julilili42/papers huggingface dataset:
The use of gabapentin in chronic cluster headache patients refractory to first‐line therapy
2007-05-29

Chronic cluster headache (CCH) is a rare but challenging condition. About 20% of CCH patients get refractory to treatment. Gabapentin has recently been reported to be efficacious in the treatment of CCH. To test the potential of gabapentin as second‐line drug, we prospectively studied the efficacy of gabapentin as add‐on drug in eight patients suffering from CCH refractory to first‐line treatment. Six of eight CCH patients responded to treatment. After the end of the study phase, the patients’ clinical course was further followed up until January 2006. The longest period of being continuously pain‐free under gabapentin treatment was 18 months. In some individuals, increasing doses were needed with time. We conclude that gabapentin may be offered as treatment trial in patients refractory to first‐line treatment. However, patients may fail to respond to treatment and drug tolerance may occur with time.
A Semifield of Order 54Admitting a Free 4-Group of Automorphisms
2007-05-29

Abstract The purpose of this article is to give classification of semifields of order 54 admitting a free automorphism group E≅ z2 × z2, and to find their kernels (left nuclei). Notes Communicated by M. Cohen.
A Labeled-Line Code for Small and Large Numerosities in the Monkey Prefrontal Cortex
2007-05-30

How single neurons represent information about the magnitude of a stimulus remains controversial. Neurons encoding purely sensory magnitude typically show monotonic response functions (“summation coding”), and summation units are usually implemented in models of numerosity representation. In contrast, cells representing numerical quantity exhibit nonmonotonic tuning functions that peak at their preferred numerosity (“labeled-line code”), but the restricted range of tested quantities in these studies did not permit a definite answer. Here, we analyzed both behavioral and neuronal representations of a broad range of numerosities from 1 to 30 in the prefrontal cortex of monkeys. Numerosity-selective neurons showed a clear and behaviorally relevant labeled-line code for all numerosities. Moreover, both the behavioral and neuronal tuning functions obeyed the Weber–Fechner Law and were best represented on a nonlinearly compressed scale. Our single-cell study is in good agreement with functional imaging data reporting peaked tuning functions in humans, demonstrating neuronal precursors for human number competence in a nonhuman primate. Our findings also emphasize that the manner in which neurons encode and maintain magnitude information may depend on the precise task at hand as well as the type of magnitude to represent and memorize.
Molecular genetic analysis of purine nucleobase transport in Leishmania major
2007-05-30

Summary Leishmania major and all other parasitic protozoa are unable to synthesize purines de novo and are therefore reliant upon uptake of preformed purines from their hosts via nucleobase and nucleoside transporters. L. major expresses two nucleobase permeases, NT3 that is a high affinity transporter for purine nucleobases and NT4 that is a low affinity transporter for adenine. nt3 (–/–) null mutant promastigotes were unable to replicate in medium containing 10 μM hypoxanthine, guanine, or xanthine and replicated slowly in 10 μM adenine due to residual low affinity uptake of that purine. The NT3 transporter mediated the uptake of the anti‐leishmanial drug allopurinol, and the nt3 (–/–) mutants were resistant to killing by this drug. Expression of the NT3 permease was profoundly downregulated at the protein but not the mRNA level in stationary phase compared with logarithmic phase promastigotes. The nt4 (–/–) null mutant was quantitatively impaired in survival within murine bone marrow‐derived macrophages. Extensive efforts to generate an nt3 (–/–) / nt4 (–/–) dual null mutant were not successful, suggesting that one of the two nucleobase permeases must be retained for robust growth of the parasite. The phenotypes of these null mutants underscore the importance of purine nucleobase transporters in the Leishmania life cycle and pharmacology.
Stanna‐closo‐dodecaborate: The Crystal Structure of [Li(thf)3]2[SnB11H11], Vibrational Spectroscopy, Thermal Analysis and DFT Calculations.
2007-05-30

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Reactive astrocytes and activated microglial cells express EAAT1, but not EAAT2, reflecting a neuroprotective potential following ischaemia
2007-05-31

