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U Vogel

Publications and source records attributed to U Vogel.

At least 37 records · Page 2Linked to original sources
PubMed2000

DNA repair capacity: inconsistency between effect of over-expression of five NER genes and the correlation to mRNA levels in primary lymphocytes.

We have previously shown that high DNA repair capacity protects psoriasis patients against chemically induced basal cell carcinoma [Dybdahl et al. Mutat. Res. 433 (1999) 15-22]. We have used the same study persons to investigate the correlation between expression of eight genes involved in nucleotide excision repair and DNA repair capacity. mRNA levels of XPA, XPB, XPC, XPD, XPF, XPG, CSB and ERCC1 in primary lymphocytes from 33 individuals were quantified by dot-blots and normalized to beta-actin. ERCC1 and XPD mRNA quantities were highly correlated (r=0.89; P<10(-11)) while XPA, XPB, XPC, XPG, XPFand CSB mRNAs were moderately correlated (r=0.2-0.7). Thus, the mRNA expressions seem to fall in at least two groups. There was a three to sevenfold variation in the expression levels of the mRNAs. This is in contrast to the more than a hundredfold variation in mRNA levels reported in cancer patients.DNA repair capacity was measured in a host cell reactivation assay, where primary lymphocytes were transfected with an UV-irradiated plasmid encoding firefly-luciferase. Only ERCC1 and XPD mRNA levels correlated with the DNA repair capacity (P<0.03). In order to see if ERCC1 or XPD activity was limiting for DNA repair, we cotransfected with plasmids encoding NER genes, thus over-expressing either XPB, XPC, XPD, CSB or ERCC1 in the host cell reactivation assay. Only XPB over-expression increased DNA repair capacity. Thus, there is no indication that neither XPD nor ERCC1 limits the DNA repair capacity. However, our results indicate that ERCC1 and XPD mRNA levels may be used as a proxy for DNA repair capacity in lymphocytes.

Base Sequence↗
PubMed2000

A strong genotoxic effect in mouse skin of a single painting of coal tar in hairless mice and in MutaMouse.

The dorsal skin of C3H/Tif/hr hairless mice was painted with coal tar, pharmacological grade. Epidermal cells and hepatocytes were isolated after 4, 24, 48 and 96 h and DNA strand breaks were determined as tail moment by the alkaline comet assay. The tail moment of epidermal cells was significantly greater at the time points 4, 24, 48 and 96 h after exposure compared to the controls, with the most DNA strand breaks at 24 h. The DNA strand breaks in epidermal cells increased linearly with the dose of coal tar. In hepatocytes, no difference in DNA strand breaks was found between exposed animals and controls. DNA adducts were determined by the 32P-postlabeling assay. For epidermal cells, the mean DNA adduct level was 12-fold greater in coal tar painted mice after 24 h than in controls. Again, a linear dose/response relationship was seen 24 h after painting. For liver DNA, the mean DNA adduct level was 3-fold greater than for controls. The mutation frequency in epidermal and liver cells was examined in lambdalacZ transgenic mice (MutaMouse). Thirty-two days after painting, the mutation frequency in epidermal cells was 16-fold greater in coal tar treated mice compared to controls. No effect was detected in hepatocytes. We found that a single painting of coal tar resulted in strong genotoxic effects in the murine epidermis, evidenced by induction of DNA strand breaks and DNA adducts in hairless mice and lambdalacZ mutations in the MutaMouse. This demonstrates that it is possible to detect genotoxic effects of mixtures with high sensitivity in mouse skin by these end-points.

Administration, Cutaneous↗
PubMed2000

[Factors modifying frequency of publications of clinical research results exemplified by medical dissertations].

