julilili42/papers huggingface dataset:
Variant late infantile neuronal ceroid lipofuscinosis in a subset of Turkish patients is allelic to Northern epilepsy
2004-03-02

Childhood-onset neuronal ceroid lipofuscinoses (NCL) are a group of autosomal recessive progressive encephalopathies characterized by the accumulation of autofluorescent material in various tissues, notably in neurons. Based on clinical features, the country of origin of patients, and the molecular genetic background of the disorder, at least seven different forms are thought to exist. Northern epilepsy is a novel form of NCL so far described only in Finland, where all patients are homozygous for a missense mutation in the CLN8 gene. A variant form of late infantile NCL (vLINCL) present in Turkish patients has been considered a distinct clinical and genetic entity among the NCL, the underlying gene (CLN7) being unknown. Recently, we reported homozygosity over the Northern epilepsy CLN8 gene region on 8p23 in four out of five Turkish vLINCL families studied. However, no common mutation in CLN8 was found in these families. We have now extended the Turkish vLINCL family panel to 18 families, of which only one is nonconsanguineous. Nine families were excluded from CLN8 by lack of homozygosity. In the remaining families, four CLN8 gene mutations were identified indicating that in a subset of patients with Turkish vLINCL, the disorder is allelic to Northern epilepsy. There is no apparent genotype-phenotype correlation among the Turkish patients with CLN8 mutations, although their phenotype is distinct from that of Finnish Northern epilepsy patients. The molecular genetic background of the Turkish vLINCL families not linked to CLN8 remains to be clarified.
A Versatile Direct Approach to ortho‐Substituted Azobenzenes from Benzotriazoles
2004-03-02

. .. und Trumpf: Das verborgene Potenzial von Benzotriazolen als Diazonium-Synthons zeigt sich in den Reaktionen von 1-[(Nonafluorbutyl)sulfonyl]-1H-1,2,3-benzotriazol mit Natriumphenoxid zu ortho-substituierten Azobenzolen. Die Reaktion kann durch unterschiedliche Lösungsmittel in Richtung ortho- oder para-Substitution gelenkt werden (siehe das Gemälde von Mathias Hansen, das die Zweigeteiltheit symbolisiert). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2004/z52782_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The role of Shp2 serine residues 576 and 591 in insulin signalling
2004-03-02

Background: The detailed molecular mechanisms that cause insulin resistance are still not fully understood. Insulin resistance inducing signals involve serine phosphorylation of the insulin receptor substrate (IRS)-1 and IRS-1 protein degradation. Moreover, activation of protein kinase C (PKC) and protein tyrosine phosphatases, among them the cytoplasmic Shp2, have been shown to regulate insulin dependent pathways negatively. As previously shown, Shp2 is phosphorylated on serine residues 576 and 591 by PKC. However, physiological effects of these phosphorylations are not yet determined, therefore we tested whether they are involved in negative regulation of insulin action.
Growth Control In Vivo – Lessons From Growth Selected Mouse Lines
2004-03-02

Functional analysis of growth control has been successfully performed by establishing transgenic and knockout models with forced or repressed expression of a gene of interest. However, the question if a certain gene in fact is involved in altered growth e.g. during growth selection is unclear. Thus, we asked if there are general patterns of growth control or if growth control may be achieved by unique combinations of different expression levels of different growth factors. For the analysis, we made use of mouse models generated through long-term selection for high (H) or low (L) body or muscle weight. Serum levels of IGF-I and of the IGFBPs were measured in four independently generated H-lines and compared with their respective L-line or with unselected controls. While the serum IGF-I levels were significantly reduced in L-mice if compared to controls or H-mice, a reduction of serum IGFBP levels was observed in no case. In distinct L-lines only IGFBP-2 was elevated if compared to the respective H-line suggesting endocrine IGFBP-2 as an exclusive negative effector of growth regulation beyond all other IGFBPs. We next analyzed local expression of selected growth relevant genes in mouse lines significantly differing by their carcass weights. In muscle tissues from these lines we found different patterns of gene expression as quantified by RT real-time PCR and Western blots. In H-mice increased IGF-I or -II mRNA expression was found. In contrast in L-mice several inhibitory IGFBPs were increased if compared to H-mice. Beyond all other IGFBPs, IGFBP-5 displayed the highest expression level both on mRNA and protein level. Interestingly, mRNA expression of SOCS-2 was elevated in H-mice and correlated negatively with four different IGFBPs in muscle. To summarize, we found common and distinct expression patterns of growth relevant genes in different divergently selected mouse models.
Lipoapoptotic effects of free fatty acids on human coronary artery endothelial and smooth muscle cells
2004-03-02

