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F Baumann

Publications and source records attributed to F Baumann.

At least 19 recordsLinked to original sources
PubMed2006

Primary mouse hepatocytes for systems biology approaches: a standardized in vitro system for modelling of signal transduction pathways.

Complex cellular networks regulate regeneration, detoxification and differentiation of hepatocytes. By combining experimental data with mathematical modelling, systems biology holds great promises to elucidate the key regulatory mechanisms involved and predict targets for efficient intervention. For the generation of high-quality quantitative data suitable for mathematical modelling a standardised in vitro system is essential. Therefore the authors developed standard operating procedures for the preparation and cultivation of primary mouse hepatocytes. To reliably monitor the dynamic induction of signalling pathways, the authors established starvation conditions and evaluated the extent of starvation-associated stress by quantifying several metabolic functions of cultured primary hepatocytes, namely activities of glutathione-S-transferase, glutamine synthetase, CYP3A as well as secretion of lactate and urea into the culture medium. Establishment of constant metabolic activities after an initial decrease compared with freshly isolated hepatocytes showed that the cultured hepatocytes achieve a new equilibrium state that was not affected by our starving conditions. To verify the highly reproducible dynamic activation of signalling pathways in the in vitro system, the authors examined the JAK-STAT, SMAD, PI3 kinase, MAP kinase, NF-kappaB and Wnt/beta-catenin signalling pathways. For the induction of gp130, JAK1 and STAT3 phosphorylation IL6 was used, whereas TGFbeta was applied to activate the phosphorylation of SMAD1, SMAD2 and SMAD3. Both Akt/PKB and ERK1/2 phosphorylation were stimulated by the addition of hepatocyte growth factor. The time-dependent induction of a pool of signalling competent beta-catenin was monitored in response to the inhibition of GSK3beta. To analyse whether phosphorylation is actually leading to transcriptional responses, luciferase reporter gene constructs driven by multiple copies of TGFbeta-responsive motives were applied, demonstrating a dose-dependent increase in luciferase activity. Moreover, the induction of apoptosis by the TNF-like cytokine Fas ligand was studied in the in vitro system. Thus, the mouse hepatocyte in vitro system provides an important basis for the generation of high-quality quantitative data under standardised cell culture conditions that is essential to elucidate critical hepatocellular functions by the systems biology approach.

Animals↗
PubMed2006

Factors of severity at admission during an epidemic of dengue 1 in New Caledonia (South Pacific) in 2003.

We report a retrospective study of an epidemic of dengue in New-Caledonia (South Pacific) in 2003 among adult inpatients. The aim was to establish clinical and biological criteria for the severity of the infection at the time of admission. During 7 months, all inpatients older than 15 y having a laboratory-confirmed diagnosis of dengue fever (IgM or PCR) were included (n=170). Two groups were defined: severe cases (death and/or transfer to intensive care unit, n=24) and benign cases (n=146). Data were analysed using Epi-Info software. Univariate analysis showed that shock, haemorrhage and neurological complications were significantly more frequent in serious cases, respectively 37.5% vs 0.7%, 62.5% vs 32.2%, 25% vs 9.6% (p<0.05). Relevant biological criteria were: creatinine > 140 micromol/l (OR 12 (95% CI 3.93-37.44)), free bilirubin > 18 micromol/l (OR 12.69 ( 95% CI 2.88-59.5)), amylase > 220 UI/l (OR 27.34 (95% CI 4.57-210)) and platelets < 45,000/mm3 (OR 4.35 (95% CI 1.43-14.2)) with p<0.005 (VPP = 100% for association of 3 criteria). We suggest this combination of 4 biological criteria inclines to severity.

Amylases↗
PubMed2005

Distribution of Streptococcus pneumoniae serotypes responsible for penicillin resistance and the potential role of new conjugate vaccines in New Caledonia.

