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Sample records for pyroglutamate abeta pathology

  1. Pyroglutamate Abeta pathology in APP/PS1KI mice, sporadic and familial Alzheimer's disease cases.

    Science.gov (United States)

    Wirths, Oliver; Bethge, Tobias; Marcello, Andrea; Harmeier, Anja; Jawhar, Sadim; Lucassen, Paul J; Multhaup, Gerd; Brody, David L; Esparza, Thomas; Ingelsson, Martin; Kalimo, Hannu; Lannfelt, Lars; Bayer, Thomas A

    2010-01-01

    The presence of Abeta(pE3) (N-terminal truncated Abeta starting with pyroglutamate) in Alzheimer's disease (AD) has received considerable attention since the discovery that this peptide represents a dominant fraction of Abeta peptides in senile plaques of AD brains. This was later confirmed by other reports investigating AD and Down's syndrome postmortem brain tissue. Importantly, Abeta(pE3) has a higher aggregation propensity, and stability, and shows an increased toxicity compared to full-length Abeta. We have recently shown that intraneuronal accumulation of Abeta(pE3) peptides induces a severe neuron loss and an associated neurological phenotype in the TBA2 mouse model for AD. Given the increasing interest in Abeta(pE3), we have generated two novel monoclonal antibodies which were characterized as highly specific for Abeta(pE3) peptides and herein used to analyze plaque deposition in APP/PS1KI mice, an AD model with severe neuron loss and learning deficits. This was compared with the plaque pattern present in brain tissue from sporadic and familial AD cases. Abundant plaques positive for Abeta(pE3) were present in patients with sporadic AD and familial AD including those carrying mutations in APP (arctic and Swedish) and PS1. Interestingly, in APP/PS1KI mice we observed a continuous increase in Abeta(pE3) plaque load with increasing age, while the density for Abeta(1-x ) plaques declined with aging. We therefore assume that, in particular, the peptides starting with position 1 of Abeta are N-truncated as disease progresses, and that, Abeta(pE3) positive plaques are resistant to age-dependent degradation likely due to their high stability and propensity to aggregate.

  2. Pyroglutamate Abeta pathology in APP/PS1KI mice, sporadic and familial Alzheimer’s disease cases

    NARCIS (Netherlands)

    Wirths, O.; Bethge, T.; Marcello, A.; Harmeier, A.; Jawhar, S.; Lucassen, P.J.; Multhaup, G.; Brody, D.L.; Esparza, T.; Ingelsson, M.; Kalimo, H.; Lannfelt, L.; Bayer, T.A.

    2010-01-01

    The presence of A beta(pE3) (N-terminal truncated A beta starting with pyroglutamate) in Alzheimer's disease (AD) has received considerable attention since the discovery that this peptide represents a dominant fraction of A beta peptides in senile plaques of AD brains. This was later confirmed by ot

  3. Immunodominant epitope and properties of pyroglutamate-modified Abeta-specific antibodies produced in rabbits.

    Science.gov (United States)

    Acero, G; Manoutcharian, K; Vasilevko, V; Munguia, M E; Govezensky, T; Coronas, G; Luz-Madrigal, A; Cribbs, D H; Gevorkian, G

    2009-08-18

    N-truncated and N-modified forms of amyloid beta (Abeta) peptide are found in diffused and dense core plaques in Alzheimer's disease (AD) and Down's syndrome patients as well as transgenic mouse models of AD. Although the pathological significance of these shortened forms Abeta is not completely understood, previous studies have demonstrated that these peptides are significantly more resistant to degradation, aggregate more rapidly in vitro and exhibit similar or, in some cases, increased toxicity in hippocampal neuronal cultures compared to the full length peptides. In the present study we further investigated the mechanisms of toxicity of one of the most abundant N-truncated/modified Abeta peptide bearing amino-terminal pyroglutamate at position 3 (AbetaN3(pE)). We demonstrated that AbetaN3(pE) oligomers induce phosphatidyl serine externalization and membrane damage in SH-SY5Y cells. Also, we produced AbetaN3(pE)-specific polyclonal antibodies in rabbit and identified an immunodominant epitope recognized by anti-AbetaN3(pE) antibodies. Our results are important for developing new immunotherapeutic compounds specifically targeting AbetaN3(pE) aggregates since the most commonly used immunogens in the majority of vaccines for AD have been shown to induce antibodies that recognize the N-terminal immunodominant epitope (EFRH) of the full length Abeta, which is absent in N-amino truncated peptides.

  4. Abeta42 mutants with different aggregation profiles induce distinct pathologies in Drosophila.

    Directory of Open Access Journals (Sweden)

    Koichi Iijima

    Full Text Available Aggregation of the amyloid-beta-42 (Abeta42 peptide in the brain parenchyma is a pathological hallmark of Alzheimer's disease (AD, and the prevention of Abeta aggregation has been proposed as a therapeutic intervention in AD. However, recent reports indicate that Abeta can form several different prefibrillar and fibrillar aggregates and that each aggregate may confer different pathogenic effects, suggesting that manipulation of Abeta42 aggregation may not only quantitatively but also qualitatively modify brain pathology. Here, we compare the pathogenicity of human Abeta42 mutants with differing tendencies to aggregate. We examined the aggregation-prone, EOFAD-related Arctic mutation (Abeta42Arc and an artificial mutation (Abeta42art that is known to suppress aggregation and toxicity of Abeta42 in vitro. In the Drosophila brain, Abeta42Arc formed more oligomers and deposits than did wild type Abeta42, while Abeta42art formed fewer oligomers and deposits. The severity of locomotor dysfunction and premature death positively correlated with the aggregation tendencies of Abeta peptides. Surprisingly, however, Abeta42art caused earlier onset of memory defects than Abeta42. More remarkably, each Abeta induced qualitatively different pathologies. Abeta42Arc caused greater neuron loss than did Abeta42, while Abeta42art flies showed the strongest neurite degeneration. This pattern of degeneration coincides with the distribution of Thioflavin S-stained Abeta aggregates: Abeta42Arc formed large deposits in the cell body, Abeta42art accumulated preferentially in the neurites, while Abeta42 accumulated in both locations. Our results demonstrate that manipulation of the aggregation propensity of Abeta42 does not simply change the level of toxicity, but can also result in qualitative shifts in the pathology induced in vivo.

  5. The levels of soluble versus insoluble brain Abeta distinguish Alzheimer's disease from normal and pathologic aging.

    Science.gov (United States)

    Wang, J; Dickson, D W; Trojanowski, J Q; Lee, V M

    1999-08-01

    The abundance and solubility of Abeta peptides are critical determinants of amyloidosis in Alzheimer's disease (AD). Hence, we compared levels of total soluble, insoluble, and total Abeta1-40 and Abeta1-42 in AD brains with those in age-matched normal and pathologic aging brains using a sandwich enzyme-linked immunosorbent assay (ELISA). Since the measurement of Abeta1-40 and Abeta1-42 depends critically on the specificity of the monoclonal antibodies used in the sandwich ELISA, we first demonstrated that each assay is specific for Abeta1-40 or Abeta1-42 and the levels of these peptides are not affected by the amyloid precursor protein in the brain extracts. Thus, this sandwich ELISA enabled us to show that the average levels of total cortical soluble and insoluble Abeta1-40 and Abeta1-42 were highest in AD, lowest in normal aging, and intermediate in pathologic aging. Remarkably, the average levels of insoluble Abeta1-40 were increased 20-fold while the average levels of insoluble Abeta1-42 were increased only 2-fold in the AD brains compared to pathologic aging brains. Further, the soluble pools of Abeta1-40 and Abeta1-42 were the largest fractions of total Abeta in the normal brain (i.e., 50 and 23%, respectively), but they were the smallest in the AD brain (i.e., 2.7 and 0.7%, respectively) and intermediate (i.e., 8 and 0.8%, respectively) in pathologic aging brains. Thus, our data suggest that pathologic aging is a transition state between normal aging and AD. More importantly, our findings imply that a progressive shift of brain Abeta1-40 and Abeta1-42 from soluble to insoluble pools and a profound increase in the levels of insoluble Abeta1-40 plays mechanistic roles in the onset and/or progression of AD.

  6. Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota

    Science.gov (United States)

    Harach, T.; Marungruang, N.; Duthilleul, N.; Cheatham, V.; Mc Coy, K. D.; Frisoni, G.; Neher, J. J.; Fåk, F.; Jucker, M.; Lasser, T.; Bolmont, T.

    2017-01-01

    Alzheimer’s disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer’s disease is not known. To this end we sequenced bacterial 16S rRNA from fecal samples of Aβ precursor protein (APP) transgenic mouse model and found a remarkable shift in the gut microbiota as compared to non-transgenic wild-type mice. Subsequently we generated germ-free APP transgenic mice and found a drastic reduction of cerebral Aβ amyloid pathology when compared to control mice with intestinal microbiota. Importantly, colonization of germ-free APP transgenic mice with microbiota from conventionally-raised APP transgenic mice increased cerebral Aβ pathology, while colonization with microbiota from wild-type mice was less effective in increasing cerebral Aβ levels. Our results indicate a microbial involvement in the development of Abeta amyloid pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases. PMID:28176819

  7. The ratio of monomeric to aggregated forms of Abeta40 and Abeta42 is an important determinant of amyloid-beta aggregation, fibrillogenesis, and toxicity

    OpenAIRE

    Jan, Asad; Gokce, Ozgun; Luthi-Carter, Ruth; Lashuel, Hilal A.

    2008-01-01

    Aggregation and fibril formation of amyloid-beta (Abeta) peptides Abeta40 and Abeta42 are central events in the pathogenesis of Alzheimer disease. Previous studies have established the ratio of Abeta40 to Abeta42 as an important factor in determining the fibrillogenesis, toxicity, and pathological distribution of Abeta. To better understand the molecular basis underlying the pathologic consequences associated with alterations in the ratio of Abeta40 to Abeta42, we probed the concentration- an...

  8. Anti-11[E]-pyroglutamate-modified amyloid β antibodies cross-react with other pathological Aβ species: relevance for immunotherapy.

    Science.gov (United States)

    Perez-Garmendia, Roxanna; Ibarra-Bracamontes, Vanessa; Vasilevko, Vitaly; Luna-Muñoz, Jose; Mena, Raul; Govezensky, Tzipe; Acero, Gonzalo; Manoutcharian, Karen; Cribbs, David H; Gevorkian, Goar

    2010-12-15

    N-truncated/modified forms of amyloid beta (Aß) peptide are found in diffused and dense core plaques in Alzheimer's disease (AD) and Down's syndrome patients as well as animal models of AD, and represent highly desirable therapeutic targets. In the present study we have focused on N-truncated/modified Aβ peptide bearing amino-terminal pyroglutamate at position 11 (AβN11(pE)). We identified two B-cell epitopes recognized by rabbit anti-AβN11(pE) polyclonal antibodies. Interestingly, rabbit anti-AβN11(pE) polyclonal antibodies bound also to full-length Aβ1-42 and N-truncated/modified AβN3(pE), suggesting that the three peptides may share a common B-cell epitope. Importantly, rabbit anti-AβN11(pE) antibodies bound to naturally occurring Aβ aggregates present in brain samples from AD patients. These results are potentially important for developing novel immunogens for targeting N-truncated/modified Aβ aggregates as well, since the most commonly used immunogens in the majority of vaccine studies have been shown to induce antibodies that recognize the N-terminal immunodominant epitope (EFRH) of the full length Aβ, which is absent in N-amino truncated peptides.

  9. Inhibition of GSK-3 ameliorates Abeta pathology in an adult-onset Drosophila model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Oyinkan Sofola

    2010-09-01

    Full Text Available Abeta peptide accumulation is thought to be the primary event in the pathogenesis of Alzheimer's disease (AD, with downstream neurotoxic effects including the hyperphosphorylation of tau protein. Glycogen synthase kinase-3 (GSK-3 is increasingly implicated as playing a pivotal role in this amyloid cascade. We have developed an adult-onset Drosophila model of AD, using an inducible gene expression system to express Arctic mutant Abeta42 specifically in adult neurons, to avoid developmental effects. Abeta42 accumulated with age in these flies and they displayed increased mortality together with progressive neuronal dysfunction, but in the apparent absence of neuronal loss. This fly model can thus be used to examine the role of events during adulthood and early AD aetiology. Expression of Abeta42 in adult neurons increased GSK-3 activity, and inhibition of GSK-3 (either genetically or pharmacologically by lithium treatment rescued Abeta42 toxicity. Abeta42 pathogenesis was also reduced by removal of endogenous fly tau; but, within the limits of detection of available methods, tau phosphorylation did not appear to be altered in flies expressing Abeta42. The GSK-3-mediated effects on Abeta42 toxicity appear to be at least in part mediated by tau-independent mechanisms, because the protective effect of lithium alone was greater than that of the removal of tau alone. Finally, Abeta42 levels were reduced upon GSK-3 inhibition, pointing to a direct role of GSK-3 in the regulation of Abeta42 peptide level, in the absence of APP processing. Our study points to the need both to identify the mechanisms by which GSK-3 modulates Abeta42 levels in the fly and to determine if similar mechanisms are present in mammals, and it supports the potential therapeutic use of GSK-3 inhibitors in AD.

  10. Inhibition of GSK-3 ameliorates Abeta pathology in an adult-onset Drosophila model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Oyinkan Sofola

    2010-09-01

    Full Text Available Abeta peptide accumulation is thought to be the primary event in the pathogenesis of Alzheimer's disease (AD, with downstream neurotoxic effects including the hyperphosphorylation of tau protein. Glycogen synthase kinase-3 (GSK-3 is increasingly implicated as playing a pivotal role in this amyloid cascade. We have developed an adult-onset Drosophila model of AD, using an inducible gene expression system to express Arctic mutant Abeta42 specifically in adult neurons, to avoid developmental effects. Abeta42 accumulated with age in these flies and they displayed increased mortality together with progressive neuronal dysfunction, but in the apparent absence of neuronal loss. This fly model can thus be used to examine the role of events during adulthood and early AD aetiology. Expression of Abeta42 in adult neurons increased GSK-3 activity, and inhibition of GSK-3 (either genetically or pharmacologically by lithium treatment rescued Abeta42 toxicity. Abeta42 pathogenesis was also reduced by removal of endogenous fly tau; but, within the limits of detection of available methods, tau phosphorylation did not appear to be altered in flies expressing Abeta42. The GSK-3-mediated effects on Abeta42 toxicity appear to be at least in part mediated by tau-independent mechanisms, because the protective effect of lithium alone was greater than that of the removal of tau alone. Finally, Abeta42 levels were reduced upon GSK-3 inhibition, pointing to a direct role of GSK-3 in the regulation of Abeta42 peptide level, in the absence of APP processing. Our study points to the need both to identify the mechanisms by which GSK-3 modulates Abeta42 levels in the fly and to determine if similar mechanisms are present in mammals, and it supports the potential therapeutic use of GSK-3 inhibitors in AD.

  11. MicroRNAs 99b-5p/100-5p regulated by endoplasmic reticulum stress are involved in Abeta-induced pathologies

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    Xiaoyang eYe

    2015-11-01

    Full Text Available Alzheimer’s disease (AD is the most common cause of dementia. Amyloid beta (Abeta deposition and intracellular tangles are the pathological hallmarks of AD. MicroRNAs (miRNAs are small non-coding RNAs which have been found to play very important roles and have the potential to serve as diagnostic markers during neuronal pathogenesis. In this study, we aimed to determine the roles of miR-99b-5p and miR-100-5p in Abeta-induced neuronal pathologies. We detected the expression levels of miR-99b-5p and miR-100-5p in the brains of APPswe/PS1ΔE9 double transgenic mice (APP/PS1 mice at different age stages and found both miRNAs were decreased at early stages while increased at late stages of APP/PS1 mice when compared with the age-matched wild type (WT mice. Similar phenomenon was also observed in Abeta-treated cultured cells. We also confirmed that mTOR (mammalian target of rapamycin is one of the targets of miR-99b-5p/100-5p, which is consistent with previous studies in cancer. MiR-99b-5p/100-5p have been found to promote cell apoptosis with the Abeta treatment. This effect may be induced via the mTOR pathway. In our study, we find both miR-99b-5p and miR-100-5p affect neuron survival by targeting mTOR. We also speculate that dynamic change of miR-99b-5p/100-5p levels during Abeta-associated pathologies might be attributed to Abeta-induced endoplasmic reticulum stress (ER stress, suggesting the potential role of the ER stress –miRNAs – mTOR axis in Abeta-related AD pathogenesis.

  12. Intracellular and extracellular Abeta, a tale of two neuropathologies.

    Science.gov (United States)

    Cuello, A Claudio

    2005-01-01

    The central pathological cause of Alzheimer disease (AD) is hypothesized to be an excess of beta-amyloid (Abeta) which accumulates into toxic fibrillar deposits within extracellular areas of the brain. These deposits disrupt neural and synaptic function and ultimately lead to neuronal degeneration and dementia. In addition to the pathological roles attributed to Abeta, evidence from our laboratory would suggest that Abeta serves a physiological role in the modulation of CRE-directed gene expression. This commentary also highlights some of the pathological consequences of the accumulation of intracellular Abeta. Finally it discusses the impact of cortical Abeta burden on transmitter-specific synaptic numbers as well as the generation of dystrophic neurites. The fundamental thesis of my proposal is that the Abeta pathology seen in AD is a continuous process from an initial abnormal Abeta intracellular accumulation to the well-established extracellular Abeta aggregation, culminating in the formation of amyloid plaques and dystrophic neurites.

  13. Abeta ion channels. Prospects for treating Alzheimer's disease with Abeta channel blockers.

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    Arispe, Nelson; Diaz, Juan C; Simakova, Olga

    2007-08-01

    The main pathological features in the Alzheimer's brain are progressive depositions of amyloid protein plaques among nerve cells, and neurofibrillary tangles within the nerve cells. The major components of plaques are Abeta peptides. Numerous reports have provided evidence that Abeta peptides are cytotoxic and may play a role in the pathogenesis of AD. An increasing number of research reports support the concept that the Abeta-membrane interaction event may be followed by the insertion of Abeta into the membrane in a structural configuration which forms an ion channel. This review summarizes experimental procedures which have been designed to test the hypothesis that the interaction of Abeta with a variety of membranes, both artificial and natural, results in the subsequent formation of Abeta ion channels We describe experiments, by ourselves and others, that support the view that Abeta is cytotoxic largely due to the action of Abeta channels in the cell membrane. The interaction of Abeta with the surface of the cell membrane may results in the activation of a chain of processes that, when large enough, become cytotoxic and induce cell death by apoptosis. Remarkably, the blockage of Abeta ion channels at the surface of the cell absolutely prevents the activation of these processes at different intracellular levels, thereby preserving the life of the cells. As a prospect for therapy for Alzheimer's disease, our findings at cellular level may be testable on AD animal models to elucidate the potential role and the magnitude of the contribution of the Abeta channels for induction of the disease.

  14. Pathological Hallmarks, Clinical Parallels, and Value for Drug Testing in Alzheimer's Disease of the APP[V717I] London Transgenic Mouse Model

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    An Tanghe

    2010-01-01

    Full Text Available The APP[V717I] London (APP-Ld mouse model recapitulates important pathological and clinical hallmarks of Alzheimer's disease (AD and is therefore a valuable paradigm for evaluating therapeutic candidates. Historically, both the parenchymal and vascular amyloid deposits, and more recently, truncated and pyroglutamate-modified Abeta3(pE-42 species, are perceived as important hallmarks of AD-pathology. Late stage symptoms are preceded by robust deficits in orientation and memory that correlate in time with Abeta oligomerization and GSK3-mediated phosphorylation of endogenous murine Tau, all markers that have gained considerable interest during the last decade. Clinical parallels with AD patients and the value of the APP-Ld transgenic mouse model for preclinical in vivo testing of candidate drugs are discussed.

  15. Anti-Abeta: The good, the bad, and the unforeseen.

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    Broytman, Oleg; Malter, James S

    2004-02-01

    Alzheimer's disease (AD) is characterized in part by the deposition of amyloid beta protein (Abeta) in compact fibrillar plaques. These structures can induce an innate immune response in the brain, which triggers progressive inflammation, neuronal loss, and further acceleration of Abeta plaque formation. Compared with the case in normal individuals, the T and B lymphocytes in AD patients and murine models are hyporesponsive to Abeta. However, depending on the route of delivery, tolerance can be overcome by vaccination, with the induction of an anti-Abeta-mediated immune response. Through mechanisms that are incompletely understood, immunized APP transgenic animals show markedly reduced Abeta deposition, preservation of normal neuronal architecture, and improved performance in memory and spatial learning tasks. In human trials, Abeta vaccination stabilized cognition and slowed the progression of dementia. Neuropathologic examination of a vaccinated subject showed reduced cortical Abeta without changes in other AD-associated pathology. However, in some patients, vaccination induced severe meningoencephalitis, causing the trial to be terminated. Thus, vaccination appears to activate both beneficial and deleterious anti-Abeta immunity, suggesting that the vaccine can have potent clinical utility if an appropriate immunologic response can be generated.

  16. Abeta immunotherapy: intracerebral sequestration of Abeta by an anti-Abeta monoclonal antibody 266 with high affinity to soluble Abeta

    National Research Council Canada - National Science Library

    Yamada, Kaoru; Yabuki, Chiori; Seubert, Peter; Schenk, Dale; Hori, Yukiko; Ohtsuki, Sumio; Terasaki, Tetsuya; Hashimoto, Tadafumi; Iwatsubo, Takeshi

    2009-01-01

    Amyloid beta (Abeta) immunotherapy is emerging as a promising disease-modifying therapy for Alzheimer's disease, although the precise mechanisms whereby anti-Abeta antibodies act against amyloid deposition and cognitive...

  17. A two-year study with fibrillar beta-amyloid (Abeta) immunization in aged canines: effects on cognitive function and brain Abeta.

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    Head, Elizabeth; Pop, Viorela; Vasilevko, Vitaly; Hill, MaryAnn; Saing, Tommy; Sarsoza, Floyd; Nistor, Michaela; Christie, Lori-Ann; Milton, Saskia; Glabe, Charles; Barrett, Edward; Cribbs, David

    2008-04-02

    Aged canines (dogs) accumulate human-type beta-amyloid (Abeta) in diffuse plaques in the brain with parallel declines in cognitive function. We hypothesized that reducing Abeta in a therapeutic treatment study of aged dogs with preexisting Abeta pathology and cognitive deficits would lead to cognitive improvements. To test this hypothesis, we immunized aged beagles (8.4-12.4 years) with fibrillar Abeta(1-42) formulated with aluminum salt (Alum) for 2.4 years (25 vaccinations). Cognitive testing during this time revealed no improvement in measures of learning, spatial attention, or spatial memory. After extended treatment (22 vaccinations), we observed maintenance of prefrontal-dependent reversal learning ability. In the brain, levels of soluble and insoluble Abeta(1-40) and Abeta(1-42) and the extent of diffuse plaque accumulation was significantly decreased in several cortical regions, with preferential reductions in the prefrontal cortex, which is associated with a maintenance of cognition. However, the amount of soluble oligomers remained unchanged. The extent of prefrontal Abeta was correlated with frontal function and serum anti-Abeta antibody titers. Thus, reducing total Abeta may be of limited therapeutic benefit to recovery of cognitive decline in a higher mammalian model of human brain aging and disease. Immunizing animals before extensive Abeta deposition and cognitive decline to prevent oligomeric or fibrillar Abeta formation may have a greater impact on cognition and also more directly evaluate the role of Abeta on cognition in canines. Alternatively, clearing preexisting Abeta from the brain in a treatment study may be more efficacious for cognition if combined with a second intervention that restores neuron health.

  18. Peripheral elevation of IGF-1 fails to alter Abeta clearance in multiple in vivo models.

    Science.gov (United States)

    Lanz, Thomas A; Salatto, Christopher T; Semproni, Anthony R; Marconi, Michael; Brown, Tracy M; Richter, Karl E G; Schmidt, Kari; Nelson, Frederick R; Schachter, Joel B

    2008-03-01

    Increasing beta-amyloid (Abeta) clearance may alter the course of Alzheimer's disease progression and attenuate amyloid plaque pathology. Insulin-like growth factor I (IGF-1) augmentation has been suggested to increase Abeta clearance by facilitating transport of Abeta out of the brain. The availability of safe agents that increase IGF-1 levels therefore makes IGF-1 elevation an attractive target for disease modifying therapy in AD. The present series of studies sought to replicate published paradigms in which peripheral IGF-1 administration lowered brain Abeta acutely, with reduction in plaque pathology after chronic treatment. Thus Abeta levels were measured in several animal models following treatments that elevated IGF-1. Administration of IGF-1 to young or old rats for up to 3 days had no effect on Abeta levels in brain, CSF, or plasma. In adult beagles, 4 days of dosing with the growth hormone secretagogue, CP-424391, doubled baseline plasma IGF-1 levels, yet failed to alter CSF or plasma Abeta. 5-day treatment of young Tg2576 mice with IGF-1 produced robust elevations of IGF-1 levels in plasma, but no effects on Abeta were detected in brain, CSF, or plasma. Finally, 11-month-old Tg2576 mice were implanted with subcutaneous minipumps delivering IGF-1 for 1 month. No significant changes in Abeta (by ELISA or Western blot), plaque pathology, or phospho-tau epitopes were detected. These results do not demonstrate acute or chronic actions of peripherally administered IGF-1 on Abeta levels or the phosphorylation state of tau and therefore do not suggest any disease-modifying benefits of IGF-1 restorative therapy for AD through these mechanisms.

  19. The antioxidant effect of derivatives pyroglutamic lactam

    Energy Technology Data Exchange (ETDEWEB)

    Rohadi, Atisya; Lazim, Azwani Mat; Hasbullah, Siti Aishah [School of Chemical Sciences and Food Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor Darul Ehsan (Malaysia)

    2013-11-27

    Diphenylpicrylhydrazyl (DPPH) is widely used for quickly accessing the ability of polyphenols to transfer labile H atoms to radicals. The antioxidant activity of all the synthesized compounds was screened by DPPH method. Compound (4) showed 54% antioxidant potential while all other compounds were found to have moderate to have moderate to mild antioxidant activity ranging from 47–52%. Pyroglutamic lactams have been synthesized stereoselectively in racemic form from levulinic acid as bifunctional adduct using convertible isocyanide in one-pot Ugi 4-center-3-component condensation reaction (U-4C-3CR). The product formed provides biologically interesting products in excellent yields in a short reaction time. The structures of the synthesized compounds were elucidated using spectroscopic data and elemental analysis.

  20. Small molecule, non-peptide p75 ligands inhibit Abeta-induced neurodegeneration and synaptic impairment.

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    Tao Yang

    Full Text Available The p75 neurotrophin receptor (p75(NTR is expressed by neurons particularly vulnerable in Alzheimer's disease (AD. We tested the hypothesis that non-peptide, small molecule p75(NTR ligands found to promote survival signaling might prevent Abeta-induced degeneration and synaptic dysfunction. These ligands inhibited Abeta-induced neuritic dystrophy, death of cultured neurons and Abeta-induced death of pyramidal neurons in hippocampal slice cultures. Moreover, ligands inhibited Abeta-induced activation of molecules involved in AD pathology including calpain/cdk5, GSK3beta and c-Jun, and tau phosphorylation, and prevented Abeta-induced inactivation of AKT and CREB. Finally, a p75(NTR ligand blocked Abeta-induced hippocampal LTP impairment. These studies support an extensive intersection between p75(NTR signaling and Abeta pathogenic mechanisms, and introduce a class of specific small molecule ligands with the unique ability to block multiple fundamental AD-related signaling pathways, reverse synaptic impairment and inhibit Abeta-induced neuronal dystrophy and death.

  1. Apolipoprotein E protects cultured pericytes and astrocytes from D-Abeta(1-40)-mediated cell death

    NARCIS (Netherlands)

    Bruinsma, I.B.; Wilhelmus, M.M.; Kox, M.; Veerhuis, R.; Waal, R.M.W. de; Verbeek, M.M.

    2010-01-01

    Cerebral amyloid angiopathy (CAA) is a common pathological finding in Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis of the Dutch type; in this latter condition it is caused by deposition of mutated amyloid beta protein (Abeta Glu22Gln; D-Abeta(1-40)). Previously, we found a

  2. Intracellular sAPP retention in response to Abeta is mapped to cytoskeleton-associated structures.

    Science.gov (United States)

    Henriques, Ana Gabriela; Vieira, Sandra Isabel; Crespo-López, Maria Elena; Guiomar de Oliveira, Márcio A; da Cruz e Silva, Edgar F; da Cruz e Silva, Odete A B

    2009-05-01

    Amyloid beta (Abeta) contributes to neurodegeneration in Alzheimer's disease and provides a close association between molecular events and pathology, although the underlying molecular mechanisms are unclear. In the work described here, Abeta did not induce amyloid precursor protein (APP) expression, but APP processing/trafficking was markedly affected. In COS-7 cells, Abeta provokes retention of intracellular sAPPalpha (isAPPalpha). Intracellular holo-APP levels remain unchanged, and extracellular total sAPP increases, although extracellular sAPPalpha alone was not altered significantly. In primary neuronal cultures and PC12 cells, isAPP also increased, but this was mirrored by a decrease in extracellular total sAPP. The isAPP retention was particularly associated with the cytoskeletal fraction. The retention "per se" occurred in vesicular-like densities, negative for a C-terminal antibody and strongly positive for the 6E10 antibody, clearly showing abnormal intracellular accumulation of sAPPalpha in response to Abeta. Our data support a dynamic model for intracellular retention of sAPPalpha as an early response to Abeta exposure. Particularly noteworthy was the observation that removal of Abeta reversed the isAPP accumulation. Mechanistically, these findings disclose an attractive physiological response, revealing the capacity of cells to deal with adverse effects induced by Abeta.

  3. Key residues for the oligomerization of A{beta}42 protein in Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Ngo, Sam [Department of Neurology, Brain Research Institute, Molecular Biology Institute, University of California, Los Angeles, CA 90095 (United States); Guo, Zhefeng, E-mail: zhefeng@ucla.edu [Department of Neurology, Brain Research Institute, Molecular Biology Institute, University of California, Los Angeles, CA 90095 (United States)

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer A{beta} oligomers are neurotoxins and likely the causing agents for Alzheimer's disease. Black-Right-Pointing-Pointer A{beta}42 fusion protein form globular oligomers. Black-Right-Pointing-Pointer A{beta}42 fusion protein oligomers contain SDS-resistant tetramers and hexamers. Black-Right-Pointing-Pointer Cysteine substitutions at residues 31, 32, 34, 39-41 disrupt A{beta}42 oligomerization. -- Abstract: Deposition of amyloid fibrils consisting of amyloid {beta} (A{beta}) protein as senile plaques in the brain is a pathological hallmark of Alzheimer's disease. However, a growing body of evidence shows that soluble A{beta} oligomers correlate better with dementia than fibrils, suggesting that A{beta} oligomers may be the primary toxic species. The structure and oligomerization mechanism of these A{beta} oligomers are crucial for developing effective therapeutics. Here we investigated the oligomerization of A{beta}42 in the context of a fusion protein containing GroES and ubiquitin fused to the N-terminus of A{beta} sequence. The presence of fusion protein partners, in combination with a denaturing buffer containing 8 M urea at pH 10, is unfavorable for A{beta}42 aggregation, thus allowing only the most stable structures to be observed. Transmission electron microscopy showed that A{beta}42 fusion protein formed globular oligomers, which bound weakly to thioflavin T and Congo red. SDS-PAGE shows that A{beta}42 fusion protein formed SDS-resistant hexamers and tetramers. In contrast, A{beta}40 fusion protein remained as monomers on SDS gel, suggesting that the oligomerization of A{beta}42 fusion protein is not due to the fusion protein partners. Cysteine scanning mutagenesis at 22 residue positions further revealed that single cysteine substitutions of the C-terminal hydrophobic residues (I31, I32, L34, V39, V40, and I41) led to disruption of hexamer and tetramer formation, suggesting that hydrophobic interactions

  4. Persistent amyloidosis following suppression of Abeta production in a transgenic model of Alzheimer disease.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available BACKGROUND: The proteases (secretases that cleave amyloid-beta (Abeta peptide from the amyloid precursor protein (APP have been the focus of considerable investigation in the development of treatments for Alzheimer disease. The prediction has been that reducing Abeta production in the brain, even after the onset of clinical symptoms and the development of associated pathology, will facilitate the repair of damaged tissue and removal of amyloid lesions. However, no long-term studies using animal models of amyloid pathology have yet been performed to test this hypothesis. METHODS AND FINDINGS: We have generated a transgenic mouse model that genetically mimics the arrest of Abeta production expected from treatment with secretase inhibitors. These mice overexpress mutant APP from a vector that can be regulated by doxycycline. Under normal conditions, high-level expression of APP quickly induces fulminant amyloid pathology. We show that doxycycline administration inhibits transgenic APP expression by greater than 95% and reduces Abeta production to levels found in nontransgenic mice. Suppression of transgenic Abeta synthesis in this model abruptly halts the progression of amyloid pathology. However, formation and disaggregation of amyloid deposits appear to be in disequilibrium as the plaques require far longer to disperse than to assemble. Mice in which APP synthesis was suppressed for as long as 6 mo after the formation of Abeta deposits retain a considerable amyloid load, with little sign of active clearance. CONCLUSION: This study demonstrates that amyloid lesions in transgenic mice are highly stable structures in vivo that are slow to disaggregate. Our findings suggest that arresting Abeta production in patients with Alzheimer disease should halt the progression of pathology, but that early treatment may be imperative, as it appears that amyloid deposits, once formed, will require additional intervention to clear.

  5. Persistent amyloidosis following suppression of Abeta production in a transgenic model of Alzheimer disease.

    Directory of Open Access Journals (Sweden)

    Joanna L Jankowsky

    2005-12-01

    Full Text Available The proteases (secretases that cleave amyloid-beta (Abeta peptide from the amyloid precursor protein (APP have been the focus of considerable investigation in the development of treatments for Alzheimer disease. The prediction has been that reducing Abeta production in the brain, even after the onset of clinical symptoms and the development of associated pathology, will facilitate the repair of damaged tissue and removal of amyloid lesions. However, no long-term studies using animal models of amyloid pathology have yet been performed to test this hypothesis.We have generated a transgenic mouse model that genetically mimics the arrest of Abeta production expected from treatment with secretase inhibitors. These mice overexpress mutant APP from a vector that can be regulated by doxycycline. Under normal conditions, high-level expression of APP quickly induces fulminant amyloid pathology. We show that doxycycline administration inhibits transgenic APP expression by greater than 95% and reduces Abeta production to levels found in nontransgenic mice. Suppression of transgenic Abeta synthesis in this model abruptly halts the progression of amyloid pathology. However, formation and disaggregation of amyloid deposits appear to be in disequilibrium as the plaques require far longer to disperse than to assemble. Mice in which APP synthesis was suppressed for as long as 6 mo after the formation of Abeta deposits retain a considerable amyloid load, with little sign of active clearance.This study demonstrates that amyloid lesions in transgenic mice are highly stable structures in vivo that are slow to disaggregate. Our findings suggest that arresting Abeta production in patients with Alzheimer disease should halt the progression of pathology, but that early treatment may be imperative, as it appears that amyloid deposits, once formed, will require additional intervention to clear.

  6. Complement C1q expression induced by Abeta in rat hippocampal organotypic slice cultures.

    Science.gov (United States)

    Fan, Rong; Tenner, Andrea J

    2004-02-01

    Amyloid beta peptide (Abeta) is a major component of senile plaques, one of the principle pathological features in Alzheimer's disease (AD) brains. Fibrillar Abeta has been shown to bind C1 via C1q, the recognition component of the classical complement pathway, resulting in the activation of the complement pathway, thereby initiating an inflammatory cascade in the brain. C1q has also been shown to enhance phagocytic activities of microglia, which could benefit in clearance of apoptotic cells or cellular debris. To begin to define the role of C1q in tissue injury mediated by Abeta, we assessed the appearance of C1q in hippocampal slice cultures treated with freshly solubilized or fibrillar Abeta 1-42. Here we demonstrate a dose- and time-dependent uptake of exogenously applied Abeta by pyramidal neurons in organotypic slice cultures from rat hippocampus. Importantly, when slices were immunostained with antibody against rat C1q, a distinct reactivity for C1q in cells within the neuronal cell layer of cornu ammonis (CA) of hippocampus, primarily the CA1/CA2, was observed in the Abeta-treated slices. No such immunoreactivity was detected in untreated cultures or upon addition of control peptides. ELISA assays also showed an increase in C1q in tissue extracts from slices of the treated group. Similarly, the mRNA level of C1q in slices was increased within 24 h after Abeta treatment. These data demonstrate that upon exposure to Abeta, C1q is expressed in neurons in this organotypic system. The induction of C1q may be an early, perhaps beneficial, tissue or cellular response to injury triggered by particular pathogenic stimuli.

  7. Brain alterations and clinical symptoms of dementia in diabetes: Abeta/tau-dependent and independent mechanisms

    Directory of Open Access Journals (Sweden)

    Naoyuki eSato

    2014-09-01

    Full Text Available Emerging evidence suggests that diabetes affects cognitive function and increases the incidence of dementia. However, the mechanisms by which diabetes modifies cognitive function still remains unclear. Morphologically, diabetes is associated with neuronal loss in the frontal and temporal lobes including the hippocampus, and aberrant functional connectivity of the posterior cingulate cortex and medial frontal/temporal gyrus. Clinically, diabetic patients show decreased executive function, information processing, planning, visuospatial construction, and visual memory. Therefore, in comparison with the characteristics of AD brain structure and cognition, diabetes seems to affect cognitive function through not only simple AD pathological feature-dependent mechanisms, but also independent mechanisms. As an Abeta/tau-independent mechanism, diabetes compromises cerebrovascular function, increases subcortical infarction and might alter the blood brain barrier (BBB. Diabetes also affects glucose metabolism, insulin signaling and mitochondrial function in the brain. Diabetes also modifies metabolism of Abeta and tau and causes Abeta/tau-dependent pathological changes. Moreover, there is evidence that suggests an interaction between Abeta/tau-dependent and independent mechanisms. Therefore, diabetes modifies cognitive function through Abeta/tau-dependent and independent mechanisms. Interaction between these two mechanisms forms a vicious cycle.

  8. Abeta-degrading enzymes in Alzheimer's disease.

    Science.gov (United States)

    Miners, James Scott; Baig, Shabnam; Palmer, Jennifer; Palmer, Laura E; Kehoe, Patrick G; Love, Seth

    2008-04-01

    In Alzheimer's disease (AD) Abeta accumulates because of imbalance between the production of Abeta and its removal from the brain. There is increasing evidence that in most sporadic forms of AD, the accumulation of Abeta is partly, if not in some cases solely, because of defects in its removal--mediated through a combination of diffusion along perivascular extracellular matrix, transport across vessel walls into the blood stream and enzymatic degradation. Multiple enzymes within the central nervous system (CNS) are capable of degrading Abeta. Most are produced by neurons or glia, but some are expressed in the cerebral vasculature, where reduced Abeta-degrading activity may contribute to the development of cerebral amyloid angiopathy (CAA). Neprilysin and insulin-degrading enzyme (IDE), which have been most extensively studied, are expressed both neuronally and within the vasculature. The levels of both of these enzymes are reduced in AD although the correlation with enzyme activity is still not entirely clear. Other enzymes shown capable of degrading Abetain vitro or in animal studies include plasmin; endothelin-converting enzymes ECE-1 and -2; matrix metalloproteinases MMP-2, -3 and -9; and angiotensin-converting enzyme (ACE). The levels of plasmin and plasminogen activators (uPA and tPA) and ECE-2 are reported to be reduced in AD. Reductions in neprilysin, IDE and plasmin in AD have been associated with possession of APOEepsilon4. We found no change in the level or activity of MMP-2, -3 or -9 in AD. The level and activity of ACE are increased, the level being directly related to Abeta plaque load. Up-regulation of some Abeta-degrading enzymes may initially compensate for declining activity of others, but as age, genetic factors and diseases such as hypertension and diabetes diminish the effectiveness of other Abeta-clearance pathways, reductions in the activity of particular Abeta-degrading enzymes may become critical, leading to the development of AD and CAA.

  9. Ellagic acid promotes A{beta}42 fibrillization and inhibits A{beta}42-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Ying [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Yang, Shi-gao; Du, Xue-ting; Zhang, Xi; Sun, Xiao-xia; Zhao, Min [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Sun, Gui-yuan, E-mail: sungy2004@sohu.com [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Liu, Rui-tian, E-mail: rtliu@tsinghua.edu.cn [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China)

    2009-12-25

    Smaller, soluble oligomers of {beta}-amyloid (A{beta}) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of A{beta} oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against A{beta} neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on A{beta}42 aggregation and neurotoxicity in vitro. EA promoted A{beta} fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited A{beta} aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in A{beta}42 samples co-incubated with EA in earlier phases of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic A{beta} aggregates to render them harmless, our MTT results showed that EA could significantly reduce A{beta}42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD.

  10. Selective binding of soluble Abeta1-40 and Abeta1-42 to a subset of senile plaques.

    OpenAIRE

    Prior, R.; D'Urso, D.; Frank, R; Prikulis, I.; Cleven, S.; Ihl, R; Pavlakovic, G.

    1996-01-01

    Alzheimer's disease is characterized by the progressive accumulation of amyloid-beta protein (Abeta) in senile plaques and cerebral amyloid angiopathy. It is not known whether the plaque growth is a continuous and homogeneous process or whether some plaques have a more rapid evolution. As plaques grow by the deposition of Abeta, we used an in situ binding technique to analyze the deposition of fluorescein-conjugated and biotinylated Abeta1 40 and Abeta1-42 in cryosections of brains from Alzhe...

  11. IMMUNODOMINANT EPITOPE AND PROPERTIES OF PYROGLUTAMATE-MODIFIED Aβ-SPECIFIC ANTIBODIES PRODUCED IN RABBITS

    Science.gov (United States)

    Acero, G.; Manoutcharian, K.; Vasilevko, V.; Munguia, M.E.; Govezensky, T.; Coronas, G.; Luz-Madrigal, A.; Cribbs, DH.; Gevorkian, G.

    2009-01-01

    N-truncated and N-modified forms of amyloid beta (Aß) peptide are found in diffused and dense core plaques in Alzheimer’s disease (AD) and Down’s syndrome patients as well as transgenic mouse models of AD. Although the pathological significance of these shortened forms Aβ is not completely understood, previous studies have demonstrated that these peptides are significantly more resistant to degradation, aggregate more rapidly in vitro and exhibit similar or, in some cases, increased toxicity in hippocampal neuronal cultures compared to the full-length peptides. In the present study we further investigated the mechanisms of toxicity of one of the most abundant Ntruncated/modified Aβ peptide bearing amino-terminal pyroglutamate at position 3 (AβN3(pE)). We demonstrated that AβN3(pE) oligomers induce phosphatidyl serine externalization and membrane damage in SH-SY5Y cells. Also, we produced AβN3(pE)-specific polyclonal antibodies in rabbit and identified an immunodominant epitope recognized by anti-AβN3(pE) antibodies. Our results are important for developing new immunotherapeutic compounds specifically targeting AβN3(pE) aggregates since the most commonly used immunogens in the majority of vaccines for AD have been shown to induce antibodies that recognize the N-terminal immunodominant epitope (EFRH) of the full length Aβ, which is absent in N-amino truncated peptides. PMID:19545911

  12. Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers II: Sigma-2/PGRMC1 receptors mediate Abeta 42 oligomer binding and synaptotoxicity.

    Science.gov (United States)

    Izzo, Nicholas J; Xu, Jinbin; Zeng, Chenbo; Kirk, Molly J; Mozzoni, Kelsie; Silky, Colleen; Rehak, Courtney; Yurko, Raymond; Look, Gary; Rishton, Gilbert; Safferstein, Hank; Cruchaga, Carlos; Goate, Alison; Cahill, Michael A; Arancio, Ottavio; Mach, Robert H; Craven, Rolf; Head, Elizabeth; LeVine, Harry; Spires-Jones, Tara L; Catalano, Susan M

    2014-01-01

    Amyloid beta (Abeta) 1-42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI) and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding of Abeta oligomers to several putative receptor proteins is reported to inhibit long-term potentiation, affect membrane trafficking and induce reversible spine loss in neurons, leading to impaired cognitive performance and ultimately to anterograde amnesia in the early stages of Alzheimer's disease (AD). We have identified a receptor not previously associated with AD that mediates the binding of Abeta oligomers to neurons, and describe novel therapeutic antagonists of this receptor capable of blocking Abeta toxic effects on synapses in vitro and cognitive deficits in vivo. Knockdown of sigma-2/PGRMC1 (progesterone receptor membrane component 1) protein expression in vitro using siRNA results in a highly correlated reduction in binding of exogenous Abeta oligomers to neurons of more than 90%. Expression of sigma-2/PGRMC1 is upregulated in vitro by treatment with Abeta oligomers, and is dysregulated in Alzheimer's disease patients' brain compared to age-matched, normal individuals. Specific, high affinity small molecule receptor antagonists and antibodies raised against specific regions on this receptor can displace synthetic Abeta oligomer binding to synaptic puncta in vitro and displace endogenous human AD patient oligomers from brain tissue sections in a dose-dependent manner. These receptor antagonists prevent and reverse the effects of Abeta oligomers on membrane trafficking and synapse loss in vitro and cognitive deficits in AD mouse models. These findings suggest sigma-2/PGRMC1 receptors mediate saturable oligomer binding to synaptic puncta on neurons and that brain penetrant, small molecules can displace endogenous and synthetic oligomers and improve cognitive deficits in AD models. We propose that sigma-2/PGRMC1 is a key mediator of the pathological effects of

  13. Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers II: Sigma-2/PGRMC1 receptors mediate Abeta 42 oligomer binding and synaptotoxicity.

    Directory of Open Access Journals (Sweden)

    Nicholas J Izzo

    Full Text Available Amyloid beta (Abeta 1-42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding of Abeta oligomers to several putative receptor proteins is reported to inhibit long-term potentiation, affect membrane trafficking and induce reversible spine loss in neurons, leading to impaired cognitive performance and ultimately to anterograde amnesia in the early stages of Alzheimer's disease (AD. We have identified a receptor not previously associated with AD that mediates the binding of Abeta oligomers to neurons, and describe novel therapeutic antagonists of this receptor capable of blocking Abeta toxic effects on synapses in vitro and cognitive deficits in vivo. Knockdown of sigma-2/PGRMC1 (progesterone receptor membrane component 1 protein expression in vitro using siRNA results in a highly correlated reduction in binding of exogenous Abeta oligomers to neurons of more than 90%. Expression of sigma-2/PGRMC1 is upregulated in vitro by treatment with Abeta oligomers, and is dysregulated in Alzheimer's disease patients' brain compared to age-matched, normal individuals. Specific, high affinity small molecule receptor antagonists and antibodies raised against specific regions on this receptor can displace synthetic Abeta oligomer binding to synaptic puncta in vitro and displace endogenous human AD patient oligomers from brain tissue sections in a dose-dependent manner. These receptor antagonists prevent and reverse the effects of Abeta oligomers on membrane trafficking and synapse loss in vitro and cognitive deficits in AD mouse models. These findings suggest sigma-2/PGRMC1 receptors mediate saturable oligomer binding to synaptic puncta on neurons and that brain penetrant, small molecules can displace endogenous and synthetic oligomers and improve cognitive deficits in AD models. We propose that sigma-2/PGRMC1 is a key mediator of the pathological

  14. Transnasal delivery of human A-beta peptides elicits impaired learning and memory performance in wild type mice.

    Science.gov (United States)

    Endres, Kristina; Reinhardt, Sven; Geladaris, Anastasia; Knies, Julia; Grimm, Marcus; Hartmann, Tobias; Schmitt, Ulrich

    2016-07-04

    Murine models of Alzheimer's disease (AD) are mainly based on overexpression of pathologic amyloid precursor protein and/or presenilins. Those genes resemble underlying cause of early onset type of AD while about 99 % of all human cases are to be characterized as sporadic, late onset. Appropriate animal models for this type of AD are still missing. We here investigated, if transnasal delivery of A-beta 42 peptides might serve to mimic pathological effects in mice. A-beta 42 peptides, used for the behavioral study, showed the expected dose-dependent toxicity in neur oblastoma cell line SH-SY5Y and were able to form higher molecular weight species in vitro. Upon delivery into nostrils of wild type mice, protein bands that might represent aggregation products of the exogenously applied human A-beta 42 were only observed in total brain homogenates from mice pre-treated with mannitol. By using TAMRA-labeled A-beta 42 peptides we demonstrated, that transport throughout the brain was achieved already 1 h after administration. FVB/N mice treated with A-beta 42 for 3 days were significantly impaired in the cue-retention condition of the fear conditioning task as compared to controls whereas A-beta-treated C57B6/J mice were impaired in the context condition. In the Morris water maze test, these mice also displayed a delayed learning performance, indicated by significantly longer time to find the platform. Those deficits were also seen for memory performance in the probe trial as measured by number of crossings of the former platform position and time spent in the goal quadrant. Existing AD mouse models are of genetic origin and need prolonged housing time before onset of pathology. Our short-term treatment induced learning and memory deficits via exogenous application of A-beta peptides comparable to those observed for the transgenic animals. With the transnasal A-beta 42 treatment we present an approach to investigate purely A-beta related changes suitable as a model for

  15. The tissue plasminogen activator-plasminogen proteolytic cascade accelerates amyloid-beta (Abeta) degradation and inhibits Abeta-induced neurodegeneration.

    Science.gov (United States)

    Melchor, Jerry P; Pawlak, Robert; Strickland, Sidney

    2003-10-01

    Accumulation of the amyloid-beta (Abeta) peptide depends on both its generation and clearance. To better define clearance pathways, we have evaluated the role of the tissue plasminogen activator (tPA)-plasmin system in Abeta degradation in vivo. In two different mouse models of Alzheimer's disease, chronically elevated Abeta peptide in the brain correlates with the upregulation of plasminogen activator inhibitor-1 (PAI-1) and inhibition of the tPA-plasmin system. In addition, Abeta injected into the hippocampus of mice lacking either tPA or plasminogen persists, inducing PAI-1 expression and causing activation of microglial cells and neuronal damage. Conversely, Abeta injected into wild-type mice is rapidly cleared and does not cause neuronal degeneration. Thus, the tPA-plasmin proteolytic cascade aids in the clearance of Abeta, and reduced activity of this system may contribute to the progression of Alzheimer's disease.

  16. Transthyretin Protects against A-Beta Peptide Toxicity by Proteolytic Cleavage of the Peptide: A Mechanism Sensitive to the Kunitz Protease Inhibitor

    Science.gov (United States)

    Costa, Rita; Ferreira-da-Silva, Frederico; Saraiva, Maria J.; Cardoso, Isabel

    2008-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of amyloid β-peptide (A-Beta) in the brain. Transthyretin (TTR) is a tetrameric protein of about 55 kDa mainly produced in the liver and choroid plexus of the brain. The known physiological functions of TTR are the transport of thyroid hormone T4 and retinol, through binding to the retinol binding protein. TTR has also been established as a cryptic protease able to cleave ApoA-I in vitro. It has been described that TTR is involved in preventing A-Beta fibrilization, both by inhibiting and disrupting A-Beta fibrils, with consequent abrogation of toxicity. We further characterized the nature of the TTR/A-Beta interaction and found that TTR, both recombinant or isolated from human sera, was able to proteolytically process A-Beta, cleaving the peptide after aminoacid residues 1, 2, 3, 10, 13, 14,16, 19 and 27, as determined by mass spectrometry, and reversed phase chromatography followed by N-terminal sequencing. A-Beta peptides (1–14) and (15–42) showed lower amyloidogenic potential than the full length counterpart, as assessed by thioflavin binding assay and ultrastructural analysis by transmission electron microscopy. A-Beta cleavage by TTR was inhibited in the presence of an αAPP peptide containing the Kunitz Protease Inhibitor (KPI) domain but not in the presence of the secreted αAPP derived from the APP isoform 695 without the KPI domain. TTR was also able to degrade aggregated forms of A-Beta peptide. Our results confirmed TTR as a protective molecule in AD, and prompted A-Beta proteolysis by TTR as a protective mechanism in this disease. TTR may prove to be a useful therapeutic agent for preventing or retarding the cerebral amyloid plaque formation implicated in AD pathology. PMID:18682830

  17. Transthyretin protects against A-beta peptide toxicity by proteolytic cleavage of the peptide: a mechanism sensitive to the Kunitz protease inhibitor.

    Directory of Open Access Journals (Sweden)

    Rita Costa

    Full Text Available Alzheimer's disease (AD is a neurodegenerative disorder characterized by the deposition of amyloid beta-peptide (A-Beta in the brain. Transthyretin (TTR is a tetrameric protein of about 55 kDa mainly produced in the liver and choroid plexus of the brain. The known physiological functions of TTR are the transport of thyroid hormone T(4 and retinol, through binding to the retinol binding protein. TTR has also been established as a cryptic protease able to cleave ApoA-I in vitro. It has been described that TTR is involved in preventing A-Beta fibrilization, both by inhibiting and disrupting A-Beta fibrils, with consequent abrogation of toxicity. We further characterized the nature of the TTR/A-Beta interaction and found that TTR, both recombinant or isolated from human sera, was able to proteolytically process A-Beta, cleaving the peptide after aminoacid residues 1, 2, 3, 10, 13, 14,16, 19 and 27, as determined by mass spectrometry, and reversed phase chromatography followed by N-terminal sequencing. A-Beta peptides (1-14 and (15-42 showed lower amyloidogenic potential than the full length counterpart, as assessed by thioflavin binding assay and ultrastructural analysis by transmission electron microscopy. A-Beta cleavage by TTR was inhibited in the presence of an alphaAPP peptide containing the Kunitz Protease Inhibitor (KPI domain but not in the presence of the secreted alphaAPP derived from the APP isoform 695 without the KPI domain. TTR was also able to degrade aggregated forms of A-Beta peptide. Our results confirmed TTR as a protective molecule in AD, and prompted A-Beta proteolysis by TTR as a protective mechanism in this disease. TTR may prove to be a useful therapeutic agent for preventing or retarding the cerebral amyloid plaque formation implicated in AD pathology.

  18. Dickkopf-related protein 3 is a potential Abeta-associated protein in Alzheimer's Disease

    NARCIS (Netherlands)

    Bruggink, K.A.; Kuiperij, H.B.; Gloerich, J.; Otte-Holler, I.; Rozemuller, A.J.; Claassen, J.A.H.R.; Kusters, B.; Verbeek, M.M.

    2015-01-01

    Amyloid-beta (Abeta) is the most prominent protein in Alzheimer's disease (AD) senile plaques. In addition, Abeta interacts with a variety of Abeta-associated proteins (AAPs), some of which can form complexes with Abeta and influence its clearance, aggregation or toxicity. Identification of novel AA

  19. Dickkopf-related protein 3 is a potential Abeta-associated protein in Alzheimer's Disease

    NARCIS (Netherlands)

    Bruggink, K.A.; Kuiperij, H.B.; Gloerich, J.; Otte-Holler, I.; Rozemuller, A.J.; Claassen, J.A.H.R.; Kusters, B.; Verbeek, M.M.

    2015-01-01

    Amyloid-beta (Abeta) is the most prominent protein in Alzheimer's disease (AD) senile plaques. In addition, Abeta interacts with a variety of Abeta-associated proteins (AAPs), some of which can form complexes with Abeta and influence its clearance, aggregation or toxicity. Identification of novel

  20. Identification of Glutaminyl Cyclase Genes Involved in Pyroglutamate Modification of Fungal Lignocellulolytic Enzymes

    Directory of Open Access Journals (Sweden)

    Vincent W. Wu

    2017-01-01

    Full Text Available The breakdown of plant biomass to simple sugars is essential for the production of second-generation biofuels and high-value bioproducts. Currently, enzymes produced from filamentous fungi are used for deconstructing plant cell wall polysaccharides into fermentable sugars for biorefinery applications. A post-translational N-terminal pyroglutamate modification observed in some of these enzymes occurs when N-terminal glutamine or glutamate is cyclized to form a five-membered ring. This modification has been shown to confer resistance to thermal denaturation for CBH-1 and EG-1 cellulases. In mammalian cells, the formation of pyroglutamate is catalyzed by glutaminyl cyclases. Using the model filamentous fungus Neurospora crassa, we identified two genes (qc-1 and qc-2 that encode proteins homologous to mammalian glutaminyl cyclases. We show that qc-1 and qc-2 are essential for catalyzing the formation of an N-terminal pyroglutamate on CBH-1 and GH5-1. CBH-1 and GH5-1 produced in a Δqc-1 Δqc-2 mutant, and thus lacking the N-terminal pyroglutamate modification, showed greater sensitivity to thermal denaturation, and for GH5-1, susceptibility to proteolytic cleavage. QC-1 and QC-2 are endoplasmic reticulum (ER-localized proteins. The pyroglutamate modification is predicted to occur in a number of additional fungal proteins that have diverse functions. The identification of glutaminyl cyclases in fungi may have implications for production of lignocellulolytic enzymes, heterologous expression, and biotechnological applications revolving around protein stability.

  1. Identification of Glutaminyl Cyclase Genes Involved in Pyroglutamate Modification of Fungal Lignocellulolytic Enzymes

    Science.gov (United States)

    Wu, Vincent W.; Dana, Craig M.; Iavarone, Anthony T.; Clark, Douglas S.

    2017-01-01

    ABSTRACT The breakdown of plant biomass to simple sugars is essential for the production of second-generation biofuels and high-value bioproducts. Currently, enzymes produced from filamentous fungi are used for deconstructing plant cell wall polysaccharides into fermentable sugars for biorefinery applications. A post-translational N-terminal pyroglutamate modification observed in some of these enzymes occurs when N-terminal glutamine or glutamate is cyclized to form a five-membered ring. This modification has been shown to confer resistance to thermal denaturation for CBH-1 and EG-1 cellulases. In mammalian cells, the formation of pyroglutamate is catalyzed by glutaminyl cyclases. Using the model filamentous fungus Neurospora crassa, we identified two genes (qc-1 and qc-2) that encode proteins homologous to mammalian glutaminyl cyclases. We show that qc-1 and qc-2 are essential for catalyzing the formation of an N-terminal pyroglutamate on CBH-1 and GH5-1. CBH-1 and GH5-1 produced in a Δqc-1 Δqc-2 mutant, and thus lacking the N-terminal pyroglutamate modification, showed greater sensitivity to thermal denaturation, and for GH5-1, susceptibility to proteolytic cleavage. QC-1 and QC-2 are endoplasmic reticulum (ER)-localized proteins. The pyroglutamate modification is predicted to occur in a number of additional fungal proteins that have diverse functions. The identification of glutaminyl cyclases in fungi may have implications for production of lignocellulolytic enzymes, heterologous expression, and biotechnological applications revolving around protein stability. PMID:28096492

  2. Activation of PERK signaling attenuates Abeta-mediated ER stress.

    Directory of Open Access Journals (Sweden)

    Do Yeon Lee

    Full Text Available Alzheimer's disease (AD is characterized by the deposition of aggregated beta-amyloid (Abeta, which triggers a cellular stress response called the unfolded protein response (UPR. The UPR signaling pathway is a cellular defense system for dealing with the accumulation of misfolded proteins but switches to apoptosis when endoplasmic reticulum (ER stress is prolonged. ER stress is involved in neurodegenerative diseases including AD, but the molecular mechanisms of ER stress-mediated Abeta neurotoxicity still remain unknown. Here, we show that treatment of Abeta triggers the UPR in the SK-N-SH human neuroblastoma cells. Abeta mediated UPR pathway accompanies the activation of protective pathways such as Grp78/Bip and PERK-eIF2alpha pathway, as well as the apoptotic pathways of the UPR such as CHOP and caspase-4. Knockdown of PERK enhances Abeta neurotoxicity through reducing the activation of eIF2alpha and Grp8/Bip in neurons. Salubrinal, an activator of the eIF2alpha pathway, significantly increased the Grp78/Bip ER chaperone resulted in attenuating caspase-4 dependent apoptosis in Abeta treated neurons. These results indicate that PERK-eIF2alpha pathway is a potential target for therapeutic applications in neurodegenerative diseases including AD.

  3. Infrared spectroscopic studies of the effect of elevated temperature on the association of pyroglutamic acid with clay and other minerals

    Science.gov (United States)

    Macklin, J. W.; White, D. H.

    1985-01-01

    Fourier transform i.r. measurements of L-pyroglutamic acid dispersed in a matrix of a clay, silica or alumina have been obtained at various temperatures between 25 and 220 degrees C. The i.r. spectrum of L-pyroglutamic acid varies in a manner dependent upon the matrix material and shows considerable change as the temperature of the mixtures is increased. The differences in the spectrum at elevated temperatures are explained in terms of a chemical reaction between hydroxyl groups in the matrix and the carboxylic acid. The i.r. spectra of trimethylsilyl derivatives of L-pyroglutamic acid and aluminum pyroglutamate were also measured to assist the understanding of spectra and interpretation of the spectral changes dependent upon increasing temperature.

  4. Abeta-induced meningoencephalitis is IFN-gamma-dependent and is associated with T cell-dependent clearance of Abeta in a mouse model of Alzheimer's disease

    DEFF Research Database (Denmark)

    Monsonego, Alon; Imitola, Jaime; Petrovic, Sanja

    2006-01-01

    Vaccination against amyloid beta-peptide (Abeta) has been shown to be successful in reducing Abeta burden and neurotoxicity in mouse models of Alzheimer's disease (AD). However, although Abeta immunization did not show T cell infiltrates in the brain of these mice, an Abeta vaccination trial...... resulted in meningoencephalitis in 6% of patients with AD. Here, we explore the characteristics and specificity of Abeta-induced, T cell-mediated encephalitis in a mouse model of the disease. We demonstrate that a strong Abeta-specific T cell response is critically dependent on the immunizing T cell...... epitope and that epitopes differ depending on MHC genetic background. Moreover, we show that a single immunization with the dominant T cell epitope Abeta10-24 induced transient meningoencephalitis only in amyloid precursor protein (APP)-transgenic (Tg) mice expressing limited amounts of IFN-gamma under...