Aims: Glutamate receptor antagonists have failed clinical stroke trials and it has been proposed that the action of N‐methyl d ‐aspartate receptors is necessary for neuronal survival. Thus, excitatory amino acid transporters (EAATs) might be a promising therapeutic target. The aim of this study was to investigate glial expression of EAATs following ischaemia. Methods and results: Expression of EAAT1 (GLAST) and EAAT2 (Glt‐1) in 24 cases of ischaemia was examined by immunohistochemistry. Cortical expression of both EAATs in the lesion decreased within 24 h ( P &lt; 0.01, each). Whereas EAAT1+ white matter cells increased 18‐fold ( P &lt; 0.05) within 24 h in the lesion and remained elevated for months in adjacent (469‐fold, P &lt; 0.01) and remote areas (20‐fold, P &lt; 0.05), EAAT2+ white matter cells were equivalent in ischaemia and controls. In the first week after stroke mainly activated (ramified and amoeboid) microglia expressed EAAT1, whereas monocytic cells in perivascular spaces and foamy macrophages lacked EAAT1. After more than 1 week, predominantly reactive astrocytes expressed EAAT1. Conclusions: Microglial EAAT1 expression is restricted to the early/intermediate stage of activation and blood‐derived (perivascular) monocytes do not contribute to EAAT1+ cells following ischaemia. Whether a pharmacological increase in glial EAAT expression may compensate for loss of cortical EAAT expression and reduce neuronal damage following stroke requires investigation by further functional studies.
Are MAP Kinases Drug Targets? Yes, but Difficult Ones
2007-05-31

Abstract Pharmaceutical companies are facing an increasing interest in new target identification and validation. In particular, extensive efforts are being made in the field of protein kinase inhibitors research and development, and the past ten years of effort in this field have altered our perception of the potential of kinases as drug targets. Therefore, in the drug discovery process, the selection of relevant, susceptible protein kinase targets combined with searches for leads and candidates have become a crucial approach. The success of recent launches of protein kinase inhibitors (Gleevec, Imatinib, Sutent, Iressa, Nexavar, Sprycel) gave another push to this field. Numerous other kinase inhibitors are currently undergoing clinical trials or clinical development. Some questions are nevertheless unanswered, mostly related to the great number of known kinases in the human genome, to their similarity with each other, to the existence of functionally redundant kinases for specific pathways, and also because the connection between particular pathways and diseases is not always clear. The review is leading the reader through a panoramic view of protein kinase inhibition with a major focus on MAPK, successful examples and clinical candidates.
Novel Markers for the Prospective Isolation of Human MSC
2007-06-01

Abstract: The isolation of mesenchymal stem cells (MSC) from primary tissue is hampered by the limited selectivity of available markers. So far, CD271 is one of the most specific markers for bone marrow (BM)‐derived MSC. In search of additional markers, monoclonal antibodies (mAbs) with specificity for immature cells were screened by flow cytometry for their specific reactivity with the rare CD271 + population. The recognized CD271 + populations were fractionated by fluorescence‐activated cell sorting and the clonogenic capacity of the sorted cells was analyzed for their ability to give rise to CFU‐F. The results showed that only the CD271 bright but not the CD271 dim population contained CFU‐F. Two‐color flow cytometry analysis revealed that only the CD271 bright population was positive for the established MSC markers CD10, CD13, CD73, and CD105. In addition, a variety of mAbs specific for novel and partially unknown antigens selectively recognized the CD271 bright population but no other BM cells. The new MSC‐specific molecules included the platelet‐derived growth factor receptor‐β (CD140b), HER‐2/erbB2 (CD340), frizzled‐9 (CD349), the recently described W8B2 antigen, as well as cell‐surface antigens defined by the antibodies W1C3, W3D5, W4A5, W5C4, W5C5, W7C6, 9A3, 58B1, F9‐3C2F1, and HEK‐3D6. In conclusion, the described markers are suitable for the prospective isolation of highly purified BM‐MSC. These MSC may be used as an improved starting population for transplantation in diseases like osteogenesis imperfecta, cartilage repair, and myocardial infarction.
Impact of CYP2B6 Polymorphism on Hepatic Efavirenz Metabolismin Vitro
2007-06-01

