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Biomedical subjects

S Hauser

Publications and source records attributed to S Hauser.

At least 19 recordsLinked to original sources

Interleukin-2/interferon-alpha2a/13-retinoic acid-based chemoimmunotherapy in advanced renal cell carcinoma: results of a prospectively randomised trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).

We performed a prospectively randomised clinical trial to compare the efficacy of four subcutaneous interleukin-2-(sc-IL-2) and sc interferon-alpha2a (sc-IFN-alpha2a)-based outpatient regimens in 379 patients with progressive metastatic renal cell carcinoma. Patients with lung metastases, an erythrocyte sedimentation rate < or =70 mm h(-1) and neutrophil counts < or =6000 microl(-1) (group I) were randomised to arm A: sc-IL-2, sc-IFN-alpha2a, peroral 13-cis-retinoic acid (po-13cRA) (n=78), or arm B: arm A plus inhaled-IL-2 (n=65). All others (group II) were randomised to arm C: arm A plus intravenous 5-fluorouracil (iv-5-FU) (n=116), or arm D: arm A plus po-Capecitabine (n=120). Median overall survival (OS) was 22 months (arm A; 3-year OS: 29.7%) and 18 months (arm B; 3-year OS: 29.2%) in group I, and 18 months (arm C; 3-year OS: 25.7%) and 16 months (arm D; 3-year OS: 32.6%) in group II. There were no statistically significant differences in OS, progression-free survival, and objective response between arms A and B, and between arms C and D, respectively. Given the known therapeutic efficacy of sc-IL-2/sc-INF-alpha2a/po-13cRA-based outpatient chemoimmunotherapies, our results did not establish survival advantages in favour of po-Capecitabine vs iv-5-FU, and in favour of short-term inhaled-IL-2 in patients with advanced renal cell carcinoma receiving systemic cytokines.

Adult↗

Characterisation of submarine groundwater discharge offshore south-eastern Sicily.

A complex approach in characterisation of submarine groundwater discharge (SGD) off south-eastern Sicily comprising applications of radioactive and non-radioactive tracers, direct seepage measurements, geophysical surveys and a numerical modelling is presented. SGD fluxes in the Donnalucata boat basin were estimated by direct seepage measurements to be from 4 to 12Ls(-1), which are comparable with the total SGD flux in the basin of 17Ls(-1) obtained from radon measurements. The integrated SGD flux over the Donnalucata coast estimated on the basis of Ra isotopes was around 60m(3)s(-1) per km of the coast. Spatial variations of SGD were observed in the Donnalucata boat basin, the average (222)Rn activity concentration in seawater varied from approximately 0.1kBqm(-3) to 3.7kBqm(-3) showing an inverse relationship with salinity. The continuous monitoring carried out at the site closest to the coast has revealed an inverse relationship of (222)Rn activity concentration on the tide. The (222)Rn concentrations in seawater varied from 2.3kBqm(-3) during high tides to 4.8kBqm(-3) during low tides, thus confirming an influence of the tide on submarine groundwater discharge. Stable isotopes (delta(2)H and delta(18)O) showed that SGD samples consist up to 50% of groundwater. Geo-electrical measurements showed a spatial variability of the salt/fresh water interface and its complex transformation in the coastal zone. The presented results imply that in the studied Donnalucata site there are at least two different sources of SGD, one superficial, represented by mixed fresh water and seawater, and the second one which originates in a deeper limestone aquifer.

Sicily↗

Toxic effects seen in a herd of beef cattle following exposure to ash residues contaminated by lead and mercury.

