julilili42/papers huggingface dataset:
Amyloidogenicity and cytotoxicity of islet amyloid polypeptide
2001-01-01

Insoluble amyloid formation by islet amyloid polypeptide (IAPP) in the islets of Langerhans of the pancreas is a major pathophysiological feature of noninsulin dependent diabetes mellitus (NIDDM) or type II diabetes. Because in vivo formed amyloid colocalizes with areas of cell degeneration and IAPP amyloid aggregates are cytotoxic per se, the process of IAPP amyloid formation has been strongly associated with the progressive pancreatic cell degeneration and thus much of the pathology of type II diabetes. IAPP is a pancreatic polypeptide of 37 residues that, in its soluble form, is believed to play a role as a regulator of glucose homeostasis. The molecular cause and mechanism of the conversion of soluble IAPP into insoluble amyloid aggregates in vivo and its role in disease progress still remain to be clarified. Nevertheless, in the past few years significant progress has been made in understanding the amyloidogenesis pathway of IAPP in vitro and gaining insight into the structural and conformational "requirements" of IAPP amyloidogenesis and related cytotoxic effects. Importantly, several of the studies have revealed significant similarities of the above features of IAPP to other amyloidogenic polypeptides such as the beta-amyloid polypeptide Abeta. This suggests that, at the molecular level, amyloidogenesis, and possibly related cell degeneration and disease pathogenesis by completely different polypeptide sequences, may obey to common structural and conformational "rules" and follow similar molecular pathways. This review describes studies on the structural and conformational features of IAPP amyloid formation and cytotoxicity, and the application of the obtained knowledge for the understanding of the molecular mechanism of the IAPP amyloidogenesis pathway and the related cytotoxicity.
The Prevalence of Parasite Infestation and House Dust Mite Sensitization in Gabonese Schoolchildren
2001-01-01

&lt;i&gt;Background:&lt;/i&gt; Allergic diseases seem less prevalent in communities in less developed parts of the world, where parasite infections are highly prevalent. Altogether not much is known about the association between chronic infections with tissue and blood-dwelling parasites and atopy. &lt;i&gt;Methods:&lt;/i&gt; In an area in Gabon endemic for blood and tissue parasites, 520 schoolchildren were parasitologically examined and skin prick-tested for a set of common environmental aeroallergens. Levels of allergen-specific IgE and polyclonal IgE were measured. &lt;i&gt;Results:&lt;/i&gt; In schoolchildren schistosome and filarial infections increased with age, whereas malaria was more prevalent in younger children. In contrast to allergen sensitization that increased with age, skin test reactivity tended to decline. The number of children with mite-specific IgE antibodies (47%) by far exceeded the number responding to skin prick testing (11%). Mite sensitization was found to be the highest in children infected with schistosomes and/or filariae whereas skin test reactivity was lowest. The multiple logistic regression showed that the risk of a positive skin test was 8-fold higher with increasing levels of mite-specific IgE but was reduced by 72% when infected with blood stage helminths. &lt;i&gt;Conclusions:&lt;/i&gt; Chronic blood and tissue parasite infections that are often capable of modulating immune responses in the host are negatively associated with skin test reactivity in a sensitized population.
Synthesis of conjugatedbridged triphenylenes and application in OLEDs
2001-01-01

Novel conjugated-bridged triphenylene derivatives with electroluminescent properties were synthesized. A six step synthesis yields the cyanomethyltriphenylene derivatives (7a–7d). These were condensed by applying a Knoevenagel reaction with the alkoxy substituted dialdehyde 8 to PPV analogous short chain compounds 9a–9d. The products 9a–9d show bright orange to red photoluminescence. They are suitable as the emissive layer in organic light-emitting diodes (OLEDs), both in single and double layer arrangements with copper phthalocyanine as the hole transport layer.
Utilisation of Intramyocellular Lipids (IMCLs) During Exercise as Assessed by Proton Magnetic Resonance Spectroscopy (1H-MRS)
2001-01-01

