The human priondiseases comprise sporadic, genetic, and acquired disorders... can be used to determine the major categories of human priondisease... biochemical data to allow an accurate diagnosis of a human priondisease and facilitates subclassification into recognized disease subtypes, for example in ... The spectrum of human priondiseases continues to expand and neuropathology will play a key role ...
Prion Diseases (5), Creutzfeldt-Jakob Syndrome (1), Gliosis (1), more mentions
Gerstmann-Sträussler-Scheinker disease (GSS) is an autosomal, dominantly inherited priondisease. In this study, we present different complicated brain pathologies determined postmortem of monozygotic GSS twin sisters. Case 1 showed cerebellar ataxia at the age of 58 years, and died at 66 years. Case 2 became symptomatic at the age of 75 years, and died at 79 years.
During the course of prion infection, the normally soluble and protease-sensitive mammalian prion protein (PrP(C)) is refolded into an insoluble, partially protease-resistant, and infectious form called PrP(Sc). The conformational conversion of PrP(C) to PrP(Sc) is a critical event during prion infection and is essential for the production of prion infectivity. This chapter briefly summarizes the ways in which cell biological approaches have enhanced our understanding of how PrP contributes to different aspects of prion pathogenesis.
... of asymptomatic prion carriers who will potentially go on to develop a priondisease or who will unknowingly transmit the prion agent to another individual... for novel therapeutics that have the potential to prevent, as for inherited priondisorders; slow, as for all priondisorders; and ultimately stop disease progression.
Across the spectrum of sporadic human priondiseases (also known as transmissible spongiformencephalopathies: TSE), there is considerable phenotypic diversity ... Cumulative scientific evidence supports that prions, the infectious agents of priondiseases, are constituted predominantly, if not exclusively, by misfolded, typically protease ... tissue deposition of PrP(res) is considered a hallmark of priondisease pathology, and this can be visualized by Western blotting after ...
Prion Diseases (6), Creutzfeldt-Jakob Syndrome (1), more mentions
Therapy of priondiseases represents an extremely challenging effort for scientists working in the field... those efforts that have contributed to strengthen the drug discovery process in priondiseases... In this respect, the multifactorial nature of priondiseases provides a strong foundation to the development of small molecules directed to ...
Prion Diseases (4), Neurodegenerative Diseases (1), more mentions
BACKGROUND: This study aimed to evaluate the effects of two different concentrations of topical hyaluronic-acid on post-operative patient discomfort and wound healing of palatal donor sites following free gingival graft (FGG) surgery.
METHODS: Thirty-six patients requiring FGG were randomly assigned into three groups in an examiner-blind, randomized-controlled clinical trial. After harvesting palatal grafts, 0.2% and 0.8% hyaluronic-acid gels were used in the test-1 and -2 groups, respectively. Gels were applied on donor sites and protected with periodontal dressing in the test groups whereas the wound was covered only with periodontal dressing in the control group. On days 3-7-14 and 21, pain and burning sensation were recorded by using visual analog scale (VAS) as well as other parameters such as complete epithelization (CE) and color match on days 3-7-14-21-42.
RESULTS: Test groups experienced less pain than the control group on days 3 and 7 (P<0.001 and P<0.001, respectively). The mean VAS score for burning sensation was higher in the control group on day 3 compared to the test-1 and -2 groups (P=0.033 and P=0.020, respectively). CE in all patients was achieved on day 21 in both test groups while it was achieved on day 42 in the control group. The test groups showed higher color match scores than the control group on days 21 (P<0.001 and P<0.001, respectively) and 42 (P=0.004 and P=0.002, respectively).
CONCLUSION: Topical application of hyaluronic-acid exhibits positive impact on post-operative pain, burning sensation and accelerates palatal wound healing in terms of epithelization and color match.
Priondiseases or transmissible spongiformencephalopathies constitute a group of fatal neurodegenerative diseases that can be ... The central molecular event of priondiseases is the conformational conversion of the physiological cellular prion protein ... Spontaneous generation of prions in genetic priondiseases is caused by mutations in the human prion protein gene ...
Prion Diseases (5), Neurodegenerative Diseases (1), more mentions
... in neurodegenerative diseases to reinstate energy homeostasis and degrade misfolded proteins. In this review article, we discuss briefly the role of AMPK signaling in energy homeostasis, the structure of AMPK, activation mechanisms of AMPK, regulation of AMPK, the role of AMPK in autophagy, the role of AMPK in neurodegenerative diseases, and finally the role of autophagic flux in priondiseases.
The target of focal therapy (FT) in prostate cancer (PC) is partial treatment of the prostate aiming at preserving surrounding anatomical structures. The intention is to minimize typical side effects of radical treatment options combined with local tumor control. Numerous established and new technologies are used. Results of published studies showed a good safety profile, few side effects and good preservation of functional results. Oncologic long-term data are lacking so far. Photodynamic therapy (PDT) is the only technology that has been studied in a published prospective randomized trial. The FT is challenged by the multifocality of PC; therefore, the quality of prostate biopsy, histopathological assessment as well as imaging are of paramount importance. Multiparametric magnetic resonance imaging (MRI) has gained increasing importance. The FT is experimental and should only be offered within clinical trials.
Oncology (2) Prostatic Neoplasms (2), Neoplasms (1), more mentions
Many natural priondiseases are acquired peripherally, such as following the oral consumption of contaminated food or ... activation status of the microglial in the brain can also influence progression of priondisease pathogenesis is provided. Priondisease susceptibility may also be influenced by additional factors such as chronic inflammation, coinfection ...
