extremities and thorax were most frequently affected. Younger age and traffic accidents lead more often to C-type fracture (fracture dislocation) and polytrauma. An increased number of multisegmental or multilevel lesions were observed in polytraumatized patients. There were 16% with incomplete paraplegia (Frankel/ASIA B-D) and 5% with complete paraplegia (Frankel/ASIA A). The rate of patients with initial neurologic deficits significantly increased with the severity of spinal injury according to the Magerl classification. Until discharge a neurologic improvement (at least 1 Frankel/ASIA grade) was observed in 32% of the partially paralyzed (Frankel/ASIA B-D) and in 12% of the patients with complete paraplegia (Frankel/ASIA A). A neurologic deterioration occurred in 3 patients (0.4%). As a base for further follow-up and late results the individual starting point was determined by collecting relevant data of the patients' history: 277 (40.6%) patients suffered from simultaneous diseases, one half was spine related. At the time of injury 559 (82.0%) patients were employed; 429 (62.9%) doing manual work. 369 (54.1%) patients stated sportive activities before the injury and 561 (82.3%) designated their "back function" as normal. For the time before injury the patients scored an average of 93.4 points in the Hannover Spine Score (0-100 points concerning complaints and function of the back/spine).

Adolescent↗

Chondromatosis of the ankle joint (Reichel syndrome).

A case of chondromatosis of the upper ankle joint in childhood is described. It is a monoarticular disease with a good prognosis, frequently without known prior trauma or inflammation, although often free fragments of cartilage are seen in the joint cavities. It originates from the synovium of the joint, and is known in the literature as Reichel syndrome.

Acute Disease↗

[Acute myocardial infarction in Germany between 1996 and 1998: therapy and intrahospital course. Results of the Myocardial Infarction Registry (MIR) in Germany].

The "Myocardial Infarction Registry" in Germany (MIR) is a multicenter and prospective registry of consecutively included, unselected patients with acute myocardial infarction. The purpose of MIR is to document the actual praxis of decision making and prescribing of an optimized infarction therapy in AMI patients. Optimized infarction therapy is defined as the combination of reperfusion therapy and ASS, betablocker, and ACE inhibitor.14,598 patients with acute myocardial infarction were included between 12/96 and 5/98 in 217 hospitals throughout Germany. 68% of the patients were male; mean age was 67 years. The prehospital delay time was 195 minutes in median, the first ECG was diagnostic in 66% of the patients. A reperfusion therapy was applied in 46.1% of the patients (thrombolysis 36.2%, primary PTCA 9.9%). During the acute phase, the following adjunctive therapy was used: ASS in 90.3%, betablockers in 53.8%, and ACE inhibitors in 52.5%. Intrahospital mortality was 15.4%. Compared to hospitals without cardiologists, the hospitals with cardiologist had a lower intrahospital mortality (13.8% versus 16.1%; p < 0.001). Reasons are the more frequent use of a reperfusion therapy by cardiologists (54.3% versus 42.3%; p < 0. 001) and the availability of a catheter laboratory with PTCA facilities.A lower intrahospital mortality was associated with each therapy of the optimized infarction therapy: reperfusion therapy (odds ratio 0.7; 95% CI: 0.5-0.8), ASS (odds ratio 0.6; 95% CI: 0. 5-0.8), betablocker (odds ratio 0.6; 95% CI: 0.5-0.7) and ACE inhibitor (odds ratio: 0.5; 95% CI: 0.4-0.7). However, patients with poor initial prognosis - such as cardiogenic shock, hypotension and/or bradycardia - could not benefit from the orally adjunctive therapy. This fact may have led to an overestimation of the influence on intrahospital mortality. In representative communal German hospitals, a reperfusion therapy in combination with an optimized adjunctive therapy in patients with acute myocardial infarction is associated with a reduction in intrahospital mortality. Compared to previous registries, the application of betablockers and ACE inhibitors was clearly increased. Reasons could be the participation in a quality registry, the obligation to document why a therapy has not been given and repeated and intensified education of the treating physicians.Thus, the mainly communal hospitals in Germany are increasingly following recommendations about the early treatment of acute myocardial infarction. Myocardial infarction registries such as MIR reflect daily prescribing habits in hospitals and describe the implementation of the results of randomized trials into daily routine.

Adrenergic beta-Antagonists↗

Growth characteristics and influence of antibiotics on rough/smooth phenotypic variants of Helicobacter pylori.

Helicobacter pylori shows a rather high variability of several biochemical markers including lipopolysaccharide structures. This study aimed to determine whether Helicobacter pylori has a potential for phenotypic variability and to describe its effects on bacterial pathogenesis. From colonies of three clinical strains of Helicobacter pylori with rough (R) colony morphology, spontaneous phenotypic variants with smooth (S) colony morphology were isolated that occurred with a frequency of 10(-2) to 10(-3), irrespective of growth conditions. R-variant bacteria produced exclusively low-molecular-mass lipopolysaccharide. They exhibited increased lysis in the presence of plain air. In contrast, the S variants produced low- and high-molecular-mass lipopolysaccharide and did not exhibit increased lysis in the presence of plain air. Cocultivation of bacterial cells with AGS stomach cancer cells revealed that R-variant bacteria but not S-variant bacteria effected an inhibition of high molecular-weight glycoprotein biosynthesis and secretion by the host cells. Skirrow supplement added as selective agent to liquid and/or solid media was tolerated to a similar extent among R- and S-variant bacteria, while all variants proved sensitive to metronidazole, amoxicillin and clarithromycin except for the R and S isolates of strain Hp57, which showed resistance to the latter compound. It was concluded that R- and S-variants of Helicobacter pylori may have distinct roles in pathogenesis; nevertheless, these bacteria may be isolated by traditional methods and eradicated by conventional anti-infective therapy.

Anti-Bacterial Agents↗