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New Clues (new + clue)
Selected AbstractsTransplant Glomerulopathy: New Clues in the Puzzle of Chronic Allograft Nephropathy?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2003Claudio Ponticelli No abstract is available for this article. [source] Glia cells in amyotrophic lateral sclerosis: New clues to understanding an old disease?MUSCLE AND NERVE, Issue 6 2007Clemens Neusch MD Abstract In classic neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), the pathogenic concept of a cell-autonomous disease of motor neurons has been challenged increasingly in recent years. Macro- and microglial cells have come to the forefront for their role in multistep degenerative processes in ALS and respective disease models. The activation of astroglial and microglial cells occurs early in the pathogenesis of the disease and seems to greatly influence disease onset and promotion. The role of oligodendrocytes and Schwann cells remains elusive. In this review we highlight the impact of nonneuronal cells in ALS pathology. We discuss diverse glial membrane proteins that are necessary to control neuronal activity and neuronal cell survival, and summarize the contribution of these proteins to motor neuron death in ALS. We also describe recently discovered glial mechanisms that promote motor neuron degeneration using state-of-the-art genetic mouse technology. Finally, we provide an outlook on the extent to which these new pathomechanistic insights may offer novel therapeutic approaches. Muscle Nerve, 2007 [source] How to successfully apply animal studies in experimental allergic encephalomyelitis to research on multiple sclerosisANNALS OF NEUROLOGY, Issue 1 2006Lawrence Steinman MD In their Point of View entitled "Experimental Allergic Encephalomyelitis: A Misleading Model of Multiple Sclerosis," Sriram and Steiner1 wrote, "The most disappointing aspect of EAE [experimental allergic encephalomyelitis] as a potential model for MS is its almost total inability to point toward a meaningful therapy or therapeutic approach for MS." Actually, EAE has led directly to the development of three therapies approved for use in multiple sclerosis (MS): glatiramer acetate, mitoxantrone, and natalizumab. Several new approaches to MS are in clinical trials based on positive indications in preclinical work relying on EAE. New clues to the pathogenesis of MS and new potential surrogate markers for MS are shown from research involving EAE when it is critically coupled with actual findings in MS. There are pitfalls in overreliance on the EAE model, or on any animal model for any human disease. Nevertheless, over the past 73 years, the EAE model has proved itself remarkably useful for aiding research on MS. Ann Neurol 2006;60:12,21 [source] Electric-Field-Assisted Nanostructuring of a Mott InsulatorADVANCED FUNCTIONAL MATERIALS, Issue 17 2009Vincent Dubost Abstract Here, the first experimental evidence for a strong electromechanical coupling in the Mott insulator GaTa4Se8 that allows highly reproducible nanoscaled writing by means of scanning tunneling microscopy (STM) is reported. The local electric field across the STM junction is observed to have a threshold value above which the clean (100) surface of GaTa4Se8 becomes mechanically instable: at voltage biases >1.1,V, the surface suddenly inflates and comes in contact with the STM tip, resulting in nanometer-sized craters. The formed pattern can be indestructibly "read" by STM at a lower voltage bias, thus allowing 5,Tdots inch,2 dense writing/reading at room temperature. The discovery of the electromechanical coupling in GaTa4Se8 might give new clues in the understanding of the electric pulse induced resistive switching recently observed in this stoichiometric Mott insulator. [source] Life at Lofty HeightsGERMAN RESEARCH, Issue 1 2006Christian H. Schulze Dr. Studies of moths in Borneo provide new clues to understanding the diversity of tropical species and in assessing the consequences of deforestation [source] Mitochondrial copper metabolism and delivery to cytochrome c oxidaseIUBMB LIFE, Issue 7 2008Darryl Horn Abstract Metals are essential elements of all living organisms. Among them, copper is required for a multiplicity of functions including mitochondrial oxidative phosphorylation and protection against oxidative stress. Here we will focus on describing the pathways involved in the delivery of copper to cytochrome c oxidase (COX), a mitochondrial metalloenzyme acting as the terminal enzyme of the mitochondrial respiratory chain. The catalytic core of COX is formed by three mitochondrially-encoded subunits and contains three copper atoms. Two copper atoms bound to subunit 2 constitute the CuA site, the primary acceptor of electrons from ferrocytochrome c. The third copper, CuB, is associated with the high-spin heme a3 group of subunit 1. Recent studies, mostly performed in the yeast Saccharomyces cerevisiae, have provided new clues about 1) the source of the copper used for COX metallation; 2) the roles of Sco1p and Cox11p, the proteins involved in the direct delivery of copper to the CuA and CuB sites, respectively; 3) the action mechanism of