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Biomedical subjects

S Schuster

Publications and source records attributed to S Schuster.

At least 19 recordsLinked to original sources
PubMed2005

[Violence against women in the context of migration].

Since the eighties the percentage of migrant women is increasing continually in Switzerland and presents a new challenge for the public health system. The article will point out specific aspects of migration which are particularly associated with violence against women, besides domestic and sexual violence in their marriages. A successful communication serves as a basis for a reasonable diagnosis, therapy and counselling in health services. Beyond overcoming language barriers, it is essential to consider the physician-patient interaction influenced by the social status and cultural background of each. By using two vignettes specific difficulties in medical encounters with migrant women will be demonstrated and possible interventionsfor clinical practice will be offered complemented by references on existing services in Switzerland. By an interdisciplinary co-operation of physicians, social workers, mediators, lawyers and anthropologists a professional care in face of these complex issues will be guaranteed.

Adolescent↗
PubMed2005

Intensive graft-versus-host disease prophylaxis is required after unrelated-donor nonmyeloablative stem cell transplantation.

Nonmyeloablative stem cell transplantation (NST) harnesses the graft-versus-tumor effect while minimizing regimen-related toxicity, and can result in donor chimerism and remission. Acute graft-versus-host disease (GVHD) and infections are major complications after sibling NST. Toxicity of unrelated-donor (UD) NST and the most appropriate GVHD prophylaxis in this setting remain poorly defined. We describe 25 patients who received UD-NST conditioned with fludarabine and cyclophosphamide. The first six patients received cyclosporine (Cs) and mycophenolate mofetil (MMF) (n=5) or methotrexate (MTX) (n=1) as GVHD prophylaxis (group 1) and all developed grade III-IV acute GVHD. The next 19 patients received the same conditioning regimen with the addition of alemtuzumab, and all received Cs/MTX post-transplant. Engraftment and donor chimerism were achieved in all but one evaluable patient. In all, 15 patients died: five of six deaths in group 1 were attributable to acute GVHD, while deaths in group 2 were due to infection or progressive disease (P=0.05). The combination of Cs/MMF is inadequate GVHD prophylaxis for UD-NST. The use of Cs, MTX, and alemtuzumab eliminated severe acute GVHD; its impact on response merits further study.

Adult↗
PubMed2004

Evaluation of water quality projects in the Lake Tahoe basin.

Lake Tahoe is a large sub alpine lake located in the Sierra Nevada Range in the states of California and Nevada. The Lake Tahoe watershed is relatively small (800 km(20) and is made up of soils with a very low nutrient content and when combined with the Lake's enormous volume (156 km(3)) produces water of unparalleled clarity. However, urbanization around the Lake during the past 50 yr has greatly increased nutrient flux into the Lake resulting in increased algae production and rapidly declining water clarity. Lake transition from nitrogen limiting to phosphorous limiting during the last 30 yr suggests the onset of cultural eutrophication of Lake Tahoe. Protecting Lake Tahoe's water quality has become a major public concern and much time, effort, and money has been, and will be, spent on this undertaking. The effectiveness of remedial actions is the subject of some debate. Local regulatory agencies have mandated implementation of best management practices (BMPs) to mitigate the effects of development, sometimes at great additional expense for developers and homeowners who question their effectiveness. Conclusive studies on the BMP effectiveness are also expensive and can be difficult to accomplish such that very few such studies have been completed. However, several project evaluations have been completed and more are underway. Such study usually demonstrates support of the project's effectiveness in decreasing nutrient flux to Lake Tahoe. Here, we review the existing state of knowledge of nutrient loading to the Lake and to highlight the need for further evaluative investigations of BMPs in order to improve their performance in present and future regulatory actions.

Animals↗
PubMed2004

Analysis of structural robustness of metabolic networks.

We study the structural robustness of metabolic networks on the basis of the concept of elementary flux modes. It is shown that the number of elementary modes itself is not an appropriate measure of structural robustness. Instead, we introduce three new robustness measures. These are based on the relative number of elementary modes remaining after the knockout of enzymes. We discuss the relevance of these measures with the help of simple examples, as well as with larger, realistic metabolic networks. Thereby we demonstrate quantitatively that the metabolism of Escherichia coli, which must be able to adapt to varying conditions, is more robust than the metabolism of the human erythrocyte, which lives under much more homeostatic conditions.

Adaptation, Physiological↗
PubMed2002

Reaction routes in biochemical reaction systems: algebraic properties, validated calculation procedure and example from nucleotide metabolism.

