Showing papers by "University of Graz published in 1997"

Evidence that 4-Hydroxynonenal Mediates Oxidative Stress-Induced Neuronal Apoptosis

Abstract: Oxidative stress is believed to play important roles in neuronal cell death associated with many different neurodegenerative conditions (e.g., Alzheimer's disease, Parkinson's disease, and cerebral ischemia), and it is believed also that apoptosis is an important mode of cell death in these disorders. Membrane lipid peroxidation has been documented in the brain regions affected in these disorders as well as in cell culture and in vivo models. We now provide evidence that 4-hydroxynonenal (HNE), an aldehydic product of membrane lipid peroxidation, is a key mediator of neuronal apoptosis induced by oxidative stress. HNE induced apoptosis in PC12 cells and primary rat hippocampal neurons. Oxidative insults (FeSO4 and amyloid beta-peptide) induced lipid peroxidation, cellular accumulation of HNE, and apoptosis. Bcl-2 prevented apoptosis of PC12 cells induced by oxidative stress and HNE. Antioxidants that suppress lipid peroxidation protected against apoptosis induced by oxidative insults, but not that induced by HNE. Glutathione, which binds HNE, protected neurons against apoptosis induced by oxidative stress and HNE. PC12 cells expressing Bcl-2 exhibited higher levels of glutathione and lower levels of HNE after oxidative stress. Collectively, the data identify that HNE is a novel nonprotein mediator of oxidative stress-induced neuronal apoptosis and suggest that the antiapoptotic action of glutathione may involve detoxification of HNE.

Infection by Borrelia burgdorferi and cutaneous B-cell lymphoma.

Abstract: In past years, association of primary cutaneous B-cell lymphoma (CBCL) with infection by Borrelia burgdorferi has been reported in a few patients. The evidence for a pathogenetic role was based on clinical grounds or raised titre of antibodies in serum. Both methods, however, do not prove the association between the micro-organism and the CBCL, especially in countries where infection by Borrelia burgdorferi is endemic. Moreover, the exact percentage of Borrelia burgdorferi-positive CBCL is not known. We retrieved from our files 50 cases of CBCL to perform PCR analysis of Borrelia burgdorferi DNA on paraffin-embedded tissue sections. Only patients with primary CBCL were selected. In all cases, monoclonality of the infiltrate was confirmed by immunohistological pattern of immunoglobulin light chains or molecular analysis of J H gene rearrangement, or both. Specific DNA sequences of Borrelia burgdorferi were identified in cutaneous lesions from 9 patients (follicle center lymphoma: 3/20; immunocytoma: 3/4; marginal zone B-cell lymphoma: 2/20; diffuse large B-cell lymphoma: 1/6). Specificity was confirmed by Southern blot hybridisation in all positive cases. We could show that Borrelia burgdorferi DNA is present in skin lesions from a small proportion of patients (18%) with various types of CBCL. Our results may have therapeutic implications. In analogy to Helicobacter pylori-associated MALT-lymphomas, which in some cases can be cured by eradication of Helicobacter pylori infection, a proportion of CBCL may be cured with antibiotic therapy against Borrelia burgdorferi. Although yet speculative, adequate antibiotic treatment for patients with primary CBCL should be considered before more aggressive therapeutic options are applied, particularly in countries where infection by Borrelia burgdorferi is endemic. PCR analysis of Borrelia burgdorferi DNA is a fast test that should be performed in all patients with CBCL to identify those who more likely could benefit from an early antibiotic treatment.

A Reexamination of the Mechanism of the Biginelli Dihydropyrimidine Synthesis. Support for an N-Acyliminium Ion Intermediate1

Abstract: The mechansim of the three-component Biginelli dihydropyrimidine synthesis was reinvestigated using 1H and 13C NMR spectroscopy. Condensation of benzaldehyde, ethyl acetoacetate, and urea (or N-methylurea) in CD3OH according to the procedure described by Biginelli produced the expected 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylates. According to NMR measurements, there is no evidence that the first step in the Biginelli reaction is an acid-catalyzed aldol reaction of ethyl acetoacetate and benzaldehyde leading to a carbenium ion intermediate, as has been suggested previously. In contrast, all experimental evidence points to a mechanism involving an N-acyliminium ion as the key intermediate, formed by acid-catalyzed condensation of benzaldehyde and urea (or N-methylurea). Interception of this iminium ion by ethyl acetoacetate produces open-chain ureides which subsequently cyclize to the Biginelli dihydropyrimidines.

