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Biomedical subjects

Andrea Peters

Publications and source records attributed to Andrea Peters.

13 recordsLinked to original sources
PubMed2006

The stability and anti-apoptotic function of A1 are controlled by its C terminus.

Most Bcl-2 family members can localize to intracellular membranes via hydrophobic sequences within their C-terminal portion. We found that the C terminus of the anti-apoptotic family member A1 did not function as a membrane anchor. Instead, this stretch of the protein rendered A1 highly unstable by mediating its polyubiquitination and rapid proteasomal degradation. Moreover, the domain did not only function independently of its position within the A1 protein but when transferred could even destabilize unrelated proteins like enhanced green fluorescent protein and caspase-3. A1 was, however, much more stable in the presence of the Bcl-2 homology-only protein BimEL, suggesting that direct interaction of A1 with pro-apoptotic members of the Bcl-2 family strongly reduces its rate of turnover. We further show that the C-terminal end of A1 also contributes to the anti-apoptotic capacity of the protein. In conclusion, our data demonstrate that the C terminus serves a dual function by controlling the stability of A1 and by amplifying the capacity of the protein to protect cells against apoptosis.

Amino Acid Sequence↗
PubMed2006

Pattern reversal ERG and VEP--comparison of stimulation by LED, monitor and a Maxwellian-view system.

PURPOSE: Pattern stimulation is widely used to detect inner retinal dysfunction. In this work we describe a pattern stimulation technique with LEDs and compare the results with conventional methods. METHODS: PERG and VEP were derived from three normal subjects. Three different techniques were used to generate a checkerboard pattern reversal stimulus: a 70 Hz monitor, a Maxwellian-view system equipped with a Xenon-arc lamp and a mechanical mirror system, and a LED array (Roland Consult) consisting of 100 white LEDs. Two kinds of luminance (125 and 340 cd/m2) and four temporal frequencies (4, 8, 12 and 24 reversals per second) were studied on three healthy subjects. Additionally, a luminance tuning experiment (30, 60, 90, 125 and 340 cd/m2) was performed on one subject. RESULTS: Comparison of different stimulation techniques shows reproducible responses of PERG and VEP with all three methods. The LED array leads to slightly smaller amplitudes than both other techniques, which we ascribe to the design of the LED field. No difference of peak times or phases was noticed between different stimulation techniques. A luminance dependency of PERG and VEP is noticeable using stimulation with LED: with decreasing luminance we measured increasing peak times of PERG and VEP and decreasing amplitude of PERG. CONCLUSION: We conclude that central retinal stimulation with checkerboard pattern reversal is possible with LED. It gives comparable results to monitor and Maxwellian-view system.

Adult↗
PubMed2006

Improving glaucoma diagnosis by the combination of perimetry and HRT measurements.

PURPOSE: The aim of this study was to determine, whether the combination of morphologic data of the optic nerve head and visual field (VF) data would improve diagnosis of glaucoma, on the basis of the measurements alone. PATIENTS AND METHODS: Eighty-eight perimetric glaucomatous and 88 normal optic discs from the Erlangen Glaucoma Registry were matched for age. All normals and patients were examined in a standardized manner (Slitlamp biomicroscopy, gonioscopy, 24 h-applanation tonometry, automated VF testing, 15-degree optic disc stereographs, and Heidelberg Retina Tomograph (HRT)-scanning of the optic disc). The HRT variables were calculated in 4 optic disc sectors. All variables were calculated with the software's standard reference plane. To gain the same allocation of sectors as provided by the HRT software, the VF responses were averaged within 4 sectors. Classification results of these VF responses were compared with the summarized results within 4 sectors. Six different combinations of morphologic and VF data were used to assess their suitability to diagnose the disease. HRT measurements, and the standard output of the Octopus (HRT/PERI1), HRT measurements and the summarized sectors and their standard deviations (HRT/PERI2), HRT measurements, standard output of the octopus and the summarized sectors and their standard deviations (HRT/PERI1/PERI2), standard output of the Octopus (PERI1), summarized sectors of the Octopus and their standard deviations (PERI2) and HRT measurements. To assess the diagnostic value of the different data sets machine learning classifiers, stabilized linear discriminant analysis, classification trees, bagging, and double-bagging were applied. RESULTS: Combination of morphologic and VF data improved the automated classification rules. The accuracy to diagnose glaucoma just by VF and HRT indices was maximized for double-bagging using both diagnostic tools. An estimated misclassification probability of less than 0.07 could be achieved for the primary open angle glaucoma patients combining HRT and VF sectors by double bagging. So highest sensitivity was 95% and specificity 91%, achieved by double-bagging and combination of HRT, PERI1, and PERI2. CONCLUSIONS: The combination of optic disc measurements and VF data could not only improve glaucoma diagnosis in future, but could also help to find an objective way to diagnose glaucomatous optic atrophy. The limitation of the topographic relationship between structure and function is the individual variability of the optic disc morphology and the subjective variability of VF testing.