  5. Evidence for the accumulation of Abeta immunoreactive material in the human brain and in transgenic animal models.

    Science.gov (United States)

    Cuello, A Claudio; Allard, Simon; Ferretti, Maria Teresa

    2012-12-10

    In this review we highlight the evidence for an intracellular origin of Abeta (Aβ) amyloid peptides as well as the observations for a pathological accumulation of these peptides in Alzheimer's disease and Down syndrome, as well as in transgenic animal models. We deliberate on the controversy as to whether the intracellular Aβ immunoreactive material is simply an accumulation of unprocessed full length amyloid precursor protein (APP) or a mix of processed APP fragments including Aβ. Finally, we discuss the possible pathological significance of these intracellular APP fragments and the expected future research directions regarding this thought-provoking problem. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Purification and Characterization of Recombinant N-Terminally Pyroglutamate-Modified Amyloid-β Variants and Structural Analysis by Solution NMR Spectroscopy

    Science.gov (United States)

    Dammers, Christina; Gremer, Lothar; Neudecker, Philipp; Demuth, Hans-Ulrich; Schwarten, Melanie; Willbold, Dieter

    2015-01-01

    Alzheimer’s disease (AD) is the leading cause of dementia in the elderly and is characterized by memory loss and cognitive decline. Pathological hallmark of AD brains are intracellular neurofibrillary tangles and extracellular amyloid plaques. The major component of these plaques is the highly heterogeneous amyloid-β (Aβ) peptide, varying in length and modification. In recent years pyroglutamate-modified amyloid-β (pEAβ) peptides have increasingly moved into the focus since they have been described to be the predominant species of all N-terminally truncated Aβ. Compared to unmodified Aβ, pEAβ is known to show increased hydrophobicity, higher toxicity, faster aggregation and β-sheet stabilization and is more resistant to degradation. Nuclear magnetic resonance (NMR) spectroscopy is a particularly powerful method to investigate the conformations of pEAβ isoforms in solution and to study peptide/ligand interactions for drug development. However, biophysical characterization of pEAβ and comparison to its non-modified variant has so far been seriously hampered by the lack of highly pure recombinant and isotope-enriched protein. Here we present, to our knowledge, for the first time a reproducible protocol for the production of pEAβ from a recombinant precursor expressed in E. coli in natural isotope abundance as well as in uniformly [U-15N]- or [U-13C, 15N]-labeled form, with yields of up to 15 mg/l E. coli culture broth. The chemical state of the purified protein was evaluated by RP-HPLC and formation of pyroglutamate was verified by mass spectroscopy. The recombinant pyroglutamate-modified Aβ peptides showed characteristic sigmoidal aggregation kinetics as monitored by thioflavin-T assays. The quality and quantity of produced pEAβ40 and pEAβ42 allowed us to perform heteronuclear multidimensional NMR spectroscopy in solution and to sequence-specifically assign the backbone resonances under near-physiological conditions. Our results suggest that the

  7. Purification and Characterization of Recombinant N-Terminally Pyroglutamate-Modified Amyloid-β Variants and Structural Analysis by Solution NMR Spectroscopy.

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    Christina Dammers

    Full Text Available Alzheimer's disease (AD is the leading cause of dementia in the elderly and is characterized by memory loss and cognitive decline. Pathological hallmark of AD brains are intracellular neurofibrillary tangles and extracellular amyloid plaques. The major component of these plaques is the highly heterogeneous amyloid-β (Aβ peptide, varying in length and modification. In recent years pyroglutamate-modified amyloid-β (pEAβ peptides have increasingly moved into the focus since they have been described to be the predominant species of all N-terminally truncated Aβ. Compared to unmodified Aβ, pEAβ is known to show increased hydrophobicity, higher toxicity, faster aggregation and β-sheet stabilization and is more resistant to degradation. Nuclear magnetic resonance (NMR spectroscopy is a particularly powerful method to investigate the conformations of pEAβ isoforms in solution and to study peptide/ligand interactions for drug development. However, biophysical characterization of pEAβ and comparison to its non-modified variant has so far been seriously hampered by the lack of highly pure recombinant and isotope-enriched protein. Here we present, to our knowledge, for the first time a reproducible protocol for the production of pEAβ from a recombinant precursor expressed in E. coli in natural isotope abundance as well as in uniformly [U-15N]- or [U-13C, 15N]-labeled form, with yields of up to 15 mg/l E. coli culture broth. The chemical state of the purified protein was evaluated by RP-HPLC and formation of pyroglutamate was verified by mass spectroscopy. The recombinant pyroglutamate-modified Aβ peptides showed characteristic sigmoidal aggregation kinetics as monitored by thioflavin-T assays. The quality and quantity of produced pEAβ40 and pEAβ42 allowed us to perform heteronuclear multidimensional NMR spectroscopy in solution and to sequence-specifically assign the backbone resonances under near-physiological conditions. Our results suggest

  8. Influence of l-pyroglutamic acid on the color formation process of non-enzymatic browning reactions.

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    Wegener, Steffen; Kaufmann, Martin; Kroh, Lothar W

    2017-10-01

    Heating aqueous d-glucose model reactions with l-glutamine and l-alanine yielded similar colored solutions. However, size-exclusion chromatography (SEC) revealed that both non-enzymatic browning reactions proceeded differently. Due to a fast occurring cyclization of l-glutamine to pyroglutamic acid, the typical amino-carbonyl reaction was slowed down. However, l-glutamine and l-alanine model reactions showed the same browning index. Closer investigations could prove that l-pyroglutamic acid was able to influence non-enzymatic browning reactions. SEC analyses of d-glucose model reactions with and without l-pyroglutamic acid revealed an increase of low molecular colored compounds in the presence of l-pyroglutamic acid. Polarimetric measurements showed a doubling of d-glucose mutarotation velocity and HPLC analyses of d-fructose formation during thermal treatment indicated a tripling of aldose-ketose transformation in the presence of l-pyroglutamic acid, which are signs of a faster proceeding non-enzymatic browning process. 2-Pyrrolidone showed no such behavior, thus the additional carboxylic group should be responsible for the observed effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Computational selection of inhibitors of Abeta aggregation and neuronal toxicity.

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    Chen, Deliang; Martin, Zane S; Soto, Claudio; Schein, Catherine H

    2009-07-15

    Alzheimer's disease (AD) is characterized by the cerebral accumulation of misfolded and aggregated amyloid-beta protein (Abeta). Disease symptoms can be alleviated, in vitro and in vivo, by 'beta-sheet breaker' pentapeptides that reduce plaque load. However the peptide nature of these compounds, made them biologically unstable and unable to penetrate membranes with high efficiency. The main goal of this study was to use computational methods to identify small molecule mimetics with better drug-like properties. For this purpose, the docked conformations of the active peptides were used to identify compounds with similar activities. A series of related beta-sheet breaker peptides were docked to solid state NMR structures of a fibrillar form of Abeta. The lowest energy conformations of the active peptides were used to design three dimensional (3D)-pharmacophores, suitable for screening the NCI database with Unity. Small molecular weight compounds with physicochemical features and a conformation similar to the active peptides were selected, ranked by docking and biochemical parameters. Of 16 diverse compounds selected for experimental screening, 2 prevented and reversed Abeta aggregation at 2-3microM concentration, as measured by Thioflavin T (ThT) fluorescence and ELISA assays. They also prevented the toxic effects of aggregated Abeta on neuroblastoma cells. Their low molecular weight and aqueous solubility makes them promising lead compounds for treating AD.

  10. Structural Analysis and Aggregation Propensity of Pyroglutamate Aβ(3-40 in Aqueous Trifluoroethanol.

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    Christina Dammers

    Full Text Available A hallmark of Alzheimer's disease (AD is the accumulation of extracellular amyloid-β (Aβ plaques in the brains of patients. N-terminally truncated pyroglutamate-modified Aβ (pEAβ has been described as a major compound of Aβ species in senile plaques. pEAβ is more resistant to degradation, shows higher toxicity and has increased aggregation propensity and β-sheet stabilization compared to non-modified Aβ. Here we characterized recombinant pEAβ(3-40 in aqueous trifluoroethanol (TFE solution regarding its aggregation propensity and structural changes in comparison to its non-pyroglutamate-modified variant Aβ(1-40. Secondary structure analysis by circular dichroism spectroscopy suggests that pEAβ(3-40 shows an increased tendency to form β-sheet-rich structures in 20% TFE containing solutions where Aβ(1-40 forms α-helices. Aggregation kinetics of pEAβ(3-40 in the presence of 20% TFE monitored by thioflavin-T (ThT assay showed a typical sigmoidal aggregation in contrast to Aβ(1-40, which lacks ThT positive structures under the same conditions. Transmission electron microscopy confirms that pEAβ(3-40 aggregated to large fibrils and high molecular weight aggregates in spite of the presence of the helix stabilizing co-solvent TFE. High resolution NMR spectroscopy of recombinantly produced and uniformly isotope labeled [U-15N]-pEAβ(3-40 in TFE containing solutions indicates that the pyroglutamate formation affects significantly the N-terminal region, which in turn leads to decreased monomer stability and increased aggregation propensity.

  11. Structural Analysis and Aggregation Propensity of Pyroglutamate Aβ(3-40) in Aqueous Trifluoroethanol

    Science.gov (United States)

    Dammers, Christina; Gremer, Lothar; Reiß, Kerstin; Klein, Antonia N.; Neudecker, Philipp; Hartmann, Rudolf; Sun, Na; Demuth, Hans-Ulrich; Schwarten, Melanie; Willbold, Dieter

    2015-01-01

    A hallmark of Alzheimer’s disease (AD) is the accumulation of extracellular amyloid-β (Aβ) plaques in the brains of patients. N-terminally truncated pyroglutamate-modified Aβ (pEAβ) has been described as a major compound of Aβ species in senile plaques. pEAβ is more resistant to degradation, shows higher toxicity and has increased aggregation propensity and β-sheet stabilization compared to non-modified Aβ. Here we characterized recombinant pEAβ(3–40) in aqueous trifluoroethanol (TFE) solution regarding its aggregation propensity and structural changes in comparison to its non-pyroglutamate-modified variant Aβ(1–40). Secondary structure analysis by circular dichroism spectroscopy suggests that pEAβ(3–40) shows an increased tendency to form β-sheet-rich structures in 20% TFE containing solutions where Aβ(1–40) forms α-helices. Aggregation kinetics of pEAβ(3–40) in the presence of 20% TFE monitored by thioflavin-T (ThT) assay showed a typical sigmoidal aggregation in contrast to Aβ(1–40), which lacks ThT positive structures under the same conditions. Transmission electron microscopy confirms that pEAβ(3–40) aggregated to large fibrils and high molecular weight aggregates in spite of the presence of the helix stabilizing co-solvent TFE. High resolution NMR spectroscopy of recombinantly produced and uniformly isotope labeled [U-15N]-pEAβ(3–40) in TFE containing solutions indicates that the pyroglutamate formation affects significantly the N-terminal region, which in turn leads to decreased monomer stability and increased aggregation propensity. PMID:26600248

  12. Multifunctional liposomes interact with Abeta in human biological fluids: Therapeutic implications for Alzheimer's disease.

    Science.gov (United States)

    Conti, Elisa; Gregori, Maria; Radice, Isabella; Da Re, Fulvio; Grana, Denise; Re, Francesca; Salvati, Elisa; Masserini, Massimo; Ferrarese, Carlo; Zoia, Chiara Paola; Tremolizzo, Lucio

    2017-02-23

    The accumulation of extracellular amyloid beta (Abeta42) both in brain and in cerebral vessels characterizes Alzheimer's disease (AD) pathogenesis. Recently, the possibility to functionalize nanoparticles (NPs) surface with Abeta42 binding molecules, making them suitable tools for reducing Abeta42 burden has been shown effective in models of AD. Aim of this work consisted in proving that NPs might be effective in sequestering Abeta42 in biological fluids, such as CSF and plasma. This demonstration is extremely important considering that these Abeta42 pools are in continuum with the brain parenchyma with drainage of Abeta from interstitial brain tissue to blood vessel and plasma. In this work, liposomes (LIP) were functionalized as previously shown in order to promote high-affinity Abeta binding, i.e., either with, phosphatidic acid (PA), or a modified Apolipoprotein E-derived peptide (mApo), or with a curcumin derivative (TREG); Abeta42 levels were determined by ELISA in CSF and plasma samples. mApo-PA-LIP (25 and 250 μM) mildly albeit significantly sequestered Abeta42 proteins in CSF samples obtained from healthy subjects (p < 0.01). Analogously a significant binding (∼20%) of Abeta42 (p < 0.001) was demonstrated following exposure to all functionalized liposomes in plasma samples obtained from selected AD or Down's syndrome patients expressing high levels of Abeta42. The same results were obtained by quantifying Abeta42 content after removal of liposome-bound Abeta by using gel filtration chromatography or ultracentrifugation on a discontinuous sucrose density gradient. In conclusion, we demonstrate that functionalized liposomes significantly sequester Abeta42 in human biological fluids. These data may be critical for future in vivo administration tests using NPs for promoting sink effect.

  13. Alzheimer's disease amyloid-beta links lens and brain pathology in Down syndrome.

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    Juliet A Moncaster

    Full Text Available Down syndrome (DS, trisomy 21 is the most common chromosomal disorder and the leading genetic cause of intellectual disability in humans. In DS, triplication of chromosome 21 invariably includes the APP gene (21q21 encoding the Alzheimer's disease (AD amyloid precursor protein (APP. Triplication of the APP gene accelerates APP expression leading to cerebral accumulation of APP-derived amyloid-beta peptides (Abeta, early-onset AD neuropathology, and age-dependent cognitive sequelae. The DS phenotype complex also includes distinctive early-onset cerulean cataracts of unknown etiology. Previously, we reported increased Abeta accumulation, co-localizing amyloid pathology, and disease-linked supranuclear cataracts in the ocular lenses of subjects with AD. Here, we investigate the hypothesis that related AD-linked Abeta pathology underlies the distinctive lens phenotype associated with DS. Ophthalmological examinations of DS subjects were correlated with phenotypic, histochemical, and biochemical analyses of lenses obtained from DS, AD, and normal control subjects. Evaluation of DS lenses revealed a characteristic pattern of supranuclear opacification accompanied by accelerated supranuclear Abeta accumulation, co-localizing amyloid pathology, and fiber cell cytoplasmic Abeta aggregates (approximately 5 to 50 nm identical to the lens pathology identified in AD. Peptide sequencing, immunoblot analysis, and ELISA confirmed the identity and increased accumulation of Abeta in DS lenses. Incubation of synthetic Abeta with human lens protein promoted protein aggregation, amyloid formation, and light scattering that recapitulated the molecular pathology and clinical features observed in DS lenses. These results establish the genetic etiology of the distinctive lens phenotype in DS and identify the molecular origin and pathogenic mechanism by which lens pathology is expressed in this common chromosomal disorder. Moreover, these findings confirm increased Abeta

  14. Abeta mediated diminution of MTT reduction--an artefact of single cell culture?

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    Raik Rönicke

    Full Text Available The 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl-tetrazoliumbromide (MTT reduction assay is a frequently used and easily reproducible method to measure beta-amyloid (Abeta toxicity in different types of single cell culture. To our knowledge, the influence of Abeta on MTT reduction has never been tested in more complex tissue. Initially, we reproduced the disturbed MTT reduction in neuron and astroglia primary cell cultures from rats as well as in the BV2 microglia cell line, utilizing four different Abeta species, namely freshly dissolved Abeta (25-35, fibrillar Abeta (1-40, oligomeric Abeta (1-42 and oligomeric Abeta (1-40. In contrast to the findings in single cell cultures, none of these Abeta species altered MTT reduction in rat organotypic hippocampal slice cultures (OHC. Moreover, application of Abeta to acutely isolated hippocampal slices from adult rats and in vivo intracerebroventricular injection of Abeta also did not influence the MTT reduction in the respective tissue. Failure of Abeta penetration into the tissue cannot explain the differences between single cells and the more complex brain tissue. Thus electrophysiological investigations disclosed an impairment of long-term potentiation (LTP in the CA1 region of hippocampal slices from rat by application of oligomeric Abeta (1-40, but not by freshly dissolved Abeta (25-35 or fibrillar Abeta (1-40. In conclusion, the experiments revealed a glaring discrepancy between single cell cultures and complex brain tissue regarding the effect of different Abeta species on MTT reduction. Particularly, the differential effect of oligomeric versus other Abeta forms on LTP was not reflected in the MTT reduction assay. This may indicate that the Abeta oligomer effect on synaptic function reflected by LTP impairment precedes changes in formazane formation rate or that cells embedded in a more natural environment in the tissue are less susceptible to damage by Abeta, raising cautions against the

  15. Enhanced clearance of Abeta in brain by sustaining the plasmin proteolysis cascade.

    Science.gov (United States)

    Jacobsen, J Steven; Comery, Thomas A; Martone, Robert L; Elokdah, Hassan; Crandall, David L; Oganesian, Aram; Aschmies, Suzan; Kirksey, Yolanda; Gonzales, Cathleen; Xu, Jane; Zhou, Hua; Atchison, Kevin; Wagner, Erik; Zaleska, Margaret M; Das, Indranil; Arias, Robert L; Bard, Jonathan; Riddell, David; Gardell, Stephen J; Abou-Gharbia, Magid; Robichaud, Albert; Magolda, Ronald; Vlasuk, George P; Bjornsson, Thorir; Reinhart, Peter H; Pangalos, Menelas N

    2008-06-24

    The amyloid hypothesis states that a variety of neurotoxic beta-amyloid (Abeta) species contribute to the pathogenesis of Alzheimer's disease. Accordingly, a key determinant of disease onset and progression is the appropriate balance between Abeta production and clearance. Enzymes responsible for the degradation of Abeta are not well understood, and, thus far, it has not been possible to enhance Abeta catabolism by pharmacological manipulation. We provide evidence that Abeta catabolism is increased after inhibition of plasminogen activator inhibitor-1 (PAI-1) and may constitute a viable therapeutic approach for lowering brain Abeta levels. PAI-1 inhibits the activity of tissue plasminogen activator (tPA), an enzyme that cleaves plasminogen to generate plasmin, a protease that degrades Abeta oligomers and monomers. Because tPA, plasminogen and PAI-1 are expressed in the brain, we tested the hypothesis that inhibitors of PAI-1 will enhance the proteolytic clearance of brain Abeta. Our data demonstrate that PAI-1 inhibitors augment the activity of tPA and plasmin in hippocampus, significantly lower plasma and brain Abeta levels, restore long-term potentiation deficits in hippocampal slices from transgenic Abeta-producing mice, and reverse cognitive deficits in these mice.

  16. Abeta42-induced neurodegeneration via an age-dependent autophagic-lysosomal injury in Drosophila.

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    Daijun Ling

    Full Text Available The mechanism of widespread neuronal death occurring in Alzheimer's disease (AD remains enigmatic even after extensive investigation during the last two decades. Amyloid beta 42 peptide (Abeta(1-42 is believed to play a causative role in the development of AD. Here we expressed human Abeta(1-42 and amyloid beta 40 (Abeta(1-40 in Drosophila neurons. Abeta(1-42 but not Abeta(1-40 causes an extensive accumulation of autophagic vesicles that become increasingly dysfunctional with age. Abeta(1-42-induced impairment of the degradative function, as well as the structural integrity, of post-lysosomal autophagic vesicles triggers a neurodegenerative cascade that can be enhanced by autophagy activation or partially rescued by autophagy inhibition. Compromise and leakage from post-lysosomal vesicles result in cytosolic acidification, additional damage to membranes and organelles, and erosive destruction of cytoplasm leading to eventual neuron death. Neuronal autophagy initially appears to play a pro-survival role that changes in an age-dependent way to a pro-death role in the context of Abeta(1-42 expression. Our in vivo observations provide a mechanistic understanding for the differential neurotoxicity of Abeta(1-42 and Abeta(1-40, and reveal an Abeta(1-42-induced death execution pathway mediated by an age-dependent autophagic-lysosomal injury.

  17. The degradation of Abeta(25-35) by the serine protease plasmin is inhibited by aluminium.

    Science.gov (United States)

    Korchazhkina, Olga V; Ashcroft, Alison E; Kiss, Tamas; Exley, Christopher

    2002-10-01

    The catabolism of amyloid beta peptides (Abeta) may be important in their accumulation in the brain in both early and late-onset Alzheimer's disease (AD). The serine protease plasmin is one of a suite of proteases implicated in AD. It is a promoter of alpha-cleavage of the amyloid beta precursor protein (AbetaPP) and will degrade Abeta in vitro. Herein we have demonstrated cleavage of the amyloidogenic Abeta(25-35) by plasmin to produce the non-amyloidogenic fragment Abeta(29-35). The activity of plasmin was halved by pre-mixing it with aluminium (Al) prior to its addition to the peptide. An interaction between Al and proteases involved in the catabolism of Abeta might define the putative link between Al and AD.

  18. LRP-mediated clearance of Abeta is inhibited by KPI-containing isoforms of APP.

    Science.gov (United States)

    Moir, Robert D; Tanzi, Rudolph E

    2005-04-01

    The pathogenesis of Alzheimer's disease (AD) involves the abnormal accumulation and deposition of beta-amyloid in cerebral blood vessels and in the brain parenchyma. Critical in modulating beta-amyloid deposition in brain is the flux of Abeta across the blood brain barrier. The low-density lipoprotein receptor-related protein (LRP), is a large endocytic receptor that mediates the efflux of Abeta out of brain and into the periphery. The first step in the LRP-mediated clearance of Abeta involves the formation of a complex between Abeta and the LRP ligands apolipoprotein E (apoE) or alpha(2)-macroglobulin (alpha(2)M). The Abeta/chaperone complexes then bind to LRP via binding sites on apoE or alpha(2)M. The efflux of Abeta/chaperone complexes out of the neuropil and into the periphery may be attenuated by LRP-ligands that compete with apoE or alpha(2)M for LRP binding. LRP is also the cell surface receptor for Kunitz Protease Inhibitor (KPI) containing isoforms of Abeta's parent protein, the amyloid protein precursor (APP). Protein and mRNA levels of KPI-containing APP isoforms (APP-KPI) are elevated in AD brain and are associated with increased Abeta production. In this study we show that soluble non-amyloidogenic APP-KPI can also inhibit the uptake of Abeta/alpha(2)M in a cell culture model of LRP mediated Abeta clearance. Clearance of Abeta/apoE complexes was not inhibited by APP-KPI. Our findings are consistent with studies showing that apoE and alpha(2)M have discrete binding sites on LRP. Most significantly, our data suggests that the elevated levels of APP-KPI in AD brain may attenuate the clearance of Abeta, the proteins own amyloidogenic catabolic product.

  19. AbetaPP/APLP2 family of Kunitz serine proteinase inhibitors regulate cerebral thrombosis.

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    Xu, Feng; Previti, Mary Lou; Nieman, Marvin T; Davis, Judianne; Schmaier, Alvin H; Van Nostrand, William E

    2009-04-29

    The amyloid beta-protein precursor (AbetaPP) is best recognized as the precursor to the Abeta peptide that accumulates in the brains of patients with Alzheimer's disease, but less is known about its physiological functions. Isoforms of AbetaPP that contain a Kunitz-type serine proteinase inhibitor (KPI) domain are expressed in brain and, outside the CNS, in circulating blood platelets. Recently, we showed that KPI-containing forms of AbetaPP regulates cerebral thrombosis in vivo (Xu et al., 2005, 2007). Amyloid precursor like protein-2 (APLP2), a closely related homolog to AbetaPP, also possesses a highly conserved KPI domain. Virtually nothing is known of its function. Here, we show that APLP2 also regulates cerebral thrombosis risk. Recombinant purified KPI domains of AbetaPP and APLP2 both inhibit the plasma clotting in vitro. In a carotid artery thrombosis model, both AbetaPP(-/-) and APLP2(-/-) mice exhibit similar significantly shorter times to vessel occlusion compared with wild-type mice indicating a prothrombotic phenotype. Similarly, in an experimental model of intracerebral hemorrhage, both AbetaPP(-/-) and APLP2(-/-) mice produce significantly smaller hematomas with reduced brain hemoglobin content compared with wild-type mice. Together, these results indicate that AbetaPP and APLP2 share overlapping anticoagulant functions with regard to regulating thrombosis after cerebral vascular injury.

  20. Identification of N-terminally truncated pyroglutamate amyloid-β in cholesterol-enriched diet-fed rabbit and AD brain.

    Science.gov (United States)

    Perez-Garmendia, Roxanna; Hernandez-Zimbron, Luis Fernando; Morales, Miguel Angel; Luna-Muñoz, José; Mena, Raul; Nava-Catorce, Miriam; Acero, Gonzalo; Vasilevko, Vitaly; Viramontes-Pintos, Amparo; Cribbs, David H; Gevorkian, Goar

    2014-01-01

    The main amyloid-β peptide (Aβ) variants detected in the human brain are Aβ1-40 and Aβ1-42; however, a significant proportion of Aβ in Alzheimer's disease (AD) brain also consists of N-terminal truncated/modified species. AβN3(pE), Aβ peptide bearing amino-terminal pyroglutamate at position 3, has been demonstrated to be a major N-truncated/modified constituent of intracellular, extracellular, and vascular Aβ deposits in AD and Down syndrome brain tissue. It has been previously demonstrated that rabbits fed a diet enriched in cholesterol and given water containing trace copper levels developed AD-like pathology including intraneuronal and extracellular Aβ accumulation, tau hyperphosphorylation, vascular inflammation, astrocytosis, microgliosis, reduced levels of acetylcholine, as well as learning deficits and thus, may be used as a non-transgenic animal model of sporadic AD. In the present study, we have demonstrated for the first time the presence of AβN3(pE) in blood vessels in cholesterol-enriched diet-fed rabbit brain. In addition, we detected AβN3(pE) immunoreactivity in all postmortem AD brain samples studied. We believe that our results are potentially important for evaluation of novel therapeutic molecules/strategies targeting Aβ peptides in a suitable non-transgenic animal model.

  1. An anti-pyroglutamate-3 Aβ vaccine reduces plaques and improves cognition in APPswe/PS1ΔE9 mice

    Science.gov (United States)

    Frost, Jeffrey L.; Liu, Bin; Rahfeld, Jens-Ulrich; Kleinschmidt, Martin; O'Nuallain, Brian; Le, Kevin X.; Lues, Inge; Caldarone, Barbara J.; Schilling, Stephan; Demuth, Hans-Ulrich; Lemere, Cynthia A.

    2015-01-01

    Pyroglutamate-3 amyloid-beta (pGlu-3 Aβ) is an N-terminally truncated Aβ isoform likely playing a decisive role in Alzheimer's disease (AD) pathogenesis. Here, we describe a prophylactic passive immunization study in APPswe/PS1ΔE9 mice using a novel pGlu-3 Aβ IgG1 monoclonal antibody (mAb), 07/1 (150 and 500μg i.p. weekly), and compare its efficacy with a general Aβ IgG1 mAb, 3A1 (200μg i.p. weekly) as a positive control. After 28 weeks of treatment, plaque burden was reduced and cognitive performance of 07/1-immunized Tg mice, especially at the higher dose, was normalized to wild-type (Wt) levels in two hippocampal-dependent tests and partially spared compared to PBS-treated Tg mice. Mice that received 3A1 had reduced plaque burden but showed no cognitive benefit. In contrast to 3A1, treatment with 07/1 did not increase the concentration of Aβ in plasma, suggesting different modes of Aβ plaque clearance. In conclusion, early selective targeting of pGlu-3 Aβ by immunotherapy may be effective in lowering cerebral Aβ plaque burden and preventing cognitive decline in the clinical setting. Targeting this pathologically-modified form of Aβ thereby is unlikely to interfere with potential physiologic function(s) of Aβ that have been proposed. PMID:26453001

  2. Astrocytes containing amyloid beta-protein (Abeta)-positive granules are associated with Abeta40-positive diffuse plaques in the aged human brain.

    OpenAIRE

    Funato, H.; Yoshimura, M.; T. Yamazaki; Saido, T C; Ito, Y; Yokofujita, J.; Okeda, R.; Ihara, Y.

    1998-01-01

    Amyloid beta-protein (Abeta) is the major component of senile plaques that emerge in the cortex during aging and appear most abundantly in Alzheimer's disease. In the course of our immunocytochemical study on a large number of autopsy cases, we noticed, in many aged nondemented cases, the presence of unique diffuse plaques in the cortex distinct from ordinary diffuse plaques by immunocytochemistry. The former were amorphous, very faintly Abeta-immunoreactive plaques resembling diffuse plaques...

  3. Design, synthesis, and biophysical properties of a helical Abeta1-42 analog: Inhibition of fibrillogenesis and cytotoxicity.

    Science.gov (United States)

    Matsuzaki, Katsumi; Okada, Takuma; Tsukuda, Miho; Ikeda, Keisuke; Sohma, Youhei; Chiyomori, Yousuke; Taniguchi, Atsuhiko; Nakamura, Setsuko; Ito, Nui; Hayashi, Yoshio; Kiso, Yoshiaki

    2008-07-11

    The aggregation of amyloid beta-peptide (Abeta) into beta-sheet-rich aggregates is a crucial step in the etiology of Alzheimer's disease. Helical forms of Abeta have been suggested to be intermediates in the aggregation process of the peptide in aqueous phase, micelles and membranes. A stable helical Abeta analog would be useful to investigate the role of helical intermediates in fibrillization by Abeta. Here we designed a helical analog by simply cross-linking the Cys residues of A30C, G37C-Abeta1-42 with 1,6-bismaleimidohexane. The analog assumed a weak alpha-helical conformation in model membranes mimicking lipid raft microdomains of neuronal membranes under conditions in which the wild-type Abeta1-42 formed a beta-sheet, indicating the cross-linking locally induced a helical conformation. Furthermore, addition of equimolar helical Abeta analog significantly reduced the amyloid formation and cytotoxicity by Abeta1-42. Thus, our helical Abeta1-42 is not only a model peptide to investigate the role of helical intermediates in fibrillization by Abeta, but also an inhibitor of Abeta-induced cytotoxicity.

  4. Defective lysosomal proteolysis and axonal transport are early pathogenic events that worsen with age leading to increased APP metabolism and synaptic Abeta in transgenic APP/PS1 hippocampus

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    Torres Manuel

    2012-11-01

    Full Text Available Abstract Background Axonal pathology might constitute one of the earliest manifestations of Alzheimer disease. Axonal dystrophies were observed in Alzheimer’s patients and transgenic models at early ages. These axonal dystrophies could reflect the disruption of axonal transport and the accumulation of multiple vesicles at local points. It has been also proposed that dystrophies might interfere with normal intracellular proteolysis. In this work, we have investigated the progression of the hippocampal pathology and the possible implication in Abeta production in young (6 months and aged (18 months PS1(M146L/APP(751sl transgenic mice. Results Our data demonstrated the existence of a progressive, age-dependent, formation of axonal dystrophies, mainly located in contact with congophilic Abeta deposition, which exhibited tau and neurofilament hyperphosphorylation. This progressive pathology was paralleled with decreased expression of the motor proteins kinesin and dynein. Furthermore, we also observed an early decrease in the activity of cathepsins B and D, progressing to a deep inhibition of these lysosomal proteases at late ages. This lysosomal impairment could be responsible for the accumulation of LC3-II and ubiquitinated proteins within axonal dystrophies. We have also investigated the repercussion of these deficiencies on the APP metabolism. Our data demonstrated the existence of an increase in the amyloidogenic pathway, which was reflected by the accumulation of hAPPfl, C99 fragment, intracellular Abeta in parallel with an increase in BACE and gamma-secretase activities. In vitro experiments, using APPswe transfected N2a cells, demonstrated that any imbalance on the proteolytic systems reproduced the in vivo alterations in APP metabolism. Finally, our data also demonstrated that Abeta peptides were preferentially accumulated in isolated synaptosomes. Conclusion A progressive age-dependent cytoskeletal pathology along with a reduction of

  5. Mitochondrial Ca2+ overload underlies Abeta oligomers neurotoxicity providing an unexpected mechanism of neuroprotection by NSAIDs.

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    Sara Sanz-Blasco

    Full Text Available Dysregulation of intracellular Ca(2+ homeostasis may underlie amyloid beta peptide (Abeta toxicity in Alzheimer's Disease (AD but the mechanism is unknown. In search for this mechanism we found that Abeta(1-42 oligomers, the assembly state correlating best with cognitive decline in AD, but not Abeta fibrils, induce a massive entry of Ca(2+ in neurons and promote mitochondrial Ca(2+ overload as shown by bioluminescence imaging of targeted aequorin in individual neurons. Abeta oligomers induce also mitochondrial permeability transition, cytochrome c release, apoptosis and cell death. Mitochondrial depolarization prevents mitochondrial Ca(2+ overload, cytochrome c release and cell death. In addition, we found that a series of non-steroidal anti-inflammatory drugs (NSAIDs including salicylate, sulindac sulfide, indomethacin, ibuprofen and R-flurbiprofen depolarize mitochondria and inhibit mitochondrial Ca(2+ overload, cytochrome c release and cell death induced by Abeta oligomers. Our results indicate that i mitochondrial Ca(2+ overload underlies the neurotoxicity induced by Abeta oligomers and ii inhibition of mitochondrial Ca(2+ overload provides a novel mechanism of neuroprotection by NSAIDs against Abeta oligomers and AD.

  6. CCL2 accelerates microglia-mediated Abeta oligomer formation and progression of neurocognitive dysfunction.

    Directory of Open Access Journals (Sweden)

    Tomomi Kiyota

    Full Text Available BACKGROUND: The linkages between neuroinflammation and Alzheimer's disease (AD pathogenesis are well established. What is not, however, is how specific immune pathways and proteins affect the disease. To this end, we previously demonstrated that transgenic over-expression of CCL2 enhanced microgliosis and induced diffuse amyloid plaque deposition in Tg2576 mice. This rodent model of AD expresses a Swedish beta-amyloid (Abeta precursor protein mutant. METHODOLOGY/PRINCIPAL FINDINGS: We now report that CCL2 transgene expression accelerates deficits in spatial and working memory and hippocampal synaptic transmission in beta-amyloid precursor protein (APP mice as early as 2-3 months of age. This is followed by increased numbers of microglia that are seen surrounding Abeta oligomers. CCL2 does not suppress Abeta degradation. Rather, CCL2 and tumor necrosis factor-alpha directly facilitated Abeta uptake, intracellular Abeta oligomerization, and protein secretion. CONCLUSIONS/SIGNIFICANCE: We posit that CCL2 facilitates Abeta oligomer formation in microglia and propose that such events accelerate memory dysfunction by affecting Abeta seeding in the brain.

  7. Hydrogen sulfide prevents Abeta-induced neuronal apoptosis by attenuating mitochondrial translocation of PTEN.

    Science.gov (United States)

    Cui, Weigang; Zhang, Yinghua; Yang, Chenxi; Sun, Yiyuan; Zhang, Min; Wang, Songtao

    2016-06-14

    Neuronal cell apoptosis is an important pathological change in Alzheimer's disease (AD). Hydrogen sulfide (H(2)S) is known to be a novel gaseous signaling molecule and a cytoprotectant in many diseases including AD. However, the molecular mechanism of the antiapoptosis activity of H(2)S in AD is not yet fully understood. The aim of the present study is to evaluate the inhibitory effects of H(2)S on Abeta (Aβ)-induced apoptosis and the molecular mechanisms underlying primary neuron cells. Our results showed that sodium hydrosulfide (NaHS), a donor of H(2)S, significantly ameliorated Aβ-induced cell apoptosis. NaHS also reversed the Aβ-induced translocation of the phosphatase and tensin homologs deleted on chromosome 10 (PTEN) from the cytosol to the mitochondria. Furthermore, H(2)S increased the level of p-AKT/AKT significantly. Interestingly, the antiapoptosis effects of H(2)S were blocked down by specific PI3K/AKT inhibitor wortmannin. In conclusion, these data indicate that H(2)S inhibits Aβ-induced neuronal apoptosis by attenuating mitochondrial translocation of PTEN and that activation of PI3K/AKT signaling pathway plays a critical role in H(2)S-mediated neuronal protection. Our findings provide a novel route into the molecular mechanisms of neuronal apoptosis in AD.

  8. Alzheimer's abeta(1-40) amyloid fibrils feature size-dependent mechanical properties.

    Science.gov (United States)

    Xu, Zhiping; Paparcone, Raffaella; Buehler, Markus J

    2010-05-19

    Amyloid fibrils are highly ordered protein aggregates that are associated with several pathological processes, including prion propagation and Alzheimer's disease. A key issue in amyloid science is the need to understand the mechanical properties of amyloid fibrils and fibers to quantify biomechanical interactions with surrounding tissues, and to identify mechanobiological mechanisms associated with changes of material properties as amyloid fibrils grow from nanoscale to microscale structures. Here we report a series of computational studies in which atomistic simulation, elastic network modeling, and finite element simulation are utilized to elucidate the mechanical properties of Alzheimer's Abeta(1-40) amyloid fibrils as a function of the length of the protein filament for both twofold and threefold symmetric amyloid fibrils. We calculate the elastic constants associated with torsional, bending, and tensile deformation as a function of the size of the amyloid fibril, covering fibril lengths ranging from nanometers to micrometers. The resulting Young's moduli are found to be consistent with available experimental measurements obtained from long amyloid fibrils, and predicted to be in the range of 20-31 GPa. Our results show that Abeta(1-40) amyloid fibrils feature a remarkable structural stability and mechanical rigidity for fibrils longer than approximately 100 nm. However, local instabilities that emerge at the ends of short fibrils (on the order of tens of nanometers) reduce their stability and contribute to their disassociation under extreme mechanical or chemical conditions, suggesting that longer amyloid fibrils are more stable. Moreover, we find that amyloids with lengths shorter than the periodicity of their helical pitch, typically between 90 and 130 nm, feature significant size effects of their bending stiffness due the anisotropy in the fibril's cross section. At even smaller lengths (50 nm), shear effects dominate lateral deformation of amyloid fibrils

  9. Research progress on pyroglutamic acid detection methods in monosodium glutamate%味精中焦谷氨酸检测方法的研究进展

    Institute of Scientific and Technical Information of China (English)

    潘馨; 冯旭东; 刘明明

    2013-01-01

      焦谷氨酸是一种环状氨基酸,是许多氨基酸和蛋白质生成过程中的中间产物,广泛存在于动植物界。在味精生产过程中,谷氨酸受热会脱水环化成焦谷氨酸,影响谷氨酸的提取收率,所以为了对焦谷氨酸进行控制,在味精生产过程中对其检测是非常必要的。本文综述了焦谷氨酸的结构及性质,并对味精生产过程可能产生焦谷氨酸的环节做了阐述,重点介绍了焦谷氨酸的检测方法:化学法和高压液相色谱法,并对高压液相色谱法进行了展望。%Pyroglutamic acid is a cyclic amino acid. It is an intermediate during amino acid and protein biosyn-thesis. It is widely distributed in plants and animals. When heated, glutamate is highly unstable and prone to sponta-neous cyclization into pyroglutamic acid during the monosodium glutamate production, which could reduce the yielding amount of glutamic acid. So in order to control the content of pyroglutamic, it was detected during the mo-nosodium glutamate production. This paper provides a brief overview of the structure and chemical properties of py-roglutamic acid and the possible reasons of pyroglutamic acid generation in monosodium glutamate production proc-ess. Focus on chemical method and high pressure liquid chromatography, the development of detection of pyroglu-tamic acid is also viewed.

  10. Identification of distinct physiochemical properties of toxic prefibrillar species formed by A{beta} peptide variants

    Energy Technology Data Exchange (ETDEWEB)

    Goeransson, Anna-Lena, E-mail: anngo@ifm.liu.se [Division of Molecular Biotechnology, Department of Physics, Chemistry and Biology, Linkoeping University (Sweden); Nilsson, K. Peter R., E-mail: petni@ifm.liu.se [Division of Organic Chemistry, Department of Physics, Chemistry and Biology, Linkoeping University (Sweden); Kagedal, Katarina, E-mail: katarina.kagedal@liu.se [Department of Clinical and Experimental Medicine, Linkoeping University (Sweden); Brorsson, Ann-Christin, E-mail: anki@ifm.liu.se [Division of Molecular Biotechnology, Department of Physics, Chemistry and Biology, Linkoeping University (Sweden)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer Identification of toxic prefibrillar A{beta} species. Black-Right-Pointing-Pointer Fluorescence measurements using a combined set of fluorophores. Black-Right-Pointing-Pointer Morphology studies using transmission electron microscopy. -- Abstract: The formation of amyloid-{beta} peptide (A{beta}) aggregates at an early stage during the self-assembly process is an important factor in the development of Alzheimer's disease. The toxic effect is believed to be exerted by prefibrillar species of A{beta}. It is therefore important to identify which prefibrillar species are toxic and characterize their distinct properties. In the present study, we investigated the in vitro aggregation behavior of A{beta}-derived peptides possessing different levels of neurotoxic activity, using fluorescence spectroscopy in combination with transmission electron microscopy. The toxicity of various A{beta} aggregates was assessed by using cultures of human neuroblastoma cells. Through combined use of the fluorescence probe 8-anilino-1-napthalenesulfonate (ANS) and the novel luminescent probe pentamer formyl thiophene acetic acid (p-FTAA), we were able to identify those A{beta} peptide-derived prefibrillar species which exhibited cellular toxicity. In particular, species, which formed early during the aggregation process and showed strong p-FTAA and ANS fluorescence, were the species that possessed toxic activities. Moreover, by manipulating the aggregation conditions, it was possible to change the capacity of the A{beta} peptide to form nontoxic versus toxic species.

  11. Physiological mouse brain Abeta levels are not related to the phosphorylation state of threonine-668 of Alzheimer's APP.

    Directory of Open Access Journals (Sweden)

    Yoshitake Sano

    Full Text Available BACKGROUND: Amyloid-beta peptide species ending at positions 40 and 42 (Abeta40, Abeta42 are generated by the proteolytic processing of the Alzheimer's amyloid precursor protein (APP. Abeta peptides accumulate in the brain early in the course of Alzheimer's disease (AD, especially Abeta42. The cytoplasmic domain of APP regulates intracellular trafficking and metabolism of APP and its carboxyl-terminal fragments (CTFalpha, CTFbeta. The role of protein phosphorylation in general, and that of the phosphorylation state of APP at threonine-668 (Thr668 in particular, has been investigated in detail by several laboratories (including our own. Some investigators have recently proposed that the phosphorylation state of Thr668 plays a pivotal role in governing brain Abeta levels, prompting the current study. METHODOLOGY: In order to evaluate whether the phosphorylation state of Thr668 controlled brain Abeta levels, we studied the levels and subcellular distributions of holoAPP, sAPPalpha, sAPPbeta, CTFalpha, CTFbeta, Abeta40 and Abeta42 in brains from "knock-in" mice in which a non-phosphorylatable alanyl residue had been substituted at position 668, replacing the threonyl residue present in the wild-type protein. CONCLUSIONS: The levels and subcellular distributions of holoAPP, sAPPalpha, sAPPbeta, CTFalpha, CTFbeta, Abeta40 and Abeta42 in the brains of Thr668Ala mutant mice were identical to those observed in wild-type mice. These results indicate that, despite speculation to the contrary, the phosphorylation state of APP at Thr668 does not play an obvious role in governing the physiological levels of brain Abeta40 or Abeta42 in vivo.

  12. Incorporation of N-amidino-pyroglutamic acid into peptides using intramolecular cyclization of alpha-guanidinoglutaric acid.

    Science.gov (United States)

    Burov, Sergey; Moskalenko, Yulia; Dorosh, Marina; Shkarubskaya, Zoya; Panarin, Evgeny

    2009-11-01

    N-terminal modification of peptides by unnatural amino acids significantly affects their enzymatic stability, conformational properties and biological activity. Application of N-amidino-amino acids, positively charged under physiological conditions, can change peptide conformation and its affinity to the corresponding receptor. In this article, we describe synthesis of short peptides, containing a new building block-N-amidino-pyroglutamic acid. Although direct guanidinylation of pyroglutamic acid and oxidation of N-amidino-proline using RuO(4) did not produce positive results, N-amidino-Glp-Phe-OH was synthesized on Wang polymer by cyclization of alpha-guanidinoglutaric acid residue. In the course of synthesis, it was found that literature procedure of selective Boc deprotection using TMSOTf/TEA reagent is accompanied by concomitant side reaction of triethylamine alkylation by polymer linker fragment. It should be mentioned that independently from cyclization time and coupling agent (DIC or HCTU), the lactam formation was incomplete. Separation of the cyclic product from the linear precursor was achieved by HPLC in ammonium formate buffer at pH 6. HPLC analysis showed N-amidino-Glp-Phe-OH stability at acidic and physiological pH and fast ring opening in water solution at pH 9. The suggested method of N-amidino-Glp residue formation can be applied in the case of short peptide chains, whereas synthesis of longer ones will require fragment condensation approach.

  13. Distribution of neprilysin and deposit patterns of Abeta subtypes in the brains of aged squirrel monkeys (Saimiri sciureus).

    Science.gov (United States)

    Chambers, James K; Kuribayashi, Hiroyuki; Ikeda, Shu-Ichi; Une, Yumi

    2010-06-01

    Beta-amyloid (Abeta) is deposited in the parenchyma and blood vessel walls of the senescent brain, and forms lesions termed senile plaques (SPs) and cerebral amyloid angiopathy (CAA). Since in Alzheimer's disease (AD) excessive Abeta is linked to cognitive deterioration, the mechanisms of degradation and clearance of Abeta are now being researched for use in AD therapy. We conducted an immunohistochemical study of the patterns of deposition of two Abeta subtypes (Abeta40 and Abeta42) and the distribution of the Abeta degrading enzyme neprilysin (NEP) in the brains of aged squirrel monkeys, a species known to develop CAA and SPs. Abeta deposits were observed mainly in the cerebral cortex of five older monkeys, and were absent in monkeys under 12 years of age. NEP expression was observed in the caudate nucleus, putamen, globus pallidus, substantia nigra and the molecular layer of the dentate gyrus, and thus exhibited a distribution complementary to those of CAA and SPs in cerebral cortex and hippocampus. It is known that CAA is more prominent than SPs in squirrel monkey brains. However, we confirmed that Abeta40 is deposited predominantly in the arterioles of the meninges and penetrates vertically into the cerebral cortex, whereas Abeta42 is deposited predominantly in the capillaries of the cerebral cortex. These distinct patterns of deposition of Abeta subtypes are likely related to the difference in biochemical character of these two subtypes. We have demonstrated for the first time the distribution of NEP in the brain of a non-human primate, the squirrel monkey, which appears useful for research on AD treatment.

  14. The structure of Abeta42 C-terminal fragments probed by a combined experimental and theoretical study.

    Science.gov (United States)

    Wu, Chun; Murray, Megan M; Bernstein, Summer L; Condron, Margaret M; Bitan, Gal; Shea, Joan-Emma; Bowers, Michael T

    2009-03-27

    The C-terminus of amyloid beta-protein (Abeta) 42 plays an important role in this protein's oligomerization and may therefore be a good therapeutic target for the treatment of Alzheimer's disease. Certain C-terminal fragments (CTFs) of Abeta42 have been shown to disrupt oligomerization and to strongly inhibit Abeta42-induced neurotoxicity. Here we study the structures of selected CTFs [Abeta(x-42); x=29-31, 39] using replica exchange molecular dynamics simulations and ion mobility mass spectrometry. Our simulations in explicit solvent reveal that the CTFs adopt a metastable beta-structure: beta-hairpin for Abeta(x-42) (x=29-31) and extended beta-strand for Abeta(39-42). The beta-hairpin of Abeta(30-42) is converted into a turn-coil conformation when the last two hydrophobic residues are removed, suggesting that I41 and A42 are critical in stabilizing the beta-hairpin in Abeta42-derived CTFs. The importance of solvent in determining the structure of the CTFs is further highlighted in ion mobility mass spectrometry experiments and solvent-free replica exchange molecular dynamics simulations. A comparison between structures with solvent and structures without solvent reveals that hydrophobic interactions are critical for the formation of beta-hairpin. The possible role played by the CTFs in disrupting oligomerization is discussed.

  15. A neural cell adhesion molecule-derived peptide reduces neuropathological signs and cognitive impairment induced by Abeta25-35

    DEFF Research Database (Denmark)

    Klementiev, B; Novikova, T; Novitskaya, V;

    2007-01-01

    By means of i.c.v. administration of preaggregated oligomeric beta-amyloid (Abeta)25-35 peptide it was possible in rats to generate neuropathological signs related to those of early stages of Alzheimer's disease (AD). Abeta25-35-administration induced the deposition of endogenously produced amyloid...

  16. A[Beta] Deposits in Older Non-Demented Individuals with Cognitive Decline Are Indicative of Preclinical Alzheimer's Disease

    Science.gov (United States)

    Villemagne, V. L.; Pike, K. E.; Darby, D.; Maruff, P.; Savage, G.; Ng, S.; Ackermann, U.; Cowie, T. F.; Currie, J.; Chan, S. G.; Jones, G.; Tochon-Danguy, H.; O'Keefe, G.; Masters, C. L.; Rowe, C. C.

    2008-01-01

    Approximately 30% of healthy persons aged over 75 years show A[beta] deposition at autopsy. It is postulated that this represents preclinical Alzheimer's disease (AD). We evaluated the relationship between A[beta] burden as assessed by PiB PET and cognitive decline in a well-characterized, non-demented, elderly cohort. PiB PET studies and…

  17. Do amyloid beta-associated factors co-deposit with Abeta in mouse models for Alzheimer's disease?

    NARCIS (Netherlands)

    Timmer, N.M.; Kuiperij, H.B.; Waal, R.M.W. de; Verbeek, M.M.

    2010-01-01

    Senile plaques and cerebral amyloid angiopathy in Alzheimer's disease (AD) patients not only consist of the amyloid-beta protein (Abeta), but also contain many different Abeta-associated factors, such as heparan sulfate proteoglycans, apolipoproteins, and complement factors. These factors may all

  18. RNA aptamers generated against oligomeric Abeta40 recognize common amyloid aptatopes with low specificity but high sensitivity.

    Directory of Open Access Journals (Sweden)

    Farid Rahimi

    Full Text Available Aptamers are useful molecular recognition tools in research, diagnostics, and therapy. Despite promising results in other fields, aptamer use has remained scarce in amyloid research, including Alzheimer's disease (AD. AD is a progressive neurodegenerative disease believed to be caused by neurotoxic amyloid beta-protein (Abeta oligomers. Abeta oligomers therefore are an attractive target for development of diagnostic and therapeutic reagents. We used covalently-stabilized oligomers of the 40-residue form of Abeta (Abeta40 for aptamer selection. Despite gradually increasing the stringency of selection conditions, the selected aptamers did not recognize Abeta40 oligomers but reacted with fibrils of Abeta40, Abeta42, and several other amyloidogenic proteins. Aptamer reactivity with amyloid fibrils showed some degree of protein-sequence dependency. Significant fibril binding also was found for the naïve library and could not be eliminated by counter-selection using Abeta40 fibrils, suggesting that aptamer binding to amyloid fibrils was RNA-sequence-independent. Aptamer binding depended on fibrillogenesis and showed a lag phase. Interestingly, aptamers detected fibril formation with > or =15-fold higher sensitivity than thioflavin T (ThT, revealing substantial beta-sheet and fibril formation undetected by ThT. The data suggest that under physiologic conditions, aptamers for oligomeric forms of amyloidogenic proteins cannot be selected due to high, non-specific affinity of oligonucleotides for amyloid fibrils. Nevertheless, the high sensitivity, whereby aptamers detect beta-sheet formation, suggests that they can serve as superior amyloid recognition tools.

  19. Limited expression of heparan sulphate proteoglycans associated with Abeta deposits in the APPswe/PS1dE9 mouse model for Alzheimer's disease.

    NARCIS (Netherlands)

    Timmer, N.M.; Herbert, M.K.; Kleinovink, J.W.; Kiliaan, A.J.; Waal, R.M.W. de; Verbeek, M.M.

    2010-01-01

    AIMS: Alzheimer's disease (AD) is characterized by deposition of the amyloid beta (Abeta) peptide in brain parenchyma and vasculature. Several proteins co-deposit with Abeta, including heparan sulphate proteoglycans (HSPG). HSPG have been suggested to contribute to Abeta aggregation and deposition,

  20. [5-0xoproline (pyroglutamic acid) acidosis and acetaminophen- a differential diagnosis in high anion gap metabolic acidosis].

    Science.gov (United States)

    Weiler, Stefan; Bellmann, Romuald; Kullak-Ublick, Gerd A

    2015-12-01

    Rare cases of high anion gap metabolic acidosis during long-term paracetamol administration in therapeutic doses with causative 5-oxoproline (pyroglutamic acid} accumulation have been reported. Other concomitant risk factors such as malnutrition, alcohol abuse, renal or hepatic dysfunction, comedication with flue/oxacillin, vigabatrin, netilmicin or sepsis have been described. The etiology seems to be a drug-induced reversible inhibition of glutathione synthetase or 5-oxoprolinase leading to elevated serum and urine levels of 5-oxoproline. Other more frequent differential diagnoses, such as intoxications, ketoacidosis or lactic acidosis should be excluded. Causative substances should be stopped. 5-oxoproline concentrations in urine can be quantified to establish the diagnosis. Adverse drug reactions, which are not listed or insufficiently described in the respective Swiss product information, should be reported to the regional pharmacovigilance centres for early signal detection. 5-0 xoproline acidosis will be integrated as a potential adverse drug reaction in the Swiss product information for paracetamol.

  1. Native pyroglutamation of huwentoxin-IV: a post-translational modification that increases the trapping ability to the sodium channel.

    Directory of Open Access Journals (Sweden)

    Mingqiang Rong

    Full Text Available Huwentoxin-IV (HWTX-IV, a tetrodotoxin-sensitive (TTX-s sodium channel antagonist, is found in the venom of the Chinese spider Ornithoctonus huwena. A naturally modified HWTX-IV (mHWTX-IV, having a molecular mass 18 Da lower than HWTX-IV, has also been isolated from the venom of the same spider. By a combination of enzymatic fragmentation and MS/MS de novo sequencing, mHWTX-IV has been shown to have the same amino acid sequence as that of HWTX-IV, except that the N-terminal glutamic acid replaced by pyroglutamic acid. mHWTX-IV inhibited tetrodotoxin-sensitive voltage-gated sodium channels of dorsal root ganglion neurons with an IC50 nearly equal to native HWTX-IV. mHWTX-IV showed the same activation and inactivation kinetics seen for native HWTX-IV. In contrast with HWTX-IV, which dissociates at moderate voltage depolarization voltages (+50 mV, 180000 ms, mHWTX-IV inhibition of TTX-sensitive sodium channels is not reversed by strong depolarization voltages (+200 mV, 500 ms. Recovery of Nav1.7current was voltage-dependent and was induced by extreme depolarization in the presence of HWTX-IV, but no obvious current was elicited after application of mHWTX-IV. Our data indicate that the N-terminal modification of HWTX-IV gives the peptide toxin a greater ability to trap the voltage sensor in the sodium channel. Loss of a negative charge, caused by cyclization at the N-terminus, is a possible reason why the modified toxin binds much stronger. To our knowledge, this is the first report of a pyroglutamic acid residue in a spider toxin; this modification seems to increase the trapping ability of the voltage sensor in the sodium channel.

  2. HH domain of Alzheimer's disease Abeta provides structural basis for neuronal binding in PC12 and mouse cortical/hippocampal neurons.

    Directory of Open Access Journals (Sweden)

    Joseph F Poduslo

    Full Text Available A key question in understanding AD is whether extracellular Abeta deposition of parenchymal amyloid plaques or intraneuronal Abeta accumulation initiates the AD process. Amyloid precursor protein (APP is endocytosed from the cell surface into endosomes where it is cleaved to produce soluble Abeta which is then released into the brain interstitial fluid. Intraneuronal Abeta accumulation is hypothesized to predominate from the neuronal uptake of this soluble extracellular Abeta rather than from ER/Golgi processing of APP. We demonstrate that substitution of the two adjacent histidine residues of Abeta40 results in a significant decrease in its binding with PC12 cells and mouse cortical/hippocampal neurons. These substitutions also result in a dramatic enhancement of both thioflavin-T positive fibril formation and binding to preformed Abeta fibrils while maintaining its plaque-binding ability in AD transgenic mice. Hence, alteration of the histidine domain of Abeta prevented neuronal binding and drove Abeta to enhanced fibril formation and subsequent amyloid plaque deposition--a potential mechanism for removing toxic species of Abeta. Substitution or even masking of these Abeta histidine residues might provide a new therapeutic direction for minimizing neuronal uptake and subsequent neuronal degeneration and maximizing targeting to amyloid plaques.

  3. Binding of an oxindole alkaloid from Uncaria tomentosa to amyloid protein (Abeta1-40).

    Science.gov (United States)

    Frackowiak, Teresa; Baczek, Tomasz; Roman, Kaliszana; Zbikowska, Beata; Gleńsk, Michał; Fecka, Izabela; Cisowski, Wojciech

    2006-01-01

    The primary aim of this work was to determine the interactions of an oxindole alkaloid (mitraphylline) isolated from Uncaria tomentosa with beta-amyloid 1-40 (Abeta1-40 protein) applying the capillary electrophoresis (CE) method. Specifically the Hummel-Dreyer method and Scatchard analysis were performed to study the binding of oxindole alkaloids with Abeta1-40 protein. Prior to these studies extraction of the alkaloid of interest was carried out. Identification of the isolated alkaloid was performed by the use of thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) combined with electrospray ionization mass spectrometry (ESI-MS). The proposed approach was proved to be an efficient and accurate method for specific compound isolation and identification purposes. Moreover, analytical information from the CE approach can be considered as the valuable tool for binding constant determination. The binding constant of mitraphylline with Abeta1-40 protein determined by the Hummel-Dreyer method and Scatchard analysis equals K = 9.95 x 10(5) M(-1). The results obtained showed the significant binding of the tested compound with Abeta1-40 protein. These results are discussed and interpreted in the view of developing a strategy for identification of novel compounds of great importance in Alzheimer disease therapy.

  4. Ginkgo biloba extract ameliorates oxidative phosphorylation performance and rescues abeta-induced failure.

    Science.gov (United States)

    Rhein, Virginie; Giese, Maria; Baysang, Ginette; Meier, Fides; Rao, Stefania; Schulz, Kathrin L; Hamburger, Matthias; Eckert, Anne

    2010-08-24

    Energy deficiency and mitochondrial failure have been recognized as a prominent, early event in Alzheimer's disease (AD). Recently, we demonstrated that chronic exposure to amyloid-beta (Abeta) in human neuroblastoma cells over-expressing human wild-type amyloid precursor protein (APP) resulted in (i) activity changes of complexes III and IV of the oxidative phosphorylation system (OXPHOS) and in (ii) a drop of ATP levels which may finally instigate loss of synapses and neuronal cell death in AD. Therefore, the aim of the present study was to investigate whether standardized Ginkgo biloba extract LI 1370 (GBE) is able to rescue Abeta-induced defects in energy metabolism. We used a high-resolution respiratory protocol to evaluate OXPHOS respiratory capacity under physiological condition in control (stably transfected with the empty vector) and APP cells after treatment with GBE. In addition, oxygen consumption of isolated mitochondria, activities of mitochondrial respiratory enzymes, ATP and reactive oxygen species (ROS) levels as well as mitochondrial membrane mass and mitochondrial DNA content were determined. We observed a general antioxidant effect of GBE leading to an increase of the coupling state of mitochondria as well as energy homeostasis and a reduction of ROS levels in control cells and in APP cells. GBE effect on OXPHOS was even preserved in mitochondria after isolation from treated cells. Moreover, these functional data were paralleled by an up-regulation of mitochondrial DNA. Improvement of the OXPHOS efficiency was stronger in APP cells than in control cells. In APP cells, the GBE-induced amelioration of oxygen consumption most likely arose from the modulation and respective normalization of the Abeta-induced disturbance in the activity of mitochondrial complexes III and IV restoring impaired ATP levels possibly through decreasing Abeta and oxidative stress level. Although the underlying molecular mechanisms of the mode of action of GBE remain to be

  5. Transient dynamics of Abeta contribute to toxicity in Alzheimer's disease

    NARCIS (Netherlands)

    Hubin, E.; Nuland, van N.; Broersen, K.; Pauwels, K.

    2014-01-01

    The aggregation and deposition of the amyloid-β peptide (Aβ) in the brain has been linked with neuronal death, which progresses in the diagnostic and pathological signs of Alzheimer’s disease (AD). The transition of an unstructured monomeric peptide into self-assembled and more structured aggregates

  6. Functions of A[beta], sAPP[alpha] and sAPP[beta] : similarities and differences

    National Research Council Canada - National Science Library

    Chasseigneaux, Stephanie; Allinquant, Bernadette

    2012-01-01

    ...), which also generates the soluble peptide APP[beta] (sAPP[beta]). An antagonist and major APP metabolic pathway involves cleavage by alpha secretase, which releases sAPP[alpha]. Although soluble A[beta...

  7. Phosphate and HEPES buffers potently affect the fibrillation and oligomerization mechanism of Alzheimer's A{beta} peptide

    Energy Technology Data Exchange (ETDEWEB)

    Garvey, Megan; Tepper, Katharina [Max-Planck-Forschungsstelle fuer Enzymologie der Proteinfaltung, Weinbergweg 22, D-06120 Halle (Saale) (Germany); Haupt, Caroline [Institute fuer Physik, Biophysik, Martin-Luther Universitaet Halle-Wittenberg, Betty-Heimann-Str. 7, D-06120 Halle (Saale) (Germany); Knuepfer, Uwe [Leibniz-Institute for Infection Biology and Natural Product Research, Beutenbergstr. 11a, D-07745 Jena (Germany); Klement, Karolin; Meinhardt, Jessica [Leibniz-Institute for Age Research (FLI), Beutenbergstr. 11, D-07745 Jena (Germany); Horn, Uwe [Leibniz-Institute for Infection Biology and Natural Product Research, Beutenbergstr. 11a, D-07745 Jena (Germany); Balbach, Jochen [Institute fuer Physik, Biophysik, Martin-Luther Universitaet Halle-Wittenberg, Betty-Heimann-Str. 7, D-06120 Halle (Saale) (Germany); Faendrich, Marcus, E-mail: fandrich@enzyme-halle.mpg.de [Max-Planck-Forschungsstelle fuer Enzymologie der Proteinfaltung, Weinbergweg 22, D-06120 Halle (Saale) (Germany); Bio zentrum, Martin-Luther Universitaet Halle-Wittenberg, Weinbergweg 22, D-06120 Halle (Saale) (Germany)

    2011-06-10

    Highlights: {yields} Sodium phosphate buffer accelerated A{beta}(1-40) nucleation relative to HEPES. {yields} A{beta}(1-40) fibrils formed in the two buffers show only minor structural differences. {yields} NMR revealed that A{beta}(1-40) histidine residues mediate buffer dependent changes. -- Abstract: The oligomerization of A{beta} peptide into amyloid fibrils is a hallmark of Alzheimer's disease. Due to its biological relevance, phosphate is the most commonly used buffer system for studying the formation of A{beta} and other amyloid fibrils. Investigation into the characteristics and formation of amyloid fibrils frequently relies upon material formed in vitro, predominantly in phosphate buffers. Herein, we examine the effects on the fibrillation and oligomerization mechanism of A{beta} peptide that occur due solely to the influence of phosphate buffer. We reveal that significant differences in amyloid fibrillation are observed due to fibrillation being initiated in phosphate or HEPES buffer (at physiological pH and temperature). Except for the differing buffer ions, all experimental parameters were kept constant. Fibril formation was assessed using fluorescently monitored kinetic studies, microscopy, X-ray fiber diffraction and infrared and nuclear magnetic resonance spectroscopies. Based on this set up, we herein reveal profound effects on the mechanism and speed of A{beta} fibrillation. The three histidine residues at positions 6, 13 and 14 of A{beta}(1-40) are instrumental in these mechanistic changes. We conclude that buffer plays a more significant role in fibril formation than has been generally acknowledged.

  8. Low-Vacuum Deposition of Glutamic Acid and Pyroglutamic Acid: A Facile Methodology for Depositing Organic Materials beyond Amino Acids.