Cardiovascular disease is a major cause of morbidity and mortality in patients with insulin resistance and type 2 diabetes. Recent studies have shown that apoptosis is involved in the progression of atherosclerotic lesions and in complications of advanced atheroma. Since free fatty acids (FFA) induce peripheral insulin resistance on the one hand and apoptosis in certain cell types on the other hand, we tested whether different FFA are able to exert lipoapoptotic effects in human coronary artery endothelial (CAEC) and smooth muscle cells (CASMC). CAEC or CASMC were incubated with saturated (palmitate, stearate) and unsaturated (palmitoleate, oleate, linoleate) FFA (1 mM, 24h). Apoptosis (sub-G1 formation) was assessed by flow cytometry. Necrosis was discriminated from apoptosis by flow cytometry (propidium iodide and annexin-V double-staining).
Genetic determinants of pre-diabetic phenotypes in polycystic ovary syndrome
2004-03-02

Background and aim: Insulin resistance is one of the main features of both polycystic ovary syndrome (PCOS) and type 2 diabetes. Several polymorphisms in genes related to insulin action have been demonstrated to be associated with type 2 diabetes mellitus (T2DM). However, less is known about the association of such susceptibility genes for T2DM with PCOS.
Expression and regulation of the adiponectin gene (apM1) in human myotubes
2004-03-02

The adipokine adiponectin has been postulated to play an important role in the modulation of glucose and lipid metabolism in insulin-sensitive tissues. Up to now, adiponectin gene (apM1) expression was exclusively found in white adipose tissue. In our study, we show for the first time apM1 expression in human myotubes and investigated its hormonal regulation. In vitro differentiated human myotubes were incubated with an adiponectin-containing HEK293 cell culture supernatant and agents were added as indicated. After 48 hours, adiponectin mRNA was assessed by RT-PCR. Adiponectin protein was visualized by immunoblotting and quantified by radioimmunoassay.
An overgrowth phenotype of in vitro produced bovine fetuses is associated with marked changes in plasma IGF-IIR and other IGF-system components but is not caused by imprinting failure at the IGF2R locus
2004-03-02

Epigenetic perturbations that lead to clinical phenotypes, e.g. Beckwith-Wiedemann syndrome, have been observed at an increased frequency in children born after in vitro fertilization (IVF). We have developed an animal model that consistently produces bovine IVF-fetuses with an overgrowth phenotype, to study IVF-related epigenetic phenomena. We produced embryos according to two different protocols, transferred them to recipient cattle at day 7 after fertilization, and terminated resulting pregnancies at day 80 to recover fetuses. Fetuses from protocol I were significantly heavier than controls derived from protocol II or from natural matings (95.1±3.4 vs. 80.4±3.2, P<0.006) and also showed significantly different organ weights. The overgrowth phenotype was observed in two independent experiments that involved different breeds of cattle and was thus shown to be truly caused by the in vitro environment. Fetal overgrowth was accompanied by marked changes in the IGF-system, such as elevated plasma IGF-I (27.2±1.3 ng/ml vs. 21.6±1.3 ng/ml, P<0.003) and free plasma IGF-IIR concentrations (82700±6400 AU vs. 49400±6400 AU, P<0.002). Significant changes in IGF-system components, including free plasma IGF-IIR, were also observed in ovine IVF-fetuses with an overgrowth phenotype (Young et al. 2001, Nat Genet 27:153). This phenotype involved altered expression of IGF2R in fetal tissues that correlated with differences in methylation levels in a differentially methylated region of the IGF2R gene, indicating imprinting failure. We have, therefore, developed genetic markers from 3' UTR fragments of bovine IGF2R, and analyzed the expression of paternal and maternal alleles in normal and overgrown fetuses. Our data clearly show that (i) IGF2R is expressed from the maternal allele in various bovine fetal tissues and (ii) the imprinting status of IGF2R is not altered in overgrown fetuses. This suggests that epigenetic changes responsible for overgrowth phenotypes of in vitro produced fetuses are species-specific or dependent on specific experimental conditions.
Responses to Toll‐Like Receptor Ligands in Children Living in Areas Where Schistosome Infections Are Endemic
2004-03-04