National rates and regional differences in sensitization to allergens of the standard series : Population-adjusted frequencies of sensitization (PAFS) in 40,000 patients from a multicenter study (IVDK)

Abstract: Sensitization rates to contact allergens vary between centers and are influenced by sex and age. Eliminating the latter 2 factors by standardization of data by age and sex, the present analysis addresses possible differences between centers remaining after elimination of these confounders, and analyzes other factors which might influence rates, e.g., the MOAHL index. Overall standardized rates were well within the range reported in previous studies and may be regarded as representing the rates of the "patch test population" in Central Europe (e.g., nickel sulfate 12.9%, fragrance mix 10.5%, balsam of Peru 7.3%, thimerosal 5.6%). For this analysis, data of those departments which contributed more than 2000 patients, or of those with extreme proportions concerning sex, age and occupational cases were selected. Patients from these 10 departments differed considerably with regard to the items of the MOAHL index and with regard to standardized rates. The items of the MOAHL index proved to be suitable for describing different patch test populations and for explaining some differences between centers. Only 'atopic dermatitis' seems to have little influence on (standardized) rates. Face dermatitis is not yet represented in the MOAHL index, but should be included, together with age > 40 years, in an extended index (acronym: MOAHLFA). Regional allergen exposure (with striking differences between East Germany, West Germany and, to a lesser extent, Austria) seems to have a great influence on the sensitization pattern observed in a department. In addition, sociological factors may influence sensitization rates, which is exemplified by high rates of nickel allergy in a socially defined subgroup. Future studies should focus on these factors, as well as on factors concerning patch test practices and quality control.

The Quadratic Assignment Problem

Abstract: The quadratic assignment problem (QAP) was introduced by Koopmans and Beckmann in 1957 as a mathematical model for the location of a set of indivisible economical activities [113]. Consider the problem of allocating a set of facilities to a set of locations, with the cost being a function of the distance and flow between the facilities, plus costs associated with a facility being placed at a certain location. The objective is to assign each facility to a location such that the total cost is minimized. Specifically, we are given three n x n input matrices with real elements F = (f ij ), D = (d kl ) and B = (b ik ), where f ij is the flow between the facility i and facility j, d kl is the distance between the location k and location l, and b ik is the cost of placing facility i at location k. The Koopmans-Beckmann version of the QAP can be formulated as follows: Let n be the number of facilities and locations and denote by N the set N = {1, 2,..., n}.

The effects of programmed administration of human parathyroid hormone fragment (1-34) on bone histomorphometry and serum chemistry in rats

Abstract: PTH treatment can result in dramatic increases in cancellous bone volume in normal and osteopenic rats. However, this potentially beneficial response is only observed after pulsatile treatment; continuous infusion of PTH leads to hypercalcemia and bone abnormalities. The purpose of these studies was to determine the optimal duration of the PTH pulses. A preliminary study revealed that human PTH-(1-34) (hPTH) is cleared from circulation within 6 h after sc administration of an anabolic dose of the hormone (80 microg/kg). To establish the effects of gradually extending the duration of exposure to hPTH without increasing the daily dose, we programmed implanted Alzet osmotic pumps to deliver the 80 microg/kg x day dose of the hormone during pulses of 1, 2, and 6 h/day, or 40 microg/kg x day continuously. Discontinuous infusion was accomplished by alternate spacing of external tubing with hPTH solution and sesame oil. After 6 days of treatment, we evaluated serum chemistry and bone histomorphometry. As negative and positive controls, groups of rats received pumps that delivered vehicle only and 80 microg/kg x day hPTH by daily sc injection, respectively. Dynamic and static bone histomorphometry revealed that the daily sc injection and 1 h/day infusion dramatically increased osteoblast number and bone formation in the proximal tibial metaphysis, whereas longer infusion resulted in systemic side-effects, including up to a 10% loss in body weight, hypercalcemia, and histological changes in the proximal tibia resembling abnormalities observed in patients with chronic primary hyperparathyroidism, including peritrabecular marrow fibrosis and focal bone resorption. Infusion for as little as 2 h/day resulted in minor weight loss and changes in bone histology that were intermediate between sc and continuous administration. The results demonstrate that the therapeutic interval for hPTH exposure is brief, but that programmed administration of implanted hormone is a feasible alternative to daily injection as a route for administration of the hormone.