    Science.gov (United States)

    Sugimoto, Iwao; Maeda, Shunsaku; Suda, Yoriko; Makihara, Kenji; Takahashi, Kazuhiko

    2014-01-01

    Thin layers of pyroglutamic acid (Pygl) have been deposited by thermal evaporation of the molten L-glutamic acid (L-Glu) through intramolecular lactamization. This deposition was carried out with the versatile handmade low-vacuum coater, which was simply composed of a soldering iron placed in a vacuum degassing resin chamber evacuated by an oil-free diaphragm pump. Molecular structural analyses have revealed that thin solid film evaporated from the molten L-Glu is mainly composed of L-Pygl due to intramolecular lactamization. The major component of the L-Pygl was in β-phase and the minor component was in γ-phase, which would have been generated from partial racemization to DL-Pygl. Electron microscopy revealed that the L-Glu-evaporated film generally consisted of the 20 nm particulates of Pygl, which contained a periodic pattern spacing of 0.2 nm intervals indicating the formation of the single-molecular interval of the crystallized molecular networks. The DL-Pygl-evaporated film was composed of the original DL-Pygl preserving its crystal structures. This methodology is promising for depositing a wide range of the evaporable organic materials beyond amino acids. The quartz crystal resonator coated with the L-Glu-evaporated film exhibited the pressure-sensing capability based on the adsorption-desorption of the surrounding gas at the film surface.

  9. Low-Vacuum Deposition of Glutamic Acid and Pyroglutamic Acid: A Facile Methodology for Depositing Organic Materials beyond Amino Acids

    Directory of Open Access Journals (Sweden)

    Iwao Sugimoto

    2014-01-01

    Full Text Available Thin layers of pyroglutamic acid (Pygl have been deposited by thermal evaporation of the molten L-glutamic acid (L-Glu through intramolecular lactamization. This deposition was carried out with the versatile handmade low-vacuum coater, which was simply composed of a soldering iron placed in a vacuum degassing resin chamber evacuated by an oil-free diaphragm pump. Molecular structural analyses have revealed that thin solid film evaporated from the molten L-Glu is mainly composed of L-Pygl due to intramolecular lactamization. The major component of the L-Pygl was in β-phase and the minor component was in γ-phase, which would have been generated from partial racemization to DL-Pygl. Electron microscopy revealed that the L-Glu-evaporated film generally consisted of the 20 nm particulates of Pygl, which contained a periodic pattern spacing of 0.2 nm intervals indicating the formation of the single-molecular interval of the crystallized molecular networks. The DL-Pygl-evaporated film was composed of the original DL-Pygl preserving its crystal structures. This methodology is promising for depositing a wide range of the evaporable organic materials beyond amino acids. The quartz crystal resonator coated with the L-Glu-evaporated film exhibited the pressure-sensing capability based on the adsorption-desorption of the surrounding gas at the film surface.

  10. The clinical significance of plasmatic amyloid A{beta}-40 peptide levels in Alzheimer's disease patients treated with galantamine.

    Science.gov (United States)

    Modrego, Pedro J; Monleon, Inmaculada; Sarasa, Manuel

    2008-01-01

    To date there are no conclusive reports on the usefulness of determining amyloid peptides in the serum of patients with Alzheimer's disease (AD). Only anecdotal works deal with the changes in the peptides produced by cholinesterase inhibitors. In this study, the authors investigated and studied the clinical significance of plasmatic Abeta-40 and Abeta-42 peptide levels in a series of 34 consecutive patients with AD. The baseline levels of the Abeta-40 peptide correlated negatively with the Mini Examen Cognoscitivo (Spanish version of the Mini-Mental test) score. Complete follow-up was possible in 22 patients. After 6 months of treatment with galantamine, the mean Abeta-40 peptide levels decreased from 31.86 to 24.22 pg/mL. The baseline levels of Abeta-40 were predictive of response to treatment in the Alzheimer's Disease Assessment Scale-Cognitive Subscale. The authors conclude that determining plasmatic Abeta-40 peptide levels could be useful in predicting and monitoring response to treatment in AD.

  11. Cu(II) coordination structure determinants of the fibrillization switch in Abeta peptides

    Science.gov (United States)

    Hernandez-Guzman, Jessica; Sun, Li; Mehta, Anil; Lynn, David; Warncke, Kurt

    2010-03-01

    Alzheimer's Disease (AD) is associated with the aggregation and fibrillization of the beta-amyloid protein (Abeta). The coordination of Cu(II) by peptide histidine imidazole sidechains is proposed to play an important role in determining the fibrillization ``switch'' [1]. We have developed techniques of powder X-band electron spin echo envelope modulation (ESEEM) spectroscopy to determine the 3D molecular structure of the Cu(II)-histidine imidazole coordination in cryotrapped soluble and fibrillar forms of Abeta peptides, in order to gain insight into the factors that govern fibrillization. We use hybrid optimization-based OPTESIM [2] simulation of the double quantum harmonic feature to determine the mutual orientation of the imidazole rings in Cu(II)--bis-imidazole complexes and in Abeta(13-21) peptides. The Cu(II) coordination mode and assembly constraints in fibrils are revealed. [1] Dong , J., et al., Proc. Natl. Acad. Sci., 2007, 104, 13313. [2] Sun, L., et al., J. Magn. Reson. 2009, 200, 21.

  12. Energy landscapes of the monomer and dimer of the Alzheimer's peptide Abeta(1-28).

    Science.gov (United States)

    Dong, Xiao; Chen, Wei; Mousseau, Normand; Derreumaux, Philippe

    2008-03-28

    The cytotoxicity of Alzheimer's disease has been linked to the self-assembly of the 4042 amino acid of the amyloid-beta (Abeta) peptide into oligomers. To understand the assembly process, it is important to characterize the very first steps of aggregation at an atomic level of detail. Here, we focus on the N-terminal fragment 1-28, known to form fibrils in vitro. Circular dichroism and NMR experiments indicate that the monomer of Abeta(1-28) is alpha-helical in a membranelike environment and random coil in aqueous solution. Using the activation-relaxation technique coupled with the OPEP coarse grained force field, we determine the structures of the monomer and of the dimer of Abeta(1-28). In agreement with experiments, we find that the monomer is predominantly random coil in character, but displays a non-negligible beta-strand probability in the N-terminal region. Dimerization impacts the structure of each chain and leads to an ensemble of intertwined conformations with little beta-strand content in the region Leu17-Ala21. All these structural characteristics are inconsistent with the amyloid fibril structure and indicate that the dimer has to undergo significant rearrangement en route to fibril formation.

  13. CD45RB is a novel molecular therapeutic target to inhibit Abeta peptide-induced microglial MAPK activation.

    Directory of Open Access Journals (Sweden)

    Yuyan Zhu

    Full Text Available BACKGROUND: Microglial activation, characterized by p38 MAPK or p44/42 MAPK pathway signal transduction, occurs in Alzheimer's disease (AD. Our previous studies demonstrated CD45, a membrane-bound protein tyrosine phosphatase (PTP, opposed beta-amyloid (Abeta peptide-induced microglial activation via inhibition of p44/42 MAPK. Additionally we have shown agonism of the RB isoform of CD45 (CD45RB abrogates lipopolysaccharide (LPS-induced microglial activation. METHODOLOGY AND RESULTS: In this study, CD45RB modulation of Abeta peptide or LPS-activated primary cultured microglial cells was further investigated. Microglial cells were co-treated with "aged" FITC-Abeta(1-42 and multiple CD45 isoform agonist antibodies. Data revealed cross-linking of CD45, particularly the CD45RB isoform, enhances microglial phagocytosis of Abeta(1-42 peptide and inhibits LPS-induced activation of p44/42 and p38 pathways. Co-treatment of microglial cells with agonist CD45 antibodies results in significant inhibition of LPS-induced microglial TNF-alpha and IL-6 release through p44/42 and/or p38 pathways. Moreover, inhibition of either of these pathways augmented CD45RB cross-linking induced microglial phagocytosis of Abeta(1-42 peptide. To investigate the mechanism(s involved, microglial cells were co-treated with a PTP inhibitor (potassium bisperoxo [1,10-phenanthroline oxovanadate; Phen] and Abeta(1-42 peptides. Data showed synergistic induction of microglial activation as evidenced by TNF-alpha and IL-6 release; both of which are demonstrated to be dependent on increased p44/42 and/or p38 activation. Finally, it was observed that cross-linking of CD45RB in the presence of Abeta(1-42 peptide, inhibits co-localization of microglial MHC class II and Abeta peptide; suggesting CD45 activation inhibits the antigen presenting phenotype of microglial cells. CONCLUSION: In summary, p38 MAPK is another novel signaling pathway, besides p44/42, in which CD45RB cross

  14. Ginkgo biloba extract ameliorates oxidative phosphorylation performance and rescues abeta-induced failure.

    Directory of Open Access Journals (Sweden)

    Virginie Rhein

    Full Text Available BACKGROUND: Energy deficiency and mitochondrial failure have been recognized as a prominent, early event in Alzheimer's disease (AD. Recently, we demonstrated that chronic exposure to amyloid-beta (Abeta in human neuroblastoma cells over-expressing human wild-type amyloid precursor protein (APP resulted in (i activity changes of complexes III and IV of the oxidative phosphorylation system (OXPHOS and in (ii a drop of ATP levels which may finally instigate loss of synapses and neuronal cell death in AD. Therefore, the aim of the present study was to investigate whether standardized Ginkgo biloba extract LI 1370 (GBE is able to rescue Abeta-induced defects in energy metabolism. METHODOLOGY/PRINCIPAL FINDINGS: We used a high-resolution respiratory protocol to evaluate OXPHOS respiratory capacity under physiological condition in control (stably transfected with the empty vector and APP cells after treatment with GBE. In addition, oxygen consumption of isolated mitochondria, activities of mitochondrial respiratory enzymes, ATP and reactive oxygen species (ROS levels as well as mitochondrial membrane mass and mitochondrial DNA content were determined. We observed a general antioxidant effect of GBE leading to an increase of the coupling state of mitochondria as well as energy homeostasis and a reduction of ROS levels in control cells and in APP cells. GBE effect on OXPHOS was even preserved in mitochondria after isolation from treated cells. Moreover, these functional data were paralleled by an up-regulation of mitochondrial DNA. Improvement of the OXPHOS efficiency was stronger in APP cells than in control cells. In APP cells, the GBE-induced amelioration of oxygen consumption most likely arose from the modulation and respective normalization of the Abeta-induced disturbance in the activity of mitochondrial complexes III and IV restoring impaired ATP levels possibly through decreasing Abeta and oxidative stress level. CONCLUSIONS

  15. Reducing amyloid plaque burden via ex vivo gene delivery of an Abeta-degrading protease: a novel therapeutic approach to Alzheimer disease.

    Directory of Open Access Journals (Sweden)

    Matthew L Hemming

    2007-08-01

    Full Text Available Understanding the mechanisms of amyloid-beta protein (Abeta production and clearance in the brain has been essential to elucidating the etiology of Alzheimer disease (AD. Chronically decreasing brain Abeta levels is an emerging therapeutic approach for AD, but no such disease-modifying agents have achieved clinical validation. Certain proteases are responsible for the catabolism of brain Abeta in vivo, and some experimental evidence suggests they could be used as therapeutic tools to reduce Abeta levels in AD. The objective of this study was to determine if enhancing the clearance of Abeta in the brain by ex vivo gene delivery of an Abeta-degrading protease can reduce amyloid plaque burden.We generated a secreted form of the Abeta-degrading protease neprilysin, which significantly lowers the levels of naturally secreted Abeta in cell culture. We then used an ex vivo gene delivery approach utilizing primary fibroblasts to introduce this soluble protease into the brains of beta-amyloid precursor protein (APP transgenic mice with advanced plaque deposition. Brain examination after cell implantation revealed robust clearance of plaques at the site of engraftment (72% reduction, p = 0.0269, as well as significant reductions in plaque burden in both the medial and lateral hippocampus distal to the implantation site (34% reduction, p = 0.0020; and 55% reduction, p = 0.0081, respectively.Ex vivo gene delivery of an Abeta-degrading protease reduces amyloid plaque burden in transgenic mice expressing human APP. These results support the use of Abeta-degrading proteases as a means to therapeutically lower Abeta levels and encourage further exploration of ex vivo gene delivery for the treatment of Alzheimer disease.

  16. Acute Blast Injury Reduces Brain Abeta in Two Rodent Species

    Directory of Open Access Journals (Sweden)

    Rita eDe Gasperi

    2012-12-01

    Full Text Available Blast-induced traumatic brain injury (TBI has been a major cause of morbidity and mortality in the conflicts in Iraq and Afghanistan. How the primary blast wave affects the brain is not well understood. In particular, it is unclear whether blast injures the brain through mechanisms similar to those found in non-blast closed impact injuries (nbTBI. The β-amyloid (Aβ peptide associated with the development of Alzheimer’s disease (AD is elevated acutely following TBI in humans as well as in experimental animal models of nbTBI. We examined levels of brain Aβ following experimental blast injury using enzyme-linked immunosorbent assays for Aβ 40 and 42. In both rat and mouse models of blast injury, rather than being increased, endogenous rodent brain Aβ levels were decreased acutely following injury. Levels of the amyloid precursor protein (APP were increased following blast exposure although there was no evidence of axonal pathology based on APP immunohistochemical staining. Unlike the findings in nbTBI animal models, levels of the β-secretase, BACE-1, and the γ-secretase component presenilin-1 were unchanged following blast exposure. These studies have implications for understanding the nature of blast injury to the brain. They also suggest that strategies aimed at lowering Aβ production may not be effective for treating acute blast injury to the brain.

  17. Polyalanine and Abeta Aggregation Kinetics: Probing Intermediate Oligomer Formation and Structure Using Computer Simulations

    Science.gov (United States)

    Phelps, Erin Melissa

    2011-12-01

    The aggregation of proteins into stable, well-ordered structures known as amyloid fibrils has been associated with many neurodegenerative diseases. Amyloid fibrils are long straight, and un-branched structures containing several proto-filaments, each of which exhibits "cross beta structure," -- ribbon-like layers of large beta sheets whose strands run perpendicular to the fibril axis. It has been suggested in the literature that the pathway to fibril formation has the following steps: unfolded monomers associate into transient unstable oligomers, the oligomers undergo a rearrangement into the cross-beta structure and form into proto-filaments, these proto-filaments then associate and grow into fully formed fibrils. Recent experimental studies have determined that the unstable intermediate structures are toxic to cells and that their presence may play a key role in the pathogenesis of the amyloid diseases. Many efforts have been made to determine the structure of intermediate oligomer aggregates that form during the fibrillization process. The goal of this work is to provide details about the structure and formation kinetics of the unstable oligomers that appear in the fibril formation pathway. The specific aims of this work are to determine the steps in the fibril formation pathway and how the kinetics of fibrillization changes with variations in temperature and concentration. The method used is the application of discontinuous molecular dynamics to large systems of peptides represented with an intermediate resolution model, PRIME, that was previously developed in our group. Three different peptide sequences are simulated: polyalanine (KA14K), Abeta17-40, and Abeta17-42; the latter two are truncated sequences of the Alzheimer's peptide. We simulate the spontaneous assembly of these peptide chains from a random initial configuration of random coils. We investigate aggregation kinetics and oligomer formation of a system of 192 polyalanine (KA14K) chains over a

  18. A novel transgenic rat model with a full Alzheimer's-like amyloid pathology displays pre-plaque intracellular amyloid-beta-associated cognitive impairment.

    Science.gov (United States)

    Leon, Wanda Carolina; Canneva, Fabio; Partridge, Vanessa; Allard, Simon; Ferretti, Maria Teresa; DeWilde, Arald; Vercauteren, Freya; Atifeh, Ramtin; Ducatenzeiler, Adriana; Klein, William; Szyf, Moshe; Alhonen, Leena; Cuello, A Claudio

    2010-01-01

    Alzheimer's disease (AD) is a neurodegenerative pathology in which amyloid-beta (Abeta) peptide accumulates in different brain areas leading to deposition of plaques and a progressive decline of cognitive functions. After a decade in which a number of transgenic (Tg) mouse models mimicking AD-like amyloid-deposition pathology have been successfully generated, few rat models have been reported that develop intracellular and extracellular Abeta accumulation, together with impairment of cognition. The generation of a Tg rat reproducing the full AD-like amyloid pathology has been elusive. Here we describe the generation and characterization of a new transgenic rat line, coded McGill-R-Thy1-APP, developed to express the human amyloid-beta precursor protein (AbetaPP) carrying both the Swedish and Indiana mutations under the control of the murine Thy1.2 promoter. The selected mono-transgenic line displays an extended phase of intraneuronal Abeta accumulation, already apparent at 1 week after birth, which is widespread throughout different cortical areas and the hippocampus (CA1, CA2, CA3, and dentate gyrus). Homozygous Tg animals eventually produce extracellular Abeta deposits and, by 6 months of age, dense, thioflavine S-positive, amyloid plaques are detected, associated with glial activation and surrounding dystrophic neurites. The cognitive functions in transgenic McGill-R-Thy1-APP rats, as assessed using the Morris water maze task, were found already altered as early as at 3 months of age, when no CNS plaques are yet present. The spatial cognitive impairment becomes more prominent in older animals (13 months), where the behavioral performance of Tg rats positively correlates with the levels of soluble Abeta (trimers) measured in the cortex.

  19. Limitations of the hCMEC/D3 cell line as a model for Abeta clearance by the human blood-brain barrier

    NARCIS (Netherlands)

    Biemans, E.A.; Jakel, L.; Waal, R.M.W. de; Kuiperij, H.B.; Verbeek, M.M.

    2017-01-01

    Alzheimer's disease and cerebral amyloid angiopathy are characterized by accumulation of amyloid-beta (Abeta) at the cerebrovasculature due to decreased clearance at the blood-brain barrier (BBB). However, the exact mechanism of Abeta clearance across this barrier has not been fully elucidated. The

  20. F-18 Polyethyleneglycol stilbenes as PET imaging agents targeting A{beta} aggregates in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Wei [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Oya, Shunichi [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Kung Meiping [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Hou, Catherine [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Maier, Donna L. [Department of Neuroscience, AstraZeneca, Wilmington, DE 19850 (United States); Kung, Hank F. [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States) and Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 (United States)]. E-mail: kunghf@sunmac.spect.upenn.edu

    2005-11-01

    This paper describes a novel series of {sup 18}F-labeled polyethyleneglycol (PEG)-stilbene derivatives as potential {beta}-amyloid (A{beta}) plaque-specific imaging agents for positron emission tomography (PET). In these series of compounds, {sup 18}F is linked to the stilbene through a PEG chain, of which the number of ethoxy groups ranges from 2 to 5. The purpose of adding PEG groups is to lower the lipophilicity and improve bioavailability. The syntheses of the 'cold' compounds and the {sup 18}F-labeled PEG stilbene derivatives are successfully achieved. All of the fluorinated stilbenes displayed high binding affinities in an assay using postmortem AD brain homogenates (K {sub i}=2.9-6.7 nM). Labeling was successfully performed by a substitution of the mesylate group of 10a-d by [{sup 18}F]fluoride giving the target compounds [{sup 18}F]12a-d (EOS, specific activity, 900-1500 Ci/mmol; radiochemical purity >99%). In vivo biodistribution of these novel {sup 18}F ligands in normal mice exhibited excellent brain penetrations and rapid washouts after an intravenous injection (6.6-8.1 and 1.2-2.6% dose/g at 2 and 60 min, respectively). Autoradiography of postmortem AD brain sections of [{sup 18}F]12a-d confirmed the specific binding related to the presence of A{beta} plaques. In addition, in vivo plaque labeling can be clearly demonstrated with these {sup 18}F-labeled agents in transgenic mice (Tg2576), a useful animal model for Alzheimer's disease. In conclusion, the preliminary results strongly suggest these fluorinated PEG stilbene derivatives are suitable candidates as A{beta} plaque imaging agents for studying patients with Alzheimer's disease.

  1. MMPBSA decomposition of the binding energy throughout a molecular dynamics simulation of amyloid-beta (Abeta(10-35)) aggregation.

    Science.gov (United States)

    Campanera, Josep M; Pouplana, Ramon

    2010-04-15

    Recent experiments with amyloid-beta (Abeta) peptides indicate that the formation of toxic oligomers may be an important contribution to the onset of Alzheimer's disease. The toxicity of Abeta oligomers depend on their structure, which is governed by assembly dynamics. However, a detailed knowledge of the structure of at the atomic level has not been achieved yet due to limitations of current experimental techniques. In this study, replica exchange molecular dynamics simulations are used to identify the expected diversity of dimer conformations of Abeta(10-35) monomers. The most representative dimer conformation has been used to track the dimer formation process between both monomers. The process has been characterized by means of the evolution of the decomposition of the binding free energy, which provides an energetic profile of the interaction. Dimers undergo a process of reorganization driven basically by inter-chain hydrophobic and hydrophilic interactions and also solvation/desolvation processes.

  2. Abeta(1-42) injection causes memory impairment, lowered cortical and serum BDNF levels, and decreased hippocampal 5-HT(2A) levels

    DEFF Research Database (Denmark)

    Christensen, R; Marcussen, Anders Bue; Wörtwein, Gitta;

    2008-01-01

    Aggregation of the beta-amyloid protein (Abeta) is a hallmark of Alzheimer's disease (AD) and is believed to be causally involved in a neurodegenerative cascade. In patients with AD, reduced levels of serum Brain Derived Neurotrophic Factor (BDNF) and cortical 5-HT(2A) receptor binding has recently...... been reported but it is unknown how these changes are related to beta-amyloid accumulation. In this study we examined in rats the effect of intrahippocampal injections of aggregated Abeta(1-42) (1 microg/microl) on serum and brain BDNF or 5-HT(2A) receptor levels. A social recognition test paradigm...... was used to monitor Abeta(1-42) induced memory impairment. Memory impairment was seen 22 days after injection of Abeta(1-42) in the experimental group and until termination of the experiments. In the Abeta(1-42) injected animals we saw an abolished increase in serum BDNF levels that was accompanied...

  3. Omega-3 fatty acid obtained from Nannochloropsis oceanica cultures grown under low urea protect against Abeta-induced neural damage

    OpenAIRE

    Lai, Ying-Jang

    2014-01-01

    Amyloid-beta (Abeta) protein is a key factor in the pathogenesis of Alzheimer’s disease (AD). Moreover, it has been reported that oxidative stress is involved in the biochemical pathway by which Abeta can lead to neuronal dysfunction. Recently, docosahexaenoic acid (DHA; C22:6) and eicosapentaenoic acid (EPA; C20:5n-3) have been reported to protect against AD. However, these omega-3 fatty acids are frequently obtained from fish oil and may contain heavy metals. In this study, we utilized Nann...

  4. Annular structures as intermediates in fibril formation of Alzheimer Abeta17-42.

    Science.gov (United States)

    Zheng, Jie; Jang, Hyunbum; Ma, Buyong; Nussinov, Ruth

    2008-06-05

    We report all-atom molecular dynamics simulations of annular beta-amyloid (17-42) structures, single- and double-layered, in solution. We assess the structural stability and association force of Abeta annular oligomers associated through different interfaces, with a mutated sequence (M35A), and with the oxidation state (M35O). Simulation results show that single-layered annular models display inherent structural instability: one is broken down into linear-like oligomers, and the other collapses. On the other hand, a double-layered annular structure where the two layers interact through their C-termini to form an NC-CN interface (where N and C are the N and C termini, respectively) exhibits high structural stability over the simulation time due to strong hydrophobic interactions and geometrical constraints induced by the closed circular shape. The observed dimensions and molecular weight of the oligomers from atomic force microscopy (AFM) experiments are found to correspond well to our stable double-layered model with the NC-CN interface. Comparison with K3 annular structures derived from the beta 2-microglobulin suggests that the driving force for amyloid formation is sequence specific, strongly dependent on side-chain packing arrangements, structural morphologies, sequence composition, and residue positions. Combined with our previous simulations of linear-like Abeta, K3 peptide, and sup35-derived GNNQQNY peptide, the annular structures provide useful insight into oligomeric structures and driving forces that are critical in amyloid fibril formation.

  5. A thermodynamic study of Abeta(16-21) dissociation from a fibril using computer simulations

    Science.gov (United States)

    Dias, Cristiano; Mahmoudinobar, Farbod; Su, Zhaoqian

    Here, I will discuss recent all-atom molecular dynamics simulations with explicit water in which we studied the thermodynamic properties of Abeta(16-21) dissociation from an amyloid fibril. Changes in thermodynamics quantities, e.g., entropy, enthalpy, and volume, are computed from the temperature dependence of the free-energy computed using the umbrella sampling method. We find similarities and differences between the thermodynamics of peptide dissociation and protein unfolding. Similarly to protein unfolding, Abeta(16-21) dissociation is characterized by an unfavorable change in enthalpy, a favorable change in the entropic energy, and an increase in the heat capacity. A main difference is that peptide dissociation is characterized by a weak enthalpy-entropy compensation. We characterize dock and lock states of the peptide based on the solvent accessible surface area. The Lennard-Jones energy of the system is observed to increase continuously in lock and dock states as the peptide dissociates. The electrostatic energy increases in the lock state and it decreases in the dock state as the peptide dissociates. These results will be discussed as well as their implication for fibril growth.

  6. Subcellular and metabolic examination of amyloid-beta peptides in Alzheimer disease pathogenesis: evidence for Abeta(25-35).

    NARCIS (Netherlands)

    Kaminsky, Y.G.; Marlatt, M.W.; Smith, M.A.; Kosenko, E.A.

    2010-01-01

    Amyloid-beta peptide (Abeta) is a central player in the pathogenesis and diagnosis of Alzheimer disease. It aggregates to form the core of Alzheimer disease-associated plaques found in coordination with tau deposits in diseased individuals. Despite this clinical relevance, no single hypothesis

  7. "Clicked" bivalent ligands containing curcumin and cholesterol as multifunctional abeta oligomerization inhibitors: design, synthesis, and biological characterization.

    Science.gov (United States)

    Lenhart, James A; Ling, Xiao; Gandhi, Ronak; Guo, Tai L; Gerk, Phillip M; Brunzell, Darlene H; Zhang, Shijun

    2010-08-26

    In our effort to develop multifunctional compounds that cotarget beta-amyloid oligomers (AbetaOs), cell membrane/lipid rafts (CM/LR), and oxidative stress, a series of bivalent multifunctional Abeta oligomerization inhibitors (BMAOIs) containing cholesterol and curcumin were designed, synthesized, and biologically characterized as potential treatments for Alzheimer's disease (AD). The in vitro assay results established that the length of spacer that links cholesterol and curcumin and the attaching position of the spacer on curcumin are important structural determinants for their biological activities. Among the BMAOIs tested, 14 with a 21-atom-spacer was identified to localize to the CM/LR of human neuroblastoma MC65 cells, to inhibit the formation of AbetaOs in MC65 cells, to protect cells from AbetaOs-induced cytotoxicity, and to retain antioxidant properties of curcumin. Furthermore, 14 was confirmed to have the potential to cross the blood-brain barrier (BBB) as demonstrated in a Caco-2 cell model. Collectively, these results strongly encourage further optimization of 14 as a new hit to develop more potent BMAOIs.

  8. The hydrophobic environment of Met35 of Alzheimer's Abeta(1-42) is important for the neurotoxic and oxidative properties of the peptide.

    Science.gov (United States)

    Kanski, Jaroslaw; Aksenova, Marina; Butterfield, D Allan

    2002-05-01

    In Alzheimer's disease (AD) brain increased lipid peroxidation is found. Amyloid beta-peptide [Abeta(1-42)] induces oxidative stress (including lipid peroxidation) and neurotoxicity, and the single methionine residue (Met35) is important for these properties. In the current study, we tested the hypothesis that removal of Met35 from lipid bilayer would abrogate the oxidative stress and neurotoxic properties of Abeta(1-42), i.e. we tested the hypothesis and found that lipid peroxidation initiated by oxidation of the Met35 is an early event in Abeta(1-42) neurotoxicity. Substitution of negatively charged aspartic acid for glycine residue 37 is not predicted to bring the Met35 residue out of the hydrophobic lipid bilayer. In this study, we showed that G37D substitution in Abeta(1-42) completely abolishes neurotoxic and oxidative processes associated with the parent peptide. This is demonstrated by the lack of cell toxicity and protein oxidation in contrast to the treatment with native Abeta(1-42). Additionally, the G37D peptide does not display the aggregation properties that are associated with native Abeta as seen in the thioflavin T (ThT) assay and fibril morphology. The results presented in this work are thus consistent with the notion of the importance of methionine 35 of Abeta(1-42) in the lipid-initiated oxidative cascade and subsequent neurotoxicity in AD brain.

  9. Modulation of the humoral and cellular immune response in Abeta immunotherapy by the adjuvants monophosphoryl lipid A (MPL), cholera toxin B subunit (CTB) and E. coli enterotoxin LT(R192G).

    Science.gov (United States)

    Maier, Marcel; Seabrook, Timothy J; Lemere, Cynthia A

    2005-10-25

    Abeta vaccination or passive transfer of human-specific anti-Abeta antibodies are approaches under investigation to prevent and/or treat Alzheimer's disease (AD). Successful active Abeta vaccination requires a strong and safe adjuvant to induce anti-Abeta antibody formation. We compared the adjuvants monophosphoryl lipid A (MPL)/trehalose dicorynomycolate (TDM), cholera toxin B subunit (CTB) and Escherichia coli heat-labile enterotoxin LT(R192G) for their ability to induce a humoral and cellular immune reaction, using fibrillar Abeta1-40/42 as a common immunogen in wildtype B6D2F1 mice. Subcutaneous (s.c.) administration with MPL/TDM resulted in anti-Abeta antibodies levels up to four times higher compared to s.c. LT(R192G). Using MPL/TDM, the anti-Abeta antibodies induced were mainly IgG2b, IgG1 and lower levels of IgG2a and IgM, with a moderate splenocyte proliferation and IFN-gamma production in vitro upon stimulation with Abeta1-40/42. LT(R192G), previously shown by us to induce robust titers of anti-Abeta antibodies, generated predominantly IgG2b and IgG1 anti-Abeta antibodies with very low splenocyte proliferation and IFN-gamma production. Weekly intranasal (i.n.) administration over 11 weeks of Abeta40/42 with CTB induced only moderate levels of antibodies. All immunogens generated antibodies that recognized mainly the Abeta1-7 epitope and specifically detected amyloid plaques on AD brain sections. In conclusion, MPL/TDM, in addition to LT(R192G), is an effective adjuvant when combined with Abeta40/42 and may aid in the design of Abeta immunotherapy.

  10. Transient formation of nano-crystalline structures during fibrillation of an Abeta-like peptide.

    Science.gov (United States)

    Otzen, Daniel E; Oliveberg, Mikael

    2004-05-01

    During the first few minutes of fibrillation of a 14-residue peptide homologous to the hydrophobic C-terminal part of the Abeta-peptide, EM micrographs reveal small crystalline areas (100 to 150 nm, repeating unit 47 A) scattered in more amorphous material. On a longer time scale, these crystalline areas disappear and are replaced by tangled clusters resembling protofilaments (hours), and eventually by more regular amyloid fibrils of 60 A to 120 A diameter (days). The transient population of the crystalline areas indicates the presence of ordered substructures in the early fibrillation process, the diameter of which matches the length of the 14-mer peptide in an extended beta-strand conformation.

  11. Pediatric respiratory and systemic effects of chronic air pollution exposure: nose, lung, heart, and brain pathology.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; Torres-Jardón, Ricardo; Henriquez-Roldán, Carlos; Barragán-Mejía, Gerardo; Valencia-Salazar, Gildardo; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderón, Rafael; Reed, William

    2007-01-01

    Exposures to particulate matter and gaseous air pollutants have been associated with respiratory tract inflammation, disruption of the nasal respiratory and olfactory barriers, systemic inflammation, production of mediators of inflammation capable of reaching the brain and systemic circulation of particulate matter. Mexico City (MC) residents are exposed to significant amounts of ozone, particulate matter and associated lipopolysaccharides. MC dogs exhibit brain inflammation and an acceleration of Alzheimer's-like pathology, suggesting that the brain is adversely affected by air pollutants. MC children, adolescents and adults have a significant upregulation of cyclooxygenase-2 (COX2) and interleukin-1beta (IL-1beta) in olfactory bulb and frontal cortex, as well as neuronal and astrocytic accumulation of the 42 amino acid form of beta -amyloid peptide (Abeta 42), including diffuse amyloid plaques in frontal cortex. The pathogenesis of Alzheimer's disease (AD) is characterized by brain inflammation and the accumulation of Abeta 42, which precede the appearance of neuritic plaques and neurofibrillary tangles, the pathological hallmarks of AD. Our findings of nasal barrier disruption, systemic inflammation, and the upregulation of COX2 and IL-1beta expression and Abeta 42 accumulation in brain suggests that sustained exposures to significant concentrations of air pollutants such as particulate matter could be a risk factor for AD and other neurodegenerative diseases.

  12. Reducing AD-like pathology in 3xTg-AD mouse model by DNA epitope vaccine - a novel immunotherapeutic strategy.

    Directory of Open Access Journals (Sweden)

    Nina Movsesyan

    Full Text Available BACKGROUND: The development of a safe and effective AD vaccine requires a delicate balance between providing an adequate anti-Abeta antibody response sufficient to provide therapeutic benefit, while eliminating an adverse T cell-mediated proinflammatory autoimmune response. To achieve this goal we have designed a prototype chemokine-based DNA epitope vaccine expressing a fusion protein that consists of 3 copies of the self-B cell epitope of Abeta(42 (Abeta(1-11 , a non-self T helper cell epitope (PADRE, and macrophage-derived chemokine (MDC/CCL22 as a molecular adjuvant to promote a strong anti-inflammatory Th2 phenotype. METHODS AND FINDINGS: We generated pMDC-3Abeta(1-11-PADRE construct and immunized 3xTg-AD mouse model starting at age of 3-4 months old. We demonstrated that prophylactic immunizations with the DNA epitope vaccine generated a robust Th2 immune response that induced high titers of anti-Abeta antibody, which in turn inhibited accumulation of Abeta pathology in the brains of older mice. Importantly, vaccination reduced glial activation and prevented the development of behavioral deficits in aged animals without increasing the incidence of microhemorrhages. CONCLUSIONS: Data from this transitional pre-clinical study suggest that our DNA epitope vaccine could be used as a safe and effective strategy for AD therapy. Future safety and immunology studies in large animals with the goal to achieve effective humoral immunity without adverse effects should help to translate this study to human clinical trials.

  13. LA PROTEINA NEUROLIGINA ES UN AGENTE NUCLEADOR DEL PEPTIDO BETA-AMILOIDE IN VITRO Y UNE LOS OLIGOMEROS DE ABETA A LA SINAPSIS NEURONAL

    OpenAIRE

    2009-01-01

    LA POLIMERIZACION Y AGREGACION DEL PEPTIDO BETA-AMILOIDE (AB) EN FIBRAS AMILOIDE ES UN PROCESO MUY ESTUDIADO EN EL ANALISIS DEL MECANISMO DE LA ENFERMEDAD DE ALZHEIMER (EA). RECIENTEMENTE, SE HA SUGERIDO QUE LA ACUMULACION DE FORMAS SOLUBLES DEL ABETA EN LA SINAPSIS NEURONAL SERIA EL PRIMER PASO QUE CONDUCE AL DAÃ?O COGNITIVO EN LOS PACIENTES DE LA EA. ESTE EFECTO NEUROTOXICO DEL ABETA SOBRE LA SINAPSIS GENERA UNA DISMINUCION DE LAS PROTEINAS POSTSINAPTICAS EXCITATORIAS, UNA ALTERACION EN EL ...

  14. Mixtures of wild-type and a pathogenic (E22G) form of Abeta40 in vitro accumulate protofibrils, including amyloid pores

    OpenAIRE

    Lashuel, Hilal A.; Hartley, Dean M; Petre, Benjamin M.; Wall, Joseph S.; Simon, Martha N.; Walz, Thomas; Lansbury, Peter T.

    2003-01-01

    Although APP mutations associated with inherited forms of Alzheimer's disease (AD) are relatively rare, detailed studies of these mutations may prove critical for gaining important insights into the mechanism(s) and etiology of AD. Here, we present a detailed biophysical characterization of the structural properties of protofibrils formed by the Arctic variant (E22G) of amyloid-beta protein (Abeta40(ARC)) as well as the effect of Abeta40(WT) on the distribution of the protofibrillar species f...

  15. Alzheimer amyloid beta-peptide A-beta25-35 blocks adenylate cyclase-mediated forms of hippocampal long-term potentiation.

    Science.gov (United States)

    Bisel, Blaine E; Henkins, Kristen M; Parfitt, Karen D

    2007-02-01

    Progressive memory loss and deposition of amyloid beta (Abeta) peptides throughout cortical regions are hallmarks of Alzheimer's disease (AD). Several studies in mice and rats have shown that overexpression of amyloid precursor protein (APP) or pretreatment with Abeta peptide fragments results in the inhibition of hippocampal long-term potentiation (LTP) as well as impairments in learning and memory of hippocampal-dependent tasks. For these studies we have investigated the effects of the Abeta(25-35) peptide fragment on LTP induced by adenylate cyclase stimulation followed immediately by application of Mg(++)-free aCSF ("chemLTP"). Treatment of young adult slices with the Abeta(25-35) peptide had no significant effect on basal synaptic transmission in area CA1, but treatment with the peptide for 20 min before inducing chemLTP with isoproterenol (ISO; 1 microM) or forskolin (FSK;10 microM) + Mg(++)-free aCSF resulted in complete blockade of LTP. In contrast, normal ISO-chemLTP was observed after treatment with the control peptide Abeta(35-25). The ability of the Abeta(25-35) peptide fragment to block this and other forms of synaptic plasticity may help elucidate the mechanisms underlying hippocampal deficits observed in animal models of AD and/or AD individuals.

  16. Osler's pathology.

    Science.gov (United States)

    Pai, S A

    2000-12-01

    Sir William Osler, one of the giants of clinical medicine, had his initial training as a pathologist. He was one of the physicians responsible for the impact that autopsies have had on medicine. He also contributed to the development of laboratory medicine. Osler made significant discoveries in anatomic pathology and hematology. His expertise was restricted not just to human pathology, but also to veterinary pathology. His mentors played a fundamental role in his achievements in academics.

  17. [Pathological jealousy].

    Science.gov (United States)

    Zacher, A

    2004-10-28

    Pathological jealousy can make life unbearable for all concerned. The proximity of this condition to obsessive-compulsive phenomena has given rise to the notion that it might respond to substances of proven value in the treatment of obsessive-compulsive disorders. This case history exemplifies the successful treatment of pathological jealousy with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. The substance not only proved to be a successful antidepressant, but also effectively mitigated the anguish of the patient's pathological jealousy. On the basis of these findings, fluoxetine--as also other SSRIs--should always be considered as a possible effective pharmacological strategy for the treatment of pathological jealousy.

  18. Apolipoprotein E modulates Alzheimer's Abeta(1-42)-induced oxidative damage to synaptosomes in an allele-specific manner.

    Science.gov (United States)

    Lauderback, Christopher M; Kanski, Jaroslaw; Hackett, Janna M; Maeda, Noboyo; Kindy, Mark S; Butterfield, D Allan

    2002-01-01

    Several functional differences have been reported among the three human e2, e3, and e4 alleles of apolipoprotein E (apoE). One functional difference lies in the antioxidant potential of these alleles; e4 has the poorest potential. Interestingly, e4 also correlates with increased oxidative damage in the Alzheimer's disease (AD) brain, which may explain why the inheritance of the e4 allele is a risk factor for the onset of AD. Beta-amyloid (Abeta) is also intimately involved in AD and promotes oxidative damage in vitro; therefore, we have examined the role of the different apoE alleles in modulating Abeta(1-42)-induced oxidation to synaptosomes. Measurement of specific markers of oxidation in synaptosomes isolated from mice that express one of the human apoE alleles indicates that Abeta-induced increases of these markers can be modulated by apoE in an allele-dependent manner (e2>e3>e4). Increases in reactive oxygen species formation and protein and lipid oxidation were always greatest in e4 synaptosomes as compared to e2 and e3 synaptosomes. Our data support the role of apoE as a modulator of Abeta toxicity and, consistent with the antioxidant potentials of the three alleles, suggest that the e4 allele may not be as effective in this role as the e2 or e3 alleles of apoE. These results are discussed with reference to mechanistic implications for neurodegeneration in the AD brain.

  19. Altered emotionality leads to increased pain tolerance in amyloid beta (Abeta1-40) peptide-treated mice.

    Science.gov (United States)

    Pamplona, Fabrício A; Pandolfo, Pablo; Duarte, Filipe S; Takahashi, Reinaldo N; Prediger, Rui D S

    2010-09-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the decline in cognitive functions, but it is also related to emotional disturbances. Since pain experience results from a complex integration of sensory, cognitive and affective processes, it is not surprising that AD patients display a distinct pattern of pain responsivity. We evaluated whether mice treated with amyloid beta (Abeta) peptide-thought to be critical in the pathogenesis of AD-exhibit altered pain responses and its relation to altered emotionality. Mice received a single i.c.v. injection of vehicle (PBS) or Abeta fragment (1-40) (400pmol/mice) and after 30 days, they were evaluated in tests of pain (hotplate, footshock-sensitivity), learning/memory (water-maze), emotionality (elevated plus-maze, forced swim) and locomotion (open-field). Abeta(1-40)-treated mice presented similar latencies to the control group in the hotplate test and similar nociceptive flinch threshold in the footshock-sensitivity test. However, they presented an increased jump threshold in footshock-sensitivity, suggesting increased pain tolerance. Altered emotionality was observed in the elevated plus-maze (EPM) and forced-swim tests (FST), suggesting anxiogenic-like and depressive-like states, respectively. A multifactorial principal component analysis (PCA) revealed that jump threshold of the footshock-sensitivity test falls within 'Emotionality' and 'Pain', showing moderate correlation with each one of the components of behavior. Acute treatment with the antidepressant desipramine (10mg/kg, i.p.) reduced the jump threshold (i.e. pain tolerance) and time of immobility in FST (i.e. depressive-like state). Flinch threshold (i.e. pain sensitivity), locomotion and anxiety were not altered with desipramine treatment. These results suggest that Abeta(1-40) peptide increases pain tolerance, but not pain sensitivity in mice, which seems to be linked to alterations in cognitive/emotional components of pain

  20. Stability of the transthyretin molecule as a key factor in the interaction with a-beta peptide--relevance in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Carlos A Ribeiro

    Full Text Available Transthyretin (TTR protects against A-Beta toxicity by binding the peptide thus inhibiting its aggregation. Previous work showed different TTR mutations interact differently with A-Beta, with increasing affinities correlating with decreasing amyloidogenecity of the TTR mutant; this did not impact on the levels of inhibition of A-Beta aggregation, as assessed by transmission electron microscopy. Our work aimed at probing differences in binding to A-Beta by WT, T119M and L55P TTR using quantitative assays, and at identifying factors affecting this interaction. We addressed the impact of such factors in TTR ability to degrade A-Beta. Using a dot blot approach with the anti-oligomeric antibody A11, we showed that A-Beta formed oligomers transiently, indicating aggregation and fibril formation, whereas in the presence of WT and T119M TTR the oligomers persisted longer, indicative that these variants avoided further aggregation into fibrils. In contrast, L55PTTR was not able to inhibit oligomerization or to prevent evolution to aggregates and fibrils. Furthermore, apoptosis assessment showed WT and T119M TTR were able to protect against A-Beta toxicity. Because the amyloidogenic potential of TTR is inversely correlated with its stability, the use of drugs able to stabilize TTR tetrameric fold could result in increased TTR/A-Beta binding. Here we showed that iododiflunisal, 3-dinitrophenol, resveratrol, [2-(3,5-dichlorophenylamino] (DCPA and [4-(3,5-difluorophenyl] (DFPB were able to increase TTR binding to A-Beta; however only DCPA and DFPB improved TTR proteolytic activity. Thyroxine, a TTR ligand, did not influence TTR/A-Beta interaction and A-Beta degradation by TTR, whereas RBP, another TTR ligand, not only obstructed the interaction but also inhibited TTR proteolytic activity. Our results showed differences between WT and T119M TTR, and L55PTTR mutant regarding their interaction with A-Beta and prompt the stability of TTR as a key factor in this

  1. Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers I: Abeta 42 oligomer binding to specific neuronal receptors is displaced by drug candidates that improve cognitive deficits.

    Science.gov (United States)

    Izzo, Nicholas J; Staniszewski, Agnes; To, Lillian; Fa, Mauro; Teich, Andrew F; Saeed, Faisal; Wostein, Harrison; Walko, Thomas; Vaswani, Anisha; Wardius, Meghan; Syed, Zanobia; Ravenscroft, Jessica; Mozzoni, Kelsie; Silky, Colleen; Rehak, Courtney; Yurko, Raymond; Finn, Patricia; Look, Gary; Rishton, Gilbert; Safferstein, Hank; Miller, Miles; Johanson, Conrad; Stopa, Edward; Windisch, Manfred; Hutter-Paier, Birgit; Shamloo, Mehrdad; Arancio, Ottavio; LeVine, Harry; Catalano, Susan M

    2014-01-01

    Synaptic dysfunction and loss caused by age-dependent accumulation of synaptotoxic beta amyloid (Abeta) 1-42 oligomers is proposed to underlie cognitive decline in Alzheimer's disease (AD). Alterations in membrane trafficking induced by Abeta oligomers mediates reduction in neuronal surface receptor expression that is the basis for inhibition of electrophysiological measures of synaptic plasticity and thus learning and memory. We have utilized phenotypic screens in mature, in vitro cultures of rat brain cells to identify small molecules which block or prevent the binding and effects of Abeta oligomers. Synthetic Abeta oligomers bind saturably to a single site on neuronal synapses and induce deficits in membrane trafficking in neuronal cultures with an EC50 that corresponds to its binding affinity. The therapeutic lead compounds we have found are pharmacological antagonists of Abeta oligomers, reducing the binding of Abeta oligomers to neurons in vitro, preventing spine loss in neurons and preventing and treating oligomer-induced deficits in membrane trafficking. These molecules are highly brain penetrant and prevent and restore cognitive deficits in mouse models of Alzheimer's disease. Counter-screening these compounds against a broad panel of potential CNS targets revealed they are highly potent and specific ligands of the sigma-2/PGRMC1 receptor. Brain concentrations of the compounds corresponding to greater than 80% receptor occupancy at the sigma-2/PGRMC1 receptor restore cognitive function in transgenic hAPP Swe/Ldn mice. These studies demonstrate that synthetic and human-derived Abeta oligomers act as pharmacologically-behaved ligands at neuronal receptors--i.e. they exhibit saturable binding to a target, they exert a functional effect related to their binding and their displacement by small molecule antagonists blocks their functional effect. The first-in-class small molecule receptor antagonists described here restore memory to normal in multiple AD models

  2. Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers I: Abeta 42 oligomer binding to specific neuronal receptors is displaced by drug candidates that improve cognitive deficits.

    Directory of Open Access Journals (Sweden)

    Nicholas J Izzo

    Full Text Available Synaptic dysfunction and loss caused by age-dependent accumulation of synaptotoxic beta amyloid (Abeta 1-42 oligomers is proposed to underlie cognitive decline in Alzheimer's disease (AD. Alterations in membrane trafficking induced by Abeta oligomers mediates reduction in neuronal surface receptor expression that is the basis for inhibition of electrophysiological measures of synaptic plasticity and thus learning and memory. We have utilized phenotypic screens in mature, in vitro cultures of rat brain cells to identify small molecules which block or prevent the binding and effects of Abeta oligomers. Synthetic Abeta oligomers bind saturably to a single site on neuronal synapses and induce deficits in membrane trafficking in neuronal cultures with an EC50 that corresponds to its binding affinity. The therapeutic lead compounds we have found are pharmacological antagonists of Abeta oligomers, reducing the binding of Abeta oligomers to neurons in vitro, preventing spine loss in neurons and preventing and treating oligomer-induced deficits in membrane trafficking. These molecules are highly brain penetrant and prevent and restore cognitive deficits in mouse models of Alzheimer's disease. Counter-screening these compounds against a broad panel of potential CNS targets revealed they are highly potent and specific ligands of the sigma-2/PGRMC1 receptor. Brain concentrations of the compounds corresponding to greater than 80% receptor occupancy at the sigma-2/PGRMC1 receptor restore cognitive function in transgenic hAPP Swe/Ldn mice. These studies demonstrate that synthetic and human-derived Abeta oligomers act as pharmacologically-behaved ligands at neuronal receptors--i.e. they exhibit saturable binding to a target, they exert a functional effect related to their binding and their displacement by small molecule antagonists blocks their functional effect. The first-in-class small molecule receptor antagonists described here restore memory to normal in

  3. Alzheimer's Therapeutics Targeting Amyloid Beta 1–42 Oligomers I: Abeta 42 Oligomer Binding to Specific Neuronal Receptors Is Displaced by Drug Candidates That Improve Cognitive Deficits

    Science.gov (United States)

    Izzo, Nicholas J.; Staniszewski, Agnes; To, Lillian; Fa, Mauro; Teich, Andrew F.; Saeed, Faisal; Wostein, Harrison; Walko, Thomas; Vaswani, Anisha; Wardius, Meghan; Syed, Zanobia; Ravenscroft, Jessica; Mozzoni, Kelsie; Silky, Colleen; Rehak, Courtney; Yurko, Raymond; Finn, Patricia; Look, Gary; Rishton, Gilbert; Safferstein, Hank; Miller, Miles; Johanson, Conrad; Stopa, Edward; Windisch, Manfred; Hutter-Paier, Birgit; Shamloo, Mehrdad; Arancio, Ottavio; LeVine, Harry; Catalano, Susan M.

    2014-01-01

    Synaptic dysfunction and loss caused by age-dependent accumulation of synaptotoxic beta amyloid (Abeta) 1–42 oligomers is proposed to underlie cognitive decline in Alzheimer's disease (AD). Alterations in membrane trafficking induced by Abeta oligomers mediates reduction in neuronal surface receptor expression that is the basis for inhibition of electrophysiological measures of synaptic plasticity and thus learning and memory. We have utilized phenotypic screens in mature, in vitro cultures of rat brain cells to identify small molecules which block or prevent the binding and effects of Abeta oligomers. Synthetic Abeta oligomers bind saturably to a single site on neuronal synapses and induce deficits in membrane trafficking in neuronal cultures with an EC50 that corresponds to its binding affinity. The therapeutic lead compounds we have found are pharmacological antagonists of Abeta oligomers, reducing the binding of Abeta oligomers to neurons in vitro, preventing spine loss in neurons and preventing and treating oligomer-induced deficits in membrane trafficking. These molecules are highly brain penetrant and prevent and restore cognitive deficits in mouse models of Alzheimer's disease. Counter-screening these compounds against a broad panel of potential CNS targets revealed they are highly potent and specific ligands of the sigma-2/PGRMC1 receptor. Brain concentrations of the compounds corresponding to greater than 80% receptor occupancy at the sigma-2/PGRMC1 receptor restore cognitive function in transgenic hAPP Swe/Ldn mice. These studies demonstrate that synthetic and human-derived Abeta oligomers act as pharmacologically-behaved ligands at neuronal receptors - i.e. they exhibit saturable binding to a target, they exert a functional effect related to their binding and their displacement by small molecule antagonists blocks their functional effect. The first-in-class small molecule receptor antagonists described here restore memory to normal in multiple AD

  4. Stable isotope dilution HILIC-MS/MS method for accurate quantification of glutamic acid, glutamine, pyroglutamic acid, GABA and theanine in mouse brain tissues.

    Science.gov (United States)

    Inoue, Koichi; Miyazaki, Yasuto; Unno, Keiko; Min, Jun Zhe; Todoroki, Kenichiro; Toyo'oka, Toshimasa

    2016-01-01

    In this study, we developed the stable isotope dilution hydrophilic interaction liquid chromatography with tandem mass spectrometry (HILIC-MS/MS) technique for the accurate, reasonable and simultaneous quantification of glutamic acid (Glu), glutamine (Gln), pyroglutamic acid (pGlu), γ-aminobutyric acid (GABA) and theanine in mouse brain tissues. The quantification of these analytes was accomplished using stable isotope internal standards and the HILIC separating mode to fully correct the intramolecular cyclization during the electrospray ionization. It was shown that linear calibrations were available with high coefficients of correlation (r(2)  > 0.999, range from 10 pmol/mL to 50 mol/mL). For application of the theanine intake, the determination of Glu, Gln, pGlu, GABA and theanine in the hippocampus and central cortex tissues was performed based on our developed method. In the region of the hippocampus, the concentration levels of Glu and pGlu were significantly reduced during reality-based theanine intake. Conversely, the concentration level of GABA increased. This result showed that transited theanine has an effect on the metabolic balance of Glu analogs in the hippocampus.

  5. Acetaminophen toxicity and 5-oxoproline (pyroglutamic acid): a tale of two cycles, one an ATP-depleting futile cycle and the other a useful cycle.

    Science.gov (United States)

    Emmett, Michael

    2014-01-01

    The acquired form of 5-oxoproline (pyroglutamic acid) metabolic acidosis was first described in 1989 and its relationship to chronic acetaminophen ingestion was proposed the next year. Since then, this cause of chronic anion gap metabolic acidosis has been increasingly recognized. Many cases go unrecognized because an assay for 5-oxoproline is not widely available. Most cases occur in malnourished, chronically ill women with a history of chronic acetaminophen ingestion. Acetaminophen levels are very rarely in the toxic range; rather, they are usually therapeutic or low. The disorder generally resolves with cessation of acetaminophen and administration of intravenous fluids. Methionine or N-acetyl cysteine may accelerate resolution and methionine is protective in a rodent model. The disorder has been attributed to glutathione depletion and activation of a key enzyme in the γ-glutamyl cycle. However, the specific metabolic derangements that cause the 5-oxoproline accumulation remain unclear. An ATP-depleting futile 5-oxoproline cycle can explain the accumulation of 5-oxoproline after chronic acetaminophen ingestion. This cycle is activated by the depletion of both glutathione and cysteine. This explanation contributes to our understanding of acetaminophen-induced 5-oxoproline metabolic acidosis and the beneficial role of N-acetyl cysteine therapy. The ATP-depleting futile 5-oxoproline cycle may also play a role in the energy depletions that occur in other acetaminophen-related toxic syndromes.

  6. Cyclooxygenase-1 and -2 in the different stages of Alzheimer's disease pathology.

    Science.gov (United States)

    Hoozemans, J J M; Rozemuller, J M; van Haastert, E S; Veerhuis, R; Eikelenboom, P

    2008-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of beta amyloid (Abeta) protein and the formation of neurofibrillary tangles. In addition, there is an increase of inflammatory proteins in the brains of AD patients. Epidemiological studies, indicating that non-steroidal anti-inflammatory drugs (NSAIDs) decrease the risk of developing AD, have encouraged the study on the role of inflammation in AD. The best-characterized action of most NSAIDs is the inhibition of cyclooxygenase (COX). The expression of the constitutively expressed COX-1 and the inflammatory induced COX-2 has been intensively investigated in AD brain and different disease models for AD. Despite these studies, clinical trials with NSAIDs or selective COX-2 inhibitors showed little or no effect on clinical progression of AD. The expression levels of COX-1 and COX-2 change in the different stages of AD pathology. In an early stage, when low-fibrillar Abeta deposits are present and only very few neurofibrillary tangles are observed in the cortical areas, COX-2 is increased in neurons. The increased neuronal COX-2 expression parallels and colocalizes with the expression of cell cycle proteins. COX-1 is primarily expressed in microglia, which are associated with fibrillar Abeta deposits. This suggests that in AD brain COX-1 and COX-2 are involved in inflammatory and regenerating pathways respectively. In this review we will discuss the role of COX-1 and COX-2 in the different stages of AD pathology. Understanding the physiological and pathological role of cyclooxygenase in AD pathology may facilitate the design of therapeutics for the treatment or prevention of AD.

  7. Oral pathology.

    Science.gov (United States)

    Niemiec, Brook A

    2008-05-01

    Oral disease is exceedingly common in small animal patients. In addition, there is a very wide variety of pathologies that are encountered within the oral cavity. These conditions often cause significant pain and/or localized and systemic infection; however, the majority of these conditions have little to no obvious clinical signs. Therefore, diagnosis is not typically made until late in the disease course. Knowledge of these diseases will better equip the practitioner to effectively treat them. This article covers the more common forms of oral pathology in the dog and cat, excluding periodontal disease, which is covered in its own chapter. The various pathologies are presented in graphic form, and the etiology, clinical signs, recommended diagnostic tests, and treatment options are discussed. Pathologies that are covered include: persistent deciduous teeth, fractured teeth, intrinsically stained teeth, feline tooth resorption, caries, oral neoplasia, eosinophilic granuloma complex, lymphoplasmacytic gingivostomatitis, enamel hypoplasia, and "missing" teeth.

  8. Pathology Milestones

    Directory of Open Access Journals (Sweden)

    J. Stacey Klutts MD, PhD

    2015-10-01

    Full Text Available All Accreditation Council for Graduate Medical Education accredited pathology residency training programs are now required to evaluate residents using the new Pathology Milestones assessment tool. Similar to implementation of the 6 Accreditation Council for Graduate Medical Education competencies a decade ago, there have been challenges in implementation of the new milestones for many residency programs. The pathology department at the University of Iowa has implemented a process that divides the labor of the task in rating residents while also maintaining consistency in the process. The process is described in detail, and some initial trends in milestone evaluation are described and discussed. Our experience indicates that thoughtful implementation of the Pathology Milestones can provide programs with valuable information that can inform curricular changes.

  9. Comparison of {sup 11}C-PiB and {sup 18}F-florbetaben for A{beta} imaging in ageing and Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Villemagne, Victor L. [Austin Health, Department of Nuclear Medicine and Centre for PET, Heidelberg, VIC (Australia); University of Melbourne, Department of Medicine, Parkville, VIC (Australia); The Mental Health Research Institute of Victoria, Parkville, VIC (Australia); Mulligan, Rachel S.; Pejoska, Svetlana; Ong, Kevin; Jones, Gareth; O' Keefe, Graeme; Chan, J.G.; Young, Kenneth; Tochon-Danguy, Henri [Austin Health, Department of Nuclear Medicine and Centre for PET, Heidelberg, VIC (Australia); Masters, Colin L. [The Mental Health Research Institute of Victoria, Parkville, VIC (Australia); Rowe, Christopher C. [Austin Health, Department of Nuclear Medicine and Centre for PET, Heidelberg, VIC (Australia); University of Melbourne, Department of Medicine, Parkville, VIC (Australia)

    2012-06-15

    Amyloid imaging with {sup 18}F-labelled radiotracers will allow widespread use of this technique, facilitating research, diagnosis and therapeutic development for Alzheimer's disease (AD). The purpose of this analysis was to compare data on cortical A{beta} deposition in subjects who had undergone both {sup 11}C-PiB (PiB) and {sup 18}F-florbetaben (FBB) PET imaging. We identified ten healthy elderly controls (HC) and ten patients with AD who had undergone PET imaging after intravenous injection of 370 MBq of PiB and 300 MBq of FBB under separate research protocols. PiB and FBB images were coregistered so that placement of regions of interest was identical on both scans and standard uptake value ratios (SUVR) using the cerebellar cortex as reference region were calculated between 40 and 70 min and between 90 and 110 min after injection for PiB and FBB, respectively. Significantly higher SUVR values (p < 0.0001) in most cortical areas were observed in AD patients when compared with HC with both radiotracers. Global SUVR values in AD patients were on average 75% higher than in HC with PiB and 56% higher with FBB. There was an excellent linear correlation between PiB and FBB global SUVR values (r = 0.97, p < 0.0001) with similar effect sizes for distinguishing AD from HC subjects for both radiotracers (Cohen's d 3.3 for PiB and 3.0 for FBB). FBB, while having a narrower dynamic range than PiB, clearly distinguished HC from AD patients, with a comparable effect size. FBB seems a suitable {sup 18}F radiotracer for imaging AD pathology in vivo. (orig.)

  10. Concordant association of insulin degrading enzyme gene (IDE variants with IDE mRNA, Abeta, and Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Minerva M Carrasquillo

    Full Text Available BACKGROUND: The insulin-degrading enzyme gene (IDE is a strong functional and positional candidate for late onset Alzheimer's disease (LOAD. METHODOLOGY/PRINCIPAL FINDINGS: We examined conserved regions of IDE and its 10 kb flanks in 269 AD cases and 252 controls thereby identifying 17 putative functional polymorphisms. These variants formed eleven haplotypes that were tagged with ten variants. Four of these showed significant association with IDE transcript levels in samples from 194 LOAD cerebella. The strongest, rs6583817, which has not previously been reported, showed unequivocal association (p = 1.5x10(-8, fold-increase = 2.12,; the eleven haplotypes were also significantly associated with transcript levels (global p = 0.003. Using an in vitro dual luciferase reporter assay, we found that rs6583817 increases reporter gene expression in Be(2-C (p = 0.006 and HepG2 (p = 0.02 cell lines. Furthermore, using data from a recent genome-wide association study of two Croatian isolated populations (n = 1,879, we identified a proxy for rs6583817 that associated significantly with decreased plasma Abeta40 levels (ss = -0.124, p = 0.011 and total measured plasma Abeta levels (b = -0.130, p = 0.009. Finally, rs6583817 was associated with decreased risk of LOAD in 3,891 AD cases and 3,605 controls. (OR = 0.87, p = 0.03, and the eleven IDE haplotypes (global p = 0.02 also showed significant association. CONCLUSIONS: Thus, a previously unreported variant unequivocally associated with increased IDE expression was also associated with reduced plasma Abeta40 and decreased LOAD susceptibility. Genetic association between LOAD and IDE has been difficult to replicate. Our findings suggest that targeted testing of expression SNPs (eSNPs strongly associated with altered transcript levels in autopsy brain samples may be a powerful way to identify genetic associations with LOAD that would otherwise be difficult to detect.