Elementary flux modes (direct reaction routes) are minimal sets of enzymes that can operate at steady state, with all irreversible reactions used in the appropriate direction. They can be interpreted as component pathways of a (bio)chemical reaction network. Here, two different definitions of elementary modes are given and their equivalence is proved. Several algebraic properties of elementary modes are then presented and proved. This concerns, amongst other features, the minimal number of enzymes of the network not used in an elementary mode and the situations where irreversible reactions are replaced by reversible ones. Based on these properties, a refined algorithm is presented, and it is formally proved that this algorithm will exclusively generate all the elementary flux modes of an arbitrary network containing reversible or irreversible reactions or both. The algorithm is illustrated by a biochemical example relevant in nucleotide metabolism. The computer implementation in two different programming languages is discussed.

Adenine Nucleotides↗
PubMed2002

Analysis of the B cell repertoire against autoantigens in patients with giant cell arteritis and polymyalgia rheumatica.

The analysis of the antibody repertoire of patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) might identify target antigens of the autoimmune response with potential relevance to our understanding of the pathogenesis of the disease and to the development of serodiagnostic tests. To detect such antigens, we screened a cDNA library derived from normal human testis for antigens reacting with IgG antibodies in the 1 : 250 diluted sera of three patients with untreated GCA using SEREX, the serological identification of antigens by recombinant cDNA expression cloning. Of 100 000 clones screened with each serum, six, 28 and six clones, respectively, were positive, representing a total of 33 different antigens. Most of the antigens reacted only with the serum used for identification and/or at a similar frequency with normal control sera. However, lamin C and the nuclear antigen of 14 kD reacted specifically with 32% of GCA/PMR, but with none of the control sera, while human cytokeratin 15, mitochondrial cytochrome oxidase subunit II, and a new gene product were detected preferentially, but not exclusively by sera from GCA/PMR patients. We conclude that patients with GCA/PMR develop antibodies against a broad spectrum of human autoantigens. Antibodies against human lamin C, the nuclear autoantigen of 14 kD as well as human cytokeratin 15, mitochondrial cytochrome oxidase subunit II and the product of a new gene should be investigated further to determine their value as tools for the diagnosis and/or the definition of clinical subgroups of patients with GCA/PMR.

Adult↗
PubMed2002

Exploring the pathway structure of metabolism: decomposition into subnetworks and application to Mycoplasma pneumoniae.

MOTIVATION: Reconstructing and analyzing the metabolic map of microorganisms is an important challenge in bioinformatics. Pathway analysis of large metabolic networks meets with the problem of combinatorial explosion of pathways. Therefore, appropriate algorithms for an automated decomposition of these networks into smaller subsystems are needed. RESULTS: A decomposition algorithm for metabolic networks based on the local connectivity of metabolites is presented. Interrelations of this algorithm with alternative methods proposed in the literature and the theory of small world networks are discussed. The applicability of our method is illustrated by an analysis of the metabolism of Mycoplasma pneumoniae, which is an organism of considerable medical interest. The decomposition gives rise to 19 subnetworks. Three of these are here discussed in biochemical terms: arginine degradation, the tetrahydrofolate system, and nucleotide metabolism. The interrelations of pathway analysis of biochemical networks with Petri net theory are outlined.

Algorithms↗
PubMed2001

Cooperation and competition in the evolution of ATP-producing pathways.

Heterotrophic organisms generally face a trade-off between rate and yield of adenosine triphosphate (ATP) production. This trade-off may result in an evolutionary dilemma, because cells with a higher rate but lower yield of ATP production may gain a selective advantage when competing for shared energy resources. Using an analysis of model simulations and biochemical observations, we show that ATP production with a low rate and high yield can be viewed as a form of cooperative resource use and may evolve in spatially structured environments. Furthermore, we argue that the high ATP yield of respiration may have facilitated the evolutionary transition from unicellular to undifferentiated multicellular organisms.

Adenosine Triphosphate↗
PubMed2001

Immunomagnetic enrichment of CD138 positive cells from weakly infiltrated myeloma patients samples enables the determination of the tumor clone specific IgH rearrangement.

In multiple myeloma, the polymerase chain reaction (PCR) of the Ig heavy chain with allele-specific oligonucleotide (ASO) primers is a common and well-described method of identifying the tumor clone in peripheral blood (PB), bone marrow (BM) or leukapheresis products (LA). A factor which is crucial to the detection of clonal Ig rearrangements lies in the 'purity' of the tumor tissue used for the consensus PCR. We describe the application of a method to enrich CD138 positive myeloma cells derived from weakly infiltrated PB-, BM- and LA-samples. These are subjected to immunomagnetic enrichment with the MACS system, using an CD138 antibody directly conjugated to magnetic beads to obtain an enriched tumor cell population and the subsequent amplification of tumor specific IgH rearrangements. We investigated 29 samples (ten PB, ten BM, nine LA) with a median myeloma cell content of 0.5%. The approach led to a median enrichment factor of 118. Tumor-specific rearrangements could be amplified reproducibly from samples containing less than 0.1% myeloma cells.

