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Showing papers by "University of Graz published in 2000"


Journal ArticleDOI
TL;DR: A rapid evaluation for antioxidants, using two TLC screening methods, showed that thymoquinone and the components carvacrol, t‐anethole and 4‐terpineol demonstrated respectable radical scavenging property.
Abstract: The essential oil of black cumin seeds, Nigella sativa L., was tested for a possible antioxidant activity. A rapid evaluation for antioxidants, using two TLC screening methods, showed that thymoquinone and the components carvacrol, t-anethole and 4-terpineol demonstrated respectable radical scavenging property. These four constituents and the essential oil possessed variable antioxidant activity when tested in the diphenylpicrylhydracyl assay for non-specific hydrogen atom or electron donating activity. They were also effective.OH radical scavenging agents in the assay for non-enzymatic lipid peroxidation in liposomes and the deoxyribose degradation assay. GC-MS analysis of the essential oil obtained from six different samples of Nigella sativa seeds and from a commercial fixed oil showed that the qualitative composition of the volatile compounds was almost identical. Differences were mainly restricted to the quantitative composition.

1,807 citations


Journal ArticleDOI
TL;DR: This review highlights recent developments in the synthesis of functionalized 3,4-dihydropyrimidin-2(1H)-ones with a focus on the DHPMs recently developed as calcium channel modulators, alpha(1a) adrenoceptor-selective antagonists and compounds that target the mitotic machinery.

1,191 citations


Journal ArticleDOI
Kappe Co1
TL;DR: This Account highlights recent developments in the Biginelli reaction in areas such as solid-phase synthesis, combinatorial chemistry, and natural product synthesis.
Abstract: In 1893, P. Biginelli reported the synthesis of functionalized 3, 4-dihydropyrimidin-2(1H)-ones (DHPMs) via three-component condensation reaction of an aromatic aldehyde, urea, and ethyl acetoacetate. In the past decade, this long-neglected multicomponent reaction has experienced a remarkable revival, mainly due to the interesting pharmacological properties associated with this dihydropyrimidine scaffold. In this Account, we highlight recent developments in the Biginelli reaction in areas such as solid-phase synthesis, combinatorial chemistry, and natural product synthesis.

971 citations


Journal ArticleDOI
TL;DR: In this article, the effect of 10 mg of alendronate or placebo, given daily, on bone mineral density in 241 men with osteoporosis, was studied in a double-blind trial.
Abstract: Background Despite its association with disability, death, and increased medical costs, osteoporosis in men has been relatively neglected as a subject of study There have been no large, controlled trials of treatment in men Methods In a two-year double-blind trial, we studied the effect of 10 mg of alendronate or placebo, given daily, on bone mineral density in 241 men (age, 31 to 87 years; mean, 63) with osteoporosis Approximately one third had low serum free testosterone concentrations at base line; the rest had normal concentrations Men with other secondary causes of osteoporosis were excluded All the men received calcium and vitamin D supplements The main outcome measures were the percent changes in lumbar-spine, hip, and total-body bone mineral density Results The men who received alendronate had a mean (±SE) increase in bone mineral density of 71±03 percent at the lumbar spine, 25±04 percent at the femoral neck, and 20±02 percent for the total body (P<0001 for all comparisons with base