BACKGROUND AND OBJECTIVE: The problem of so-called "publication bias"--distortion of statements about an event by selective publication--is receiving growing attention. Assessment of the results of a given study can be affected by knowing the factors that favour or inhibit the publication of its results. METHODS: The data were based on an analysis of 371 medical doctoral dissertations on clinical research. Characteristic features of the dissertations were obtained by questionnaire, supplemented by MEDLINE search and, additionally, by personal enquiry about the publications. Bivariate and multivariate analysis of the characteristic features was used to evaluate the factors that influenced publication of a dissertation. RESULTS: There were mainly three factors that influenced the decision whether or not a dissertation was published: (1) a positive result of the study (odds ratio 2.5, 95% confidence interval 1.12-5.75); (2) the publishing activity of the dissertation's referee (odds ratio 3.8, 95% confidence interval 1.77-7.97; and (3) the quality of the statistical analysis of the dissertation's data (odds ratio 1.67, 95% confidence interval 0.99-2.80). CONCLUSION: A distinct publication bias can be demonstrated also in the case of doctoral dissertations in that positive results are clearly published more often than negative ones.

Academic Dissertations as Topic↗
PubMed2000

Conventional high resolution versus fast T(2)-weighted MR imaging of the heart: assessment of reperfusion induced myocardial injury in an animal model.

Cardiac image quality in terms of spatial resolution and signal contrast was assessed for conventional and newly developed T(2)-weighted fast spin-echo imaging with high k-space segmentation. The capability in revealing regional myocardial edema and cellular damage was examined by a porcine model using histopathologic correlation. Twelve porcine hearts were excised from slaughtered animals and instantly perfused with 1000 mL cold cardioplegic solution. After 4 h of cold ischemia the hearts were reperfused for one hour using a "Langendorff" perfusion model followed by MR imaging at 1.5 Tesla. Three additional pig hearts served as controls and were studied by MR directly after harvesting. Histopathological analysis of regional tissue changes was performed macro- and microscopically. Short axis T(2)-weighted (3000/45 and 90) high quality fast spin-echo (FSE) images were recorded without cardiac action and signal intensity was correlated with histology. These images also served as gold standard for evaluation of newly developed faster sequences allowing measuring times shorter than 20 s. Fast T(2)-weighted imaging comprised single-slice fast spin echo (moderate echo train length of 23 echoes, FSE(m)), and multi-slice single-shot half-Fourier fast spin-echo (71 echoes, FSE(HASTE)) sequences, supplemented by versions with inversion recovery preparation (FSE(m)IR and FSE(HASTE)IR). Systolic function after reperfusion was restored in 10 porcine hearts. Tissue alterations included myocardial edema and contraction band necrosis which was found to be most severe in myocardium with maximum T(2) SI. Especially FSE(m) and FSE(m)IR sequences allowed differentiation of all categories of tissue damage on a high level of significance. In contrast, single-shot FSE(HASTE) and FSE(HASTE)IR sequences did not provide sufficient image quality to discriminate moderate and severe myocardial damage (p > 0.05). Different degrees of myocardial injury after ischemia and reperfusion can be staged by MR imaging, especially using conventional high resolution T(2)-weighted FSE sequences. The animal study indicates that fast T(2)-weighted FSE(m) and FSE(m)IR sequences lead to superior image quality and diagnostic accuracy compared to FSE(HASTE) and FSE(HASTE)IR imaging.

Analysis of Variance↗
PubMed2000

The evolution of human pathogens: examples and clinical implications.

Recent advances in sequencing of complete bacterial genomes, molecular typing of micro-organisms, and research on microbial pathogenicity factors changed our view on the evolution of human bacterial pathogens. We review current evolutionary concepts on plague and meningococcal disease to illustrate the interplay of molecular phylogeny, epidemiology, and pathogenicity research. Furthermore, examples of the tremendous velocity of bacterial evolution under changing environmental conditions will be discussed.

Adaptation, Physiological↗
PubMed2000

Distribution of the meningococcal insertion sequence IS1301 in clonal lineages of Neisseria meningitidis.

