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Herpes simplex virus induced oral and genital ulcerating lesions will fluoresce brightly yellow and yellow-orange, respectively, if treated with a chlorinated solution of neutral red and exposed to ultraviolet-A light. An orange to red fluorescence is seen with similarly treated and illuminated Herpes zoster virus induced shingles; while treated human papillomavirus induced genital warts display more of a purplish fluorescence. Pain and discomfort commonly disappear soon after the treatment and all lesions undergo expedited healing that is readily observable within 24 h. The mechanism of healing is thought to involve an interaction between neutral red and alternative cellular energy pigments (ACE pigments) present within the viral lesions that enhances responsiveness to ultraviolet light energy. The healing effects are not restricted to the treated lesions and may involve transmission of a biological energy throughout the body. Beyond its obvious clinical and diagnostic utility, this model system may help usher in a new era of energy-based medicine.
Exp Mol Pathol 2005 Apr
PMID:Symptomatic relief of herpetic skin lesions utilizing an energy-based approach to healing. 1571 38

The first reported reference to delayed onset muscle soreness (DOMS) was that by Theodore Hough in 1902. Hough stated that when an untrained skeletal muscle performed exercise, it often resulted in discomfort that did not manifest until 8-10 h post-exercise, and concluded that this could not be solely attributed to fatigue. Since Hough's initial observation there has been a proliferation in research into DOMS, and despite this, the exact aetiology remains unclear. This review explores the concept of DOMS in relation to the likely causative factors and also discusses possible reasons for the equivocal findings in the literature. Free radicals are unquestionably produced during and following various forms of contractile activity and are known to result in skeletal muscle damage. Given the link between DOMS and contraction-induced muscle damage, post-exercise free radical production has been associated with DOMS; however, the precise nature of this relationship remains unsubstantiated. This review will address free radical production during and following exercise, discuss methods of assessing their generation, and critically evaluate their relationship with DOMS. There is increasing literature to suggest that free radicals act as signalling molecules, specifically activating redox sensitive transcription factors, which are necessary for muscle regeneration and adaptation following damage. Consequently free radicals may play a key physiological role in the aetiology of DOMS as opposed to a pathological role. Evidence for and against free radicals causing DOMS will be presented, and finally a suggested role of free radicals in DOMS will be proposed.
Comp Biochem Physiol A Mol Integr Physiol 2005 Nov
PMID:The emerging role of free radicals in delayed onset muscle soreness and contraction-induced muscle injury. 1615 65

Biomaterials are regularly used in various types of artificial tissues and organs, such as oxygenators, plasmapheresis equipment, hemodialysers, catheters, prostheses, stents, vascular grafts, miniature pumps, sensors and heart aids. Although progress has been made regarding bioincompatibility, many materials and procedures are associated with side effects, in particular bioincompatibility-induced inflammation, infections and subsequent loss of function. After cardiopulmonary bypass, coagulopathies can occur and lead to cognitive disturbances, stroke and extended hospitalization. Hemodialysis is associated with anaphylatoid reactions that cause whole-body inflammation and may contribute to accelerated arteriosclerosis. Stents cause restenosis and, in severe cases, thrombotic reactions. This situation indicates that there is still a need to try to understand the mechanisms involved in these incompatibility reactions in order to be able to improve the biomaterials and to develop treatments that attenuate the reactions and thereby reduce patients' discomfort, treatment time and cost. This overview deals with the role of complement in the incompatibility reactions that occur when biomaterials come in contact with blood and other body fluids.
Mol Immunol 2007 Jan
PMID:The role of complement in biomaterial-induced inflammation. 1690 92

One major goal in pain research is to identify novel pain targets. Tissue injury, inflammation, and ischemia are usually accompanied by local tissue acidosis, the degree of associated pain or discomfort well correlated with the magnitude of acidification. Proton-sensing ion channels, transient receptor potential/vanilloid receptor subtype 1, and acid-sensing ion channel 3 are involved in acidosis-linked pain. However, whether recently identified proton-sensing G-protein-coupled receptors (GPCRs) also have some contributions is unclear. Proton-sensing GPCRs, including OGR1, GPR4, G2A, and TDAG8, are fully activated at pH 6.4-6.8 in vitro. To understand whether the proton-sensing GPCRs are expressed in nociceptors, we cloned the four mouse genes and examined their tissue distribution and localization in pain-relevant loci, the dorsal root ganglion (DRG). The OGR1 family members were widely expressed in neuronal and non-neuronal tissues. Their transcripts were expressed in the DRG, and most (75-82%) were present in small-diameter neurons responsible for nociception. Approximately 31-40% of total DRG neurons expressed at least two proton-sensing GPCRs. We have also demonstrated that gene expression of proton-sensing GPCRs is changed in ASIC3 knockout mice. Our finding suggests that proton-sensing GPCRs could have some roles in nociception or in compensation of loss of ASIC3 gene.
Mol Cell Neurosci 2007 Oct
PMID:Nociceptors of dorsal root ganglion express proton-sensing G-protein-coupled receptors. 1772 May 33