Lead poisoning was diagnosed in three cattle along with increased mercury levels in the liver and kidney tissues of two of these animals. The clinical signs were different in each case and included salivation, anorexia, delayed menace response, delayed withdrawal reflex, head pressing, localized muscle fasciculation, reduced tongue tone, ataxia, rumen atony and seizures. Blood lead concentration was increased in all three cases to 0.76, 0.37 and 0.454ppm. Post mortem changes characteristic of lead poisoning were only recognized in one case and included cerebro-cortical oedema, cortical neuronal necrosis and endothelial proliferation, especially at the tips of the cerebral gyri. The animals were poisoned by ingestion of lead-contaminated ash residues from a bonfire. The abnormal levels of mercury in the liver and kidney tissues of two animals may also be at least partly attributable to the intake of the metal in the ash residues. The levels of mercury in the three samples from the ash residue were relatively low (1.31, 0.7 and 2.1ppm).

Animals↗

[Primitive neuroectodermal tumor of the kidney].

Primitive neuroectodermal Tumor (PNET) is a rare malignant tumor of young adult. Patients often present with the classical trias of renal cancer (pain, haematuria, palpable tumor). Specific radiological signs are missing, and therefore a PNET is often diagnosed postoperatively. It is characterized by the expression of MIC2, neural markers (Vimentin, S-100, Synaptophysin) and EWS/FLI1-translocation. The tumor is often diagnosed in advanced stage, and prognosis is poor despite of multimodal treatment including radical nephrectomy, polychemotherapy (vincristine, adriamycin, cyclophosphamid, etoposide, ifosfamide) and radiation in case of metastases or incomplete resection of primary tumor. We represent two cases of metastatic renal PNET in a 28- and 39-year-old patient. Due to the multimodal treatment a partial and a complete remission was achieved, respectively.

Adult↗

Characterizing the mechanisms of progression in multiple sclerosis: evidence and new hypotheses for future directions.

Major advancements have been achieved in our ability to diagnose multiple sclerosis (MS) and to commence treatment intervention with agents that can favorably affect the disease course. Although MS exacerbations and the emergence of disability constitute the more conspicuous aspects of the disease process, evidence has confirmed that most of the disease occurs on a constitutive and occult basis. Disease-modifying therapies appear to be modest in the magnitude of their treatment effects, particularly in the progressive stage of the disease. Therapeutic strategies currently used for MS primarily target the inflammatory cascade. Several potential mechanisms appear to be involved in the progression of MS. Characterizing these mechanisms will result in a better understanding of the various forms of the disorder and how to effectively treat its clinical manifestations. It is our objective within this 2-part series on progression in MS to offer both evidence-based observations and hypothesis-driven expert perspectives on what constitutes the cause of progression in MS. We have chosen areas of inquiry that appear to have been most productive in helping us to better conceptualize the landscape of what MS looks like pathologically, immunologically, neuroscientifically, radiographically, and genetically. We have attempted to advance hypotheses focused on a deeper understanding of what contributes to the progression of this illness and to illustrate new technical capabilities that are catalyzing novel research initiatives targeted at achieving a more complete understanding of progression in MS.

Disease Progression↗

Measuring and modelling plant area index in beech stands.

For some beech ( Fagus sylvatica L.) stands with different stand densities the plant area index (PAI) was measured by means of a Licor LAI-2000 plant canopy analyser. The stands are located on the slopes of a valley in south-west Germany and had been treated by different types of silvicultural management (heavy shelterwood felling, light shelterwood felling, control plot). The analyser was used (a) to investigate the light conditions on plots of the same thinning regime, (b) to quantify the differences between the different treatments and (c) to obtain absolute values of PAI for interdisciplinary research. PAI was measured at three different phenological stages (leafless, leaf-unfolding and fully leafed season in 2000) and was found to be about 5.2 for the fully developed canopy on the control plots, 3.2 on the light fellings and about 2.0 for the heavy fellings. In the leafless period PAI was between 1.1 (control) and 0.4 (heavy felling). Measurements made in summer 2000 and summer 2002 were compared, and showed an increase of PAI, especially on the thinned plots. Measurements of photosynthetically active radiation (PAR) above and below the canopy in combination with measured PAI were used to apply Beer's Law of radiation extinction to calculate the extinction coefficient k for different sky conditions and for the different growing seasons on the control plots. The extinction coefficient k for the beech stands was found to be between 0.99 and 1.39 in the leafless period, 0.62 to 0.91 during leaf unfolding and between 0.68 and 0.83 in the fully leafed period. Using PAR measurements and the k values obtained, the annual cycle of PAI was modelled inverting Beer's Law.

