Human Disease

Source: au.rd.yahoo.com --- 18 days ago
MADISON, Wisconsin (Reuters) - Advances in stem cell research offer a new way of studying Human Disease, allowing scientists to move beyond fruit flies and lab mice to see how Human cells go awry and how drugs and other therapies might help, U. S. researchers said on Monday. ...

Source: www.reuters.com --- 18 days ago
MADISON, Wisconsin (Reuters) - Advances in stem cell research offer a new way of studying Human Disease, allowing scientists to move beyond fruit flies and lab mice to see how Human cells go awry and how drugs and other therapies might help, U. S. researchers said on Monday. ...

Source: www.ncbi.nlm.nih.gov --- 33 days ago
Human Borna Disease virus-infection and its therapy in affective disorders. APMIS Suppl. 2008;(124):61-5 Authors: Dietrich DE, Bode L Patients with affective disorders show an enhanced prevalence of Borna Disease virus (BDV)-infection. Furthermore, BDV causes latent infection preferably in limbic central nervous structures and is suggested to be causally related to subtypes of affective disorders, especially with melancholic clinical features or bipolarity. Such a possible link was highlighted by the first report of amantadine showing an antidepressive and an antiviral efficacy against BDV in a patient with a bipolar disorder. This article summarizes clinical studies which followed this first report on the use of amantadine in BDV-infected patients with an affective disorder. A special focus is given on an open clinical study in patients with depression (n = 25), a study in remitted patients with affective disorders (n = 16), and the effect of amantadine on severe hypomanic or moderately manic patients with a bipolar disorder in an on-off-on study. In these studies amantadine reduced clinical symptoms paralleled by a reduction of BDV-infection in depressive patients, it also reduced all three BDV-parameters (BDV-Ab, -AG, and -CICs) in remitted patients, and it even reduced severe hypomania and moderate mania in bipolar patients. These data suggest the existence of an etiopathogenetic link between BDV and subtypes of affective disorders ...

Source: www.ncbi.nlm.nih.gov --- 29 days ago
Related Articles Targets of caspase-6 activity in Human neurons and Alzheimer Disease. Mol Cell Proteomics. 2008 Aug;7(8):1541-55 Authors: Klaiman G, Petzke TL, Hammond J, Leblanc AC Caspase-6 activation occurs early in Alzheimer Disease and sometimes precedes the clinical manifestation of the Disease in aged individuals. The active Caspase-6 is localized in neuritic plaques, in neuropil threads, and in neurofibrillary tangles containing neurons that are not morphologically apoptotic in nature. To investigate the potential consequences of the activation of Caspase-6 in neurons, we conducted a proteomics analysis of Caspase-6-mediated cleavage of Human neuronal proteins. Proteins from the cytosolic and membrane subcellular compartments were treated with recombinant active Caspase-6 and compared with undigested proteins by two-dimensional gel electrophoresis. LC/MS/MS analyses of the proteins that were cleaved identified 24 different potential protein substrates. Of these, 40% were cytoskeleton or cytoskeleton-associated proteins. We focused on the cytoskeleton proteins because these are critical for neuronal structure and function. Caspase-6 cleavage of alpha-Tubulin, alpha-Actinin-4, Spinophilin, and Drebrin was confirmed. At least one Caspase-6 cleavage site was identified for Drebrin, Spinophilin, and alpha-Tubulin. A neoepitope antiserum to alpha-Tubulin cleaved by Caspase-6 immunostained neurons, neurofibrillary tangles, neuropil t ...

Source: www.ncbi.nlm.nih.gov --- 17 days ago
Related Articles Viral infection and Human Disease--insights from minimotifs. Front Biosci. 2008;13:6455-71 Authors: Kadaveru K, Vyas J, Schiller MR Short functional peptide motifs cooperate in many molecular functions including protein interactions, protein trafficking, and posttranslational modifications. Viruses exploit these motifs as a principal mechanism for hijacking cells and many motifs are necessary for the viral life-cycle. A virus can accommodate many short motifs in its small genome size providing a plethora of ways for the virus to acquire host molecular machinery. Host enzymes that act on motifs such as kinases, proteases, and lipidation enzymes, as well as protein interaction domains, are commonly mutated in Human Disease, suggesting that the short peptide motif targets of these enzymes may also be mutated in Disease; however, this is not observed. How can we explain why viruses have evolved to be so dependent on motifs, yet these motifs, in general do not seem to be as necessary for Human viability? We propose that short motifs are used at the system level. This system architecture allows viruses to exploit a motif, whereas the viability of the host is not affected by mutation of a single motif. PMID: 18508672 [PubMed - indexed for MEDLINE] ...