  11. Digital pathology

    CERN Document Server

    Sucaet, Yves

    2014-01-01

    Digital pathology has experienced exponential growth, in terms of its technology and applications, since its inception just over a decade ago. Though it has yet to be approved for primary diagnostics, its values as a teaching tool, facilitator of second opinions and quality assurance reviews and research are becoming, if not already, undeniable. It also offers the hope of providing pathology consultant and educational services to under-served areas, including regions of the world that could not possibly sustain this level of services otherwise. And this is just the beginning, as its adoption b

  12. 鲜人参及其加工品中腺苷和L-焦谷氨酸含量比较研究%Comparative Study on Adenosine and L-pyroglutamic Acid Content of Fresh Ginseng and Its Processed Products

    Institute of Scientific and Technical Information of China (English)

    马东升; 高飞飞; 李伟; 弓晓杰; 郑毅男

    2013-01-01

    以六年生鲜人参、生晒参、红参为试验材料,建立腺苷和L-焦谷氨酸的含量测定方法:RP-HPLC法分析样品中腺苷含量,依利特Hypersil ODS2(4.6 mm× 250 mm,5μm)色谱柱,流动相为甲醇—水(10∶90),流速0.8mL/min,检测波长260 nm,柱温40℃;RP-HPLC法分析样品中L-焦谷氨酸含量,COSMOSIL 5C18-PAQ(4.6 mm× 250 mm,5μm)色谱柱,流动相为甲醇—5 mmol/L醋酸钠水溶液(8∶92),流速0.5 mL/min,检测波长210 nm,柱温40℃.测得鲜人参及其加工品中腺苷含量为0.332 ~ 0.457 mg/g,L-焦谷氨酸含量为0.315 ~1.056 mg/g.结果表明:腺苷和L焦谷氨酸含量在鲜人参及其加工品中呈规律性变化,鲜人参中腺苷和L-焦谷氨酸含量最高,加工品次之.因此在抗糖尿病活性方面,鲜人参较其加工品应更具研究价值.%This study is to establish the methods for assaying adenosine and L-pyroglutamic acid in ginseng. Six-year-old fresh ginseng, sun-dried ginseng and red ginseng were used as materials. RP- HPLC was used to analyze adenosine in samples. Separation was carried out using a chromatographic column (Hypersil ODS2, 4.6 mm×250 mm, 5 μm). Column temperature and detection wavelength were set at 40℃ and 260 nm, respectively. Mobile phase containing methanol-water (10:90) was used and the flow rate was 0.8 mL/min. Chromatographic column (COSMOSIL 5C18-PAQ, 4.6 mm×250 mm, 5 μm) was applied to analyze L-pyroglutamic acid in ginseng. Mobile phase contained methanol-sodium acetate water solution of 5 mmol/L (8:92), and the flow rate was 0.5 mL/min. Column temperature and detection wavelength for analyzing L-pyroglutamic acid were set at 40℃ and 210 nm, respectively. Adenosine in fresh ginseng and its processed products ranged from 0.332 mg/g to 0.457 mg/g, the amount of L-pyroglutamic acid ranged from 0.315 mg/g to 1.056 mg/g. The results showed that: the amount of adenosine and L-pyroglutamic acid showed regular changes in fresh ginseng and its processed

  13. Inguinoscrotal pathology

    Science.gov (United States)

    Guerra, Luis; Leonard, Michael

    2017-01-01

    Infants, children, and adolescents with inguinoscrotal pathology comprise a significant proportion of emergency department and outpatient visits. Visits to the emergency department primarily comprise individuals presenting with scrotal pain due to testicular torsion or torsion of the testicular appendages. At such time, immediate urological consultation is sought. Outpatient visits comprise those individuals with undescended testes, hydroceles, and varicoceles. Rare, but important problems, such as pediatric testicular tumours, may also present in the office setting. Many of these outpatient visits are to primary care physicians, who should have an appreciation of the timing and need for referral. The purpose of this review is to familiarize the general urologist and primary care physician with these varied pathologies and give insight into their assessment and management. Some of these same conditions are seen in adult patients, but there are some significant differences in their management in the pediatric group. In addition, the utility of imaging studies, such as ultrasound, are discussed within each pathological entity. It is hoped that this overview will assist our general urology and primary care colleagues in patient management for diverse inguinoscrotal pathologies. PMID:28265317

  14. Study on the content determination of pyroglutamic acid in Cornu caprae hircus's extraction%山羊角提取物中焦谷氨酸含量测定研究

    Institute of Scientific and Technical Information of China (English)

    李江海; 王伯初; 王建; 刘绍勇; 薛东升

    2011-01-01

    Objective:Study on the content determination of pyroglutamic acid in cornu caprae hircus. Methods: Through automatic amino acid analyzer and fourier transform ion cyclotron resonance mass spectrometry to determine Cornu caprae hircus's extraction contain pyroglutamic acid. And develop an special method for detection of pyroglutamic acid by using high performance liquid chromatography ( HPLC). HPLC method: Sionchrom ODS - BP column (200 mm ×4. 6 mm,5 μm),acetonitrile -3. 5 mmol · L-1 phosphate buffer(1:99) adjusted to pH 3 as mobile phase, the flow rate was 1. 0 mL · Min -1, detection wavelength was set at 205 nm, the temperature of column was 27 ℃. Results:The detected ion peaks was m/z 128 by ESI/MS high - resolution spectrum. Moreover,the results showed that the content of pyroglutamic acid in the Cornu caprae hircus's Extraction was 7. 65%. Conclusion: The detection method was rapid and stable. It can improve the examination standard of Cornu caprae hircus's extraction.%目的:对山羊角提取物中的焦谷氨酸进行含量测定研究.方法:通过氨基酸自动分析仪及傅立叶变换离子回旋共振质谱确认山羊角提取物中含有焦谷氨酸,并建立专属高效液相色谱方法对焦谷氨酸进行含量检测.色谱条件为:色谱柱为Sionchrom ODS- BP(200 mm ×4.6 mm,5μm),流动相为乙腈-3.5 mmol·L-1磷酸氢二钠缓冲液(1∶99),调pH =3,流速为1.0mL·min -1,检测波长205 nm,柱温27℃.结果:高分辨质谱有m/z128离子峰,并且检测出该批山羊角提取物中含有焦谷氨酸7.65%.结论:所建立的方法可快速、稳定地检测山羊角提取物中的焦谷氨酸,从而有效提高山羊角提取物的检测标准.

  15. The amyloid pathology progresses in a neurotransmitter-specific manner.

    Science.gov (United States)

    Bell, Karen F S; Ducatenzeiler, Adriana; Ribeiro-da-Silva, Alfredo; Duff, Karen; Bennett, David A; Cuello, A Claudio

    2006-11-01

    Past studies using transgenic models of early-staged amyloid pathology, have suggested that the amyloid pathology progresses in a neurotransmitter-specific manner where cholinergic terminals appear most vulnerable, followed by glutamatergic terminals and finally by somewhat more resistant GABAergic terminals. To determine whether this neurotransmitter-specific progression persists at later pathological stages, presynaptic bouton densities, and the areas of occupation and localization of plaque adjacent dystrophic neurites were quantified in 18-month-old APP(K670N, M671L)+PS1(M146L) doubly transgenic mice. Quantification revealed that transgenic animals had significantly lower cholinergic, glutamatergic and GABAergic presynaptic bouton densities. Cholinergic and glutamatergic dystrophic neurites appear to be heavily influenced by fibrillar Abeta as both types displayed a decreasing area of occupation with respect to increasing plaque size. Furthermore, cholinergic dystrophic neurites reside in closer proximity to plaques than glutamatergic dystrophic neurites, while GABAergic dystrophic neurites were minimal regardless of plaque size. To investigate whether similarities exist in the human AD pathology, a monoclonal antibody (McKA1) against the human vesicular glutamate transporter 1 (VGluT1) was developed. Subsequent staining in AD brain tissue revealed the novel presence of glutamatergic dystrophic neurites, to our knowledge the first evidence of a structural glutamatergic deficit in the AD pathology.

  16. Aluminium and iron, but neither copper nor zinc, are key to the precipitation of beta-sheets of Abeta_{42} in senile plaque cores in Alzheimer's disease.

    Science.gov (United States)

    Exley, Christopher

    2006-11-01

    A number of metals including Fe(II)/Fe(III), Al(III), Zn(II) and Cu(II) are found co-localised with beta-sheets of Abeta_{42} in senile plaque cores in AD brain. We know neither why nor how the co-localisation takes place or, indeed, if it is entirely aberrant or partly protective. There are data from in vitro studies which may begin to explain some of these unanswered questions and in considering these I have summised that Al(III) and Fe(III)/Fe(II) are directly involved in the precipitation of beta-sheets of Abeta_{42} in senile plaque cores whereas the presence of Cu(II) and Zn(II) is adventitious. The co-deposition of Al(III), Fe(III) and beta-sheets of Abeta_{42} could act as a source of reactive oxygen species and begin to explain some of the oxidative damage found in the immediate vicinity of senile plaques. Whether such metal-Abeta_{42} synergisms are an integral part of the aetiology of AD remains to be confirmed.

  17. Receptor-associated protein (RAP plays a central role in modulating Abeta deposition in APP/PS1 transgenic mice.

    Directory of Open Access Journals (Sweden)

    Guilian Xu

    Full Text Available BACKGROUND: Receptor associated protein (RAP functions in the endoplasmic reticulum (ER to assist in the maturation of several membrane receptor proteins, including low density lipoprotein receptor-related protein (LRP and lipoprotein receptor 11 (SorLA/LR11. Previous studies in cell and mouse model systems have demonstrated that these proteins play roles in the metabolism of the amyloid precursor protein (APP, including processes involved in the generation, catabolism and deposition of beta-amyloid (Abeta peptides. METHODOLOGY/PRINCIPAL FINDINGS: Mice transgenic for mutant APPswe and mutant presenilin 1 (PS1dE9 were mated to mice with homozygous deletion of RAP. Unexpectedly, mice that were homozygous null for RAP and transgenic for APPswe/PS1dE9 showed high post-natal mortality, necessitating a shift in focus to examine the levels of amyloid deposition in APPswe/PS1dE9 that were hemizygous null for RAP. Immunoblot analysis confirmed 50% reductions in the levels of RAP with modest reductions in the levels of proteins dependent upon RAP for maturation [LRP trend towards a 20% reduction ; SorLA/LR11 statistically significant 15% reduction (p<0.05]. Changes in the levels of these proteins in the brains of [APPswe/PS1dE9](+/-/RAP(+/- mice correlated with 30-40% increases in amyloid deposition by 9 months of age. CONCLUSIONS/SIGNIFICANCE: Partial reductions in the ER chaperone RAP enhance amyloid deposition in the APPswe/PS1dE9 model of Alzheimer amyloidosis. Partial reductions in RAP also affect the maturation of LRP and SorLA/LR11, which are each involved in several different aspects of APP processing and Abeta catabolism. Together, these findings suggest a central role for RAP in Alzheimer amyloidogenesis.

  18. Receptor-associated protein (RAP) plays a central role in modulating Abeta deposition in APP/PS1 transgenic mice.

    Science.gov (United States)

    Xu, Guilian; Karch, Celeste; Li, Ning; Lin, Nianwei; Fromholt, David; Gonzales, Victoria; Borchelt, David R

    2008-09-08

    Receptor associated protein (RAP) functions in the endoplasmic reticulum (ER) to assist in the maturation of several membrane receptor proteins, including low density lipoprotein receptor-related protein (LRP) and lipoprotein receptor 11 (SorLA/LR11). Previous studies in cell and mouse model systems have demonstrated that these proteins play roles in the metabolism of the amyloid precursor protein (APP), including processes involved in the generation, catabolism and deposition of beta-amyloid (Abeta) peptides. Mice transgenic for mutant APPswe and mutant presenilin 1 (PS1dE9) were mated to mice with homozygous deletion of RAP. Unexpectedly, mice that were homozygous null for RAP and transgenic for APPswe/PS1dE9 showed high post-natal mortality, necessitating a shift in focus to examine the levels of amyloid deposition in APPswe/PS1dE9 that were hemizygous null for RAP. Immunoblot analysis confirmed 50% reductions in the levels of RAP with modest reductions in the levels of proteins dependent upon RAP for maturation [LRP trend towards a 20% reduction ; SorLA/LR11 statistically significant 15% reduction (pRAP(+/-) mice correlated with 30-40% increases in amyloid deposition by 9 months of age. Partial reductions in the ER chaperone RAP enhance amyloid deposition in the APPswe/PS1dE9 model of Alzheimer amyloidosis. Partial reductions in RAP also affect the maturation of LRP and SorLA/LR11, which are each involved in several different aspects of APP processing and Abeta catabolism. Together, these findings suggest a central role for RAP in Alzheimer amyloidogenesis.

  19. Combining the rapid MTT formazan exocytosis assay and the MC65 protection assay led to the discovery of carbazole analogs as small molecule inhibitors of Abeta oligomer-induced cytotoxicity.

    Science.gov (United States)

    Hong, Hyun-Seok; Maezawa, Izumi; Yao, Nianhuan; Xu, Bailing; Diaz-Avalos, Ruben; Rana, Sandeep; Hua, Duy H; Cheng, R Holland; Lam, Kit S; Jin, Lee-Way

    2007-01-26

    The discovery of small molecule inhibitors of cytotoxicity induced by amyloid-beta (Abeta) oligomers, either applied extracellularly or accumulated intraneuronally, is an important goal of drug development for Alzheimer's disease (AD), but has been limited by the lack of efficient screening methods. Here we describe our approach using two cell-based methods. The first method takes advantage of the unique ability of extracellularly applied Abeta oligomers to rapidly induce the exocytosis of formazan formed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). We employed a short protocol to quantify this toxicity, and quickly identified two novel inhibitors, code-named CP2 and A5, from two compound libraries. A second independent screen of the same libraries using our previously published MC65 protection assay, which identifies inhibitors of toxicity related to intracellular Abeta oligomers, also selected the same two leads, suggesting that both assays select for the same anti-Abeta oligomer properties displayed by these compounds. We further demonstrated that A5 attenuated the progressive aggregation of existing Abeta oligomers, reduced the level of intracellular Abeta oligomers, and prevented the Abeta oligomer-induced death of primary cortical neurons, effects similar to those demonstrated by CP2. Our results suggest that, when combined, the two methods would generate fewer false results and give a high likelihood of identifying leads that show promises in ameliorating Abeta oligomer-induced toxicities within both intraneuronal and extracellular sites. Both assays are simple, suitable for rapid screening of a large number of medicinal libraries, and amenable for automation.

  20. Tau neurofibrillary pathology and microtubule stability.

    Science.gov (United States)

    Michaelis, Mary L; Dobrowsky, Rick T; Li, Guibin

    2002-12-01

    We previously reported that nonomolar concentrations of Taxol and several structurally diverse microtubule (MT)-stabilizing agents significantly enhanced the survival of neurons in the presence of fibrils of amyloid beta peptide (Abeta). Pretreatment of neurons with MT-stabilizing drugs also blocked Abeta-induced activation of tau hyperphosphorylation. Although tau is a substrate for several kinases, we initially focused on cdk5, as this tau kinase has been shown to be activated in Abeta-treated neurons and Alzheimer's disease (AD) brain. In an in vitro kinase assay, Taxol inhibited activation of cdk5 by Abeta. In addition, the proposed cellular cascade in which calpain activation leads to cleavage of the cdk5 regulator, p35, to the strong kinase activator p25 was also prevented. Taxol did not directly inhibit the activity of either cdk5 or calpain, indicating that other cellular components are required for the effect of the drug on Abeta activation of tau phosphorylation. Our results suggest that drugs that interact with MTs can alter signaling events in neurons, possibly because some MTs play a role in organizing protein complexes involved in responses to Abeta. Thus the cytoskeletal network may serve as a biosensor of cellular well-being.

  1. Plaque deposition dependent decrease in 5-HT2A serotonin receptor in AbetaPPswe/PS1dE9 amyloid overexpressing mice

    DEFF Research Database (Denmark)

    Holm, Peter; Ettrup, Anders; Klein, Anders B

    2010-01-01

    -HT2A receptor regulation in double transgenic AbetaPPswe/PS1dE9 mice which display excess production of Abeta and age-dependent increase in amyloid plaques. Three different age-groups, 4-month-old, 8- month-old, and 11-month-old were included in the study. [3H]-MDL100907, [3H]-escitalopram, and [11C]-PIB...... in 5-HT2A receptor binding in mPFC in the 11-month-old group. The changes in 5-HT2A receptor binding correlated negatively with [11C]-PIB binding and were not accompanied by decreases in SERT binding. Correspondingly, 11-month-old transgenic mice showed diminished DOI-induced HTR and reduced increase...

  2. Molecular structures of quiescently grown and brain-derived polymorphic fibrils of the Alzheimer amyloid abeta9-40 peptide: a comparison to agitated fibrils.

    Directory of Open Access Journals (Sweden)

    Chun Wu

    2010-03-01

    Full Text Available The presence of amyloid deposits consisting primarily of Amyloid-beta (Abeta fibril in the brain is a hallmark of Alzheimer's disease (AD. The morphologies of these fibrils are exquisitely sensitive to environmental conditions. Using molecular dynamics simulations combined with data from previously published solid-state NMR experiments, we propose the first atomically detailed structures of two asymmetric polymorphs of the Abeta(9-40 peptide fibril. The first corresponds to synthetic fibrils grown under quiescent conditions and the second to fibrils derived from AD patients' brain-extracts. Our core structure in both fibril structures consists of a layered structure in which three cross-beta subunits are arranged in six tightly stacked beta-sheet layers with an antiparallel hydrophobic-hydrophobic and an antiparallel polar-polar interface. The synthetic and brain-derived structures differ primarily in the side-chain orientation of one beta-strand. The presence of a large and continually exposed hydrophobic surface (buried in the symmetric agitated Abeta fibrils may account for the higher toxicity of the asymmetric fibrils. Our model explains the effects of external perturbations on the fibril lateral architecture as well as the fibrillogenesis inhibiting action of amphiphilic molecules.

  3. Experimental diabetes mellitus exacerbates tau pathology in a transgenic mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Yazi D Ke

    Full Text Available Diabetes mellitus (DM is characterized by hyperglycemia caused by a lack of insulin, insulin resistance, or both. There is increasing evidence that insulin also plays a role in Alzheimer's disease (AD as it is involved in the metabolism of beta-amyloid (Abeta and tau, two proteins that form Abeta plaques and neurofibrillary tangles (NFTs, respectively, the hallmark lesions in AD. Here, we examined the effects of experimental DM on a pre-existing tau pathology in the pR5 transgenic mouse strain that is characterized by NFTs. pR5 mice express P301L mutant human tau that is associated with dementia. Experimental DM was induced by administration of streptozotocin (STZ, which causes insulin deficiency. We determined phosphorylation of tau, using immunohistochemistry and Western blotting. Solubility of tau was determined upon extraction with sarkosyl and formic acid, and Gallyas silver staining was employed to reveal NFTs. Insulin depletion by STZ administration in six months-old non-transgenic mice causes increased tau phosphorylation, without its deposition or NFT formation. In contrast, in pR5 mice this results in massive deposition of hyperphosphorylated, insoluble tau. Furthermore, they develop a pronounced tau-histopathology, including NFTs at this early age, while the pathology in sham-treated pR5 mice is moderate. Whereas experimental DM did not result in deposition of hyperphosphorylated tau in non-transgenic mice, a predisposition to develop a tau pathology in young pR5 mice was both sufficient and necessary to exacerbate tau deposition and NFT formation. Hence, DM can accelerate onset and increase severity of disease in individuals with a predisposition to developing tau pathology.

  4. The iA{beta}5p {beta}-breaker peptide regulates the A{beta}(25-35) interaction with lipid bilayers through a cholesterol-mediated mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Vitiello, Giuseppe [Department of Chemistry, University of Naples ' Federico II' , Naples (Italy); CSGI (Consorzio per lo Sviluppo dei Sistemi a Grande Interfase), Florence (Italy); Grimaldi, Manuela; D' Ursi, Anna Maria [Department of Pharmaceutical Science, University of Salerno, Fisciano (Italy); D' Errico, Gerardino, E-mail: gerardino.derrico@unina.it [Department of Chemistry, University of Naples ' Federico II' , Naples (Italy); CSGI (Consorzio per lo Sviluppo dei Sistemi a Grande Interfase), Florence (Italy)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer iA{beta}5p shows a significant tendency to deeply penetrates the hydrophobic core of lipid membrane. Black-Right-Pointing-Pointer A{beta}(25-35) locates in the external region of the membrane causing a re-positioning of CHOL. Black-Right-Pointing-Pointer iA{beta}5p withholds cholesterol in the inner hydrophobic core of the lipid membrane. Black-Right-Pointing-Pointer iA{beta}5p prevents the A{beta}(25-35) release from the lipid membrane. -- Abstract: Alzheimer's disease is characterized by the deposition of aggregates of the {beta}-amyloid peptide (A{beta}) in the brain. A potential therapeutic strategy for Alzheimer's disease is the use of synthetic {beta}-sheet breaker peptides, which are capable of binding A{beta} but unable to become part of a {beta}-sheet structure, thus inhibiting the peptide aggregation. Many studies suggest that membranes play a key role in the A{beta} aggregation; consequently, it is strategic to investigate the interplay between {beta}-sheet breaker peptides and A{beta} in the presence of lipid bilayers. In this work, we focused on the effect of the {beta}-sheet breaker peptide acetyl-LPFFD-amide, iA{beta}5p, on the interaction of the A{beta}(25-35) fragment with lipid membranes, studied by Electron Spin Resonance spectroscopy, using spin-labeled membrane components (either phospholipids or cholesterol). The ESR results show that iA{beta}5p influences the A{beta}(25-35) interaction with the bilayer through a cholesterol-mediated mechanism: iA{beta}5p withholds cholesterol in the inner hydrophobic core of the bilayer, making the interfacial region more fluid and capable to accommodate A{beta}(25-35). As a consequence, iA{beta}5p prevents the A{beta}(25-35) release from the lipid membrane, which is the first step of the {beta}-amyloid aggregation process.

  5. Curriculum Guidelines for Pathology and Oral Pathology.

    Science.gov (United States)

    Journal of Dental Education, 1985

    1985-01-01

    Guidelines for dental school pathology courses describe the interrelationships of general, systemic, and oral pathology; primary educational goals; prerequisites; a core curriculum outline and behavioral objectives for each type of pathology. Notes on sequencing, faculty, facilities, and occupational hazards are included. (MSE)

  6. Disrupted cross-laminar cortical processing in β amyloid pathology precedes cell death.

    Science.gov (United States)

    Lison, H; Happel, M F K; Schneider, F; Baldauf, K; Kerbstat, S; Seelbinder, B; Schneeberg, J; Zappe, M; Goldschmidt, J; Budinger, E; Schröder, U H; Ohl, F W; Schilling, S; Demuth, H-U; Scheich, H; Reymann, K G; Rönicke, R

    2014-03-01

    Disruption of neuronal networks in the Alzheimer-afflicted brain is increasingly recognized as a key correlate of cognitive and memory decline in Alzheimer patients. We hypothesized that functional synaptic disconnections within cortical columnar microcircuits by pathological β-amyloid accumulation, rather than cell death, initially causes the cognitive impairments. During development of cortical β-amyloidosis with still few plaques in the transgenic 5xFAD mouse model single cell resolution mapping of neuronal thallium uptake revealed that electrical activity of pyramidal cells breaks down throughout infragranular cortical layer V long before cell death occurs. Treatment of 5xFAD mice with the glutaminyl cyclase inhibitor, PQ 529, partially prevented the decline of pyramidal cell activity, indicating pyroglutamate-modified forms, potentially mixed oligomers of Aβ are contributing to neuronal impairment. Laminar investigation of cortical circuit dysfunction with current source density analysis identified an early loss of excitatory synaptic input in infragranular layers, linked to pathological recurrent activations in supragranular layers. This specific disruption of normal cross-laminar cortical processing coincided with a decline of contextual fear learning. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Aluminum exposure through the diet: metal levels in AbetaPP transgenic mice, a model for Alzheimer's disease.

    Science.gov (United States)

    Gómez, Mercedes; Esparza, José L; Cabré, María; García, Tania; Domingo, José L

    2008-07-30

    Aluminum (Al), iron (Fe), copper (Cu), and zinc (Zn) cause have been implicated in the etiology of certain neurodegenerative disorders. Moreover, these elements cause the conformational changes of Alzheimer's amyloid beta protein. In this study, we determined the concentrations of Al, Cu, Zn, Fe, and Mn in various tissues of Tg 2576 (AbetaPP transgenic) Al-treated mice. Female Tg 2576 mice and wild-type littermates were exposed through the diet to 1mg Al/g for 6 months. At 11 months of age, metal concentrations were measured in various tissues. In brain, Al levels were higher in hippocampus than in cortex and cerebellum. In hippocampus, Cu concentrations decreased in non-treated Tg 2576 mice, while Zn levels were higher in Al-treated mice. Copper, Zn, Mn and Fe concentrations in liver, kidney and bone were not affected by Al exposure. The current results show that Al exposure of Tg 2576 and wild-type mice did not produce important metal changes related with the genotype, responding similarly both groups of animals. As Tg 2576 mice have been considered as a potential model for Alzheimer's disease (AD), the present results would not support the hypothetical role of Al in the etiology of AD.

  8. pRB is required for interferon-gamma-induction of the MHC class II abeta gene.

    Science.gov (United States)

    Zhu, X; Pattenden, S; Bremner, R

    1999-09-02

    pRB is required for IFN-gamma-induction of MHC class II in human tumor cell lines, providing a potential link between tumor suppressors and the immune system. However, other genes, such as cyclin D1, show pRB-dependency only in tumor cells, so by analogy, pRB may not be necessary for cII-regulation in normal cells. Here, we demonstrate that induction of the mouse MHC class II I-A heterodimer is normal in RB+/+ mouse embryonic fibroblasts (MEFs), but deficient in RB-/- MEFs. Inducibility is restored in RB-/- MEFs stably transfected with wild type RB cDNA or infected with an adenovirus expressing pRB. Thus, involvement of pRB in MHC class II expression is conserved in the mouse and is not an aberrant feature of tumorigenic, aneuploid, human tumor cells. Although cII genes are generally induced in a coordinate fashion, suggesting a common mechanism, we found that pRB was specifically required for induction of the Abeta, but not Aalpha or other MHC cII genes including Ebeta, Ii and H2-Malpha. Finally, IFN-gamma-induction of class II transactivator (CIITA), was pRB-independent, suggesting that pRB works downstream of this master-regulator of MHC class II expression.

  9. Imaging of peripheral benzodiazepine receptor expression as biomarkers of detrimental versus beneficial glial responses in mouse models of Alzheimer's and other CNS pathologies.

    Science.gov (United States)

    Ji, Bin; Maeda, Jun; Sawada, Makoto; Ono, Maiko; Okauchi, Takashi; Inaji, Motoki; Zhang, Ming-Rong; Suzuki, Kazutoshi; Ando, Kiyoshi; Staufenbiel, Matthias; Trojanowski, John Q; Lee, Virginia M Y; Higuchi, Makoto; Suhara, Tetsuya

    2008-11-19

    We demonstrate the significance of peripheral benzodiazepine receptor (PBR) imaging in living mouse models of Alzheimer's disease (AD) as biomarkers and functional signatures of glial activation. By radiochemically and immunohistochemically analyzing murine models of the two pathological hallmarks of AD, we found that AD-like Abeta deposition is concurrent with astrocyte-dominant PBR expression, in striking contrast with nonastroglial PBR upregulation in accumulations of AD-like phosphorylated tau. Because tau-induced massive neuronal loss was distinct from the marginal neurodegeneration associated with Abeta plaques in these models, cellular localization of PBR reflected deleterious and beneficial glial reactions to tau versus Abeta pathologies, respectively. This notion was subsequently examined in models of various non-AD neuropathologies, revealing the following reactive glial dynamics underlying differential PBR upregulation: (1) PBR(-) astrogliosis uncoupled with microgliosis or coupled with PBR(+) microgliosis associated with irreversible neuronal insults; and (2) PBR(+) astrogliosis coupled with PBR(- or +/-) microgliosis associated with minimal or reversible neuronal toxicity. Intracranial transplantation of microglia also indicated that nontoxic microglia drives astroglial PBR expression. Moreover, levels of glial cell line-derived neurotrophic factor (GDNF) in astrocytes were correlated with astroglial PBR, except for increased GDNF in PBR(-) astrocytes in the model of AD-like tau pathology, thereby suggesting that PBR upregulation in astrocytes is an indicator of neurotrophic support. Together, PBR expressions in astrocytes and microglia reflect beneficial and deleterious glial reactions, respectively, in diverse neurodegenerative disorders including AD, pointing to new applications of PBR imaging for monitoring the impact of gliosis on the pathogenesis and treatment of AD.

  10. Effects of Abeta1-42 fibrils and of the tetrapeptide Pr-IIGL on the phosphorylation state of the tau-protein and on the alpha7 nicotinic acetylcholine receptor in vitro.

    Science.gov (United States)

    Lain, Enzo; Penke, Botond; Delacourte, André; Gündisch, Daniela; Schröder, Hannsjörg; Witter, Brigitte

    2005-02-01

    In order to investigate the possible links connecting beta-amyloid (Abeta) accumulation, tau-hyperphosphorylation and nicotinic receptor expression, rat embryonic primary hippocampal cultures were incubated with amyloidogenic peptides. Exposure to 0.5 microm fibrillar Abeta(1-42) for 3 days caused retraction of dendrites, shrinkage of cell bodies and a decrease in the expression of microtubule-associated proteins 2b (MAP2b), without affecting the total number of neurons and their viability. No impact on the tau-phosphorylation sites Ser-202, Thr231/Ser235, Ser262 and Ser396/Ser404 was found. The total number of homomeric alpha7-nicotinic receptors (alpha7-nAChRs) and their affinity for [(125)I]alpha-bungarotoxin remained unaltered. Upon incubation with the putatively protective tetrapeptide propionyl-isoleucine-isoleucine-glycine-leucine (Pr-IIGL), an analogue of the region [31-34] of Abeta, cell bodies were swollen in the region of the apical dendrite. These morphological alterations, different from those elicited by Abeta(1-42), did not involve MAP2 expression changes. In contrast to Abeta(1-42), Pr-IIGL caused a massive hyperphosphorylation of the tau-protein at Ser-202 and at Ser396/Ser404. The total number of homomeric alpha7-nAChRs and their affinity for [(125)I]alpha-bungarotoxin were unaffected. In conclusion, the present results show a toxic effect of Abeta(1-42) on the cytoskeletal structure at concentrations normally present in the brains of Alzheimer's disease patients, but raise some doubts about the role of Abeta(1-42) fibrils as a direct trigger of tau-hyperphosphorylation. The tetrapeptide Pr-IIGL cannot be considered protective with regard to cell morphology. Although it prevents the Abeta(1-42)-induced retraction of dendrites, it exhibits other toxic properties. The homomeric alpha7-nAChRs were not affected either by Abeta(1-42) incubation or by Pr-IIGL-induced tau-hyperphosphorylation.

  11. The Danish Pathology Register

    DEFF Research Database (Denmark)

    Bjerregaard, Beth; Larsen, Ole B

    2011-01-01

    The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established.......The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established....

  12. Curcumin promotes A-beta fibrillation and reduces neurotoxicity in transgenic Drosophila.

    Directory of Open Access Journals (Sweden)

    Ina Caesar

    Full Text Available The pathology of Alzheimer's disease (AD is characterized by the presence of extracellular deposits of misfolded and aggregated amyloid-β (Aβ peptide and intraneuronal accumulation of tangles comprised of hyperphosphorylated Tau protein. For several years, the natural compound curcumin has been proposed to be a candidate for enhanced clearance of toxic Aβ amyloid. In this study we have studied the potency of feeding curcumin as a drug candidate to alleviate Aβ toxicity in transgenic Drosophila. The longevity as well as the locomotor activity of five different AD model genotypes, measured relative to a control line, showed up to 75% improved lifespan and activity for curcumin fed flies. In contrast to the majority of studies of curcumin effects on amyloid we did not observe any decrease in the amount of Aβ deposition following curcumin treatment. Conformation-dependent spectra from p-FTAA, a luminescent conjugated oligothiophene bound to Aβ deposits in different Drosophila genotypes over time, indicated accelerated pre-fibrillar to fibril conversion of Aβ(1-42 in curcumin treated flies. This finding was supported by in vitro fibrillation assays of recombinant Aβ(1-42. Our study shows that curcumin promotes amyloid fibril conversion by reducing the pre-fibrillar/oligomeric species of Aβ, resulting in a reduced neurotoxicity in Drosophila.

  13. Forensic Pathology Education in Pathology Residency

    Science.gov (United States)

    Ross, Wayne K.; Domen, Ronald E.

    2017-01-01

    Forensic pathology is a fundamental part of anatomic pathology training during pathology residency. However, the lack of information on forensic teaching suggests the highly variable nature of forensic education. A survey of pathology residency program directors was performed to determine key aspects of their respective forensic rotations and curriculum. A total of 38.3% of programs from across the country responded, and the survey results show 5.6% don’t require a forensic pathology rotation. In those that do, most forensic pathology rotations are 4 weeks long, are done at a medical examiner’s office, and require set prerequisites. A total of 21.1% of responding programs have residents who are not receiving documented evaluations for this rotation. While 39.6% of programs have a defined forensics curriculum, as many as 15% do not. Furthermore, nearly 43% of programs place no limit on counting forensic autopsies when applying for pathology board examinations. Our survey confirmed the inconsistent nature of forensic pathology training in resident education. Additionally, our curriculum was reorganized to create a more robust educational experience. A pre- and post-forensic lecture quiz and Resident In-Service Examination scores were analyzed to determine our curriculum’s impact and effectiveness. Analysis of our pre- and post-lecture quiz showed an improved overall average as well as an increase in Resident In-Service Examination scores, indicating improved general forensic pathology knowledge. Using this knowledge, along with changes in our curriculum, we generated a number of recommendations for improving forensic pathology education in pathology residency. PMID:28913415

  14. Differential protection among fractionated blueberry polyphenolic families against DA-, Abeta(42)- and LPS-induced decrements in Ca(2+) buffering in primary hippocampal cells.

    Science.gov (United States)

    Joseph, James A; Shukitt-Hale, Barbara; Brewer, Gregory J; Weikel, Karen A; Kalt, Wilhelmina; Fisher, Derek R

    2010-07-28

    It has been postulated that at least part of the loss of cognitive function in aging may be the result of deficits in Ca(2+) recovery (CAR) and increased oxidative/inflammatory (OX/INF) stress signaling. However, previous research showed that aged animals supplemented with blueberry (BB) extract showed fewer deficits in CAR, as well as motor and cognitive functional deficits. A recent subsequent experiment has shown that DA- or Abeta(42)-induced deficits in CAR in primary hippocampal neuronal cells (HNC) were antagonized by BB extract, and (OX/INF) signaling was reduced. The present experiments assessed the most effective BB polyphenol fraction that could protect against OX/INF-induced deficits in CAR, ROS generation, or viability. HNCs treated with BB extract, BB fractions (e.g., proanthocyanidin, PAC), or control medium were exposed to dopamine (DA, 0.1 mM), amyloid beta (Abeta(42), 25 muM) or lipopolysaccharide (LPS, 1 microg/mL). The results indicated that the degree of protection against deficits in CAR varied as a function of the stressor and was generally greater against Abeta(42) and LPS than DA. The whole BB, anthocyanin (ANTH), and PRE-C18 fractions offered the greatest protection, whereas chlorogenic acid offered the lowest protection. Protective capabilities of the various fractions against ROS depended upon the stressor, where the BB extract and the combined PAC (high and low molecular weight) fraction offered the best protection against LPS and Abeta(42) but were less effective against DA-induced ROS. The high and low molecular weight PACs and the ANTH fractions enhanced ROS production regardless of the stressor used, and this reflected increased activation of stress signals (e.g., P38 MAPK). The viability data indicated that the whole BB and combined PAC fraction showed greater protective effects against the stressors than the more fractionated polyphenolic components. Thus, these results suggest that, except for a few instances, the lesser the

  15. Comparison of the binding characteristics of [{sup 18}F]THK-523 and other amyloid imaging tracers to Alzheimer's disease pathology

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Ryuichi; Okamura, Nobuyuki; Yoshikawa, Takeo; Yanai, Kazuhiko [Tohoku University School of Medicine, Department of Pharmacology, Sendai (Japan); Furumoto, Shozo [Tohoku University School of Medicine, Department of Pharmacology, Sendai (Japan); Tohoku University, Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Sendai (Japan); Tago, Tetsuro; Iwata, Ren [Tohoku University, Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Sendai (Japan); Maruyama, Masahiro; Higuchi, Makoto [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba (Japan); Arai, Hiroyuki [Tohoku University, Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Sendai (Japan); Kudo, Yukitsuka [Tohoku University, Innovation of New Biomedical Engineering Center, Sendai (Japan)

    2013-01-15

    Extensive deposition of senile plaques and neurofibrillary tangles in the brain is a pathological hallmark of Alzheimer's disease (AD). Although several PET imaging agents have been developed for in vivo detection of senile plaques, no PET probe is currently available for selective detection of neurofibrillary tangles in the living human brain. Recently, [{sup 18}F]THK-523 was developed as a potential in vivo imaging probe for tau pathology. The purpose of this study was to compare the binding properties of [{sup 18}F]THK-523 and other amyloid imaging agents, including PiB, BF-227 and FDDNP, to synthetic protein fibrils and human brain tissue. In vitro radioligand binding assays were conducted using synthetic amyloid {beta}{sub 42} and K18{Delta}K280-tau fibrils. Nonspecific binding was determined by the addition of unlabelled compounds at a concentration of 2 {mu}M. To examine radioligand binding to neuropathological lesions, in vitro autoradiography was conducted using sections of AD brain. [{sup 18}F]THK-523 showed higher affinity for tau fibrils than for A{beta} fibrils, whereas the other probes showed a higher affinity for A{beta} fibrils. The autoradiographic analysis indicated that [{sup 18}F]THK-523 accumulated in the regions containing a high density of tau protein deposits. Conversely, PiB and BF-227 accumulated in the regions containing a high density of A{beta} plaques. These findings suggest that the unique binding profile of [{sup 18}F]THK-523 can be used to identify tau deposits in AD brain. (orig.)

  16. Dementia and visual hallucinations associated with limbic pathology in Parkinson's disease.

    Science.gov (United States)

    Kalaitzakis, M E; Christian, L M; Moran, L B; Graeber, M B; Pearce, R K B; Gentleman, S M

    2009-03-01

    The pathological basis of dementia and visual hallucinations in Parkinson's disease (PD) is not yet fully understood. To investigate this further we have conducted a clinico-pathological study based on 30 post-mortem PD brains. PD cases were stratified into groups according to clinical characteristics as follows: (1) cognitively intact (n=9); (2) cases with severe dementia and visual hallucinations (n=12); (3) cases with severe dementia and no visual hallucinations (n=4); and (4) cases with severe visual hallucinations and no dementia (n=5). The extent of alpha-synuclein (alphaSyn), tau and amyloid beta peptide (Abeta) deposition was then examined in the CA2 sector of the hippocampus and in neocortical and subcortical areas known to subserve cognitive function. We find that dementia in PD is significantly associated with alphaSyn in the anterior cingulate gyrus, superior frontal gyrus, temporal cortex, entorhinal cortex, amygdaloid complex and CA2 sector of the hippocampus. Abeta in the anterior cingulate gyrus, entorhinal cortex, amygdaloid complex and nucleus basalis of Meynert is also associated with dementia as is tau in the CA2 sector of the hippocampus. alphaSyn burden in the amygdala is strongly related to the presence of visual hallucinations but only in those PD cases with concomitant dementia. Statistical analysis revealed that alphaSyn burden in the anterior cingulate gyrus could differentiate demented from non-demented PD cases with high sensitivity and specificity. We conclude that alphaSyn in limbic regions is related to dementia in PD as well as to visual hallucinations when there is an underlying dementia.

  17. Application of Molecular Pathology in Endocrine Pathology.

    Science.gov (United States)

    Linke, Ebru Serinsoz; Tezel, Gaye Güler

    2015-01-01

    Rapid growth in knowledge of cell and molecular biology led to the increased usage of molecular techniques in anatomical pathology. This is also due to the advances achieved in the techniques introduced in the last few years which are less laborious as compared to the techniques used at the beginning of the "molecular era". The initial assays were also very expensive and were not performed except for selected centers. Moreover, the clinicians were not sure how to make use of the accumulating molecular information. That situation has also changed and molecular techniques are being performed in a wide variety of medical settings which also has a reflection on the endocrine system pathology among other organ systems. This review will provide an update of genetic changes observed in different endocrine system pathologies and their diagnostic, therapeutic and prognostic values.

  18. Aluminium, iron, zinc and copper influence the in vitro formation of amyloid fibrils of Abeta42 in a manner which may have consequences for metal chelation therapy in Alzheimer's disease.

    Science.gov (United States)

    House, Emily; Collingwood, Joanna; Khan, Ayesha; Korchazkina, Olga; Berthon, Guy; Exley, Christopher

    2004-06-01

    Metals are found associated with beta-pleated sheets of Abeta42 in vivo and may be involved in their formation. Metal chelation has been proposed as a therapy for Alzheimer's disease on the basis that it may safely dissolve precipitated Abeta peptides. We have followed fibrillisation of Abeta42 in the presence of an additional metal ion (Al(III), Fe(III), Zn(II), Cu(II)) over a period of 32 weeks and we have investigated the dissolution of these aged peptide aggregates in the presence of both desferrioxamine (DFO) and ethylenediaminetetraacetic acid (EDTA). Abeta42 either alone or in the presence of Al(III) or Fe(III) formed beta-pleated sheets of plaque-like amyloids which were dissolved upon incubation with either chelator. Zn(II) inhibited whilst Cu(II) prevented the formation of beta-pleated sheets of Abeta42and neither of these influences were affected by incubation of the aged peptide aggregates with either DFO or EDTA. Freshly prepared solutions of Abeta42 either alone or in the presence of added Al(III) or Fe(III) did not form beta-pleated amyloid in the presence of DFO when incubated for up to 8 weeks. EDTA did not prevent beta-pleated amyloid formation in the same treatments and promoted beta-pleated amyloid formation in the presence of either Zn(II) or Cu(II). The presence of significant concentrations of Al(III) and Fe(III) as contaminants of 'Abeta42 only' preparations suggested that both of these metals were involved in either triggering the formation or stabilising the structure of beta-pleated amyloid. If the formation of such amyloid is critical to the aetiology of AD then the chelation of Al(III) and Fe(III) may prove to be a protective mechanism whilst the chelation of Cu(II) and Zn(II) without also chelating Al(III) and Fe(III) might actually exacerbate the condition.

  19. Handheld computing in pathology

    Directory of Open Access Journals (Sweden)

    Seung Park

    2012-01-01

    Full Text Available Handheld computing has had many applications in medicine, but relatively few in pathology. Most reported uses of handhelds in pathology have been limited to experimental endeavors in telemedicine or education. With recent advances in handheld hardware and software, along with concurrent advances in whole-slide imaging (WSI, new opportunities and challenges have presented themselves. This review addresses the current state of handheld hardware and software, provides a history of handheld devices in medicine focusing on pathology, and presents future use cases for such handhelds in pathology.

  20. Handheld computing in pathology

    Science.gov (United States)

    Park, Seung; Parwani, Anil; Satyanarayanan, Mahadev; Pantanowitz, Liron

    2012-01-01

    Handheld computing has had many applications in medicine, but relatively few in pathology. Most reported uses of handhelds in pathology have been limited to experimental endeavors in telemedicine or education. With recent advances in handheld hardware and software, along with concurrent advances in whole-slide imaging (WSI), new opportunities and challenges have presented themselves. This review addresses the current state of handheld hardware and software, provides a history of handheld devices in medicine focusing on pathology, and presents future use cases for such handhelds in pathology. PMID:22616027

  1. Pathology in Greece.

    Science.gov (United States)

    Sakellariou, S; Patsouris, E

    2015-11-01

    Pathology is the field of medicine that studies diseases. Ancient Greece hosted some of the earliest societies that laid the structural foundations of pathology. Initially, knowledge was based on observations but later on the key elements of pathology were established based on the dissection of animals and the autopsy of human cadavers. Christianized Greece under Ottoman rule (1453-1821) was not conducive to the development of pathology. After liberation, however, a series of events took place that paved the way for the establishment and further development of the specialty. The appointment in 1849 of two Professors of Pathology at the Medical School of Athens for didactical purposes proved to be the most important step in fostering the field of pathology in modern Greece. Presently in Greece there are seven university departments and 74 pathology laboratories in public hospitals, employing 415 specialized pathologists and 90 residents. The First Department of Pathology at the Medical School of Athens University is the oldest (1849) and largest in Greece, encompassing most pathology subspecialties.

  2. Lipid-induced conformational transition of the amyloid core fragment Abeta(28-35) and its A30G and A30I mutants.

    Science.gov (United States)

    Nagarajan, Sureshbabu; Ramalingam, Kirubagaran; Neelakanta Reddy, P; Cereghetti, Damiano M; Padma Malar, E J; Rajadas, Jayakumar

    2008-05-01

    The interaction of the beta-amyloid peptide (Abeta) with neuronal membranes could play a key role in the pathogenesis of Alzheimer's disease. Recent studies have focused on the interactions of Abeta oligomers to explain the neuronal toxicity accompanying Alzheimer's disease. In our study, we have investigated the role of lipid interactions with soluble Abeta(28-35) (wild-type) and its mutants A30G and A30I in their aggregation and conformational preferences. CD and Trp fluorescence spectroscopic studies indicated that, immediately on dissolution, these peptides adopted a random coil structure. Upon addition of negatively charged 1,2-dipalmitoyl-syn-glycero-3-phospho-rac-(glycerol) sodium salt (PG) lipid, the wild-type and A30I mutant underwent reorganization into a predominant beta-sheet structure. However, no conformational changes were observed in the A30G mutant on interaction with PG. In contrast, the presence of zwitterionic 1,2-dipalmitoyl-syn-glycero-3-phosphatidylcholine (PC) lipid had no effect on the conformation of these three peptides. These observations were also confirmed with atomic force microscopy and the thioflavin-T assay. In the presence of PG vesicles, both the wild-type and A30I mutant formed fibrillar structures within 2 days of incubation in NaCl/P(i), but not in their absence. Again, no oligomerization was observed with PC vesicles. The Trp studies also revealed that both ends of the three peptides are not buried deep in the vesicle membrane. Furthermore, fluorescence spectroscopy using the environment-sensitive probe 1,6-diphenyl-1,3,5-hexatriene showed an increase in the membrane fluidity upon exposure of the vesicles to the peptides. The latter effect may result from the lipid head group interactions with the peptides. Fluorescence resonance energy transfer experiments revealed that these peptides undergo a random coil-to-sheet conversion in solution on aging and that this process is accelerated by negatively charged lipid vesicles

  3. Hip joint pathology

    DEFF Research Database (Denmark)

    Tijssen, M; van Cingel, R E H; de Visser, E

    2016-01-01

    The purpose of this retrospective cohort study was to (a) describe the clinical presentation of femoroacetabular impingement (FAI) and hip labral pathology; (b) describe the accuracy of patient history and physical tests for FAI and labral pathology as confirmed by hip arthroscopy. Patients (18-6...

  4. Updates in ophthalmic pathology.

    Science.gov (United States)

    Mendoza, Pia R; Grossniklaus, Hans E

    2017-05-01

    Ophthalmic pathology has a long history and rich heritage in the field of ophthalmology. This review article highlights updates in ophthalmic pathology that have developed significantly through the years because of the efforts of committed individuals and the confluence of technology such as molecular biology and digital pathology. This is an exciting period in the history of ocular pathology, with cutting-edge techniques paving the way for new developments in diagnostics, therapeutics, and research. Collaborations between ocular oncologists and pathologists allow for improved and comprehensive patient care. Ophthalmic pathology continues to be a relevant specialty that is important in the understanding and clinical management of ocular disease, education of eye care providers, and overall advancement of the field.

  5. The Use of Recently Developed Histochemical Markers for Localizing Neurotoxicant Induced Regional Brain Pathologies

    Directory of Open Access Journals (Sweden)

    Sumit Sarkar

    2014-04-01

    Full Text Available Neuronal and vascular brain components are interrelated morphologically, physiologically and developmentally. Due to this close interrelationship, it is often difficult to understand the cause and effect relationship between neuronal vs. vascular dysfunction and pathology. This review will discuss four of the more promising recent developments for detecting vascular pathology, and will compare them with the labeling pattern seen with markers of glial and neuronal pathology; following exposure to well characterized neurotoxicants. To detect the vascular dysfunction in the brain, we recently developed a Fluoro-Turquoise gelatin conjugate (FT-gel, a fluorescent probe that helps to delineate between healthy vs. sclerotic vessels. Similarly, we have investigated the potential for Fluoro-Gold to label in vivo all the endothelial cells in the brain as they co-localize with RECA, an endothelial cell marker. We have also developed Amylo-Glo, a fluorescent tracer that can detect neurotoxic A-beta aggregates in the brain. In this article, we will discuss the potential use of these novel histochemical markers to study the neurotoxicant induced brain. We will also discuss neurovascular strategies that may offer novel therapeutic opportunities for neurodegenerative disorders.

  6. [Pathology- a new revival].

    Science.gov (United States)

    Barshack, Iris

    2013-06-01

    The field of pathology has undergone considerable change in recent years. The editor and editorial board of this journal are to be commended for their decision to devote a special issue to the field of pathology. Pathology deals with the characterization, investigation, and diagnosis of disease and disease processes and as such, has Long been considered one of the foundations of medicine. It is a rich and multi-faceted field which has retained its breadth of scope in the face of ever-increasing specialization and sub-specialization in medicine. In addition to its classic roles in autopsy, case description, and the diagnosis of pathoLogic processes, new and innovative spheres of activity are becoming integral to the field, especially in the realm of molecular pathology. Pathology is a Leading player in the new age of "personalized cancer therapy", where pathologists are responsible not only for diagnosing disease in the tissue, but also for conducting additional tests which may predict its response to specific drug therapies. In this context, moLecular pathology has become essential to the field both in the provision of cLinical service and research. To fully implement this trend, we are witness to the rise of tissue collection and tissue banking initiatives for both diagnostic and research purposes. A national tissue banking project in Israel has recently received considerable attention.

  7. [Gunshot wounds: forensic pathology].

    Science.gov (United States)

    Lorin de la Grandmaison, Geoffroy

    2012-02-01

    Gunshot wounds are among the most complex traumatic lesions encountered in forensic pathology. At the time of autopsy, careful scrutiny of the wounds is essential for correct interpretation of the lesions. Complementary pathological analysis has many interests: differentiation between entrance and exit wounds, estimation of firing distance, differentiation between vital and post mortem wounds and wounds dating. In case of multiple headshots, neuropathological examination can provide arguments for or against suicide. Sampling of gunshot wounds at autopsy must be systematic. Pathological data should be confronted respectively to autopsy and death scene investigation data and also ballistic studies. Forensic pathologist must be aware of the limits of optic microscopy.

  8. Determinants of pathologic mineralization.

    Science.gov (United States)

    Kirsch, Thorsten

    2008-01-01

    Physiologic mineralization is necessary for the formation of skeletal tissues and for their appropriate functions during adulthood. Mineralization has to be controlled and restricted to specific regions. If the mineralization process occurs in regions that normally do not mineralize, there can be severe consequences (pathologic or ectopic mineralization). Recent findings have indicated that physiologic and pathologic mineralization events are initiated by matrix vesicles, membrane-enclosed particles released from the plasma membranes of mineralization-competent cells. The understanding of how these vesicles are released from the plasma membrane and initiate the mineralization process may provide novel therapeutic strategies to prevent pathologic mineralization. In addition, other regulators (activators and inhibitors) of physiologic mineralization have been identified and characterized, and there is evidence that the same factors also contribute to the regulation of pathologic mineralization. Finally, programmed cell death (apoptosis) may be a contributor to physiologic mineralization and if occurring after tissue injury may induce pathologic mineralization and mineralization-related differentiation events in the injured and surrounding areas. This review describes how the understanding of mechanisms and factors regulating physiologic mineralization can be used to develop new therapeutic strategies to prevent pathologic or ectopic mineralization events.

  9. Isotopic variants of light and heavy L-pyroglutamic acid succinimidyl esters as the derivatization reagents for DL-amino acid chiral metabolomics identification by liquid chromatography and electrospray ionization mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Mochizuki, Toshiki; Todoroki, Kenichiro; Inoue, Koichi; Min, Jun Zhe; Toyo’oka, Toshimasa, E-mail: toyooka@u-shizuoka-ken.ac.jp

    2014-02-06

    Graphical abstract: -- Highlights: •Isotopic variants of chiral labeling reagents were newly synthesized. •Analysis of DL-amino acids was performed by UPLC–ESI–MS/MS. •Highly efficient enantioseparation and detection of DL-amino acids were performed. •Differential analysis of DL-amino acid was successfully performed in real samples. -- Abstract: L-Pyroglutamic acid succinimidyl ester (L-PGA-OSu) and its isotopic variant (L-PGA[d{sub 5}]-OSu) were newly synthesized and evaluated as the chiral labeling reagents for the enantioseparation of amino acids, in terms of separation efficiency by reversed-phase chromatography and detection sensitivity by ESI-MS/MS. The enantiomers of amino acids were easily labeled with the reagents at 60 °C within 10 min in an alkaline medium containing triethylamine. Although all the diastereomers derived from 18 proteolytic amino acids could not be satisfactorily separated, the pairs of 9 amino acids were completely separated by reversed-phase chromatography using the small particle (1.7 μm) ODS column (Rs = 1.95–8.05). The characteristic daughter ions, i.e., m/z 84.04 and m/z 89.04, were detected from all the derivatives by the collision induced dissociation of the protonated molecular ions. A highly sensitive detection at a low-fmol level (0.5–3.2 fmol) was also obtained from the selected reaction monitoring (SRM) chromatograms. An isotope labeling strategy using light and heavy L-PGA-OSu for the differential analysis of the DL-amino acids in different sample groups is also presented in this paper. The differential analysis of biological sample (i.e., human serum) and food product (i.e., yogurt) were tried to demonstrate the efficiency of the proposed method. The ratios of the DL-amino acids in human serum samples, spiked with the different concentrations of D-amino acids, were determined by the procedures using L-PGA-OSu and L-PGA[d{sub 5}]-OSu. The D/L ratios in the two sample groups at different concentrations of

  10. Eponyms in forensic pathology.

    Science.gov (United States)

    Nečas, Pavel; Hejna, Petr

    2012-12-01

    The phenomenon of eponymous terms in forensic pathology is described in this paper. The authors analyzed representative textbooks (monographs) dealing with forensic pathology in both English and German and identified several eponymous terms. The paper aims to present to the reader the most important eponymous terms in forensic pathology. Included in the paper are the following terms: Beckwith's Sign, Casper's Rule, Krönlein's Shot, Lichtenberg's Figures, Nysten's Law, Paltauf's Spots, Puppe's Rule, Sehrt's Sign, Simon's Sign, Sveshnikov's Sign, Tardieu's Spots, Wischnewski Spots, Wydler's Sign. The spread of eponymous terms throughout various languages is mentioned. The linguistic basis of such terms as well as their advantages and disadvantages in specialist fields, and indeed in even wider circles, is discussed. The authors state that the main function of these terms is to facilitate the open flow of unambiguous information among scholars. Eponymous terms in forensic pathology are characteristic for the German speaking countries and for all countries influenced by the German school of forensic pathology. Their usage in the Anglo-Saxon world is much less widespread, meaning they do not occur very often in English monographs and textbooks.

  11. Searching for disease modifiers-PKC activation and HDAC inhibition - a dual drug approach to Alzheimer's disease that decreases Abeta production while blocking oxidative stress.

    Science.gov (United States)

    Kozikowski, Alan P; Chen, Yihua; Subhasish, Tapadar; Lewin, Nancy E; Blumberg, Peter M; Zhong, Zhenyu; D'Annibale, Melissa A; Wang, Weng-Long; Shen, Yong; Langley, Brett

    2009-07-01

    A series of benzolactam compounds were synthesized, some of which caused a concentration-dependent increase in sAPPalpha and decrease in Abeta production in the concentration range of 0.1-10 microM. Moreover, some compounds showed neuroprotective effects in the 10-20 microM range in the HCA cortical neuron model of oxidative stress and no toxicity in measurements of neuron viability by MTT assay, even at the highest concentrations tested (20 microM). Alzheimer's disease (AD) is a well-studied neurodegenerative process characterized by the presence of amyloid plaques and neurofibrillary tangles. In this study, a series of protein kinase C (PKC) activators were investigated, some of which also exhibit histone deacetylase (HDAC) inhibitory activity, under the hypothesis that such compounds might provide a new path forward in the discovery of drugs for the treatment of AD. The PKC-activating properties of these drugs were expected to enhance the alpha-secretase pathway in the processing of amyloid precursor protein (APP), while their HDAC inhibition was anticipated to confer neuroprotective activity. We found that benzolactams 9 and 11-14 caused a concentration-dependent increase in sAPPalpha and decrease in beta-amyloid (Abeta) production in the concentration range of 0.1-10 microM, consistent with a shift of APP metabolism toward the alpha-secretase-processing pathway. Moreover, compounds 9-14 showed neuroprotective effects in the 10-20 microM range in the homocysteate (HCA) cortical neuron model of oxidative stress. In parallel, we found that the most neuroprotective compounds caused increased levels of histone acetylation (H4), thus indicating their likely ability to inhibit HDAC activity. As the majority of the compounds studied also show nanomolar binding affinities for PKC, we conclude that it is possible to design, de novo, agents that combine both PKC-activating properties along with HDAC inhibitory properties. Such agents would be capable of modulating

  12. Pathological Gambling Subtypes

    Science.gov (United States)

    Vachon, David D.; Bagby, R. Michael

    2009-01-01

    Although pathological gambling (PG) is regarded in the 4th edition of the "Diagnostic and Statistical Manual of Mental Disorders" (American Psychiatric Association, 1994) as a unitary diagnostic construct, it is likely composed of distinct subtypes. In the current report, the authors used cluster analyses of personality traits with a…

  13. Next-Generation Pathology.

    Science.gov (United States)

    Caie, Peter D; Harrison, David J

    2016-01-01

    The field of pathology is rapidly transforming from a semiquantitative and empirical science toward a big data discipline. Large data sets from across multiple omics fields may now be extracted from a patient's tissue sample. Tissue is, however, complex, heterogeneous, and prone to artifact. A reductionist view of tissue and disease progression, which does not take this complexity into account, may lead to single biomarkers failing in clinical trials. The integration of standardized multi-omics big data and the retention of valuable information on spatial heterogeneity are imperative to model complex disease mechanisms. Mathematical modeling through systems pathology approaches is the ideal medium to distill the significant information from these large, multi-parametric, and hierarchical data sets. Systems pathology may also predict the dynamical response of disease progression or response to therapy regimens from a static tissue sample. Next-generation pathology will incorporate big data with systems medicine in order to personalize clinical practice for both prognostic and predictive patient care.

  14. Pathological Gambling: Psychiatric Models

    Science.gov (United States)

    Westphal, James R.

    2008-01-01

    Three psychiatric conceptual models: addictive, obsessive-compulsive spectrum and mood spectrum disorder have been proposed for pathological gambling. The objectives of this paper are to (1) evaluate the evidence base from the most recent reviews of each model, (2) update the evidence through 2007 and (3) summarize the status of the evidence for…

  15. Pathology informatics fellowship training: Focus on molecular pathology

    Directory of Open Access Journals (Sweden)

    Diana Mandelker

    2014-01-01

    Full Text Available Background: Pathology informatics is both emerging as a distinct subspecialty and simultaneously becoming deeply integrated within the breadth of pathology practice. As specialists, pathology informaticians need a broad skill set, including aptitude with information fundamentals, information systems, workflow and process, and governance and management. Currently, many of those seeking training in pathology informatics additionally choose training in a second subspecialty. Combining pathology informatics training with molecular pathology is a natural extension, as molecular pathology is a subspecialty with high potential for application of modern biomedical informatics techniques. Methods and Results: Pathology informatics and molecular pathology fellows and faculty evaluated the current fellowship program′s core curriculum topics and subtopics for relevance to molecular pathology. By focusing on the overlap between the two disciplines, a structured curriculum consisting of didactics, operational rotations, and research projects was developed for those fellows interested in both pathology informatics and molecular pathology. Conclusions: The scope of molecular diagnostics is expanding dramatically as technology advances and our understanding of disease extends to the genetic level. Here, we highlight many of the informatics challenges facing molecular pathology today, and outline specific informatics principles necessary for the training of future molecular pathologists.

  16. High dietary consumption of trans fatty acids decreases brain docosahexaenoic acid but does not alter amyloid-beta and tau pathologies in the 3xTg-AD model of Alzheimer's disease.

    Science.gov (United States)

    Phivilay, A; Julien, C; Tremblay, C; Berthiaume, L; Julien, P; Giguère, Y; Calon, F

    2009-03-03

    Dietary consumption of trans fatty acids (TFA) has increased during the 20th century and is a suspected risk factor for cardiovascular diseases. More recently, high TFA intake has been associated with a higher risk of developing Alzheimer's disease (AD). To investigate the impact of TFA on an animal model genetically programmed to express amyloid-beta (Abeta) and tau pathological markers of AD, we have fed 3xTg-AD mice with either control (0% TFA/total fatty acid), high TFA (16% TFA) or very high TFA (43% TFA) isocaloric diets from 2 to 16 months of age. Effects of TFA on plasma hepatic enzymes, glucose and lipid profile were minimal but very high TFA intake decreased visceral fat of non-transgenic mice. Importantly, dietary TFA increased brain TFA concentrations in a dose-related manner. Very high TFA consumption substantially modified the brain fatty acid profile by increasing mono-unsaturated fatty acids and decreasing polyunsaturated fatty acids (PUFA). Very high TFA intake induced a shift from docosahexaenoic acid (DHA, 22:6n-3) toward n-6 docosapentaenoic acid (DPA, 22:5n-6) without altering the n-3:n-6 PUFA ratio in the cortex of both control and 3xTg-AD mice. Changes in levels of Abeta(40), Abeta(42), tau protein, phosphorylated tau protein and synaptic markers were not statistically significant in the three groups of 3xTg-AD mice, despite a trend toward decreased insoluble tau in very high TFA-fed 3xTg-AD animals. In summary, TFA intake modulated brain fatty acid profiles but had no significant effect on major brain neuropathological hallmarks of AD in an animal model.

  17. Feline oral pathology

    OpenAIRE

    Costa, S.; Pais, B.; Almeida, D.; Simões, J.; Mega, A. C.; Vala, Helena

    2013-01-01

    The main pathologies of the oral cavity are of utmost importance, not only by the number of exposed individuals, but also by the consequences which stems. With the development of this work, we intend to conduct a brief approach to the same, since, specifically affecting domestic felines. Feline Lymphoplasmatic Gingivostomatitis (GELF), the Feline Odontoclastic Reabsorption Lesions (LROF) Complex and gingivitis-stomatitis-pharyngitis, have been studied, some of which are considered an enigma i...

  18. Envy's pathology: Historical contexts.

    Science.gov (United States)

    Minou, Lina

    2017-01-01

    This article is concerned with the physicality of envy primarily in early -modern, but also in eighteenth-century health contexts. The discussion brings together descriptions of the effects of envy on the body of the envier, mainly from works of physiology and health preservation, but also from literary and spiritual writings. These depictions of envy are studied beyond their symbolism and with a view to establish whether they are meaningful according to the medical theories of the time in which they occur. The discussion begins by acknowledging the status of envy as a 'disease' and looks to the specific ways in which the discourse of envy conveys this sense. I find that in the early modern discourse envy is always pathological, that is, it is experienced as disease and signifies disease in general and several diseases in particular. Moreover, envy is uniquely placed to convey pathology on account of its being connected to inherently pathogenic elements of the humoural theory. Specifically, envy is physiologically connected to melancholy, and the way it is presented comes close to attributes assigned to black bile. In addition, envy realizes pathology, the occurrence of disease in the body, by impairing the vital process of digestion and thus depriving the person from proper nourishment and sustenance. The analysis further considers how this impairment of the body fits with the physiological manifestation of envy as 'corrosion' and 'consumption'. Finding commonalities with other maladies mediated by these physiological signs the article concludes by considering the function of pathology in the conception of early modern envy.