Consensus Sequence↗
PubMed2001

Gene expression of adrenomedullin, leptin, their receptors and neuropeptide Y in hormone-secreting and non-functioning pituitary adenomas, meningiomas and malignant intracranial tumours in humans.

The aim of this study was to assess human intracranial tumours for their gene expression pattern of the vasoactive peptide adrenomedullin (AM), its receptor (AM-R) and leptin, which exerts multiple biological effects including proliferation and angiogenesis via the leptin receptor (OB-Rb). Gene activity of neuropeptide Y (NPY) was monitored additionally. We investigated whether there was a characteristic gene expression pattern of AM and leptin in different intracranial tumours, depending on their proliferation activity and biological behaviour. We investigated 35 non-functioning pituitary adenomas (including eight null cell, four silent plurihormonal, 23 silent gonadotroph adenomas), seven somatotropinomas, seven prolactinomas, eight meningiomas, five astrocytomas, two glioblastoma multiformes and unaffected temporal lobe (n = 8). Quantitative reverse transcriptase-polymerase chain reaction (TaqMan RT-PCR) was performed. AM mRNA was detectable in all tumour specimens. AM/GAPDH (glyceraldehyde-3-phosphate dehydrogenase) ratio was significantly higher in somatotropinomas, as was AM/CD31 ratio in prolactinomas, compared with inactive adenomas (P < 0.05). AM-R mRNA was found in all tumour subgroups in small quantities but, in general, higher in tumours than in temporal lobe tissue, respectively. AM-R/CD31 ratio was significantly higher in prolactinomas than in inactive adenomas (P < 0.05). Leptin was detectable in very low quantities in each subgroup. OB-Rb gene expression was found in all tumour subgroups, OB-Rb/GAPDH ratio was highest for meningiomas (P < 0.0001, compared with temporal lobe). NPY mRNA was detectable in temporal lobe in higher quantities than in tumours (P < 0.0001), and almost undetectable in prolactinomas and astrocytomas. Our data demonstrate that AM and AM-R, NPY, as well as leptin and OB-Rb, are expressed in various intracranial tumours in humans but their particular function has to be elucidated further. At present, there is no evidence for a cross-talk on transcriptional level between the peptidergic vasodilative system AM and the putative angiogenic and proliferation affecting factor leptin.

Adenoma↗
PubMed2001

SHP-1 expression by malignant small B-cell lymphomas reflects the maturation stage of their normal B-cell counterparts.

SHP-1 is a protein phosphotyrosine phosphatase that plays an important role in modulating intracellular signaling, which regulates cell activation, proliferation, differentiation, and migration. It is a negative regulator of signal transduction induced by a number of cell receptors. Our immunohistochemical examination of paraffin-embedded reactive lymph nodes and lymphoid tissues revealed that B lymphocytes in follicle germinal centers do not express SHP-1. A weak staining of the B cells in the germinal center light zones was detected when an ultrasensitive amplification system was used. In contrast, normal B cells in mantle and marginal zones as well as interfollicular B lymphocytes and plasma cells displayed strong immunoreactivity. This pattern of SHP-1 expression was repeated in small B-cell lymphomas. All cases of mantle cell lymphoma (12 of 12), marginal zone lymphoma (10 of 10), and chronic lymphocytic leukemia/small lymphocytic lymphoma (13 of 13) expressed SHP-1 protein. However, only 1 of 30 cases of grade 1 follicle center cell lymphoma expressed SHP-1. Our observations highlight the biologic functions of SHP-1 and demonstrate that the SHP-1 expression pattern by small B-cell lymphomas reflects the maturation stage of their normal cell counterparts. These results indicate that determination of SHP-1 expression may help in the differential diagnosis of small B-cell lymphomas.

B-Lymphocytes↗
PubMed2001

Count and spark? The echo response of the weakly electric fish Gnathonemus petersii to series of pulses.

Weakly electric fish of the pulse type electrolocate objects in the dark by emitting discrete electric organ discharges (EODs) separated by intervals of silence. Two neighbouring pulse-type fish often reduce the risk of discharging simultaneously by means of an 'echo response': one fish will respond to a neighbour's EOD with a discharge of its own following at a fixed short latency so that its EOD will occur long before the next EOD of its neighbour. Although working elegantly for two partners, this simple strategy should fail in larger groups because two fish could discharge in response to the same EOD of a third fish. Here, I show that the mormyrid fish Gnathonemus petersii could use a simple mechanism to reduce this problem. Individuals were stimulated with two closely spaced pulses, the second following so as to coincide with an echo given in response to the first. All the fish examined were able to respond more to the second pulse so that most of their echoes did not collide with the second pulse. An analysis was made of how echoing more to the second pulse depends on (i) the delay at which the stimulus followed the last spontaneous EOD, (ii) the spontaneous firing rate, (iii) the intensity of the stimulus, (iv) the number of stimulus pulses, (v) the interval between stimulus pulses, and (vi) the level of previous stimulation with double pulses. The results suggest that echoing more in response to the second pulse is probably because the first pulse causes an after-effect whose inferred properties would be compatible with the properties of the mormyromast afferences thought to be involved in the echo response.