We have shown that CYP2B6 genetic polymorphism markedly influences the metabolism of efavirenz in human liver microsomes. Importantly, the CYP2B6*6 allele harboring the SNPs c.516G>T [Q172H] and c.785A>G [K262R] was significantly associated with a pronounced decrease in CYP2B6 expression and activity, as well as a low rate of efavirenz 8-hydroxylation. These results represent a first step towards elucidating the mechanism by which this allele identifies patients exhibiting very high efavirenz plasma concentrations.
Value of contrast-enhanced multiphase CT in combined PET/CT protocols for oncological imaging
2007-06-01

To evaluate the additional value of contrast-enhanced multiphase CT in comparison with low-dose non-contrast CT in combined positron emission tomography (PET)/CT protocols for oncological imaging, we retrospectively analysed 100 patients with different malignant tumours. All patients underwent a PET/CT consisting of a multiphase CT protocol including a low-dose non-enhanced attenuation scan and an arterial and portal-venous contrast-enhanced scan followed by a whole-body PET. PET/CT studies were analysed by different categories to determine the added value of contrast-enhanced CT. The additional value was defined as new information provided by diagnostic CT and not available from the low-dose CT, resulting in change of PET/CT interpretation. The results were validated either by histopathology or by clinical-radiological follow up at > or =6 months. The clinical impact was evaluated with respect to changes in patient management. Diagnostic multiphase CT was of additional value in 52 out of 100 patients with 85 suspected lesions. In 40 out of 100 patients, no additional value could be detected. Eight patients were excluded due to inconclusive diagnosis in both methods including fusion. The analysis showed the greatest benefit of diagnostic CT in the categories localization of pathological fluorodeoxyglucose (FDG) uptake and precise tumour delineation, changing PET/CT interpretation in 42% and 31% of patients, respectively. The benefit of diagnostic CT was influenced by the tumour type demonstrating the highest impact in gastrointestinal, lung and neuroendocrine tumours. Diagnostic CT changed clinical management in 21 patients (21%). Diagnostic multiphase CT as part of the combined PET/CT protocol has the potential to provide considerable additional value in specific clinical conditions with resultant change of management in a substantial proportion of patients.
Defensins and other antimicrobial peptides in inflammatory bowel disease
2007-06-01

Unlike ulcerative colitis, ileal and colonic Crohn's disease are characterized by localized deficiencies of antibacterial peptides. Understanding the precise molecular mechanisms of the defective antibacterial barrier function might provide new therapeutic directions.
Variable switching rates of malaria virulence genes are associated with chromosomal position
2007-06-01

Summary Antigenic variation in Plasmodium falciparum malaria is mediated by transcriptional switches between different members of the multicopy var gene family. Each var gene encodes a member of a group of heterogeneous surface proteins collectively referred to as PfEMP1. Mutually exclusive expression ensures that an individual parasite only transcribes a single var gene at a time. In this work we studied var gene switching to determine if transcriptional switches favour expression of particular subgroups of var genes and if var gene activation within a clonal population of parasites follows a predetermined order. We show that in clonal parasite populations, expression of var genes located in the central regions of chromosomes is remarkably stable and that they rarely undergo transcriptional switches in the absence of selection. In contrast, parasites expressing subtelomerically located var genes readily switched to alternative var loci. We confirmed these observations by generating transgenic parasites carrying drug selectable markers in subtelomeric and central var loci and monitoring switching after release from selection. Our data show that different var genes have different intrinsic switching rates that correlate with chromosomal location, and that there is no predetermined order of expression.
Pretreatment 18F-FAZA PET Predicts Success of Hypoxia-Directed Radiochemotherapy Using Tirapazamine
2007-06-01

This study provides compelling evidence that hypoxia imaging using (18)F-FAZA PET is able to predict the success of RCT of tumor-bearing mice using the hypoxia-activated chemotherapeutic agent tirapazamine. Pretreatment (18)F-FAZA PET, therefore, offers a way for the individualization of tumor treatment involving radiation. The data suggest that by reserving hypoxia-directed therapy to tumors with high (18)F-FAZA uptake, improvement of the therapeutic ratio is possible, as the therapeutic effect of tirapazamine seems to be restricted to hypoxic tumors.
Functional cross-talk between two-component and phytochrome B signal transduction in Arabidopsis
2007-06-01