Cox17p, a copper chaperone that provides copper to Sco1p and Cox11p; 4) the existence of at least four Cox17p homologues carrying a similar twin CX9C domain suggestive of metal binding, Cox19p, Cox23p, Pet191p and Cmc1p, that could be part of the same pathway; and 5) the presence of a disulfide relay system in the intermembrane space of mitochondria that mediates import of proteins with conserved cysteines motifs such as the CX9C characteristic of Cox17p and its homologues. The different pathways are reviewed and discussed in the context of both mitochondrial COX assembly and copper homeostasis. © 2008 IUBMB IUBMB Life, 60(7): 421,429, 2008 [source] Mitochondrial alterations in Parkinson's disease: new cluesJOURNAL OF NEUROCHEMISTRY, Issue 2 2008Miquel Vila Abstract Mitochondrial dysfunction has long been associated with Parkinson's disease (PD). In particular, complex I impairment and subsequent oxidative stress have been widely demonstrated in experimental models of PD and in post-mortem PD samples. A recent wave of new studies is providing novel clues to the potential involvement of mitochondria in PD. In particular, (i) mitochondria-dependent programmed cell death pathways have been shown to be critical to PD-related dopaminergic neurodegeneration, (ii) many disease-causing proteins associated with familial forms of PD have been demonstrated to interact either directly or indirectly with mitochondria, (iii) aging-related mitochondrial changes, such as alterations in mitochondrial DNA, are increasingly being associated with PD, and (iv) anomalies in mitochondrial dynamics and intra-neuronal distribution are emerging as critical participants in the pathogenesis of PD. These new findings are revitalizing the field and reinforcing the potential role of mitochondria in the pathogenesis of PD. Whether a primary or secondary event, or part of a multi-factorial pathogenic process, mitochondrial dysfunction remains at the forefront of PD research and holds the promise as a potential molecular target for the development of new therapeutic strategies for this devastating, currently incurable, disease. [source] Color and Golden Shine of Silver Islamic LusterJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 8 2010P. Carolina Gutierrez Golden-like luster decorations on glazed ceramics from early Islamic times (9,12th centuries AD) consist of a nanocomposite submicrometric layer made of silver metal nanoparticles. The color and golden-like reflectivity of these decorations are dominated by the nonlinear optical response and Mie scattering of the silver nanoparticles. We demonstrate that the enhanced golden-like reflectivity occurs only for dense nanoparticulated layers and that they were obtained by adding PbO to the alkaline glaze. This resulted in reduced diffusivity of silver in the glaze leading to more concentrated and thinner luster layers that formed closer to the glaze surface. The result obtained adds new insights into the high technological level attained during Islamic times and also has important historical implications, giving both new clues concerning the lead enrichment of the glazes during this period, and some basis for the medieval Alchemy search for the production of "gold" from other metals. [source] Efficacy of a short-term ribavirin plus interferon alpha combination therapy followed by interferon alpha alone in previously untreated patients with chronic hepatitis C: a randomized multicenter trialLIVER INTERNATIONAL, Issue 6 2000Thomas Berg Abstract:Background: Combination therapy with interferon alpha (IFN,) plus ribavirin has been shown to improve the sustained response rate in patients with chronic hepatitis C but there is little information regarding the lengths of time for this therapeutic regimen. In this study we therefore tried to evaluate whether the analysis of different virological parameters could provide new clues with respect to the early determination of the efficacy of this form of combination therapy. Furthermore, we also examined whether short-term induction combination therapy followed by IFN, alone is more effective than monotherapy in mounting an initial as well as a sustained virological response. Methods: 185 patients with histologically proven chronic hepatitis C (mean age 42 years (range 19,65 years); 110 males, 75 females) were enrolled in the study. The patients were randomly assigned to receive, over the first 12 weeks, either interferon alpha 2a 6 million units (MU) three times weekly plus ribavirin 14 mg/kg per day (n=93) or the same dose of IFN, alone (n=92). Patients with a virological response (serum HCV RNA undetectable) after 12 weeks were subsequently treated with 3 MU IFN, alone thrice weekly for a further 40 weeks. Otherwise, treatment was discontinued. After the end of treatment, patients were followed up for 24 weeks. Results: Patient characteristics at baseline were not significantly different in the two treatment groups. An initial virological response at week 12 was seen in 61 (66%) patients receiving IFN, plus ribavirin and in 44 (48%) being treated with IFN, alone (p=0.015) and this improvement in the response rate was mainly restricted to HCV genotype 1-infected