  19. Masochism and pathological gambling.

    Science.gov (United States)

    Rosenthal, Richard J

    2015-03-01

    That all pathological gamblers have an "unconscious wish to lose," an idea first expressed by Freud and Bergler, is neither true nor useful; wrong as well, however, are the reasons for neglecting masochism in relation to gambling. There is a small but clinically significant subgroup of pathological gamblers who are masochistic. I present clinical vignettes and a more extended treatment account to illustrate its importance. Masochism has been a confusing concept. As used here it refers to the deliberate seeking of pain, loss, suffering, or humiliation. There may be pleasure in pain, or an obligatory combining of pleasure and pain. A sense of power and control may be achieved through suffering. The case material illustrates clinically useful types (sexual masochism, masochistic personality disorder, moral masochism, relational masochism) as well as some common masochistic dynamics encountered in the treatment of pathological gamblers. These masochistic patterns are often identifiable during the initial evaluation. Distinguishing features may include a reversal of normal attitudes about winning and losing, the absence of an early winning phase, sometimes a memorable early loss. Gamblers may sabotage opportunities for success or create unnecessary obstacles for themselves. Losing may be more comfortable than winning or may be overtly sexualized.

  20. Detection of cerebral microbleeds with quantitative susceptibility mapping in the ArcAbeta mouse model of cerebral amyloidosis

    Science.gov (United States)

    Klohs, Jan; Deistung, Andreas; Schweser, Ferdinand; Grandjean, Joanes; Dominietto, Marco; Waschkies, Conny; Nitsch, Roger M; Knuesel, Irene; Reichenbach, Jürgen R; Rudin, Markus

    2011-01-01

    Cerebral microbleeds (CMBs) are findings in patients with neurological disorders such as cerebral amyloid angiopathy and Alzheimer's disease, and are indicative of an underlying vascular pathology. A diagnosis of CMBs requires an imaging method that is capable of detecting iron-containing lesions with high sensitivity and spatial accuracy in the presence of potentially confounding tissue abnormalities. In this study, we investigated the feasibility of quantitative magnetic susceptibility mapping (QSM), a novel technique based on gradient-recalled echo (GRE) phase data, for the detection of CMBs in the arcAβ mouse, a mouse model of cerebral amyloidosis. Quantitative susceptibility maps were generated from phase data acquired with a high-resolution T2*-weighted GRE sequence at 9.4 T. We examined the influence of different regularization parameters on susceptibility computation; a proper adjustment of the regularization parameter minimizes streaking artifacts and preserves fine structures. In the present study, it is shown that QSM provides increased detection sensitivity of CMBs and improved contrast when compared with GRE magnitude imaging. Furthermore, QSM corrects for the blooming effect observed in magnitude and phase images and depicts both the localization and spatial extent of CMBs with high accuracy. Therefore, QSM may become an important tool for diagnosing CMBs in neurological diseases. PMID:21847134

  1. Cortical myoclonus and cerebellar pathology

    NARCIS (Netherlands)

    Tijssen, MAJ; Thom, M; Ellison, DW; Wilkins, P; Barnes, D; Thompson, PD; Brown, P

    2000-01-01

    Objective To study the electrophysiologic and pathologic findings in three patients with cortical myoclonus. In two patients the myoclonic ataxic syndrome was associated with proven celiac disease. Background: The pathologic findings in conditions associated with cortical myoclonus commonly involve

  2. Pathology Gross Photography: The Beginning of Digital Pathology.

    Science.gov (United States)

    Rampy, B Alan; Glassy, Eric F

    2015-06-01

    The underutilized practice of photographing anatomic pathology specimens from surgical pathology and autopsies is an invaluable benefit to patients, clinicians, pathologists, and students. Photographic documentation of clinical specimens is essential for the effective practice of pathology. When considering what specimens to photograph, all grossly evident pathology, absent yet expected pathologic features, and gross-only specimens should be thoroughly documented. Specimen preparation prior to photography includes proper lighting and background, wiping surfaces of blood, removing material such as tubes or bandages, orienting the specimen in a logical fashion, framing the specimen to fill the screen, positioning of probes, and using the right-sized scale.

  3. Extracellular and intraneuronal HMW-AbetaOs represent a molecular basis of memory loss in Alzheimer's disease model mouse

    Directory of Open Access Journals (Sweden)

    Yamamoto Naoki

    2011-03-01

    Full Text Available Abstract Background Several lines of evidence indicate that memory loss represents a synaptic failure caused by soluble amyloid β (Aβ oligomers. However, the pathological relevance of Aβ oligomers (AβOs as the trigger of synaptic or neuronal degeneration, and the possible mechanism underlying the neurotoxic action of endogenous AβOs remain to be determined. Results To specifically target toxic AβOs in vivo, monoclonal antibodies (1A9 and 2C3 specific to them were generated using a novel design method. 1A9 and 2C3 specifically recognize soluble AβOs larger than 35-mers and pentamers on Blue native polyacrylamide gel electrophoresis, respectively. Biophysical and structural analysis by atomic force microscopy (AFM revealed that neurotoxic 1A9 and 2C3 oligomeric conformers displayed non-fibrilar, relatively spherical structure. Of note, such AβOs were taken up by neuroblastoma (SH-SY5Y cell, resulted in neuronal death. In humans, immunohistochemical analysis employing 1A9 or 2C3 revealed that 1A9 and 2C3 stain intraneuronal granules accumulated in the perikaryon of pyramidal neurons and some diffuse plaques. Fluoro Jade-B binding assay also revealed 1A9- or 2C3-stained neurons, indicating their impending degeneration. In a long-term low-dose prophylactic trial using active 1A9 or 2C3 antibody, we found that passive immunization protected a mouse model of Alzheimer's disease (AD from memory deficits, synaptic degeneration, promotion of intraneuronal AβOs, and neuronal degeneration. Because the primary antitoxic action of 1A9 and 2C3 occurs outside neurons, our results suggest that extracellular AβOs initiate the AD toxic process and intraneuronal AβOs may worsen neuronal degeneration and memory loss. Conclusion Now, we have evidence that HMW-AβOs are among the earliest manifestation of the AD toxic process in mice and humans. We are certain that our studies move us closer to our goal of finding a therapeutic target and/or confirming the

  4. Pathology of intrahepatic cholangiocarcinoma

    Science.gov (United States)

    Vijgen, Sandrine; Terris, Benoit

    2017-01-01

    Intrahepatic cholangiocarcinoma (iCC) is a primary carcinoma of the liver with increasing significance and major pathogenic, clinical and therapeutic challenges. Classically, it arises from malignant transformation of cholangiocytes bordering small portal bile duct (BD) to second-order segmental large BDs. It has three major macroscopic growth pattern [mass-forming (MF), periductal infiltrative (PI), and intraductal growth (IG)] and histologically is a desmoplastic stroma-rich adenocarcinoma with cholangiocyte differentiation. Recent data pointed out noteworthy degree of heterogeneity in regards of their epidemiology and risk factors, pathological and molecular features, pathogenesis, clinical behaviors and treatment. Notably, several histological variants are described and can coexist within the same tumor. Several different cells of origin have also been depicted in a fraction of iCCs, amongst which malignant transformation of ductules, of hepatic stem/progenitor cells, of periductal glands or through oncogenic reprogramming of adult hepatocytes. A degree of pathological overlap with hepatocellular carcinoma (HCC) may be observed in a portion of iCC. A series of precursor lesions are today characterized and emphasize the existence of a multistep carcinogenesis process. Overall, these new data have brought up in proposal of new histological or molecular classifications, which could soon replace current anatomic-based classification and could have major impact on establishment of prognosis and on development of novel target treatment approaches. PMID:28261592

  5. [(Impending) pathological fracture].

    Science.gov (United States)

    Sutter, P M; Regazzoni, P

    2002-01-01

    Pathological fractures will be encountered in increasing frequency due to more patients with cancer, surviving a longer period. The skeleton is the third most frequent localization for metastases. Breast cancer is still the most common primary tumor, but bone metastases from lung cancer seem to be diagnosed more and more. Despite of finding metastases most often in the spinal column, fractures are seen mostly at the femoral site. A pathological fracture and, in almost all cases, an impending fracture are absolute indication for operation. An exact definition of an "impending fracture" is still lacking; it is widely accepted, that 50 per cent of bone mass must be destroyed before visualization in X-ray is possible, thus defining an impending fracture. The score system by Mirels estimates the fracture risk by means of four parameters (localization, per cent of destructed bone mass, type of metastasis, pain). Improving quality of life, relieving pain, preferably with a single operation and a short length of stay are the goals of (operative) treatment. For fractures of the proximal femur, prosthetic replacement, for fractures of the subtrochanteric region or the shaft, intramedullary nails are recommended. Postoperative radiation therapy possibly avoids tumor progression. In patient with a good long term prognosis, tumor should be removed locally aggressive.

  6. Pathology of the vestibulocochlear nerve

    Energy Technology Data Exchange (ETDEWEB)

    De Foer, Bert [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: bert.defoer@GZA.be; Kenis, Christoph [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: christophkenis@hotmail.com; Van Melkebeke, Deborah [Department of Neurology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: Deborah.vanmelkebeke@Ugent.be; Vercruysse, Jean-Philippe [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: jphver@yahoo.com; Somers, Thomas [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: Thomas.somers@GZA.be; Pouillon, Marc [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: marc.pouillon@GZA.be; Offeciers, Erwin [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: Erwin.offeciers@GZA.be; Casselman, Jan W. [Department of Radiology, AZ Sint-Jan AV Hospital, Ruddershove 10, Bruges (Belgium); Consultant Radiologist, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium); Academic Consultent, University of Ghent (Belgium)], E-mail: jan.casselman@azbrugge.be

    2010-05-15

    There is a large scala of pathology affecting the vestibulocochlear nerve. Magnetic resonance imaging is the method of choice for the investigation of pathology of the vestibulocochlear nerve. Congenital pathology mainly consists of agenesis or hypoplasia of the vestibulocochlear nerve. Tumoral pathology affecting the vestibulocochlear nerve is most frequently located in the internal auditory canal or cerebellopontine angle. Schwannoma of the vestibulocochlear nerve is the most frequently found tumoral lesion followed by meningeoma, arachnoid cyst and epidermoid cyst. The most frequently encountered pathologies as well as some more rare entities are discussed in this chapter.

  7. No pain, no pathology?

    Science.gov (United States)

    Sharma, Devesh; Govind, Abha

    2012-10-26

    A 22-year-old girl who had a background of reflux nephropathy and urinary tact infection presented during the night with renal angle pain and vomiting. She was treated on the emergency department (ED) pyelonephritis protocol and admitted to the short stay ward. When reviewed the next morning she was aymptomatic and feeling better. It seemed likely that she would be discharged but an ED ultrasound showed right-sided hydronephrosis and some fluid between the liver and the right kidney. CT examination confirmed the suspicion of renal tract obstruction and ruptured calyx. An 8 mm calculus was found to be the cause of the pathology. Urgent urological review was organised and the system formally decompressed with a J-J stent inserted cystoscopically later that day.

  8. Digital pathology: Attitudes and practices in the Canadian pathology community

    Directory of Open Access Journals (Sweden)

    Magdaleni Bellis

    2013-01-01

    Full Text Available Digital pathology is a rapidly evolving niche in the world of pathology and is likely to increase in popularity as technology improves. We performed a questionnaire for pathologists and pathology residents across Canada, in order to determine their current experiences and attitudes towards digital pathology; which modalities digital pathology is best suited for; and to assess the need for training in digital pathology amongst pathology residents and staff. An online survey consisting of 24 yes/no, multiple choice and free text questions regarding digital pathology was sent out via E-mail to all members of the Canadian Association of Pathologists and pathology residents across Canada. Survey results showed that telepathology (TP is used in approximately 43% of institutions, primarily for teaching purposes (65%, followed by operating room consults (46%. Seventy-one percent of respondents believe there is a need for TP in their practice; 85% use digital images in their practice. The top two favored applications for digital pathology are teaching and consultation services, with the main advantage being easier access to cases. The main limitations of using digital pathology are cost and image/diagnostic quality. Sixty-two percent of respondents would attend training courses in pathology informatics and 91% think informatics should be part of residency training. The results of the survey indicate that Pathologists and residents across Canada do see a need for TP and the use of digital images in their daily practice. Integration of an informatics component into resident training programs and courses for staff Pathologists would be welcomed.

  9. Nontraditional applications in clinical pathology.

    Science.gov (United States)

    Jordan, Holly L; Register, Thomas C; Tripathi, Niraj K; Bolliger, Anne Provencher; Everds, Nancy; Zelmanovic, David; Poitout, Florence; Bounous, Denise I; Wescott, Debra; Ramaiah, Shashi K

    2014-10-01

    Most published reviews of preclinical toxicological clinical pathology focus on the fundamental aspects of hematology, clinical chemistry, coagulation, and urinalysis in routine toxicology animal species, for example, rats, mice, dogs, and nonhuman primates. The objective of this continuing education course was to present and discuss contemporary examples of nonroutine applications of clinical pathology endpoints used in the drug development setting. Area experts discussed bone turnover markers of laboratory animal species, clinical pathology of pregnant and growing laboratory animals, clinical pathology of nonroutine laboratory animal species, and unique applications of the Siemens Advia(®) hematology analyzer. This article is a summary based on a presentation given at the 31st Annual Symposium of the Society of Toxicologic Pathology, during the Continuing Education Course titled "Nontraditional Applications of Clinical Pathology in Drug Discovery and Preclinical Toxicology."

  10. [Psychiatric comorbidity in pathological gambling].

    Science.gov (United States)

    Skokauskas, Norbertas; Satkeviciūte, Regina; Burba, Benjaminas

    2003-01-01

    In this article the peculiarities of psychiatric comorbidity in pathological gambling were investigated. The authors were based both on the data of many foreign scientists and on their own one. Our data on 77 cases of pathological gambling were collected based on interviews of Lithuanian psychiatrists and psychotherapists about their patients with gambling addiction in period from 1991 to 2001. The data that we publish and analyze allows us to make conclusions that pathological gambling can reveal together with very wide spectrum of psychiatric disorders, but more often with alcoholism and depression. The mechanism of psychiatric comorbidity in pathological gambling is very complex.

  11. Recommendations for pathology peer review.

    Science.gov (United States)

    Morton, Daniel; Sellers, Rani S; Barale-Thomas, Erio; Bolon, Brad; George, Catherine; Hardisty, Jerry F; Irizarry, Armando; McKay, Jennifer S; Odin, Marielle; Teranishi, Munehiro

    2010-12-01

    Pathology peer review verifies and improves the accuracy and quality of pathology diagnoses and interpretations. Pathology peer review is recommended when important risk assessment or business decisions are based on nonclinical studies. For pathology peer review conducted before study completion, the peer-review pathologist reviews sufficient slides and pathology data to assist the study pathologist in refining pathology diagnoses and interpretations. Materials to be reviewed are selected by the peer-review pathologist. Consultations with additional experts or a formal (documented) pathology working group may be used to resolve discrepancies. The study pathologist is solely responsible for the content of the final pathology data and report, makes changes resulting from peer-review discussions, initiates the audit trail for microscopic observations after all changes resulting from peer-review have been made, and signs the final pathologist's report. The peer-review pathologist creates a signed peer-review memo describing the peer-review process and confirming that the study pathologist's report accurately and appropriately reflects the pathology data. The study pathologist also may sign a statement of consensus. It is not necessary to archive working notes created during the peer-review process.

  12. [Diagnostic significance of pathologic synkinesis for detection of pyramidal pathology].

    Science.gov (United States)

    Baliasnyĭ, M M

    1991-01-01

    Five types of pathological synkinesis (++blepharo-ocular, ++blepharo-facial, ++bucco-manual, ++digito-digital on the hands, ++pedo-digital) are described. They are of definite importance for revealing pyramidal pathology including its early stages as well as for objective evaluation and observation of the time-course of changes in the illness.

  13. CT in vascular pathologies

    Energy Technology Data Exchange (ETDEWEB)

    Bartolozzi, C.; Neri, E.; Caramella, D. [Diagnostic and Interventional Radiology Department of Oncology, University of Pisa, Via Roma 67, I-56100 Pisa (Italy)

    1998-06-02

    Since the introduction of helical scanners, CT angiography (CTA) has achieved an essential role in many vascular applications that were previously managed with conventional angiography. The performance of CTA is based on the accurate selection of collimation width, pitch, reconstruction spacing and scan delay, which must be modulated on the basis of the clinical issue. However, the major improvement of CT has been provided by the recent implementation of many post-processing techniques, such as multiplanar reformatting, shaded surface display, maximum intensity projections, 3D perspectives of surface and volume rendering, which simulate virtual intravascular endoscopy. The integration of the potentialities of the scanner and of the image processing techniques permitted improvement of: (a) the evaluation of aneurysms, dissection and vascular anomalies involving the thoracic aorta; (b) carotid artery stenosis; (c) aneurysms of abdominal aorta; (d) renal artery stenosis; (e) follow-up of renal artery stenting; and (f) acute or chronic pulmonary embolism. Our experience has shown that the assessment of arterial pathologies with CTA requires the integration of 3D post-processing techniques in most applications. (orig.) With 4 figs., 34 refs.

  14. A longitudinal study of cognition, proton MR spectroscopy and synaptic and neuronal pathology in aging wild-type and AbetaPPswe-PS1dE9 mice.

    NARCIS (Netherlands)

    Jansen, D.; Zerbi, V.; Janssen, C.I.F.; Dederen, P.J.W.C.; Mutsaers, M.P.; Hafkemeijer, A.; Janssen, A.L.; Nobelen, C.L.; Veltien, A.A.; Asten, J.J.A. van; Heerschap, A.; Kiliaan, A.J.

    2013-01-01

    Proton magnetic resonance spectroscopy ((1)H MRS) is a valuable tool in Alzheimer's disease research, investigating the functional integrity of the brain. The present longitudinal study set out to characterize the neurochemical profile of the hippocampus, measured by single voxel (1)H MRS at 7

  15. Podocyte Pathology and Nephropathy

    Directory of Open Access Journals (Sweden)

    Sandra eMerscher

    2014-07-01

    Full Text Available Sphingolipids are components of the lipid rafts in plasma membranes, which are important for proper function of podocytes, a key element of the glomerular filtration barrier. Research revealed an essential role of sphingolipids and sphingolipid metabolites in glomerular disorders of genetic and non-genetic origin. The discovery that glucocerebrosides accumulate in Gaucher disease in glomerular cells and are associated with clinical proteinuria initiated intensive research into the function of other sphingolipids in glomerular disorders. The accumulation of sphingolipids in other genetic diseases including Tay-Sachs, Sandhoff, Fabry, hereditary inclusion body myopathy 2, Niemann-Pick and nephrotic syndrome of the Finnish type and its implications with respect to glomerular pathology will be discussed. Similarily, sphingolipid accumulation occurs in glomerular diseases of non-genetic origin including diabetic kidney disease (DKD, HIV-associated nephropathy, focal segmental glomerulosclerosis (FSGS and lupus nephritis. Sphingomyelin metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate have also gained tremendous interest. We recently described that sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b is expressed in podocytes where it modulates acid sphingomyelinase (ASMase activity and acts as a master modulator of danger signaling. Decreased SMPDL3b expression in post-reperfusion kidney biopsies from transplant recipients with idiopathic FSGS correlates with the recurrence of proteinuria in patients and in experimental models of xenotransplantation. Increased SMPDL3b expression is associated with DKD. The consequences of differential SMPDL3b expression in podocytes in these diseases with respect to their pathogenesis will be discussed. Finally, the role of sphingolipids in the formation of lipid rafts in podocytes and their contribution to the maintenance of a functional slit diaphragm in the glomerulus will be discussed.

  16. Utilization management in anatomic pathology.

    Science.gov (United States)

    Lewandrowski, Kent; Black-Schaffer, Steven

    2014-01-01

    There is relatively little published literature concerning utilization management in anatomic pathology. Nonetheless there are many utilization management opportunities that currently exist and are well recognized. Some of these impact only the cost structure within the pathology department itself whereas others reduce charges for third party payers. Utilization management may result in medical legal liabilities for breaching the standard of care. For this reason it will be important for pathology professional societies to develop national utilization guidelines to assist individual practices in implementing a medically sound approach to utilization management.

  17. Multiple factors contribute to the peripheral induction of cerebral beta-amyloidosis

    NARCIS (Netherlands)

    Eisele, Y.S.; Fritschi, S.K.; Hamaguchi, T.; Obermüller, U.; Füger, P.; Skodras, A.; Schäfer, C.; Odenthal, J.; Heikenwalder, M.; Staufenbiel, M.; Jucker, M.

    2014-01-01

    Deposition of aggregated amyloid-beta (Abeta) peptide in brain is an early event and hallmark pathology of Alzheimer's disease and cerebral Abeta angiopathy. Experimental evidence supports the concept that Abeta multimers can act as seeds and structurally corrupt other Abeta peptides by a

  18. MLE's bias pathology motivates MCMLE

    OpenAIRE

    Yatracos, Yannis G.

    2013-01-01

    Maximum likelihood estimates are often biased. It is shown that this pathology is inherent to the traditional ML estimation method for two or more parameters, thus motivating from a different angle the use of MCMLE.

  19. Systemic disorders affecting dental pathology

    Directory of Open Access Journals (Sweden)

    Knežević Milan R

    2014-12-01

    Full Text Available A retrospective overview of systemic disorders which might be associated with dental pathology is made. They are grouped as follows: (a congenital dental developmental disorders, (b chromosomal anomalies, (c radiations, (d immune disorders, (e intoxications, (f neurological alterations, (g gastrointestinal diseases, (h osteodystrophy and associated conditions, (i skin diseases, (j metabolic and endocrine disorders, (k craniofacial malformation syndromes and other congenital general malformations. The associated dental pathology is described in each case.

  20. [Methods and methodology of pathology].

    Science.gov (United States)

    Lushnikov, E F

    2016-01-01

    The lecture gives the state-of-the-art of the methodology of human pathology that is an area of the scientific and practice activity of specialists to produce and systematize objective knowledge of pathology and to use the knowledge in clinical medicine. It considers the objects and subjects of an investigation, materials and methods of a pathologist, and the results of his/her work.

  1. Development of pathology in Turkey

    Directory of Open Access Journals (Sweden)

    Gökhan GEDİKOĞLU

    2007-05-01

    Full Text Available Autospy is an important tool for the development of pathology as a science. In western civilisation dissection of human body became widespread with Renaissance, in contrast in the Ottoman Empire first dissection was not performed until the 19th century. Mustafa Behçet Efendi, head physician of the Empire, was one of the Ottoman physician who suggested the importance of dissection in the medical education. The first dissection was however performed by Charles Ambroise Bernard, a foreign physician who had been invited to help establishing a new medical school; “Mekteb-i Tıbbiye-i Adliye-i Şâhâne”, in 1843. The first modern medical schools called “Tıphane” and “Cerrahhane-i Amire” which were founded in 1827, did not have pathology courses. Pathology courses began in “Mekteb-i Tıbbiye-i Adliyei Şâhâne”. Dr. Hamdi Suat (Aknar, educated in anatomic pathology in Germany, was the first pathologist who established the modern pathology in Turkey in “İstanbul Darülfünun” medical school. In 1933 “Darülfünün” was closed and İstanbul University was built and the “University Reform Commission” invited many scientists escaping from Nazi government to study in İstanbul University. Dr. Philipp Schwartz had an important role both in the invitation of these scientists and establishment of the pathology department in İstanbul University. Practical courses were increased, clinicopathologic courses were organized for the first time and a lot of autopsies were performed, as high as 1000 autopsy per year, by Dr. Philipp Schwartz. More progress has takes place in Turkey over the years since pathology was first established. Today Turkey has many pathology departments which keep up with the worldwide advances in the field.

  2. Crystallization and preliminary X-ray diffraction analysis of the Fab fragment of WO2, an antibody specific for the A[beta] peptides associated with Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Wun, Kwok S.; Miles, Luke A.; Crespi, Gabriela A.N.; Wycherley, Kaye; Ascher, David B.; Barnham, Kevin J.; Cappai, Roberto; Beyreuther, Konrad; Masters, Colin L.; Parker, Michael W.; McKinstry, William J. (SVIMR-A); (HeidelbergU); (WEHI); (Melbourne)

    2008-05-28

    The murine monoclonal antibody WO2 specifically binds the N-terminal region of the amyloid {beta} peptide (A{beta}) associated with Alzheimer's disease. This region of A{beta} has been shown to be the immunodominant B-cell epitope of the peptide and hence is considered to be a basis for the development of immunotherapeutic strategies against this prevalent cause of dementia. Structural studies have been undertaken in order to characterize the molecular basis for antibody recognition of this important epitope. Here, details of the crystallization and X-ray analysis of the Fab fragment of the unliganded WO2 antibody in two crystal forms and of the complexes that it forms with the truncated Az{beta} peptides A{beta}{sub 1-16} and A{beta}{sub 1-28} are presented. These crystals were all obtained using the hanging-drop vapour-diffusion method at 295 K. Crystals of WO2 Fab were grown in polyethylene glycol solutions containing ZnSO{sub 4}; they belonged to the orthorhombic space group P2{sub 1}2{sub 1}2{sub 1} and diffracted to 1.6 {angstrom} resolution. The complexes of WO2 Fab with either A{beta}{sub 1-16} or A{beta}{sub 1-28} were cocrystallized from polyethylene glycol solutions. These two complex crystals grew in the same space group, P2{sub 1}2{sub 1}2{sub 1}, and diffracted to 1.6 {angstrom} resolution. A second crystal form of WO2 Fab was grown in the presence of the sparingly soluble A{beta}{sub 1-42} in PEG 550 MME. This second form belonged to space group P2{sub 1} and diffracted to 1.9 {angstrom} resolution.

  3. Inhibition of gamma-secretase activity reduces Abeta production, reduces oxidative stress, increases mitochondrial activity and leads to reduced vulnerability to apoptosis: Implications for the treatment of Alzheimer's disease.

    Science.gov (United States)

    Sheng, Baiyang; Gong, Kai; Niu, Ying; Liu, Lingling; Yan, Yufang; Lu, Guangyuan; Zhang, Lihai; Hu, Min; Zhao, Nanming; Zhang, Xiufang; Tang, Peifu; Gong, Yandao

    2009-05-15

    It has been argued that gamma-secretase should be considered as a pharmacological target, as there are few mechanism-based experimental and clinical studies on gamma-secretase treatment. In this study, we found that N2a cells bearing APP695 or its Swedish mutant exhibited increased basal levels of ROS, nitric oxide (NO), protein carbonyls, MDA and intracellular calcium, as well as reduced level of the mitochondrial membrane potential and ATP. When the activity of gamma-secretase was inhibited by expression of the D385A PS1 variant, cells (N2a/Swe.D385A) showed reduced basal levels of ROS, nitric oxide (NO), protein carbonyls, MDA and intracellular calcium, as well as increased mitochondrial membrane potential and ATP level. In addition, N2a/Swe.D385A cells showed reduced vulnerability to H(2)O(2)-induced apoptosis. The Bcl-2 and JNK/ERK pathways were proven to be involved in the change of vulnerability to H(2)O(2)-induced apoptosis. Moreover, we discovered that inhibition of gamma-secretase by DAPT would lead to a reduction of ROS levels and stabilization of mitochondrial function in APP (N2a/APP695) and APP Swedish mutant (N2a/APPswe) transfected cells. At last, it was shown that Abeta antibody and antiserum prevented increase of ROS and reduction of mitochondrial membrane potential in N2a/Swe.DeltaE9 cells but not in N2a/Swe.D385A cells, which indicated that reduced formation of Abeta was the reason for reduction of ROS formation and increase of mitochondrial membrane potential when PS-1 activity was impaired in N2a/Swe.D385A cells. We concluded that neurotoxicity was positively correlated with the activity of gamma-secretase, which suggested inhibition of gamma-secretase is a rational pharmacological target for Alzheimer's disease treatment.

  4. IMAGING OF HIP JOINT PATHOLOGIES

    Directory of Open Access Journals (Sweden)

    Parul Dutta

    2016-08-01

    Full Text Available The hip joint is a large and complex articulation and can be involved by numerous pathologic conditions like congenital and developmental, infective, arthritic, and neoplastic. Early diagnosis and characterisation of pathology has vital role in proper management and follow up of the disease for the clinicians. Present study was conducted in 45 patients who underwent clinical, radiological, and pathological examination in GMCH. Maximum no of patient between age group of 10-30 yrs. male-female ratio was 1.8:1 and 30% cases are unilateral. FSE STAIR images were most useful in delineating pathologies. Gadolinium-enhanced scan were used to evaluate the extent of the disease and the pattern of involvement. AVN was the most common pathology detected comprising 29%. The next common abnormality detected was infective arthritis found in 26% of cases. In case of Legg-Calve-Perthes disease, there was abnormal linear increase in the signal intensity at junction of the epiphyseal cartilage. Ultrasonography is useful for the screening of paediatric hip cases and also for guided aspiration for histopathology. CT scan shows better resolution of soft tissue then the radiograph. The importance of early diagnosis can be gauzed from the fact that early initiation of treatment creates the difference between a responsible, worthwhile life, and a cripple handicapped life. The role of imaging can never be undermined considering the fact that early suspicion and detection is within the realms of imaging.

  5. Fellowship trends of pathology residents.

    Science.gov (United States)

    Lagwinski, Nikolaj; Hunt, Jennifer L

    2009-09-01

    Recent changes in pathology residency education have included a decrease in the program length (from 5 years to 4 years for combined anatomic and clinical pathology training) and a national mandate for programs to assess 6 general competencies of trainees. These have undoubtedly led to changes in program curricula and in residents' desires to seek fellowship training. This study was designed to gather information about what residents are seeking from fellowship training programs. This study used an online survey to assess attitudes of residents in training programs toward fellowship training. The survey instrument had 26 questions pertaining to fellowship choices, motivations for pursuing fellowships, expectations of the fellowships, and postresidency concerns. There were 213 respondents from a mix of program types and representing each postgraduate year. Most residents will seek at least 1 or 2 fellowships after residency training. The most popular first-choice fellowship was surgical pathology (26%), followed by cytopathology (16%), hematopathology (15%), gastrointestinal pathology (10%), dermatopathology (8%), and forensic pathology (5%). The most common reasons for pursuing fellowship training were to "increase marketability" (43%) or to "become an expert in a particular area" (33%). Most trainees got their information about fellowship training programs from Internet sources. Fellowship programs will benefit from an optimally designed Web site because residents seek information predominantly from the Internet. Residents seeking fellowships are particularly concerned with selecting programs that provide job connections, an increase in their marketability, and the opportunity to develop diagnostic expertise.

  6. Communication skills in diagnostic pathology.

    Science.gov (United States)

    Lehr, Hans-Anton; Bosman, Fred T

    2016-01-01

    Communication is an essential element of good medical practice also in pathology. In contrast to technical or diagnostic skills, communication skills are not easy to define, teach, or assess. Rules almost do not exist. In this paper, which has a rather personal character and cannot be taken as a set of guidelines, important aspects of communication in pathology are explored. This includes what should be communicated to the pathologist on the pathology request form, communication between pathologists during internal (interpathologist) consultation, communication around frozen section diagnoses, modalities of communication of a final diagnosis, with whom and how critical and unexpected findings should be communicated, (in-)adequate routes of communication for pathology diagnoses, who will (or might) receive pathology reports, and what should be communicated and how in case of an error or a technical problem. An earlier more formal description of what the responsibilities are of a pathologist as communicator and as collaborator in a medical team is added in separate tables. The intention of the paper is to stimulate reflection and discussion rather than to formulate strict rules.

  7. [Pathological buying -- a literature review].

    Science.gov (United States)

    Müller, Astrid; Reinecker, Hans; Jacobi, Corinna; Reisch, Lucia; de Zwaan, Martina

    2005-01-01

    This review summarizes the literature on pathological buying published during the past 15 years. Pathological or compulsive buying is defined as frequent preoccupation with buying or impulses to buy that are experienced as irresistible, intrusive, and/or senseless. The buying behavior causes marked distress, interferes with social functioning, and often results in financial problems. Studies on the phenomenology, diagnosis, classification, comorbidity, epidemiology, and treatment are presented. Pathological buying should be diagnosed as impulse control disorder not otherwise specified (ICD-10 F63.9). Psychiatric comorbidity is frequent, particulary mood, anxiety, substance use, eating, impulse control and obsessive-compulsive disorders. The positive results of pharmacological treatment with antidepressants (usually SSRI) and opioid antagonists could not be confirmed in controlled trials. A disorder specific cognitive-behavioral group treatment manual was published in USA. A controlled study is currently conducted in USA and since 2003 at the Department of Psychosomatics and Psychotherapy at the University Hospital Erlangen.

  8. [Pathology of the vitreomacular interface].

    Science.gov (United States)

    Pop, Monica; Gheorghe, Alina

    2014-01-01

    Vitreous role in the pathophysiology of retinal diseases has increased importantly over the recent years. This was possible using Optical Coherence Tomography which reviewed the way the vitreoretinal interface should be looked at and defined and classified new pathologies such as Vitreoretinal Traction Syndrome. Vitreous is not an empty space but an important anatomical structure with role in ocular physiology. With age biochemical changes occur so that vitreous starts to liquefy. Once the vitreous is liquefied (sinchisis) it collapses and passes in the retrohialoid space (sineresis). In complete PVD besides sinchisis there is a weakness of the adherence between the posterior cortex and ILM with total detachment of posterior cortex. Abnormal adhesions are associated with incomplete PVD. The definition and understanting of vitreoretinal pathology is an active and continuous process, PVD being the trigger of a lot of retinal pathologies: epiretinal membrane, macular hole, tractional macular oedema, VMTS, myopic traction maculopathy, exacerbations of exudative ARMD.

  9. Pathology Imagebase - A Reference Image Database for Standardization of Pathology.

    Science.gov (United States)

    Egevad, Lars; Cheville, John; Evans, Andrew J; Hörnblad, Jonas; Kench, James G; Kristiansen, Glen; Leite, Katia R M; Magi-Galluzzi, Cristina; Pan, Chin-Chen; Samaratunga, Hemamali; Srigley, John R; True, Lawrence; Zhou, Ming; Clements, Mark; Delahunt, Brett

    2017-07-19

    Despite efforts to standardize histopathology practice through the development of guidelines, the interpretation of morphology is still hampered by subjectivity. We here describe Pathology Imagebase, a novel mechanism for establishing an international standard for the interpretation of pathology specimens. The International Society of Urological Pathology (ISUP) established a reference image database through the input of experts in the field. Three panels were formed, one each for prostate, urinary bladder and renal pathology, consisting of 24 international experts. Each of the panel members uploaded microphotographs of cases into a non-public database. The remaining 23 experts were asked to vote from a multiple-choice menu. Prior to and while voting panel members were unable to access the results of voting by the other experts. When a consensus level of at least 2/3 or 16 votes was reached, cases were automatically transferred to the main database. Consensus was reached in a total of 287 cases across five projects on the grading of prostate, bladder and renal cancer and classification of renal tumours and flat lesions of the bladder. The full database is available to all ISUP members at www.isupweb.org. Non-members may access a selected number of cases. It is anticipated that the database will assist pathologists in calibrating their grading and will also promote consistency in the diagnosis of difficult cases. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Pathological Gambling in Parkinson's Disease

    DEFF Research Database (Denmark)

    Callesen, Mette Buhl; Linnet, Jakob; Thomsen, Kristine Rømer

    Pathological Gambling in Parkinson’s Disease Mette Buhl Callesen, Jakob Linnet, Kristine Rømer Thomsen, Albert Gjedde, Arne Møller PET Center, Aarhus University Hospital and Center of Functionally Integrative Neuroscience, Aarhus University.   The neurotransmitter dopamine is central to many...... aspects of human functioning, e.g., reward, learning, and addiction, including Pathological Gambling (PG), and its loss is key to Parkinson’s Disease (PD). PD is a neurodegenrative disorder caused by progressive loss of dopamine-producing cells in the midbrain [1]. One type of treatment of PD symptoms...

  11. Optimal breast cancer pathology manifesto.

    Science.gov (United States)

    Tot, T; Viale, G; Rutgers, E; Bergsten-Nordström, E; Costa, A

    2015-11-01

    This manifesto was prepared by a European Breast Cancer (EBC) Council working group and launched at the European Breast Cancer Conference in Glasgow on 20 March 2014. It sets out optimal technical and organisational requirements for a breast cancer pathology service, in the light of concerns about variability and lack of patient-centred focus. It is not a guideline about how pathology services should be performed. It is a call for all in the cancer community--pathologists, oncologists, patient advocates, health administrators and policymakers--to check that services are available that serve the needs of patients in a high quality, timely way.

  12. Pathologies sociales de la communication

    OpenAIRE

    Durand, Pascal

    2009-01-01

    La communication, dans sa généralité et dans la perspective des travaux récents de l'Ecole de Francfort, est généralement pensée comme solution à diverses pathologies sociales (isolement, malentendus réciproques, aliénation, etc.). Le présent article l'envisage comme un vecteur de pathologies spécifiques : anomie, censure, propagande, production d'idéologèmes divers. Peer reviewed

  13. Mathematical Pathologies as Pathways into Creativity

    Science.gov (United States)

    Sriraman, Bharath; Dickman, Benjamin

    2017-01-01

    In this paper, the role of mathematical pathologies as a means of fostering creativity in the classroom is discussed. In particular, it delves into what constitutes a mathematical pathology, examines historical mathematical pathologies as well as pathologies in contemporary classrooms, and indicates how the Lakatosian heuristic can be used to…

  14. Long-term neprilysin gene transfer is associated with reduced levels of intracellular Abeta and behavioral improvement in APP transgenic mice

    Directory of Open Access Journals (Sweden)

    Patrick Christina

    2008-11-01

    Full Text Available Abstract Background Proteolytic degradation has emerged as a key pathway involved in controlling levels of the Alzheimer's disease (AD-associated amyloid-β (Aβ peptide in the brain. The endopeptidase, neprilysin, has been implicated as a major Aβ degrading enzyme in mice and humans. Previous short and intermediate term studies have shown the potential therapeutic application of neprilysin by delivering this enzyme into the brain of APP transgenic mice using gene transfer with viral vectors. However the effects of long-term neprilysin gene transfer on other aspects of Aβ associated pathology have not been explored yet in APP transgenic mice. Results We show that the sustained expression of neprilysin for up to 6 months lowered not only the amyloid plaque load but also reduced the levels of intracellular Aβ immunoreactivity. This was associated with improved behavioral performance in the water maze and ameliorated the dendritic and synaptic pathology in the APP transgenic mice. Conclusion These data support the possibility that long-term neprilysin gene therapy improves behavioral and neurodegenerative pathology by reducing intracellular Aβ.

  15. SYSTEMIC DISORDERS AFFECTING DENTAL PATHOLOGY

    OpenAIRE

    Knezevic R. Milan; Andjelic S. Gordana; Knezevic M. Milena

    2014-01-01

    A retrospective overview of systemic disorders which might be associated with dental pathology is made. They are grouped as follows: (a) congenital dental developmental disorders, (b) chromosomal anomalies, (c) radiations, (d) immune disorders, (e) intoxications, (f) neurological alterations, (g) gastrointestinal diseases, (h) osteodystrophy and associated conditions, (i) skin diseases, (j) metabolic and endocrine disorders, (k) craniofacial malformation syndromes and other congenital g...

  16. Giving your heart to pathology.

    Science.gov (United States)

    Klaassen, Jim

    2015-10-17

    Jim KIaassen recently joined Axiom Veterinary Laboratories as a clinical pathologist. During his career, Dr Klaassen has worked in small animal practice, lectured in clinical pathology, undertaken preclinical research and held senior roles in commercial veterinary laboratories in the USA, including as chief medical officer of Antech Diagnostics.

  17. Physiological and pathological cardiac hypertrophy.

    Science.gov (United States)

    Shimizu, Ippei; Minamino, Tohru

    2016-08-01

    The heart must continuously pump blood to supply the body with oxygen and nutrients. To maintain the high energy consumption required by this role, the heart is equipped with multiple complex biological systems that allow adaptation to changes of systemic demand. The processes of growth (hypertrophy), angiogenesis, and metabolic plasticity are critically involved in maintenance of cardiac homeostasis. Cardiac hypertrophy is classified as physiological when it is associated with normal cardiac function or as pathological when associated with cardiac dysfunction. Physiological hypertrophy of the heart occurs in response to normal growth of children or during pregnancy, as well as in athletes. In contrast, pathological hypertrophy is induced by factors such as prolonged and abnormal hemodynamic stress, due to hypertension, myocardial infarction etc. Pathological hypertrophy is associated with fibrosis, capillary rarefaction, increased production of pro-inflammatory cytokines, and cellular dysfunction (impairment of signaling, suppression of autophagy, and abnormal cardiomyocyte/non-cardiomyocyte interactions), as well as undesirable epigenetic changes, with these complex responses leading to maladaptive cardiac remodeling and heart failure. This review describes the key molecules and cellular responses involved in physiological/pathological cardiac hypertrophy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Pathological Gambling in Parkinson's Disease

    DEFF Research Database (Denmark)

    Callesen, Mette Buhl; Linnet, Jakob; Thomsen, Kristine Rømer

    Pathological Gambling in Parkinson’s Disease Mette Buhl Callesen, Jakob Linnet, Kristine Rømer Thomsen, Albert Gjedde, Arne Møller PET Center, Aarhus University Hospital and Center of Functionally Integrative Neuroscience, Aarhus University.   The neurotransmitter dopamine is central to many...... aspects of human functioning, e.g., reward, learning, and addiction, including Pathological Gambling (PG), and its loss is key to Parkinson’s Disease (PD). PD is a neurodegenrative disorder caused by progressive loss of dopamine-producing cells in the midbrain [1]. One type of treatment of PD symptoms...... is medication that binds to dopamine receptors in the brain, i.e., dopamine agonists [1]. Unfortunately, for some PD patients a very serious side effect to this specific kind of treatment is developing PG. PG is an Impulse Control Disorder characterized by recurrent maladaptive behavior associated with personal...

  19. Lung Pathology in Antiphospholipid Syndrome

    Directory of Open Access Journals (Sweden)

    T. M. Reshetnyak

    2005-01-01

    Full Text Available Functional lesions of organs depend on the size of a diseased vessel and frequently require the use of intensive therapy methods. The commonest manifestation of antiphospholipid syndrome (APS is deep vein thrombosis of the leg and pulmonary thromboembolism (PTE.Objective: to estimate the frequency of lung lesions in primary APS (PAPS, secondary (in the presence of systemic lupus erythematosus (SLE and catastrophic APS and to assess a relationship between lung pathology and other clinical and laboratory manifestations of the disease.Subjects and methods. The study covered 372 patients followed up at the Institute of Rheumatology, Russian Academy of Medical Sciences, since 1990, of whom 290 and 82 patients had SLE and PAPS, respectively. Among the 290 patients with SLE, there were 96 males and 194 females. At the moment of the study, the patients’ age was 31.2±11.1 years and the duration of the disease was 8.6±7.2 years. The group of patients with PAPS comprised 20 males and 62 females. Their mean age was 35.6±9.9 years and the duration of the disease was 11.9±8.5 years. Thrombotic events were verified only by instrumental studies. Lung pathology was instrumentally confirmed; all the patients underwent lung X-ray study, if required, scintigraphy and computed tomography.Results. Lung lesion associated with the pathology of vessels was revealed in 28% of the examined patients (105/372. There were prevalent patients with PTE, followed by the development of lung infarcts, which was present in 96 (91% of the 105 patients with pulmonary vascular pathology. Autopsy revealed pulmonary microangiopathy was in 12 patients, which was concurrent with focal pneumonia in 7 of them, with pneumonitis and exudative pleuritis in 5. Hemorrhagic alveolitis detected at autopsy in combination with occlusions of the pulmonary arterioles was in 3 patients who had been diagnosed as having thromboembolism of small branches of the pulmonary artery. Thrombosis of the

  20. Pharmacological Treatments in Pathological Gambling

    DEFF Research Database (Denmark)

    Grant, Jon E; Odlaug, Brian Lawrence; Schreiber, Liana R N

    2012-01-01

    demonstrated mixed results in controlled clinical trials. Although limited information is available, opioid antagonists and glutamatergic agents have demonstrated efficacious outcomes, especially for individuals with PG suffering from intense urges to engage in the behavior. CONCLUSIONS: Given that several......AIMS: Pathological gambling (PG) is a relatively common and often disabling psychiatric condition characterized by intrusive urges to engage in deleterious gambling behavior. Although common and financially devastating to individuals and families, there currently exist no formally approved...... pharmacotherapeutic interventions for this disorder. This review seeks to examine the history of medication treatments for PG. METHODS: A systematic review of the 18 double-blind, placebo-controlled pharmacotherapy studies conducted for the treatment of pathological gambling was conducted. Study outcome and the mean...

  1. Innovations in teaching plant pathology.

    Science.gov (United States)

    Schumann, G L

    2003-01-01

    The teaching environment for plant pathology is changing in both positive and negative ways. Teaching expectations are increasing and resources are decreasing, but recent educational research and instructional technology offer new approaches to meet these challenges. Plant pathologists are teaching courses that may attract new students to the discipline or at least improve agricultural awareness. The Internet offers rapid access to information and images for both students and instructors. Instructional technology provides new tools for classroom presentations, communication with students, reaching new audiences, and distance learning, but using these new tools to enhance learning requires skilled and creative instructors. In the past, many plant pathology instructors worked in relative isolation, but new communication technologies and publishing opportunities for teaching scholarship should improve the sharing of instructional resources and methods.

  2. Interleukin-22: immunobiology and pathology

    Science.gov (United States)

    Dudakov, Jarrod A.; Hanash, Alan M.; van den Brink, Marcel R.M.

    2015-01-01

    Interleukin-22 (IL-22) is a recently described IL-10 family cytokine that is produced by T-helper (Th)-17 cells, γδ T cells, NKT cells and newly described innate lymphoid cells (ILCs). Knowledge of IL-22 biology has rapidly evolved since its discovery in 2000, and a role for IL-22 has been identified in numerous tissues including the intestines, lung, liver, kidney, thymus, pancreas and skin. IL-22 primarily targets non-hematopoietic epithelial and stromal cells where it can promote proliferation and play a role in tissue regeneration. In addition, IL-22 regulates host defense at barrier surfaces. However, IL-22 has also been linked to several conditions involving inflammatory tissue pathology. In this review, we will assess the current understanding of this cytokine, including its physiologic and pathologic effects on epithelial cell function. PMID:25706098

  3. Quality in pathology laboratory practice.

    Science.gov (United States)

    Weinstein, S

    1995-06-01

    Quality refers not only to analytical quality control, a traditional area of laboratory excellence, but to the entire science of quality management. As measures of quality, structural indicators refer to staffing and physical facilities, process indicators to the institutions operations and, perhaps most importantly, outcome indicators address the ultimate patient care uses that pathology information is put to. Comparison of performance to peer laboratories, external quality control, is a practical, if limited, yardstick of performance. Customer satisfaction and turn-around-time of tests are receiving more recent attention as quality measures. Blood banking, because of its inherently complex cycle from donor phlebotomy to product infusion, requires special considerations with regard to quality management. Reporting of anatomical pathology, where the only gold standard is a consensus of experts, also does not lend itself to classical numerical quality assessment.

  4. Pathological fear of cot death.

    Science.gov (United States)

    Weightman, H; Dalal, B M; Brockington, I F

    1998-01-01

    Cot death (sudden infant death syndrome) is one of the most common causes of death in the first year of life. Four cases with a pathological fear of cot death are presented. All the patients were depressed and in 2 cases the fear of cot death had an obsessional quality. In all cases there were complications during pregnancy (miscarriage, threatened abortion, recurrent vomiting in last trimester). In 1 case, the patient knew 3 mothers who had suffered cot deaths; in another, the infant was gravely ill in the neonatal period. Pathological fear of cot death can be recognised by the presence of two central features - overvigilance and excessive nocturnal checking of the baby's breathing. Therapeutic interventions are discussed.

  5. Insulin dysfunction and Tau pathology

    Directory of Open Access Journals (Sweden)

    Noura eEl Khoury

    2014-02-01

    Full Text Available The neuropathological hallmarks of Alzheimer's disease (AD include senile plaques of β-amyloid (Aβ peptides (a cleavage product of the Amyloid Precursor Protein, or APP and neurofibrillary tangles (NFT of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF. NFT pathology is important since it correlates with the degree of cognitive impairment in AD.Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99% is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease.Insulin dysfunction, manifested by diabetes mellitus (DM might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM and type 2 diabetes (T2DM are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment.Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting on Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia.

  6. Informational pathologies and interest bubbles

    DEFF Research Database (Denmark)

    Hendricks, Vincent Fella; Wiewiura, Joachim Schmidt

    2017-01-01

    This article contends that certain configurations of information networks facilitate specific cognitive states that are instrumental for decision and action on social media. Group-related knowledge and belief states—in particular common knowledge and pluralistic ignorance—may enable strong public...... signals. Indeed, some network configurations and attitude states foster informational pathologies that may fuel interest bubbles affecting agenda-setting and the generation of narratives in public spheres....

  7. Canine and feline oral pathology

    OpenAIRE

    Costa, S.; Pais, B.; Almeida, D.; Simões, J.; Mega, A. C.; Vala, Helena

    2013-01-01

    The aim of this work was to present a brief review of the main conditions affecting the oral cavity of dogs and cats. In recent years there has been increased attention with regard to veterinary dentistry, being several and frequent the pathologies located in the oral cavity of our pets. These diseases mainly affect the teeth and the mucous membranes of the oral cavity, and may, in chronic cases, also affect vital organs. This condition could have different causes, including hereditary, conge...

  8. [The normal and the pathological].

    Science.gov (United States)

    Hofmann, B

    1995-12-10

    The main problem of modern health care is to express its goals and its limits. To do this it is necessary to answer the fundamental question: what is normal and what is pathological? The French physician and philosopher Georges Canguilhem has tried to answer this question. He claims that for medicine, the difference between these fundamentals is determined by normativity and not by science. In doing this he wishes to save the autonomy of the individual patient and to delimit medicine from science.

  9. Medical discourse in pathological anatomy.

    Science.gov (United States)

    Moskalenko, R; Tatsenko, N; Romanyuk, A; Perelomova, O; Moskalenko, Yu

    2012-05-01

    The paper is devoted to the peculiarities of medical discourse in pathological anatomy as coherent speech and as a linguistic correlate of medical practice taking into account the analysis of its strategies and tactics. The purpose of the paper is to provide a multifaceted analysis of the speech strategies and tactics of pathological anatomy discourse and ways of their implementation. The main strategies of medical discourse in pathological anatomy are an anticipating strategy, a diagnosing strategy and an explaining one. The supporting strategies are pragmatic, conversational and a rhetorical one. The pragmatic strategy is implemented through contact establishing tactics, the conversational one - with the help of control tactics, the rhetorical one - with the help of attention correction tactics. The above mentioned tactics and strategies are used in the distinguishing of major, closely interrelated strategies: "the contact strategy" (to establish contact with a patient's relatives - phatic replicas of greeting and addressing) and "the strategy of explanation" (used in the practice of a pathologist for a detailed explanation of the reasons of a patient's death). The ethic aspect of speech conduct of a doctor-pathologist is analyzed.

  10. Diagnostic pathology in 2012: development of digital pathology in an open access journal

    Directory of Open Access Journals (Sweden)

    Kayser Klaus

    2013-01-01

    Full Text Available Abstract Herein we describe and interpret the digital world of diagnostic surgical pathology, and take the in Pathology leading Open Access Journal Diagnostic Pathology as example. Virtual slide http://www.diagnosticpathology.diagnomx.eu/vs/1944221953867351

  11. Extensive renovation the pathology of heritage building

    DEFF Research Database (Denmark)

    Rasmussen, Torben Valdbjørn

    2015-01-01

    The pathology of heritage buildings is often related to renovation initiatives typically initiated by implementing energy savings measures.......The pathology of heritage buildings is often related to renovation initiatives typically initiated by implementing energy savings measures....

  12. Extensive renovation the pathology of heritage buildings

    DEFF Research Database (Denmark)

    Rasmussen, Torben Valdbjørn

    2015-01-01

    The pathology of heritage buildings is often related to renovation initiatives typically initiated by implementing energy savings measures.......The pathology of heritage buildings is often related to renovation initiatives typically initiated by implementing energy savings measures....

  13. Congruence Couple Therapy for Pathological Gambling

    Science.gov (United States)

    Lee, Bonnie K.

    2009-01-01

    Couple therapy models for pathological gambling are limited. Congruence Couple Therapy is an integrative, humanistic, systems model that addresses intrapsychic, interpersonal, intergenerational, and universal-spiritual disconnections of pathological gamblers and their spouses to shift towards congruence. Specifically, CCT's theoretical…

  14. Personality dimensions and disorders in pathological gambling

    DEFF Research Database (Denmark)

    Odlaug, Brian Lawrence; Schreiber, Liana R N; Grant, Jon E

    2013-01-01

    This review presents the most current research in personality dimensions and disorders with respect to pathological gambling.......This review presents the most current research in personality dimensions and disorders with respect to pathological gambling....

  15. Ethics and Professionalism in Pathology

    Directory of Open Access Journals (Sweden)

    R Baral

    2016-03-01

    Full Text Available Pathologists spend most of their professional lives beyond direct view of the public, mostly inside the four walls of the lab. It is the clinicians who face the wrath of the public when something goes wrong. However, with the growing awareness of the public into the decisive role played by the Pathologists in the definitive diagnosis of the disease, the pathologists will soon be the target of the aggrieved patients and relatives.1 The issue of ethics can be dealt when professionalism comes before profession. "Professionalism in medicine requires that physician serve the interests of the patient above his or her own selfinterest." Professionalism aspires to philanthropy, answerability, excellence, duty, service and respect for others. "Professionalism in Pathology is based on the same tenets, but has additional dimensions."The qualities of professionalism for pathologists include 1. Communication with the patients and the clinicians. A small phone call with the clinician will solve most of the clinical mysteries not written in the lab requisition forms; 2. Empathy and Compassion towards patients', colleagues', and laboratory personnel's culture, age, gender, and disabilities; 3. Demonstration of passion, respect and understanding towards the patients; 4. Adherence to guidelines and regulations of the regulatory and accrediting bodies; and 5.Profeciency and knowledge in one's work is valued by the patients more than the credentials, which also enables one to identify deficiencies in peer performance. The basic competencies of professionalism are vital to every pathology report, which in turn is the mirror of the ethics practiced by the pathologist. Evaluating oneself is perhaps the most important tool in maintaining professionalism in the practice of pathology. One colleague recently defined professionalism as “all the things one does when no one is watching,” thus placing personal integrity at the top of the list.

  16. 42 CFR 493.853 - Condition: Pathology.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Pathology. 493.853 Section 493.853 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.853 Condition: Pathology. The specialty of pathology includes, for purposes...

  17. Iliopsoas: Pathology, Diagnosis, and Treatment.

    Science.gov (United States)

    Anderson, Christian N

    2016-07-01

    Disorders of the iliopsoas can be a significant source of groin pain in the athletic population. Commonly described pathologic conditions include iliopsoas bursitis, tendonitis, impingement, and snapping. The first-line treatment for iliopsoas disorders is typically conservative, including activity modification, physical therapy, nonsteroidal anti-inflammatory drugs, and corticosteroid injections. Surgical treatment can be considered if the patient fails conservative measures and typically involves arthroscopic lengthening of the musculotendinous unit and treatment of concomitant intra-articular abnormality. Tendon release has been described: in the central compartment, in the peripheral compartment, and at the lesser trochanter, with similar outcomes observed between the techniques. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Pathologic pancreatic endocrine cell hyperplasia

    Institute of Scientific and Technical Information of China (English)

    Debra Ouyang; Deepti Dhall; Run Yu

    2011-01-01

    Pathologic hyperplasia of various pancreatic endocrine cells is rare but has been long known. β cell hyperplasia contributes to persistent hyperinsulinemic hypoglycemia of infancy, which is commonly caused by mutations in the islet ATP-sensitive potassium channel, and to noninsulinoma pancreatogenous hypoglycemia in adults,which may or may not be associated with bariatric surgery.α cell hyperplasia may cause glucagonoma syndrome or induce pancreatic neuroendocrine tumors. An inactivating mutation of the glucagon receptor causes α cell hyperplasia and asymptomatic hyperglucagonemia.Pancreatic polypeptide cell hyperplasia has been described without a clearly-characterized clinical syndrome and hyperplasia of other endocrine cells inside the pancreas has not been reported to our knowledge.Based on morphological evidence, the main pathogenetic mechanism for pancreatic endocrine cell hyperplasia is increased endocrine cell neogenesis from exocrine ductal epithelium. Pancreatic endocrine cell hyperplasia should be considered in the diagnosis and management of hypoglycemia, elevated islet hormone levels,and pancreatic neuroendocrine tumors. Further studies of pathologic pancreatic endocrine cell hyperplasia will likely yield insights into the pathogenesis and treatment of diabetes and pancreatic neuroendocrine tumors.

  19. Dopamine Agonists and Pathologic Behaviors

    Directory of Open Access Journals (Sweden)

    Brendan J. Kelley

    2012-01-01

    Full Text Available The dopamine agonists ropinirole and pramipexole exhibit highly specific affinity for the cerebral dopamine D3 receptor. Use of these medications in Parkinson’s disease has been complicated by the emergence of pathologic behavioral patterns such as hypersexuality, pathologic gambling, excessive hobbying, and other circumscribed obsessive-compulsive disorders of impulse control in people having no history of such disorders. These behavioral changes typically remit following discontinuation of the medication, further demonstrating a causal relationship. Expression of the D3 receptor is particularly rich within the limbic system, where it plays an important role in modulating the physiologic and emotional experience of novelty, reward, and risk assessment. Converging neuroanatomical, physiological, and behavioral science data suggest the high D3 affinity of these medications as the basis for these behavioral changes. These observations suggest the D3 receptor as a therapeutic target for obsessive-compulsive disorder and substance abuse, and improved understanding of D3 receptor function may aid drug design of future atypical antipsychotics.

  20. Fibroadenomas: Sonographic-pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Sung; Choi, Hye Young; Kim, Eun Ah; Lee, Sun Wha; Sung, Soon Hee [Ewha Womans University, Seoul (Korea, Republic of)

    1999-09-15

    To correlate sonographic appearance and histopathologic findings of fibroadenomas. Forty-one biopsy-proven fibroadenomas were retrospectively evaluate for sonographic-pathologic correlation. The fibroadenomas were histologically classified into sclerotic, myxoid, glandular and mixed type. The stromal cellularity and fibrosis were also classified into mild and severe. The internal echotexture and posterior acoustic enhancement of mass in ultrasonogram were correlated with histopathologic findings. The pathologic types of fibroadenomas were sclerotic in sixteen, myxoid in thirteen, and glandular or mixed in each of six cases. Most of the sclerotic type showed hypoechoic internal echotexture (68.8%) and myxoid and glandular types showed isoechoic internal echotexture (84.6%, 83.3% respectively). The hypoechoic masses showed 12 cases of mild (75.0%) and 4 cases of severe (25.0%) in cellularity and 3 cases of mild (18.7%) and 13 cases (81.3%) of sever degree in fibrosis. Most of the myxoid type (77%) showed posterior enhancement, and most of the sclerotic type (87.5%) did not show posterior enhancement on ultrasonogram. Posterior enhancement was absent in 22 cases, in which 4 cases (18.2%) showed mild and 18 cases (81.2%) showed severe degree of fibrosis. Sclerotic type with mild cellularity and severe fibrosis on histopathology showed hypoechogenicity on ultrasonogram; whereas myxoid and glandular types were predominantly isoechoic. Most of the myxoid type showed posterior enhancement. Sclerotic type with mild cellularity and severe fibrosis did not show posterior enhancement.

  1. Pathologic pancreatic endocrine cell hyperplasia

    Science.gov (United States)

    Ouyang, Debra; Dhall, Deepti; Yu, Run

    2011-01-01

    Pathologic hyperplasia of various pancreatic endocrine cells is rare but has been long known. β cell hyperplasia contributes to persistent hyperinsulinemic hypoglycemia of infancy, which is commonly caused by mutations in the islet ATP-sensitive potassium channel, and to non-insulinoma pancreatogenous hypoglycemia in adults, which may or may not be associated with bariatric surgery. α cell hyperplasia may cause glucagonoma syndrome or induce pancreatic neuroendocrine tumors. An inactivating mutation of the glucagon receptor causes α cell hyperplasia and asymptomatic hyperglucagonemia. Pancreatic polypeptide cell hyperplasia has been described without a clearly-characterized clinical syndrome and hyperplasia of other endocrine cells inside the pancreas has not been reported to our knowledge. Based on morphological evidence, the main pathogenetic mechanism for pancreatic endocrine cell hyperplasia is increased endocrine cell neogenesis from exocrine ductal epithelium. Pancreatic endocrine cell hyperplasia should be considered in the diagnosis and management of hypoglycemia, elevated islet hormone levels, and pancreatic neuroendocrine tumors. Further studies of pathologic pancreatic endocrine cell hyperplasia will likely yield insights into the pathogenesis and treatment of diabetes and pancreatic neuroendocrine tumors. PMID:21245985

  2. The Norm___ and the Pathological

    Directory of Open Access Journals (Sweden)

    Kevin Gotkin

    2016-03-01

    Full Text Available In this paper, I read The Normal and the Pathological by French philosopher Georges Canguilhem for what it can offer disability theory. I examine how the field has already taken up the text but further, I argue for The Normal and the Pathological as a keystone of disability theory (currently taken up with curiously reserved energy. I start with a précis on the text before offering a condensed citation analysis of the book. In the latter part of the paper, I suggest how the monograph might inform current conversations and I offer possibilities for it to deepen and complicate core notions about disability, including the social model, norms, normalcy, and the normate. I conclude by suggesting that Canguilhem’s philosophical intervention can be understood as "propulsive atavism" – an excavation of medical epistemology in order to map and reconfigure its legacies – and I propose this as one methodological template for disability scholarship.

  3. Anatomical pathology is dead? Long live anatomical pathology.

    Science.gov (United States)

    Nicholls, John M; Francis, Glenn D

    2011-10-01

    The standard diagnostic instrument used for over 150 years by anatomical pathologists has been the optical microscope and glass slide. The advent of immunohistochemistry in the routine laboratory in the 1980s, followed by in situ hybridisation in the 1990s, has increased the armamentaria available to the diagnostic pathologist, and this technology has led to changed patient management in a limited number of neoplastic diseases. The first decade of the 21 century has seen an increasing number of publications using proteomic technologies that promise to change disease diagnosis and management, the traditional role of an anatomical pathologist. Despite the plethora of publications on proteomics and pathology, to date there are actually limited data where proteomic technologies do appear to be of greater diagnostic value than the standard histological slide. Though proteomic techniques will become more prevalent in the future, it will need the expertise of an anatomical pathologist to dissect out and validate this added information.