Source: www.ncbi.nlm.nih.gov --- 4 days ago
Related Articles Thymidine-dependent Staphylococcus aureus small-colony-variants: relevant Human pathogens not only in cystic fibrosis lung Disease. J Clin Microbiol. 2008 Oct 1; Authors: Besier S, Zander J, Siegel E, Saum SH, Hunfeld KP, Ehrhart A, Brade V, Wichelhaus TA We report the isolation of thymidine-dependent small-colony-variants of Staphylococcus aureus (TD-SCVs) from unusual infection sites of patients with chronic soft tissue infection, tympanitis, bronchitis, peritonitis, and septicemia. Further we provide evidence that the essential growth factor for TD-SCVs, i.e. thymidine, and its metabolite dTMP, are present in various Human specimens. PMID: 18832128 [PubMed - as supplied by publisher] ...

Source: www.ncbi.nlm.nih.gov --- 5 days ago
Related Articles The Role of Lmx1a in the Differentiation of Human Embryonic Stem Cells into Midbrain Dopamine Neurons in Culture and after Transplantation into a Parkinson's Disease Model. Stem Cells. 2008 Oct 2; Authors: Cai J, Donaldson A, Yang M, German MS, Enikolopov G, Iacovitti L Recent studies have provided important insight into the homeoprotein Lmx1a and its role in the commitment of cells to a midbrain dopamine (mDA) fate in the developing mouse. We show here that Lmx1a also plays a pivotal role in the mDA differentiation of Human embryonic stem (hES) cells. Thus, as indicated by siRNA experiments, the transient early expression of Lmx1a is necessary for the coordinated expression of all other DA-specific phenotypic traits as hES cells move from multipotent neural progenitors (hNPs) to more restricted precursor cells in vitro. Moreover, only Lmx1a-specified hNPs have the potential to differentiate into bona fide midbrain mDA neurons after transplantation into the 6-hydroxydopamine treated rat striatum. In contrast, cortical HNPCs and mouse SVZ cells do not express Lmx1a or become mDA neurons even when placed in an environment that fosters their DA differentiation in vitro or in vivo. These findings suggest that Lmx1a may be critical to the development of mDA neurons from hES cells and, that along with other key early DA markers (Aldh1a1), may prove to be extremely useful for the selection of appropriately staged and suitabl ...

Source: www.ncbi.nlm.nih.gov --- 9 days ago
Related Articles What is the biopsychosocial role of Human immunodeficiency virus positivity in patients with end-stage liver Disease who undergo orthotopic liver transplantation? Transplant Proc. 2008 Jul-Aug;40(6):1910-2 Authors: Barbanti Silva V, Ferrara M, Mazzi F, Pingani L, Cocchi S, Romano A, Masetti M, Gerunda GE, Guaraldi G, Rigatelli M INTRODUCTION: Since 2003 the National Research Program for Solid Organ Transplantation in patients with Human immunodeficiency virus (HIV) is active at our liver transplantation center. Patients with HIV who enter this protocol are assessed by the Consultation Liaison Psychiatry Service. The aim of the present study was to evaluate their psychiatric comorbidity. METHODS: An observational prospective study was conducted comparing end-stage liver Disease (ESLD) patients with and without HIV. After the assessment, the psychiatrist compiled the Transplant Evaluation Rating Scale (TERS) and the Montgomery Asberg Depression Rating Scale (MADRS). Baseline evaluation was made before inclusion on the OLT waiting list and the follow-up evaluation was made 12 months later. RESULTS: From January 2003 to December 2006 we assessed 553 patients: 39 (6%) with HIV and 361 (94%) without HIV. The 2 groups were homogeneous for gender (75% of male patients; P=not significant [NS]) but not for age (46+/-5 vs 56+/-9; P=NS). Psychiatric history was negative in 176 (49%) patients without HIV and in 6 (15%) patients wi ...

Source: www.moreover.com --- 11 days ago
MedWire News: A pig model of cystic fibrosis (CF) has been developed that appears to closely mimic the Disease in Human infants, US researchers report in the journal Science. ...

Source: nihroadmap.nih.gov --- 5 days ago
The purpose of this notice is to clarify the Research Objectives (Program Components) located in the Funding Opportunity Description and the Review and Selection Process located in the Award Information for the funding opportunity announcement (FOA), RFA-RM-08-017, Epigenomics of Human Health and Disease. ...

Source: www.nih.gov --- 15 days ago
For the first time, researchers have developed a genetically altered animal model for cystic fibrosis (CF) that closely matches the characteristics of the Disease in humans. By studying the complex and multi-organ Disease process in the pig model, researchers can now better understand how the complications of CF develop, an advancement that may lead to new avenues for research in prevention and treatment. The study, published in the Sept. 26 edition of "Science," was funded in part by the National Heart, Lung, and Blood Institute (NHLBI), along with the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), both of the National Institutes of Health, as well as the Cystic Fibrosis Foundation. ...