Recently, a 1H-MRS method became available to quantify intramyocellular lipids (IMCL) non-invasively. Currently, little is known about the regulation of this lipid pool. During prolonged exercise of moderate intensity, non-plasma-derived fatty acids play an important role as an energy source; lipids located within the skeletal muscle are considered to be a major source for these fatty acids. To see whether IMCL are reduced by exercise, 12 male runners were studied before and after exercising at different workloads and duration. Six subjects participated in a non-competitive run (NCR), three runners in a competitive half marathon (HM, 21 km) and another three in a competitive marathon (M, 42 km). Intra- and extramyocellular lipids were quantified by 1H-MR spectroscopy in the tibialis anterior (TA) and soleus (SOL) muscles prior to and after the exercise bout. Moderate intensity (MI; 60-70% VO2max in NCR) with a mean exercise time (MET) ranging between 105-110 min decreased IMCL by 10 - 36% in both muscles. Prolonged MI exercise (MET 210-240 min; 68-70% VO2max in M) reduced IMCL by 42-57% in TA and 27 - 56% in SOL. In contrast, high intensity exercise (HI; MET 80-120 min; 83-85% VO2max in HM) did not alter IMCL in either muscle. Extramyocellular lipids (EMCL) did not show any significant change in any group. The data show that one bout of moderate-intensity (60-70% VO2max) aerobic exercise markedly reduces the IMCL in TA and SOL muscles in a time-dependent fashion as assessed by 1H-MRS. However, exercise of similar duration but higher workload (> 80% VO2max) does not reduce IMCL. These data suggest that both exercise duration and workload are important factors in determining the reduction of IMCL.
Tissue Factor – A Receptor Involved in the Control of Cellular Properties, Including Angiogenesis
2001-01-01

Summary Tissue factor (TF), the major initiator of blood coagulation, serves as a regulator of angiogenesis, tumor growth and metastasis. In several models, TF expression mediates upregulation of the proangiogenic vasular endothelial growth factor (VEGF) that can directly act on endothelial cells to promote vessel formation. This occurs through ligand binding, activation of signaling cascades, signal transduction and alteration of growth factor expression and is mediated by both, coagulation-dependent and -independent pathways. Depending on the cell type and the biological settings, TF seems to affect cellular properties through (i) factor VIIa (FVIIa)-dependent proteolysis of factor Xa (FXa) and thrombin and subsequent activation of proteinase activated receptor (PAR) -1 and PAR-2, (ii) through direct FVIIa signaling and mitogen activated protein (MAP) kinase activation, that is conferred by a not yet identified receptor, (iii) through interaction of FVII(a) proteolytic activity and signaling of the cytoplasmic domain and (iv) through cytoplasmic signaling independent of ligand binding. The role of phosphorylation of the cytoplasmic domain and the pathways controlling phosphorylation of TF remain poorly understood.
In vivo dual inhibition of cyclooxygenase and lipoxygenase by ML-3000 reduces the progression of experimental osteoarthritis: Suppression of collagenase 1 and interleukin-1? synthesis
2001-01-01

ML-3000 significantly reduced the development of lesions in experimental dog OA. The drug acts by reducing the synthesis of the inflammation mediators PGE2 and LTB4 and catabolic factors such as collagenase 1 and IL-1beta, which are known to play an important role in the pathophysiology of OA lesions. The effect of the drug on catabolic factors could possibly be related to its inhibitory action on LTB4 synthesis.
Multicomponent gas mixture analysis using a single tin oxide sensor and dynamic pattern recognition
2001-01-01

A new method, which is based on the discrete wavelet transform, is presented for extracting important features from the response transients of a micromachined, tin oxide-based gas sensor. It is shown that two components in a mixture can be simultaneously and accurately quantified by processing the response dynamics of a single sensor operated in a temperature-modulated mode. The discrete wavelet transform outperforms the fast Fourier transform (classical approach) because it is more appropriate for the non- linear frequency-time problem encountered here.
N-[3,4-dimethoxycinnamoyl]-anthranilic acid (tranilast) inhibits transforming growth factor-? release and reduces migration and invasiveness of human malignant glioma cells
2001-01-01