Female↗
PubMed2006

The complementary Erlangen active simulator for interventional endoscopy training is superior to solely clinical education in endoscopic hemostasis--the French training project: a prospective trial.

BACKGROUND: The Erlangen Active Simulator for Interventional Endoscopy (EASIE) using ex-vivo porcine organs was introduced in 1997. The present study should analyze whether repeated EASIE simulator training in endoscopic hemostasis led to superior performance compared with a traditionally educated group. The results were compared with a similar project in New York. METHODS: Thirty-five French GI fellows were enrolled. Baseline skills evaluation was performed in four disciplines (manual skills, injection/coagulation, clip application and variceal ligation) using the compactEASIE-simulator equipped with an upper gastrointestinal organ package for bleeding simulation. The same, translated evaluation forms (from the prior New York project) were used. Subsequently, fellows were randomized into group A (n=17, only clinical education) and group B (n=18, additional three simulator trainings). Group B was trained the next day and after 4 and 7 months by experts of the French Society of Gastrointestinal Endoscopy. Both groups performed routine and emergency endoscopies at their home hospitals during the study period. Both groups were re-evaluated blindly after 9 months. RESULTS: The learning curve for group B showed a significant improvement in all disciplines (P<0.004) whereas group A improved significantly in only two of four disciplines at blinded final evaluation (manual skills P=0.02, injection/coagulation P=0.013). The direct comparison of groups B and A at blinded final evaluation showed significantly superior ratings for group B in all disciplines (P<0.006) and significantly shorter performance times in two disciplines (P=0.016 each). The comparison with the similar 'New York project' revealed that preexisting differences in skills were adjusted by the training. CONCLUSION: Complementary trainings (three workshops in 7 months) in endoscopic hemostasis using the compactEASIE improved skills compared with a solely clinical education. The results of the 'New York project' were confirmed and benefits were independent from the medical educational system.

Animals↗
PubMed2005

Microarray versus conventional prediction of lymph node metastasis in colorectal carcinoma.

BACKGROUND: The authors investigated whether microarray-based gene expression analysis of primary tumor biopsy material could be used to predict lymph node status in patients with colorectal carcinoma (CRC). Lymphatic metastasis strongly determines treatment algorithms in CRC. Currently, postoperative histology results are needed to determine lymph node status. Reliable preoperative information would be useful to advance treatment strategies. METHODS: In specimens from 66 patients with CRC from the Erlangen Registry of Colorectal Cancer, 41 shock-frozen samples of International Union Against Cancer (UICC) Stage I-II CRC and 25 samples of UICC Stage III CRC were microdissected manually, RNA was isolated, and gene chips (HG-U133A; Affymetrix) were hybridized. Prediction rates for lymphatic metastasis were calculated using conventional clinicopathologic parameters, gene expression data, and a combination of both. Prediction error, specificity, and sensitivity were analyzed using six different statistical classifiers. RESULTS: Analysis of conventional parameters produced a positive prediction rate that ranged between 53% and 61%, sensitivity of 42%, and specificity of 72%. Microarray prediction rates were between 62% and 67% for lymphatic metastasis. Specificity was between 76% and 83%, and sensitivity was between 38% and 48%, depending on the statistical procedure. The conventional estimates were improved by 9-12% when array data were added. CONCLUSIONS: Current data show that the prediction of lymphatic metastasis can be improved by gene expression profiling of the primary tumor biopsy, alone or in combination with conventional parameters. Gene expression profiling may become valuable increasingly in planning treatment for patients with CRC.

