julilili42/papers huggingface dataset:
Genetic impact of pathogenesis and prognosis of ANCA-associated vasculitides.
2004-01-01

Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and the Churg-Strauss syndrome (CSS) are small vessel vasculitides associated with anti-neutrophil cytoplasmic antibodies (ANCA). Cytoplasmic (c)-ANCA mainly target proteinase 3 (PR3) and are often observed in WG patients, while perinuclear (p)-ANCA predominantly bind to myeloperoxidase (MPO) and are common in patients with MPA and CSS. It is suspected that a genetic background contributes to disease formation since the diseases are more prevalent in Caucasian populations. This article provides a detailed review of the genetic impact of the pathogenesis and prognosis of ANCA-associated vasculitides. Alpha-1 anti-trypsin is the physiological inhibitor of PR3 and carriage of the defective allele PI*Z was observed as the first genetic risk factor for the development of PR3-ANCA-associated vasculitis. Expression analyses have revealed that PR3 surface expression is genetically determined. Elevated levels of PR3 expression have been observed in WG patients and high levels of PR3 expression corresponded to increased risk of disease relapses. Furthermore, the non-carriage of CTLA-4 allele 86 was associated with WG formation, while homocygotic carriage of the CCR5 allele delta 32 seemed to prevent ANCA-negative WG. MPO-ANCA vasculitides were associated with certain alleles of CD18 polymorphisms. Lack of or only weak allelic associations of ANCA-vasculitides with polymorphic cytokine, HLA, and Fcgamma receptor genes have been shown. Although, in practice, it is sometimes difficult to differentiate between WG and MPA, the diseases appear to be based on different genetic backgrounds.
Species-Specific Ultrastructure of Neuronal Lipofuscin in Hippocampus and Neocortex of Subhuman Mammals and Humans
2004-01-01

Lipofuscin represents an integral part of neurons and glial cells in mammals and in submammalian species. It is a special lysosomal organelle, takes part of cellular metabolism, and is a structural expression of catabolic pathways. Species-specific differences of lipofuscin indicate metabolic differences of the relevant neurons. The authors have studied the ultrastructure of neuronal lipofuscin in the hippocampus and cerebral neocortex of dogs, horses, cows, elephants, rats, mice, apes, and humans to answer the question of species-specific differences of this organelle. Paraffin sections of formalin-fixed material were investigated by hematoxylin-eosin and PAS staining, by fluorescence microscopy for autofluorescence, with a laser scanning confocal microscope and by electron microscopy. In the animals studied and in humans the lipofuscin displayed, in addition to the general trilaminar substructure, species-specific appearances. No differences were found in the lipofuscin structure between neocortical and hippocampal neurons of the separate animal species. In contrast, in humans, neurons of the hippocampus showed a particular lipofuscin structure, not only different from the neocortical one, but also with differences between CA1 and CA3/4 sectors. Interestingly, in apes a transitional situation was found with slight differences between neocortical and hippocampal lipofuscin, especially in the rhesus monkey. This peculiarity was corroborated by the distribution of special pentilaminar linear structures in the lipofuscin pigment in all animals, only sparsely in the rhesus monkey and not in humans. The results indicate that lipofuscin ultrastructure of neocortical and hippocampal neurons is species specific and that lipofuscin in the human hippocampal neurons displays structures characteristic of man differing from the neocortical neuronal lipofuscin. The neuronal lipofuscin of apes, especially of the rhesus monkey displays structures in between humans and lower mammals. Nothing is known about the functional significance of these findings. They may indicate metabolic and/or functional characteristics of the relevant neurons.
Functional characterization of the postulated intramolecular sphingolipid activator protein domain of human acid sphingomyelinase
2004-01-01