  4. Slot Machine Response Frequency Predicts Pathological Gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Rømer Thomsen, Kristine; Møller, Arne

    2013-01-01

    Slot machines are among the most addictive forms of gambling, and pathological gambling slot machine players represent the largest group of treatment seekers, accounting for 35% to 93% of the population. Pathological gambling sufferers have significantly higher response frequency (games / time......) on slot machines compared with non-problem gamblers, which may suggest increased reinforcement of the gambling behavior in pathological gambling. However, to date it is unknown whether or not the increased response frequency in pathological gambling is associated with symptom severity of the disorder....... This study tested the hypothesis that response frequency is associated with symptom severity in pathological gambling. We tested response frequency among twenty-two pathological gambling sufferers and twenty-one non-problem gamblers on a commercially available slot machine, and screened for pathological...

  5. Telescoping phenomenon in pathological gambling

    DEFF Research Database (Denmark)

    Grant, Jon E; Odlaug, Brian Lawrence; Mooney, Marc E

    2012-01-01

    The course of pathological gambling (PG) in women has been described as having a later age of initiation but a shorter time to problematic gambling ("telescoped"). This study examined evidence for telescoping and its relationship with comorbidities. Seventy-one treatment-seeking individuals with PG...... underwent a diagnostic interview to examine gambling behaviors, age at initiation of gambling, and time from initiation to meeting criteria for PG. The women had a higher mean age at gambling initiation compared with that of the men (mean [SD] age, 31.3 [13.0] years, compared with 22.4 [7.9] years; p = 0...... and suggests a need for greater clinical focus on the gender differences of gambling behavior....

  6. Pathology of hepatic iron overload

    Institute of Scientific and Technical Information of China (English)

    Yves Deugnier; Bruno Turlin

    2007-01-01

    Although progress in imaging and genetics allow for a noninvasive diagnosis of most cases of genetic iron overload, liver pathology remains often useful (1) to assess prognosis by grading fibrosis and seeking for associated lesions and (2) to guide the etiological diagnosis, especially when no molecular marker is available.Then, the type of liver siderosis (parenchymal, mesenchymal or mixed) and its distribution throughout the lobule and the liver are useful means for suggesting its etiology: HLA-linked hemochromatosis gene (HFE) hemochromatosis or other rare genetic hemochromatosis,nonhemochromatotic genetic iron overload (ferroportin disease, aceruloplasminemia), or iron overload secondary to excessive iron supply, inflammatory syndrome,noncirrhotic chronic liver diseases including dysmetabolic iron overload syndrome, cirrhosis, and blood disorders.

  7. Placental pathology in pregnancy complications.

    Science.gov (United States)

    Huppertz, Berthold

    2011-02-01

    Among pregnancy pathologies preeclampsia and fetal growth restriction are among the leading causes of maternal and perinatal mortality and morbidity. For both syndromes, the etiologies are still unclear in many facets. For the development of preeclampsia the presence of the placenta is a prerequisite, while for FGR a variety of other factors may be decisive. Cases with a combination of FGR and preeclampsia are the most severe cases and need clinical intervention. Studies on such cases have misled scientists and clinicians to hypothesize that a failure of trophoblast invasion is a specific feature of the early onset type of preeclampsia. Recent development in preeclampsia specific biomarkers and the intense use of Doppler ultrasound measurements already in the first trimester of pregnancy has resulted in a new understanding of the pathways leading to preeclampsia or FGR.

  8. Radiologic Imaging of Diaphragmatic Pathologies

    Directory of Open Access Journals (Sweden)

    Hatice Öztürkmen Akay

    2004-01-01

    Full Text Available We researched the images methods in the evaluation of diaphragmaticpathologies. The study was done with 30 patients (21 males, 9 females. Themedian age of the patients was 36.1 years (Range 1-74 years. Firstly,lateraly and posteroanterior chest X-Ray were done in all patients the otherradiological images were the Barium examination, ultrasonography,computerized tomography and magnetic rezonans imaging. We determineddiaphragmatic pseudotumour in 4 patients, congenital diaphragmatichernia in 6 patients, diaphragmatic paralysis in 2 patients, diaphragmaticelevation in 8 patients, hiatal hernia in 5 patients, and diaphragmaticrupture in 5 patients.Although radiological images were developed all, we believe that thediaphragmatic pathologies should be evaluated with both clinically andradiologically in all patients.

  9. [Ductoscopy for pathologic nipple discharge].

    Science.gov (United States)

    Waaijer, Laurien; van Diest, Paul J; van der Pol, Carmen C; Verolme, Berna; Hennink, Annelies; Witkamp, Arjen J

    2013-01-01

    Pathologic nipple discharge is a symptom that frequently causes female patients to visit the outpatient breast clinic. In the vast majority of cases, the symptom is caused by a benign intraductal laesion. The options for diagnosis and treatment have long been limited; surgery was not infrequently the treatment of choice. With the advent of breast ductoscopy, a micro-endoscopic procedure, it is possible to visualise abnormalities in the ductal system. Tissue for histopathological investigation can be retrieved from the duct and the condition can be treated. The patient with nipple discharge is consequently prevented from having to undergo an invasive and fairly 'blindly' executed procedure under general anaesthesia. The miniscule dimensions of the duct in which the technique is carried out pose the greatest challenge to the further development of the ductoscope.

  10. Contemporary pharmacotherapy and iatrogenic pathology

    Directory of Open Access Journals (Sweden)

    Trailović D.R.

    2005-01-01

    Full Text Available During the past few decades, the pharmaceutical industry has developed into a powerful human activity highly influencing modern medicine. Thousands of synthetic therapeuticals have been developed, and these formulations enabled the successful treatment of many diseases, some of which were considered incurable. An increase in drug consumption followed the development of the pharmaceutical industry and the introduction of synthetic drugs. The widespread use of new medicals enabled the collection of data confirming their effectiveness, but also more and more data concerning side and unwanted effects were reported. Frequent side/unwanted effect reports gave rise to development of iatrogenic pathology, a new branch of clinical pathology. The knowledge of the possible unwanted effects of drugs on macro organisms did not enable the effective withdrawal of such formulations from the market. At the beginning, the reports concerning unwanted effects were not verealed. Consequently some potentially harmful formulations were used for years without methodical analyses of their side/unwanted effects. Some potentially dangerous formulations are still on the market such as drugs containing ulcerogenic, hepatotoxic, nephrotoxic substances as well as those inducing bone marrow aplasia. The administration of these potentially dangerous formulations is understandable in the case of clear therapeutic indications allowing no alternatives. In these cases the risk of harmful side effects is greatly overwhelmed by the risk from the primary disease. Otherwise the administration of the potentially harmful drug is unjustified, especially if the indication is not a disease. Many potentially harmful drugs are formulated for use in healthy animals, recommended as growth, laying and milk stimulators, those allowing higher speed and strength in sport and racing horses, estrus inducers and suppressors. The misuse or maluse medication is highly present in sport horses daily

  11. Long-term electromagnetic pulse exposure induces Abeta deposition and cognitive dysfunction through oxidative stress and overexpression of APP and BACE1.

    Science.gov (United States)

    Jiang, Da-Peng; Li, Jin-Hui; Zhang, Jie; Xu, Sheng-Long; Kuang, Fang; Lang, Hai-Yang; Wang, Ya-Feng; An, Guang-Zhou; Li, Jing; Guo, Guo-Zhen

    2016-07-01

    A progressively expanded literature has been devoted in the past years to the noxious or beneficial effects of electromagnetic field (EMF) to Alzheimer׳s disease (AD). This study concerns the relationship between electromagnetic pulse (EMP) exposure and the occurrence of AD in rats and the underlying mechanisms, focusing on the role of oxidative stress (OS). 55 healthy male Sprague Dawley (SD) rats were used and received continuous exposure for 8 months. Morris water maze (MWM) test was conducted to test the ability of cognitive and memory. The level of OS was detected by superoxide dismutase (SOD) activity and glutathione (GSH) content. We found that long-term EMP exposure induced cognitive damage in rats. The content of β-amyloid (Aβ) protein in hippocampus was increased after long-term EMP exposure. OS of hippocampal neuron was detected. Western blotting and immunohistochemistry (IHC) assay showed that the content of Aβ protein and its oligomers in EMP-exposed rats were higher than that of sham-exposed rats. The content of Beta Site App Cleaving Enzyme (BACE1) and microtubule-associated protein 1 light chain 3-II (LC3-II) in EMP-exposed rats hippocampus were also higher than that of sham-exposed rats. SOD activity and GSH content in EMP-exposed rats were lower than sham-exposed rats (pEMP exposure-induced OS, including increased amyloid precursor protein (APP) aberrant cleavage. Although further study is needed, the present results suggest that long-term EMP exposure is harmful to cognitive ability in rats and could induce AD-like pathological manifestation.

  12. Pathologic mitoses and pathology of mitosis in tumorigenesis

    Directory of Open Access Journals (Sweden)

    RG Steinbeck

    2009-12-01

    Full Text Available The gist of my hypothesis (.. is a certain abnormal chromatin constitution. Each process, which brings about this chromatin constitution, would result in the origin of a malignant tumour. Certainly, I consider irregularities with mitosis as the normal mode of the origin of an incorrectly assembled nucleus. This statement by Boveri (1914 has considered earlier observations of asymmetric divisions in human cancers (Hansemann, 1890. The hypothesis is based on the understanding of mitosis as an equational bipartition of the hereditary substance (Flemming, 1879; Roux, 1883. Latest since it was known that genes are located on chromosomes (Sturtevant, 1913, their balanced transport in anaphase appeared as a condition of correct somatic proliferation. True mitoses guarantee the constancy of terminally differentiated tissues. Politzer (1934 has performed X-ray experiments to investigate abnormal karyokinesis with regard to anomalous chromatin condensation, chromosome breakage, spindle malformation, and failure in cytokinesis. On the basis of light microscopy, further significant progress in understanding the pathology of mitosis was not possible. Tumour cases with reduced chromosome numbers seduced to the idea that mitotic activity is rather under cytoplasmic than under nuclear control (Koller, 1947.

  13. The pathological interaction between diabetes and presymptomatic Alzheimer's disease.

    Science.gov (United States)

    Burdo, Joseph R; Chen, Qi; Calcutt, Nigel A; Schubert, David

    2009-12-01

    Since diabetes is a risk factor for Alzheimer's disease (AD), we asked if there is a functional interaction between high glucose and elevated beta amyloid peptide (Abeta) in cultured brain microvascular endothelial cells and presymptomatic AD transgenic mice. When cultured brain microvascular endothelial cells are exposed to both high glucose and low levels of Abeta, there is a synergistic interaction to cause an increased accumulation of advanced glycation products (AGE) and reactive oxygen species (ROS). When presymptomatic mice expressing mutant human amyloid precursor protein and presenilin are made diabetic, they have a decrease in cognitive function relative to control mice. Associated with the cognitive deficit are increases in brain microvascular AGE and iNOS expression, and the loss of the synaptic spine protein drebrin. No amyloid plaques or tangles are observed within the brains of any group. These data show that diabetes causes a synergistic potentiation of some indices of AD in transgenic animals that are presymptomatic for the classical features of the disease.

  14. Gray matter pathology and multiple sclerosis.

    Science.gov (United States)

    Wegner, Christiane; Stadelmann, Christine

    2009-09-01

    Gray matter demyelination is frequent and extensive in most patients with multiple sclerosis (MS) and has recently received much attention in neuropathologic and imaging studies. Gray matter lesions show distinct pathologic features that make their detection difficult with conventional imaging techniques. Thus, despite their high prevalence, their impact on clinical symptoms has not been defined well so far. This review focuses on recent information from pathologic and imaging studies and summarizes our current knowledge on cortical pathology derived from human and experimental studies.

  15. Pathology of the region of the knee

    Energy Technology Data Exchange (ETDEWEB)

    Aufdermaur, M.

    1981-09-01

    Radiological, clinical and pathologic-anatomical findings seen in four types of disorders of the region of the knee jointare described. An attempt is made to explain the clinical symptomatology on the basis of pathologic-anatomical findings. It is demonstrated that the histology of a giant cell neoplasm does not permit conclusions as to prognosis. Etiology and pathogenesis of villonodular synovitis and of chondrocalcinosis are unexplained. Pathologic-anatomical findings of chondromalacia patellae are those of early osteoarthrosis.

  16. Predicting pathology in impacted mandibular third molars

    OpenAIRE

    Aveek Mukherji; Mohit Pal Singh; Prashant Nahar; Bhuvaneshwari S Balaji; Hemant Mathur; Saurabh Goel

    2017-01-01

    Introduction: The rising incidence of the impacted mandibular third molars and their association with pathologies is now considered a public health problem. Aims and Objectives: The objective of this study was to assess the position of impacted mandibular third molars that are prone to developing pathologies and to determine the frequency and type of pathological conditions associated with these impacted teeth to facilitate planning for their prophylactic removal. Materials and Methods: Conse...

  17. Spiritual Pathology: The Case of Adolf Hitler

    Directory of Open Access Journals (Sweden)

    W. George Scarlett

    2012-04-01

    Full Text Available Hitler had a noble purpose (to save the world and a strong faith in the laws of Nature as he understood Nature. He was, then, a spiritual person, though his spirituality was pathological and destructive. Here, the example of Hitler, his faith, and his spiritual pathology is given to both understand spiritual pathology in general and, through contrast, to understand positive spiritual development.

  18. Practical pathology of aging mice

    Directory of Open Access Journals (Sweden)

    Piper M. M. Treuting

    2011-06-01

    Full Text Available Old mice will have a subset of lesions as part of the progressive decline in organ function that defines aging. External and palpable lesions will be noted by the research, husbandry, or veterinary staff during testing, cage changing, or physical exams. While these readily observable lesions may cause alarm, not all cause undue distress or are life-threatening. In aging research, mice are maintained until near end of life that, depending on strain and genetic manipulation, can be upwards of 33 months. Aging research has unique welfare issues related to age-related decline, debilitation, fragility, and associated pain of chronic diseases. An effective aging research program includes the collaboration and education of the research, husbandry, and veterinary staff, and of the members of the institution animal care and use committee. This collaborative effort is critical to humanely maintaining older mice and preventing excessive censorship due to non-lethal diseases. Part of the educational process is becoming familiar with how old mice appear clinically, at necropsy and histopathologically. This baseline knowledge is important in making the determination of humane end points, defining health span, contributing causes of death and effects of interventions. The goal of this paper is to introduce investigators to age-associated diseases and lesion patterns in mice from clinical presentation to pathologic assessment. To do so, we present and illustrate the common clinical appearances, necropsy and histopathological lesions seen in subsets of the aging colonies maintained at the University of Washington.

  19. Fetal Programming and Cardiovascular Pathology

    Science.gov (United States)

    Alexander, Barbara T.; Dasinger, John Henry; Intapad, Suttira

    2016-01-01

    Low birth weight serves as a crude proxy for impaired growth during fetal life and indicates a failure for the fetus to achieve its full growth potential. Low birth weight can occur in response to numerous etiologies that include complications during pregnancy, poor prenatal care, parental smoking, maternal alcohol consumption or stress. Numerous epidemiological and experimental studies demonstrate that birth weight is inversely associated with blood pressure and coronary heart disease. Sex and age impact the developmental programming of hypertension. In addition, impaired growth during fetal life also programs enhanced vulnerability to a secondary insult. Macrosomia, which occurs in response to maternal obesity, diabetes and excessive weight gain during gestation, is also associated with increased cardiovascular risk. Yet, the exact mechanisms that permanently change the structure, physiology and endocrine health of an individual across their lifespan following altered growth during fetal life are not entirely clear. Transmission of increased risk from one generation to the next in the absence of an additional prenatal insult indicates an important role for epigenetic processes. Experimental studies also indicate that the sympathetic nervous system, the renin angiotensin system, increased production of oxidative stress and increased endothelin play an important role in the developmental programming of blood pressure in later life. Thus, this review will highlight how adverse influences during fetal life and early development program an increased risk for cardiovascular disease including high blood pressure and provide an overview of the underlying mechanisms that contribute to the fetal origins of cardiovascular pathology. PMID:25880521

  20. Pathology of the parathyroid glands in hyperparathyroidism.

    Science.gov (United States)

    Baloch, Zubair W; LiVolsi, Virginia A

    2013-08-01

    This paper reviews the embryology, histology and pathology of the human parathyroid glands. It emphasizes those pathologic lesions which are found in the setting of clinical hyperparathyroidism. Also discussed are certain molecular features of hyperfunctioning parathyroid glands. The difficulties encountered in parathyroid FNA are reviewed and illustrated.

  1. Magnetic resonance imaging assessment of labyrinthine pathology

    Energy Technology Data Exchange (ETDEWEB)

    Marsot-Dupuch, K. [Hopital Saint-Antoine, Service de Radiologie, 75 - Paris (France); Vignaud, J. [Val de Grace, Hopital d`Instruction du Service de Sante des Armees, 75 - Paris (France); Mehdi, M. [Hopital Saint-Antoine, Service de Radiologie, 75 - Paris (France); Pharaboz, C. [Hopital Begin, Hopital d`Instruction des Armees, 94 - Saint-Mande (France); Meyer, B. [Hopital Saint-Antoine, Service d`ORL, 75 - Paris (France)

    1996-10-01

    Membranous labyrinth pathologies are quite rare. They were until recently difficult to demonstrate by imaging technics, CT being the modality of choice. Our purpose was to stress the interest of MR examination for investigating patients complaining of vertigo, tinnitus, and profound sensorineural hearing loss. Normal anatomy as well as the main pathologically encountered changes are illustrated. (orig.)

  2. Trends in pathology graduate medical education.

    Science.gov (United States)

    Alexander, C B

    2001-07-01

    Comprehensive data show trends in graduate medical education in pathology with regard to the numbers of accredited programs, persons certified from those programs, and demographics of the population of first year-trainees in pathology. Experience with US seniors and foreign-trained physicians in the PGY match process for pathology from 1991 through 2000 is presented, along with data on the types of medical schools generating pathology trainees for the PGY-1 year and the top medical schools of origin of US medical graduates who completed the program and became certified in pathology between 1995 and 1999. The impact of reimbursement of the credentialing year is also addressed through data collected from the PRODS Survey 2000, and those results are reviewed. Finally, turnover rates among pathology program directors of combined AP/CP programs and subspecialty programs since 1994 are presented. An analysis of these trends is provided, along with suggestions to improve both the perception of careers in pathology and the actual choice of a career in pathology.

  3. Pathological Gambling and Related Problems among Adolescents.

    Science.gov (United States)

    Ladouceur, Robert; Boudreault, Normand; Jacques, Christian; Vitaro, Frank

    1999-01-01

    Evaluates the prevalence of pathological gambling and related problems among 3,426 students in junior and senior high schools in Quebec City. Results indicate that 77% have gambled in the last twelve months and 13% gamble at least once a week. Results also reveal that pathological gambling is associated with drug and alcohol use, poor grades, and…

  4. Pathological Demand Avoidance: Exploring the Behavioural Profile

    Science.gov (United States)

    O'Nions, Elizabeth; Viding, Essi; Greven, Corina U; Ronald, Angelica; Happé, Francesca

    2014-01-01

    "Pathological Demand Avoidance" is a term increasingly used by practitioners in the United Kingdom. It was coined to describe a profile of obsessive resistance to everyday demands and requests, with a tendency to resort to "socially manipulative" behaviour, including outrageous or embarrassing acts. Pathological demand…

  5. Shifted risk preferences in pathological gambling

    NARCIS (Netherlands)

    Ligneul, R.; Sescousse, G.T.; Barbalat, G.; Domenech, P.; Dreher, J.C.

    2013-01-01

    BACKGROUND: Pathological gambling (PG) is an impulse control disorder characterized by excessive monetary risk seeking in the face of negative consequences. We used tools from the field of behavioral economics to refine our description of risk-taking behavior in pathological gamblers. This theoretic

  6. Pathological characteristics of gastric leiomyoblastoma

    Institute of Scientific and Technical Information of China (English)

    Xiao-Feng Huang; Chun-Mei Wang; Bo-Rong Pan; Xiao-Wen Dai; Li Fang; Jia-Ji Yang; Hua Yu; Jun Ren

    2004-01-01

    AIM: To determine the pathological characteristics of gastric leiomyoblastoma.METHODS: All tissues were obtained during surgery or gastroscopy. Tissue specimens for examination by light microscope were 1 cm×1 cm×1 cm in size, fixed in 40 g/L neutral buffered formaldehyde, embedded in paraffin, and stained with hematoxylin and eosin. The fresh tissues obtained for electron microscopy were 1 mm×1 mm×1 mm in size,and fixed in phosphate buffered 30 g/L glutaraldehyde,postfixed in 10 g/L osmium tetroxide and dehydrated in graded alcohol, embebbed in Epon 812. Ultrathin sections of 50 nm were stained with uranyl acetate and lead citrate and examined under a JEM-2000 EX transmission electron microscope.RESULTS: The most important histopathological feature of leiomyoblastoma was the predominance of large, rounded or polygonal cells with characteristic perinuclear clear zone in cytoplasms. The tumor cells arranged in patch, cell junction or junctional complex could be found occasionally between cells under electron microscope. Most of the neoplastic cytoplasms were filled with myofilaments, dense bodies, and dense patches. Rough endoplasmic reticulum dilatated as lakes, and large quantities of protein secretions of intermediate electron density were found in the dilated cisternae. Intracisternal segregation could also be found.The nuclei were round or oval, and anomalous nuclei were found in part of cells.CONCLUSION: The diagnosis of gastric leiomyoblastoma can be confirmed by electron microscopy. The clear appearance of tumor cells is due to the dilation of rough endoplasmic reticulum, not fat droplets, glycogens or mucus in cytoplasm.

  7. Decreased rhythmic GABAergic septal activity and memory-associated theta oscillations after hippocampal amyloid-beta pathology in the rat.

    Science.gov (United States)

    Villette, Vincent; Poindessous-Jazat, Frédérique; Simon, Axelle; Léna, Clément; Roullot, Elodie; Bellessort, Brice; Epelbaum, Jacques; Dutar, Patrick; Stéphan, Aline

    2010-08-18

    The memory deficits associated with Alzheimer's disease result to a great extent from hippocampal network dysfunction. The coordination of this network relies on theta (symbol) oscillations generated in the medial septum. Here, we investigated in rats the impact of hippocampal amyloid beta (Abeta) injections on the physiological and cognitive functions that depend on the septohippocampal system. Hippocampal Abeta injections progressively impaired behavioral performances, the associated hippocampal theta power, and theta frequency response in a visuospatial recognition test. These alterations were associated with a specific reduction in the firing of the identified rhythmic bursting GABAergic neurons responsible for the propagation of the theta rhythm to the hippocampus, but without loss of medial septal neurons. Such results indicate that hippocampal Abeta treatment leads to a specific functional depression of inhibitory projection neurons of the medial septum, resulting in the functional impairment of the temporal network.

  8. [Current issues in pulmonary pathology. Report of the working group on pulmonary pathology of the German Society of Pathology].

    Science.gov (United States)

    Schnabel, Ph A; Petersen, I; Junker, K

    2012-11-01

    The working group on pulmonary pathology of the German Society of Pathology (Deutsche Gesellschaft für Pathologie, DGP) developed very actively in the last year. Apart from the autumn meeting in Heidelberg in 2011 and the sessions at the annual DGP meeting in Berlin it was possible to realize a first publication with support and coauthorship of several members of the working group dealing with the classification of lung adenocarcinoma. In this report the key aspects of the activity related to the following issues are summarized including non-small cell lung carcinoma, neuroendocrine tumors of the lungs, interstitial pulmonary diseases, cell blocks in cytology and banking in thoracic pathology.

  9. Discussion on Improvement of Toxicological Pathology Study

    Institute of Scientific and Technical Information of China (English)

    RenJin

    2003-01-01

    Toxicological pathology plays a key role in drug safety assessment. To enhance the research level of toxicological pathology, the following stud-ies should be carried out urgently: setting up a standard operation procedure (SOP) for toxico-logical pathology assessment; emphasizing on immunotoxicology evaluation; adopting a new ex-periment model of replacement, featuring high speed and reliability; introducing new techniques and new models in toxicological mechanism re-search; and establishing a new appraisal system to screen innovative drug and rapid and high pre-cision methods for early security assessment, de-tection and measurement.

  10. MRI and pathology in persistent postherniotomy pain

    DEFF Research Database (Denmark)

    Aasvang, Eske Kvanner; Jensen, Karl-Erik; Fiirgaard, Bente

    2009-01-01

    groins versus unoperated and pain-free groins. RESULTS: Interobserver agreement was poor, ranging from kappa = 0.24 to 0.55 ("fair" to "moderate") except for "contrast enhancement in groin" (kappa = 0.69, substantial). Pathologic changes in the form of "contrast enhancement in groin," "edema......: Interobserver agreement is low and MRI-assessed pathology unspecific for persistent postherniotomy pain. Additional studies are required on interobserver agreement for pathology before MRI can be recommended as guidance and indication for surgical treatment of persistent postherniotomy pain....

  11. Pathological narcissism and the obstruction of love.

    Science.gov (United States)

    Kealy, David; Ogrodniczuk, John S

    2014-03-01

    Pathological narcissism is a form of maladaptive self-regulation that impedes the capacity to love. Although narcissism is often construed as excessive self-love, individuals with pathological narcissism are impaired in being able to love themselves as well as others. With the subject of impaired love in mind, we review selected conceptualizations from an enormous and diverse psychodynamic literature on narcissism. Major theoretical approaches illustrate a number of psychodynamics associated with narcissistic self-regulatory problems. This paper provides a concise overview of major conceptual themes regarding pathological narcissism and impaired capacity to love.

  12. Hygrothermal Behavior, Building Pathology and Durability

    CERN Document Server

    Delgado, JMPQ

    2013-01-01

    The main purpose of this book, Hygrothermal, Building Pathology and Durability, is to provide a collection of recent research works to contribute to the systematization and dissemination of knowledge related to construction pathology, hygrothermal behaviour of buildings, durability and diagnostic techniques and, simultaneously, to show the most recent advances in this domain. It includes a set of new developments in the field of building physics and hygrothermal behaviour, durability approach for historical and old buildings and building pathology vs. durability. The book is divided in several chapters that are a resume of the current state of knowledge for benefit of professional colleagues, scientists, students, practitioners, lecturers and other interested parties to network.

  13. Latin American forensic pathology: scope and needs

    Directory of Open Access Journals (Sweden)

    Gabriel M. Fonseca

    2012-10-01

    Full Text Available Pathology pertains to the study of a disease; from ancient times it has sought to explain the cause of death through postmortem examination. The advancement of science and technology has led to a greater definition of roles and has favored its development through different subspecialties among which we stands out forensic pathology. This discipline has its own characteristics, scope, case series, procedures and terminology. Likewise, although forensic pathology does not differ substantially from clinical pathology, significant differences can be found between the Anglo American approach and the Latin American approach. Beyond semantics of these alleged differences, the article reviews the concepts involved and discusses the scope and requirements needed to qualify experts, in the understanding that globalizing criteria should establish new paradigms and define the specific roles of the specialty.

  14. BILHARZIA INDUCED PATHOLOGIES AND TECHNIQUES OF ...

    African Journals Online (AJOL)

    2010-07-07

    Jul 7, 2010 ... include various radiographic techniques isotope ... E. I. Odongo-Aginya, Department of Medical Microbiology, Faculty of Medicine Gulu ... after treatment there was reversibility of pathological conditions introduced by the.

  15. Curriculum Guidelines for Pathology for Dental Hygienists.

    Science.gov (United States)

    Journal of Dental Education, 1987

    1987-01-01

    Guidelines for structuring a pathology curriculum for dental hygienists include: definition of the field and its subfields; relationships with other fields; primary educational goals, prerequisites, core content, specific behavioral objectives; and suggestions for sequencing, faculty, facilities, and occupational safety. (MSE)

  16. Clinical pathology of amphibians: a review.

    Science.gov (United States)

    Forzán, María J; Heatley, Jill; Russell, Karen E; Horney, Barbara

    2017-03-01

    Amphibian declines and extinctions have worsened in the last 2 decades. Partly because one of the main causes of the declines is infectious disease, veterinary professionals have increasingly become involved in amphibian research, captive husbandry, and management. Health evaluation of amphibians, free-living or captive, can benefit from employing the tools of clinical pathology, something that is commonly used in veterinary medicine of other vertebrates. The present review compiles what is known of amphibian clinical pathology emphasizing knowledge that may assist with the interpretation of laboratory results, provides diagnostic recommendations for common amphibian diseases, and includes RIs for a few amphibian species estimated based on peer-reviewed studies. We hope to encourage the incorporation of clinical pathology in amphibian practice and research, and to highlight the importance of applying veterinary medicine principles in furthering our knowledge of amphibian pathophysiology. © 2017 American Society for Veterinary Clinical Pathology.

  17. Pathological narcissism and narcissistic personality disorder.

    Science.gov (United States)

    Pincus, Aaron L; Lukowitsky, Mark R

    2010-01-01

    We review the literature on pathological narcissism and narcissistic personality disorder (NPD) and describe a significant criterion problem related to four inconsistencies in phenotypic descriptions and taxonomic models across clinical theory, research, and practice; psychiatric diagnosis; and social/personality psychology. This impedes scientific synthesis, weakens narcissism's nomological net, and contributes to a discrepancy between low prevalence rates of NPD and higher rates of practitioner-diagnosed pathological narcissism, along with an enormous clinical literature on narcissistic disturbances. Criterion issues must be resolved, including clarification of the nature of normal and pathological narcissism, incorporation of the two broad phenotypic themes of narcissistic grandiosity and narcissistic vulnerability into revised diagnostic criteria and assessment instruments, elimination of references to overt and covert narcissism that reify these modes of expression as distinct narcissistic types, and determination of the appropriate structure for pathological narcissism. Implications for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders and the science of personality disorders are presented.

  18. Problem and Pathological Gambling among College Students

    Science.gov (United States)

    Stinchfield, Randy; Hanson, William E.; Olson, Douglas H.

    2006-01-01

    This chapter examines problem and pathological gambling among college students and reports on prevalence rate, risk and protective factors, prevention and intervention, and recommendations for college student personnel and other university administrators.

  19. Recurrent femoral hernia and associated ovarian pathology.

    Science.gov (United States)

    Gately, Ryan Patrick; Concannon, Elizabeth Sarah; Hogan, A; Ryan, R S; O'Leary, M; Barry, K

    2012-08-27

    The following case describes an ovarian tumour presenting in a highly unusual manner-in the form of a recurrent femoral hernia. Recurrent femoral herniae are unusual and should prompt awareness of underlying pathology causing increased intra-abdominal pressure.

  20. Predicting pathology in impacted mandibular third molars

    Directory of Open Access Journals (Sweden)

    Aveek Mukherji

    2017-01-01

    Full Text Available Introduction: The rising incidence of the impacted mandibular third molars and their association with pathologies is now considered a public health problem. Aims and Objectives: The objective of this study was to assess the position of impacted mandibular third molars that are prone to developing pathologies and to determine the frequency and type of pathological conditions associated with these impacted teeth to facilitate planning for their prophylactic removal. Materials and Methods: Consecutive panoramic radiographs and clinical examination of 300 patients with impacted mandibular third molars were collected. They were segregated according to Pell and Gregory’s classification, Winter’s classification, and according to their state of eruption. These were correlated with associated pathologies based on clinical and radiological criteria. Statistical Analysis Used: Descriptive statistics included computation of percentages, mean, and standard deviations. The statistical test applied for the analysis was Pearson’s Chi-square test (χ2. For this test, confidence interval and P value were set at 93% and ≤0.03, respectively. Results: The pathology most commonly associated with impacted third molars was pericoronitis, which had the highest frequency of occurrence in partially erupted, distoangular, and IA positioned (as per Pell and Gregory classification impacted teeth. Impacted mandibular third molars, which were in IA position, placed mesially, and partially erupted, were prone to develop pathologies such as dental caries and periodontitis. Conclusion: The clinical and radiographical features of impacted third molar may be correlated to the development of their pathological complications. The partially impacted mandibular third molars with mesioangularly aligned in IA position have the highest potential to cause pathological complications.

  1. White Matter Glial Pathology in Autism

    Science.gov (United States)

    2015-11-01

    that the use of the instrument’s UV laser and its prism-guided movement is the causal factor. Arrangements were then made to complete the grant... uses innovative methods and a novel approach to investigate the pathology of the brain in autism spectrum disorder (ASD). This research employed laser ...cellular pathology of the ASD brain that could be used for the development of therapeutic alternatives for ASD patients. 15. SUBJECT TERMS Laser capture

  2. Mast cells in pathological and surgical scars

    OpenAIRE

    Beer, T; Baldwin, H; West, L; Gallagher, P.; Wright, D.

    1998-01-01

    AIM—To investigate the role of mast cells in surgical and pathological scar reactions by their identification and quantification using immunohistochemistry.
METHODS—Surgical scars and pathological scar reactions were stained immunohistochemically for tryptase to identify mast cells. These were quantified in the scar tissue and surrounding dermis. Statistical analyses were performed to test the hypothesis that mast cell numbers were different in the varying types of scar reaction.
RESULTS—A si...

  3. Human Vision Pathology Diagnostics by Photogrammetrics Means

    Science.gov (United States)

    Murynin, A.; Knyaz, V.; Mateev, I.

    2014-06-01

    One of the reasons of such vision pathology as human stereoscopic vision capability dysfunction is an asymmetry of a human face. As a rule, such dysfunctions occur as early as in the babyhood, when diagnostic methods applied for adults are ineffective. Early diagnostics and prophylaxis could help in treatment of such pathology and face 3D modeling is one of the promising ways to solve this problem.

  4. Determining customer satisfaction in anatomic pathology.

    Science.gov (United States)

    Zarbo, Richard J

    2006-05-01

    Measurement of physicians' and patients' satisfaction with laboratory services has become a standard practice in the United States, prompted by national accreditation requirements. Unlike other surveys of hospital-, outpatient care-, or physician-related activities, no ongoing, comprehensive customer satisfaction survey of anatomic pathology services is available for subscription that would allow continual benchmarking against peer laboratories. Pathologists, therefore, must often design their own local assessment tools to determine physician satisfaction in anatomic pathology. To describe satisfaction survey design that would elicit specific information from physician customers about key elements of anatomic pathology services. The author shares his experience in biannually assessing customer satisfaction in anatomic pathology with survey tools designed at the Henry Ford Hospital, Detroit, Mich. Benchmarks for physician satisfaction, opportunities for improvement, and characteristics that correlated with a high level of physician satisfaction were identified nationally from a standardized survey tool used by 94 laboratories in the 2001 College of American Pathologists Q-Probes quality improvement program. In general, physicians are most satisfied with professional diagnostic services and least satisfied with pathology services related to poor communication. A well-designed and conducted customer satisfaction survey is an opportunity for pathologists to periodically educate physician customers about services offered, manage unrealistic expectations, and understand the evolving needs of the physician customer. Armed with current information from physician customers, the pathologist is better able to strategically plan for resources that facilitate performance improvements in anatomic pathology laboratory services that align with evolving clinical needs in health care delivery.

  5. Enterprise Implementation of Digital Pathology: Feasibility, Challenges, and Opportunities.

    Science.gov (United States)

    Hartman, D J; Pantanowitz, L; McHugh, J S; Piccoli, A L; OLeary, M J; Lauro, G R

    2017-01-23

    Digital pathology is becoming technically possible to implement for routine pathology work. At our institution, we have been using digital pathology for second opinion intraoperative consultations for over 10 years. Herein, we describe our experience in converting to a digital pathology platform for primary pathology diagnosis. We implemented an incremental rollout for digital pathology on subspecialty benches, beginning with cases that contained small amounts of tissue (biopsy specimens). We successfully scanned over 40,000 slides through our digital pathology system. Several lessons (both challenges and opportunities) were learned through this implementation. A successful conversion to digital pathology requires pre-imaging adjustments, integrated software and post-imaging evaluations.

  6. Alzheimer's disease: synaptic dysfunction and Abeta

    LENUS (Irish Health Repository)

    Shankar, Ganesh M

    2009-11-23

    Abstract Synapse loss is an early and invariant feature of Alzheimer\\'s disease (AD) and there is a strong correlation between the extent of synapse loss and the severity of dementia. Accordingly, it has been proposed that synapse loss underlies the memory impairment evident in the early phase of AD and that since plasticity is important for neuronal viability, persistent disruption of plasticity may account for the frank cell loss typical of later phases of the disease. Extensive multi-disciplinary research has implicated the amyloid β-protein (Aβ) in the aetiology of AD and here we review the evidence that non-fibrillar soluble forms of Aβ are mediators of synaptic compromise. We also discuss the possible mechanisms of Aβ synaptotoxicity and potential targets for therapeutic intervention.

  7. Mitochondrial accumulation of APP and Abeta

    DEFF Research Database (Denmark)

    Pavlov, Pavel F; Petersen, Anna Camilla Hansson; Glaser, Elzbieta

    2009-01-01

    Accumulating evidence suggest that alterations in energy metabolism are among the earliest events that occur in the Alzheimer disease (AD) affected brain. Energy consumption is drastically decreased in the AD-affected regions of cerebral cortex and hippocampus pointing towards compromised mitocho...

  8. Veterinary Forensic Pathology: The Search for Truth.

    Science.gov (United States)

    McDonough, S P; McEwen, B J

    2016-09-01

    Veterinary forensic pathology is emerging as a distinct discipline, and this special issue is a major step forward in establishing the scientific basis of the discipline. A forensic necropsy uses the same skill set needed for investigations of natural disease, but the analytical framework and purpose of forensic pathology differ significantly. The requirement of legal credibility and all that it entails distinguishes the forensic from routine diagnostic cases. Despite the extraordinary depth and breadth of knowledge afforded by their training, almost 75% of veterinary pathologists report that their training has not adequately prepared them to handle forensic cases. Many veterinary pathologists, however, are interested and willing to develop expertise in the discipline. Lessons learned from tragic examples of wrongful convictions in medical forensic pathology indicate that a solid foundation for the evolving discipline of veterinary forensic pathology requires a commitment to education, training, and certification. The overarching theme of this issue is that the forensic necropsy is just one aspect in the investigation of a case of suspected animal abuse or neglect. As veterinary pathologists, we must be aware of the roles filled by other veterinary forensic experts involved in these cases and how our findings are an integral part of an investigation. We hope that the outcome of this special issue of the journal is that veterinary pathologists begin to familiarize themselves with not only forensic pathology but also all aspects of veterinary forensic science.

  9. Molecular imaging of Alzheimer disease pathology.

    Science.gov (United States)

    Kantarci, K

    2014-06-01

    Development of molecular imaging agents for fibrillar β-amyloid positron-emission tomography during the past decade has brought molecular imaging of Alzheimer disease pathology into the spotlight. Large cohort studies with longitudinal follow-up in cognitively normal individuals and patients with mild cognitive impairment and Alzheimer disease indicate that β-amyloid deposition can be detected many years before the onset of symptoms with molecular imaging, and its progression can be followed longitudinally. The utility of β-amyloid PET in the differential diagnosis of Alzheimer disease is greatest when there is no pathologic overlap between 2 dementia syndromes, such as in frontotemporal lobar degeneration and Alzheimer disease. However β-amyloid PET alone may be insufficient in distinguishing dementia syndromes that commonly have overlapping β-amyloid pathology, such as dementia with Lewy bodies and vascular dementia, which represent the 2 most common dementia pathologies after Alzheimer disease. The role of molecular imaging in Alzheimer disease clinical trials is growing rapidly, especially in an era when preventive interventions are designed to eradicate the pathology targeted by molecular imaging agents. © 2014 by American Journal of Neuroradiology.

  10. Content and formal problems of teaching pathology.

    Science.gov (United States)

    Jellinek, H

    1981-09-01

    The present comment of mine will dwell mainly on my impressions about the format of teaching. It seems to be very difficult to judge how much classic practical training should be given since for example in histology, it may often go deep into details probably irrelevant for the students. It must be realized, however, that the rapid increase in general knowledge and in the special demands of various medical specialities also impose an ever-increasing stress on the pathologist himself. Therefore it is necessary to define certain limits, however difficult a problem this may be. I have proposed an integrated presentation. The integration should, however, not be made by the clinician as the first and the pathologist as the second violinist. In this case the clinician may misinterpret pathology and may interfere with the pathologist in presenting pathology with appropriate weight and adequate importance. The moderator is the director of the pathology department. No special clinical details are given but those sufficient to ensure a better understanding of the pathological changes presented. Under these conditions the pathologist has full control of the essential views and details given to the student, thus demonstrating the importance of pathology in medicine.

  11. Clinical and Pathological Features of Riedel's Thyroiditis

    Institute of Scientific and Technical Information of China (English)

    Lin Lu; Feng Gu; Wei-xin Dai; Wu-yi Li; Jie Chen; Yu Xiao; Zheng-pei Zeng

    2010-01-01

    Objective To evaluate the clinical and pathological features of Riedel's thyroiditis (RT), and current diagnostic and treatment methods for that disease.Methods Five RT cases identified by surgery and pathological examinations at Peking Union Medi-cal College Hospital from 1985 to 2009 were analyzed and compared with the cases reported in the litera-ture in terms of clinical and pathological features. Immunohistochemical staining of kappa and lambda light chains was carried out for RT tissues from all the five patients.Results All the five cases were females, aged 45-55 years. Elevation of serum thyroid autoantibodies was found in only one patient, who had longer disease duration than the others. Pathological examination re-vealed invasive fibrosclerosis of the thyroid follicles, thyroid capsule, and the surrounding tissues. In RT tis-sues, the number of cells containing lambda chains was a little higher than those containing kappa chains.Conclusions RT is a rare disease which might be more common in middle-aged females than in other populations. Pathological features include the destruction of thyroid follicle, extension into surround-ing tissues by inflammatory cells and fibrous tissues. Immunohistochemical staining of kappa and lambda chains could help diagnose RT.

  12. Anencephaly: A pathological study of 41 cases

    Directory of Open Access Journals (Sweden)

    C Panduranga

    2012-01-01

    Full Text Available Background : Anencephaly is a lethal neural tube defect which is due to the defective closure of rostral pore of neural tube. In more than 50% of cases it is associated with other systemic anomalies. Hence this study was undertaken to assess pathological parameters associated with anencephaly in particular attention to associated systemic anomalies. Materials and Methods: It is a study on 41 anencephaly fetuses conducted in the Department of Pathology. The period of study is from January 2001 to December 2011. Results: Out of 41 cases, 30 (73% cases showed presence of systemic anomalies, 48.5% of the cases were observed in primigravida. Most common associated anomaly was spina bifida followed by gastrointestinal anomalies. Conclusion: Pathological examination of the abortus is essential to document the associated anomalies.

  13. Hygrothermal behavior, building pathology and durability

    Energy Technology Data Exchange (ETDEWEB)

    Peixoto de Freitas V.; Delgado, J.M.P.Q. (eds.) [Porto Univ. (Portugal). Building Physics Lab.

    2013-03-01

    Includes a set of new developments in the field of building physics and hygrothermal behavior. Presents a new durability approach for historical and old buildings. Reviews the current state of knowledge. The main purpose of this book, Hygrothermal, Building Pathology and Durability, is to provide a collection of recent research works to contribute to the systematization and dissemination of knowledge related to construction pathology, hygrothermal behaviour of buildings, durability and diagnostic techniques and, simultaneously, to show the most recent advances in this domain. It includes a set of new developments in the field of building physics and hygrothermal behaviour, durability approach for historical and old buildings and building pathology vs. durability. The book is divided in several chapters that are a resume of the current state of knowledge for benefit of professional colleagues, scientists, students, practitioners, lecturers and other interested parties to network.

  14. Pathological assessment of liver fibrosis regression

    Directory of Open Access Journals (Sweden)

    WANG Bingqiong

    2017-03-01

    Full Text Available Hepatic fibrosis is the common pathological outcome of chronic hepatic diseases. An accurate assessment of fibrosis degree provides an important reference for a definite diagnosis of diseases, treatment decision-making, treatment outcome monitoring, and prognostic evaluation. At present, many clinical studies have proven that regression of hepatic fibrosis and early-stage liver cirrhosis can be achieved by effective treatment, and a correct evaluation of fibrosis regression has become a hot topic in clinical research. Liver biopsy has long been regarded as the gold standard for the assessment of hepatic fibrosis, and thus it plays an important role in the evaluation of fibrosis regression. This article reviews the clinical application of current pathological staging systems in the evaluation of fibrosis regression from the perspectives of semi-quantitative scoring system, quantitative approach, and qualitative approach, in order to propose a better pathological evaluation system for the assessment of fibrosis regression.

  15. Inflammatory breast carcinoma: pathological or clinical entity?

    Science.gov (United States)

    Amparo, R S; Angel, C D; Ana, L H; Antonio, L C; Vicente, M S; Carlos, F M; Vicente, G P

    2000-12-01

    Inflammatory breast carcinoma (IBC) diagnosis is usually based in the presence of typical clinical symptoms (redness and edema in more than 2/3 of the breast), which are not always associated with pathologic characteristics (subdermal lymphatics involvement). Whether exclusively pathologic findings without clinical symptoms are sufficient for IBC diagnosis remains controversial. A retrospective analysis of 163 clinically diagnosed IBC (CIC) either with dermal lymphatics invasion or not, was compared with another group of 99 patients with dermal lymphatics invasion without clinical symptoms (occult inflammatory carcinoma) (OIC). The following clinical and pathological characteristics have been analyzed and compared: age, menopausal status, clinical axillar node involvement, symptoms duration before diagnosis, grade, estrogen receptors, presence of metastases at diagnosis, local recurrence, metastasic dissemination, disease-free (DFS) and overall survival (OS). Median age was younger in CIC (52.3 vs. 63.8 years; p Prognosis of CIC patients is poorer, so this two entities should be clearly differentiated when therepeutic results are reported.

  16. Sleep Pathology in Creutzfeldt-Jakob Disease

    Science.gov (United States)

    Kang, Peter; de Bruin, Gabriela S.; Wang, Leo H.; Ward, Beth A.; Ances, Beau M.; Lim, Miranda M.; Bucelli, Robert C.

    2016-01-01

    Study Objectives: Associations between sleep and neurodegenerative diseases have become increasingly evident. This study aims to characterize the prevalence and type of sleep pathology in Creutzfeldt-Jakob disease (CJD), a rapidly progressive, fatal neurodegenerative disease. Methods: In this observational cross-sectional cohort study, we performed a retrospective analysis of sleep signs and symptoms in a consecutive group of patients with definite CJD at a tertiary care medical center (n = 28). Polysomnography was performed in 14 patients. Results: Although only 5 of 28 patients carried a premorbid sleep diagnosis, signs/symptoms of sleep pathology were present in 25 patients. Eleven reported hypersomnia whereas 13 reported insomnia. Seven had restless legs symptoms and/or periodic limb movements of sleep, and nine reported parasomnias. Of the 14 patients who underwent polysomnography, 1 did not show sleep, 9 (69%) had poorly formed or absent sleep spindles and/or K-complexes, and 10 (77%) had sleep-disordered breathing. Of the 8 patients who experienced rapid eye movement (REM) sleep during the polysomnography, 3 (38%) showed REM sleep without atonia, and 2 patients met criteria for REM sleep behavior disorder. Median total sleep time was 226 (interquartile range [IQR] = 195–282) min. Median sleep efficiency was 58.5% (IQR = 41–65.5 %). Median REM time was 0.35% (IQR = 0–7.125%). Five patients (38%) demonstrated periodic limb movements during polysomnography. One case is presented. Conclusions: Sleep pathology is common in CJD, and screening for sleep pathology is indicated in the evaluation of patients with rapidly progressive dementias. Early identification and treatment of sleep pathology may provide an intervenable target for CJD. Citation: Kang P, de Bruin GS, Wang LH, Ward BA, Ances BM, Lim MM, Bucelli RC. Sleep pathology in Creutzfeldt-Jakob disease. J Clin Sleep Med 2016;12(7):1033–1039. PMID:27250807

  17. Musculoskeletal ultrasound including definitions for ultrasonographic pathology

    DEFF Research Database (Denmark)

    Wakefield, RJ; Balint, PV; Szkudlarek, Marcin

    2005-01-01

    Ultrasound (US) has great potential as an outcome in rheumatoid arthritis trials for detecting bone erosions, synovitis, tendon disease, and enthesopathy. It has a number of distinct advantages over magnetic resonance imaging, including good patient tolerability and ability to scan multiple joints...... pathologies. This article presents the first report from the OMERACT ultrasound special interest group, which has compared US against the criteria of the OMERACT filter. Also proposed for the first time are consensus US definitions for common pathological lesions seen in patients with inflammatory arthritis....

  18. Treatment of pathological gambling - integrative systemic model.

    Science.gov (United States)

    Mladenović, Ivica; Lažetić, Goran; Lečić-Toševski, Dušica; Dimitrijević, Ivan

    2015-03-01

    Pathological gambling was classified under impulse control disorders within the International Classification of Diseases (ICD-10) (WHO 1992), but the most recent Diagnostic and Statistical Manual, 5th edition (DSM-V), (APA 2013), has recognized pathological gambling as a first disorder within a new diagnostic category of behavioral addictions - Gambling disorder. Pathological gambling is a disorder in progression, and we hope that our experience in the treatment of pathological gambling in the Daily Hospital for Addictions at The Institute of Mental Health, through the original "Integrative - systemic model" would be of use to colleagues, dealing with this pathology. This model of treatment of pathological gambling is based on multi-systemic approach and it primarily represents an integration of family and cognitive-behavioral therapy, with traces of psychodynamic, existential and pharmacotherapy. The model is based on the book "Pathological gambling - with self-help manual" by Dr Mladenovic and Dr Lazetic, and has been designed in the form of a program that lasts 10 weeks in the intensive phase, and then continues for two years in the form of "extended treatment" ("After care"). The intensive phase is divided into three segments: educational, insight with initial changes and analysis of the achieved changes with the definition of plans and areas that need to be addressed in the extended treatment. "Extended treatment" lasts for two years in the form of group therapy, during which there is a second order change of the identified patient, but also of other family members. Pathological gambling has been treated in the form of systemic-family therapy for more than 10 years at the Institute of Mental Health (IMH), in Belgrade. For second year in a row the treatment is carried out by the modern "Integrative-systemic model". If abstinence from gambling witihin the period of one year after completion of the intensive phase of treatment is taken as the main criterion of

  19. Mammary gland pathologies in the parturient buffalo

    Directory of Open Access Journals (Sweden)

    G N Purohit

    2014-12-01

    Full Text Available Parturition related mammary gland pathologies in the buffalo appear to be low on accord of anatomic (longer teat length, thicker streak canal and physiologic (lower cisternal storage of secreted milk, lower milk production differences with cattle. Hemolactia, udder edema and hypogalactia usually occur in the buffalo due to physiologic changes around parturition however mastitis involves pathologic changes in the udder and teats; the incidence of mastitis is however lower compared to cattle. The incidence and therapy of hemolactia, udder edema and hypogalactia are mentioned and the risk factors, incidence, diagnosis, therapy and prevention for mastitis in buffalo are also described.

  20. Pathologic approach to spinal cord infections.

    Science.gov (United States)

    Tihan, Tarik

    2015-05-01

    The pathologic evaluation of spinal cord infections requires comprehensive clinical, radiological, and laboratory correlation, because the histologic findings in acute, chronic, or granulomatous infections rarely provide clues for the specific cause. This brief review focuses on the pathologic mechanisms as well as practical issues in the diagnosis and reporting of infections of the spinal cord. Examples are provided of the common infectious agents and methods for their diagnosis. By necessity, discussion is restricted to the infections of the medulla spinalis proper and its meninges, and not bone or soft tissue infections.

  1. LIPOFUSCIN ROLE IN INVOLUTIVE AND PATHOLOGICAL PROCESSES

    Directory of Open Access Journals (Sweden)

    Maslyakova

    2009-03-01

    Full Text Available The modern data on the lipofuscin role in the processes of intracellular exchange have been analysed in the review. The ambiguity of the interpretation of lipofuscin accumulation according to its importance in involutive and pathological processes has been considered in the study. Nowadays there are no data of morphological character, which allow objectively (in a digital equivalent to find out the solution of the question about the functional importance of lipofuscin during the ageing of an organism or development of pathological processes.

  2. Exhaustion and the Pathologization of Modernity.

    Science.gov (United States)

    Schaffner, Anna Katharina

    2016-09-01

    This essay analyses six case studies of theories of exhaustion-related conditions from the early eighteenth century to the present day. It explores the ways in which George Cheyne, George Beard, Richard von Krafft-Ebing, Sigmund Freud, Alain Ehrenberg and Jonathan Crary use medical ideas about exhaustion as a starting point for more wide-ranging cultural critiques related to specific social and technological transformations. In these accounts, physical and psychological symptoms are associated with particular external developments, which are thus not just construed as pathology-generators but also pathologized. The essay challenges some of the persistently repeated claims about exhaustion and its unhappy relationship with modernity.

  3. Cesare Lombroso on mediumship and pathology.

    Science.gov (United States)

    Alvarado, Carlos S; Biondi, Massimo

    2017-06-01

    During the nineteenth century and the first decade of the twentieth, students of pathology such as Cesare Lombroso (1835-1909), the author of the excerpt presented here, became involved in observing, investigating and theorizing about the phenomena of Spiritualism, and mediumship in particular. The Classic Text presented here consists of an excerpt from Lombroso's writings which focus on the Italian medium Eusapia Palladino (1854-1918), who greatly influenced Lombroso's beliefs. Lombroso illustrates neglected theoretical ideas combining the interaction of pathology and what seem to be real psychic phenomena that have not received much attention in historical studies.

  4. Peripapillary intrachoroidal cavitation in pathological myopia.

    Science.gov (United States)

    Marticorena-Álvarez, P; Clement-Fernández, F; Iglesias-Ussel, L

    2014-08-01

    A 54 year old woman with pathological myopia, presented with an elevated, yellowish-white lesion at the inferior border of the myopic conus in her left eye. The optical coherence tomography (OCT) demonstrated an intrachoroidal hyporeflective space. The fluorescein angiography examination (FA) showed early hypofluorescence with delayed staining, with no leakage of contrast. Recognition of «peripapillary intrachoroidal cavitation» as an own entity associated with pathological myopia is important to avoid confusion with other possible retinal lesions which require further investigation and treatment. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  5. Musculoskeletal ultrasound including definitions for ultrasonographic pathology

    DEFF Research Database (Denmark)

    Wakefield, RJ; Balint, PV; Szkudlarek, Marcin

    2005-01-01

    in a short period of time. However, there are scarce data regarding its validity, reproducibility, and responsiveness to change, making interpretation and comparison of studies difficult. In particular, there are limited data describing standardized scanning methodology and standardized definitions of US...... pathologies. This article presents the first report from the OMERACT ultrasound special interest group, which has compared US against the criteria of the OMERACT filter. Also proposed for the first time are consensus US definitions for common pathological lesions seen in patients with inflammatory arthritis....

  6. [Growth: responses to pathology. Preliminary study].

    Science.gov (United States)

    Ferri, J; Bennani, K; Sebille, S; Caprioli, F

    2000-09-01

    Many pathologies involve face. Among them, many have craniofacial growth consequences. The authors' aims are to analyze some of these pathologies, where clinical observations emphasize the role of the different craniofacial growth patterns. Despite a complex relation between the malformative part and the deformative one, untreated observations provide a better understanding of some craniofacial growth defects. Syndromes can be classified in 4 categories, involving the primitive causes of the clinical finding: 1. organic abnormalities of one or many functional matrix, 2. localized abnormalities of the anatomical structures, 3. general abnormalities of the conjunctive tissue, 4. mixed syndromes. Many observations will presented.

  7. [To an integrative management of pathological gamblers].

    Science.gov (United States)

    Bonnaire, C

    2011-12-01

    Recent researches on pathological gambling indicate that the various gambling activities are heterogeneous by nature. Indeed, some findings support the view that gambling cannot be seen as a homogeneous activity. Therefore, pathological gamblers do not represent a homogeneous population. However, treatment does not appear to take into account this heterogeneity and studies in the field have assessed the efficacy of the various types of treatment. Furthermore, recent empirical data emphasize the need for delineating distinct subtypes of pathological gambling presenting similar symptoms but which, at the same time, differ on certain variables. These subtypes will be essential in the management, treatment, and prognosis of pathological gambling. Blaszczynski and Nower (2002) identified three subtypes of gamblers. The first subtype, referred to as the "emotionally vulnerable problem gamblers", includes gamblers who mainly gamble to escape painful emotional experiences. The second includes "antisocial impulsivist problem gamblers" who are mainly driven by impulsivity and sensation seeking. The last one, referred to as the "behaviourally conditioned problem gamblers", includes gamblers who gamble because of behavioural contingencies offered by the game, rather than psychological difficulties. Each group is characterized by specific psychological variables, and each may require a different treatment approach. Hence, these subgroups should be used and taken into account in the choice of the treatment. The purpose of this article is to provide an integrative model of treatment of this disorder based on the typology of pathological gamblers. Many studies have tried to understand this pathological behaviour by exploring motivational, psychological, biological and ecological correlates of gambling to explain the aetiology. An approach integrating various orientations, at the same time cognitive-behavioural, motivational, psychoanalytical and bodily-centred is the most relevant

  8. Detection of pathological lesions in slaughtered rabbits

    Directory of Open Access Journals (Sweden)

    Guido Grilli

    2010-01-01

    Full Text Available The slaughterhouse is considered an important control point for the monitoring of rabbit diseases. In our study, 59,440 rabbit carcasses were examined, but only 1% of pathological lesions were recorded at postmortem inspection. Mainly affected were tegumentary, digestive and urinary systems. The most consistent lesion was the subcutaneous abscess; nephritis, probably caused by Encephalitozoon cuniculi, was also frequent. Pathological alterations of the liver, classified as “necrotizing hepatitis” and localized at the caudate lobe, were observed for the first time.

  9. TDP-43 pathology and memory impairment in elders without pathologic diagnoses of AD or FTLD.

    Science.gov (United States)

    Nag, Sukriti; Yu, Lei; Wilson, Robert S; Chen, Er-Yun; Bennett, David A; Schneider, Julie A

    2017-02-14

    To investigate the association of TAR DNA-binding protein 43 (TDP-43) pathology with memory, other cognitive domains, and dementia in community-dwelling elders without pathologic diagnoses of Alzheimer disease (AD) or frontotemporal lobar degeneration (FTLD). Of 1,058 autopsied participants, 343 (32.4%) did not have pathologic diagnoses of AD or FTLD. Diagnosis of dementia was based on clinical evaluation and cognitive performance tests, which were used to create summary measures of global cognition and of 5 cognitive domains. TDP-43 pathology evaluated in 6 brain regions by immunohistochemistry was converted into a summary measure of TDP-43 severity. Of 343 participants, 135 (39.4%) had TDP-43 pathology with a mean TDP-43 severity score of 0.394 (SD 0.490). TDP-43 inclusions were confined to the amygdala (stage 1) in 43.7% of participants, 40% showed additional involvement of the hippocampus or entorhinal cortex (stages 2), while fewer (16.3%) showed additional TDP-43 pathology in the temporal and frontal cortices (stage 3). Severity of TDP-43 pathology was independently related to lower function in global cognition and episodic and semantic memory while increased odds of dementia was only a trend. When participants with hippocampal sclerosis (HS) were excluded from the models, TDP-43 pathology remained associated with lower episodic memory but relationships with global cognition, semantic memory, and dementia were attenuated. TDP-43 pathology in elders, without pathologic diagnoses of AD or FTLD, is common and independently associated with lower function in episodic memory, while its associations with global cognitive impairment and dementia are difficult to separate from HS. © 2017 American Academy of Neurology.

  10. Internet images of the speech pathology profession.

    Science.gov (United States)

    Byrne, Nicole

    2017-06-05

    Objective The Internet provides the general public with information about speech pathology services, including client groups and service delivery models, as well as the professionals providing the services. Although this information assists the general public and other professionals to both access and understand speech pathology services, it also potentially provides information about speech pathology as a prospective career, including the types of people who are speech pathologists (i.e. demographics). The aim of the present study was to collect baseline data on how the speech pathology profession was presented via images on the Internet.Methods A pilot prospective observational study using content analysis methodology was conducted to analyse publicly available Internet images related to the speech pathology profession. The terms 'Speech Pathology' and 'speech pathologist' to represent both the profession and the professional were used, resulting in the identification of 200 images. These images were considered across a range of areas, including who was in the image (e.g. professional, client, significant other), the technology used and the types of intervention.Results The majority of images showed both a client and a professional (i.e. speech pathologist). While the professional was predominantly presented as female, the gender of the client was more evenly distributed. The clients were more likely to be preschool or school aged, however male speech pathologists were presented as providing therapy to selected age groups (i.e. school aged and younger adults). Images were predominantly of individual therapy and the few group images that were presented were all paediatric.Conclusion Current images of speech pathology continue to portray narrow professional demographics and client groups (e.g. paediatrics). Promoting images of wider scope to fully represent the depth and breadth of speech pathology professional practice may assist in attracting a more diverse group

  11. Microvascular brain pathology on high resolution MRI

    NARCIS (Netherlands)

    Veluw, S.J. van

    2015-01-01

    Cerebral small vessel disease (SVD) is a common finding in the aging human brain and is associated with stroke, cognitive decline, and dementia. On autopsy, SVD encompasses pathological processes affecting small arteries and arterioles. Magnetic resonance imaging (MRI) detects the consequences of th

  12. [Quality Management System in Pathological Laboratory].

    Science.gov (United States)

    Koyatsu, Junichi; Ueda, Yoshihiko

    2015-07-01

    Even compared to other clinical laboratories, the pathological laboratory conducts troublesome work, and many of the work processes are also manual. Therefore, the introduction of the systematic management of administration is necessary. It will be a shortcut to use existing standards such as ISO 15189 for this purpose. There is no standard specialized for the pathological laboratory, but it is considered to be important to a pathological laboratory in particular. 1. Safety nianagement of the personnel and environmental conditions. Comply with laws and regulations concerning the handling of hazardous materials. 2. Pre-examination processes. The laboratory shall have documented procedures for the proper collection and handling of primary samples. Developed and documented criteria for acceptance or rejection of samples are applied. 3. Examination processes. Selection, verification, and validation of the examination procedures. Devise a system that can constantly monitor the traceability of the sample. 4. Post-examination processes. Storage, retention, and disposal of clinical samples. 5. Release of results. When examination results fall within established alert or critical intervals, immediately notify the physicians. The important point is to recognize the needs of the client and be aware that pathological diagnoses are always "the final diagnoses".