Aged↗
PubMed2004

Diagnostic value of multifocal VEP using cross-validation and noise reduction in glaucoma research.

BACKGROUND: The diagnostic value of multifocal visual evoked potentials (mf VEP) in glaucoma research is still under debate. Several previous studies proclaim it to be a useful tool for clinical applications, but according to other studies, different problems (low specificity, poor records, and interindividual variation) still retard its clinical use. The aim of the present study was to examine whether the mf VEP data obtained with the RETIscan system are appropriate for formulating a classification rule for glaucoma. METHOD: We examined and evaluated 65 eyes in 38 advanced glaucoma patients and 27 normal subjects, using four occipital gold cup electrodes (cross layout) for bipolar recording and a CRT monitor (display diameter 60 degrees, chequerboard pattern reversal, 60 segments in dartboard layout) for stimulation. In each case, eight cumulative measurements (77 s each) were made. The data of the 60 segments were cross-correlated with a RETIscan-internal VEP norm ("VEP finder"), combined in 16 sectors, and evaluated via the classification technique "double-bagging" and the Wilcoxon U-test. RESULTS: In three out of the 16 sectors, the VEP amplitudes of the patients were significantly reduced (Wilcoxon U-test). Applying double-bagging on the cross-correlated data (with VEP finder) resulted in a sensitivity of 75% and a specificity of 71%, and the estimated misclassification rate was 27%. For uncorrelated data (without VEP finder), the same analysis achieved a sensitivity of about 60% and a specificity of 40%. CONCLUSIONS: Estimated sensitivity and specificity suggest that by using the RETIscan system for recording, a classification of the VEP data--i.e. a separation between normal and glaucoma subjects--is possible.

Biomedical Research↗
PubMed2003

Superiority of age and weight as variables in predicting osteoporosis in postmenopausal white women.

UNLABELLED: Identification of women at risk for osteoporosis is of great importance for the prevention of osteoporotic fractures. Routine BMD measurement of all women is not feasible for most populations, hence identification of a high-risk subset of women is an important element of effective preventive strategies. METHODS: We identified 959 postmenopausal non-Hispanic women aged 51 years and above from the NHANES III study to assess the relative contribution of risk predictors for low BMD at the whole proximal femur and the femoral neck regions. Based on recognized risk factors for osteoporosis identified by a systematic literature search, we ran several multiple linear regression models based on the results of preceding bivariate analyses. We show several models based on their explanatory ability assessed by adjusted r(2), ROC, and C-value analyses rather than on the coefficients and P values. We furthermore examined the sensitivity, specificity, and predictive values of our preferred models for various cutoff T-scores-the choice of which will vary depending on different study goals and population characteristics. RESULTS: Age and weight were by far the most informative predictors for low bone mineral density out of a list of 20 candidate risk predictors. Our preferred prediction models for the two regions hence contained only two variables: i.e., age and measured weight. The resulting parsimonious model to predict BMD at whole proximal femur had an adjusted r(2) of 0.43, an area under the ROC curve of 0.85, and a C-value of 0.70. Similarly, prediction for BMD at the femoral neck had adjusted r(2), area under the curve, and C-value of 0.39, 0.83, and 0.66, respectively. CONCLUSIONS: The model equations, predicted T-score = -1.332-0.0404 x (age) + 0.0386 x (measured weight) and predicted T-score = -1.318-0.0360 x (age) + 0.0314 x (measured weight) for whole proximal femur and femoral neck, respectively, can be used in field conditions for screening purposes. More complex prediction equations add little explanatory power. Based on the study goals and the population characteristics, specific cutoff T-scores have to be decided before using these equations.

Age Factors↗
PubMed2003

Novel photochromic compounds based on the 1-thienyl-2-vinylcyclopentene backbone.