Environmental Monitoring↗

Biological properties and molecular characterization of beet chlorosis virus (BChV).

Two distinct viruses belonging to the Polerovirus genus, in the family Luteoviridae, have been described as being able to induce mild yellowing on sugar beet: Beet mild yellowing virus (BMYV) and more recently, beet chlorosis virus (BChV). We have analysed biological properties and molecular organisation of two strains of BChV, one collected in England and the second from California. The biological data suggested that BChV displayed a narrower host range compared to BMYV and Beet western yellows virus lettuce isolate (BWYV). The complete genomic RNA sequence of the American isolate BChV-California and the European isolate BChV-2a showed a genetic organisation and expression typical of other Polerovirus members including 6 open reading frames (ORFs). Interspecific and intraspecific phylogenetic studies suggested that BChV arose by recombination events between a Polerovirus-like ancestor donating P0 and the replicase complex and either a BMYV or a BWYV progenitor providing the 3' ORFs [3, 4 and 5]. The 5'- and 3'-parts of the BChV genome have evolved differently in the two continents, possibly due to different selection pressures to allow adaptation to the various environments, hosts and vectors. BChV is a distinct species of the Polerovirus genus.

Amino Acid Sequence↗

Environmental radioactivity at Stromboli (Aeolian Islands).

HPGe gamma spectrometry, thermoluminescence dosimetry, X-ray diffractometry and fluorescence techniques have been used to analyze the natural radionuclides content of soil and rock samples, air kerma and geochemical features on the island of Stromboli, belonging to the Aeolian Islands, in the Mediterranean Sea. The 214Bi, 238Ac, and 40K contents obtained are in agreement with the magmatic evolution of the rock formation, as shown by the correlations between radionuclide and chemical elements abundacies, depending on the various magmatic differentiation mechanisms. Correlations between radiometric, lithological and geochemical data have been assessed in order to obtain some hints on the geochronology of the magmatic products.

Journal Article↗

[Therapy of carcinoma of the kidney pelvis].

Transitional cell carcinoma of the renal pelvis is relatively uncommon, and only 5% of all urothelial carcinomas occur in the renal collecting system. Invasive tumors are often aggressive in their biological behavior and show a high tendency for systemic progression. Conservative therapy should only be considered an option in patients with imperative indications (solitary functioning kidney, bilateral tumor, renal insufficiency). In some cases, organ-sparing techniques such as open resection or endourological treatment (percutaneous or by ureteroscopy) can be performed. However, nephroureterectomy with excision of a bladder cuff is considered to be the standard treatment and should be performed whenever possible.

Carcinoma, Transitional Cell↗

Seasonal variation of air kerma in the "Vulcano Porto" area (Aeolian Islands, Italy).

Air kerma was measured in the "Vulcano Porto" area of the Vulcano Island, belonging to the Aeolian Islands, in the Mediterranean Sea. Measurements were carried out using thermoluminescence dosimeters. The relationship between observed dose values and source lithology has been assessed. Data show a seasonal variation due to weather conditions but also probably related to features of the soils, making the variation more evident.

Air↗

Gamma activity and geochemical features of building materials: estimation of gamma dose rate and indoor radon levels in Sicily.

A high-purity germanium detector has been used to measure the abundance of radium (Ra), thorium (Th) and potassium (K) in building materials used in Sicilian dwellings. The measurements were performed to evaluate which material was suitable for the construction of an enclosure, which would have a low background emission. The materials examined in this work showed concentrations of 226Ra, 232Th and 40K dramatically variable depending on the lithologies, particularly in the case of blocks, sands and aggregates commonly used in building materials in Sicily. The results are discussed and a criterion is indicated to reduce the radiation dose to humans. Since radon inlet is a major health problem, all the radiometric data and the geochemical features have been used to determine the radon exhalation, which arises from the disintegration of 226Ra in soils and walls of houses. From our experimental data it can be seen out that one of the geochemical parameters, Total Alkali (TA), may be an appropriate index to select materials of low radiological risk.

