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A Hauser

Publications and source records attributed to A Hauser.

At least 19 recordsLinked to original sources
PubMed2005

[Comparison of different stool tests for the detection of cancer of the colon].

BACKGROUND AND OBJECTIVE: Colonoscopy is the gold standard for the diagnosis of colonic neoplasia. Because of the low compliance, the discomfort of bowel preparation and the procedure itself and the (albeit small) risk of perforation or bleeding alternative procedures such as stool tests are being focused on. PATIENTS AND METHODS: After informed consent stool samples of 116 patients (44 male, 72 female, median age 47 years), scheduled for colonoscopy and 22 patients (17 m, 5 f, 69 y) with known colorectal cancer stool samples were collected. The samples were investigated by three methods: a biochemical (Guajak) test for fecal occult blood, an immunological test for fecal occult blood and a test determining the dimer pyruvat kinase M2 (tumor M2-PK). RESULTS: Sensitivity for detection of colorectal cancer or polyps was 27 % and 10 % for the biochemical test, 91 % and 19 % for the immunological test and 77 % and 48 % for the M2-PK-test, respectively. Specificity was 89 %, 94 % and 72 %, respectively. CONCLUSIONS: Both methods for detection of occult blood had a similar specificity. The sensitivity of the immunological test for the detection of colorectal cancer was significantly higher. The M2-PK-test had a markedly lower specificity in diagnosing cancer. Because of the low sensitivity for polyps the usefulness of stool tests is questionable. Reducing incidence and mortality of colorectal cancer should be achieved by colonoscopy, a recommendation that requires specific communication to the public.

Aged↗
PubMed2004

Proof of principle for the use of 11C-labelled peptides in tumour diagnosis with PET.

PURPOSE: The future significance of peptide radiopharmaceuticals in diagnostic imaging with PET will be dependent on methodological aspects, as well as other requirements such as availability of the radionuclide and cost-effectiveness of its production. The aim of this study was to evaluate whether recent improvements in the modification of peptide pharmacokinetics by carbohydration may open a niche for the use of 11C-labelled peptide receptor binding tracers. METHODS: A carbohydrated analogue of Tyr3-octreotate was used as a clinically relevant peptide. Oxime-mediated coupling between 4-[11C]methoxy-benzaldehyde and an aminooxy-conjugated peptide precursor provided the 11C-labelled peptide in 21+/-5% decay-corrected yield (n=4) in a synthesis time of about 1 h. RESULTS: In rat pancreas carcinoma xenografted mice, the compound displayed predominant and fast renal clearance combined with high tumour uptake (18.5+/-2.8% ID/g) at 30 min post injection. Corresponding values for kidney, liver and intestine were 18.5+/-2.4% ID/g, 3.2+/-0.5% ID/g and 2.1+/-0.3% ID/g, respectively. In a PET study with xenografted mice, the tumour (0.2-0.3 g) was clearly delineated as early as 20 min after injection. Somatostatin receptor (sstr)-specific uptake was demonstrated by reduction of tumour uptake to 20% of control by co-injection of TOC (0.4 mg/kg; 30 min p.i.). CONCLUSION: A 11C-labelled octreotate derivative has been prepared which shows suitable pharmacokinetics for in vivo imaging of sstr-overexpressing tumours and thus represents the first proof of principle for the potential of 11C-labelled peptides in tumour imaging.

Animals↗
PubMed2004

Synthesis and preclinical evaluation of the choline transport tracer deshydroxy-[18F]fluorocholine ([18F]dOC).