941 citations


Journal ArticleDOI
TL;DR: In this paper, the authors systematically quantified acute axonal injury, defined by immunoreactivity for beta-amyloid-precursor-protein in dystrophic neurites, in the central nervous system of 22 MS patients and 18 rats with myelin-oligodendrocyte glycoprotein (MOG)-induced chronic autoimmune encephalomyelitis (EAE).
Abstract: Recent magnetic resonance (MR) studies of multiple sclerosis lesions indicate that axonal injury is a major correlate of permanent clinical deficit. In the present study we systematically quantified acute axonal injury, defined by immunoreactivity for beta-amyloid-precursor-protein in dystrophic neurites, in the central nervous system of 22 multiple sclerosis patients and 18 rats with myelin-oligodendrocyte glycoprotein (MOG)-induced chronic autoimmune encephalomyelitis (EAE). The highest incidence of acute axonal injury was found during active demyelination, which was associated with axonal damage in periplaque and in the normal appearing white matter of actively demyelinating cases. In addition, low but significant axonal injury was also observed in inactive demyelinated plaques. In contrast, no significant axonal damage was found in remyelinated shadow plaques. The patterns of axonal pathology in chronic active EAE were qualitatively and quantitatively similar to those found in multiple sclerosis. Our studies confirm previous observations of axonal destruction in multiple sclerosis lesions during active demyelination, but also indicate that ongoing axonal damage in inactive lesions may significantly contribute to the clinical progression of the disease. The results further emphasize that MOG-induced EAE may serve as a suitable model for testing axon-protective therapies in inflammatory demyelinating conditions.

891 citations


Journal ArticleDOI
TL;DR: A strong dependence of the plasmon lifetime and resonance wavelength on the grating constant is found and it is found that gold nanoparticles arranged in regular two-dimensional patterns have regular grating effects.
Abstract: We probe the influence of grating effects on plasmon excitations in gold nanoparticles arranged in regular two-dimensional patterns. Samples produced by electron-beam lithography are investigated by femtosecond time-resolved and spectroscopic methods. We find a strong dependence of the plasmon lifetime and resonance wavelength on the grating constant.

575 citations


Journal ArticleDOI
TL;DR: In this paper, the authors used Kratky slit collimation to measure the absolute intensity of small-angle scattering, of X-rays (SAXS) and neutrons (SANS), which is the ratio of the scattering intensity to the primary intensity.
Abstract: For small-angle scattering, of X-rays (SAXS) and neutrons (SANS), the importance of absolute calibration has been recognized since the inception of the technique. The work reported here focuses on SAXS measurements using Kratky slit systems. In former days, only molecular weights or scattering per particle were determined, but today absolute calibration implies the use of the unit of cm−1 for the scattering curve. It is necessary to measure the so-called absolute intensity, which is the ratio of the scattering intensity to the primary intensity P0. Basically there are two possible ways to determine the absolute intensity. The first one is the direct method, which involves the mechanical attenuation of the primary beam by a rotating disc or a moving slit. The second is the indirect method, using secondary standards. Water is well suited as a calibration standard because of the angle-independent scattering. The essential advantage is that the scattering of water only depends on the physical property of isothermal compressibility. Before presenting an example of the practical performance of this method, the most important theoretical equations for an SAS experiment on the absolute scale are summarized. With the slit collimation system, the scattering curve of water can be measured with high enough statistical accuracy. As a first example, the scattering curve of the protein lysozyme on the absolute scale is presented. The second example is the determination of the aggregation number of a triblock copolymer P94 (EO17–PO42–EO17). Taking into account that at least 10% of the polymer sample consists of diblocks, the accuracy of around 10% for the determined aggregation number is rather good. The data of P94 are also considered on the particle scale in order to obtain the radial scattering-length density distribution.

556 citations


Journal ArticleDOI
TL;DR: Three common mutations in the 3′ untranslated region of the VEGF gene are found; one of them, a 936 C/T exchange, may be an important determinant of V EGF plasma levels.
Abstract: Background: Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. Strong interindividual variations of VEGF plasma levels have been reported previousl