patients (58% vs. 38%). In contrast, end-of-treatment (week 52) and sustained virological response rates were similar in both groups (37% vs. 29% and 26% vs. 17% [p=0.1], respectively). Interestingly, patients with HCV genotype 3, however, clearly benefited from short-term combination therapy. Thus, sustained virological response rates in these patients significantly increased from 25% (IFN, monotherapy) to 59% (combination therapy) (p=0.05). Conclusions: Short-term combined therapy for 12 weeks is more effective than the monotherapy with respect to the induction of an initial virological response but this effect applies only to genotype 1-infected patients. However, there is no significant difference between both therapeutic schedules with regard to the induction of sustained response. Although HCV genotype 3-infected patients seem to benefit from this short-term combined therapy, prolonged combined therapy may be necessary in HCV genotype 1-infected patients. [source] Recent strategies in the development of new human cytomegalovirus inhibitorsMEDICINAL RESEARCH REVIEWS, Issue 3 2001Ana Martinez Abstract Human cytomegalovirus (HCMV) is one of the most common opportunistic infections in immunucompromised individuals, such as AIDS patients and organ transplant recipients, and is the most frequent congenital viral infection in humans. Despite a reduction of the incidence of AIDS-related opportunistic infections in patients under highly active antiretroviral treatment, attention should be paid to the HCMV risk factor in these individuals. Furthermore, HCMV may have an important role in atherosclerosis. Existing antiviral treatments for the HCMV infection suffer from poor bioavailability, toxicity, and limited effectiveness, mainly due to the development of drug resistance. Fortunately there are novel and potentially very effective new compounds undergoing pre-clinical and clinical evaluation. This review provides an overview in the last five years of new HCMV inhibitors (chemical structures, SAR, and new mechanisms of action) with the aim to provide new clues for the development of future drugs against this opportunistic virus. © 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 3, 227,244, 2001 [source] Biology, clinical characteristics, and management of adrenocortical tumors in childrenPEDIATRIC BLOOD & CANCER, Issue 3 2005Carlos Rodriguez-Galindo MD Abstract Childhood adrenocortical tumors (ACT) are very aggressive endocrine neoplasms whose incidence is quite low. Little is known about their pathogenesis, clinical presentation, and optimal treatment. In recent years, however, new information has been derived from the International Pediatric Adrenocortical Tumor Registry (IPACTR), and new clues to its pathogenesis have emerged. To provide an overview of the available data that may apply to pediatric ACT, we reviewed the epidemiology, pathogenesis, and treatment of ACT in adults and in children. Germline TP53 mutation is almost always the predisposing factor in childhood ACT. A unique germline mutation (TP53,R337H) has been described in Southern Brazil, where the incidence of ACT is 10,15 times the general incidence. Childhood ACT typically present during the first 5 years of life and has female predominance. Hormone hyperproduction is almost universal, and most patients present with virilization. Two-thirds of patients have resectable tumors. Surgery is the definitive treatment for ACT, and a curative complete resection should always be attempted. Cisplatin-based chemotherapy with mitotane is indicated for unresectable or metastatic disease, although its impact on overall outcome is slight. In childhood ACT, age, tumor size, and tumor resectability are the most important prognostic indicators. Outcome is stage-dependent; patients with small, resectable tumors have survival rates in excess of 80%, whereas the outcome for patients with unresectable disease is dismal. Patients with large, resectable tumors have an intermediate outcome. Childhood ACT are rare, but their unique epidemiology appear to implicate novel oncogenic pathways that are unique to the pediatric population. Multi-institutional and prospective studies are necessary to further our understanding of the pathogenesis and to improve outcomes. © 2005 Wiley-Liss, Inc. [source] Food vacuole proteome of the malarial parasite Plasmodium falciparumPROTEOMICS - CLINICAL APPLICATIONS, Issue 9 2008Mauld Lamarque Abstract The Plasmodium falciparum food vacuole (FV) is a lysosome-like organelle where erythrocyte hemoglobin digestion occurs. It is a favorite target in the development of antimalarials. We have used a tandem mass spectrometry approach to investigate the proteome of an FV-enriched fraction and identified 116 proteins. The electron microscopy analysis and the Western blot data showed that the major component of the fraction was the FV and, as expected, the majority of previously known FV markers were recovered. Of particular interest, several proteins involved in vesicle-mediated trafficking were identified, which are likely to play a key role in FV biogenesis and/or FV protein trafficking. Recovery of parasite surface proteins lends support to the cytostomal