Invasive pneumococcal disease is a significant cause of morbidity and mortality worldwide. The aim of this study was to establish the serotypes responsible for pneumococcal disease and the serotypes responsible for penicillin resistance in Noumea, New Caledonia. Isolates of Streptococcus pneumoniae from all body sites referred to the Microbiology Department of the Pasteur Institute in New Caledonia between May 1999 and May 2001 had serotyping and susceptibility testing performed. Basic demographic data on patients were also collected. A total of 298 isolates were included in the study. The most common serotypes were types 1 (20%), 23F (10%), 12F (8%), 19F (8%), and 6B (5%). The serotype distribution differed significantly with age, site of collection, and ethnicity. Overall, 280 of 298 (94%) of the isolates had serogroups that are included in the 23-valent vaccine. However, only 14 of 20 (70%) of the isolates associated with invasive disease from children younger than 5 years of age and 26 of 113 (23%) of invasive isolates from patients more than 5 years of age were included in the new 7-valent conjugate vaccine. Overall, reduced susceptibility to penicillin was found in 43 of 298 (14.4%) of the isolates, with 13% falling into the intermediate resistance category and only 5 (2%) being high-level resistant. A higher prevalence of penicillin resistance occurred in younger age groups and in European patients and involved specifically certain serotypes. The 7-valent conjugate pneumococcal vaccine has potential benefit for the New Caledonian population under 5 years of age and should be considered for future vaccines schedules.

Adult↗
PubMed2004

CYP3A4, CYP2C9 and CYP2B6 expression and ifosfamide turnover in breast cancer tissue microsomes.

Ifosfamide is a prodrug that requires bioactivation by cytochrome P450 for antitumour activity. Up to now, little is known, to what extent in addition to the liver the ifosfamide metabolism may occur intratumorally. For this purpose, we investigated the expression of CYP3A4, CYP2C9 and CYP2B6 in breast cancer tissue using Western Blotting. Ifosfamide turnover was determined by detection of metabolites of the ifosfamide 4-hydroxylation and N-dechloroethylation in tumour microsomal incubations using HPLC/UV and LC/MS. The results demonstrate that all mammary tumours (n=11) reveal CYP3A4 expression; contents varied from 0.5 to 63 pmol mg(protein)(-1). CYP2C9 (n=9) was present in all tested breast tumour samples, too, while CYP2B6 (n=10) protein could not be detected. All measured breast cancer microsomes (n=4) showed an ifosfamide N-dechloroethylation capacity in the range from 0.04 to 0.21 pmol min(-1) mg(protein)(-1), while metabolites of the 4-hydroxylation could not be determined. In conclusion, the detected presence of CYP3A4 and CYP2C9 in breast tumours offers the possibility of intratumoral turnover of ifosfamide. For the first time in the literature, we could demonstrate a turnover of ifosfamide by microsomal preparations from human breast cancer tissue. A calculated modulation of intratumoral ifosfamide turnover could considerably influence its therapeutic efficiency.

Aged↗
PubMed2002

[Knowledge of "Hardship Exemptions" in statutory sickness insurance].