Source: www.moreover.com --- 14 days ago
Medical Research News For the first time, researchers have developed a genetically altered animal model for cystic fibrosis (CF) that closely matches the characteristics of the Disease in humans. ...

Source: www.ncbi.nlm.nih.gov --- 19 days ago
Related Articles Being a mouse in a man's world: what TMEV has taught us about Human Disease. Front Biosci. 2008;13:3775-85 Authors: Drescher KM, Sosnowska D Choosing an appropriate animal model to study a Disease is guided by a variety of factors including but not limited to the questions being asked, availability of reagents, knowledge of the animal species, personal biases of the researcher, and in some cases, cost and availability of facilities to effectively investigate the model. The validity of an animal model can be further complicated when the etiology of the Disease is incompletely defined. Examples of these diseases include multiple sclerosis (MS) and type 1 diabetes (T1D). In addition to host genetics, epidemiological studies have implicated infectious agents, in particular viruses as triggers of these diseases. Thus many studies of these diseases have focused on modeling the interactions of viruses and the host immune response in vivo in small animals. Theiler's murine encephalomyelitis virus (TMEV) infection of mice has been used for over 30 years as a model of virus-induced demyelination. TMEV induces a MS-like Disease in susceptible strains of mice but does not cause pathology in humans. While some researchers may question the rationale for using a non-Human pathogen to model Human Disease, the TMEV model of central nervous system (CNS) demyelination has permitted study of some aspects of Human MS which would have been ...

Source: www.ncbi.nlm.nih.gov --- 15 days ago
Related Articles NTPDase and 5'-nucleotidase activities in physiological and Disease conditions: New perspectives for Human health. Biofactors. 2007;31(2):77-98 Authors: Schetinger MR, Morsch VM, Bonan CD, Wyse AT Extracellular nucleotides and nucleosides act as signaling molecules involved in a wide spectrum of biological effects. Their levels are controlled by a complex cell surface-located group of enzymes called ectonucleotidases. There are four major families of ectonucleotidases, nucleoside triphosphate diphosphohydrolases (NTPDases/CD39), ectonucleotide pyrophosphatase/phosphodiesterases (E-NPPs), alkaline phosphatases and ecto-5'-nucleotidase. In the last few years, substantial progress has been made toward the molecular identification of members of the ectonucleotidase families and their enzyme structures and functions. In this review, there is an emphasis on the involvement of NTPDase and 5'-nucleotidase activities in Disease processes in several tissues and cell types. Brief background information is given about the general characteristics of these enzymes, followed by a discussion of their roles in thromboregulatory events in diabetes, hypertension, hypercholesterolemia and cancer, as well as in pathological conditions where platelets are less responsive, such as in chronic renal failure. In addition, immunomodulation and cell-cell interactions involving these enzymes are considered, as well as ATP and ADP hydrolysis under ...

Source: www.ncbi.nlm.nih.gov --- 13 days ago
Related Articles Hippocampal Estrogen Receptor-Alpha Splice Variant TADDI in the Human Brain in Aging and Alzheimer's Disease. Neuroendocrinology. 2008 Sep 25; Authors: Ishunina TA, Swaab DF Background/Aims: Estrogen receptor-alpha (ERalpha) splice variants are important for understanding estrogen effects on the brain and estrogen therapy pitfalls. We addressed the question whether a novel ERalpha splice variant TADDI is expressed at the protein level in the Human brain and whether it changes in relation to aging and Alzheimer's Disease (AD). Methods: Immunoreactivity (-ir) for TADDI was assessed on postmortem Human brain material from a total of 116 cases. Results: The highest levels of this splice form were found in the hypothalamic supraoptic nucleus (SON), pontine nuclei, medulla oblongata, gray matter of the spinal cord, the hippocampus, glomeruli of the cerebellum, the nucleus basalis of Meynert (NBM), and the tuberomamillary nucleus (TMN). TADDI-ir was mainly confined to the cytoplasm but was also determined in the nuclei of hippocampal neurons from young patients. In the hippocampus, the NBM, and the TMN, TADDI-ir was higher in postmenopausal women than in women </=50 years old. In these brain areas and in the SON, it was diminished in AD women. In the NBM of AD men, TADDI-ir was enhanced. Conclusion: Aging- and AD-related changes in TADDI-ir show that it should be considered for the sensitivity of the neural tissue to estroge ...