528 citations


Journal ArticleDOI
TL;DR: The ability of HNE to modulate cell proliferation through interference with the activity of cyclins and protein kinases and with the apoptotic machinery is of interest and pursuing investigation of the role of H NE in signal transduction and gene expression seems very promising.
Abstract: Here we review the current knowledge on the biochemistry and molecular pathology of oxidative stress with specific regard to a major aldehydic end-product stemming from peroxidation of biomembranes, that is 4-hydroxynonenal (HNE). This multifunctional molecule, which derives from the most represented class of polyunsaturated fatty acids in the membranes, is potentially able to undergo a number of reactions with proteins, phospholipids, and nucleic acids. Despite an active metabolism in most of the cell types, HNE can be detected in several biological tissues by means of sufficiently precise methods, although with different sensitivity. In particular, relatively high steady-state levels of HNE are often detectable in a large variety of human disease processes, pointing to some involvement of the aldehyde in their pathogenesis. Among the prominent pathobiochemical effects of HNE is its remarkable stimulation of fibrogenesis and inflammation, which indicates a potential contribution of the aldehyde to the pathogenesis of several chronic diseases, whose progression is indeed supported by inflammatory reactions and characterized by fibrosis. Further, of interest appears to be the ability of HNE to modulate cell proliferation through interference with the activity of cyclins and protein kinases and with the apoptotic machinery. Finally, on the basis of the already achieved evidence, pursuing investigation of the role of HNE in signal transduction and gene expression seems very promising.

304 citations


Journal ArticleDOI
TL;DR: Experimental autoimmune encephalomyelitis and neuritis are focused on as models in rat and mouse strains, and their distinct histopathology and the roles played by different autoantigens are discussed.

299 citations


Journal ArticleDOI
TL;DR: It is concluded that coassembly of Trp1 and Trp3 resulted in the formation of oligomeric Trp channels that are subject to regulation by phospholipase C and Ca(2+).

Journal ArticleDOI
TL;DR: DTI with a phase navigated interleaved echo planar imaging technique may be used to detect abnormalities of isotropic and anisotropic diffusion in the NAWM and selected fiber tracts of patients with MS throughout the entire brain, and it demonstrates substantial differences between various types of focal lesions.
Abstract: High-resolution diffusion tensor imaging (DTI) was performed in 14 patients with clinically definite multiple sclerosis (MS) and the trace of the diffusion tensor (〈D〉) and the fractional anisotropy (FA) were determined in normal appearing white matter (NAWM) and in different types of focal MS lesions. A small but significant increase of the 〈D〉 in NAWM compared to control white matter ((840 ± 85) × 10–6 mm2/sec vs. (812 ± 59) × 10–6 mm2/sec; P < 0.01) was found. In addition, there was a significant decrease in the FA of normal-appearing regions containing well-defined white matter tracts, such as the genu of the internal capsule. In non-acute lesions, the 〈D〉 of T1-hypointense areas was significantly higher than that of T1-isointense lesions ((1198 ± 248) × 10–6 mm2/sec vs. (1006 ± 142) × 10–6 mm2/sec; P < 0.001), and there was a corresponding inverse relation of FA. Diffusion characteristics of active lesions with different enhancement patterns were also significantly different. DTI with a phase navigated interleaved echo planar imaging technique may be used to detect abnormalities of isotropic and anisotropic diffusion in the NAWM and selected fiber tracts of patients with MS throughout the entire brain, and it demonstrates substantial differences between various types of focal lesions. Magn Reson Med 44:583–591, 2000. © 2000 Wiley-Liss, Inc.

Journal ArticleDOI
TL;DR: The chemotherapeutic oxaliplatin causes a sensory-motor neuropathy with predominantly hyperpathic symptoms and the mechanism underlying this hyperexcitability was investigated using rat sensory nerve preparations, dorsal root ganglia and hippocampal neurons, suggesting an interaction with voltage-gated Na(+) channels.

Journal ArticleDOI
TL;DR: A review of recent advances in the concepts of generation and nature of pathogenetic autoantibodies, their potential modes of action, mechanisms of their long‐term persistence, and the role of the inflamed brain tissue as a B‐cell–supporting microenvironment in MS suggests it seems possible to define distinct MS subgroups in the near future.
Abstract: A variety of cellular and humoral immunological abnormalities have been observed in multiple sclerosis (MS). In the past few years, several lines of evidence converged to imply an important role of autoreactive antibodies and B cells in the pathogenesis of MS. Recent data suggest that autoantibodies may be harmful in lesion formation but also potentially beneficial in repair. This review surveys recent advances in the concepts of generation and nature of pathogenetic autoantibodies, their potential modes of action, mechanisms of their long-term persistence, and the role of the inflamed brain tissue as a B-cell-supporting microenvironment in MS. Based on the presence of specific autoantibodies, it seems possible to define distinct MS subgroups in the near future. The therapeutic relevance of these new findings is presented.