OBJECTIVES: The German Statutory Sickness Fund comprises about 90 % of the total population. There are special relief or 'hardship' regulations in the Statutory Sickness Fund (the 'Härtefallregelungen') exempting those insured persons from co-payment for whom the co-payments would be an undue financial burden. The most important research questions are: How many of the insured persons do actually know about the possibility of being exempted? How did this group learn about the possibility? How many insured are not exempted from co-payment although they are entitled to be exempted? Why didn't they apply? According to our knowledge there is no comparable national or international study in this field of research. METHODS: The data for the empirical study are collected in a Statutory Sickness Fund in the city of Augsburg (Southern Germany). 18 238 insured (pre-selected as not being exempted from co-payments, but probably entitled to be exempted) were addressed with a very short questionnaire in September 2000. They were asked about their household income, the number of the household members and the money spent for co-payments for medicaments, dental prostheses and other health-related services, in order to identify those entitled to be exempted, and a control group. Among those who responded 1.002 persons were interviewed by CATI (Computer Assisted Telephone Interview). RESULTS: Within the study group interviewed by CATI there was only limited knowledge about the "Härtefallregelungen". About two-thirds of the respondents (61.58 %) were unfamiliar with the possibility of getting an annual reimbursement of the co-payments. Less than one-third (27.78 %) knew nothing about the regulation of being totally exempted from co-payments. Most persons learnt about the regulations from friends and relatives, but few from physicians and other health professionals. One of the reasons most frequently mentioned for not applying for the "Härtefallregelungen" was a presumably too high income. Reasons which lie within the formalities of the application or refer to the potentially embarrassing situation were reported less often. CONCLUSION: Knowledge about the possibilities of being exempted from co-payments for medicaments and other health-related services and goods should be increased. With most of the respondents having learnt about the "Härtefallregelungen" from friends and relatives, patients could get relevant information from physicians and other health professionals more frequently. As financial aspects are the reasons reported most for not applying for the "Härtefallregelungen", the information policy could be enhanced e. g. by simplified examples for calculating the relevant income for being entitled. This way there is a chance that all insured persons who are entitled will actually benefit from the "Härtefallregelungen".

Eligibility Determination↗
PubMed2002

[The seroprevalence of HIV in pregnant women in New Caledonia: an assessment of 1 year of surveillance].

OBJECTIVES: To evaluate the HIV prevalence among pregnant women in New-Caledonia and to analyse the uptake of testing among the patients according to their demographic data. METHOD: The study was based on statistical exploitation of anonymously recorded HIV test results during the follow-up of pregnant women. The first 12-month assessment of this monitoring (April 1999--March 2000) is reported. RESULTS: 88.6% of the 3380 patients were tested for HIV, significantly less in Wallisian and Melanesian groups of women. Two results were positive, which corresponds to a prevalence of 0.66 +/- 0.45 per thousand (0.21-1.11 per 1000) within the studied group. Although our study is not representative of this situation, lack of testing for women undergoing an abortion was frequent. CONCLUSION: This study indicates that offering HIV testing in pregnancy follow-up is fairly systematic and most often accepted. Evidently, there is a need for adjusting of pre-test counselling to the cultural and ethnic characteristics of the woman, to the preparedness of medical staff as well as to the problem of HIV screening in abortion management. Our prevalence data also show that New-Caledonia ranks among countries of low endemicity for HIV where pregnant women are concerned.

AIDS Serodiagnosis↗
PubMed2001

Cyclophosphamide and related anticancer drugs.

This article presents an overview of the methods of bioanalysis of oxazaphosphorines, in particular, cyclophosphamide, ifosfamide, and trofosfamide as well as their metabolites. The metabolism of oxazaphosphorines is complex and leads to a large variety of metabolites and therefore the spectrum of methods used is relatively broad. The various methods used are shown in a table and the particularly important assays are described.

Antineoplastic Agents, Alkylating↗
PubMed2000

Ecm10, a novel hsp70 homolog in the mitochondrial matrix of the yeast Saccharomyces cerevisiae.

Members of the heat shock protein 70 (Hsp70) family are found in most of the compartments of eukaryotic cells where they play essential roles in protein metabolism. In yeast mitochondria, two Hsp70 proteins are known: Ssc1 and Ssq1. We identified Ecm10 as a third Hsp70 protein in the mitochondrial matrix. Ecm10 shares 82% amino acid identity with Ssc1 and 54% with Ssq1. Overexpression of Ecm10 mitigates protein import defects in ssc1 mutants suggesting that Ecm10 can play a role in protein translocation. Like Ssc1, Ecm10 interacts with the nucleotide exchange factor Mge1 in an ATP-dependent manner. Deletion of ecm10 leads to synthetic growth defects with ssc1 mutations at low temperature. Our data suggest an overlapping function of Ecm10 and Ssc1.