pathway of hemoglobin ingestion as a FV trafficking route. We have identified 32 proteins described as hypothetical in the databases. This insight into FV protein content provides new clues towards understanding the biological function of this organelle in P. falciparum. [source] What can humans learn from flies about adenomatous polyposis coli?BIOESSAYS, Issue 9 2002Angela I.M. Barth Somatic or inherited mutations in the adenomatous polyposis coli (APC) gene are a frequent cause of colorectal cancer in humans. APC protein has an important tumor suppression function to reduce cellular levels of the signaling protein ,-catenin and, thereby, inhibit ,-catenin and T-cell-factor-mediated gene expression. In addition, APC protein binds to microtubules in vertebrate cells and localizes to actin-rich adherens junctions in epithelial cells of the fruit fly Drosophila (Fig. 1). Very little is known, however, about the function of these cytoskeletal associations. Recently, Hamada and Bienz have described a potential role for Drosophila E-APC in cellular adhesion,1 which offers new clues to APC function in embryonic development, and potentially colorectal adenoma formation and tumor progression in humans. BioEssays 24:771,774, 2002. © 2002 Wiley Periodicals, Inc. [source] First Record of Protorosaurid Reptile (Order Protorosauria) from the Middle Triassic of ChinaACTA GEOLOGICA SINICA (ENGLISH EDITION), Issue 4 2003LI Chun Abstract, A new genus and species of the family Tanystropheidae, Dinocephalosaurus orientalis gen. et sp. nov., is described based on a nearly complete skull. This is the first record of the order Protorosauria from China. It also represents the only known occurrence of Tanystropheidae outside Europe, the Middle East and North America. Dinocephalosaurus is quite similar to Tanystropheus from Monte San Giorgio, Switzerland. Primarily it is distinguished from Tanystropheus in the shape of the premaxilla, maxilla, jugal and parietal. Although the family Tanystropheidae is now referred to the order Protorosauria, the new material from China indicates that the archosauromorph affinities of tanystropheids need further investigation. The discovery of Dinocephalosaurus provides new clues for the study of the evolution and radiation of Protorosauria and Tanystropheidae. It is also important for the study of the eastern Tethyan Fauna and the paleobiogeographical relationship between Europe and southern China in the Triassic. [source] Estrogen signaling pathway and its imaging in human breast cancerCANCER SCIENCE, Issue 10 2009Shin-ichi Hayashi Recent remarkable progress in hormonal therapy has provided great benefit to breast cancer patients, but it also evokes novel issues: how accurately can the efficacy of each hormonal therapy be predicted and how can hormonal therapy,resistant patients be treated? These clinically important issues must be closely related to the biological events in each cancer, such as the alteration of intracellular multiple estrogen signaling pathways and the estrogen-related cancer microenvironment, which has recently revealed by molecular biological studies on estrogen and its receptors. However, the estrogen signaling status in individual breast cancers has not been clarified yet. Here we present the context of these issues and introduce our study of new tools which enable the visualization of estrogen signals in individual cancers. The assessment of estrogen receptor (ER)-, activity in individual cancers or ER-activating ability of the cancer microenvironment in each breast cancer patient revealed several new findings and interesting observations. We hope that these approaches provide new clues about the estrogen-dependent mechanisms of breast cancer development, and will be useful to advance the diagnosis and treatment of breast cancer patients. (Cancer Sci 2009; 100: 1773,1778) [source] Update on genetic and clinical aspects of primary hyperparathyroidismCLINICAL ENDOCRINOLOGY, Issue 5 2003S. Miedlich Summary Primary hyperparathyroidism (pHPT) is a common endocrine disorder that predominantly affects postmenopausal women. It is mostly caused by solitary tumours within the parathyroid glands. Although the pathophysiology of pHPT is still incompletely understood, recent studies provide new clues on the development and cellular growth of tumours within the parathyroids associated with hypersecretion of parathyroid hormone and hypercalcaemia. The natural course of pHPT is rather benign. Nowadays, it has become an oligo- or asymptomatic disease often only detected by routine blood tests. These facts raise the question whether to perform parathyroidectomy on oligo- and asymptomatic patients with pHPT or whether it is possible to monitor these patients without surgery. The aim of this article is to review the literature as regards (i) the pathophysiological mechanisms that underlie parathyroid neoplasia and (ii) the defective calcium-sensing in patients with pHPT (iii) environmental and/or genetic risk factors that predispose to or promote parathyroid neoplasia, as well as (iv) alternative approaches to treat oligo- and asymptomatic patients with pHPT medically. [source] | |||||||||||||||||||||||||