Journal ArticleDOI
TL;DR: Tryptophan degradation due to immune activation may exert impact on the pathogenesis of AD and increased Kyn/Trp was associated with reduced cognitive performance.
Abstract: Alzheimer's disease (AD) is likely associated with systemic immune activation. During immune response, interferon-gamma stimu-lates indoleamine 2,3-dioxygenase (IDO) converting tryptophan to N-formylkynurenine followed by kynurenine in an ensuing step. Thus, IDO activity is estimated by the kynurenine per tryptophan quotient (Kyn/Trp). In 21 patients suffering from AD, in 20 controls of similar age, and in 49 blood donors we measured serum tryptophan and kynurenine concentrations by HPLC. Lower tryptophan concentrations were found in elderly control subjects compared to blood donors (62.1 vs. 73.0 μM, p < 0.005). Tryptophan concentrations tended to be still lower in AD patients (54.4 μM, p = 0.07) compared to elderly controls. Enhanced tryptophan degradation in patients was reflected by significantly increased Kyn/Trp (46.1 vs. 34.1 in elderly controls, p < 0.05). Correlations were found in patients between Kyn/Trp and concentrations of soluble immune markers in serum, i.e., neopterin, interleukin-2 receptor and tumor necrosis factor receptor (all p < 0.001). Increased Kyn/Trp was associated with reduced cognitive performance. Tryptophan degradation due to immune activation may exert impact on the pathogenesis of AD.

Journal ArticleDOI
TL;DR: In metal nanoparticles the resonance wavelength of light-driven collective electron oscillations is determined by the particle shape, so the storage density can be increased by at least a factor of 5 compared with that for conventional optical storage principles.
Abstract: In metal nanoparticles the resonance wavelength of light-driven collective electron oscillations is determined by the particle shape. This shape dependence can be used for optical data storage by spectral coding. In this way the storage density can be increased by at least a factor of 5 compared with that for conventional optical storage principles.

Journal ArticleDOI
TL;DR: The diameter of a patent foramen ovale is an independent risk factor for ischemic events, especially recurrent strokes.

Journal ArticleDOI
TL;DR: In this article, the authors compared graphite powders and carbon fibres as model materials for X-ray photoemission spectroscopy (XPS) studies of the effects of surface pre-treatment.

Journal ArticleDOI
TL;DR: The colocalization of immunoreactive MPO and HOCl-modified-epitopes in serial sections of human atheroma, fibroatheroma (type V) and complicated (type VI) lesions provides further convincing evidence for MPO/H2O2/halide system-mediated oxidation of (lipo)proteins under in vivo conditions.
Abstract: The 'oxidation theory' of atherosclerosis proposes that oxidation of low density lipoprotein (LDL) contributes to atherogenesis. Although the precise mechanisms of in vivo oxidation are widely unknown, increasing evidence suggests that myeloperoxidase (MPO, EC 1.11.1.7), a protein secreted by activated phagocytes, generates modified/oxidized (lipo)proteins via intermediate formation of hypochlorous acid (HOCl). In vitro generation of HOCl transforms lipoproteins into high uptake forms for macrophages giving rise to cholesterol-engorged foam cells. To identify HOCl-modified-epitopes in human plaque tissues we have raised monoclonal antibodies (directed against human HOCl-modified LDL) that do not cross-react with other LDL modifications, i.e. peroxynitrite-LDL, hemin-LDL, Cu2+-oxidized LDL, 4-hydroxynonenal-LDL, malondialdehyde-LDL, glycated-LDL, and acetylated-LDL. The antibodies recognized a specific epitope present on various proteins after treatment with OCl- added as reagent or generated by the MPO/H2O2/halide system. Immunohistochemical studies revealed pronounced staining for HOCl-modified-epitopes in fibroatheroma (type V) and complicated (type VI) lesions, while no staining was observed in aortae of lesion-prone location (type I). HOCl-oxidation-specific epitopes are detected in cells in the majority of atherosclerotic plaques but not in control segments. Staining was shown to be inside and outside monocytes/macrophages, endothelial cells, as well as in the extracellular matrix. A similar staining pattern using immunohistochemistry could be obtained for MPO. The colocalization of immunoreactive MPO and HOCl-modified-epitopes in serial sections of human atheroma (type IV), fibroatheroma (type V) and complicated (type VI) lesions provides further convincing evidence for MPO/H2O2/halide system-mediated oxidation of (lipo)proteins under in vivo conditions. We propose that MPO could act as an important link between the development of atherosclerotic plaque in the artery wall and chronic inflammatory events.