To study the effect of repeated challenge of the innate immune system with pathogen-associated molecular patterns, cytokine responses to schistosomal lipids and bacterial lipopolysaccharide (LPS) were analyzed in schoolchildren living in an area in Gabon where schistosomiasis, a helminth infection that is chronic in nature, is endemic. A schistosomal phosphatidylserine (PS) fraction containing the Toll-like receptor (TLR)-2 ligand lyso-PS stimulated the production of interleukin (IL)-8, IL-10, IL-6, and tumor necrosis factor (TNF)-alpha in children without Schistosoma haematobium infection. However, in infected children, the responses to this stimulus were lower, in particular for production of IL-8 and TNF-alpha. Responses to the TLR4 ligand, LPS, followed a similar pattern. In contrast, schistosomal adult worm glycolipids that did not stimulate any of the TLRs tested induced IL-8 and IL-6 responses that were significantly higher in schistosome-infected children than in schistosome-uninfected children. These results indicate that relentless exposure to pathogens can lead to altered responses to TLR ligands.
Effects of Putative Epididymal Osmolytes on Sperm Volume Regulation of Fertile and Infertile c‐ros Transgenic Mice
2004-03-04

ABSTRACT: Volume regulation by spermatozoa has been demonstrated to be crucial in both mice and men for transport in the female tract. In order to determine the nature of osmolytes used by spermatozoa, they were released from the cauda epididymis of fertile c‐ros heterozygous mice into incubation medium of uterine osmolality (representing an osmotic challenge), containing increasing concentrations of compounds that are major epididymal fluid components and known osmolytes in somatic cells. This should nullify the concentration gradients for osmolytes that mediate volume regulation, prevent osmolyte efflux, and lead to swelling. Of the osmolytes tested, K + caused the most rapid and extensive volume increases; glutamate, taurine, l ‐carnitine, and myo‐inositol also were effective, but glycerophosphocholine was not. Such effects were not observed in cauda sperm from the infertile knockout mice, demonstrating a defect in normal volume regulation. K + concentrations in cauda epididymal fluid were 21 mM higher in the knockout than the heterozygous mice, but no differences were found in caudal fluid glutamate, carnitine, or myo‐inositol. The carnitine content of cauda sperm from knockout males was not different from that of fertile males, but lower amounts of glutamate and inositol were found that could explain the poor volume regulation. In heterozygous mice, cauda but not caput sperm responded to the K + channel blocker quinine by swelling, demonstrating development of volume regulation during epididymal transit, whereas knockout cauda sperm showed no response, as with the osmolytes. Major epididymal secretions could serve as osmolytes in murine spermatozoa for volume regulation in response to physiological osmotic challenge in the normal fertile mice; the reduced sperm content of inositol and glutamate in the c‐ros knockout mice might reflect maturational abnormalities in volume regulation.
Imaging of activated microglia with PET and [11C]PK 11195 in corticobasal degeneration
2004-03-04

Abstract Positron emission tomography (PET) using [ 11 C]PK 11195, a ligand for peripheral benzodiazepine receptor binding sites, offers the opportunity to image activated microglia in vivo. This tool may therefore be used to display the occurrence of microglial activation in the course of neurodegeneration. A patient with the clinical diagnosis of corticobasal degeneration (CBD) and left‐sided symptoms was studied using fluorodeoxyglucose (FDG) and [ 11 C]PK 11195 PET. We found a marked right hemispheric hypometabolism and asymmetric microglial activation in corresponding areas of the basal ganglia and right temporal and parietal cortex. [ 11 C]PK 11195 PET suggests involvement of microglial activation in the pathogenesis of CBD. © 2004 Movement Disorder Society
Routine MRI visibility of ipsilateral cortico-spinal pathways in congenital hemiparesis
2004-03-04

Objective: During our studies on congenital hemiparesis, we noted that several patients showed abnormal T2-hyperintensities in the course of the pyramidal tract of the intact hemisphere. Here, we searched for a possible association of this sign with the presence of ipsilateral cortico-spinal pathways originating in the intact hemisphere.
Prenatal multicystic encephalomalacia caused by an anomaly of the aortic arch
2004-03-04