Algorithms↗

Bone mineral density in prepubertal asthmatics receiving corticosteroid treatment.

OBJECTIVE: To examine whether bone mass is reduced in prepubertal, asthmatics receiving high doses of inhaled corticosteroids. METHODOLOGY: A cross-sectional comparison of lumbar spine-bone mineral density (LS-BMD) was undertaken in 76 subjects after stratifying them according to dosage and administration route of corticosteroid. RESULTS: Weight was the only independent predictor of LS-BMD (r(2) = 0.38). Children receiving greater than 800 microg/day of inhaled corticosteroid plus intermittent oral corticosteroid had a significantly lower weight-adjusted LS-BMD than children treated with 400-800 microg/day of inhaled corticosteroid (mean difference: 0.06 g/cm(2), 95% confidence interval (CI): - 0.02 to - 0.10). A significant difference in weight-adjusted LS-BMD persisted when all children receiving greater than 800 microg/day of inhaled corticosteroid, irrespective of additional oral corticosteroid treatment, were compared with children receiving 400-800 microg/day of inhaled corticosteroid (mean difference: - 0.05 g/cm(2), 95%CI interval: -0.02 to - 0.09). Bone mass was similar in children not receiving any inhaled corticosteroid and those treated with 400-800 microg/day of inhaled corticosteroid. CONCLUSIONS: A reduced bone mass in prepubertal asthmatic children receiving high doses of inhaled corticosteroids may predetermine a compromised peak bone mass and increase osteoporotic fracture risk in adulthood.

Absorptiometry, Photon↗

Nicotine use in early mediaeval Kirchheim/Teck, Germany.

Human bone samples of 123 Alemans of the 5th to 7th c AD were investigated for nicotine. In 23 individuals nicotine was found at levels between 31 and 150 ng/g, and in 49 others nicotine was found in traces. The results indicate that in Germany plants of the genus Nicotiana should have been present, known and used, well before Columbus. The purposes behind this use might have been domestic/medical or ritual, or possibly even as a luxury as occurs today.

Bone and Bones↗

Degradation of the peroxisome proliferator-activated receptor gamma is linked to ligand-dependent activation.

The nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR) gamma is a ligand-activated transcription factor that regulates several crucial biological processes such as adipogenesis, glucose homeostasis, and cell growth. It is also the functional receptor for a new class of insulin-sensitizing drugs, the thiazolidinediones, now widely used in the treatment of type 2 diabetes mellitus. Here we report that PPARgamma protein levels are significantly reduced in adipose cells and fibroblasts in response to specific ligands such as thiazolidinediones. Studies with several doses of different ligands illustrate that degradation of PPARgamma correlates well with the ability of ligands to activate this receptor. However, analyses of PPARgamma mutants show that, although degradation does not strictly depend on the transcriptional activity of the receptor, it is dependent upon the ligand-gated activation function 2 (AF2) domain. Proteasome inhibitors inhibited the down-regulation of PPARgamma and ligand activation enhanced the ubiquitination of this receptor. These data indicate that, although ligand binding and activation of the AF2 domain increase the transcriptional function of PPARgamma, these same processes also induce ubiquitination and subsequent degradation of this receptor by the proteasome.

3T3 Cells↗

A synthetic antagonist for the peroxisome proliferator-activated receptor gamma inhibits adipocyte differentiation.

While searching for natural ligands for the peroxisome proliferator-activated receptor (PPAR) gamma, we identified a synthetic compound that binds to this receptor. Bisphenol A diglycidyl ether (BADGE) is a ligand for PPARgamma with a K(d(app)) of 100 microM. This compound has no apparent ability to activate the transcriptional activity of PPARgamma; however, BADGE can antagonize the ability of agonist ligands such as rosiglitazone to activate the transcriptional and adipogenic action of this receptor. BADGE also specifically blocks the ability of natural adipogenic cell lines such as 3T3-L1 and 3T3-F442A cells to undergo hormone-mediated cell differentiation. These results provide the first pharmacological evidence that PPARgamma activity is required for the hormonally induced differentiation of adipogenic cells.