11C-labeled choline ([11C]CHO) and 18F-fluorinated choline analogues have been demonstrated to be valuable tracers for in vivo imaging of neoplasms by means of positron emission tomography (PET). The objective of the present study was to evaluate whether deshydroxy-[18F]fluorocholine, ([18F]dOC), a non-metabolizable [18F]fluorinated choline analogue, can serve as a surrogate for cholines that are able to be phosphorylated and thus allow PET-imaging solely by addressing the choline transport system. The specificity of uptake of [18F]dOC was compared with that of [11C]choline ([11C]CHO) in cultured rat pancreatic carcinoma and PC-3 human prostate cancer cells in vitro. In addition, biodistribution of [18F]dOC and [11C]CHO was compared in AR42J- and PC-3 tumor bearing mice. The in vitro studies revealed that membrane transport of both compounds can be inhibited in a concentration dependent manner by similar concentrations of cold choline (IC50 [18F]dOC= 11 microM; IC50 [11C]CHO=13 microM. In vitro studies with PC-3 and AR42J cells revealed that the internalized fraction of [18F]dOC after 5 min incubation time is comparable to that of [11C]CHO, whereas the uptake of [11C]CHO was superior after 20 min incubation time. As for [11C]CHO, kidney and liver were also the primary sites of uptake for [18F]dOC in vivo. Biodistribution data after simultaneous injection of both tracers into AR42J tumor bearing mice revealed slightly higher tumor uptake for [18F]dOC at 10 min post-injection, whereas [11C]CHO uptake was higher at later time points. In conclusion, [18F]dOC is taken up into AR42J rat pancreatic carcinoma and PC-3 human prostate cancer cells by a choline specific transport system. Similar transport rates of [18F]dOC and [11C]CHO result in comparable cellular uptake levels at early time points. In contrast to [18F]dOC, which is transported but not intracellularly trapped, the choline kinase substrate [11C]CHO is transported into tumor cells and retained. Thus, the signal obtained by imaging early after injection is mainly reflecting transport, whereas a valid quantification of choline kinase activity needs imaging at later time points. Further studies have to clarify whether quantification of the transport capacity or the choline kinase activity result in a better pathophysiological correlate and thus is the more useful process for tumor characterization.

Animals↗
PubMed2001

Biphasic behavior of the high-spin-->low-spin relaxation of [Fe(btpa)](PF6)2 in solution (btpa = N,N,N',N'-tetrakis(2-pyridylmethyl)-6,6'-bis(aminomethyl)-2,2'- bipyridine).

The light-induced high-spin-->low-spin relaxation for the Fe(II) spin-crossover compounds [Fe(btpa)](PF6)2 and [Fe(b(bdpa))](PF6)2 in solution, where btpa is the potentially octadentate ligand N,N,N',N'-tetrakis(2-pyridylmethyl)-6,6'-bis(aminomethyl)-2,2'-bipyridine and b(bdpa) is the analogous hexadentate ligand N,N'-bis(benzyl)-N,N'-bis(2-pyridylmethyl)-6,6'-bis(aminomethyl)-2,2'- bipyridine, respectively, has been studied by temperature-dependent laser flash photolysis. [Fe(b(bdpa))](PF6)2 shows single-exponential 5T2-->1A1 relaxation kinetics, whereas [Fe(btpa)](PF6)2 exhibits solvent-independent biphasic relaxation kinetics. The fast process of [Fe(btpa)](PF6)2 with a rate constant, kHL, of 2.5 x 10(7) s-1 at 295 K and an activation energy, Ea, of 1294(26) cm-1 in methanol can be assigned to the 5T2-->1A1 relaxation as well. The slow process with a kHL(295 K) of 3.7 x 10(5) s-1 and a Ea of 2297(32) cm-1 in methanol--which is the slowest light-induced relaxation process observed so far for an Fe(II) spin-crossover complex in solution--is assigned to a coupling of the 5T2-->1A1 relaxation process to a geometrical rearrangement within the pendent pyridyl arms.

Journal Article↗
PubMed2001

Inflamed kidneys of NZB / W mice are a major site for the homeostasis of plasma cells.

(NZB x NZW)F1 (NZB / W) mice develop a disease similar to human systemic lupus erythematosus (SLE), including autoantibody production, hypergammaglobulinaemia and inflammation of the kidneys. It is known that large numbers of lymphocytes infiltrate the kidneys of these mice. Here, we compare the roles of bone marrow, spleen and inflamed kidneys of NZB / W mice in the activation of B cells and the persistence of antibody-secreting cells (ASC). ASC are present in the kidneys of NZB / W mice with full-blown disease, as many as in the spleen and bone marrow. The specificity of the ASC in the inflamed kidneys is not restricted to self-antigens. After immunization of NZB / W mice with ovalbumin (OVA) the OVA-specific ASC are found initially in the spleen. Weeks later, OVA-specific ASC are found in high numbers in the bone marrow and the kidneys of these mice, but no longer in the spleen. As determined by FACS, B cells with a germinal center phenotype (B220(+) / PNA(+)) are found only in very low numbers in the kidneys, but in high numbers in the spleen of NZB / W mice. Germinal centers could not be detected in the kidneys, but in the spleen, and plasma cells appear to be scattered over the tissue. These data suggest that in autoimmune NZB / W mice, plasma cells generated in immune reactions of secondary lymphoid organs, later accumulate and persist in the inflamed kidneys, were they enhance the local concentrations of Ab and immunocomplexes. These experiments identify the inflamed kidneys of NZB / W mice as a site of prime relevance for the homeostasis of plasma cells, irrespective of their specificity.