Degradation of membrane-bound sphingomyelin to phosphorylcholine and ceramide is catalyzed by the water-soluble lysosomal acid sphingomyelinase (A-SMase). The presence of sphingolipid activator proteins (Saps: saposins A-D; GM2 activator) is not essential to mediate this reaction at the water-lipid interface in vivo . A hypothesis based on amino acid sequence alignments suggests that the enzyme possesses an N-terminal saposin-homologous domain, which may facilitate the enzymatic reaction at the interface. We mutated one homologous and three conserved amino acid residues of this domain and studied the activity of the variant enzymes using different sphingomyelin degradation assays. A variant with an exchange of a conserved amino acid residue, Pro153Ala, still exhibited enzyme activity of approximately 52% of normal in a detergent-containing micellar assay, but only 13% of normal in a detergent-free liposomal assay system, which suggests that the Sap-homologous domain fulfills membrane-disturbing functions. Addition of saposin C to the liposomal assay mixtures increased the Pro153Ala variant sphingomyelinase activity to 46% of normal, indicating that the variant saposin-like domain can be substituted by the presence of the sphingolipid activator protein. On the other hand, the addition of saposin C did not result in complete restoration of the variant activity. Thus, the Sap-like domain may also have another role, e.g., to stabilize the fold of acid sphingomyelinase, which cannot be compensated by the presence of saposin C or a detergent. Such an essential second function of the saposin-like domain as an integral part of acid sphingomyelinase is confirmed by our observation that the Lys118Glu, Cys120Ser and Cys131Ser variants were almost completely devoid of activity in the detergent-containing micellar assay system as well as in the liposomal assay system in the presence of saposin C.
Cl<sup>-</sup> Channel Blockers NPPB and Niflumic Acid Blunt Ca<sup>2+</sup>-induced Erythrocyte ‘Apoptosis’
2004-01-01

Exposure to Ca2+ ionophore ionomycin, osmotic shock, oxidative stress and glucose depletion trigger cell shrinkage and scramblase-mediated phosphatidylserine exposure at the outer leaflet of the erythrocyte cell membrane. The effects are partially due to activation of GARDOS channels and subsequent cellular K+ loss leading not only to cell shrinkage but also participating in the triggering of erythrocyte scramblase. As conductive loss of K+ would depend on the parallel loss of anions we hypothesised that activation of scramblase is similarly dependent on the activity of Cl- channels. To test this hypothesis, we used Cl- channel blockers NPPB and niflumic acid. It is shown here that treatment of erythrocytes with 1 microM ionomycin leads to cellular K+ loss, decrease of hematocrit and decrease of forward scatter in FACS analysis reflecting cell shrinkage as well as increase of annexin positive cells reflecting phosphatidylserine exposure. Those events were significantly blunted in the presence of 100 microM NPPB by 34% (K+ loss), 45% (hematocrit), 32% (forward scatter) and 69% (annexin binding), or in the presence of 100 microM niflumic acid by 15% (forward scatter) and 45% (annexin binding), respectively. Moreover, oxidative stress triggered annexin binding which was again significantly inhibited (by 51%) in the presence of 100 microM NPPB. In conclusion, Cl- channels presumably participate in the regulation of erythrocyte 'apoptosis'.
The Innate Immune Response in the Central Nervous System and Its Role in Glioma Immune Surveillance
2004-01-01

The innate immune system encompasses natural killer (NK) cells, macrophages and granulocytes, the complement system and antimicrobial peptides. Recognition pathways of the innate immune system include microbial non-self recognition, missing-self recognition and induced- self recognition. The central nervous system (CNS) participates in responses of the innate immune system. However, immune inhibitory and anti-inflammatory mechanisms physiologically outbalance and counteract immune activity and thereby limit immune-mediated tissue damage in the brain. Human gliomas appear to take advantage of this immunosuppressive milieu. Moreover, glioma cells themselves interfere with anti-tumor immune responses by expressing immune inhibitory cell surface molecules, such as HLA-G, or by releasing soluble immunosuppressants such as transforming growth factor (TGF)-beta. Yet, although glioma cells exhibit all cellular features of malignancy, these tumors very rarely metastasize outside the brain, raising the possibility of immune-mediated control of these cells outside, but not inside, the brain. Accordingly, activating the innate immune system by forcing glioma cells to express danger signals such as NKG2D ligands is a promising strategy of immunotherapy for these tumors.
Inversion strategy in crosshole radar tomography using information of data subsets
2004-01-01