Journal ArticleDOI
TL;DR: Observations of increased HDL cholesteryl ester uptake and reduced cellular cholesterol efflux suggest that displacement of apolipoprotein A-I by SAA results in considerable altered metabolic properties of its main physiological carrier.
Abstract: The serum amyloid A (SAA) family of proteins is encoded by multiple genes that display allelic variation and a high degree of homology in mammals. Triggered by inflammation after stimulation of hepatocytes by lymphokine-mediated processes, the concentrations of SAA may increase during the acute-phase reaction to levels 1000-fold greater than those found in the noninflammatory state. In addition to its role as an acute-phase reactant, SAA (104 amino acids, 12 kDa) is considered to be the precursor protein of secondary reactive amyloidosis, in which the N-terminal portion is incorporated into the bulk of amyloid fibrils. However, the association with lipoproteins of the high-density range and subsequent modulation of the metabolic properties of its physiological carrier appear to be the principal role of SAA. Because SAA may displace apolipoprotein A-I, the major protein component of native high density lipoprotein (HDL), during the acute-phase reaction, the present study was aimed at (1) investigating binding properties of native and acute-phase (SAA-enriched) HDL by J774 macrophages, (2) elucidating whether the presence of SAA on HDL particles affects selective uptake of HDL-associated cholesteryl esters, and (3) comparing cellular cholesterol efflux mediated by native and acute-phase HDL. Both the total and the specific binding at 4 degrees C of rabbit acute-phase HDL were approximately 2-fold higher than for native HDL. Nonlinear regression analysis revealed K(d) values of 7.0 x 10(-7) mol/L (native HDL) and 3.1 x 10(-7) mol/L (acute-phase HDL), respectively. The corresponding B(max) values were 203 ng of total lipoprotein per milligram of cell protein (native HDL) and 250 ng of total lipoprotein per milligram of cell protein (acute-phase HDL). At 37 degrees C, holoparticle turnover was slightly enhanced for acute-phase HDL, a fact reflected by 2-fold higher degradation rates. In contrast, the presence of SAA on HDL specifically increased (1. 7-fold) the selective uptake of HDL cholesteryl esters from acute-phase HDL by J774 macrophages, a widely used in vitro model to study foam cell formation and cholesterol efflux properties. Although ligand blotting experiments with solubilized J774 membrane proteins failed to identify the scavenger receptor-BI as a binding protein for both native and acute-phase HDL, 2 binding proteins with molecular masses of 100 and 72 kDa, the latter comigrating with CD55 (also termed decay-accelerating factor), were identified. During cholesterol efflux studies, it became apparent that the ability of acute-phase HDL with regard to cellular cholesterol removal was considerably lower than that for native HDL. This was reflected by a 1.7-fold increase in tau/2 values (22 versus 36 hours; native versus acute-phase HDL). Our observations of increased HDL cholesteryl ester uptake and reduced cellular cholesterol efflux (acute-phase versus native HDL) suggest that displacement of apolipoprotein A-I by SAA results in considerable altered metabolic properties of its main physiological carrier. These changes in the apolipoprotein moieties appear (at least in the in vitro system tested) to transform an originally antiatherogenic into a proatherogenic lipoprotein particle.

