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Biomedical subjects

J Weber

Publications and source records attributed to J Weber.

At least 127 records · Page 7Linked to original sources
PubMed2000

A phase I trial of a human papillomavirus (HPV) peptide vaccine for women with high-grade cervical and vulvar intraepithelial neoplasia who are HPV 16 positive.

Eighteen women with high-grade cervical or vulvar intraepithelial neoplasia who were positive for human papillomavirus (HPV) 16 and were HLA-A2 positive were treated with escalating doses of a vaccine consisting of a 9-amino acid peptide from amino acids 12-20 encoded by the E7 gene emulsified with incomplete Freund's adjuvant. Starting with the eleventh patient, an 8-amino acid peptide 86-93 linked to a helper T-cell epitope peptide with a covalently linked lipid tail was added. Patients with colposcopically and biopsy-proven cervical intraepithelial neoplasia/vulvar intraepithelial neoplasia II/III received four immunizations of increasing doses of the vaccine each 3 weeks apart, followed by a repeat colposcopy and definitive removal of dysplastic tissue 3 weeks after the fourth immunization. Patients were skin tested with the E7 12-20 peptide as well as control candida, mumps, and saline prior to and after the series of immunizations. Peripheral blood mononuclear cells were obtained by leucopheresis prior to and after the series of immunizations for analyses of CTL reactivity to the E7 12-20 and 86-93 epitope sequences. The presence of HPV 16 was assessed by DNA PCR on cervical scrapings and the biopsy specimens after vaccination. Pathology specimens were analyzed before and after vaccination for the presence of dysplasia, and the intralesional infiltrate of CD4/CD8 T-cells and dendritic cells was measured by immunohistochemical staining. Only 3 of 18 patients cleared their dysplasia after vaccine, but an increased S100+ dendritic cell infiltrate was observed in 6 of 6 patients tested. Cytokine release and cytolysis assays to measure E7-specific reactivity revealed increases in 10 of 16 patients tested. No positive delayed type hypersensitivity skin test reactivity was shown in any patient to HPV E7 12-20 before or after vaccinations. Virological assays showed that 12 of 18 patients cleared the virus from cervical scrapings by the fourth vaccine injection, but all biopsy samples were still positive by in situ RNA hybridization after vaccination. Six patients had partial colposcopically measured regression of their cervical intraepithelial neoplastic lesions in addition to the three complete responders. The data establish that a HPV-16 peptide vaccine may have important biological and clinical effects and suggest that future refinements of an HPV vaccine strategy to boost antigen-specific immunity should be explored.

Adult↗
PubMed2000

The French Virtual Medical University.

This paper is the description of a French Virtual Medical University based on the federation of existing or currently being developed resources in several Medical Schools in France. The objectives of the project is not only to share experiences across the country but also to integrate several resources using the New Information and Communication Technologies to support new pedagogical approaches for medical students and also for continuing medical education. The project includes: A virtual Medical Campus using secure access from several sites, The Integration of new interactive resources based on pedagogical methods, Implementation of new indexing and search engines based on medical vocabularies and ontologies, The definition of general and specific portals, the evaluation of the system for ergonomics and contents.

Computer-Assisted Instruction↗
PubMed1999

Importance of F1-ATPase residue alpha-Arg-376 for catalytic transition state stabilization.

The functional role of essential residue alpha-Arg-376 in the catalytic site of F1-ATPase was studied. The mutants alpha R376C, alpha R376Q, and alpha R376K were constructed, and combined with the mutation beta Y331W, to investigate catalytic site nucleotide-binding parameters, and to assess catalytic transition state formation by measurement of MgADP-fluoroaluminate binding. Each mutation caused large impairment of ATP synthesis and hydrolysis. Despite the apparent proximity of alpha-Arg-376 to bound nucleoside di- and triphosphate in published X-ray structures, the mutations had little effect on MgADP or MgATP binding affinities, particularly at the highest affinity catalytic site, site 1. Both Cys and Gln mutants abolished transition state formation, demonstrating that alpha-Arg-376 is normally involved at this step of catalysis. A model of the F1-ATPase catalytic transition state structure is presented and discussed. The Lys mutant, although severely impaired, supported transition state formation, suggesting that an additional essential role for the alpha-Arg-376 guanidinium group exists, likely in alpha/beta conformational signal transmission required for steady-state catalysis. Parallels between alpha-Arg-376 and GAP/G-protein "arginine finger" residues are evident.

Adenosine Diphosphate↗
PubMed1999

[Cost comparison of hospital and ambulatory i.v. therapy in adult cystic fibrosis patients. Results of a controlled prospective study].