Detecting discrete anomalies, such as cavities or tunnels, is an important application of crosshole radar tomography. However, crosshole tomographic inversion results are frequently ambiguous, showing smearing effects and inversion artifacts. These ambiguities lead to uncertainties in interpretation; hence, the size and position of anomalies can only be interpreted with limited accuracy and reliability. We present an inversion strategy for investigating discrete anomalies with crosshole radar tomography. In addition to the full traveltime data set, we use subsets of specified ray‐angle intervals for tomographic inversion. By analyzing inversion results from different ray‐angle intervals, a more accurate interpretation of anomalies is possible. The second step of our strategy is to develop a good inhomogeneous starting model from joint interpretation of the inversion results from different subsets. The third step is to invert the full data set using this new starting model and to evaluate the inversion results by analyzing the distributions of mean square traveltime residuals with respect to the ray angles. We use a synthetic model with two discrete anomalies located roughly at the same depth to demonstrate and evaluate our approach. This inversion strategy is also applied to a field data set collected to investigate karst cavities in limestone. From the inversion results of both examples, we show that horizontal smearing of anomalies can be reduced by eliminating near‐horizontal rays. A good starting model can be obtained based on the joint interpretation of the inversion results of the different subsets; it leads to a high‐resolution final image of the full data set.
Excited state properties of monomeric and dimeric axially bridged indium phthalocyanines upon UV–Vis laser irradiation
2004-01-01

This contribution presents a series of results from different photophysical experiments realized at both resonance and off-resonance conditions on a group of newly synthesized cofacial bridged phthalocyanines. The most relevant aspect of the present study is the identification of a common photoexcited state, which can be reached by the same compound via two substantially different irradiation pathways.
Habituation of the Acoustic and the Tactile Startle Responses in Mice: Two Independent Sensory Processes.
2004-01-01

To test whether habituation is specific to the stimulus modality, the authors analyzed cross-habituation between the tactile startle response' (TSR) and the acoustic startle response (ASR). The acoustic artifacts of airpuffs used to elicit the TSR were reduced by using a silencer and were effectively masked by background noise of 90-100 dB sound-pressure level. ASR was elicited by 14-kHz tones. TSR and ASR habituated in DBA and BALB mice: both the TSR and ASR habituated to a greater extent in DBA mice than in BALB mice. In both strains, habituation of the TSR did not generalize to the ASR, and vice versa. From this, the authors concluded that habituation of startle is located in the sensory afferent branches of the pathway.
Response-related fMRI of veridical and false recognition of words
2004-01-01

Abstract Objectives. – Studies on the relation between local cerebral activation and retrieval success usually compared high and low performance conditions, and thus showed performance-related activation of different brain areas. Only a few studies directly compared signal intensities of different response categories during retrieval. During verbal recognition, we recently observed increased parieto-occipital activation related to false alarms. The present study intends to replicate and extend this observation by investigating common and differential activation by veridical and false recognition. Methods. – Fifteen healthy volunteers performed a verbal recognition paradigm using 160 learned target and 160 new distracter words. The subjects had to indicate whether they had learned the word before or not. Echo-planar MRI of blood-oxygen-level-dependent signal changes was performed during this recognition task. Words were classified post hoc according to the subjects’ responses, i.e. hits, false alarms, correct rejections and misses. Response-related fMRI-analysis was used to compare activation associated with the subjects’ recognition success, i.e. signal intensities related to the presentation of words were compared by the above-mentioned four response types. Results. – During recognition, all word categories showed increased bilateral activation of the inferior frontal gyrus, the inferior temporal gyrus, the occipital lobe and the brainstem in comparison with the control condition. Hits and false alarms activated several areas including the left medial and lateral parieto-occipital cortex in comparison with subjectively unknown items, i.e. correct rejections and misses. Hits showed more pronounced activation in the medial, false alarms in the lateral parts of the left parieto-occipital cortex. Conclusions. – Veridical and false recognition show common as well as different areas of cerebral activation in the left parieto-occipital lobe: increased activation of the medial parietal cortex by hits may correspond to true recognition, increased activation of the parieto-occipital cortex by false alarms may correspond to familiarity decisions. Further studies are needed to investigate the reasons for false decisions in healthy subjects and patients with memory problems.
An Interleukin-6 Promoter Variant Is Not Associated with an Increased Risk for Alzheimer’s Disease
2004-01-01