Animals↗
PubMed2000

The tumor necrosis factor-related apoptosis-inducing ligand receptors TRAIL-R1 and TRAIL-R2 have distinct cross-linking requirements for initiation of apoptosis and are non-redundant in JNK activation.

Overexpression of the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptors, TRAIL-R1 and TRAIL-R2, induces apoptosis and activation of NF-kappaB in cultured cells. In this study, we have demonstrated differential signaling capacities by both receptors using either epitope-tagged soluble TRAIL (sTRAIL) or sTRAIL that was cross-linked with a monoclonal antibody. Interestingly, sTRAIL was sufficient for induction of apoptosis only in cell lines that were killed by agonistic TRAIL-R1- and TRAIL-R2-specific IgG preparations. Moreover, in these cell lines interleukin-6 secretion and NF-kappaB activation were induced by cross-linked or non-cross-linked anti-TRAIL, as well as by both receptor-specific IgGs. However, cross-linking of sTRAIL was required for induction of apoptosis in cell lines that only responded to the agonistic anti-TRAIL-R2-IgG. Interestingly, activation of c-Jun N-terminal kinase (JNK) was only observed in response to either cross-linked sTRAIL or anti-TRAIL-R2-IgG even in cell lines where both receptors were capable of signaling apoptosis and NF-kappaB activation. Taken together, our data suggest that TRAIL-R1 responds to either cross-linked or non-cross-linked sTRAIL which signals NF-kappaB activation and apoptosis, whereas TRAIL-R2 signals NF-kappaB activation, apoptosis, and JNK activation only in response to cross-linked TRAIL.

Antibodies, Monoclonal↗
PubMed2000

Detection of BRCA1 and BRCA2 mutations in breast cancer families by a comprehensive two-stage screening procedure.

We have developed a 2-stage protocol for BRCA1 and BRCA2 mutation screening from blood spot paper. Stage 1 screening was aimed to analyze patients at highest risk for the most common disease-associated sequence variants listed in the BIC database. Accordingly, stage1 testing implied detection of 18 disease- associated BRCA1 and 9 BRCA2 mutations by adapting the 5' nuclease assay to heterozygote screening. For stage 2 screening, we applied the conformation sensitive gel electrophoresis (CSGE) method by adapting this technique to automated heteroduplex analysis of BRCA1 and BRCA2 using fragment scanning on an ABI 377 sequencing device. Of the 120 patients with a family history of breast and ovarian cancer who took part in this study so far, 45 entered stage 1 testing. Disease-associated mutations were detected in 6 patients by stage 1 testing (13%). For these patients, the final result was available within 10 days. Mutation 300T-->G was found in 2 patients. One patient with mutation 3036delACAA in BRCA2 reported only 1 sister with a multifocal bilateral breast cancer. New disease-associated mutations were detected in 2 of the 114 patients who entered the stage 2 test (1.7%). Of particular interest was 1 patient who was diagnosed with a medullary breast carcinoma at age 39 and who had no family history of breast cancer. We conclude that pre-screening by 5' nuclease assay for the mutations most frequently seen in a given population represents a relatively effective first line of analysis. Subsequent detailed analysis by fluorescence conformation sensitive gel electrophoresis (F-CSGE) and fragment sequencing is a sensitive alternative to full nucleotide sequencing.

Adult↗
PubMed2000

A thermal spin transition in [Co(bpy)3][LiCr(ox)3] (ox = C2O4(2-); bpy = 2,2'-bipyridine).