The A-type response regulator ARR4 is an element in the two-component signalling network of Arabidopsis. ARR4 interacts with the N-terminus of the red/far-red light photoreceptor phytochrome B (phyB) and functions as a modulator of photomorphogenesis. In concert with other A-type response regulators, ARR4 also participates in the modulation of the cytokinin response pathway. Here evidence is presented that ARR4 directly modulates the activity state of phyB in planta, not only under inductive but also under extended irradiation with red light. Mutation of the phosphorylatable aspartate to asparagine within the receiver domain creates a version of ARR4 that negatively affects photomorphogenesis. Additional evidence suggests that ARR4 activity is regulated by a phosphorelay mechanism that depends on the AHK family of cytokinin receptors. Accordingly, the ability of ARR4 to function on phyB is modified by exogenous application of cytokinin. These results implicate a cross-talk between cytokinin and light signalling mediated by ARR4. This cross-talk enables the plant to adjust light reponsiveness to endogenous requirements in growth and development.
Vestibular labyrinth diversity in diprotodontian marsupial mammals
2007-06-01

ABSTRACT The bony labyrinth of specimens representing eight diprotodontian species were visualized by high-resolution computed tomography. Linear measurements of the labyrinth were taken, e.g., the height and width of the arc of each semicircular canal. The relative sizes and spatial arrangements of the semicircular canals were compared and some of the variation was atomized into 17 characters, which were then phylogenetically interpreted. There has been a change both in size and in relative arrangement of the semicircular canals that for some aspects maps onto the ecological change from arboreality to terrestriality. In particular, there are differences among diprotodontians in the height of the anterior semicircular canal in relation to the posterior one. In arboreal species, the lateral semicircular canal is relatively longer than the equivalent semicircular canals of terrestrial species. A rounder anterior semicircular canal is widespread for Diprotodontia with a shift in Pseudocheiridae, where it is more flattened. Dendrolagus shows features typical of terrestrial species in spite of its arboreal lifestyle. The fact that it shows the derived character state is congruent with the fact that it has secondarily and only recently evolved an arboreal lifestyle.
Flt3 in Regulation of Type I Interferon‐Producing Cell and Dendritic Cell Development
2007-06-01

Abstract: Flt3‐ligand is a nonredundant cytokine in type I interferon‐producing cell (IPC) and dendritic cell (DC) development. We demonstrated that IPC and DC differentiation potential is confined to Flt3 + ‐hematopoietic progenitor cells, that Flt3‐ligand drives development along both lymphoid and myeloid developmental pathways from Flt3 + ‐progenitors to Flt3 + ‐IPCs and ‐DCs, and that in vivo pharmacologic inhibition of Flt3‐signaling leads to disruption of IPC and DC development in spite of consecutive Flt3‐ligand upregulation in treated animals. We here summarize our recent findings that overexpression of human Flt3 in Flt3 − and Flt3 + hematopoietic progenitors rescues and enhances their IPC and DC differentiation potential, respectively. Based on these data, we propose an instructive, demand‐regulated, cytokine‐driven IPC and DC regeneration model, where high Flt3‐ligand levels initiate a self‐sustaining, Flt3‐STAT3 and ‐PU.1‐mediated IPC and DC differentiation program in Flt3 + ‐hematopoietic progenitor cells.
ANATOMY AND DEVELOPMENT OF THE BONY INNER EAR IN THE WOOLLY OPOSSUM, Caluromys philander (DIDELPHIMORPHIA, MARSUPIALIA)
2007-06-01

The ontogenetic changes of the skeletal tissue of the vestibular and cochlear system of Caluromys philander were investigated using CT scans of an adult skull and 3D reconstructions of histological serial sections of three pouch-youngs. The bony labyrinth of C. philander differs in several aspects from what has been reported for other marsupials. Some of the proportions of the semicircular canals (SC) are probably characteristic of arboreal as opposed to terrestrial species. Several significant changes in the SCs shape occur postnatally. The most remarkable difference among stages is the different height of the anterior SC and posterior SC in relation to the common crus. In the adult the posterior arm of the lateral SC and the inferior arm of the posterior SC build a common crus, a condition of several basal metatherians and crown-group marsupials. The number of turns of the cochlea in the adult is 2.4.
Identification and Characterization of T-Cell Epitopes Deduced from RGS5, a Novel Broadly Expressed Tumor Antigen
2007-06-01