Recent studies have implicated interleukin-6 (IL-6) in the pathogenesis of Alzheimer’s disease (AD). Neuro-inflammatory processes surrounding the amyloid plaques contribute to the progression of AD-related neurodegeneration. IL-6 is a multifunctional inflammatory cytokine which possibly acts as a mediator in the local immune response in the brain of AD patients. In this study we investigated whether the risk of developing AD is altered in carriers of the C allele of a G/C polymorphism at position –174. 113 AD patients and 108 age- and gender-matched nondemented control subjects were analysed. Genotyping of IL-6 was performed using standard PCR and restriction fragment length polymorphism methods. The results were adjusted for age, gender and apolipoprotein E &amp;#917;4 status. There was no evidence for an association between the polymorphism and the risk of developing AD. No evidence of an earlier age at onset for carriers of the C allele was evaluated. We conclude that IL-6 (–174) polymorphism does not influence the risk of developing AD in our cohort.
Current aspects of hearing loss from occupational and leisure noise.
2004-01-01

Hearing loss from occupational and leisure noise numbers amongst the most frequent causes of an acquired sensorineural hearing loss. Here we present a review of up-to-date findings on the pathophysiology of acoustic injury to the inner ear, with special attention being paid to its molecular-biological and genetic aspects. Epidemiological aspects shall also be dealt with, as shall the roles of lacking recovery from occupational noise due to additional exposure by leisure noise and the combined exposure of noise and chemicals. Based on the epidemiological and pathophysiological findings and against the background of published animal-experimental, pre-clinical and clinical findings, the various approaches for prevention, protection and therapeutic intervention with acoustic trauma are discussed. Pharmacological strategies involving anti-oxidative, anti-excitotoxic and anti-apoptotic substances as well as non-pharmacological strategies like "sound conditioning" are given attention. Furthermore, systemic and local substance application as well as the therapy of acute acoustic trauma and chronic hearing problems (including modern therapy forms for comorbidities such as tinnitus) shall be delved into.
The Elementary Process of Bremsstrahlung
2004-01-01

Abstract In this report we review the experimental and theoretical developments concerning the elementary process of electron bremsstrahlung. The term “elementary process” means that not only the emitted bremsstrahlung photons are considered but also the partinent decelerated electrons. Experimentally the elementary process is observed by detecting the photons in coincidence with outgoing electrons scattered into a particular direction. The results of such electron-photon coincidence experiments yield stringent tests for theoretical predictions of the fully differential cross section. Much deeper insight into the bremsstrahlung process is achieved by also taking into account polarization variables such as the spin orientation of the incoming electron or the polarization of the emitted photon. Thus conspicuous effects of the weak spin-orbit interaction can be observed which are usually masked in non-coincidence experiments. Bremsstrahlung is produced not only in the Coulomb field of an atomic nucleus but also in a collision between an incoming electron and an atomic electron which then is ejected. By using the electron-phonon coincidence technique it is possible to differentiate exactly between electron-electron bremsstrahlung and electron-nucleus bremsstrahlung. All coincidence experiments done for studying the elementary bremsstrahlung process have been performed in the energy region of a few hundred keV. In the MeV to GeV region the coincidence method is mainly used to test radiative corrections from quantum electrodynamics or to obtain “monochromatic” tagged photon beams for further applications.
Aspochalamins A-D and Aspochalasin Z Produced by the Endosymbiotic Fungus Aspergillus niveus LU 9575: I. Taxonomy, Fermentation, Isolation and Biological Activities
2004-01-01