In the three-dimensional oxalate network structures [M(II)(bpy)3][M(I)-M(III)(ox)3] (ox= C2O4(2-); bpy = 2,2'-bipyridine) the negatively charged oxalate backbone provides perfect cavities for tris-bipyridyl complex cations. The size of the cavity can be adjusted by variation of the metal ions of the oxalate backbone. In [Co(bpy)3][NaCr(ox)3], the [Co(bpy)3]2 + complex is in its usual 4T1(t2g5e(g)2) high-spin ground state. Substituting Na+ by Li+ reduces the size of the cavity. The resulting chemical pressure destabilises the high-spin state of [Co(bpy)3]2+ to such an extent that the 2E(t2g6e(g)1) low-spin state becomes the actual ground state. As a result. [Co(bpy)3][LiCr(ox)3] becomes a spin-crossover system, as shown by temperature-dependent magnetic susceptibility measurements and single-crystal optical spectroscopy, as well as by an X-ray structure determination at 290 and 10 K.

Journal Article↗
PubMed2000

The arginine finger domain of ExoT contributes to actin cytoskeleton disruption and inhibition of internalization of Pseudomonas aeruginosa by epithelial cells and macrophages.

Pseudomonas aeruginosa, an important nosocomial pathogen of humans, expresses a type III secretion system that is required for virulence. Previous studies demonstrated that the lung-virulent strain PA103 has the capacity to be either cytotoxic or invasive. Analyses of mutants suggest that PA103 delivers a negative regulator of invasion, or anti-internalization factor, to host cells via a type III secretion system. In this work we show that the type III secreted protein ExoT inhibits the internalization of PA103 by polarized epithelial cells (Madin-Darby canine kidney cells) and J774.1 macrophage-like cells. ExoS, which is closely related to ExoT but has additional ADP-ribosylating activity, can substitute for ExoT as an anti-internalization factor. ExoT contains a signature arginine finger domain found in GTPase-activating proteins. Mutation of the conserved arginine in ExoT diminished its anti-internalization activity and altered its ability to disrupt the actin cytoskeleton. Cell fractionation experiments showed that ExoT is translocated into host cells and that mutation of the arginine finger did not disrupt translocation. In a mouse model of acute pneumonia, PA103DeltaUDeltaT reached the lungs as efficiently as PA103DeltaU but showed reduced colonization of the liver. This finding suggests that the ability to resist internalization may be important for virulence in vivo.

ADP Ribose Transferases↗
PubMed2000

[High dosage therapy and autologous peripheral stem cell transplantation in breast carcinoma].

42 breast cancer patients were treated by high-dose chemotherapy (HDC) and autologous peripheral stem-cell transplantation (ASTx) in the Donauspital between 1992 and 1999. 24 patients had stage II/III breast cancer with high risk for relapse. The other 18 patients underwent HDC and ASTx in chemosensitive stage IV. After previous conventional chemotherapy peripheral stem-cells were harvested by one cycle of mobilisation chemotherapy (epirubicin/taxol, FEC 120 or cyclophosphamide) followed by cytokine stimulation. 16 patients were treated by a tandem transplantation (conditioning protocol for 1st ASTx was melphalan 200 mg/m2 and for 2nd transplant it was CTC: cyclophosphamide 6 g/m2; thiotepa 500 mg/m2; carboplatin 800 mg/m2). The other 26 patients received one HDC with CTC as conditioning protocol. The HDC was well tolerated by all patients, there was no transplant-related mortality. The median survival and the progression-free survival (PFS) after HDC and ASTx in stage IV breast cancer patients were 28 and 11 months, respectively. The median survival and PFS were not yet reached in stage II/III patients after 55 months. The actuarial survival and PFS in that patient group were 70% after 55 months. Our data confirm the low risk and good efficacy of HDC and ASTx in breast cancer patients. Nevertheless randomised studies are necessary to evaluate the importance of HDC compared to intensified conventional protocols without ASTx.

Adult↗
PubMed1991

Cor triatriatum dexter: recognition and percutaneous transluminal correction.

Cor triatriatum dexter is a rare congenital anomaly in which an obstructive membrane is located in the right atrium. The detection usually occurs after the sequelae of systemic congestion, coagulopathy, and hepatic dysfunction have set in, leading up to a high surgical risk. A percutaneous balloon correction of cor triatriatum dexter in a patient with advanced right-sided congestive symptoms and hepatic dysfunction is presented. This efficacious method is an alternative to surgical correction and could be extended to the more common cor triatriatum sinistra.