BACKGROUND: The regular i.v.-therapy of adults with cystic fibrosis (CF) on an in-patient basis is regarded as expensive. Home treatment is supposed to be cheaper. During a prospective controlled study to compare in-patient treatment (SIT) with home i.v.-treatment (HIT) in regard to clinical, psychosocial and economic parameters, delivered health services and costs in the German setting were evaluated in a comparable manner. PATIENTS AND METHODS: During the study period 4/95 to 9/96 45 patients with altogether 56 hospital and 40 home i.v.-courses of approximately 14 days were included in the study. Principal instruments to record the resource consumption were documentation sheets kept by the medical staff and the patients. In addition, pharmacy accounts in HIT and patient records and hospital controlling data in SIT were used. RESULTS: The average costs of a course were 14,038 DM for HIT and 18,702 DM for SIT. Striking are the large differences in medication costs. Two main reasons could be identified for the cost difference: 1, the use of a mobile infusion system in HIT and 2, the much higher prices of pharmaceuticals in the ambulatory care sector compared to the hospital sector, where extremely high profits of the home care service firms or the pharmacy can be supposed. The social costs of HIT (when antibiotics are valued to opportunity costs) are estimated at less than 10,500 DM. From a societal perspective HIT is preferable, from the perspective of the statutory health insurance funds hospital therapy is preferable. CONCLUSIONS: 1. The widely accepted hypothesis that ambulatory care is cheaper than hospital care is--at least in the German setting--not a-priori true. 2. In the treatment of CF patients incentive failures exist which induce unnecessary and avoidable hospital stays if the perspective of the statutory sickness funds is dominant. 3. Changes in system conditions as e.g. the permission of mail-order pharmacies might help to implement a more rational allocation of resources.

Adult↗
PubMed1999

Effect of the epsilon-subunit on nucleotide binding to Escherichia coli F1-ATPase catalytic sites.

The influence of the epsilon-subunit on the nucleotide binding affinities of the three catalytic sites of Escherichia coli F1-ATPase was investigated, using a genetically engineered Trp probe in the adenine-binding subdomain (beta-Trp-331). The interaction between epsilon and F1 was not affected by the mutation. Kd for binding of epsilon to betaY331W mutant F1 was approximately 1 nM, and epsilon inhibited ATPase activity by 90%. The only nucleotide binding affinities that showed significant differences in the epsilon-depleted and epsilon-replete forms of the enzyme were those for MgATP and MgADP at the high-affinity catalytic site 1. Kd1(MgATP) and Kd1(MgADP) were an order of magnitude higher in the absence of epsilon than in its presence. In contrast, the binding affinities for MgATP and MgADP at sites 2 and 3 were similar in the epsilon-depleted and epsilon-replete enzymes, as were the affinities at all three sites for free ATP and ADP. Comparison of MgATP binding and hydrolysis parameters showed that in the presence as well as the absence of epsilon, Km equals Kd3. Thus, in both cases, all three catalytic binding sites have to be occupied to obtain rapid (Vmax) MgATP hydrolysis rates.

Adenosine Triphosphate↗
PubMed1999

The role of beta-Arg-182, an essential catalytic site residue in Escherichia coli F1-ATPase.

Beta-Arg-182 in Escherichia coli F1-ATPase (beta-Arg-189 in bovine mitochondrial F1) is a residue which lies close to catalytic site bound nucleotide (Abrahams et al. (1994) Nature 370, 621-628). Here we investigated the role of this residue by characterizing two mutants, betaR182Q and betaR182K. Oxidative phosphorylation and steady-state ATPase activity of purified F1 were severely impaired by both mutations. Catalytic site nucleotide-binding parameters were measured using the fluorescence quench of beta-Trp-331 that occurred upon nucleotide binding to purified F1 from betaR182Q/betaY331W and betaR182K/betaY331W double mutants. It was found that (a) beta-Arg-182 interacts with the gamma-phosphate of MgATP, particularly at catalytic sites 1 and 2, (b) beta-Arg-182 has no functional interaction with the beta-phosphate of MgADP or with the magnesium of the magnesium-nucleotide complex in the catalytic sites, and (c) beta-Arg-182 is directly involved in the stabilization of the catalytic transition state. In these features the role of beta-Arg-182 resembles that of another positively charged residue in the catalytic site, the conserved lysine of the Walker A motif, beta-Lys-155. A further role of beta-Arg-182 is suggested, namely involvement in conformational change at the catalytic site beta-alpha subunit interface that is required for multisite catalysis.