1-Methyl-3-isobutylxanthine↗

Improved detection and differentiation of poleroviruses infecting beet or rape by multiplex RT-PCR.

Three distinct species of virus inducing yellowing of beet, Beet mild yellowing virus (BMYV), Brassica yellows virus (BrYV, synonym BWYV) and Beet chlorosis virus (BChV) have been characterised from the genus Polerovirus. Until recently, no available tools were available to allow accurate and reliable distinction of the three species. Based on previous nucleotide sequence alignments and phylogenetic studies, we show that the use of molecular methods enabled the discrimination of these three beet Polerovirus species, but with differences in efficiency and specificity. Primers CP+ and CP- encompassing ORF-3, which encodes the coat protein, allowed the amplification by RT-PCR of a fragment of 563 bp for all isolates. Molecular methods such as SSCP or RFLP were able to discriminate these fragments by utilizing the differences in sequence. However, SSCP is a highly sensitive technique and was not suitable for the distinction of the Polerovirus species, because all isolates tested displayed a unique pattern. Analysis of the ORF3 RT-PCR products, digested with SmaI, RsaI and AccI restriction enzymes revealed four distinct patterns specific for the three species. However, point mutations can alter the RFLP patterns, making the interpretation of the results difficult. Primers were designed to amplify specifically sequences corresponding to ORF-0 of the three viral species. By using the three new sets of ORF-0 specific primers and CP+/CP- primers in a single multiplex RT-PCR, the detection and discrimination of the three beet Polerovirus species was possible in infected plants. The multiplex RT-PCR method provides a reliable and highly sensitive method to detect and identify viral species and will be of great interest for epidemiological studies of beet poleroviruses.

Brassica↗

A case of a persistent left vena cava superior with atresia of the right atrial ostium of the coronary sinus.

A persistent left vena cava superior with an atretic ostium of the coronary sinus was found during the routine dissecting course in the embalmed cadaver of an 83-year-old woman who had died from cardiac infarction. The left vena cava superior was very narrow in diameter (4 mm), originated at the lateral part of the left vena brachiocephalica and ran down between the venae pulmonales sinistrae and the auricula sinistra. The vena cava opened into the sinus coronarius of the heart, which terminated as a blind sac due to an atretic ostium. The vena coronaria sinistra as well as the vena interventricularis posterior drained into the sinus coronarius. Congenital atresia of the coronary opening is a rare malformation and is usually associated with other anomalies. The congenital ostial atresia could be the cause of a persistent left vena cava superior, which then takes over the drainage of the cardiac veins.

Aged↗

An adipogenic cofactor bound by the differentiation domain of PPARgamma.

Ligand activation of the nuclear receptor PPARgamma induces adipogenesis and increases insulin sensitivity, while activation of other PPAR isoforms (-alpha and -delta) induces little or no fat cell differentiation. Expression and activation of chimeras formed between PPARgamma and PPARdelta in fibroblasts has allowed us to localize a major domain of PPARgamma responsible for adipogenesis to the N-terminal 138 amino acids, a region with AF-1 transcriptional activity. Using this region of PPARgamma as bait, we have used a yeast two-hybrid screen to clone a novel protein, termed PGC-2, containing a partial SCAN domain. PGC-2 binds to and increases the transcriptional activity of PPARgamma but does not interact with other PPARs or most other nuclear receptors. Ectopic expression of PGC-2 in preadipocytes containing endogenous PPARgamma causes a dramatic increase in fat cell differentiation at both the morphological and molecular levels. These results suggest that interactions between PGC-2, a receptor isoform-selective cofactor and PPARgamma contribute to the adipogenic action of this receptor.

Adipocytes↗