BACKGROUND: MIF, a proinflammatory cytokine, contributes to the pathogenesis of acute, chronic, and autoimmune inflammatory disorders and balances the suppressive effect of glucocorticoids on the immune system. There is an interaction between bone metabolism and the immune system via the production of cytokines. We aimed to analyze the relationship between the MIF gene -173G > C promoter polymorphism and osteoporosis.
METHODS: In this case-control study performed in a university hospital, 286 samples (136 women with osteoporosis and 150 healthy age-matched controls) participated. The polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) assay was used to genotype the MIF gene polymorphism. The alleles and genotypes frequencies of patients and controls were compared using the χ(2) test.
RESULTS: The genotype frequencies of MIF gene -173G > C polymorphism showed statistically significant differences between patients and controls (p = 0.038). Also, the subjects carrying the variant C allele in the MIF -173 position were at significantly higher risk of osteoporosis than subjects carrying the wild-type G allele (p = 0.009, odds ratio 1.7, 95% confidence interval 1.1-2.6).
CONCLUSION: Our study suggested a strong association between MIF gene -173G > C polymorphism and osteoporosis in a Turkish population.
Muscular and Skeletal Diseases (5), Immune System Diseases (1) Osteoporosis (5), more mentions
PURPOSE: To investigate clinicopathological characteristics and oncological outcome of women with microinvasive BOTs.
METHODS: A retrospective multicenter case-control study was conducted on 902 patients with BOT, who underwent surgery from January 2002 to December 2015 at six participating gynecologic oncology centers from Turkey. Among 902 patients, 69 had microinvasive BOT. For every patient with microinvasive BOT, two controls were randomly selected from another database based on decade of age and stage of disease at diagnosis. The clinical-pathological characteristics and oncological outcomes were compared between BOT patients with and without stromal microinvasion. Risk factors for poor oncological outcomes were investigated in a multivariate analysis model. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method.
RESULTS: Patients with microinvasive BOT had a significantly higher rate of recurrence than patients without microinvasive BOT (17.4 vs 7.8%, OR 3.55, %95 CI 1.091-11.59, p = 0.03). Stage at diagnosis (stage I versus II/III) and type of surgery (cystectomy versus others) were found as other significant prognostic factors for recurrence in multivariate analysis (OR 8.63, %95 CI 2.48-29.9, p = 0.001 and OR 19.4, %95 CI 3.59-105.6, p = 0.001, respectively). Stromal microinvasion was found as a prognostic factor for significantly shorter DFS (26.7 vs 11.9 months, p = 0.031, log rank). However, there was no significant difference in OS between two groups (p = 0.99, log rank).
CONCLUSION: Stromal microinvasion is significantly associated with decreased DFS. In addition, our study confirms that the risk of recurrence is higher in patients with microinvasive BOT.
Caveolin-1 is a major component protein of the caveolae-a type of flask shaped, 50-100 nm, nonclathrin-coated, microdomain present in the plasma membrane of most mammalian cells. Caveolin-1 functions as a scaffolding protein to organize and concentrate signaling molecules within the caveolae, which may be associated with its unique physicochemical properties including oligomerization, acquisition of detergent insolubility, and association with cholesterol. Here we demonstrate that caveolin-1 is detected in all brain areas examined and recovered in both detergent-soluble and -insoluble fractions. Surprisingly, the recovered molecules from the two different fractions share a similar molecular size ranging from 200 to 2,000 kDa, indicated by gel filtration. Furthermore, both soluble and insoluble caveolin-1 molecules generate a proteinase K (PK)-resistant C-terminal core fragment upon the PK-treatment, by removing ˜36 amino acids from the N-terminus of the protein. Although it recognizes caveolin-1 from A431 cell lysate, an antibody against the C-terminus of caveolin-1 fails to detect the brain protein by Western blotting, suggesting that the epitope in the brain caveolin-1 is concealed. No significant differences in the physicochemical properties of caveolin-1 between uninfected and prion-infected brains are observed.
... a pathogenic isoform PrP(Sc), the causative agent of neurodegenerative priondiseases. Nonetheless some forms of priondisease develop in the apparent absence of infectious PrP(Sc), suggesting ... Indeed, in some inherited cases of human priondisease, the predominant form of PrP detectable in the brain is ... The relationship between the neurodegeneration occurring in priondiseases involving PrP(Sc) and that associated with (Ctm)PrP remains ...
In inherited forms of priondiseases, misfolding of cellular prion protein, PrP(C), into its pathological form, PrP(Sc), is caused ... stages of the conformational changes leading to spontaneous generation of prions in inherited forms of priondiseases may benefit from detailed structural analysis of different human (Hu) PrP variants.
Abstract: Transmissible amyloid particles called prions are associated with infectious priondiseases in mammals and inherited phenotypes in yeast. All amyloid aggregates can give rise to potentially infectious seeds that accelerate their growth. Why some amyloid seeds are highly infectious prion particles while others are less infectious or even inert, is currently not understood.
A key event in the pathogenesis of priondiseases is the change in structure of the normal cellular form of the prion protein from a predominantly α-helix form to the β-sheet-rich prion protein found in disease-associated tissue. To allow more detailed structural research into PrP misfolding, it is necessary to have techniques which enable enrichment of ...
According to the protein-only hypothesis of prion propagation, the pathogenesis of priondisease is due to the misfolding of cellular PrP (PrP(C)) which gives rise to disease-associated PrP(Sc. This misfolding results in the predominantly α-helix secondary structure of PrP becoming increasingly β-sheet. Prion protein researchers often employ circular dichroism (CD) spectroscopy to rapidly analyze ...