Journal ArticleDOI
TL;DR: In this article, the Boltzmann simplex simulated annealing (BSSA) algorithm was used to find the global minimum of the hypersurface of colloidal particles.
Abstract: The structure of colloidal particles can be studied with small-angle X-ray and neutron scattering (SAXS and SANS). In the case of randomly oriented systems, the indirect Fourier transformation (IFT) is a well established technique for the calculation of model-free real-space information. Interaction leads to an overlap of inter- and intraparticle scattering effects, preventing most detailed interpretations. The recently developed generalized indirect Fourier transformation (GIFT) technique allows these effects to be separated by assuming various models for the interaction, i.e. the so-called structure factors. The different analytical behaviour of these structure factors from that of the form factors, describing the intraparticle scattering, allows this separation. The mean-deviation surface is defined by the quality of the fit for different parameter sets of the structure factor. Its global minimum represents the solution. The former non-linear least-squares approach has proved to be inefficient and not very reliable. In this paper, the incorporation of the completely different Boltzmann simplex simulated annealing (BSSA) algorithm for finding the global minimum of the hypersurface is presented. This new method increases not only the calculation speed but also the reliability of the evaluation.

Journal ArticleDOI
TL;DR: It is indicated that HOE 901 achieves better control of fasting glucose and HbA1c levels over 4 weeks, and Hoe 901 has a possible safety benefit in terms of nocturnal hypoglycemia.
Abstract: OBJECTIVE: HOE 901 (Hoechst Marion Roussel, Frankfurt, Germany) is a biosynthetic insulin with a prolonged action. The aim of this study was to compare the effect of the long-acting insulin analog HOE 901 with NPH insulin regarding glycemic control in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 333 type 1 diabetic patients were enrolled in this multinational parallel group trial. Subjects were randomized either to two different formulations of HOE 901 (the formulations differed only in zinc content) or to NPH insulin. The study was only partially blinded because patients can distinguish HOE 901 (a clear solution) from NPH (a cloudy suspension). In addition to premeal injections of regular insulin, patients received HOE 901 at bedtime or NPH once daily at bedtime or twice daily in the morning and at bedtime. RESULTS: Fasting plasma glucose levels were significantly lower with HOE 901 (-1.88 mmol/l. P = 0.0005) as were fasting self-monitored blood glucose levels (-0.80 mmol/l, P = 0.0020). HbA1c levels also showed a significant reduction with HOE 901 (-0.14%) versus NPH (P = 0.030). The overall frequency of hypoglycemia did not differ, but the frequency of nocturnal hypoglycemia was significantly (P = 0.0037) lower with HOE 901 (36 vs. 55%). However, this effect on nocturnal hypoglycemia was significant only versus NPH once daily not NPH twice daily. The pattern of adverse events and injection site reactions with HOE 901 was similar to that with NPH. CONCLUSIONS: This study indicates that HOE 901 achieves better control of fasting glucose and HbA1c levels over 4 weeks, and HOE 901 has a possible safety benefit in terms of nocturnal hypoglycemia.

Journal ArticleDOI
01 Nov 2000-Stroke
TL;DR: MBs can be detected in more than half of the patients with pICH and appear to be quite general markers of various types of bleeding-prone microangiopathy.
Abstract: Background and Purpose —MRI is known to detect clinically silent microbleeds (MBs) in patients with primary intracerebral hemorrhage (pICH), but the frequency and diagnostic and clinical significance of this finding are still debated. Therefore, we investigated a consecutive series of pICH patients and analyzed the patterns of MB distribution in the context of clinical variables and location of the symptomatic hematoma. Methods —The study population consisted of 109 patients with pICH. There were 59 women and 50 men aged 22 to 91 years (mean 64.6 years). MRI was obtained on a 1.5-T system with use of a gradient-echo T2*-weighted sequence. A cohort of 280 community-dwelling asymptomatic elderly individuals who underwent the same imaging protocol served for comparison. Results —MBs were seen in 59 (54%) patients and ranged in number from 1 to 90 lesions (mean 14, median 6). In the majority of patients, MBs were located simultaneously in various parts of the brain, with a preference for cortical-subcortical regions (39%) and the basal ganglia/thalami (38%). There was some tendency toward a regional association between MB location and the site of the symptomatic hematoma, but we could not discern specific patterns of MB distribution. Logistic regression analysis identified MBs, periventricular hyperintensity grades, and lacunes but not risk factors as independent variables contributing to a correct classification of pICH and control individuals. Conclusions —MBs can be detected in more than half of the patients with pICH and appear to be quite general markers of various types of bleeding-prone microangiopathy.