[reaction: see text] A new class of photochromic compounds based on the hexatriene backbone has been developed. The backbone, composed of a thiophene ring, a perfluorocyclopentene ring, and a trisubstituted olefin, undergoes reversible ring-opening and ring-closing photoisomerization reactions when irradiated with ultraviolet and visible light, respectively.

Journal Article↗
PubMed2003

Electrochromism in photochromic dithienylcyclopentenes.

Both photochromic and unprecedented electrochromic properties have been observed for a class of 1,2-bis(3-thienyl)cyclopentene derivatives bearing either a thiophene or a phenyl group attached to the reactive carbon centers. These compounds can be interconverted between their colorless ring-open and colored ring-closed states using UV and visible light, respectively. They can also be catalytically transformed from their ring-closed states to their ring-open states through electrochemical or chemical oxidation.

Journal Article↗
PubMed2003

New glaucoma classification method based on standard Heidelberg Retina Tomograph parameters by bagging classification trees.

PURPOSE: In this article we propose and evaluate nonparametric tree classifiers that can handle non-normal data and a large number of possible predictors using the full set of standard Heidelberg Retina Tomograph measurements for classifying glaucoma. METHODS: The classifiers were trained and tested using standard Heidelberg Retina Tomograph parameters from examinations of 98 subjects with glaucoma and 98 normal subjects of the Erlangen Glaucoma Registry. All patients and control subjects were evaluated by 15 degrees -optic disc stereographs, Heidelberg Retina Tomograph measurements, standard computerized white-in-white perimetry, and 24-hour-intraocular pressure profiles. The subjects were matched by age and sex. Standard classification trees as well as bagged classification trees were used. The classification outcome of the trees was compared with the classification by two published linear discriminant functions based on Heidelberg Retina Tomograph variables with respect to their cross-validated misclassification error. RESULTS: The bagged classification tree had the lowest misclassification error estimate of 14.8% with a sensitivity of 81.6% at a specificity of 88.8%. The cross-validated error rates of the two linear discriminant function procedures were 20.4% (sensitivity 82.6%, specificity 76.7%) and 20.6% (sensitivity 81.4%, specificity 77.3%) for our set of observations. Bagged classification trees were able to reduce the misclassification error of glaucoma classification. CONCLUSIONS: Bagged classification trees promise to be a new and efficient approach for glaucoma classification using morphometric 2- and 3-dimensional data derived from the Heidelberg Retina Tomograph, taking into account all given variables.

Case-Control Studies↗
PubMed2002

Apoptosis as a cellular predictor for histopathologic response to neoadjuvant radiochemotherapy in patients with rectal cancer.

BACKGROUND: Tumor shrinkage by preoperative radiochemotherapy (RCT) can markedly improve surgery in locally advanced (T4) rectal cancer with clear resection margins and may enable sphincter preservation in low-lying tumors. However, tumor response varies considerably, even among tumors treated according to the same protocol. If one is able to identify patients with highly radio-responsive tumors at the time of diagnosis, a selective and individualized policy of preoperative RCT might be pursued. METHODS: The apoptotic index (AI), Ki-67, p53, and bcl-2 were evaluated by immunohistochemistry on pretreatment biopsies from 44 patients treated uniformly according to a prospective neoadjuvant RCT protocol (CAO/AIO/ARO-94). Treatment response was assessed histopathologically in the resected surgical specimen, using a five-point grading system. Expression of each marker was correlated with tumor response and relapse-free survival after curative surgery. RESULTS: Tumors with complete (n = 3) or good (n = 28) response to RCT showed significantly higher pretreatment levels of apoptosis (mean AI: 2.06%) than tumors with moderate (n = 7), minimal (n = 5), or no regression (n = 1) from RCT (AI: 1.44%, p = 0.003). The AI was significantly related to Ki-67 (p = 0.05), but not to p53 and bcl-2 status. Tumor regression and AI best predicted relapse-free survival after combined modality treatment and curative surgery. CONCLUSION: Spontaneous apoptosis in rectal cancer may serve as an important predictor of tumor regression from RCT in rectal cancer and as a significant prognosticator of relapse-free survival. Thus, this molecular marker may finally help to tailor therapy with regard to (neo-) adjuvant treatment of rectal cancer.

Adult↗