  13. When is the practice of pathology mapractice?

    NARCIS (Netherlands)

    R.W.M. Giard (Raimond)

    2010-01-01

    textabstractBecause of its complex nature, surgical pathology diagnosis has an appreciable degree of fallibility and is increasingly subject to legal scrutiny. In litigation, the first practical step is to explain why and how this adversity could happen, and the second is the question of apportionme

  14. Risk Factors and Prodromal Eating Pathology

    Science.gov (United States)

    Stice, Eric; Ng, Janet; Shaw, Heather

    2010-01-01

    Prospective studies have identified factors that increase risk for eating pathology onset, including perceived pressure for thinness, thin-ideal internalization, body dissatisfaction, dietary restraint, and negative affect. Research also suggests that body dissatisfaction and dietary restraint may constitute prodromal stages of the development of…

  15. Speech-Language Pathology: Preparing Early Interventionists

    Science.gov (United States)

    Prelock, Patricia A.; Deppe, Janet

    2015-01-01

    The purpose of this article is to explain the role of speech-language pathology in early intervention. The expected credentials of professionals in the field are described, and the current numbers of practitioners serving young children are identified. Several resource documents available from the American Speech-­Language Hearing Association are…

  16. Golden rules in practice of cancer pathology

    African Journals Online (AJOL)

    M.N. El-Bolkainy

    2016-07-21

    Jul 21, 2016 ... The pathologic diagnosis of cancer is an essential initial step in the management of .... this rule is sarcomas of the skin which may be <1 cm but behave .... ever, that survival statistics are just a rough estimate of groups of.

  17. Pathological Left-Handedness: An Explanatory Model.

    Science.gov (United States)

    Satz, Paul

    Reported was an explanatory conceptual model for pathological left-handedness (PLH) and related hypotheses, some of which could not be tested empirically due to lack of information. The model was reported to provide an explanation for the relationship between handedness and specific learning disability, and handedness and cerebral dominance for…

  18. Metallothioneins are multipurpose neuroprotectants during brain pathology

    DEFF Research Database (Denmark)

    Penkowa, Milena

    2006-01-01

    Metallothioneins (MTs) constitute a family of cysteine-rich metalloproteins involved in cytoprotection during pathology. In mammals there are four isoforms (MT-I - IV), of which MT-I and -II (MT-I + II) are the best characterized MT proteins in the brain. Accumulating studies have demonstrated MT...

  19. Pathological Findings in Feto-maternal Hemorrhage.

    Science.gov (United States)

    Carles, Dominique; André, Gwenaëlle; Pelluard, Fanny; Martin, Olivia; Sauvestre, Fanny

    2014-01-01

    Feto-maternal hemorrhage (FMH) is the cause of late fetal death in 1.6%-11% of cases. In spite of this high frequency, its pathological features have received little attention. The definitive diagnosis of lethal FMH requires confirmation of sufficient fetal blood volume loss. This is determined by tests such as the Kleihauer-Betke test, which may not have been obtained or not have been available before the autopsy. The pathologist may offer a tentative diagnosis of FMH from the autopsy findings. The objective of this study was to better characterize the placental and fetal autopsy findings in lethal FMH. This was a retrospective study of 17 cases of FMH proven by a positive Kleihauer-Betke test. The cases were selected from the autopsy files of the Department of Pathology, Centre Hospitalier Universitaire de Bordeaux. The pathological reports as well as the placental and fetal photographs and the microscopic slides of each case were systematically reviewed. The fetal autopsy findings in FMH are characterized by a eutrophic pale macerated fetus, low liver weight, absent intrathoracic petechiae, increased extramedullary hematopoiesis in the liver and kidney, and increased circulating nucleated red blood cells. The placenta shows an increased frequency of intervillous thrombi. Although nonpathognomonic, some of the pathological features are strongly suggestive of FMH. When the latter is present, a Kleihauer-Betke test should be performed, even some days after the delivery.

  20. Pathological Examples Using the TI-85.

    Science.gov (United States)

    Cruthirds, John; Dodd, Fred

    1997-01-01

    Provides pathological examples for which graphing calculators sometimes give surprising, misleading, or incorrect results. Investigates some of the more interesting of these examples encountered while using the TI-85 in a variety of undergraduate courses including calculus and matrix theory. (DDR)

  1. Lymphoid Tissue and Pathological Influences of Toxicants

    NARCIS (Netherlands)

    Schaudien, D.; Harleman, H.; Bouallala, F.; Kuper, C. F.

    2014-01-01

    Toxicologic pathology plays a crucial role in the identification and interpretation of substance-induced health effects. Histology of lymphoid organs is quite sensitive, although it does not flag every model immunotoxic substance. Subtle interferences of toxic compounds, like transmembrane signaling

  2. Quantifying Pathology in Diffusion Weighted MRI

    NARCIS (Netherlands)

    Caan, M.W.A.

    2010-01-01

    In this thesis algorithms are proposed for quantification of pathology in Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) data. Functional evidence for brain diseases can be explained by specific structural loss in the white matter of the brain. That is, certain biomarkers may exist where the

  3. When is the practice of pathology mapractice?

    NARCIS (Netherlands)

    R.W.M. Giard (Raimond)

    2010-01-01

    textabstractBecause of its complex nature, surgical pathology diagnosis has an appreciable degree of fallibility and is increasingly subject to legal scrutiny. In litigation, the first practical step is to explain why and how this adversity could happen, and the second is the question of

  4. The interpersonal core of personality pathology

    Science.gov (United States)

    Hopwood, Christopher J.; Wright, Aidan G.C.; Ansell, Emily B.; Pincus, Aaron L.

    2013-01-01

    The purpose of this paper is to demonstrate that personality pathology is, at its core, fundamentally interpersonal. We review the proposed DSM-5 Section 3 redefinition of personality pathology involving self and interpersonal dysfunction, which we regard as a substantial improvement over the DSM-IV (and DSM-5 Section 2) definition. We note similarities between the proposed scheme and contemporary interpersonal theory and interpret the DSM-5 Section 3 definition using the underlying assumptions and evidence base of the interpersonal paradigm in clinical psychology. We describe how grounding the proposed DSM-5 Section 3 definition in interpersonal theory, and in particular a focus on the “interpersonal situation”, adds to its theoretical texture, empirical support, and clinical utility. We provide a clinical example that demonstrates the ability of contemporary interpersonal theory to augment the DSM-5 definition of personality pathology. We conclude with directions for further research that could clarify the core of personality pathology, and how interpersonal theory can inform research aimed at enhancing the DSM-5 Section 3 proposal and ultimately justify its migration to DSM-5 Section 2. PMID:23735037

  5. Pathological Examples Using the TI-85.

    Science.gov (United States)

    Cruthirds, John; Dodd, Fred

    1997-01-01

    Provides pathological examples for which graphing calculators sometimes give surprising, misleading, or incorrect results. Investigates some of the more interesting of these examples encountered while using the TI-85 in a variety of undergraduate courses including calculus and matrix theory. (DDR)

  6. Psychosocial causes and consequences of pathological gaming

    NARCIS (Netherlands)

    Lemmens, J.S.; Valkenburg, P.M.; Peter, J.

    2011-01-01

    Pathological use of computer and video games has been associated with indicators of psychosocial well-being, such as loneliness, low self-esteem, low social competence, and low life satisfaction. However, few studies have decisively demonstrated whether these indicators of psychosocial well-being

  7. Diabetic nephropathy : pathology, genetics and carnosine metabolism

    NARCIS (Netherlands)

    Mooyaart, Antien Leonora

    2011-01-01

    My thesis concerns different aspects of diabetic nephropathy. A pathologic classification of diabetic nephropathy is developed, a meta-analyis of genes in diabetic nephropathy is developed and the other chapters are about the CNDP1 gene in relation to kidney disease, mainly diabetic nephropathy.

  8. Mobile Technology for the Practice of Pathology.

    Science.gov (United States)

    Hartman, Douglas J

    2016-03-01

    Recently, several technological advances have been introduced to mobile phones leading some people to refer to them as "smartphones." These changes have led to widespread consumer adoption. A similar adoption has occurred within the medical field and this revolution is changing the practice of medicine, including pathology. Several mobile applications have been published for dermatology, orthopedics, ophthalmology, neurosurgery, and clinical pathology. The applications are wide ranging, including mobile technology to increase patient engagement, self-monitoring by patients, clinical algorithm calculation, facilitation between experts to resource-poor environments. These advances have been received with mixed reviews. For anatomic pathology, mobile technology applications can be broken into 4 broad categories: (a) educational uses, (b) microscope with mobile phone, (c) mobile phone as microscope/acquisition device, and (d) miscellaneous. Using a mobile phone as an acquisition device paired with a microscope seems to be the most interesting current application because of the need for expert consultation with resource-poor environments. However, several emerging uses for mobile technology may become more prominent as the technology matures including image analysis, alternative light sources, and increased opportunities for clinician and patient engagement. The flexibility represented by mobile technology represents a burgeoning field in pathology informatics.

  9. Central airway pathology: clinic features, CT findings with pathologic and virtual endoscopy correlation.

    Science.gov (United States)

    Barnes, Daniel; Gutiérrez Chacoff, José; Benegas, Mariana; Perea, Rosario J; de Caralt, Teresa M; Ramirez, José; Vollmer, Ivan; Sanchez, Marcelo

    2017-04-01

    To describe the imaging features of the central airway pathology, correlating the findings with those in pathology and virtual endoscopy. To propose a schematic and practical approach to reach diagnoses, placing strong emphasis on multidetector computed tomography (MDCT) findings. We reviewed our thoracic pathology database and the central airway pathology-related literature. Best cases were selected to illustrate the main features of each disease. MDCT was performed in all cases. Multiplanar and volume-rendering reconstructions were obtained when necessary. Virtual endoscopy was obtained from the CT with dedicated software. Pathological conditions affecting the central airways are a heterogeneous group of diseases. Focal alterations include benign neoplasms, malignant neoplasms, and non-neoplastic conditions. Diffuse abnormalities are divided into those that produce dilation and those that produce stenosis and tracheobronchomalacia. Direct bronchoscopy (DB) visualises the mucosal layer and is an important diagnostic and therapeutic weapon. However, assessing the deep layers or the adjacent tissue is not possible. MDCT and post-processing techniques such as virtual bronchoscopy (VB) provide an excellent evaluation of the airway wall. This review presents the complete spectrum of the central airway pathology with its clinical, pathological and radiological features. • Dividing diseases into diffuse and focal lesions helps narrow the differential diagnosis. • Focal lesions with nodularity are more likely to correspond to tumours. • Focal lesions with stenosis are more likely to correspond to inflammatory disease. • Posterior wall involvement is the main feature in diffuse lesions with stenosis.

  10. Surgical pathology and the patient: a systematic review evaluating the primary audience of pathology reports.

    Science.gov (United States)

    Mossanen, Matthew; True, Lawrence D; Wright, Jonathan L; Vakar-Lopez, Funda; Lavallee, Danielle; Gore, John L

    2014-11-01

    The pathology report is a critical document that helps guide the management of patients with cancer. More and more patients read their reports, intending to participate in decisions about their care. However, a substantial subset of patients may lack the ability to comprehend this often technical and complex document. We hypothesized that most literature on pathology reports discusses reports from the perspective of other physicians and not from the perspective of patients. An expert panel of physicians developed a list of search criteria, which we used to identify articles on PubMed, MEDLINE, Cochrane Reviews, and Google Scholar databases. Two reviewers independently evaluated all articles to identify for detailed review those that met search criteria. We identified the primary audience of the selected articles and the degree to which these articles addressed clarity of communication of pathology reports with patients. Of 801 articles identified in our search, 25 involved the formatting of pathology reports for clarity of communication. Recurrent themes in proposed improvements in reports included content standardization, variation in terminology, clarity of communication, and quality improvement. No articles discussed patients as their target audience. No study evaluated the health literacy level required of patients to comprehend pathology reports. In summary, there is a scarcity of patient-centered approaches to improve pathology reports. The literature on pathology reports does not include patients as a target audience. Limited resources are available to help patients comprehend their reports. Efforts to improve patient-centered communication are desirable to address this overlooked aspect of patient care.

  11. Pathological rate matrices: from primates to pathogens

    Directory of Open Access Journals (Sweden)

    Knight Rob

    2008-12-01

    Full Text Available Abstract Background Continuous-time Markov models allow flexible, parametrically succinct descriptions of sequence divergence. Non-reversible forms of these models are more biologically realistic but are challenging to develop. The instantaneous rate matrices defined for these models are typically transformed into substitution probability matrices using a matrix exponentiation algorithm that employs eigendecomposition, but this algorithm has characteristic vulnerabilities that lead to significant errors when a rate matrix possesses certain 'pathological' properties. Here we tested whether pathological rate matrices exist in nature, and consider the suitability of different algorithms to their computation. Results We used concatenated protein coding gene alignments from microbial genomes, primate genomes and independent intron alignments from primate genomes. The Taylor series expansion and eigendecomposition matrix exponentiation algorithms were compared to the less widely employed, but more robust, Padé with scaling and squaring algorithm for nucleotide, dinucleotide, codon and trinucleotide rate matrices. Pathological dinucleotide and trinucleotide matrices were evident in the microbial data set, affecting the eigendecomposition and Taylor algorithms respectively. Even using a conservative estimate of matrix error (occurrence of an invalid probability, both Taylor and eigendecomposition algorithms exhibited substantial error rates: ~100% of all exonic trinucleotide matrices were pathological to the Taylor algorithm while ~10% of codon positions 1 and 2 dinucleotide matrices and intronic trinucleotide matrices, and ~30% of codon matrices were pathological to eigendecomposition. The majority of Taylor algorithm errors derived from occurrence of multiple unobserved states. A small number of negative probabilities were detected from the Pad�� algorithm on trinucleotide matrices that were attributable to machine precision. Although the Pad

  12. Panning artifacts in digital pathology images

    Science.gov (United States)

    Avanaki, Ali R. N.; Lanciault, Christian; Espig, Kathryn S.; Xthona, Albert; Kimpe, Tom R. L.

    2017-03-01

    In making a pathologic diagnosis, a pathologist uses cognitive processes: perception, attention, memory, and search (Pena and Andrade-Filho, 2009). Typically, this involves focus while panning from one region of a slide to another, using either a microscope in a traditional workflow or software program and display in a digital pathology workflow (DICOM Standard Committee, 2010). We theorize that during panning operation, the pathologist receives information important to diagnosis efficiency and/or correctness. As compared to an optical microscope, panning in a digital pathology image involves some visual artifacts due to the following: (i) the frame rate is finite; (ii) time varying visual signals are reconstructed using imperfect zero-order hold. Specifically, after pixel's digital drive is changed, it takes time for a pixel to emit the expected amount of light. Previous work suggests that 49% of navigation is conducted in low-power/overview with digital pathology (Molin et al., 2015), but the influence of display factors has not been measured. We conducted a reader study to establish a relationship between display frame rate, panel response time, and threshold panning speed (above which the artifacts become noticeable). Our results suggest visual tasks that involve tissue structure are more impacted by the simulated panning artifacts than those that only involve color (e.g., staining intensity estimation), and that the panning artifacts versus normalized panning speed has a peak behavior which is surprising and may change for a diagnostic task. This is work in progress and our final findings should be considered in designing future digital pathology systems.

  13. Pathological α-synuclein distribution in subjects with coincident Alzheimer's and Lewy body pathology.

    Science.gov (United States)

    Toledo, Jon B; Gopal, Pallavi; Raible, Kevin; Irwin, David J; Brettschneider, Johannes; Sedor, Samantha; Waits, Kayla; Boluda, Susana; Grossman, Murray; Van Deerlin, Vivianna M; Lee, Edward B; Arnold, Steven E; Duda, John E; Hurtig, Howard; Lee, Virginia M-Y; Adler, Charles H; Beach, Thomas G; Trojanowski, John Q

    2016-03-01

    We investigated the distribution patterns of Lewy body-related pathology (LRP) and the effect of coincident Alzheimer disease (AD) pathology using a data-driven clustering approach that identified groups with different LRP pathology distributions without any diagnostic or researcher's input in two cohorts including: Parkinson disease patients without (PD, n = 141) and with AD (PD-AD, n = 80), dementia with Lewy bodies subjects without AD (DLB, n = 13) and demented subjects with AD and LRP pathology (Dem-AD-LB, n = 308). The Dem-AD-LB group presented two LRP patterns, olfactory-amygdala and limbic LRP with negligible brainstem pathology, that were absent in the PD groups, which are not currently included in the DLB staging system and lacked extracranial LRP as opposed to the PD group. The Dem-AD-LB individuals showed relative preservation of substantia nigra cells and dopamine active transporter in putamen. PD cases with AD pathology showed increased LRP. The cluster with occipital LRP was associated with non-AD type dementia clinical diagnosis in the Dem-AD-LB group and a faster progression to dementia in the PD groups. We found that (1) LRP pathology in Dem-AD-LB shows a distribution that differs from PD, without significant brainstem or extracranial LRP in initial phases; (2) coincident AD pathology is associated with increased LRP in PD indicating an interaction; (3) LRP and coincident AD pathology independently predict progression to dementia in PD, and (4) evaluation of LRP needs to acknowledge different LRP spreading patterns and evaluate substantia nigra integrity in the neuropathological assessment and consider the implications of neuropathological heterogeneity for clinical and biomarker characterization.

  14. Pathological Image Information - Open TG-GATEs Pathological Image Database | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available Image Information Description of data contents Information regarding each high-resolution digital image in t...he Pathological Images (SVS format) section. Data file File name: open_tggates_pathological_image....zip File URL: ftp://ftp.biosciencedbc.jp/archive/open-tggates-pathological-images/LATEST/op...view/open_tggates_pathological_image#en Data acquisition method Information enter...ts. Liver or Kidney. FILE_LOCATION FTP server path to the pathological images. CA

  15. Delivering a pathology curriculum in an integrated medical course.

    Science.gov (United States)

    Carr, Norman J; Olmos, Martin; Bushnell, John

    2008-10-01

    Modern integrated medical curricula usually do not include a separate pathology course. Consequently, there is a risk that important pathological principles may be omitted. We aimed to ensure that pathology is properly represented by developing a core pathology curriculum created in consultation with local pathologists. Appropriate information technology to track the delivery of this material within the integrated curriculum structure was developed using a learning content management system in which a metadata schema was constructed. This allows a sophisticated view of where and how pathology appears in the course and can also increase the visibility of the subject by demonstrating the central place of pathology in medicine. In conclusion, a core curriculum in pathology that can be tracked by information technology with sufficient power and flexibility is a solution to the potential loss of pathology from integrated medical courses. We believe the result is superior to a stand-alone pathology course.

  16. A method for normalizing pathology images to improve feature extraction for quantitative pathology

    Energy Technology Data Exchange (ETDEWEB)

    Tam, Allison [Stanford Institutes of Medical Research Program, Stanford University School of Medicine, Stanford, California 94305 (United States); Barker, Jocelyn [Department of Radiology, Stanford University School of Medicine, Stanford, California 94305 (United States); Rubin, Daniel [Department of Radiology, Stanford University School of Medicine, Stanford, California 94305 and Department of Medicine (Biomedical Informatics Research), Stanford University School of Medicine, Stanford, California 94305 (United States)

    2016-01-15

    Purpose: With the advent of digital slide scanning technologies and the potential proliferation of large repositories of digital pathology images, many research studies can leverage these data for biomedical discovery and to develop clinical applications. However, quantitative analysis of digital pathology images is impeded by batch effects generated by varied staining protocols and staining conditions of pathological slides. Methods: To overcome this problem, this paper proposes a novel, fully automated stain normalization method to reduce batch effects and thus aid research in digital pathology applications. Their method, intensity centering and histogram equalization (ICHE), normalizes a diverse set of pathology images by first scaling the centroids of the intensity histograms to a common point and then applying a modified version of contrast-limited adaptive histogram equalization. Normalization was performed on two datasets of digitized hematoxylin and eosin (H&E) slides of different tissue slices from the same lung tumor, and one immunohistochemistry dataset of digitized slides created by restaining one of the H&E datasets. Results: The ICHE method was evaluated based on image intensity values, quantitative features, and the effect on downstream applications, such as a computer aided diagnosis. For comparison, three methods from the literature were reimplemented and evaluated using the same criteria. The authors found that ICHE not only improved performance compared with un-normalized images, but in most cases showed improvement compared with previous methods for correcting batch effects in the literature. Conclusions: ICHE may be a useful preprocessing step a digital pathology image processing pipeline.

  17. Incidental bony pathology when reporting trauma orthopantomograms

    Energy Technology Data Exchange (ETDEWEB)

    Macanovic, M., E-mail: mladenmaca@gmail.co [Derriford Hospital NHS Trust, Plymouth (United Kingdom); Gangidi, S.; Porter, G.; Brown, S.; Courtney, D. [Derriford Hospital NHS Trust, Plymouth (United Kingdom); Porter, J. [Community Dental Service, Plymouth Primary Care Trust, Plymouth, Devon (United Kingdom)

    2010-10-15

    Radiologists frequently report orthopantomograms (OPTs) and other views of the mandible, most often in patients who have suffered facial trauma. These examinations may reveal incidental pathology. It is important that radiologists are aware of the radiological appearances and the clinical significance of these lesions. In this review we will present examples of the more common odontogenic lesions including: radicular cyst, odontogenic keratocyst, dentigerous cyst, ameloblastoma, and also examples of non-odontogenic pathology: bisphosphonate-related osteonecrosis of the jaw (BRONJ) and chronic osteomyelitis. Although some of the lesions will require computed tomography (CT) or magnetic resonance imaging (MRI) for further lesion characterization and evaluation of the surrounding tissues, we are going to focus on the plain film appearances. We will also briefly discuss the pathogenesis, epidemiology, and treatment of these lesions.

  18. Pathology of Coronary Chronic Total Occlusion

    Directory of Open Access Journals (Sweden)

    Kenichi Sakakura

    2016-06-01

    Full Text Available There is an increasing need for percutaneous revascularization procedures of coronary Chronic Total Occlusion (CTO, because many patients with severe coronary artery disease have limited options for revascularization. Although the success rate of percutaneous revascularization of CTOs was unsatisfactory from the 1990s to the 2000s, recent technological advances in interventional strategies have improved the success rate to 85%. Detailed histological assessment of human autopsy studies of CTO has contributed significantly to the refinement in Percutaneous Coronary Intervention (PCI techniques and device development. We have recently reported the pathological findings and characteristics of CTOs that occur in different clinical scenarios. In this review, we discuss the pathology of CTOs to facilitate greater understanding of revascularization strategies for CTOs.

  19. Personality disorders and dimensions in pathological gambling.

    Science.gov (United States)

    Odlaug, Brian L; Schreiber, Liana R N; Grant, Jon E

    2012-06-01

    Comorbid DSM-IV Axis II personality disorders appear to be common in pathological gambling (PG) and may contribute to the chronic problems often associated with the disorder. This study sought to examine the relationship between PG, personality disorders, and impulsivity in a sample of pathological gamblers. Personality assessments included the SCID-II, Eysenck Impulsiveness Questionnaire, Tridimensional Personality Questionnaire, and Barratt Impulsiveness Scale. A total of 77 individuals with DSM-IV PG were included in this study, of which 35 (45.5%) met criteria for at least one personality disorder. Specific aspects of impulsivity were associated with certain personality disorders in PG when grouped by cluster, yet the presence of a personality disorder was not positively correlated with gambling severity. It remains unclear how the presence of a personality disorder and aspects of impulsivity may affect treatment outcome. Further exploration of these disorders and dimensions of personality may encourage a more inclusively global treatment approach.

  20. Multispectral image segmentation of breast pathology

    Science.gov (United States)

    Hornak, Joseph P.; Blaakman, Andre; Rubens, Deborah; Totterman, Saara

    1991-06-01

    The signal intensity in a magnetic resonance image is not only a function of imaging parameters but also of several intrinsic tissue properties. Therefore, unlike other medical imaging modalities, magnetic resonance imaging (MRI) allows the imaging scientist to locate pathology using multispectral image segmentation. Multispectral image segmentation works best when orthogonal spectral regions are employed. In MRI, possible spectral regions are spin density (rho) , spin-lattice relaxation time T1, spin-spin relaxation time T2, and texture for each nucleus type and chemical shift. This study examines the ability of multispectral image segmentation to locate breast pathology using the total hydrogen T1, T2, and (rho) . The preliminary results indicate that our technique can locate cysts and fibroadenoma breast lesions with a minimum number of false-positives and false-negatives. Results, T1, T2, and (rho) algorithms, and segmentation techniques are presented.

  1. Wildfire risk as a socioecological pathology

    Science.gov (United States)

    Fischer, A. Paige; Spies, Thomas A; Steelman, Toddi A; Moseley, Cassandra; Johnson, Bart R.; Bailey, John D.; Ager, Alan A; Bourgeron, Patrick S.; Charnley, Susan; Collins, Brandon M.; Kline, Jeffrey D; Leahy, Jessica E; Littell, Jeremy; Millington, James D. A.; Nielsen-Pincus, Max; Olsen, Christine S; Paveglio, Travis B; Roos, Christopher I.; Steen-Adams, Michelle M; Stevens, Forrest R; Vukomanovic, Jelena; White, Eric M; Bowman, David M J S

    2016-01-01

    Wildfire risk in temperate forests has become a nearly intractable problem that can be characterized as a socioecological “pathology”: that is, a set of complex and problematic interactions among social and ecological systems across multiple spatial and temporal scales. Assessments of wildfire risk could benefit from recognizing and accounting for these interactions in terms of socioecological systems, also known as coupled natural and human systems (CNHS). We characterize the primary social and ecological dimensions of the wildfire risk pathology, paying particular attention to the governance system around wildfire risk, and suggest strategies to mitigate the pathology through innovative planning approaches, analytical tools, and policies. We caution that even with a clear understanding of the problem and possible solutions, the system by which human actors govern fire-prone forests may evolve incrementally in imperfect ways and can be expected to resist change even as we learn better ways to manage CNHS.

  2. Frozen section diagnosis in ophthalmic pathology

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    Biswas Jyotirmay

    1993-01-01

    Full Text Available Frozen section diagnosis is extensively used in various branches of pathology, but its application in ophthalmic pathology was recognised only in the 1970s. We studied 10 sections of ocular and adenexal lesions by frozen section diagnosis, which included orbital lesions (4 cases, lid lesions (3 cases, and intraocular tissue (1 case. The time taken for processing ranged between 10 to 15 minutes. Diagnoses based on frozen section evaluation included lymphoma, mesenchymal chondrosarcoma, solar keratosis, compound naevus, silicone oil globules in cataractous lens, neurofibromatosis, pseudotumour, retinoblastoma, and chronic blepharitis. Although further histopathologic examination correlated well with the frozen section (100% observations, the diagnosis was deferred in the case of naevus and reactive lymphoid hyperplasia. Our study shows that frozen section diagnosis in ophthalmic surgery is quite reliable and is particularly useful in ocular adenexal lesions

  3. Multidetector CT of hepatic artery pathologies.

    Science.gov (United States)

    Karaosmanoglu, D; Erol, B; Karcaaltincaba, M

    2012-01-01

    The hepatic artery can be involved by a variety of pathology and diseases.Today MDCT enables high quality imaging of the hepatic artery using axial, MIP and volume rendered images. We illustrate MDCT findings of anatomical variations, aneurysm, dilatation, dissection, arteriovenous fistula, thrombosis and stenosis. Aneurysms can be saccular, fusiform and multiple and may develop due to atherosclerosis, vasculitis, trauma and biopsy. Dilatation of hepatic artery can be seen in portal hypertension, Osler-Weber-Rendu disease and hemangiomatosis. Hepatic artery can be occluded after trauma and transplantation. Dissection develops due to atherosclerosis, Marfan and Ehler Danlos syndromes and during pregnancy. Arteriovenous fistula can be congenital and acquired. We conclude that various hepatic artery pathologies can be confidently diagnosed by MDCT.

  4. Pathologic overproduction: the bad side of adenosine.

    Science.gov (United States)

    Borea, Pier Andrea; Gessi, Stefania; Merighi, Stefania; Vincenzi, Fabrizio; Varani, Katia

    2017-03-02

    Adenosine is an endogenous ubiquitous purine nucleoside, increased by hypoxia, ischemia and tissue damage that mediates a number of physiopathological effects by interacting with four G-protein-coupled receptors, identified as A1 , A2A , A2B , and A3 . Physiological and acutely-increased adenosine is associated with beneficial effects mostly including vasodilation and decrease of inflammation. In contrast chronic overproduction of adenosine occurs in important pathological states, where long lasting increases in the nucleoside levels are responsible for the bad side of adenosine associated with chronic inflammation, fibrosis and organ damage. In this review we describe and critically discuss the pathologic overproduction of adenosine analysing when, where and how adenosine exerts its detrimental effects through the body.

  5. [Pathology and viral metagenomics, a recent history].

    Science.gov (United States)

    Bernardo, Pauline; Albina, Emmanuel; Eloit, Marc; Roumagnac, Philippe

    2013-05-01

    Human, animal and plant viral diseases have greatly benefited from recent metagenomics developments. Viral metagenomics is a culture-independent approach used to investigate the complete viral genetic populations of a sample. During the last decade, metagenomics concepts and techniques that were first used by ecologists progressively spread into the scientific field of viral pathology. The sample, which was first for ecologists a fraction of ecosystem, became for pathologists an organism that hosts millions of microbes and viruses. This new approach, providing without a priori high resolution qualitative and quantitative data on the viral diversity, is now revolutionizing the way pathologists decipher viral diseases. This review describes the very last improvements of the high throughput next generation sequencing methods and discusses the applications of viral metagenomics in viral pathology, including discovery of novel viruses, viral surveillance and diagnostic, large-scale molecular epidemiology, and viral evolution.

  6. Aligning Organizational Pathologies and Organizational Resilience Indicators

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    Manuel Morales Allende

    2017-07-01

    Full Text Available Developing resilient individuals, organizations and communities is a hot topic in the research agenda in Management, Ecology, Psychology or Engineering. Despite the number of works that focus on resilience is increasing, there is not completely agreed definition of resilience, neither an entirely formal and accepted framework. The cause may be the spread of research among different fields. In this paper, we focus on the study of organizational resilience with the aim of improving the level of resilience in organizations. We review the relation between viable and resilient organizations and their common properties. Based on these common properties, we defend the application of the Viable System Model (VSM to design resilient organizations. We also identify the organizational pathologies defined applying the VSM through resilience indicators. We conclude that an organization with any organizational pathology is not likely to be resilient because it does not fulfill the requirements of viable organizations.

  7. Pathology Laboratories Productivity Evaluation in Turkey

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    Kutsal YÖRÜKOĞLU

    2011-09-01

    Full Text Available Objective: Efficiency criteria and automation in pathology laboratories have been set in a limited number of studies usually originated from the United States. A questionnaire has been prepared to determine the situation and define the criteria for adaptation in our country.Material and Method: The survey was sent to all pathology laboratories and, 302 responded. The survey questionned of pathology laboratories efficiencies, staff workloads, methods applied, devices used, and physical conditions. Work flow productivity was obtained by dividing the annual number of blocks to working hours multiplied by the number of technicians. The hospitals were categorized to 3 groups according to providing training or not and privacy, and to 4 groups according to the annual biopsy numbers. The data entered through the SPSS 16.0 statistical package program, analysis of distribution criteria, significance of the difference between means tests were used.Results: The annual biopsy numbers were significantly higher in education units, but below the limit of productivity levels for all laboratories. The device hardware and automation correlated with annual biopsy numbers. However, the laboratories of limited capacity have redundant automation. Histochemical and immunohistochemical staining numbers were high. Liquid-based cytology techniques were used more significantly in private hospitals. Archiving times were not standard. A serious shortage of working space in service hospitals was noted. Work flow productivity in education units was at the border, and low in other units.Conclusion: All pathology laboratories in our country should define and improve their productivities. Formalizing of archiving times is very important for future malpractice lawsuits.

  8. [Epstein Barr and cytomegaloviruses in ocular pathology].

    Science.gov (United States)

    Magdei, Corina; Cuşnir, Valeriu; Bârcâ, Ludmila

    2010-01-01

    Epstein-Barr virus (EBV) and Citomegalovirus (CMV) are Herpesviridae family representative and presents a real danger for human. A very high infect risk of population farther the danger The ocular pathology induced by them can affect all media and tunics of optic analyzer. An etiologic differentiation is necessary for the mentioned viruses induced diseases. The etiologic differentiation has like purpose the enforcement of an effective and optimal antiviral and immunomodulating therapy.

  9. Evolution of occlusal pathology. A literature review.

    OpenAIRE

    2013-01-01

    Introduction: Many of the guidelines on occlusion and treatment alternatives in dentate and partially edentulous patients, are based on concepts raised in the beginning of dentistry. The diversity of the occlusion schools has become some of these concepts complex to understand and apply. This diversity makes difficult the compression of the occlusal physiology and its disorders, hindering the understanding of the occlusal pathology and its proper diagnosis and management. Objective: This is w...

  10. Gynecological pelvic pain as emergency pathology.

    Science.gov (United States)

    Rivera Domínguez, A; Mora Jurado, A; García de la Oliva, A; de Araujo Martins-Romeo, D; Cueto Álvarez, L

    Acute pelvic pain is a common condition in emergency. The sources of acute pelvic pain are multifactorial, so it is important to be familiar with this type of pathologies. The purpose of this article is review the main causes of gynecological acute pelvic pain and their radiologic appearances to be able to make an accurate diagnosis and provide objective criteria for patient management. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Neurofibrillary pathology and aluminum in Alzheimer's disease

    OpenAIRE

    Shin, R. W.; Lee, V.M.Y.; Trojanowski, J.Q.

    1995-01-01

    Since the first reports of aluminum-induced neurofibrillary degeneration in experimental animals, extensive studies have been performed to clarify the role played by aluminum in the pathogenesis of Alzheimer's disease (AD). Additional evidence implicating aluminum in AD includes elevated levels of aluminum in the AD brain, epidemiological data linking aluminum exposure to AD, and interactions between aluminum and protein components in the pathological lesions o...

  12. Hearing impairment and ear pathology in Nepal.

    Science.gov (United States)

    Little, P; Bridges, A; Guragain, R; Friedman, D; Prasad, R; Weir, N

    1993-05-01

    A stratified random cluster sample of 15,845 subjects was performed in two regions of Nepal to determine the prevalence and main causes of hearing impairment (the most common disability) and the prevalence of ear disease. Subjects reporting current ear pain, or ear discharge, or hearing impairment on direct questioning by a Nepali health worker (primary screening failed), had otoscopy and audiometry (using the Liverpool Field Audiometer) performed, and a questionnaire administered relating to past history. In every fifth house subjects who passed the primary screening (1,716 subjects) were examined to assess the false negative rate of screening. An estimated 16.6 per cent of the study population have hearing impairment (either ear worse than 30 dB hearing threshold level (HTL) 1.0-4.0 kHz, or 50 dB HTL 0.5 kHz), and 7.4 per cent ear drum pathology, equivalent to respectively 2.71 and 1.48 million people extrapolated to the whole of Nepal. Most hearing impairment in the school age group (55.2 per cent) is associated with otitis media or its sequelae. Probably at least 14 per cent of sensorineural deafness is preventable (7 per cent infectious disease, 3.9 per cent trauma, 0.8 per cent noise exposure, 1 per cent cretinism, and 1 per cent abnormal pregnancy or labour). Most individuals reporting current ear pathology (61 per cent) had never attended a health post, and of those receiving ear drop treatment, 84 per cent still had serious pathology. Of subjects who reported ear drop treatment at any time, 31 per cent still had serious pathology. The use of traditional remedies was prevalent.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Infrared Spectroscopic Imaging for Prostate Pathology

    Science.gov (United States)

    2008-03-01

    definitive indicator of disease and form the gold standard of diagnosis [2]. Along with clinical history , stage, and PSA values, pathologic diagno...Ramon Llull University, Barcelona, Catalonia , Euro- pean Union Llorà X (2006) Learning Classifier Systems and other genetics-based machine learning...Arquitectura La Salle. Ramon Llull University, Barcelona, Catalonia , European Union, February, 2002. [22] X. Llorà and J. Garrell. Knowledge

  14. Pathologic research update of colorectal neuroendocrine tumors

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Colorectal neuroendocrine tumors (NETs) originate from neuroendocrine cells in the intestinal tract, and represent a small area within oncology, but one which has provided increasing new data during the past years. Although the World Health Organization has determined clinical and histological features to predict prognosis for such tumors, they may not be valid on an individual basis. We aim to give an overview of the recent findings with regard to pathology, molecular genetics and diagnosis of NETs.

  15. Pathology of cloaca anomalies with case correlation.

    Science.gov (United States)

    Gupta, Anita; Bischoff, Andrea

    2016-04-01

    During the fourth week of human embryo development, a transient common channel known as a cloaca is formed from which three cavities with three external orifices arises. Cloaca anomalies occur when there is failure of separation of the rectum, vagina, and urethra channel resulting in a single drain into the perineum. In our previous institutional studies, Runck et al. compared human and mouse cloaca development and found early mis-patterning of the embryonic cloaca deranged hedgehog and bone morphogenetic proteins (BMP) signaling. Also, our group reported the embryological correlation of the epithelial and stromal histology found in step sections of the common channel in 14 cloaca malformations in humans. In this review, we present the pathology of a 4-year-old female with a cloaca and VACTERL complex, and summarize our current knowledge of cloaca pathology. Furthermore, we suggest that careful pathological examination of cloaca specimens in conjunction with surgical orientation may result in a better understanding of the etiology of this condition. Published by Elsevier Inc.

  16. Thorax thermographic simulator for breast pathologies

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    Itzel A. Avila-Castro

    2017-04-01

    Full Text Available New diagnostic techniques for breast cancer detection have been developed and improved, in order to increase patient life expectancy. These techniques were emphasized in early detection of tumors with smaller dimensions, providing a better prognosis. Along with these new methods, it is necessary to propose training devices or tools to support health professionals to use them and rely on them. Our purpose is to develop a device to support thermographic analyses for early breast pathology detection. A programmable thorax was developed with the aim of simulating hyperthermic characteristics of breast pathologies in a defined area. Temperature distributions of breast tissue with a cancerous lesion were mathematically modeled using Pennes's equation, and a thermo-visual control system was built within the physical model in order to simulate a local thermal pattern of a patient's thermal image with infiltrating ductal carcinoma. Our results showed a good approximation of simulated thermal patterns to real images from a patient. In consequence we archived to obtain a thorax simulator device as first step in training health professionals in thermography techniques and to impulse the use of this method for early detection of breast pathologies.

  17. Clinical and experimental pathology of Moyamoya disease

    Institute of Scientific and Technical Information of China (English)

    饶明俐; 张海鸥; 刘群; 张淑琴; 胡林森; 邓方

    2003-01-01

    Objective To investigate the etiology, pathology, and mechanism of pathogenesis of Moyamoya disease.Methods A total of 15 human autopsies were analyzed. In addition, in order to create an animal model of the disease, 21 Japanese rabbits were divided randomly into two groups and subjected to injections of horse serum either intravenously or locally in the area of the sympathetic ganglia. Pathological and immunohistochemical characteristics were observed.Results The pathological features of the autopsies and the animal models both involved intima hyperplasia and stenosis or even occlusion of the lumen in the terminal ends of the internal carotid artery and the anterior and middle cerebral arteries. Disconnections or even breakages of the inner layer of the lumen were also observed, without an obvious inflammatory response. Hyperplasic smooth muscle cells of the medial membrane had extended inward through broken portions of the internal elastic lamina, with intima cell hyperplasia resulting in lumen stenosis. The hyperplastic vascular walls were positive for IgG and IgM.Conclusions The etiology of Moyamoya disease may involve allergic angiitis. A possible mechanism is that proximal portions of the circle of Willis first develop chronic stenosis or occlusion, leading to compensatory small vessel proliferation, which perforates into the cerebral parenchyma.

  18. Sensorineural Tinnitus: Its Pathology and Probable Therapies

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    Aage R. Møller

    2016-01-01

    Full Text Available Tinnitus is not a single disease but a group of different diseases with different pathologies and therefore different treatments. Regarding tinnitus as a single disease is hampering progress in understanding of the pathophysiology of tinnitus and perhaps, more importantly, it is a serious obstacle in development of effective treatments for tinnitus. Subjective tinnitus is a phantom sound that takes many different forms and has similarities with chronic neuropathic pain. The pathology may be in the cochlea, in the auditory nerve, or, most commonly, in the brain. Like chronic neuropathic pain tinnitus is not life threatening but influences many normal functions such as sleep and the ability to concentrate on work. Some forms of chronic tinnitus have two components, a (phantom sound and a component that may best be described as suffering or distress. The pathology of these two components may be different and the treatment that is most effective may be different for these two components. The most common form of treatment of tinnitus is pharmacological agents and behavioral treatment combined with sound therapy. Less common treatments are hypnosis and acupuncture. Various forms of neuromodulation are becoming in use in an attempt to reverse maladaptive plastic changes in the brain.

  19. Clinical predictive factors of pathologic tumor response

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    Choi, Chi Hwan; Kim, Won Dong; Lee, Sang Jeon; Park, Woo Yoon [Chungbuk National University College of Medicine, Cheongju (Korea, Republic of)

    2012-09-15

    The aim of this study was to identify clinical predictive factors for tumor response after preoperative chemoradiotherapy (CRT) in rectal cancer. The study involved 51 patients who underwent preoperative CRT followed by surgery between January 2005 and February 2012. Radiotherapy was delivered to the whole pelvis at a dose of 45 Gy in 25 fractions, followed by a boost of 5.4 Gy in 3 fractions to the primary tumor with 5 fractions per week. Three different chemotherapy regimens were used. Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and pathologic complete response (ypCR). Statistical analyses were performed to identify clinical factors associated with pathologic tumor response. Tumor downstaging was observed in 28 patients (54.9%), whereas ypCR was observed in 6 patients (11.8%). Multivariate analysis found that predictors of downstaging was pretreatment relative lymphocyte count (p = 0.023) and that none of clinical factors was significantly associated with ypCR. Pretreatment relative lymphocyte count (%) has a significant impact on the pathologic tumor response (tumor downstaging) after preoperative CRT for locally advanced rectal cancer. Enhancement of lymphocyte-mediated immune reactions may improve the effect of preoperative CRT for rectal cancer.

  20. Resident training in pathology: Results of questionnaires

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    İpek Işık GÖNÜL

    2008-01-01

    Full Text Available The aim of this study is to discuss the training of pathology residents from the points of wave of themselves and their tutors and reveal the problems.For this purpose, representatives of 4 Universities, 5 State hospitals and Gülhane Military Medical Academy have prepared 2 types of questionnaires in order to the serving capacities of their institutions and the opinions of the tutors working in that departments on training of pathology residents.According to the results, the number of biopsy and cytological materials together with number of faculty is sufficient for all institutions. Both histochemistry and immunohistochemistry have been applied in all institutions. However, only one state hospital has been performing immunoflourescence technique. It is noticeable to see 2 state hospitals do not have any documents on written job description, which summarizes the authority and responsibility of the pathology residents. Another significant conclusion is that the answers of the tutors for the assistant's job description and their responsibility in the training process are very heterogeneous. Time spent for gross examination by tutors was found to be insufficient by 58% of themselves. Although “written feedbacks for residents and tutors” is only being applied in 2 Universities, the majority of the tutors who have participated in the questionnaire have agreed upon the necessity of them for all institutions (95.4% and 93.8%, respectively.

  1. Acoustic analysis assessment in speech pathology detection

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    Panek Daria

    2015-09-01

    Full Text Available Automatic detection of voice pathologies enables non-invasive, low cost and objective assessments of the presence of disorders, as well as accelerating and improving the process of diagnosis and clinical treatment given to patients. In this work, a vector made up of 28 acoustic parameters is evaluated using principal component analysis (PCA, kernel principal component analysis (kPCA and an auto-associative neural network (NLPCA in four kinds of pathology detection (hyperfunctional dysphonia, functional dysphonia, laryngitis, vocal cord paralysis using the a, i and u vowels, spoken at a high, low and normal pitch. The results indicate that the kPCA and NLPCA methods can be considered a step towards pathology detection of the vocal folds. The results show that such an approach provides acceptable results for this purpose, with the best efficiency levels of around 100%. The study brings the most commonly used approaches to speech signal processing together and leads to a comparison of the machine learning methods determining the health status of the patient

  2. Talc pneumoconiosis: a pathologic and mineralogic study.

    Science.gov (United States)

    Gibbs, A E; Pooley, F D; Griffiths, D M; Mitha, R; Craighead, J E; Ruttner, J R

    1992-12-01

    Seventeen cases of "talc pneumoconiosis" were examined pathologically and mineralogically to ascertain whether a true talc pneumoconiosis existed and also to compare these results in primary, secondary, and tertiary exposures. Mineralogic analyses were performed on wet tissue or tissue blocks by a variety of techniques, including analytical transmission electron microscopy and x-ray diffraction. Overall, the pathologic appearance of the tissues was similar in primary, secondary, and tertiary exposures, although ferruginous bodies and foreign body giant cells were not always present in cases caused by secondary exposures. Mixed dust fibrotic lesions were found in two cases in which there were substantial quantities of quartz present. There was great variation in the minerals found within the lung tissues. Several cases showed significant quantities of mica and kaolin in addition to talc. One case consisted predominantly of mica and in fact could be regarded as "mica pneumoconiosis"; this diagnosis was correctly attributed because of the mineralogic findings. Tremolite fibers were found in only two cases. Substantial quantities of crocidolite and amosite fibers were found in one case. This study shows that "talcosis" frequently represents disease associated with a variety of minerals and that talc is a common denominator. It shows also the usefulness of lung dust mineral analysis, particularly in secondary industries, for evaluating the cause of a pathologic reaction when exposures are especially complex.

  3. Pathological conditions associated with rhinitis medicamentosa

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    Milošević Dušanka

    2004-01-01

    Full Text Available Rhinitis medicamentosa (nose-drop-nose" is a term used for pathological condition of the nasal mucous membrane that results from long-term abuse with intranasal vasoconstrictors. The aim of this work was to examine what lead the patients with nosedropnose rhinitis to the initial usage of intranasal vasoactive drugs, in this prospective study, 92 patients with rhinitis medicamentosa were included. The evaluation of all study subjects comprised the history, ORL, microbiological and radiological examination, skin prick tests with a battery of routine respiratory and nutritive allergens and nasal cytology. The results of this study showed that the pathological conditions for initial use of intranasal vasoactive drugs were: acute upper respiratory infections in 293%, vasomotor rhinitis in 21.7%, allergic rhinitis in 16.3%, deviated nasal septum in 13.0%, nasal polyposis in 12%, rhinitis induced by mechanical trauma in 4.4%, and hormonal rhinitis in 3.3% of patients with rhinitis medicamentosa. In conclusion, the most common pathological conditions for developing rhinitis medicamentosa were chronic inflammatory and structural diseases manifested by permanent nasal obstruction as well as acute upper respiratory infections are.

  4. [Incidental finding of pathological coagulation parameters].

    Science.gov (United States)

    Luxembourg, B; Lindhoff-Last, E

    2014-10-01

    Pathological coagulation parameters may reflect life-threatening hemorrhagic or thromboembolic diseases but may also be a laboratory result without any clinical significance, result from in vitro phenomena or preanalytical errors. This article gives an overview of potential pitfalls in coagulation diagnostics, lists the differential diagnoses of pathological coagulation parameters and describes further steps in the diagnostic approach to clarify pathological results. The focus lies on coagulation parameters that are frequently determined in routine clinical investigations, e.g. platelet count, prothrombin time, activated partial thromboplastin time (aPTT) and fibrinogen. Besides heparin, fondaparinux, danaparoid, and vitamin K antagonists, direct factor Xa inhibitors and direct thrombin inhibitors are nowadays available for therapeutic anticoagulation. This article gives an overview of the influence of anticoagulants on coagulation parameters which depends on the dose, the time of the last administration, as well as the method used for the determination of coagulation parameters. Moreover, common reasons for elevation of the fibrin degradation product D-dimer are presented. The clinical utility of D-dimer assays is limited by their poor specificity. Elevated D-dimer concentrations can be found in various diseases and also under normal physiological circumstances (e.g. in the elderly). Thus, the most useful clinical application of D-dimer is evidence of normal values to essentially rule out venous thromboembolism.

  5. [Comparative pathology of the microcirculatory bed].

    Science.gov (United States)

    Strukov, A I; Vorob'eva, A A

    1976-11-01

    This paper presents an analysis of publications, mostly by Soviet authores, on clinical studies and morphological examinations of the microcirculatory bed in different pathology. It is concluded that the microcirculatory bed should be regarded as an integral system responding to the pathological effects by a local and general reaction of its structural components and by changing the rheological properties of blood. Two types of changes develop in the microcirculatory system -- sterotyped ones, typical for extreme states (various kinds of shock, hypertensive crisis, stress situations), and those specific for certain diseases (diabetes melitus, essential hypertension, athersclerosis, collagenoses, etc.). In all the above diseases the pathological process affects the functional structures of microcirculation that undergo a rearrangement in accordance with the requirements of the body. In the initial period of the disease this re-arrangement is of a compensatory nature and passes ahead of the clinical manifestations. A comparison of the pictutrs obtained by biomicroscopy of the bulbconjunctiva of the eye and of other mucosae with film preparations of the serosae demonstrates their complete similarity. Therefore, the method of biomicroscopy of the eyeball and of the mucosae as a method reflecting the state of microcirculation in the body as a whole should become an integral part of the clinical examination of patients.

  6. [Pathology of Charcot-Marie-Tooth Disease].

    Science.gov (United States)

    Oka, Nobuyuki

    2016-01-01

    Although genetic testing is available, nerve biopsy is useful in selected patients for the diagnosis of Charcot-Marie-Tooth disease (CMT). These are sporadic cases of hereditary neuropathy, or familial cases in which genetic testing is negative. CMT is caused by mutations of various genes. The pathological features of CMT have mostly been investigated using nerve biopsy, which may shed light on the presumed functions of mutated gene products. PMP22 duplication in CMT1A induces numerous large onion bulb lesions (OB). Compared to chronic inflammatory demyelinating polyradiculoneuropathy, the differential features of CMT1A are patchy distribution of OB and non-inflammatory lesions. CMT1B also manifests as OB, but presents abnormal compaction of myelin sheaths caused by uncompacted myelin or excessive myelin folding. CMT2 includes axonal neuropathies and many causative genes have been found. CMT2A (MFN2 mutation) shows abnormal mitochondria with a spherical morphology instead of tubular in the longitudinal direction. CMT4 consists of autosomal recessive forms with demyelinating pathology. Most subtypes have mutations of genes relating to myelin maintenance, and pathologically, they show abnormal folding of the myelin structure.

  7. Pathological study on severe acute respiratory syndrome

    Institute of Scientific and Technical Information of China (English)

    郎振为; 张立洁; 张世杰; 孟忻; 李俊强; 宋晨朝; 孙琳; 周育森

    2003-01-01

    Objective To study the pathological characteristics of severe acute respiratory syndrome (SARS) and its relationship to clinical manifestation. Methods Tissue specimens from 3 autopsies of probable SARS cases were studied by microscope, and the clinical data was reviewed.Results The typical pathological changes of lungs were diffuse hemorrhaging on the surface. A combination of serous, fibrinous and hemorrhagic inflammation was seen in most of the pulmonary alveoli with the engorgement of capillaries and detection of micro-thrombosis in some of these capillaries. Pulmonary alveoli thickened with interstitial mononuclear inflammatory infiltrates, suffered diffuse alveolar damage, experienced desquamation of pneumocytes and had hyaline-membrane formation, fibrinoid materials, and erythrocytes in alveolar spaces. There were thromboembolisms in some bronchial arteries. Furthermore, hemorrhagic necrosis was also evident in lymph nodes and spleen with the attenuation of lymphocytes. Other atypical pathological changes, such as hydropic degeneration, fatty degeneration, interstitial cell proliferation and lesions having existed before hospitalization were observed in the liver, heart, kidney and pancreas.Conclusion Severe damage to the pulmonary and immunological systems is responsible for the clinical features of SARS and may lead to the death of patients.

  8. Tripartite motif 32 prevents pathological cardiac hypertrophy.

    Science.gov (United States)

    Chen, Lijuan; Huang, Jia; Ji, Yanxiao; Zhang, Xiaojing; Wang, Pixiao; Deng, Keqiong; Jiang, Xi; Ma, Genshan; Li, Hongliang

    2016-05-01

    TRIM32 (tripartite motif 32) is widely accepted to be an E3 ligase that interacts with and eventually ubiquitylates multiple substrates. TRIM32 mutants have been associated with LGMD-2H (limb girdle muscular dystrophy 2H). However, whether TRIM32 is involved in cardiac hypertrophy induced by biomechanical stresses and neurohumoral mediators remains unclear. We generated mice and isolated NRCMs (neonatal rat cardiomyocytes) that overexpressed or were deficient in TRIM32 to investigate the effect of TRIM32 on AB (aortic banding) or AngII (angiotensin II)-mediated cardiac hypertrophy. Echocardiography and both pathological and molecular analyses were used to determine the extent of cardiac hypertrophy and subsequent fibrosis. Our results showed that overexpression of TRIM32 in the heart significantly alleviated the hypertrophic response induced by pressure overload, whereas TRIM32 deficiency dramatically aggravated pathological cardiac remodelling. Similar results were also found in cultured NRCMs incubated with AngII. Mechanistically, the present study suggests that TRIM32 exerts cardioprotective action by interruption of Akt- but not MAPK (mitogen-dependent protein kinase)-dependent signalling pathways. Additionally, inactivation of Akt by LY294002 offset the exacerbated hypertrophic response induced by AB in TRIM32-deficient mice. In conclusion, the present study indicates that TRIM32 plays a protective role in AB-induced pathological cardiac remodelling by blocking Akt-dependent signalling. Therefore TRIM32 could be a novel therapeutic target for the prevention of cardiac hypertrophy and heart failure. © 2016 The Author(s).

  9. Unexpected cellular players in Rett syndrome pathology.

    Science.gov (United States)

    Cronk, James C; Derecki, Noel C; Litvak, Vladimir; Kipnis, Jonathan

    2016-08-01

    Rett syndrome is a devastating neurodevelopmental disorder, primarily caused by mutations of methyl CpG-binding protein 2 (MeCP2). Although the genetic cause of disease was identified over a decade ago, a significant gap still remains in both our clinical and scientific understanding of its pathogenesis. Neurons are known to be primary players in pathology, with their dysfunction being the key in Rett syndrome. While studies in mice have demonstrated a clear causative - and potential therapeutic - role for neurons in Rett syndrome, recent work has suggested that other tissues also contribute significantly to progression of the disease. Indeed, Rett syndrome is known to present with several common peripheral pathologies, such as osteopenia, scoliosis, gastrointestinal problems including nutritional defects, and general growth deficit. Mouse models assessing the potential role of non-neuronal cell types have confirmed both roles in disease and potential therapeutic targets. A new picture is emerging in which neurons both initiate and drive pathology, while dysfunction of other cell types and peripheral tissues exacerbate disease, possibly amplifying further neurologic problems, and ultimately result in a positive feedback loop of progressively worsening symptoms. Here, we review what is known about neuronal and non-neuronal cell types, and discuss how this new, integrative understanding of the disease may allow for additional clinical and scientific pathways for treating and understanding Rett syndrome.

  10. Hypertext atlas of fetal and neonatal pathology.

    Science.gov (United States)

    Jezová, Marta; Múcková, Katarína; Soucek, Ondrej; Feit, Josef; Vlasín, Pavel

    2008-07-15

    Hypertext atlas of fetal and neonatal pathology is a free resource for pregraduate students of medicine, pathologists and other health professionals dealing with prenatal medicine. The atlas can be found at http://www.muni.cz/atlases. The access is restricted to registered users. Concise texts summarize the gross and microscopic pathology, etiology, and clinical signs of both common and rare fetal and neonatal conditions. The texts are illustrated with over 300 images that are accompanied by short comments. The atlas offers histological pictures of high quality. Virtual microscope interface is used to access the high-resolution histological images. Fetal ultrasound video clips are included. Case studies integrate clinical history, prenatal ultrasonographic examination, gross pathology and histological features. The atlas is available in English (and Czech) and equipped with an active index. The atlas is suitable both for medical students and pathologists as a teaching and reference tool. The atlas is going to be further expanded while keeping the high quality of the images.

  11. Clinical pathology services: remapping our strategic itinerary.

    Science.gov (United States)

    Blanckaert, Norbert

    2010-07-01

    Both technological advances and economic drivers have led to major changes in clinical laboratories across the world, with vastly improved testing productivity. However, the production process capability advances have far outpaced the clinical pathologists' success in assuring optimal test utilization and interpretation. While productivity of 'commodity' testing increases, our healthcare value productivity decreases. Such developments constitute a serious threat to our clinical pathology specialty, not only because pathologists may lose direct control of the commodity testing production activities, but also because the present evolution exposes a failure of our core clinical activities, the pathologist's knowledge processes that translate 'commodity' results into medical outcomes optimization. At a time when a revolution in health care organization is inescapable in the years ahead, clinical pathology must proceed from a merely reactive strategy (to fulfill the 'more with less' demands) to a proactive strategy where we build excellence and visibility in knowledge services on a strong foothold of operational excellence. Based on a Strengths-Weaknesses-Opportunities-Threats analysis, we argue that clinical pathology should safeguard and expand its healthcare value productivity by assuming leadership in building integrated laboratory services networks. We also suggest that the core knowledge processes deserve a system approach, for example, by applying a risk-based quality management system.

  12. The Rise of Forensic Pathology in Human Medicine: Lessons for Veterinary Forensic Pathology.

    Science.gov (United States)

    Pollanen, M S

    2016-09-01

    The rise of forensic pathology in human medicine has greatly contributed to the administration of justice, public safety and security, and medical knowledge. However, the evolution of human forensic pathology has been challenging. Veterinary forensic pathologists can learn from some of the lessons that have informed the growth and development of human forensic pathology. Three main observations have emerged in the past decade. First, wrongful convictions tell us to use a truth-seeking stance rather than an a priori "think dirty" stance when investigating obscure death. Second, missed homicides and concealed homicides tell us that training and certification are the beginning of reliable forensic pathology. Third, failure of a sustainable institutional arrangement that fosters a combination of service, research, and teaching will lead to stagnation of knowledge. Forensic pathology of humans and animals will flourish, help protect society, and support justice if we embrace a modern biomedical scientific model for our practice. We must build training programs, contribute to the published literature, and forge strong collaborative institutions.

  13. Guidelines for resident training in veterinary clinical pathology. III: cytopathology and surgical pathology.

    Science.gov (United States)

    Kidney, Beverly A; Dial, Sharon M; Christopher, Mary M

    2009-09-01

    The Education Committee of the American Society for Veterinary Clinical Pathology has identified a need for improved structure and guidance of training residents in clinical pathology. This article is the third in a series of articles that address this need. The goals of this article are to describe learning objectives and competencies in knowledge, abilities, and skills in cytopathology and surgical pathology (CSP); provide options and ideas for training activities; and identify resources in veterinary CSP for faculty, training program coordinators, and residents. Guidelines were developed in consultation with Education Committee members and peer experts and with evaluation of the literature. The primary objectives of training in CSP are: (1) to develop a thorough, extensive, and relevant knowledge base of biomedical and clinical sciences applicable to the practice of CSP in domestic animals, laboratory animals, and other nondomestic animal species; (2) to be able to reason, think critically, investigate, use scientific evidence, and communicate effectively when making diagnoses and consulting and to improve and advance the practice of pathology; and (3) to acquire selected technical skills used in CSP and pathology laboratory management. These guidelines define expected competencies that will help ensure proficiency, leadership, and the advancement of knowledge in veterinary CSP and will provide a useful framework for didactic and clinical activities in resident-training programs.

  14. Role of computed tomography in the study of vascular pathology

    Energy Technology Data Exchange (ETDEWEB)

    Procacci, C.; Bicego, E.; Bergamo, I.A. and others

    1988-01-01

    The most important indications to the use of computed tomography (CT) in the study of vascular pathology are considered. They may be divided as follows: 1) demonstration of vascular involvement by thoraco-abdominal neoplasms; 2) differential diagnosis between primary vascular and extra-vascular pathology; 3) assessment of primary arterial pathology. For each group, those pathologies are considered, for which CT plays a fundamental role.

  15. Pathological and microbiological studies on pneumonic lungs from Danish calves

    DEFF Research Database (Denmark)

    Tegtmeier, Conny; Uttenthal, Åse; Friis, N.F.

    1999-01-01

    During 1 year, the association between microbiological and pathological findings in 72 lungs from calves submitted to the Danish Veterinary Laboratory for diagnostic purposes was studied. All cases mere evaluated pathologically and bacteriologically, whereas only 68 cases were examined for the pr......During 1 year, the association between microbiological and pathological findings in 72 lungs from calves submitted to the Danish Veterinary Laboratory for diagnostic purposes was studied. All cases mere evaluated pathologically and bacteriologically, whereas only 68 cases were examined...

  16. Antibodies targeted to the brain with image-guided focused ultrasound reduces amyloid-beta plaque load in the TgCRND8 mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Jessica F Jordão

    Full Text Available Immunotherapy for Alzheimer's disease (AD relies on antibodies directed against toxic amyloid-beta peptide (Abeta, which circulate in the bloodstream and remove Abeta from the brain. In mouse models of AD, the administration of anti-Abeta antibodies directly into the brain, in comparison to the bloodstream, was shown to be more efficient at reducing Abeta plaque pathology. Therefore, delivering anti-Abeta antibodies to the brain of AD patients may also improve treatment efficiency. Transcranial focused ultrasound (FUS is known to transiently-enhance the permeability of the blood-brain barrier (BBB, allowing intravenously administered therapeutics to enter the brain. Our goal was to establish that anti-Abeta antibodies delivered to the brain using magnetic resonance imaging-guided FUS (MRIgFUS can reduce plaque pathology. To test this, TgCRND8 mice received intravenous injections of MRI and FUS contrast agents, as well as anti-Abeta antibody, BAM-10. MRIgFUS was then applied transcranially. Within minutes, the MRI contrast agent entered the brain, and BAM-10 was later found bound to Abeta plaques in targeted cortical areas. Four days post-treatment, Abeta pathology was significantly reduced in TgCRND8 mice. In conclusion, this is the first report to demonstrate that MRIgFUS delivery of anti-Abeta antibodies provides the combined advantages of using a low dose of antibody and rapidly reducing plaque pathology.