Journal ArticleDOI
01 May 2000-Cancer
TL;DR: Because it presents as an often unrecognized lesion or in association with tubular carcinoma, to the authors' knowledge the clinical and biologic significance of this lesion has not been well established.
Abstract: BACKGROUND Mammary ductal intraepithelial neoplasia (DIN)-flat type (“clinging ductal carcinoma in situ [DCIS]”) generally is a subtle epithelial alteration characterized by one or a few layer(s) of atypical cells replacing the native epithelium. The “low power” appearance of DIN-flat type can be misinterpreted easily as “normal” because of the frequent absence of multilayered proliferation and often subtle cytologic atypia. Because it presents as an often unrecognized lesion or in association with tubular carcinoma, to the authors' knowledge the clinical and biologic significance of this lesion has not been well established. METHODS Using polymerase chain reaction, the authors examined DNA extracts from microdissected areas of 22 cases with extensive “clinging DCIS,” including 13 cases associated with infiltrating ductal carcinoma as well as 5 cases associated with more conventional types of DCIS. Eight polymorphic DNA markers with a high rate of loss of heterozygosity (LOH) in classic types of DCIS were selected to identify possible genetic alterations on chromosomes 2p, 3p, 11q, 16q, and 17q. Two cases also were used for the assessment of clonality by means of X chromosome inactivation (methylation pattern of the human androgen receptor [HUMARA] gene). RESULTS LOH was detected in 17 of 22 lesions (77%), and monoclonality was established in the 2 cases analyzed. The most common genetic alterations were at chromosomes 11q21-23.2, 16q23.1-24.2, and 3p14.2 with LOH in 50%, 45%, and 41%, respectively, of informative cases. The DIN-flat type showed the same genetic alterations (LOH) identified in adjacent in situ and infiltrating ductal carcinoma. In contrast to the DIN-flat type, the perfectly normal mammary epithelium was associated very infrequently (1 of 16 cases; 6%) with LOH. CONCLUSIONS The DIN-flat type represents one of the earliest, morphologically recognizable, neoplastic alterations of the breast. Recognition of the DIN-flat type is important not only for the early detection of intraductal neoplasia but also to prevent misinterpretation and utilization of this lesion as a normal control in studies. This distinctive lesion could be crucial as an explanation for at least part of the > 20% reported incidence rate of breast carcinoma recurrence observed despite ostensibly “negative” margins of breast biopsies. Cancer 2000;88:2072–81. © 2000 American Cancer Society.

Journal ArticleDOI
TL;DR: It is hypothesized that exercise would cause greater severity and incidence of acute mountain sickness in the early hours of exposure to altitude in the immediate aftermath of passive ascent to simulated high altitude.
Abstract: .—We hypothesized that exercise would cause greater severity and incidence of acute mountain sickness (AMS) in the early hours of exposure to altitude. After passive ascent to simulated high altitu...

Journal ArticleDOI
TL;DR: Lower repeatability of gait analysis data in spastic children compared to normal children is found, and restricted joint range of motion due to spasticity in the group of cerebral palsy patients may be responsible for the lower repeatability.