Immunotherapy against infectious agents and malignant tumors requires efficient priming of effector cells through direct expression and/or efficient cross-presentation of antigens by antigen-presenting cells. Electroporation is a new procedure aimed at transiently increasing cell membrane permeability and direct delivery of antigen or antigen-encoding nucleic acids inside targeted cells. We evaluated the tolerability including compliance with repeated electroporation treatments using MedPulser DDS in 24 healthy adults. Pain severity was evaluated at time of electroporation treatment, and at 1, 5, 10, and 20 minutes, and 24 hours thereafter, using two clinically validated questionnaires: McGill Pain Questionnaire (MPQ) (Present Pain Intensity) and Brief Pain Inventory (BPI). Electroporation treatments were generally well tolerated. Twenty-two out of 24 subjects returned for the second electroporation treatment 14 days after first treatment. Only two subjects reported a treatment-related systemic adverse experience following either electroporation application. For both pain assessment tools, maximum pain and/or discomfort were mostly reported immediately (within 5 minutes) after electroporation; Furthermore, no difference was observed when comparing peak-pain scores after first and second electroporation treatments. This study supports the clinical application of MedPulser DDS for the improvement of antigen-induced immune responses for prophylactic or therapeutic vaccines, especially in gene-based therapies for cancer.
Mol Ther 2009 May
PMID:Tolerability of two sequential electroporation treatments using MedPulser DNA delivery system (DDS) in healthy adults. 1927 16

The scabies mite (Sarcoptes scabiei) is a parasite responsible for major morbidity in disadvantaged communities and immuno-compromised patients worldwide. In addition to the physical discomfort caused by the disease, scabies infestations facilitate infection by Streptococcal species via skin lesions, resulting in a high prevalence of rheumatic fever/heart disease in affected communities. The scabies mite produces 33 proteins that are closely related to those in the dust mite group 3 allergen and belong to the S1-like protease family (chymotrypsin-like). However, all but one of these molecules contain mutations in the conserved active-site catalytic triad that are predicted to render them catalytically inactive. These molecules are thus termed scabies mite inactivated protease paralogues (SMIPPs). The precise function of SMIPPs is unclear; however, it has been suggested that these proteins might function by binding and protecting target substrates from cleavage by host immune proteases, thus preventing the host from mounting an effective immune challenge. In order to begin to understand the structural basis for SMIPP function, we solved the crystal structures of SMIPP-S-I1 and SMIPP-S-D1 at 1.85 A and 2.0 A resolution, respectively. Both structures adopt the characteristic serine protease fold, albeit with large structural variations over much of the molecule. In both structures, mutations in the catalytic triad together with occlusion of the S1 subsite by a conserved Tyr200 residue is predicted to block substrate ingress. Accordingly, we show that both proteases lack catalytic function. Attempts to restore function (via site-directed mutagenesis of catalytic residues as well as Tyr200) were unsuccessful. Taken together, these data suggest that SMIPPs have lost the ability to bind substrates in a classical "canonical" fashion, and instead have evolved alternative functions in the lifecycle of the scabies mite.
J Mol Biol 2009 Jul 24
PMID:Structural mechanisms of inactivation in scabies mite serine protease paralogues. 1942 18

Probiotics are live microorganisms that promote health benefits upon consumption, while prebiotics are nondigestible food ingredients that selectively stimulate the growth of beneficial microorganisms in the gastrointestinal tract. Probiotics and/or prebiotics could be used as alternative supplements to exert health benefits, including cholesterol-lowering effects on humans. Past in vivo studies showed that the administration of probiotics and/or prebiotics are effective in improving lipid profiles, including the reduction of serum/plasma total cholesterol, LDL-cholesterol and triglycerides or increment of HDL-cholesterol. However, other past studies have also shown that probiotics and prebiotics had insignificant effects on lipid profiles, disputing the hypocholesterolemic claim. Additionally, little information is available on the effective dosage of probiotics and prebiotics needed to exert hypocholesterolemic effects. Probiotics and prebiotics have been suggested to reduce cholesterol via various mechanisms. However, more clinical evidence is needed to strengthen these proposals. Safety issues regarding probiotics and/or prebiotics have also been raised despite their long history of safe use. Although probiotic-mediated infections are rare, several cases of systemic infections caused by probiotics have been reported and the issue of antibiotic resistance has sparked much debate. Prebiotics, classified as food ingredients, are generally considered safe, but overconsumption could cause intestinal discomfort. Conscientious prescription of probiotics and/or prebiotics is crucial, especially when administering to specific high risk groups such as infants, the elderly and the immuno-compromised.
Int J Mol Sci 2010 Jun 17
PMID:Cholesterol-lowering effects of probiotics and prebiotics: a review of in vivo and in vitro findings. 2064 Jan 65

Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by reduced amounts of the mitochondrial protein frataxin. Frataxin levels in research studies are typically measured via Western blot analysis from patient fibroblasts, lymphocytes, or muscle biopsies; none of these is ideal for rapid detection in large scale clinical studies. Recently, a rapid, noninvasive lateral flow immunoassay was developed to accurately measure picogram levels of frataxin protein and shown to distinguish lymphoblastoid cells from FRDA carriers, patients and controls. We expanded the immunoassay to measure frataxin directly in buccal cells and whole blood from a large cohort of controls, known carriers and patients typical of a clinical trial population. The assay in buccal cells shared a similar degree of variability with previous studies conducted in lymphoblastoid cells (~10% coefficient of variation in controls). Significant differences in frataxin protein quantity were seen between the mean group values of controls, carriers, and patient buccal cells (100, 50.2, and 20.9% of control, respectively) and in protein extracted from whole blood (100, 75.3, and 32.2%, respectively), although there was some overlap between the groups. In addition, frataxin levels were inversely related to GAA repeat length and correlated directly with age of onset. Subjects with one expanded GAA repeat and an identified frataxin point mutation also carried frataxin levels in the disease range. Some patients displaying an FRDA phenotype but carrying only a single identifiable mutation had frataxin levels in the FRDA patient range. One patient from this group has a novel deletion that included exons 2 and 3 of the FXN gene based on multiplex ligation-dependent probe amplification (MLPA) analysis of the FXN gene. The lateral flow immunoassay may be a useful means to noninvasively assess frataxin levels repetitively with minimal discomfort in FRDA patients in specific situations such as clinical trials, and as a complementary diagnostic tool to aid in identification and characterization of atypical patients.
Mol Genet Metab
PMID:A rapid, noninvasive immunoassay for frataxin: utility in assessment of Friedreich ataxia. 2067 66

This is a case report of a 66-year-old woman who consulted us with a 1-week history of postprandial epigastric discomfort and dyspepsia. Upper and lower gastrointestinal endoscopy and double-balloon enteroscopy revealed lesions in three parts: a swelling with a shallow depression in the ampulla of Vater, flat and rough nodules in the jejunum, and a mixture of lymphoid polyposis and rough surface of follicular lymphoma of the terminal ileum and Bauhin valve. The histological, immunophenotypic, and molecular findings of the duodenal lesion confirmed the diagnosis of follicular lymphoma. We initially diagnosed the ileal lesion as MALT lymphoma immunohistochemically. However, Southern blot hybridization analysis for immunoglobulin heavy chain gene rearrangement showed identical monoclonal bands in both the duodenal and ileal lesions. The molecular cytogenetic studies were also positive for the 14;18 translocation in both lesions. Therefore, the true diagnosis of this ileal lesion should be a follicular lymphoma with marginal zone differentiation. Primary follicular lymphomas of gastrointestinal tract were suggested to have intermediate features between nodal follicular lymphoma and MALT lymphoma. This case is an important clue to prove the similarity of follicular lymphoma of gastrointestinal tract to MALT lymphoma and will be crucial in considering the therapeutic strategy.
Med Mol Morphol 2010 Sep
PMID:A duodenal follicular lymphoma associated with the lesion mimicking MALT lymphoma in terminal ileum and Bauhin valve. 2085 67

To assess the recovery effect of water-soluble components of nacre on wound healing of burns, water-soluble nacre (WSN) was obtained from powdered nacre. Alterations to WSN-mediated wound healing characteristics were examined in porcine skin with deep second-degree burns; porcine skin was used as a proxy for human. When WSN was applied to a burned area, the burn-induced granulation sites were rapidly filled with collagen, and the damaged dermis and epidermis were restored to the appearance of normal skin. WSN enhanced wound healing recovery properties for burn-induced apoptotic and necrotic cellular damage and spurred angiogenesis. Additionally, WSN-treated murine fibroblast NIH3T3 cells showed increased proliferation and collagen synthesis. Collectively, the findings indicate that WSN improves the process of wound healing in burns by expeditiously restoring angiogenesis and fibroblast activity. WSN may be useful as a therapeutic agent, with superior biocompatibility to powdered nacre, and evoking less discomfort when applied to a wounded area.
Mol Biol Rep 2012 Mar
PMID:Nacre-driven water-soluble factors promote wound healing of the deep burn porcine skin by recovering angiogenesis and fibroblast function. 2168 45


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