The distribution of the meningococcal insertion sequence IS1301 was analysed in 496 strains of different serogroups and clonal lineages of Neisseria meningitidis, and in 64 neisserial strains other than N. meningitidis. IS1301 was found in meningococci, but not in apathogenic Neisseria sp. and Neisseria gonorrhoeae. The copy numbers of IS1301 varied between 2 and 17 per genome. IS1301 positive strains were mostly found among the serogroups 29E, W135, X, and Y. Clonal lineages of serogroup A, B, and C meningococci associated with epidemic meningococcal disease were rarely positive for IS1301.

Blotting, Southern↗
PubMed2000

[The MR signal behavior of a 4-week-old occlusive myocardial infarct in an animal experiment].

PURPOSE: To correlate signal behaviour in T1- and T2-weighted images after Gd-DTPA with regional histopathology in occlusive myocardial infarction (MI). METHODS: Ligation of a diagonal branch of the LAD was performed in seven sheep. Four weeks later 0.1 mmol Gd-DTPA/kg were injected in five sheep 15 min before cardiac arrest and the sheep were slaughtered. In vitro imaging was performed at 1.5 T included T1- and T2-weighted spin echo sequences in long and short axis views. Signal intensities (SI) were determined in 36 myocardial segments per slice and compared to macro- and microscopy. RESULTS: In all animals an antero-lateral infarct region was evident histologically. This region presented with increased T2 SI and T1 SI after Gd-DTPA. The number of segments with increased SI in T1-weighted images was higher (n = 195 segments) compared to segments with increased T2 SI (n = 122 segments). Granulation tissue could be differentiated from rarely vascularized connective tissue at a high level of significance (p < 0.001) by T1 and T2 SI analysis. Wall thickness was significantly decreased in necrotic myocardium (3.8 +/- 1.2 mm) compared to normal tissue (9.8 +/- 1.1 mm, p < 0.001). CONCLUSION: In four-week-old occlusive MI the extent of necrosis can be accurately assessed by analysis of post contrast T1-weighted images. Considering regional T2 SI, granulation tissue can be differentiated from regions with predominant fibrous organisation.

Animals↗
PubMed2000

Disseminated fatal human cytomegalovirus disease after severe trauma.

OBJECTIVE: Disseminated human cytomegalovirus (HCMV) disease is considered to be uncommon in critically ill but otherwise not immunosuppressed patients. We describe the case of a trauma victim who developed fatal HCMV disease that initially presented as pseudomembranous colitis and resulted in sudden cardiac death. DESIGN: Case report of fatal HCMV disease in a previously healthy patient after multiple trauma. SETTING: Surgical intensive care unit (ICU). PATIENT: A 63-yr-old male patient with multiple injuries. INTERVENTIONS AND MEASUREMENTS: Under ICU treatment, symptoms of HCMV reactivation presenting as pseudomembranous colitis appeared 32 days after trauma. Detailed laboratory examinations for HCMV infection were performed, including complement fixation titer, immunoglobulin G and M, polymerase chain reaction, and virus isolation. RESULTS: The intravital detection of HCMV DNA in serum, leukocytes, and a colonic biopsy specimen indicated HCMV reactivation. Postmortem examination findings, including positive viral cultures, showed severe disseminated HCMV disease with involvement of the colon and myocardium. CONCLUSIONS: The lack of specific clinical symptoms of HCMV disease and the delay until viral culture results are available make an exact and timely diagnosis of HCMV disease difficult. Its prevalence in critically ill but otherwise not immunosuppressed patients is currently unknown and possibly underestimated. Because severe illness or trauma can cause immunodysfunction and, thus, may contribute to an increased rate of HCMV disease, detailed studies are warranted to evaluate the real risk in the ICU setting.

Biopsy↗
PubMed2000

Differential distribution of novel restriction-modification systems in clonal lineages of Neisseria meningitidis.