Adenosine Diphosphate↗
PubMed1999

Slow deformation and lower seismic hazard at the new madrid seismic zone

Global Positioning System (GPS) measurements across the New Madrid seismic zone (NMSZ) in the central United States show little, if any, motion. These data are consistent with platewide continuous GPS data away from the NMSZ, which show no motion within uncertainties. Both these data and the frequency-magnitude relation for seismicity imply that had the largest shocks in the series of earthquakes that occurred in 1811 and 1812 been magnitude 8, their recurrence interval should well exceed 2500 years, longer than has been assumed. Alternatively, the largest 1811 and 1812 earthquakes and those in the paleoseismic record may have been much smaller than typically assumed. Hence, the hazard posed by great earthquakes in the NMSZ appears to be overestimated.

Journal Article↗
PubMed1999

Binding of the transition state analog MgADP-fluoroaluminate to F1-ATPase.

Escherichia coli F1-ATPase from mutant betaY331W was potently inhibited by fluoroaluminate plus MgADP but not by MgADP alone. beta-Trp-331 fluorescence was used to measure MgADP binding to catalytic sites. Fluoroaluminate induced a very large increase in MgADP binding affinity at catalytic site one, a smaller increase at site two, and no effect at site three. Mutation of either of the critical catalytic site residues beta-Lys-155 or beta-Glu-181 to Gln abolished the effects of fluoroaluminate on MgADP binding. The results indicate that the MgADP-fluoroaluminate complex is a transition state analog and independently demonstrate that residues beta-Lys-155 and (particularly) beta-Glu-181 are important for generation and stabilization of the catalytic transition state. Dicyclohexylcarbodiimide-inhibited enzyme, with 1% residual steady-state ATPase, showed normal transition state formation as judged by fluoroaluminate-induced MgADP binding affinity changes, consistent with a proposed mechanism by which dicyclohexylcarbodiimide prevents a conformational interaction between catalytic sites but does not affect the catalytic step per se. The fluorescence technique should prove valuable for future transition state studies of F1-ATPase.

Adenosine Diphosphate↗
PubMed1999

Prevalence of anal incontinence in 409 patients investigated for stress urinary incontinence.

A clinical questionnaire concerning anorectal symptoms and urodynamic tests was used to investigate 409 women consulting for stress urinary incontinence. To compare urodynamic data, patients were divided into three groups of women who had either stress urinary incontinence associated with incontinence for formed and/or liquid stools or with gas incontinence, or isolated stress urinary incontinence. To take in account the patients'age for data interpretation, a Mantel-Haenszel test or covariate analysis was performed. Anal incontinence was reported in 114 (28%) of the 409 women investigated. The prevalence of incontinence for gas only, for liquid, or for solid stools was 18.3, 9.3, and 1%, respectively. The duration of gas incontinence was longer than that of fecal incontinence or stress urinary incontinence. Difficult defecation was more frequently observed in patients with double incontinence than in patients with only stress urinary incontinence, and the difference was significant between patients with gas incontinence and patients with stress urinary incontinence (53% versus 37%, P = 0. 03). There was no difference in the number of bowel movements per week among the three groups of patients. The number of vaginal deliveries was surprisingly lower in patients with fecal incontinence associated with urinary incontinence than in others. There was no urodynamic feature that could distinguish patients with urinary incontinence and patients with double incontinence. This study confirmed the close relationship between anal and stress urinary incontinence. Neurourol. Urodynam. 18:579-590, 1999.

Adolescent↗
PubMed1999

Effects of L-carnitine on leukocyte function and viability in hemodialysis patients: A double-blind randomized trial.

Excess morbidity and mortality among long-term hemodialysis patients because of infectious complications is partly caused by an impairment of cellular immune defense. We hypothesized this impairment is related to an abnormal carnitine metabolism also present in these patients. In a double-blind, randomized, placebo-controlled trial, we investigated the effect of L-carnitine on phagocytic function and viability of blood leukocytes in 17 patients undergoing maintenance hemodialysis. After an observation period of 1 month, the patients received either 10 mg/kg of L-carnitine or placebo intravenously at the end of each hemodialysis session over a period of 4 months. Leukocyte oxidative metabolism was measured by means of luminol-enhanced chemiluminescence and superoxide generation after stimulation with Staphylococcus aureus or phorbol myristate acetate. Killing capacity and phagocytosis of radiolabeled staphylococci were determined. A lactate dehydrogenase (LDH) release test was applied to assess cell viability. We were unable to show an effect of L-carnitine on phagocytic function and viability in vivo. Several clinical parameters were observed during the trial. No statistically significant differences concerning dialysis-related morbidity, anemia, or reduction of blood urea nitrogen and creatinine levels were detected. Additionally, we tested the effect of L-carnitine on phagocytic function after in vitro incubation of blood leukocytes, which also showed no changes. LDH release was decreased, indicating an improved viability of these cells. The latter results were found after in vitro incubation of cells, but could not be confirmed in vivo. In summary, we could not show beneficial effects of L-carnitine administration in hemodialysis patients for the dosage and duration of treatment stated, either on phagocytic function and viability or on the clinical and biochemical parameters observed.