Aspochalamins A-D, a family of new cytochalasan antibiotics have been isolated from Aspergillus niveus, an endosymbiotic fungus isolated from the gut of a woodlouse belonging to the family Trichoniscidae. Besides aspochalamins, aspochalasin Z, a new member of the aspochalasin family, as well as the known mycotoxins aspochalasin D and citreoviridins A/C and B were isolated from the mycelium. Aspochalamins showed cytostatic effects towards various tumor cell lines and a weak antibacterial activity against Gram-positive bacteria.
Analysis of IgG with specificity for variant surface antigens expressed by placental Plasmodium falciparum isolates.
2004-01-01

Recognition of placental parasites shows a parity- and sex- dependent pattern, like that previously observed in laboratory strains selected to bind to CSA. Placental infections at delivery in primiparous women appear to be sufficient to induce functional antibodies which can both recognize the surface of the infected erythrocytes as well as block their binding to CSA. The correlation between serum reactivities of placental field isolates from different geographic locations and collected at different times is indicative of the conserved nature of the antigen(s) mediating PAM.
Object-oriented modeling and synthesis of SystemC specifications
2004-01-01

The constantly increasing complexity of today's systems demands specifications on highest levels of abstraction. In addition to a transition towards the system-level more elaborate techniques are necessary to close a growing productivity gap. Our solution to this problem is the application of the object-oriented programming paradigm together with the de facto industry standard SystemC. We show that this approach is feasible and present the integration of SystemC into a continuous object-oriented design flow. The design flow includes modeling with UML, hardware/software partitioning and synthesis of object-oriented specifications. We support our claim by results from a case study.
Aspochalamins A-D and Aspochalasin Z Produced by the Endosymbiotic Fungus Aspergillus niveus LU 9575: II. Structure Elucidation
2004-01-01

The structures of new cytochalasan fungal metabolites aspochalamins A-D have been elucidated by ESI-FTICR-MS, NMR spectroscopy, and chiral amino acid analysis. Aspochalamins A-D consist of different aspochalasin skeletons connected at position C-19 to the N terminus of the tripeptidic moiety amide anthranoyl-L-alanine-E-didehydrotryptamide. Furthermore, the structure of a new aspochalasin analog, aspochalasin Z, was derived from its molecular mass and NMR data as 10-isopropyl-14-methyl[11]-cytochalasa-6Z,13E,19E-triene-1,21-dione.
Is Sentinel Lymph Node Biopsy of Therapeutic Relevance for Melanoma?
2004-01-01

&lt;i&gt;Introduction:&lt;/i&gt; It is still unclear whether sentinel lymph node biopsy (SLNB) has an effect on the survival or recurrence-free survival of patients. It would be necessary to draw comparisons between patients with SLNB (or with selective lymph node dissection in the case of positive SLNB) and patients without SLNB who underwent only close clinical and sonographic follow-up. To date no results from prospective, randomized studies of SLNB are available. &lt;i&gt;Material and Methods:&lt;/i&gt; Patients with SLNB (n = 283) and patients in clinical stage I and II with close follow-up examinations only (n = 3,514) were studied retrospectively in this investigation with regard to prognostic factors established in the literature: sex, age, tumor thickness, histological tumor type, ulceration and localization. &lt;i&gt;Results:&lt;/i&gt; Multivariate analysis showed an independent significant advantage with regard to survival when SLNB had been performed (p = 0.017). Compared with patients in clinical stage I and II with close follow-up only (n = 2,617), patients in stage I with negative SLNB (n = 238) had a significantly lower melanoma-related mortality (p = 0.0042) and, especially, fewer recurrences in the regional lymph node station area (p = 0.0026). With regard to survival without distant metastases, patients with positive SLNB (n = 33) did not significantly benefit by comparison with patients who developed lymph node metastasis identified clinically or sonographically later during follow-up examinations (n = 246; p = 0.0084). &lt;i&gt;Conclusion:&lt;/i&gt; In the relatively short follow-up period after SLNB, patients for whom SLNB had been performed had on the whole a prognostic advantage over patients who were subject only to close follow-up monitoring. Patients for whom subclinical lymph node metastases had been removed as the result of a positive SLNB did not have a better prognosis than patients without SLNB who had developed lymph node metastases within the follow-up period.