Using representational difference analysis, we isolated novel meningococcal restriction-modification (R-M) systems. NmeBI, which is a homologue of the R-M system HgaI of Pasteurella volantium, was present in meningococci of the ET-5 complex and of lineage III. NmeAI was found in serogroup A, ET-37 complex, and cluster A4 meningococci. NmeDI was harbored by meningococci of the ET-37 complex and of cluster A4, but not by serogroup A meningococci. Two of the R-M systems, NmeBI and NmeDI, were located at homologous positions between the phenylalanyl-tRNA synthetase genes pheS and pheT, which appeared to be a preferential target for the insertion of foreign DNA in meningococci. The distribution of the three R-M systems was tested with 103 meningococcal strains comprising 49 sequence types. The vast majority of the strains had either NmeBI, NmeAI, or both NmeAI and NmeDI. Using cocultivation experiments, we could demonstrate that NmeBI, which was present in ET-5 complex meningococci, was responsible for a partial restriction of DNA transfer from meningococci of the ET-37 complex to meningococci of the ET-5 complex.

Clone Cells↗
PubMed1999

Noninvasive diagnosis of ischemia-induced wall motion abnormalities with the use of high-dose dobutamine stress MRI: comparison with dobutamine stress echocardiography.

BACKGROUND: The analysis of wall motion abnormalities with dobutamine stress echocardiography (DSE) is an established method for the detection of myocardial ischemia. With ultrafast magnetic resonance tomography, identical stress protocols as used for echocardiography can be applied. METHODS AND RESULTS: In 208 consecutive patients (147 men, 61 women) with suspected coronary artery disease, DSE with harmonic imaging and dobutamine stress magnetic resonance (DSMR) (1.5 T) were performed before cardiac catheterization. DSMR images were acquired during short breath-holds in 3 short-axis views and a 4- and a 2-chamber view (gradient echo technique). Patients were examined at rest and during a standard dobutamine-atropine scheme until submaximal heart rate was reached. Regional wall motion was assessed in a 16-segment model. Significant coronary heart disease was defined as >/=50% diameter stenosis. Eighteen patients could not be examined by DSMR (claustrophobia 11 and adipositas 6) and 18 patients by DSE (poor image quality). Four patients did not reach target heart rate. In 107 patients, coronary artery disease was found. With DSMR, sensitivity was increased from 74.3% to 86.2% and specificity from 69.8% to 85.7% (both P<0.05) compared with DSE. Analysis for women yielded similar results. CONCLUSIONS: High-dose dobutamine magnetic resonance tomography can be performed with a standard dobutamine/atropine stress protocol. Detection of wall motion abnormalities by DSMR yields a significantly higher diagnostic accuracy in comparison to DSE.

Aged↗
PubMed1999

Low DNA repair is a risk factor in skin carcinogenesis: a study of basal cell carcinoma in psoriasis patients.

We have studied DNA repair in patients with psoriasis aiming at investigating the importance of repair in chemically induced cancer. An increased risk of non-melanoma skin cancer has been observed in psoriasis patients extensively treated with tar, methotrexate and photochemotherapy (psoralen + UVA). We measured the DNA repair capacity (DRC) by a host cell reactivation (HCR) assay in lymphocytes from psoriasis patients with and without basal cell cancer and non-psoriatic persons with and without basal cell cancer (4 x 20 study persons). Among psoriasis patients we observed a significant lower DRC in patients with skin cancer compared to patients without skin cancer (P = 0.015; Mann-Whitney, one-sided). Using the median of the healthy control group (group 4) as a cutoff value to divide the psoriasis patients into groups of high and low repair, we found that individuals who had a low repair capacity had a 6.4-fold increased skin cancer risk compared to individuals with high repair (95% confidence interval (CI), 1.44-28.5). The level of DNA repair was correlated with the age at which the psoriasis patients got their first skin cancer. The lower the level of DNA repair, the earlier the psoriasis patients had their first skin tumor (P = 0.070 Spearman; one-sided). Psoriasis patients without BCC had marginally higher repair than healthy controls (P = 0.11, Mann-Whitney, two-sided). We found no difference between BCC patients without psoriasis and healthy controls. In conclusion, these findings suggest a protective role of DNA repair in a predominantly chemically induced cancer.