Amino Acid Sequence↗
PubMed2000

The cytochrome bc1 and cytochrome c oxidase complexes associate to form a single supracomplex in yeast mitochondria.

The mitochondrial electron transport chain complexes are large multisubunit complexes embedded in the inner membrane. We report here that in the yeast Saccharomyces cerevisiae, the cytochrome bc(1) and cytochrome c oxidase complexes co-exist as a larger complex of approximately 1000 kDa in the mitochondrial membrane. Following solubilization with a mild detergent, the cytochrome bc(1)-cytochrome c oxidase complex remains stable. It was analyzed using the techniques of gel filtration and blue native-polyacrylamide gel electrophoresis. Direct physical association of subunits of the cytochrome bc(1) complex with those of the cytochrome c oxidase complex was verified by co-immunoprecipitation analysis. Our data indicate that the cytochrome bc(1) complex is exclusively in association with the cytochrome c oxidase complex in yeast mitochondria. We term this complex the cytochrome bc(1)-cytochrome c oxidase supracomplex.

Electron Transport↗
PubMed1999

Determination of cyclophosphamide and its metabolites in human plasma by high-performance liquid chromatography-mass spectrometry.

A sensitive HPLC-MS method was developed for the simultaneous determination of cyclophosphamide and its metabolites 4-hydroxycyclophosphamide (aldocyclophosphamide), 4-ketocyclophosphamide, caboxyphosphamide and 3-dechloroethylifosfamide in human plasma. 4-Hydroxycyclophosphamide was converted with methylhydroxylamine to the stable methyloxime form. We used a solid-phase extraction with C18 cartridges followed by HPLC-MS with the single mass spectrometer SSQ 7000 of Finnigan. The limits of detection were 15 ng/ml for cyclophosphamide, 3-dechloroethylifosfamide and ketocyclophosphamide in each case and 30 ng/ml for carboxyphosphamide and 4-hydroxycyclophosphamide, respectively. First results of pharmacokinetics are shown.

Antineoplastic Agents, Alkylating↗
PubMed1997

[Late results of joint-preserving femur head necrosis surgery].

Early diagnosis of nontraumatic avascular necrosis of the femoral head has been much improved by introduction of magnetic resonance imaging (MRI). Intertrochanteric osteotomies are dominating in operative treatment of advanced necrosis of the femoral head. Studies concerning with long-term results are rare in literature. The aim of the present study was the assessment of the long-term results (> 10 years) of advanced avascular necrosis (n = 33 hips, 8 stage Ficat II, 19 stage Ficat III, 6 stage Ficat IV). In 29 cases of joint-preserving operation was primarily performed. The average follow up time of the patients was 13 years. In 13 patients a joint-destructive operation (total hip replacement or arthrodesis) was secondarily necessary. The average time interval between joint-preserving and -destructive operation was 53 months (minimal 10, maximal 180 months). Quality of life is often reduced in patients after joint-preserving hip operations. Only 3 of 14 patients with still existing joint-preserving operation were painless postoperatively and could continue their former job. The other patients suffered from pain and reductions of their activity of daily life. 4 of them had to retire early.

Adult↗
PubMed1989

[Resection of the prostate after 75 years].

The authors report a series of 100 endoscopic resections performed in patients over the age of 75 years. In patients with no risk factors, there was no mortality and the morbidity was 5%. In patients with one risk factor, mortality was 5% and morbidity was 10%.

Aged↗
PubMed1983

[Bacteriological study of hands and the use of soap in the hospital environment].