Extensive infiltration of normal brain tissue and suppression of anti-tumor immune surveillance mediated by molecules such as transforming growth factor-beta (TGF-beta) are key biological features that contribute to the malignant phenotype of human gliomas. Tranilast (N-[3,4-dimethoxycinnamoyl]-anthranilic acid) is an anti-allergic compound used clinically to control atopic and fibrotic disorders. These effects are attributed to the suppression of TGF-beta1 synthesis and interference with growth factor-mediated proliferation and migration of fibroblasts and vascular smooth muscle cells. Here, we show that tranilast inhibits DNA synthesis and proliferation of human malignant glioma cells and promotes p21 accumulation in the absence of cytotoxicity. Further, tranilast reduces the release of TGF-beta1 and TGF-beta2 by glioma cells and inhibits migration, chemotactic responses and invasiveness. These effects are not associated with a reduction of alpha(v)beta(3) integrin expression at the cell surface but appear to involve inhibition of matrix metalloproteinase-2 expression and activity. Neither the tranilast-mediated inhibition of proliferation nor the inhibition of migration was counteracted by supplementation with exogenous TGF-beta. Finally, tranilast administered orally inhibited the growth of experimental 9L rat gliomas and reduced expression of TGF-beta2 in vivo. We conclude that tranilast might be a useful therapeutic agent for the treatment of human malignant glioma because of a TGF-beta-independent abrogation of the malignant phenotype of proliferation, migration and invasiveness and because of the antagonism of TGF-beta-associated immunosuppression.
Executive Dysfunction in Spinocerebellar Ataxia Type 1
2001-01-01

Fourteen patients with spinocerebellar ataxia 1 (SCA1) and 11 controls with similar mean age and IQ estimates were submitted to a neuropsychological test battery comprising tests for IQ, attention, verbal and visuospatial memory as well as executive functions. Neuropsychological assessment yielded verbal memory and executive dysfunction while tests of visuospatial memory and attention were not significantly impaired in SCA1 as compared to controls. Test performance was neither related to the repeat length, the age of onset nor the disease duration. The profile of cognitive impairment in SCA1 with prominent executive dysfunction corresponds to the concept of ‘frontal-subcortical’ dementia that is likely to be contingent upon disruption of a cerebrocerebellar circuitry that consists of afferent and efferent connections between the prefrontal cortex and the cerebellum.
Complex hyperbolic manifolds homotopy equivalent to a Riemann surface
2001-01-01

We construct isometric actions of fundamental groups of closed Riemann surfaces on the complex hyperbolic plane, which realize all possible values of Toledo's invariant r.For integer values of r these actions are discrete embeddings.The quotient complex hyperbolic surfaces are disc bundles over closed Riemann surfaces, whose topological type is described in terms of r.We relate our geometric construction to arithmetic constructions and discuss integrality properties of r.
Functional characterization of the α‐glucoside transporter Sut1p from Schizosaccharomyces pombe, the first fungal homologue of plant sucrose transporters
2001-01-01

Disaccharide transporters have not previously been identified in Schizosaccharomyces pombe . This is in contrast to Saccharomyces cerevisiae in which several maltose permeases belonging to the sugar porter (SP) family have been characterized. Here we report that a novel S. pombe gene, sut1 + , encodes a proton‐coupled disaccharide uptake transporter in the glycoside–pentoside–hexuronide (GPH):cation symporter family. Previously, members of the GPH family were restricted to bacteria and plants. The closest homologues of sut1 + are the sucrose uptake transporters (SUTs) from higher plants that transport sucrose with a higher affinity than maltose. The transport function of Sut1p was analysed by expression in S. cerevisiae . Sut1p was found to transport maltose with a K m of 6.5 ± 0.4 mM and sucrose with a K m of 36.3 ± 9.7 mM. Therefore, the substrate specificity of Sut1p from S. pombe is different from that of its plant homologues. Glucose repression of sut1 + at the transcriptional level is also consistent with a physiological function for Sut1p in maltose uptake. These results indicate that, unlike S. cerevisiae , S. pombe utilizes maltose transporters derived from a common ancestor with the plant SUTs.
Sensory Brain Areas in Mesopelagic Fishes
2001-01-01

Four areas of the brain that receive primary projections from chemical senses ([1] olfactory bulb, [2] facial and vagal lobes), the eye ([3] optic tectum), and somato- and mechanosensory systems such as the lateral line, vestibular and auditory systems ([4] trigeminal and octavolateral regions) have been studied and relative size differences used to deduce the sensory specializations of 67 species of mesopelagic fishes. One type of analysis used the average relative volumes of brain areas and identified ‘specialists’ with only one brain area above-average (36%), species ‘dominated’ by two sensory brain regions (49%), and generalists (15%), with three areas above-average. In addition, a cluster analysis was performed that separated 49 species which were mostly visually oriented from 18 non-visual species, among which 16 were characterized by an association of above-average trigeminal/octavolateral and gustatory areas, and a single species with a dominant olfactory bulb. The results support the idea that these species occupy a rich sensory environment for which the absence of sunlight is compensated by chemical and mechanosensory stimuli as well as by bioluminescent signals. This has lead to the development of specializations for the perception of single stimulus-modes, most notably for the visual system, as well as for combinations of various receptors and central processing areas, with a preference for associating either the chemical senses, including the olfactory and facial/vagal systems, or the trigeminal/octavolateral systems.
Effects of Amoxicillin, Gentamicin, and Moxifloxacin on the Hemolytic Activity of Staphylococcus aureus In Vitro and In Vivo
2001-01-01