Optical sensors for determination of heavy metal ions

Abstract: A review is given on optical means for single shot testing (“probing”) as well as continuous monitoring (“sensing”) of heavy metal ions (HMs). Following an introduction into indicator based approaches, we discuss the types of indicator dyes and polymeric supports used, as well as existing sensing schemes for HMs. The wealth of information is compiled in the form of tables and critically reviewed. Notwithstanding the tremendous work performed so far, it is obvious that still severe limitations do exist in terms of selectivity, limits of detection, dynamic ranges, applicability to specific problems, and reversibility. On the other hand, such sensors have found — and will find — their application whenever rapid and cost-effective testing is required, where personnel is scarce or unskilled, and in field tests. Despite their limitations, the number of such sensors (and of irreversible “probes”) for HMs is likely to increase in future.

Serotonin and aggressive motivation in crustaceans: Altering the decision to retreat

Abstract: In crustaceans, as in most animal species, the amine serotonin has been suggested to serve important roles in aggression. Here we show that injection of serotonin into the hemolymph of subordinate, freely moving animals results in a renewed willingness of these animals to engage the dominants in further agonistic encounters. By multivariate statistical analysis, we demonstrate that this reversal results principally from a reduction in the likelihood of retreat and an increase in the duration of fighting. Serotonin infusion does not alter other aspects of fighting behavior, including which animal initiates an encounter, how quickly fighting escalates, or which animal eventually retreats. Preliminary studies suggest that serotonin uptake plays an important role in this behavioral reversal.

Microhabitat Use, Trophic Patterns, and the Evolution of Brain Structure in African Cichlids

Abstract: The species assemblages of cichlids in the three largest African Great Lakes are among the richest concentrations of vertebrate species on earth. The faunas are broadly similar in terms of trophic div

Primary Cutaneous Marginal Zone B-Cell Lymphoma: A Recently Described Entity of Low-Grade Malignant Cutaneous B-Cell Lymphoma

Abstract: Recently a new classification of primary cutaneous B-cell lymphomas (PCBCLs) has been proposed by the European Organization for Research and Treatment of Cancer (EORTC)--Cutaneous Lymphoma Project Group. The marginal zone B-cell lymphomas (MZLs) were not included as a distinct entity because of insufficient experience and controversial opinions. We have studied 32 patients (M:F ratio 1.5:1; age range 25-93 years; mean age 49.6 years; median age 50 years) to determine the diagnostic criteria of primary cutaneous MZL and the relationship with other low-grade malignant PCBCLs. For comparison, three patients with immunocytoma were included in the study. Clinically, patients presented with solitary or clustered reddish or red-brown papules, nodules, and plaques, sometimes surrounded by an erythematous halo. Histopathologic sections showed nodular or diffuse infiltrates involving the dermis and subcutaneous fat. Cytomorphologically small to medium-sized cells with indented nuclei and abundant pale cytoplasm (marginal zone cells, centrocyte-like cells) predominated. In addition, scattered blasts, lymphoplasmacytoid cells, and plasma cells were observed below the epidermis and at the periphery of the infiltrates. Reactive germinal centers were present in 75% of the cases. The three cases of immunocytoma showed a more monomorphous pattern with predominance of lymphoplasmacytoid cells. The marginal zone cells showed a CD20+, CD79a+, CD5- and Bcl-2+ immunophenotype. They expressed immunoglobulin G in the majority of the cases. Staining with the monocytoid B cell-related antibody KiM1p gave positive results in all specimens with a typical intracytoplasmic granular pattern. A monoclonal distribution of immunoglobulin light chains was observed in marginal zone cells in 75% of the cases. Germinal centers, when present, were either polyclonal or negative for both kappa and lambda light chains. Monoclonal rearrangement of the JH gene was detected via polymerase chain reaction (PCR) in 18 of 26 investigated specimens. Analysis in 12 patients of the bcl-2/immunoglobulin heavy chain gene rearrangement using PCR yielded negative results. Lesions were treated by surgical excision followed in some patients by local radiotherapy. Systemic antibiotic therapy was administered to three patients, with good response in two. The prognosis is excellent. After a mean follow-up of 47.9 months (range 6-252; median 24) all patients are alive without signs of systemic lymphoma. Primary cutaneous MZL represents a distinct clinicopathologic subtype of low-grade malignant PCBCL.