Journal ArticleDOI
Olaf Reich1, Sigrid Regauer1, W Urdl1, Manfred Lahousen1, Raimund Winter1 
TL;DR: ER and PR expression in LGSS is heterogeneous and may have implications for hormone therapy in the management of these tumours, suggesting that ER and PR should be routinely quantified inLGSSs by immunohistochemical methods.
Abstract: We analysed oestrogen receptor (ER) and progesterone receptor (PR) expression in a retrospective series of 21 low-grade endometrial stromal sarcomas (LGSSs). Archival formalin-fixed and paraffin-embedded material was analysed by immunohistochemistry. ER and PR were measured with monoclonal antibodies and the peroxidase-antiperoxidase method and a score was calculated as for breast carcinoma based on both the percentage of positive tumour cell nuclei and the staining intensity. ER were seen in 15 (71%) and PR in 20 (95%) of tumours respectively. ER expression was scored as high in three (14%), moderate in four (19%), and low in eight (38%) tumours. Six (29%) tumours did not stain for ER and all of these were positive for PR. PR expression was scored as high in eight (38%), moderate in ten (47%) and weak in two (10%) LGSSs. Only one (5%) LGSS did not stain for PR (this tumour was positive for ER). ER and PR expression in LGSS is heterogeneous. This may have implications for hormone therapy in the management of these tumours. These results suggest that ER and PR should be routinely quantified in LGSSs by immunohistochemical methods.

Journal ArticleDOI
TL;DR: A large scale extract of the brown alga Fucus serratus was found to contain four arsenosugars (1−4) together with traces of dimethylarsinate (DMA) and arsenate by HPLC-ICP-MS as discussed by the authors.
Abstract: A large scale extract of the brown alga Fucus serratus was found to contain four arsenosugars (1–4) together with traces of dimethylarsinate (DMA) and arsenate by HPLC-ICP-MS. The extract was divided into 1500 equal subsamples which were then freeze-dried and stored at –18°C. The homogeneity of this population of subsamples was established by random sampling and quantification of total arsenic by ICP-MS (1.22 µg As ±3.2%, mean ± RSD, n = 32) and hydride generation AAS (1.27 µg As ±2.0%, n = 32), and by quantification with HPLC-ICP-MS of the individual arsenic species in 10 subsamples: arsenosugar 1, 0.10 µg As ±3.6%; arsenosugar 2, 0.086 µg As ±2.9%; arsenosugar 3, 0.62 µg As ±3.8%; arsenosugar 4, 0.40 µg As ±3.1%; dimethylarsinate, 0.005 µg As ±20%; and arsenate ca. 0.001 µg As. The identity of the arsenosugars was confirmed by LC–electrospray (ES) MS with variable fragmenter voltage which provided simultaneous elemental and molecular detection. LC-ESMS was also used to quantify the four arsenosugars, producing values within 5% (2, 3 and 4) or 14% (1) of the ICP-MS data. The subsamples of Fucus extract provide a homogeneous source of natural material containing arsenosugars for use in arsenic speciation studies.

Journal ArticleDOI
TL;DR: Behavioral changes in fighting and the development of dominance relationships were analyzed in groups of juvenile crayfish using quantitative behavioral techniques and linear hierarchies emerged which became increasingly stable over time.
Abstract: Behavioral changes in fighting and the devel- opment of dominance relationships were analyzed in groups of juvenile crayfish ( Astacus astacus) using quantitative behavioral techniques. When individuals were placed into an aquarium, the number of agonistic challenges, their mean duration, and maximum intensity reached were high initially but then decreased steadily as the hierarchy developed. In all groups, linear hierarchies emerged which became increasingly stable over time. Winning influenced subsequent fighting behavior on two distinct time scales. In the short term, recent winners be- came progressively less likely to retreat. Second, indi- viduals occupying dominant positions for days became increasingly likely to escalate to higher intensities early in the encounter. Both effects biased the outcome of fu- ture interactions such that winning enhanced further suc- cess and losing decreased an individual's subsequent chances for dominance.

Journal ArticleDOI
TL;DR: The main ideas contained in the PTAS are used to derivePTAS's for the knapsack problem and its multi-dimensional generalization which improve on the previously proposed PTAS's.