ABSTRACT In Staphylococcus aureus infection hemolysis caused by the extracellular protein α-toxin encoded by hla is thought to contribute significantly to its multifactorial virulence. In vitro, subinhibitory concentrations of β-lactam antibiotics and fluoroquinolones increase the levels of hla and α-toxin expression, whereas aminoglycosides decrease the levels of hla and α-toxin expression. In the present study we investigated the effects of subinhibitory concentrations of amoxicillin, gentamicin, and moxifloxacin on hla and α-toxin expression and total hemolysis of S. aureus strain 8325-4, a high-level α-toxin producer, and its α-toxin-negative mutant, DU 1090, in vitro and in a rat model of chronic S. aureus infection. The levels of expression of hla and α-toxin and total hemolysis did not differ significantly when amoxicillin, gentamicin, or moxifloxacin was added to cultures of S. aureus strain 8325-4. In vivo, strain 8325-4 induced a significantly increased level of hemolysis in infected pouches compared to that in uninfected control pouches, but the hemolysis was reduced to control levels by treatment with doses of amoxicillin, gentamicin, or moxifloxacin that reduced bacterial numbers by 2 orders of magnitude. Additionally, the effects of subinhibitory concentrations of the three antibiotics on total hemolysis of four methicillin-resistant S. aureus and three methicillin-sensitive S. aureus (MSSA) clinical isolates were assessed in vitro. A significant increase in total hemolysis was observed for only one MSSA strain when it was treated with amoxicillin but not when it was treated with moxifloxacin or gentamicin. When purified α-toxin was incubated with purified human neutrophil elastase, α-toxin was cleaved nearly completely. The results suggest that the penicillin-induced increases in S. aureus α-toxin expression are strain dependent, that reduction of bacterial numbers in vivo counteracts this phenomenon effectively, and finally, that in localized S. aureus infections α-toxin activity is controlled by neutrophil elastase.
Expression of the p53 and maspin protein in primary prostate cancer: Correlation with clinical features
2001-01-01

The serine protease inhibitor Maspin has been reported to inhibit the invasiveness and motility of prostate cancer tumor cells. Additionally, a p53-dependent regulatory pathway of Maspin in prostate cancer cell lines has been indicated. The first aim of our study was to determine the prognostic value of Maspin protein expression for the recurrence-free survival of patients undergoing radical prostatectomy for the treatment of clinically localized prostate cancer. Secondly, Maspin expression was correlated to p53 protein expression in order to gain additional information on a possible and previously suggested regulatory influence of the wild-type p53 protein on the Maspin protein expression. Tumor specimens obtained from 84 patients undergoing radical prostatectomy for localized prostate cancer were investigated for the expression of the Maspin and p53 protein by an immunohistochemic approach. Maspin protein expression was correlated with further patients' and tumor characteristics such as tumor stage, histologic grading, regional lymph node status, p53 protein expression and recurrence-free survival of the patients following radical prostatectomy. After a median follow-up of 64 months (24-197 months), 23 of 40 patients (58%) with a negative or decreased Maspin expression (group 1) developed local recurrence or systemic tumor progression in contrast to 8 of 44 patients (18%) with a retained expression of the Maspin protein (group 2) (p = 0.02; log-rank test). The median recurrence-free survival following radical prostatectomy was 26 months (12-37 months) for group 1 patients and 41 months (5-134 months) for patients from group 2 (p = 0.04). A positive immunohistochemic staining reaction for the p53 protein was significantly correlated with a decreased expression of the Maspin protein (p = 0.015; Spearman correlation coefficient). Additionally, loss of Maspin protein expression was correlated to higher tumor stages (p = 0.002) and an increasing histologic dedifferentiation (p = 0.03). This is the first study to indicate that Maspin protein possibly functions as a clinically relevant inhibitor of tumor progression, preventing the local invasiveness and further systemic progression of prostate cancer. Our investigation delivers first hints for a p53-dependent regulatory pathway of the Maspin protein in human prostate cancer.
Effects of the Serine/Threonine Kinase SGK1 on the Epithelial Na<sup>+</sup> Channel (ENaC) and CFTR: Implications for Cystic Fibrosis
2001-01-01