Weakly coupled bound states in quantum waveguides

Abstract: We study the eigenvalue spectrum of Dirichlet Laplacians which model quantum waveguides associated with tubular regions outside of a bounded domain. Intuitively, our principal new result in two dimensions asserts that any domain R obtained by adding an arbitrarily small "bump" to the tube a0 = R x ( 0 , l ) (i.e., 2 no, R C W2 open and connected, R = Ro outside a bounded region) produces a t least one positive eigenvalue below the essential spectrum [7r2, m) of the Dirichlet Laplacian -A:. For /R\Ro/ sufficiently small ( 1 . / abbreviating Lebesgue measure), we prove uniqueness of the ground state En of -A: and derive the "weak coupling" result En = 7r2 + 0(/R\C20/3) using a Birman-Schwinger-type T ~ / Q \ R O / ~ analysis. As a corollary of these results we obtain the following surprising fact: Starting from the tube flo with Dirichlet boundary conditions at aRo, replace the Dirichlet condition by a Neumann boundary condition on an arbitrarily small segment (a, b) x (1). a < b, of aRo. If H(a , b) denotes the resulting Laplace operator in L ' (R~) , then H(a , b) has a discrete eigenvalue in [7r2/4,7r2) no matter how small lb a1 > 0 is. Our goal in this paper is to study the bound state spectra of the Dirichlet Laplacian -A: for open regions R c Rn which are tubes outside of a bounded region (quantum waveguides). (Following the traditional notation in quantum physics, we denote the Laplacian by -A as opposed to A in the following.) In particular, let RocR2 be defined by Ro=R x (0 , l ) . Consider open connected sets R such that: (i) For some R > 0, R n{x E R2 I 1x1 > R) =Ron{x E R2 I 1x1 > R). (ii) R, cR, R, #a. Because of condition (i), (1) aess(-~:) = fless(-Ag,) = [.ir2, 00). Then one of our main goals will be to prove Received by the editors November 13, 1995. 1991 Mathematics Subject Classification. Primary 81Q10, 35P15; Secondary 47A10, 35510.

Hypercyclic and chaotic semigroups of linear operators

Abstract: We investigate hypercyclic and chaotic behavior of linear strongly continuous semigroups. We give necessary and sufficient conditions on the semigroup to be hypercyclic, and sufficient conditions on the spectrum of an operator to generate a hypercyclic semigroup. A variety of examples is provided.

4-Hydroxynonenal, a product of lipid peroxidation, inhibits dephosphorylation of the microtubule-associated protein tau.

Abstract: In Alzheimer's disease (AD) the microtubule-associated protein tau is excessively phosphorylated in degenerating neurons, but the mechanisms underlying the increased phosphorylation are unknown. Recent findings suggest that oxidative stress, and membrane lipid peroxidation in particular, contributes to the neurodegenerative process in AD. We now report that following exposure of cultured rat hippocampal neurons to 4-hydroxynonenal (HNE), an aldehydic product of membrane lipid peroxidation, tau is resistant to dephosphorylation. Immunocytochemical and Western blot analyses using phosphorylation-sensitive tau antibodies showed that HNE treatment causes a moderate increase in basal levels of tau phosphorylation, and prevents tau dephosphorylation by alkaline phosphatase in neurons pretreated with the phosphatase inhibitor okadaic acid. Studies with anti-HNE antibodies showed that HNE binds directly to tau, and that HNE immunoreactivity localizes to cell bodies and axons, cell compartments that contain tau. These data suggest a role for HNE in altered tau phosphorylation and neurofibrillary degeneration in AD.