Direct contact, especially by touching, is the most important route for the transmission of hospital infections. To examine this risk, we have investigated the frequency of bacteria present on the hands of the nursing staff on the long and medium stay wards of the Hospital Paul- Brousse in Villejuif. The study showed that the amount of bacteria after tending the patients before and after washing the hands with soap tablets is still far from negligible. Staphylococci were predominant both from the frequency and density of their cultures, the risks of transmitting the infection increased with the level of contamination. Although in far smaller amounts, enterobacteria were isolated, probably a sign of faecal contamination. Some of these organisms belonged to bacteria called "hospital infections", resistant to many types of antibiotics. The results point out the limitations of the present system for washing hands, in particular using soap tablets--the soap is a source of infection as it becomes soft when kept wet. Improvement could be achieved by instituting a few simple measures, such as rehabilitating mobile basin units using a scrubbing-brush, carefully drying the hands, using linen that is kept only for patients who have septic infections, issuing personal soap tablets or even better using liquid soap in disposable containers.

Cross Infection↗
PubMed1982

Diffuse and local effects of light adaptation in photoreceptors of the honey bee drone.

Intracellular recordings from drone photoreceptors were made by means of glass microelectrodes in superfused retinae. Exposure of a small portion of a cell to white light decreased the amplitude of responses to a small stimulus subsequently applied at different sites of the photoreceptor cell, i.e. light adaptation occurred throughout the cell. After 7 min of darkness, the responses had completely recovered. When a violet light (404 nm) was used to adapt a small portion of the cell, the responses at the site of exposure to the adapting stimulus remained depressed for at least 30 min. Illumination at the site of the violet adapting stimulus with green light (585 nm) caused an immediate recovery of the amplitude of the response. These results can be explained by the existence of two processes responsible for light adaptation: one is localized and persistent and appears to be due to changes in concentration of rhodopsin. The other affects the whole cell, is spontaneously reversible and depends upon the ability of the light to produce a receptor potential but not on any lasting change in rhodopsin concentration.

Action Potentials↗
PubMed1981

Ventral capsular denervation. An operative treatment of periarthropathia humero-scapularis.

Based on the neuro-anatomical situation and clinical observations a new method has been developed to treat the chronically recurrent humero-scapular periarthropathy together with a contraction of the joint and sometimes tendinitis and subacromial bursitis. The new method, a ventral denervation of the capsule, causes an immediate and continuing decrease or elimination of the pain in the shoulder. An increased and painless mobilization is possible until the extensive or even total rehabilitation of the joint function. Twenty shoulder joints have been treated in 19 patients. Within a period of 12 until 28 months 12 of them became continuously painless, 2 improved considerably and 4 satisfactorily. Depending on the initial clinical result the function could be restored in 85% of the patients approximately or even totally.

Adult↗
PubMed1981

Sleep deprivation: effect on sleep stages and EEG power density in man.

Sleep was analysed in 8 young adults subjects during two baseline nights and two recovery nights following 40.5 h sleep deprivation. Sleep stages were scored from the polygraph records according to conventional criteria. In addition, the EEG records of the entire nights were subjected to spectral analysis to compute the frequency distribution of the power density in the 0.25-25 Hz range for 0.5 Hz or 1.0 Hz bins. In the first recovery night, the power density in the delta band was significantly higher than baseline for total sleep time as well as for sleep stages 2, 3 and 4, 4 and REM. These changes were not restricted to the delta band, but extended to higher frequency bands. Minor, but significant, effects of sleep deprivation were seen in the power density distribution of the second recovery night. In the baseline nights, a progressive reduction of power density in the delta/theta range was present for successive non-REM-REM sleep cycles for total sleep time and stages 2, 3 and 4, and 4. The results show that effects of sleep deprivation as well as trends within the sleep periods are readily apparent from spectral analysis, but are inadequately reflected by conventional sleep scoring. When the power density values were integrated over the entire frequency range (0.75-25 Hz) for each non-REM-REM sleep cycle, an exponential decline from cycle 1 to cycle 3 was suggested. The present findings support the hypothesis that the EEG power density in the low frequency range is an indicator of a progressively declining process during sleep whose initial value is determined by the duration of prior waking.

Adult↗