Abstract Purpose: Identification of tumor-associated antigens and advances in tumor immunology resulted in the development of vaccination strategies to treat patients with malignant diseases. In a novel experimental approach that combined comparative mRNA expression analysis of defined cell types with the characterization of MHC ligands by mass spectrometry, we found that regulator of G protein signaling 5 (RGS5) is extensively up-regulated in a broad variety of malignant cells, and we identified two HLA-A2– and HLA-A3–binding peptides derived from the RGS5 protein. Interestingly, RGS5 was recently shown to be involved in tumor angiogenesis. Experimental Design: We used monocyte-derived dendritic cells pulsed with these novel antigenic peptides or transfected with RGS5-mRNA for the in vitro induction of CTLs, generated from healthy donors, to analyze the presentation of RGS5-deduced epitopes by malignant cells. Results: The generated CTL lines elicited an antigen-specific and HLA-restricted cytolytic activity against tumor cells endogenously expressing the RGS5 protein. Furthermore, we were able to induce RGS5-specific CTLs using peripheral blood mononuclear cells from a patient with acute myeloid leukemia capable of recognizing the autologous leukemic blasts while sparing nonmalignant cells. Conclusions: These results indicate that the RGS5 peptides represent interesting candidates for the development of cancer vaccines designed to target malignant cells and tumor vessels.
Comparative Study of Nest Architecture and Colony Structure of the Fungus-Growing Ants,Mycocepurus goeldiiandM. smithii
2007-06-01

Nest architecture and demography of the non leaf-cutting fungus-growing ant species Mycocepurus goeldii and M. smithii (Attini: Formicidae) were studied in an agroforest habitat near Manaus, Brazil during the excavation of 13 nests. Both species built their nests in two different ways. The first type possessed a "tree-like" architecture, in which a vertical tunnel led downwards and lateral tunnels branched off at 90 degrees angles from the main tunnel, with a chamber at the end of each side branch. Alternatively, other nests displayed a "necklace-like" architecture, where the main tunnel also led down vertically, but entered each chamber from the top and exited it at the bottom, resulting in an architecture where chambers appeared like pearls on a necklace. The nest systems of M. goeldii and M. smithii consisted of 1-21 or 1-15 chambers, respectively. Of 199 excavated chambers, 57 % contained fungus-gardens. Chambers not containing fungus gardens were filled with organic matter from decaying fungus gardens or earthworm feces. Only M. smithii workers deposited loose soil in abandoned chambers during the construction of new nest chambers. Workers of M. smithii constructed significantly smaller chambers than those of M. goeldii. In both species, fungus garden-containing chambers were larger than non-garden chambers and were homogenously distributed in the soil between 17 cm and 105 cm depth. Neither fungus gardens nor abandoned chambers were encountered more frequently in deeper or shallower soil strata indicating that ants of both species did not abandon shallower versus deeper chambers, or move the colony to deeper soil layers with increasing colony age. Fungus gardens were suspended from the ceiling of the subterranean chambers and originated as small mycelial tufts. Through continual addition of organic debris, the tufts first grew vertically to strands before they expanded laterally until most of the chamber volume was filled with fungus garden curtains. New garden chambers were found at depths ranging from 17 to 83 cm, suggesting that new garden chambers were not constructed in deeper soil strata with increasing colony age. The size of M. goeldii and M. smithii colonies was dependent on their age. Worker counts varied between a few individuals in recently founded colonies and 1352 workers in an adult M. goeldii colony. The ratio of worker number per fungus garden chamber was higher in M. goeldii colonies than M. smithii colonies; the M. goeldii colonies were more populous. Both species were oligogynous with a maximum of four and three queens observed in a single chamber of M. goeldii and M. smithii, respectively. The reproductive status of each queen was unknown. In both species the ratio of brood to workers was approximately 2:3. Larvae and pupae were unequally distributed throughout the nest, but were only located in chambers containing a garden. Their location in the chamber was dependent upon the developmental state of the fungus garden.