Adult↗
PubMed1999

Assessment of myocardial perfusion using multisection first-pass MRI and color-coded parameter maps: a comparison to 99mTc Sesta MIBI SPECT and systolic myocardial wall thickening analysis.

The most recently reported magnetic resonance first-pass myocardial perfusion studies were restricted to single slice imaging or a data analysis based on interactively placed regions of interest. This study was designed to investigate a new saturation recovery TurboFLASH sequence for multisection myocardial perfusion imaging and to develop a pixel-based software tool to calculate qualitative perfusion parameters. The findings of perfusion imaging were compared to percent systolic myocardial wall thickening analysis and 99mTc Sesta MIBI SPECT. Six healthy volunteers and twelve patients with proven coronary artery disease (CAD) or chronic myocardial infarction were examined. Diagnostic images were acquired for all volunteers and patients with the multisection saturation recovery TurboFLASH sequence. Perfusion defects could be visualized on parameter maps for signal intensity increase over baseline and signal intensity upslope. Sensitivity and specificity were 76.9% and 97.1% for first-pass perfusion MRI, and respectively 84.6% and 94.3% for CINE imaging. All perfusion defects determined with 99mTc Sesta MIBI SPECT were identified by the combined analysis of myocardial perfusion and wall thickening. The presented software demonstrated a pixel-based analysis of first-pass perfusion studies and simplified image interpretation in a clinical setting. The combination of perfusion and wall motion imaging provided complementary information for the treatment of patients suffering from CAD.

Adult↗
PubMed1999

Multislice MR perfusion imaging and regional myocardial function analysis: complimentary findings in chronic myocardial ischemia.

PURPOSE: The purpose of this study is to assess the reliability of multislice MR perfusion imaging in comparison to regional wall function and nuclear medicine and to test different qualitative and quantitative parameters for perfusion assessment. MATERIAL AND METHODS: 15 patients with chronic myocardial ischemia underwent CINE and first-pass perfusion MR imaging. Functional myocardial imaging was performed using a segmented CINE FLASH sequence and systolic myocardial wall thickening was assessed after semiautomated segmentation. MR first-pass perfusion studies were performed using a multislice saturation recovery TurboFLASH sequence. Different parameters were calculated for assessment of hypoperfused segments and results of MR imaging compared to 99mTc-SestaMIBI SPECT. RESULTS: MR perfusion imaging showed a sensitivity of 72% and a specificity of 98%. In combination with MR CINE imaging and wall thickening analysis we calculated a sensitivity of 100% and a specificity of 93%. Qualitative and quantitative perfusion parameter analysis showed significant differences between normal and hypoperfused segments for the signal intensity increase (p < 0.001), the signal intensity upslope (p < 0.001) as well as for the myocardial mean transit time (p < 0.001). CONCLUSION: The combination of systolic wall thickening analysis and myocardial perfusion can markedly improve the sensitivity of MRI in depiction of LV myocardial perfusion abnormalities. For assessment of hypoperfusion, different quantitative and qualitative parameters can be calculated showing significant differences between normal state and hypoperfusion.

Aged↗
PubMed1999

[Quality assurance in phlebography of the extremities].

By interdisciplinary cooperation with the German Societies for Radiology, Phlebology and Vascular Surgery, recommendations have been worked out which address the indication of phlebography of the veins of the extremities and which define the quality standards of phlebographic techniques. The specific clinical questions in primary varicose, acute thrombosis and postthrombotic syndrome have to be answered by employing adequate phlebographic technique, documentation, and description of relevant morphologic and functional findings.

Contraindications↗
PubMed1999

Increased tone of the rectal wall in response to feeding persists in patients with cauda equina syndrome.

The aim was to study fasting and postprandial rectal tone in patients with cauda equina injury. Electromechanical barostat measurement of rectal tone was made in 13 healthy volunteers and in five patients during a 10 min recording, while fasting and for 1 h after a 1000 kCal intake. A prompt decrease of rectal volume was observed in all control subjects and patients. The delay between the end of the meal and the onset of the rectal response was always less than 3 min in the five patients as well as in the control group. The rapidity of the rectal response to feeding observed in our five patients suggests that the rectal response was mediated via a neural or neurohumoral pathway despite severe injury of the sacral parasympathetic supply.

Adult↗