Adult↗
PubMed1999

Percutaneous tenodesis of the Achilles tendon. A new surgical method for the treatment of acute Achilles tendon rupture through percutaneous tenodesis.

Various studies have shown that the operative treatment of a freshly ruptured Achilles tendon is generally considered to be more appropriate than a nonoperative regimen. However, complications in open reconstructions are reported to occur between 11-29%. We intended to develop a method which reduces the risk of complications arising from operation but simultaneously allows early postoperative mobilization and functional treatment. We developed a percutaneous tenodesis of the Achilles tendon, using two Lengemann extension wires for adaptation of the ruptured tendon. This method of treatment has been applied in 20 patients. The postoperative observation period was one year. All patients were male, their average age was 42 years. The Achilles tendon ruptures occurred during sporting activities and were treated by operation within 22 h on average. The outcome was very good in 95%. One patient (5%) suffered a rerupture due to trauma. There was no other complication.

Achilles Tendon↗
PubMed1999

Transmyocardial laser revascularization in the acute ischaemic heart: no improvement of acute myocardial perfusion or prevention of myocardial infarction.

OBJECTIVE: Transmyocardial laser revascularization (TMLR) has been used to provide enhanced myocardial perfusion in patients not suitable for coronary revascularization or angioplasty. This study investigates the acute changes in myocardial perfusion after TMLR with a Holmium:Yttrium-Aluminium-Garnet (YAG) laser with a thermal imaging camera in a model of acute ischaemia, and confirms its midterm effects by post-mortem investigation of magnetic resonance imaging and histopathological examination. METHODS: Acute myocardial ischaemia was induced by occlusion of the dominant diagonal branch in ten sheep. Perfusion measurements were undertaken first in the unaffected myocardium, then after temporary occlusion of the coronary to obtain a control measurement for ischaemic myocardium. Myocardial perfusion was then evaluated during reperfusion after release of coronary occlusion. Then the coronary was permanently occluded and 20.5+/-2 channels were drilled with the Holmium:YAG laser and perfusion was measured again. The other four sheep served as control with untreated ischaemia. All animals were sacrificed after 28 days following administration of gadolinium i.v. to serve as contrast medium for magnetic resonance tomography. The hearts were subjected to magnetic resonance tomography and histopathological examination. RESULTS: Intraoperative perfusion measurements revealed a decreased perfusion after temporary occlusion and an increased perfusion in reperfused myocardium. After TMLR, no improvement of myocardial perfusion above the ischaemic level could be shown. Magnetic resonance images could neither confirm patent laser channels nor viable myocardium within ischaemic areas. On histology no patent endocardial laser channel could be detected. The transmural features were myocardial infarct with scar tissue. CONCLUSIONS: In the presented sheep model with acute ischaemia, TMLR with a Holmium:YAG laser did not provide acute improvement of myocardial perfusion as assessed by a thermal imaging camera. This would suggest no direct contribution of newly created laser channels to myocardial perfusion. As chronic effects are concerned, no perfused laser channels could be identified by later magnetic resonance imaging or histology.

Animals↗
PubMed1999

Mechanisms of neisserial serum resistance.

Pathogenic Neisseria use a variety of mechanisms to survive the bactericidal action of the complement system. Serum resistance is a crucial virulence factor for the development of severe meningococcal disease, meningococcal meningitis and disseminated gonococcal infection. Furthermore, local inflammation at the site of gonococcal infection exposes the bacteria to moderate concentrations of complement factors. We review current concepts of neisserial serum resistance with emphasis on porins and polysaccharides exposed on the neisserial surface and their interaction with components of normal human serum.

Animals↗