Introduction: Multicystic encephalomalacia (ME) is the typical clinical manifestation of severe hypoxic-ischemic brain damage during the late 3rd trimenon. The subclavian steal syndrome (SSS) is only rarely found in childhood; it may be caused by an anomaly of the aortic arch. This is the first report on a prenatal ME due to SSS.
Innate immunity in plants and animals: striking similarities and obvious differences
2004-03-05

Summary: Innate immunity constitutes the first line of defense against attempted microbial invasion, and it is a well‐described phenomenon in vertebrates and insects. Recent pioneering work has revealed striking similarities between the molecular organization of animal and plant systems for nonself recognition and anti‐microbial defense. Like animals, plants have acquired the ability to recognize invariant pathogen‐associated molecular patterns (PAMPs) that are characteristic of microbial organisms but which are not found in potential host plants. Such structures, also termed general elicitors of plant defense, are often indispensable for the microbial lifestyle and, upon receptor‐mediated perception, inevitably betray the invader to the plant's surveillance system. Remarkable similarities have been uncovered in the molecular mode of PAMP perception in animals and plants, including the discovery of plant receptors resembling mammalian Toll‐like receptors or cytoplasmic nucleotide‐binding oligomerization domain leucine‐rich repeat proteins. Moreover, molecular building blocks of PAMP‐induced signaling cascades leading to the transcriptional activation of immune response genes are shared among the two kingdoms. In particular, nitric oxide as well as mitogen‐activated protein kinase cascades have been implicated in triggering innate immune responses, part of which is the production of anti‐microbial compounds. In addition to PAMP‐mediated pathogen defense, disease resistance programs are often initiated upon plant‐cultivar‐specific recognition of microbial race‐specific virulence factors, a recognition specificity that is not known from animals.
Randomized controlled trial of a traditional preparation of Artemisia annua L. (Annual Wormwood) in the treatment of malaria
2004-03-06

The Chinese medicinal plant Artemisia annua L. (Annual Wormwood) contains the antimalarial compound artemisinin. The locally grown herb may offer an additional tool for the control of malaria, especially in poor countries where modern antimalarial drugs are often unavailable. In an open, randomized, controlled pilot trial, we investigated the efficacy and safety of traditional tea preparations of Artemisia annua in the treatment of uncomplicated malaria. Treatment resulted in a quick resolution of parasitaemia and of clinical symptoms. After 7 d of medication, cure rates were on average 74% for the Artemisia preparations compared with 91% for quinine. However, recrudescence rates were high in the Artemisia groups. Therefore, monotherapy with Artemisia annua L. cannot be recommended as alternative to modern antimalarials, but may deserve further investigation.
Accretion disc evolution in DW Ursae Majoris: \\nA photometric study
2004-03-09

\\n We present an analysis of CCD photometric observations\\nof the eclipsing novalike cataclysmic variable <ext-link ext-link-type="aoi">DW UMa</ext-link>\\nobtained in two different luminosity states: high and\\nintermediate. The star presents eclipses with very different\\ndepth: ~1.2 mag in the high and ~3.4 mag in the intermediate\\nstate. Eclipse mapping reveals that this difference is almost\\nentirely due to the changes in the accretion disc radius:\\nfrom ~ in the intermediate state to ~ in the high state ( is the distance from the white\\ndwarf to the first Lagrangian point). In the intermediate state, the\\nentire disc is eclipsed while in the high state, its outer part remains\\nvisible.\\nWe also find that the central intensity of the disc is nearly\\nthe same in the two luminosity states and that it is the increase of the disc\\nradius that is responsible for the final rise from the 1999/2000 low\\nstate. We find that the intensity profile of the disc is rather\\nflat and suggest a possible explanation. We also discuss the\\neffect of using a more realistic limb-darkening law on the disc\\ntemperatures inferred from eclipse mapping experiments.\\nPeriodogram analysis of the high state data reveals “positive\\nsuperhumps" with a period of in 2002 and in 2003, \\nin accord with the results of Patterson et al. However, we cannot confirm the\\nquasi-periodic oscillations reported by these authors. We obtain\\nan updated orbital ephemeris of <ext-link ext-link-type="aoi">DW UMa</ext-link>: .\\n\\n
Induction of Brain-Derived Neurotrophic Factor in Plaque-Associated Glial Cells of Aged APP23 Transgenic Mice
2004-03-10