Animals↗
PubMed2001

Bleomycin, lomustine, cyclophosphamide, vincristine, procarbazine and prednisone (BLEO-CCVPP) in patients with Hodgkin's disease who relapsed after radiotherapy alone: a long-term follow-up study of the Eastern Cooperative Oncology Group (E3481).

Thirty-three evaluable patients with Hodgkin's disease who failed radiotherapy were treated on this phase II study with bleomycin, lomustine, cyclophosphamide, vincristine, procarbazine and prednisone given every 28 days for a minimum of eight courses. Twenty-five patients (76%; 95% CI=55.6-87.1%) achieved a complete remission, the median duration of which cannot yet be determined, but the probability of remaining in continuous complete remission at 10 years is.64. The median survival from entry on this study for all evaluable patients is 10 years, and 12 patients were alive at the time of this analysis with a median follow-up for them of 15.5 years. Of the 22 patients who died, 11 died of progressive or recurrent Hodgkin's disease and 11 died of other causes including 7 second primary neoplasms and at least one myocardial infarction. Both are now well known late complications of Hodgkin's disease treatment.

Adolescent↗
PubMed2000

Molecular beacons for DNA biosensors with micrometer to submicrometer dimensions.

Ultrasensitive molecular beacon (MB) DNA biosensors, with micrometer to submicrometer sizes, have been developed for DNA/RNA analysis. The fluorescence-based biosensors have been applied in DNA/ RNA detection without the need for a dye-labeled target molecule or an intercalation reagent in the testing solution. Molecular beacons are hairpin-shaped oligonucleotides that report the presence of specific nucleic acids. We have designed a surface-immobilizable biotinylated ssDNA molecular beacon for DNA hybridization at a liquid-solid interface. The MBs have been immobilized onto ultrasmall optical fiber probes through avidin-biotin binding. The MB DNA biosensor has been used directly to detect, in real time, its target DNA molecules without the need for a competitive assay. The biosensor is stable and reproducible. The MB DNA biosensor has selectivity with single base-pair mismatch identification capability. The concentration detection limits and mass detection limits are 0.3 nM and 15 amol for a 105-microm biosensor, and 10 nM and 0.27 amol for a submicrometer biosensor, respectively. We have also prepared molecular beacon DNA biosensor arrays for simultaneous analysis of multiple DNA sequences in the same solution. The newly developed DNA biosensors have been used for the precise quantification of a specific rat gamma-actin mRNA sequence amplified by the polymerase chain reaction.

Actins↗
PubMed2000

In-hospital mortality of elderly patients with acute myocardial infarction: data from the MITRA (Maximal Individual Therapy in Acute Myocardial Infarction) registry.

BACKGROUND: Advanced age remains one of the principal determinants of mortality in patients with acute myocardial infarction (AMI). HYPOTHESIS: The aim of this study was to determine the in-hospital outcome of elderly (> 75 years) patients with AMI who were admitted to hospitals participating in the national MITRA (Maximal Individual Therapy in Acute Myocardial Infarction) registry. METHODS: MITRA is a prospective, observational German multicenter registry investigating current treatment modalities for patients presenting with AMI. All patients with AMI admitted within 96 h of onset of symptoms were included in the MITRA registry. MITRA was started in June 1994 and ended in January 1997. This registry comprises 6,067 consecutive patients with a mean age of 65 +/- 12 years, of whom 1,430 (17%) were aged > 75 years. Patients were compared with respect to patient characteristics, prehospital delays, early treatment strategies, and clinical outcome. RESULTS: In the elderly patient population, the prehospital delay was 210 min, which was significantly longer than that for younger patients (155 min, p = 0.001). Although the incidence of potential contraindications for the initiation of thrombolysis was almost equally distributed between the two age groups (8.7 vs. 8.2%, p = NS), elderly patients (> 75 years) received reperfusion therapy less frequently (35.9 vs. 64.6%) than younger patients. Mortality increased with advanced age and was 26.4% for all patients aged > 75 years. If reperfusion therapy was initiated, in-hospital mortality was 21.8 versus 28.9% in patients aged > 75 years (p = 0.001) and 29.4 versus 38.5% in patients aged > 85 years (p = 0.001). CONCLUSION: In this registry, elderly patients with AMI had a much higher in-hospital mortality than that expected from randomized trials. In MITRA, the mortality reduction with reperfusion therapy was found to be highest in the very elderly patient population.

Age Factors↗