Adult↗
PubMed1990

Effects of platelet activating factor antagonists on arachidonic acid-induced platelet aggregation and TXA2 formation.

The effects of the PAF receptor antagonists WEB 2086, WEB 2170, BN 50739 and BN 52021 on AA-induced platelet aggregation (PA) and TXA2 formation were investigated in comparison with the TXA2 synthetase inhibitor HOE 944 and the TXA2 receptor antagonist BM 13.177. All PAF antagonists tested were weak inhibitors of AA-induced PA and TXA2 formation (IC50 values between 80 and 2,737 mumol/l). HOE 944 was effective in concentrations 2-3 orders of magnitude lower than PAF antagonists in inhibiting TXA2 generation. These results imply that the inhibition of TXA2 formation is of minor relevance for the actions of the investigated PAF antagonists in AA-induced PA.

Animals↗
PubMed1988

An estimate of the prevalence of dementia in idiopathic Parkinson's disease.

A review of the records for evidence of dementia using criteria adapted from the third edition of the Diagnostic and Statistical Manual of Mental Disorders in every patient (hospitalized and outpatient) with parkinsonism at a major medical center during an 18-month period revealed an overall prevalence of 10.9% in 339 patients with idiopathic Parkinson's disease. Demented patients were older, had a later age at onset of motor manifestations, and a more rapid progression of physical disability than nondemented patients. Duration of illness and levodopa use and the presence of tremor or depression were similar in demented and nondemented patients. Demented patients more often responded poorly or developed adverse effects to levodopa than nondemented patients. When Parkinson's disease began after age 70 years, dementia was noted over three times more frequently than when the disease began at an earlier age. The age-specific prevalence rate of dementia for patients older than 70 years was more than twice that for younger patients. Moreover, the number of records with evidence for dementia with idiopathic Parkinson's disease was 3.75 times greater than expected in comparison with data from a study of the prevalence of dementia in the elderly.

Aged↗
PubMed1988

Electromechanical dissociation in human beings: an echocardiographic evaluation.

Electromechanical dissociation (EMD) has been described as "organized electrical depolarization of the heart without synchronous myocardial fiber shortening and, therefore, without cardiac output." However, little evidence demonstrating this description exists. We wished to determine whether mechanical activity is present during EMD. Twenty-two patients presenting with, or subsequently developing EMD in the emergency department from April 1986 to January 1987 were studied. Echocardiograms were performed during five-second pauses in CPR, using the subxiphoid approach. Nineteen patients (86%) had synchronous myocardial wall motion. In two others, there was a rhythmic change in the echocardiographic density of the myocardium, without visible chamber narrowing. In one there was no visible myocardial response associated with the QRS complex. One or more cardiac valves were visualized in 17 patients. Of these, valvular motion was seen in 15 (88%), but only four exhibited visible valve closure. In our study population, the majority of patients in EMD had myocardial wall and valve motion. Thus, the term "electromechanical dissociation" may be a misnomer.

Adult↗
PubMed1988

Effects of trapidil and trapidil derivatives on arachidonic acid and prostaglandin endoperoxide analogue U 46619-induced blood pressure changes in rats.

The influence of trapidil (T) and two selected 5,7-disubstituted s-triazolo (1,5-a)pyrimidine derivatives (TD: AR 12456 and AR 12463) on arachidonic acid(AA)- and prostaglandin endoperoxide analogue U 46619-induced blood pressure changes in normotensive rats was investigated in comparison with the cyclooxygenase inhibitor acetylsalicylic acid (ASA) and the thromboxane A2 (TXA2) antagonist BM 13177. ASA and AR 12456 completely eliminated the second blood pressure depression after injection of AA and simultaneously diminished TXA2, TXB2 and 6-keto-PGF1a formation in murine blood, whereas BM 13177 prevented the return of the blood pressure to preinjection level after the initial brief fall in arterial pressure. BM 13177 and AR 12463 reduced the rise in U 46619-provoked blood pressure by 75% and 58%, respectively. Trapidil had no effect on blood pressure changes stimulated by AA and U 46619.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