Source: www.ncbi.nlm.nih.gov --- 10 days ago
Related Articles Antagonism of the Human epidermal growth factor receptor family controls Disease severity in murine collagen-induced arthritis. Arthritis Rheum. 2008 Sep 29;58(10):3071-3080 Authors: Sumariwalla PF, Jin P, Zhang J, Ni I, Crawford D, Shepard HM, Paleolog EM, Feldmann M OBJECTIVE: To evaluate the therapeutic potential of the Human epidermal growth factor receptor (HER) family inhibitor, herstatin, in an animal model of arthritis. METHODS: Constructs of herstatin and modified tissue plasminogen activator (tPA)-herstatin were expressed in HEK 293T cells, and secreted protein was analyzed by Western blotting. Tissue PA-herstatin adenovirus (Ad-tPA-Her) was prepared, and titers established. Gene expression of Ad-tPA-Her was determined by polymerase chain reaction using HeLa cells. Pharmacokinetics of gene and protein expression in vivo in liver tissue and serum samples were confirmed via intravenous administration of Ad-tPA-Her. Clinical signs of Disease were monitored in arthritic DBA/1 mice after therapeutic administration of Ad-tPA-Her, and histologic analysis of hind foot specimens was performed. RESULTS: Native herstatin was not secreted in supernatants, while modified tPA-herstatin was detected in abundance. HeLa cells stably expressed the tPA-herstatin gene when infected with virus. Additionally, tPA-herstatin gene and protein expression was observed over time in mice treated with virus. Importantly, Ad-tPA-Her, when ...

Source: www.ncbi.nlm.nih.gov --- 13 days ago
Related Articles Aspects of Human Disease. 22. Schizophrenia. Dent Update. 2008 May;35(4):285 Authors: Scully C, Chaudhry SI PMID: 18557507 [PubMed - indexed for MEDLINE] ...

Source: www.ncbi.nlm.nih.gov --- 23 days ago
Related Articles Changes in the Immune Responses Against Human Herpesvirus-8 in the Disease Course of Posttransplant Kaposi Sarcoma. Transplantation. 2008 Sep 15;86(5):738-744 Authors: Barozzi P, Bonini C, Potenza L, Masetti M, Cappelli G, Gruarin P, Whitby D, Gerunda GE, Mondino A, Riva G, Vallerini D, Quadrelli C, Bosco R, Ciceri F, Bordignon C, Schulz TF, Torelli G, Luppi M In nine patients with posttransplant Kaposi sarcoma (KS) T-cell responses to Human herpesvirus (HHV)-8 latent and lytic antigens, as detected by enzyme-linked-immunospot (Elispot) assay, were absent at Disease onset. Virus-specific T-cell responses were detected in six renal recipients at remission after a reduction of calcineurin inhibitors (CIs), and in two HHV-8 seropositive renal recipients without KS. In two liver recipients undergoing switch from CIs to sirolimus (SRL), normalization of the T-cell repertoire and recovery of both HHV-8-specific effector and memory T lymphocytes were associated with complete KS remission. In a renal recipient undergoing SRL conversion, the early recovery of HHV-8-specific effector but not of memory T lymphocytes, was associated only with partial remission. Neither rejection nor changes in graft function were observed after SRL conversion. HHV-8-specific T-cell responses are required to achieve posttransplant KS remission, and may be restored under SRL, while maintaining effective immunosuppression. PMID: 18791457 [PubMed - as ...

Source: www.ncbi.nlm.nih.gov --- 18 days ago
Related Articles An NF-kB-sensitive microRNA-146a-mediated inflammatory circuit in Alzheimer's Disease and in stressed Human brain cells. J Biol Chem. 2008 Sep 18; Authors: Lukiw WJ, Zhao Y, Cui JG Human brains retain discrete populations of micro RNA (miRNA) species that support homeostatic gene expression functions, however, specific miRNA abundances are significantly altered in neurological disorders such as Alzheimer's Disease (AD) when compared to age-matched controls. Here we provide evidence in AD brains of a specific up-regulation of an NF-kB-sensitive miRNA-146a highly complementary to the 3' un-translated region (3'UTR) of complement factor H (CFH), an important repressor of the brain's inflammatory response. Up-regulation of miRNA-146a coupled to down-regulation of CFH was observed in AD brain and in IL-1ss, Ass42 and/or oxidatively-stressed Human neural (HN) cells in primary culture. Transfection of HN cells using an NF-kB-containing pre-miRNA-146a promoter-luciferase reporter construct in stressed HN cells showed significant up-regulation of luciferase activity that paralleled decreases in CFH gene expression. Treatment of stressed HN cells with the NF-kB inhibitors pyrollidine dithiocarbamate (PDTC) or the resveratrol analog CAY10512 abrogated this response. Incubation of an antisense oligonucleotide to miRNA-146a (anti-miRNA-146a; AM146a) was found to restore CFH expression levels. These data indicate that NF-kB-sensitiv ...

Source: news.ninemsn.com.au --- 5 days ago
Two piggery workers have contracted a potentially deadly heart Disease from animals bound for the abattoir. ...