Cystic fibrosis (CF) is characterized by impaired Cl(-) secretion and increased Na(+) reabsorption in several tissues including respiratory epithelium. Many CFTR mutations have been identified over the past years. However, only a poor correlation between the genotype and lung phenotype was found suggesting additional factors influencing the phenotype and course of the disease. The serine/threonine kinase SGK1 has recently been shown to stimulate the activity of the epithelial Na(+) channel ENaC. A variety of stimuli such as aldosterone, cell shrinkage, insulin or TGF-beta1 stimulate transcription and activate the SGK1 kinase. Here we further examined the effects of SGK1 on ENaC and CFTR which have mutual interactions and we analyzed sgk1 mRNA abundance in lung tissue from CF patients. Coexpression of CFTR and h-SGK1 in Xenopus oocytes increased ENaC currents as previously described. In addition CFTR mediated currents were also stimulated. h-SGK1 accelerated the expression of the amiloride sensitive Na(+)- current in Xenopus oocytes paralleled by increased ENaC-protein abundance in the oocyte membrane, an effect which was reversed by a h-SGK1(K127R) mutation lacking the ATP-binding site. The cation selectivity or Na(+) affinity were not affected. However, coexpression of h-SGK1 with ENaC altered the sensitivity of the Na(+)-channel to the inhibitors amiloride and triamterene. The inhibitory effect of CFTR expression on ENaC current was not affected by coexpression of h-SGK1 in Xenopus oocytes. Lung tissue from CF patients strongly expressed the serine/threonine kinase h-sgk1 which was not the case for non-CF lung tissue. Loss of CFTR function itself in a CF lung epithelial cell line did not increase SGK1 expression. In summary, enhanced expression of h-SGK1 in epithelial cells of CF-lung tissue may be a novel pathophysiological factor contributing to increased Na(+) channel activity and thus to increased Na(+) transport in CF.
Fast elevation of the intramyocellular lipid content in the presence of circulating free fatty acids and hyperinsulinemia: A dynamic1H-MRS study
2001-01-01

The influence of a short-term elevation of free fatty acids (FFAs) on intramyocellular lipids (IMCL) under hyperinsulinemic conditions was monitored in five healthy male subjects in the course of a 5-hr hyperinsulinemic glucose clamp. During the glucose clamp a lipid emulsion (Intralipid 20(R)) and heparin were administered intravenously. IMCL was quantified in the tibialis anterior (TA) and the soleus (SOL) muscle by (1)H-MRS. A rapid elevation of the IMCL pool was found in both muscles (61% in TA and 22% in SOL) in the 5-hr time period. A control hyperinsulinemic glucose clamp in the same study group, repeated without elevation of circulating FFAs, did not lead to significant changes in IMCL for both muscles. The present study shows for the first time that only the combination of high concentrations of FFAs and insulin lead to marked storage of lipids in skeletal muscle cells in humans. Magn Reson Med 45:179-183, 2001.
Invasion of Human Epithelial Cells by Pseudomonas aeruginosa Involves Src-Like Tyrosine Kinases p60Src and p59Fyn
2001-01-01

ABSTRACT Pseudomonas aeruginosa plays a major role in respiratory tract infections or sepsis in patients with cystic fibrosis or upon suppression of the immune system. Several P. aeruginosa strains have been shown to be internalized by human epithelial cells; however, the molecular mechanisms of the invasion process are poorly characterized. Here, we show that the internalization of P. aeruginosa into human epithelial cells results in and requires activation of the Src-like tyrosine kinases p59Fyn and p60Src and the consequent tyrosine phosphorylation of several eukaryotic proteins. The significance of Src-like tyrosine kinase activation is shown by an almost complete blockade of P. aeruginosa internalization, but not adhesion, upon inhibition of Src-like tyrosine kinases. Likewise, inhibition of P. aeruginosa binding to CFTR, which has been shown to block P. aeruginosa internalization, prevents Src and Fyn activation, supporting a pivotal role of Src-like tyrosine kinases for invasion by P. aeruginosa.