Brain-derived neurotrophic factor (BDNF) is a versatile neurotrophic factor that has been implicated in cell survival, cell differentiation, axonal growth, and activity-dependent synaptic plasticity. Changes in BDNF expression have also been reported during the course of several neurological disorders, including Alzheimer's disease (AD). The role of BDNF in AD, however, has remained elusive. To learn more about this neurotrophic factor, we investigated BDNF expression in brain of amyloid precursor protein overexpressing mice (APP23 transgenic mice). In situ hybridization revealed BDNF mRNA signals associated with amyloid plaques. Laser microdissection in combination with quantitative RT-PCR demonstrated a sixfold increase of BDNF mRNA in the immediate plaque vicinity, a threefold increase in a tissue ring surrounding the plaque, and control levels in interplaque areas comparable with those measured in age-matched nontransgenic mice. Double immunofluorescence localized BDNF to microglial cells and astrocytes surrounding the plaque. Cortical BDNF protein levels were quantified by ELISA demonstrating a &gt;10-fold increase compared with age-matched controls. This upregulation of BDNF protein significantly correlated with the β-amyloid load in the transgenic animals. Taken together, our data demonstrate a plaque-associated upregulation of BDNF in APP23 transgenic mice and implicate this neurotrophin in the regulation of inflammatory and axonal growth processes in the plaque vicinity.
Stable carbon isotope fractionation during aerobic and anaerobic transformation of trichlorobenzene
2004-03-10

Fractionation of stable carbon isotopes upon degradation of trichlorobenzenes was studied under aerobic and anaerobic conditions. Mineralization of 1,2,4-trichlorobenzene by the aerobic strain Pseudomonas sp. P51 which uses a dioxygenase for the initial enzymatic reaction was not accompanied by a significant isotope fractionation. In contrast, reductive dehalogenation by the anaerobic strain Dehalococcoides sp. strain CBDB1 revealed average isotope enrichment factors (eta) between -3.1 and -3.7 for 1,2,3- and 1,2,4-trichlorobenzene, respectively. The significant isotope fractionation during reductive dehalogenation would allow tracing the in situ biodegradation of halogenated benzenes in contaminated anoxic aquifers, whereas the lack of isotope fractionation during aerobic transformation limits the use of this approach in oxic environments.
Weak Interionic Interactions in 2‐Haloimidazolium Hexahalotellurates(IV) [1]
2004-03-11

Abstract The 2‐haloimidazolium salts [C 11 H 20 N 2 X]X [ 1 ; X = Cl ( a ), Br ( b )] react with TeX 4 to give the salts [C 11 H 20 N 2 X] 2 [TeX 6 ] [ 2 ; X = Cl ( a ), Br ( b )]. The crystal structure analyses of 2a and 2b · CH 2 Cl 2 reveal the presence of ionic pairs linked by weak halogen to halogen interactions.
2-18fluoro-deoxy-D-glucose Positron Emission Tomography Is a Reliable Predictor for Viable Tumor in Postchemotherapy Seminoma: An Update of the Prospective Multicentric SEMPET Trial
2004-03-12

Purpose To define the clinical value of 2- 18 fluoro-deoxy-D-glucose positron emission tomography (FDG PET) as a predictor for viable residual tumor in postchemotherapy seminoma residuals in a prospective multicentric trial. Patients and Methods FDG PET studies in patients with metastatic pure seminoma who had radiographically defined postchemotherapy residual masses were correlated with either the histology of the resected lesion or the clinical outcome documented by computer tomography (CT), tumor markers, and/or physical examination during follow-up. The size of the residual lesions on CT, either &gt; 3 cm or ≤ 3 cm, was correlated with the presence or absence of viable residual tumor. Results Fifty-six FDG PET scans of 51 patients were assessable. All 19 cases with residual lesions &gt; 3 cm and 35 (95%) of 37 with residual lesions ≤ 3 cm were correctly predicted by FDG PET. The specificity, sensitivity, positive predictive value, and negative predictive value of FDG PET were 100% (95% CI, 92% to 100%), 80% (95% CI, 44% to 95%), 100%, and 96%, respectively, versus 74% (95% CI, 58% to 85%), 70% (95% CI, 34% to 90%), 37%, and 92%, respectively, for CT discrimination of the residual tumor by size (&gt; 3 cm/≤ 3 cm). Conclusion This investigation confirms that FDG PET is the best predictor of viable residual tumor in postchemotherapy seminoma residuals and should be used as a standard tool for clinical decision making in this patient group.