  17. Clowns Benefit Children Hospitalized for Respiratory Pathologies

    Science.gov (United States)

    Bertini, Mario; Isola, Elena; Paolone, Giuseppe; Curcio, Giuseppe

    2011-01-01

    The study aims at evaluating health-generating function of humor therapy in a hospital ward hosting children suffering from respiratory pathologies. The main scope of this study is to investigate possible positive effects of the presence of a clown on both the clinical evolution of the on-going disease, and on some physiological and pain parameters. Forty-three children with respiratory pathologies participated in the study: 21 of them belonged to the experimental group (EG) and 22 children to the control group (CG). During their hospitalization, the children of the EG interacted with two clowns who were experienced in the field of pediatric intervention. All participants were evaluated with respect to clinical progress and to a series of physiological and pain measures both before and after the clown interaction. When compared with the CG, EG children showed an earlier disappearance of the pathological symptoms. Moreover, the interaction of the clown with the children led to a statistically significant lowering of diastolic blood pressure, respiratory frequency and temperature in the EG as compared with the control group. The other two parameters of systolic pressure and heart frequency yielded results in the same direction, without reaching statistical significance. A similar health-inducing effect of clown presence was observed on pain parameters, both by self evaluation and assessment by nurses. Taken together, our data indicate that the presence of clowns in the ward has a possible health-inducing effect. Thus, humor can be seen as an easy-to-use, inexpensive and natural therapeutic modality to be used within different therapeutic settings. PMID:21785637

  18. Pathology in drug discovery and development.

    Science.gov (United States)

    Jubb, Adrian M; Koeppen, Hartmut; Reis-Filho, Jorge S

    2014-01-01

    The rapid pace of drug discovery and drug development in oncology, immunology and ophthalmology brings new challenges; the efficient and effective development of new targeted drugs will require more detailed molecular classifications of histologically homogeneous diseases that show heterogeneous clinical outcomes. To this end, single companion diagnostics for specific drugs will be replaced by multiplex diagnostics for entire therapeutic areas, preserving tissue and enabling rapid molecular taxonomy. The field will move away from the development of new molecular entities as single agents, to which resistance is common. Instead, a detailed understanding of the pathological mechanisms of resistance, in patients and in preclinical models, will be key to the validation of scientifically rational and clinically effective drug combinations. To remain at the heart of disease diagnosis and appropriate management, pathologists must evolve into translational biologists and biomarker scientists. Herein, we provide examples of where this metamorphosis has already taken place, in lung cancer and melanoma, where the transformation has yet to begin, in the use of immunotherapies for ophthalmology and oncology, and where there is fertile soil for a revolution in treatment, in efforts to classify glioblastoma and personalize treatment. The challenges of disease heterogeneity, the regulatory environment and adequate tissue are ever present, but these too are being overcome in dedicated academic centres. In summary, the tools necessary to overcome the 'whens' and 'ifs' of the molecular revolution are in the hands of pathologists today; it is a matter of standardization, training and leadership to bring these into routine practice and translate science into patient benefit. This Annual Review Issue of the Journal of Pathology highlights the central role for pathology in modern drug discovery and development.

  19. Clowns benefit children hospitalized for respiratory pathologies.

    Science.gov (United States)

    Bertini, Mario; Isola, Elena; Paolone, Giuseppe; Curcio, Giuseppe

    2011-01-01

    The study aims at evaluating health-generating function of humor therapy in a hospital ward hosting children suffering from respiratory pathologies. The main scope of this study is to investigate possible positive effects of the presence of a clown on both the clinical evolution of the on-going disease, and on some physiological and pain parameters. Forty-three children with respiratory pathologies participated in the study: 21 of them belonged to the experimental group (EG) and 22 children to the control group (CG). During their hospitalization, the children of the EG interacted with two clowns who were experienced in the field of pediatric intervention. All participants were evaluated with respect to clinical progress and to a series of physiological and pain measures both before and after the clown interaction. When compared with the CG, EG children showed an earlier disappearance of the pathological symptoms. Moreover, the interaction of the clown with the children led to a statistically significant lowering of diastolic blood pressure, respiratory frequency and temperature in the EG as compared with the control group. The other two parameters of systolic pressure and heart frequency yielded results in the same direction, without reaching statistical significance. A similar health-inducing effect of clown presence was observed on pain parameters, both by self evaluation and assessment by nurses. Taken together, our data indicate that the presence of clowns in the ward has a possible health-inducing effect. Thus, humor can be seen as an easy-to-use, inexpensive and natural therapeutic modality to be used within different therapeutic settings.

  20. Clowns Benefit Children Hospitalized for Respiratory Pathologies

    Directory of Open Access Journals (Sweden)

    Mario Bertini

    2011-01-01

    Full Text Available The study aims at evaluating health-generating function of humor therapy in a hospital ward hosting children suffering from respiratory pathologies. The main scope of this study is to investigate possible positive effects of the presence of a clown on both the clinical evolution of the on-going disease, and on some physiological and pain parameters. Forty-three children with respiratory pathologies participated in the study: 21 of them belonged to the experimental group (EG and 22 children to the control group (CG. During their hospitalization, the children of the EG interacted with two clowns who were experienced in the field of pediatric intervention. All participants were evaluated with respect to clinical progress and to a series of physiological and pain measures both before and after the clown interaction. When compared with the CG, EG children showed an earlier disappearance of the pathological symptoms. Moreover, the interaction of the clown with the children led to a statistically significant lowering of diastolic blood pressure, respiratory frequency and temperature in the EG as compared with the control group. The other two parameters of systolic pressure and heart frequency yielded results in the same direction, without reaching statistical significance. A similar health-inducing effect of clown presence was observed on pain parameters, both by self evaluation and assessment by nurses. Taken together, our data indicate that the presence of clowns in the ward has a possible health-inducing effect. Thus, humor can be seen as an easy-to-use, inexpensive and natural therapeutic modality to be used within different therapeutic settings.

  1. Pathological narcissism and the depressive temperament.

    Science.gov (United States)

    Tritt, Shona M; Ryder, Andrew G; Ring, Angela J; Pincus, Aaron L

    2010-05-01

    Although relations between depressive and narcissistic pathologies have been proposed in both psychoanalytic and phenomenological literatures, empirical research generally fails to confirm this link. Common measures of narcissism, however, emphasize grandiose rather than vulnerable traits, and include both adaptive and maladaptive features. We therefore assessed the relation between narcissistic personality and depressive temperament (DT) using a recently developed measure designed to assess a wide range of pathological narcissistic (PN) traits. We also examined the distinctiveness of the association between DT and PN controlling other temperaments. The Pathological Narcissism Inventory (PNI; Pincus et al., 2009), the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A; Akiskal et al., 2005), and a modified Schedule of Fatigue and Anergia (SOFA; Hadzi-Pavlovic et al., 2000), were administered to 228 university students. Principal component analyses yielded two components of PN: Component 1 items reflect narcissistic vulnerability-negative affect when narcissistic needs are not met; Component 2 items reflect narcissistic grandiosity-positive affect related to self-enhancement. Component 1 significantly predicted DT, an effect that remained after controlling for Component 2 and other temperaments in the TEMPS-A and SOFA. A similar effect was observed for the anxious temperament. Our study is limited by the use of a homogenous, non-clinical university student sample unscreened for clinical depression, and by reliance on self-report questionnaires. Contrary to past research, DT is associated with narcissistic disturbance, in particular with the avoidance of narcissistic injury, when the PNI is used. Clinical intervention targeting this avoidance might help patients with a DT develop self-esteem that is not overly dependant upon recognition from others. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  2. Pigmented villonodular synovitis: radiologic-pathologic correlation.

    Science.gov (United States)

    Murphey, Mark D; Rhee, John H; Lewis, Rachel B; Fanburg-Smith, Julie C; Flemming, Donald J; Walker, Eric A

    2008-01-01

    Pigmented villonodular synovitis (PVNS) represents an uncommon benign neoplastic process that may involve the synovium of the joint diffusely or focally (PVNS) or that may occur extraarticularly in a bursa (pigmented villonodular bursitis [PVNB]) or tendon sheath (pigmented villonodular tenosynovitis [PVNTS]). Pathologic specimens of the hypertrophic synovium may appear villous, nodular, or villonodular, and hemosiderin deposition, often prominent, is seen in most cases. The knee, followed by the hip, is the most common location for PVNS or PVNB, whereas PVNTS occurs most often in the hand and foot. PVNTS is also referred to as giant cell tumor of the tendon sheath (GCTTS). PVNTS is the most common form of this disease by a ratio of approximately 3:1. Radiographs reveal nonspecific features of a joint effusion in PVNS, a focal soft-tissue mass in PVNB or PVNTS, or a normal appearance. Extrinsic erosion of bone (on both sides of the joint) may also be seen and is most frequent with intraarticular involvement of the hip (>90% of cases). Cross-sectional imaging reveals diffuse involvement of the synovium (PVNS), an intimate relationship to the tendon (PVTNS), or a typical bursal location (PVNB), findings that suggest the diagnosis. However, the magnetic resonance (MR) imaging findings of prominent low signal intensity (seen with T2-weighting) and "blooming" artifact from the hemosiderin (seen with gradient-echo sequences) are nearly pathognomonic of this diagnosis. In addition, MR imaging is optimal for evaluating lesion extent. This information is crucial to guide treatment and to achieve complete surgical resection. Recurrence is more common with diffuse intraarticular disease and is difficult to distinguish, both pathologically and radiologically, from the rare complication of malignant PVNS. Recognizing the appearances of the various types of PVNS, which reflect their pathologic characteristics, improves radiologic assessment and is important for optimal patient

  3. Cognitive plasticity in normal and pathological aging

    Science.gov (United States)

    Fernández-Ballesteros, Rocío; Botella, Juan; Zamarrón, María Dolores; Molina, María Ángeles; Cabras, Emilia; Schettini, Rocío; Tárraga, Lluis

    2012-01-01

    The main goal of the present study is to examine to what extent age and cognitive impairment contribute to learning performance (cognitive plasticity, cognitive modifiability, or learning potential). To address this question, participants coming from four studies (Longitudinal Study of Active Aging, age range, 55–75 years, N = 458; Longitudinal Study in the very old [90+], age range, 90–102, N = 188, and Cognitive Plasticity within the Course of Cognitive Impairment, 97 “Normal”, 57 mild cognitive impairment [MCI], and 98 Alzheimer’s disease [AD] patients) were examined through a measure of verbal learning (developed from Rey). The results show that all age, MCI, and AD groups learned across the five learning trials of that test, but significant differences were found due to age, pathology, and education. The effects of pathology (MCI and AD) can be expressed in a metric of “years of normal decline by age”; specifically, being MCI means suffering an impairment in performance that is equivalent to the decline of a normal individual during 15 years, whereas the impact of AD is equivalent to 22.7 years. Likewise, the improvement associated with about 5 years of education is equivalent to about 1 year less of normal aging. Also, the two pathological groups significantly differed from “normal” groups in the delayed trial of the test. The most dramatic difference is that between the “normal” group and the AD patients, which shows relatively poorer performance for the AD group in the delayed trial than in the first learning trial. The potential role of this unique effect for quick detection purposes of AD is assessed (in the 75–89 years age range, sensitivity and specificity equal 0.813 and 0.917, respectively). PMID:22291469

  4. Impaired self-awareness in pathological gamblers.

    Science.gov (United States)

    Brevers, Damien; Cleeremans, Axel; Bechara, Antoine; Greisen, Max; Kornreich, Charles; Verbanck, Paul; Noël, Xavier

    2013-03-01

    Lack of self-awareness of one's decisions remains an understudied and elusive topic in the addiction literature. The present study aimed at taking a first step towards addressing this difficult subject through the use of a combination of behavioral procedures. Here, we explored the association between a metacognitive process (the ability to reflect and evaluate the awareness of one's own decision) and poor performance on the Iowa Gambling Task (IGT) in a group of pathological gamblers (PG; n = 30), and in a comparison group (n = 35). This metacognitive process was assessed during the IGT with the post-decision wagering procedure, while a number of potential confounds (i.e., reward/loss sensitivity, dual-tasking) were controlled for. Results showed that: (1) Initial performance enhancement of the control group on IGT occurred without explicit knowledge of the task, thus confirming its implicit character; (2) compared to controls, performance of PG on the IGT failed to increase during the task; (3) taking into account increased reward sensitivity and decreased loss sensitivity as well as poorer dual-tasking in pathological gamblers, PG tended to exhibit a bias in evaluating their own performance on the IGT by maximizing their wagers independently of selecting advantageous decks. Our findings suggest that biased metacognition may affect pathological gamblers, leading to disadvantageous post-decision wagering, which is in turn linked to impaired decision making under ambiguity. Perhaps this deficit reflects the impaired insight and self-awareness that many addicts suffer from, thus providing a novel approach for capturing and measuring this impairment, and for investigating its possible causes.

  5. Cognitive plasticity in normal and pathological aging.

    Science.gov (United States)

    Fernández-Ballesteros, Rocío; Botella, Juan; Zamarrón, María Dolores; Molina, María Ángeles; Cabras, Emilia; Schettini, Rocío; Tárraga, Lluis

    2012-01-01

    The main goal of the present study is to examine to what extent age and cognitive impairment contribute to learning performance (cognitive plasticity, cognitive modifiability, or learning potential). To address this question, participants coming from four studies (Longitudinal Study of Active Aging, age range, 55-75 years, N = 458; Longitudinal Study in the very old [90+], age range, 90-102, N = 188, and Cognitive Plasticity within the Course of Cognitive Impairment, 97 "Normal", 57 mild cognitive impairment [MCI], and 98 Alzheimer's disease [AD] patients) were examined through a measure of verbal learning (developed from Rey). The results show that all age, MCI, and AD groups learned across the five learning trials of that test, but significant differences were found due to age, pathology, and education. The effects of pathology (MCI and AD) can be expressed in a metric of "years of normal decline by age"; specifically, being MCI means suffering an impairment in performance that is equivalent to the decline of a normal individual during 15 years, whereas the impact of AD is equivalent to 22.7 years. Likewise, the improvement associated with about 5 years of education is equivalent to about 1 year less of normal aging. Also, the two pathological groups significantly differed from "normal" groups in the delayed trial of the test. The most dramatic difference is that between the "normal" group and the AD patients, which shows relatively poorer performance for the AD group in the delayed trial than in the first learning trial. The potential role of this unique effect for quick detection purposes of AD is assessed (in the 75-89 years age range, sensitivity and specificity equal 0.813 and 0.917, respectively).

  6. Evolution of occlusal pathology. A literature review.

    Directory of Open Access Journals (Sweden)

    Camilo Guerrero

    2013-08-01

    Full Text Available Introduction: Many of the guidelines on occlusion and treatment alternatives in dentate and partially edentulous patients, are based on concepts raised in the beginning of dentistry. The diversity of the occlusion schools has become some of these concepts complex to understand and apply. This diversity makes difficult the compression of the occlusal physiology and its disorders, hindering the understanding of the occlusal pathology and its proper diagnosis and management. Objective: This is why we conducted a literature review about oclusal physiology and pathology, in order to gather information based on scientific evidence, which in order to clarify concepts and homogenize knowledge about physiological and morphological changesof thestomatognathic system, associated toocclusal alterations, allowing the future standardization of the occlusal diagnostic process at the Faculty of Dentistry of the National University of Colombia. Methodology: A search was conducted inMedLine, PubMed, Ovid, Ebsco, ScienceDirect and Hinari-Healthinternetwork using the Mesh terms: "Dental Occlusion" - "Stomatognathic System" - "masticatory System" - Temporomandibular Joint and the bibliographies of papers and review articles that had direct relationship to the topic; the publication deadline was not taken into account. In total, 79 articles, 10 texts and 7 websites were obtained. Conclusion: Occlusal pathology is an evolutionary process that might affect the form and/or function of any of the components of the stomatognathic system. Occlusal Harmony is a state in which each part of the system works in concert with the others to fulfill the functions of mastication, speech and swallowing; oral rehabilitation should be directed toward obtaining a harmonious occlusion.

  7. 42 CFR 493.1220 - Condition: Oral pathology.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Oral pathology. 493.1220 Section 493....1220 Condition: Oral pathology. If the laboratory provides services in the subspecialty of Oral pathology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§...

  8. The Effects of Pathological Gaming on Aggressive Behavior

    Science.gov (United States)

    Lemmens, Jeroen S.; Valkenburg, Patti M.; Peter, Jochen

    2011-01-01

    Studies have shown that pathological involvement with computer or video games is related to excessive gaming binges and aggressive behavior. Our aims for this study were to longitudinally examine if pathological gaming leads to increasingly excessive gaming habits, and how pathological gaming may cause an increase in physical aggression. For this…

  9. Manpower in pathology 1969-1975.

    Science.gov (United States)

    Greenbury, C L

    1971-09-01

    An attempt has been made to assess for the period 1969-1975 the demand for consultant pathologists and the adequacy of the trainee cadre to fulfil this demand. In addition new data have been acquired on the way in which pathologists apportion their time between specialties and the availability of specialist opinion and other derived information. The demand for consultants in all specialties, with the exception of morbid anatomy, is likely to exceed the supply. The shortfall is greatest in medical microbiology and chemical pathology, but may be felt equally in haematology in the short term.

  10. Patología puerperal Puerperal pathology

    Directory of Open Access Journals (Sweden)

    B. Bezares

    2009-01-01

    Full Text Available El puerperio es el periodo desde el final del parto hasta la aparición de la primera menstruación. Las posibles patologías acontecidas en este tiempo son la causa más frecuente de mortalidad materna incluso en nuestro medio. La patología de la lactancia incluye el fallo de lactancia, grietas en el pezón, ingurgitación mamaria y mastitis puerperal. La infección puerperal es una complicación obstétrica frecuente aunque las pautas de profilaxis han disminuido mucho la incidencia de esta patología. La patología vascular del puerperio incluye cuadros de gravedad importante, representando una de las principales causas de mortalidad materna. Se incluye la trombosis venosa profunda y el tromboembolismo pulmonar como la complicación más grave de la primera. No parece que la patología psiquiátrica sea más frecuente en el puerperio que en otra época de la vida, pero sí que se describen los cuadros relacionados con este periodo, como son el «blues», la depresión puerperal y la psicosis puerperal. Por último, otros cuadros poco frecuentes, pero que pueden constituir una emergencia médica en el puerperio son el síndrome de Sheehan, la miocardiopatía periparto y la tiroiditis postparto.The puerperium is the period from the end of labour to the appearance of the first menstruation. The possible pathologies that can occur in this period of time are the most frequent cause of maternal mortality even in our setting. The pathology of lactation includes failure of breastfeeding, cracks in the nipple, mammary ingurgitation and puerperal mastitis. Puerperal infection is a frequent obstetric complication although clinical guidelines for prophylaxis have considerably reduced its incidence. The vascular pathology of the puerperium includes clinical features of great seriousness, representing one of the main causes of maternal mortality. These include deep vein thrombosis, of which pulmonary thromboembolism is the most serious complication. It

  11. Dopamine agonist: pathological gambling and hypersexuality.

    Science.gov (United States)

    2008-10-01

    (1) Pathological gambling and increased sexual activity can occur in patients taking dopaminergic drugs. Detailed case reports and small case series mention serious familial and social consequences. The frequency is poorly documented; (2) Most affected patients are being treated for Parkinson's disease, but cases have been reported among patients prescribed a dopamine agonist for restless legs syndrome or pituitary adenoma; (3) Patients treated with this type of drug, and their relatives, should be informed of these risks so that they can watch for changes in behaviour. If such disorders occur, it may be necessary to reduce the dose or to withdraw the drug or replace it with another medication.

  12. Clinico- Pathological Study Of Ichthyosis Vulgaris

    Directory of Open Access Journals (Sweden)

    Nandy Utpal

    1997-01-01

    Full Text Available A clinico- pathological study of 28 cases of ichthyosis vulgaris appeared with in the age of 5 years. The presence of the disease since birth was also found. While most (24 patients showed a diminution of severity in summer with an aggravation during winter, 4 patients followed the opposite seasonal pattern. Only in 4 patients, fine scales in the scalp were detected. One patient showed an affection of flexures. There was also a low occurrence of palmo- planter hyperkeratosis, follicular keratosis, fissuring of hands and feet and atopy.

  13. CT colonography: methods, pathology and pitfalls

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, S.A.; Halligan, S.; Bartram, C.I

    2003-03-01

    Computed tomography colonography (CTC) is a relatively new technique that is currently challenging more established methods of large bowel imaging. Several workers have suggested CTC surpasses the barium enema and approaches conventional endoscopy for detection of colorectal neoplasia. Accurate diagnosis relies on technically good studies, the main aim of which is adequate bowel cleansing and distension. Furthermore, the learning curve is steep and normal colonic anatomy has to be re-learned in a CT context. This review aims to describe the technique, revise the imaging features of both normal and pathological colon, and to highlight potential diagnostic pitfalls and their avoidance.

  14. Noninflammatory fallopian tube pathology in children

    Energy Technology Data Exchange (ETDEWEB)

    Merlini, Laura; Anooshiravani, Mehrak; Hanquinet, Sylviane [University Hospital HUG, Unit of Pediatric Radiology, Geneva (Switzerland); Vunda, Aaron [University Hospital, Clinic of Pediatric Surgery, Geneva (Switzerland); Borzani, Irene; Napolitano, Marcello [Ospedale Buzzi, Pediatric Radiology, Milan (Italy)

    2008-12-15

    Noninflammatory tubal abnormalities are rare in children and usually not well covered by traditional educational material. The presenting symptoms are nonspecific and are common to many other conditions, so its preoperative diagnosis is rarely made. The purpose of this study was to review the hospital charts and imaging findings in children and sexually inactive adolescents who showed fallopian tube pathology. Understanding of the pertinent findings of previous imaging examinations might assist radiologists in making the correct preoperative diagnosis and increase the likelihood of preserving the fallopian tubes. The clinical entities described in this article include isolated tubal torsion, paratubal cysts, hydrosalpinx, undescended/ectopic fallopian tube, and tubal inguinal hernia. (orig.)

  15. Lumbar vertebral pedicles: radiologic anatomy and pathology

    Energy Technology Data Exchange (ETDEWEB)

    Patel, N.P.; Kumar, R.; Kinkhabwala, M.; Wengrover, S.I.

    1988-01-01

    With the advancement of high-resolution computed tomography (CT) scanning the spine has added new knowledge to the various conditions affecting the pedicles. We wish to review the entire spectrum of pedicular lesions: the embryology, normal anatomy, normal variants, pitfalls, congenital anomalies, and pathological conditions are discussed. Different imaging modalities involving CT, isotope bone scanning, and Magnetic Resonance Imaging (MRI) are used to complement plain films of the lumbar spine. This subject review is an excellent source for future reference to lumbar pedicular lesions. 27 references.

  16. Hydatidiform mole clinical and pathological characteristics

    OpenAIRE

    Pacheco D., José; Instituto de Patología, UNMSM; Instituto de Medicina Legal; Alegre, Jaime; Hospital Nacional Dos de Mayo, Lima, Perú; Paniagua, Gissela; Instituto de Patología de la UNMSM

    2013-01-01

    Objective: To determine clinical and pathological findings in hydatidiform mole. Design: Descriptive retrospective study. Material and methods: All cases de molar pregnancy attended at Dos de Mayo National Hospital (HNDM) between 1998 and 2001 were reviewed. Results: Twenty-four cases of hydatidiform mole were attended; mean age was 26,4 years ± 6,4 and gestational age 13,1 weeks ± 3,3. Past history only showed 1 and 3 cases of hyperemesis gravidarum and previous abortions, respectively; 18 p...

  17. Ureteritis Cystica: A Radiologic Pathologic Correlation

    Directory of Open Access Journals (Sweden)

    Jennifer G Rothschild

    2011-01-01

    Full Text Available Ureteritis cystica (UC is a benign condition that commonly affects the ureter and can mimic other conditions such as transitional cell carcinoma, blood clots, air bubbles, radiolucent stones, fibroepithelial polyps, and sloughed renal papillae. Radiographically, UC is characterized by multiple small, round, lucent defects, which cause scalloping of the ureteral margins when seen in profile. The scalloping is produced by the projection of the submucosal cysts into the lumen and represents an important differential feature of this disease. We present a case of UC with a radiological pathological correlation.

  18. The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide.

    Directory of Open Access Journals (Sweden)

    Stephanie J Soscia

    Full Text Available BACKGROUND: The amyloid beta-protein (Abeta is believed to be the key mediator of Alzheimer's disease (AD pathology. Abeta is most often characterized as an incidental catabolic byproduct that lacks a normal physiological role. However, Abeta has been shown to be a specific ligand for a number of different receptors and other molecules, transported by complex trafficking pathways, modulated in response to a variety of environmental stressors, and able to induce pro-inflammatory activities. METHODOLOGY/PRINCIPAL FINDINGS: Here, we provide data supporting an in vivo function for Abeta as an antimicrobial peptide (AMP. Experiments used established in vitro assays to compare antimicrobial activities of Abeta and LL-37, an archetypical human AMP. Findings reveal that Abeta exerts antimicrobial activity against eight common and clinically relevant microorganisms with a potency equivalent to, and in some cases greater than, LL-37. Furthermore, we show that AD whole brain homogenates have significantly higher antimicrobial activity than aged matched non-AD samples and that AMP action correlates with tissue Abeta levels. Consistent with Abeta-mediated activity, the increased antimicrobial action was ablated by immunodepletion of AD brain homogenates with anti-Abeta antibodies. CONCLUSIONS/SIGNIFICANCE: Our findings suggest Abeta is a hitherto unrecognized AMP that may normally function in the innate immune system. This finding stands in stark contrast to current models of Abeta-mediated pathology and has important implications for ongoing and future AD treatment strategies.

  19. Use of contextual inquiry to understand anatomic pathology workflow: Implications for digital pathology adoption

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    Jonhan Ho

    2012-01-01

    Full Text Available Background: For decades anatomic pathology (AP workflow have been a highly manual process based on the use of an optical microscope and glass slides. Recent innovations in scanning and digitizing of entire glass slides are accelerating a move toward widespread adoption and implementation of a workflow based on digital slides and their supporting information management software. To support the design of digital pathology systems and ensure their adoption into pathology practice, the needs of the main users within the AP workflow, the pathologists, should be identified. Contextual inquiry is a qualitative, user-centered, social method designed to identify and understand users′ needs and is utilized for collecting, interpreting, and aggregating in-detail aspects of work. Objective: Contextual inquiry was utilized to document current AP workflow, identify processes that may benefit from the introduction of digital pathology systems, and establish design requirements for digital pathology systems that will meet pathologists′ needs. Materials and Methods: Pathologists were observed and interviewed at a large academic medical center according to contextual inquiry guidelines established by Holtzblatt et al. 1998. Notes representing user-provided data were documented during observation sessions. An affinity diagram, a hierarchal organization of the notes based on common themes in the data, was created. Five graphical models were developed to help visualize the data including sequence, flow, artifact, physical, and cultural models. Results: A total of six pathologists were observed by a team of two researchers. A total of 254 affinity notes were documented and organized using a system based on topical hierarchy, including 75 third-level, 24 second-level, and five main-level categories, including technology, communication, synthesis/preparation, organization, and workflow. Current AP workflow was labor intensive and lacked scalability. A large number

  20. Is Abeta a sufficient Biomarker for monitoring anti-Abeta clinical studies? A critical review.

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    Jens eMoreth

    2013-07-01

    Full Text Available Amyloid-beta (Aβ in Alzheimer’s disease (AD appeared to be a promising target for disease-modifying therapeutic strategies like passive immunotherapy with anti-Aβ monoclonal antibodies (mAbs. Biochemical markers in cerebrospinal fluid (CSF include alterations of Aβ that allow the diagnosis of AD. Biomarker strategies, such as the levels of Aβ in CSF and plasma, currently play an important role in early clinical trials for AD. Indeed, these strategies have a relevant impact on the outcome of such studies, since the biomarkers are used to monitor the bioactivity of anti-Aβ mAbs. The clinical trials of Solanezumab were mainly based on the readout of Aβ levels in CSF and plasma, whereas those of Bapineuzumab were based on cognition; however, little is known about the mechanisms altering these biomarker levels, and no biomarker has yet been proven to be a successful predictor for AD therapy. In addition, the Aβ biomarkers allow for the determination of free and bound anti-Aβ mAb in order to monitor the available amount of bioactive drug and could give hints to the mechanism of action. In this review, we discuss clinical Aβ biomarker data and the latest regulatory strategies.

  1. Protection by neuroglobin expression in brain pathologies

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    Eliana Baez

    2016-09-01

    Full Text Available Astrocytes play an important role in physiological, metabolic and structural functions and, when impaired, they can be involved in various pathologies including Alzheimer, focal ischemic stroke and traumatic brain injury. These disorders involve an imbalance in the blood flow and nutrients such as glucose and lactacte, leading to biochemical and molecular changes that cause neuronal damage, which is followed by loss of cognitive and motor functions. Previous studies have shown that astrocytes are more resilient than neurons during brain insults as a consequence of their more effective antioxidant systems, transporters and enzymes, which made them less susceptible to excitotoxicity. In addition, astrocytes synthesize and release different protective molecules for neurons, including neuroglobin, a member of the globin family of proteins. After brain injury neuroglobin expression is induced in astrocytes. Since neuroglobin promotes neuronal survival, its increased expression in astrocytes after brain injury may represent an endogenous neuroprotective mechanism. Here, we review the role of neuroglobin in the CNS, its relationship with different pathologies, and the role of different factors that regulate its expression in astrocytes.

  2. Update on pathology of ocular parasitic disease

    Science.gov (United States)

    Das, Dipankar; Ramachandra, Varsha; Islam, Saidul; Bhattacharjee, Harsha; Biswas, Jyotirmay; Koul, Akanksha; Deka, Panna; Deka, Apurba

    2016-01-01

    Parasites are a group of eukaryotic organisms that may be free-living or form a symbiotic or parasitic relationship with the hosts. Consisting of over 800,000 recognized species, parasites may be unicellular (Protozoa) or multicellular (helminths and arthropods). The association of parasites with human population started long before the emergence of civilization. Parasitic zoonotic diseases are prevalent worldwide including India. Appropriate epidemiological data are lacking on existing zoonotic parasitic diseases, and newer diseases are emerging in our scenario. Systemic diseases such as cysticercosis, paragonimiasis, hydatidosis, and toxoplasmosis are fairly common. Acquired Toxoplasma infections are rising in immune-deficient individuals. Amongst the ocular parasitic diseases, various protozoas such as Cystoidea, trematodes, tissue flagellates, sporozoas etc. affect humans in general and eyes in particular, in different parts of the world. These zoonoses seem to be a real health related problem globally. Recent intensification of research throughout the world has led to specialization in biological fields, creating a conducive situation for researchers interested in this subject. The basics of parasitology lie in morphology, pathology, and with recent updates in molecular parasitology, the scope has extended further. The current review is to address the recent update in ophthalmic parasites with special reference to pathology and give a glimpse of further research in this field. PMID:27958200

  3. Virtual slides: application in pulmonary pathology consultations.

    Directory of Open Access Journals (Sweden)

    Michał Wojciechowski

    2008-02-01

    Full Text Available The Virtual Slide (VS is an interactive microscope emulator that presents a complete digitized tissue section via the Internet. A successful implementation of VS has been observed for educational, research venues and quality control. VS acquisition for consultative pathology is not so common. The purpose of this study was to explore the efficacy and usability of VS in the consultative pulmonary telepathology. 20 lung tumors entered the study. The performance was programmed for 2 medical centers specialized in pulmonary pathology (beginner and advancer in telepathology. A high-quality VSs were prepared by Coolscope (Nikon, Eclipsnet VSL, Japan, and were evaluated via the Internet. The cases were reviewed for the second time with conventional light microscope. VS diagnostic accuracy and the interobserver variability were evaluated. Also the time taken by examiners to render the diagnoses and time needed to scan the microscopic slide were analyzed. Percentage concordance between original glass-slides diagnosis and diagnosis for VSs was very high. Pathologists found the download speed of VSs adequate; experience in telepathology reduced the time of VS diagnosis. VS implementation suggests advantages for teleconsulation and education but also indicate some technical limitations. This is the first Polish trial of VS implementation in telepathology consultative service.

  4. Update on pathology of ocular parasitic disease

    Directory of Open Access Journals (Sweden)

    Dipankar Das

    2016-01-01

    Full Text Available Parasites are a group of eukaryotic organisms that may be free-living or form a symbiotic or parasitic relationship with the hosts. Consisting of over 800,000 recognized species, parasites may be unicellular (Protozoa or multicellular (helminths and arthropods. The association of parasites with human population started long before the emergence of civilization. Parasitic zoonotic diseases are prevalent worldwide including India. Appropriate epidemiological data are lacking on existing zoonotic parasitic diseases, and newer diseases are emerging in our scenario. Systemic diseases such as cysticercosis, paragonimiasis, hydatidosis, and toxoplasmosis are fairly common. Acquired Toxoplasma infections are rising in immune-deficient individuals. Amongst the ocular parasitic diseases, various protozoas such as Cystoidea, trematodes, tissue flagellates, sporozoas etc. affect humans in general and eyes in particular, in different parts of the world. These zoonoses seem to be a real health related problem globally. Recent intensification of research throughout the world has led to specialization in biological fields, creating a conducive situation for researchers interested in this subject. The basics of parasitology lie in morphology, pathology, and with recent updates in molecular parasitology, the scope has extended further. The current review is to address the recent update in ophthalmic parasites with special reference to pathology and give a glimpse of further research in this field.

  5. Genetics and underlying pathology of dementia.

    Science.gov (United States)

    Ferencz, Beata; Gerritsen, Lotte

    2015-03-01

    As the population steadily ages, dementia, in all its forms, remains a great societal challenge. Yet, our knowledge of their etiology remains rather limited. To this end, genetic studies can give us insight into the underlying mechanisms that lead to the development of dementia, potentially facilitating treatments in the future. In this review we cover the most recent genetic risk factors associated with the onset of the four most common dementia types today, including Alzheimer's disease (AD), Vascular Dementia (VaD), Frontotemporal Lobar Degeneration (FTLD) and Lewy Body Dementia (LBD). Moreover, we discuss the overlap in major underlying pathologies of dementia derived from their genetic associations. While all four dementia types appear to involve genes associated with tau-pathology and neuroinflammation only LBD, AD and VaD appear to involve amyloid genes while LBD and FTLD share alpha synuclein genes. Together these findings suggest that some of the dementias may exist along a spectrum and demonstrates the necessity to conduct large-scale studies pinpointing the etiology of the dementias and potential gene and environment interactions that may influence their development.

  6. Protection by Neuroglobin Expression in Brain Pathologies.

    Science.gov (United States)

    Baez, Eliana; Echeverria, Valentina; Cabezas, Ricardo; Ávila-Rodriguez, Marco; Garcia-Segura, Luis Miguel; Barreto, George E

    2016-01-01

    Astrocytes play an important role in physiological, metabolic, and structural functions, and when impaired, they can be involved in various pathologies including Alzheimer, focal ischemic stroke, and traumatic brain injury. These disorders involve an imbalance in the blood flow and nutrients such as glucose and lactate, leading to biochemical and molecular changes that cause neuronal damage, which is followed by loss of cognitive and motor functions. Previous studies have shown that astrocytes are more resilient than neurons during brain insults as a consequence of their more effective antioxidant systems, transporters, and enzymes, which made them less susceptible to excitotoxicity. In addition, astrocytes synthesize and release different protective molecules for neurons, including neuroglobin, a member of the globin family of proteins. After brain injury, neuroglobin expression is induced in astrocytes. Since neuroglobin promotes neuronal survival, its increased expression in astrocytes after brain injury may represent an endogenous neuroprotective mechanism. Here, we review the role of neuroglobin in the central nervous system, its relationship with different pathologies, and the role of different factors that regulate its expression in astrocytes.

  7. Subperiosteal osteoid osteoma: radiographic and pathologic manifestations

    Energy Technology Data Exchange (ETDEWEB)

    Shankman, S. [Department of Radiology, Hospital for Joint Diseases/OI, 301 East 17th Street, New York, NY 10003 (United States); Desai, P. [Department of Pathology, Hospital for Joint Diseases/OI, 301 East 17th Street, New York, NY 10003 (United States); Beltran, J. [Department of Radiology, Hospital for Joint Diseases/OI, 301 East 17th Street, New York, NY 10003 (United States)

    1997-08-01

    Objective.To demonstrate the radiologic and pathologic manifestations of osteoid osteoma arising beneath the periosteum, on the surface of the bone. Design. One hundred and sixty osteoid osteomas were seen over a 30-year period. The radiologic, pathologic and operative findings of those that were subperiosteal were reviewed. Patients. Eleven patients with subperiosteal osteoid osteoma were reviewed. The patients ranged in age from 13 to 36 years with a mean of 24 years. Eight were male and three were female. Results and conclusion. Eleven subperiosteal lesions were studied. The reactive periostitis of four lesions was atypical and misleading. Four lesions had features similar to the more common intracortical variety. Three lesions occurring within the joint like other intra-articular lesions were barely seen on plain radiographs. Bone scan and CT scan were virtually diagnostic. The histopathology of these lesions was also atypical though not misleading. In conclusion, subperiosteal osteoid osteoma is a rare lesion with atypical radiographic and histopathologic features. The unusual reactive periostitis seen in several extra-articular cases may suggest other diagnoses. (orig.). With 4 figs., 2 tabs.

  8. Adjacent Segment Pathology after Anterior Cervical Fusion.

    Science.gov (United States)

    Chung, Jae Yoon; Park, Jong-Beom; Seo, Hyoung-Yeon; Kim, Sung Kyu

    2016-06-01

    Anterior cervical fusion has become a standard of care for numerous pathologic conditions of the cervical spine. However, subsequent development of clinically significant disc disease at levels adjacent to fused discs is a serious long-term complication of this procedure. As more patients live longer after surgery, it is foreseeable that adjacent segment pathology (ASP) will develop in increasing numbers of patients. Also, ASP has been studied more intensively with the recent popularity of motion preservation technologies like total disc arthroplasty. The true nature and scope of ASP remains poorly understood. The etiology of ASP is most likely multifactorial. Various factors including altered biomechanical stresses, surgical disruption of soft tissue and the natural history of cervical disc disease contribute to the development of ASP. General factors associated with disc degeneration including gender, age, smoking and sports may play a role in the development of ASP. Postoperative sagittal alignment and type of surgery are also considered potential causes of ASP. Therefore, a spine surgeon must be particularly careful to avoid unnecessary disruption of the musculoligamentous structures, reduced risk of direct injury to the disc during dissection and maintain a safe margin between the plate edge and adjacent vertebrae during anterior cervical fusion.

  9. Human prefrontal cortex: evolution, development, and pathology.

    Science.gov (United States)

    Teffer, Kate; Semendeferi, Katerina

    2012-01-01

    The prefrontal cortex is critical to many cognitive abilities that are considered particularly human, and forms a large part of a neural system crucial for normal socio-emotional and executive functioning in humans and other primates. In this chapter, we survey the literature regarding prefrontal development and pathology in humans as well as comparative studies of the region in humans and closely related primate species. The prefrontal cortex matures later in development than more caudal regions, and some of its neuronal subpopulations exhibit more complex dendritic arborizations. Comparative work suggests that the human prefrontal cortex differs from that of closely related primate species less in relative size than it does in organization. Specific reorganizational events in neural circuitry may have taken place either as a consequence of adjusting to increases in size or as adaptive responses to specific selection pressures. Living in complex environments has been recognized as a considerable factor in the evolution of primate cognition. Normal frontal lobe development and function are also compromised in several neurological and psychiatric disorders. A phylogenetically recent reorganization of frontal cortical circuitry may have been critical to the emergence of human-specific executive and social-emotional functions, and developmental pathology in these same systems underlies many psychiatric and neurological disorders, including autism and schizophrenia.

  10. Evidence-based pathology: umbilical cord coiling.

    Science.gov (United States)

    Khong, T Y

    2010-12-01

    The generation of a pathology test result must be based on criteria that are proven to be acceptably reproducible and clinically relevant to be evidence-based. This review de-constructs the umbilical cord coiling index to illustrate how it can stray from being evidence-based. Publications related to umbilical cord coiling were retrieved and analysed with regard to how the umbilical coiling index was calculated, abnormal coiling was defined and reference ranges were constructed. Errors and other influences that can occur with the measurement of the length of the umbilical cord or of the number of coils can compromise the generation of the coiling index. Definitions of abnormal coiling are not consistent in the literature. Reference ranges defining hypocoiling or hypercoiling have not taken those potential errors or the possible effect of gestational age into account. Even the way numerical test results in anatomical pathology are generated, as illustrated by the umbilical coiling index, warrants a critical analysis into its evidence base to ensure that they are reproducible or free from errors.

  11. Virtual computed tomography cystoscopy in bladder pathologies

    Directory of Open Access Journals (Sweden)

    Halil Arslan

    2006-04-01

    Full Text Available OBJECTIVE: Assessed the usefulness of virtual cystoscopy performed with multidetector computed tomography (CT in patients with different urinary bladder pathologies compared to the conventional cystoscopy. MATERIALS AND METHODS: Eighteen patients with different bladder pathologies, which consisted of 11 tumors, 3 diverticula, 2 trabecular changes and 2 stones, were assessed with conventional cystoscopy and virtual CT cystoscopy. The results of virtual CT cystoscopy were compared with the findings of conventional cystoscopy. We determined the detection rate and positive predictive value of CT imaging based virtual cystoscopy in the diagnosis of urinary bladder lesions. RESULTS: CT scanning was well tolerated by all patients, and no complications occurred. Images in 16 (88% of the 18 virtual cystoscopic examinations were either of excellent or good quality. All tumors except one, 2 trabecular changes and 2 stones were characterized with similar findings in the both of methods. The masses ranged from 0.4 to 7.0 cm in diameter. While conventional cystoscopy could not evaluate interior part of the diverticulum, virtual CT cystoscopy could demonstrate clearly within it. There were no false-positive findings in our series. CONCLUSION: Virtual CT cystoscopy is a promising technique to be used in the detection of bladder lesions. It should be considered especially at the evaluation of bladder diverticula. In the future, it may be possible or even advantageous to incorporate into the imaging algorithm for evaluation of bladder lesion.

  12. Virtual computed tomography cystoscopy in bladder pathologies

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    Arslan, Halil; Ceylan, Kadir; Harman, Mustafa; Yilmaz, Yuksel; Temizoz, Osman; Can, Saban [Yuzuncu Yil University School of Medicine, Van (Turkey). Dept. of Radiology and Urology]. E-mail: drhalilarslan@hotmail.com

    2006-03-15

    Objective: assessed the usefulness of virtual cystoscopy performed with multidetector computed tomography (CT) in patients with different urinary bladder pathologies compared to the conventional cystoscopy.Materials and methods: eighteen patients with different bladder pathologies, which consisted of 11 tumors, 3 diverticula, 2 trabecular changes and 2 stones, were assessed with conventional cystoscopy and virtual CT cystoscopy. The results of virtual CT cystoscopy were compared with the findings of conventional cystoscopy. We determined the detection rate and positive predictive value of CT imaging based virtual cystoscopy in the diagnosis of urinary bladder lesions. Results: CT scanning was well tolerated by all patients, and no complications occurred. Images in 16 (88%) of the 18 virtual cystoscopic examinations were either of excellent or good quality. All tumors except one, 2 trabecular changes and 2 stones were characterized with similar findings in the both of methods. The masses ranged from 0.4 to 7.0 cm in diameter. While conventional cystoscopy could not evaluate interior part of the diverticulum, virtual CT cystoscopy could demonstrate clearly within it. There were no false-positive findings in our series. Conclusion: virtual CT cystoscopy is a promising technique to be used in the detection of bladder lesions. It should be considered especially at the evaluation of bladder diverticula. In the future, it may be possible or even advantageous to incorporate into the imaging algorithm for evaluation of bladder lesion. (author)

  13. Digital pathology in personalized cancer therapy

    Directory of Open Access Journals (Sweden)

    Marcial Garcia Rojo

    2012-01-01

    Full Text Available The development of small molecule inhibitors of growth factor receptors, and the discovery of somatic mutations of the thyrosine kinase domain, have resulted in new paradigms for cancer therapy. Digital microscopy is an important tool for surgical pathologists. The achievements in the digital pathology field have modified the workflow of pathomorphology labs, enhanced the pathologist’s role in diagnostics, and increased their contribution to personalized targeted medicine. Digital image analysis is now available in a variety of platforms to improve quantification performance of diagnostic pathology. We here describe the state of digital microscopy as it applies to the field of quantitative immunohistochemistry of biomarkers related to the clinical personalized targeted therapy of breast cancer, non-small lung cancer and colorectal cancer: HER-2, EGFR, KRAS and BRAF genes. The information is derived from the experience of the authors and a review of the literature. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 4, pp. 570–578

  14. The preanalytic phase in veterinary clinical pathology.

    Science.gov (United States)

    Braun, Jean-Pierre; Bourgès-Abella, Nathalie; Geffré, Anne; Concordet, Didier; Trumel, Cathy

    2015-03-01

    This article presents the general causes of preanalytic variability with a few examples showing specialists and practitioners that special and improved care should be given to this too often neglected phase. The preanalytic phase of clinical pathology includes all the steps from specimen collection to analysis. It is the phase where most laboratory errors occur in human, and probably also in veterinary clinical pathology. Numerous causes may affect the validity of the results, including technical factors, such as the choice of anticoagulant, the blood vessel sampled, and the duration and conditions of specimen handling. While the latter factors can be defined, influence of biologic and physiologic factors such as feeding and fasting, stress, and biologic and endocrine rhythms can often not be controlled. Nevertheless, as many factors as possible should at least be documented. The importance of the preanalytic phase is often not given the necessary attention, although the validity of the results and consequent clinical decision making and medical management of animal patients would likely be improved if the quality of specimens submitted to the laboratory was optimized.

  15. Protection by Neuroglobin Expression in Brain Pathologies

    Science.gov (United States)

    Baez, Eliana; Echeverria, Valentina; Cabezas, Ricardo; Ávila-Rodriguez, Marco; Garcia-Segura, Luis Miguel; Barreto, George E.

    2016-01-01

    Astrocytes play an important role in physiological, metabolic, and structural functions, and when impaired, they can be involved in various pathologies including Alzheimer, focal ischemic stroke, and traumatic brain injury. These disorders involve an imbalance in the blood flow and nutrients such as glucose and lactate, leading to biochemical and molecular changes that cause neuronal damage, which is followed by loss of cognitive and motor functions. Previous studies have shown that astrocytes are more resilient than neurons during brain insults as a consequence of their more effective antioxidant systems, transporters, and enzymes, which made them less susceptible to excitotoxicity. In addition, astrocytes synthesize and release different protective molecules for neurons, including neuroglobin, a member of the globin family of proteins. After brain injury, neuroglobin expression is induced in astrocytes. Since neuroglobin promotes neuronal survival, its increased expression in astrocytes after brain injury may represent an endogenous neuroprotective mechanism. Here, we review the role of neuroglobin in the central nervous system, its relationship with different pathologies, and the role of different factors that regulate its expression in astrocytes. PMID:27672379

  16. Multidetector CT of emergent biliary pathologic conditions.

    Science.gov (United States)

    Patel, Neel B; Oto, Aytekin; Thomas, Stephen

    2013-01-01

    Various biliary pathologic conditions can lead to acute abdominal pain. Specific diagnosis is not always possible clinically because many biliary diseases have overlapping signs and symptoms. Imaging can help narrow the differential diagnosis and lead to a specific diagnosis. Although ultrasonography (US) is the most useful imaging modality for initial evaluation of the biliary system, multidetector computed tomography (CT) is helpful when US findings are equivocal or when biliary disease is suspected. Diagnostic accuracy can be increased by optimizing the CT protocol and using multiplanar reformations to localize biliary obstruction. CT can be used to diagnose and stage acute cholecystitis, including complications such as emphysematous, gangrenous, and hemorrhagic cholecystitis; gallbladder perforation; gallstone pancreatitis; gallstone ileus; and Mirizzi syndrome. CT also can be used to evaluate acute biliary diseases such as biliary stone disease, benign and malignant biliary obstruction, acute cholangitis, pyogenic hepatic abscess, hemobilia, and biliary necrosis and iatrogenic complications such as biliary leaks and malfunctioning biliary drains and stents. Treatment includes radiologic, endoscopic, or surgical intervention. Familiarity with CT imaging appearances of emergent biliary pathologic conditions is important for prompt diagnosis and appropriate clinical referral and treatment.

  17. CLINICAL PATHOLOGICAL FEATURE OF EARLY TONGUE AMYLOIDOSIS

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To investigate the clinical pathological feature and diagnostic criteria of tongue amyloidosis (AL).Methods During 1992 to 2005, 25 patients pathologically diagnosed as tongue AL in our hospital were reviewed retrospectively, and all of them had no enlarged tongue. Haematoxylin and eosin (HE) and immunohistochemical staining were used to detect the amyloid deposition on the tongue.Results Totally 84 % (21/25) patients had symptoms of xerostomia and taste-blindness, 44 % (11/25) patients complained of activity limitation of tongue. Macroscopic observation showed mucosa pallescence, punctuate hemorrhage, red grain particles, and ulcers on the tongue. HE staining indicated amyloid depositions in basement membrane,muscle cell, vessel wall, and nerve fiber. Immunohistochemical study demonstrated kappa light-chain deposition in 64%(16/25) cases, and lambda light-chain deposition in 36 % (9/25) cases. They presented in vessel wall, nerve fiber, and muscle cells.Conclusion The biopsy is an important means for the diagnosis of early tongue AL, and the wide variety of amyloid light chain is helpful to differential diagnosis.

  18. Is pathological gambling moderated by age?

    Science.gov (United States)

    Granero, Roser; Penelo, Eva; Stinchfield, Randy; Fernandez-Aranda, Fernando; Savvidou, Lamprini G; Fröberg, Frida; Aymamí, Neus; Gómez-Peña, Mónica; Pérez-Serrano, Miriam; del Pino-Gutiérrez, Amparo; Menchón, José M; Jiménez-Murcia, Susana

    2014-06-01

    The age of a patient is a strong moderator of both the course and the evolution of disorders/diseases. However, the effects of current age in pathological gambling (PG) have rarely been examined. The aim of this study is to explore the moderating effects of the patients' current age in relation to personality traits and clinical outcomes of PG. A total sample of 2,309 treatment-seeking patients for PG, diagnosed according to DSM-IV criteria, participated in this study and were assessed with the Diagnostic Questionnaire for Pathological Gambling according to DSM-IV criteria, the South Oaks Gambling Screen, the Symptom Checklist, the Temperament and Character Inventory-R, and other clinical and psychopathological measures. Orthogonal polynomial contrasts showed linear trends in the relationship between age and PG: the older the patient, the more comorbid health problems were visible. The presence of additional quadratic trends also suggests that age plays a significant role in moderating the possibility of existing PG problems and general psychopathology. No interaction term was found between age and sex, but it was present for age and some personality traits: self-transcendence and reward dependence (these two traits were only relevant to the level of impairment due to PG at specific ages). This study suggests that the patients' age influences psychopathological and clinical aspects associated to PG. Intervention in the earliest manifestations of this complex problem is essential in order to better address the need of successful treatment planning.

  19. Pathological gambling: understanding relapses and dropouts.

    Science.gov (United States)

    Aragay, Núria; Jiménez-Murcia, Susana; Granero, Roser; Fernández-Aranda, Fernando; Ramos-Grille, Irene; Cardona, Sara; Garrido, Gemma; Anisul Islam, Mohammed; Menchón, José M; Vallès, Vicenç

    2015-02-01

    There is little available information on the factors that influence relapses and dropouts during therapy for pathological gambling (PG). The aim of this study was to determine socio-demographic, clinical, personality, and psychopathological predictors of relapse and dropout in a sample of pathological gamblers seeking treatment. A total of 566 consecutive outpatients diagnosed with PG according to DSM-IV-TR criteria were included. All patients underwent an individualized cognitive-behavioral treatment program. We analyzed predictors of relapse during 6months of treatment and during the subsequent 6months of follow-up, and predictors of dropout over the entire therapeutic program. Eighty patients (14.1%) experienced at least one relapse during the entire follow-up of the study: 50 (8.8%) within the treatment period and 12 (2.1%) during the subsequent 6-month follow-up period. The main predictors of relapse were single marital status, spending less than 100euros/week on gambling, active gambling behavior at treatment inclusion, and high scores on the TCI-R Harm Avoidance personality dimension. One hundred fifty-seven patients (27.8%) missed 3 or more therapeutic sessions over the entire therapeutic program. The main predictors of dropout were single marital status, younger age, and high scores on the TCI-R Novelty Seeking personality dimension. The presence of these factors at inclusion should be taken into account by physicians dealing with PG patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Directed peer review in surgical pathology.

    Science.gov (United States)

    Smith, Maxwell L; Raab, Stephen S

    2012-09-01

    Second pathologist peer review is used in many surgical laboratory quality-assurance programs to detect error. Directed peer review is 1 method of second review and involves the selection of specific case types, such as cases from a particular site of anatomic origin. The benefits of using the directed peer review method are unique and directed peer review detects both errors in diagnostic accuracy and precision and this detection may be used to improve practice. We utilize the Lean quality improvement A3 method of problem solving to investigate these issues. The A3 method defines surgical pathology diagnostic error and describes the current state in surgical pathology, performs root cause analysis, hypothesizes an ideal state, and provides opportunities for improvement in error reduction. Published data indicate that directed peer review practices may be used to prevent active cognitive errors that lead to patient harm. Pathologists also may use directed peer review data to target latent factors that contribute to error and improve diagnostic precision.

  1. Impulse control disorders and attention deficit disorder in pathological gamblers.

    Science.gov (United States)

    Specker, S M; Carlson, G A; Christenson, G A; Marcotte, M

    1995-12-01

    Little systematic research has been done on psychiatric comorbidity of pathological gambling, an impulse control disorder. This report describes the occurrence of attention deficit disorder and impulse control disorders in 40 pathological gamblers in treatment for gambling problems and 64 controls. Diagnoses were made by structured interviews which utilized operationalized diagnostic criteria. An impulse control disorder other than pathological gambling was noted in 35% of the pathological gamblers, compared to 3% of the controls (p buying (p behavior (p impulse control disorders. Attention deficit disorder was seen in 20% of the pathological gamblers. Rates of impulse control disorders did not differ by gender. Implications of these high rates of comorbidity are discussed.

  2. Relationship between magnification and resolution in digital pathology systems.

    Science.gov (United States)

    Sellaro, Tiffany L; Filkins, Robert; Hoffman, Chelsea; Fine, Jeffrey L; Ho, Jon; Parwani, Anil V; Pantanowitz, Liron; Montalto, Michael

    2013-08-22

    Many pathology laboratories are implementing digital pathology systems. The image resolution and scanning (digitization) magnification can vary greatly between these digital pathology systems. In addition, when digital images are compared with viewing images using a microscope, the cellular features can vary in size. This article highlights differences in magnification and resolution between the conventional microscopes and the digital pathology systems. As more pathologists adopt digital pathology, it is important that they understand these differences and how they ultimately translate into what the pathologist can see and how this may impact their overall viewing experience.

  3. PLACENTAL PATHOLOGY IN INTRA UTERINE GROWTH RETARDATION

    Directory of Open Access Journals (Sweden)

    Vijaya Sheela

    2015-04-01

    Full Text Available INTRODUCTION: The placental development is an essential step in developing effective strategies or the prediction of various maternal and fetal medical and developmental problems . Oxygen transfer and nutrients to the fetus will be actively regulated by the placenta . AIM AND OBJECTIVE: To study morphological changes of placenta in Intrauterine growth Retardation and to correlate morphological changes of placenta with fetal outcome . MATERIALS AND METHODS: Placental tissue samples were obtained from 50 pregnancies complicated by IUGR and 50 normal uncomplicated pregnancies with gestational age between 28 to 42 weeks attending King George hospital Visakhapatnam . INCLUSIVE CRITERIA : An IUGR fetuses whose estimated fetal weight less than those in 10 th percentile are included in the study . Birth weight percentiles were determined by previously published normal curves . EXCLUSIVE CRITERIA: fetuses with known syndromes , chromosomal anomalies and twins . For all patients included in the data set gestational age was estimated from the last menstrual period or early ultra - sonogram before the 12 th week of gestation . The final data set was composed of 50pregnancies complicated by IUGR and APGAR scores . Because preeclampsia is an important maternal factor associated with IUGR , these cases were further divided into t wo subgroups according to presence of hypertension . Samples were taken both from vaginal deliveries and caesarean sections . All the placentas were examined by pathologists . The placentas were weighed . For each case one or two samples from the umbilical cor ds , extra placental membrane , and parenchyma were taken . Gross pathological findings were confirmed by histology . Histological data included are ischemic necrosis , decidual vascularity , acute chorioamni oni tis , fibrinoid necrosis and choriangiosis . Appropriate statistical parameters were used . Chi - square test was conducted to compare placental pathological changes

  4. Continuum model of tendon pathology - where are we now?

    Science.gov (United States)

    McCreesh, Karen; Lewis, Jeremy

    2013-08-01

    Chronic tendon pathology is a common and often disabling condition, the causes of which remain poorly understood. The continuum model of tendon pathology was proposed to provide a model for the staging of tendon pathology and to assist clinicians in managing this often complex condition (Br. J. Sports Med., 43, 2009, 409). The model presents clinical, histological and imaging evidence for the progression of tendon pathology as a three-stage continuum: reactive tendinopathy, tendon disrepair and degenerative tendinopathy. It also provides clinical information to assist in identifying the stage of pathology, in addition to proposed treatment approaches for each stage. The usefulness of such a model is determined by its ability to incorporate and inform new and emerging research. This review examines the degree to which recent research supports or refutes the continuum model and proposes future directions for clinical and research application of the model. © 2013 The Authors. International Journal of Experimental Pathology © 2013 International Journal of Experimental Pathology.

  5. Isolated sphenoid sinus lesions: Experience with a few rare pathologies

    Directory of Open Access Journals (Sweden)

    Nishanth Sadashiva

    2017-01-01

    Full Text Available Introduction: The sphenoid sinus is often neglected because of its difficult access. The deep position of the sphenoid sinus hinders early diagnosis of pathologies in that location. Delayed diagnosis can cause serious complications due to proximity to many important structures. Objectives: The aim of this study is to demonstrate different pathologies which can affect the sphenoid sinus and elucidate the findings. Methods: Cases of isolated sphenoid sinus lesions encountered in the neurosurgical setting which had rare pathologies are discussed. Pathologies such as Langerhans cell histiocytosis, solitary plasmacytoma, chordoma, pituitary adenoma, leiomyosarcoma, fungal infection, and mucocele which appeared primarily in sphenoid sinus are discussed along with their imaging features and pathological findings. Conclusion: Multitude of different pathologies can occur in sphenoid sinus. Detailed preoperative imaging is very helpful, but transnasal biopsy and histological study are required often for definitive diagnosis. The possible advantages of early diagnosis before spread of pathology for prognosis cannot be overemphasized.

  6. The Archives of Pathology & Laboratory Medicine: The Most Widely Read Pathology Journal Today.

    Science.gov (United States)

    Allen, Timothy Craig

    2016-09-01

    The Archives of Pathology & Laboratory Medicine was first published in 1926 as a subspecialty journal of the American Medical Association. It became the official journal of the College of American Pathologists in 1995. Under the dynamic leadership of its most recent editor-in-chief, Philip T. Cagle, MD, and his vibrant editorial board, the Archives has nearly doubled its impact factor and become the most widely read general pathology journal today. Dr Cagle has consistently added leading pathologists to the editorial board, and the collective expertise of these individuals is clearly evident in new, cutting-edge journal masthead sections. The Archives has featured innovative content in the field of digital pathology, including articles on the utilization of smart phones in pathology and incorporation of whole-slide images and videos into the content of articles. Special sections have characterized the Archives during the current editorial board's tenure and have proven immensely popular with the journal's readership. As the Archives celebrates its 90th anniversary, its editorial board remains committed to providing insightful and relevant medical knowledge. The journal's open access Web site ( www.archivesofpathology.org ) allows the dissemination of this knowledge to every corner of the globe at no expense to those who wish to be educated or improve their medical practice.

  7. Accuracy of Physical Examination in Distinguish Pathologic Murmur of non Pathologic

    Directory of Open Access Journals (Sweden)

    A Tanasan

    2013-02-01

    Full Text Available Abstract Background & aim: Cardiac auscultation is one of the most useful investigative tools that the physician may use at the bedside to detect alterations in cardiovascular anatomy and physiology. However, the sensitivity and specificity vary substantially with the expertise of the examiner. The aim of this study comparing the initial evaluations of heart murmurs in neonates between neonatologist and pediatric cardiologist. Methods: This cross-sectional study was conducted on 108 neonates admitted in Be’sat and Fatemieh Hospitals of Hamadan, Iran, in 2010. First, a neonatologist recorded their clinical evaluation (Pathologic, Likely pathologic, Innocent. Then, a Pediatric cardiologist recorded the infants’ clinical evaluation. Finally, echocardiography study was performed by the cardiologists for final diagnosis. The data were analyzed by SPSS version 16 and the using Chi-square. Results: In this study, 67 patients (62% had pathologic murmur. Clinical findings of pathological murmur by neonatologist and cardiologist are 98% sensitivity versus 87/2% 84/2% specificity vs. 100% 94/1% the positive predictive value vs. 100% and 94% negative predictive value vs. 85.4%, respectively. Conclusion: Evaluations of examination show no significant difference between neonatologists and cardiologists. Hence, echocardiography is the standard for establishing the cause of murmur. Key words: Murmur, Echocardiogram, Physical Examination

  8. Anomia-Pathological Verbal Dominance. Agnosic Behavior in Anomia: A Case of Pathological Verbal Dominance

    Science.gov (United States)

    McGlannan, Frances, Ed.

    1975-01-01

    Summarized are three articles concerned with research on neurological aspects of learning disabilities entitled "Anomia-A Case of Pathological Verbal Dominance;""Brain--Right Hemisphere--Man's So Called 'Minor Hemisphere;""Neurology-A Special Neurological Examination of Children with Learning Disabilities". (DB)

  9. Cognitive plasticity in normal and pathological aging

    Directory of Open Access Journals (Sweden)

    Fernández-Ballesteros R

    2012-01-01

    Full Text Available Rocío Fernández-Ballesteros1, Juan Botella1, María Dolores Zamarrón1, María Ángeles Molina1, Emilia Cabras1, Rocío Schettini1, Lluis Tárraga21Autonomous University of Madrid, Madrid, Spain; 2ACE Foundation, Catalonian Institute of Applied Neurosciences, Barcelona, SpainAbstract: The main goal of the present study is to examine to what extent age and cognitive impairment contribute to learning performance (cognitive plasticity, cognitive modifiability, or learning potential. To address this question, participants coming from four studies (Longitudinal Study of Active Aging, age range, 55–75 years, N = 458; Longitudinal Study in the very old [90+], age range, 90–102, N = 188, and Cognitive Plasticity within the Course of Cognitive Impairment, 97 “Normal”, 57 mild cognitive impairment [MCI], and 98 Alzheimer's disease [AD] patients were examined through a measure of verbal learning (developed from Rey. The results show that all age, MCI, and AD groups learned across the five learning trials of that test, but significant differences were found due to age, pathology, and education. The effects of pathology (MCI and AD can be expressed in a metric of “years of normal decline by age”; specifically, being MCI means suffering an impairment in performance that is equivalent to the decline of a normal individual during 15 years, whereas the impact of AD is equivalent to 22.7 years. Likewise, the improvement associated with about 5 years of education is equivalent to about 1 year less of normal aging. Also, the two pathological groups significantly differed from “normal” groups in the delayed trial of the test. The most dramatic difference is that between the “normal” group and the AD patients, which shows relatively poorer performance for the AD group in the delayed trial than in the first learning trial. The potential role of this unique effect for quick detection purposes of AD is assessed (in the 75–89 years age range

  10. Pathology of Hodgkin's disease: anything new?

    Science.gov (United States)

    Wright, D H

    1989-01-01

    This presentation deals with the gross and microscopic pathology of HD. Recent advances in immunohistochemistry, gene rearrangement studies and cell culture are not discussed, except where they shed light on the pathology. Clinical and pathological experience, over the past 2 decades, suggests that HD should be divided into six subtypes, as originally proposed by Lukes et al. (1966b), rather than the four subtypes included in the Rye classification. Nodular lymphocyte/histiocyte predominant HD forms a clinicopathological entity separate from the other subtypes. It most frequently presents at a single nodal site and, even without therapy, progresses only slowly over a period of many years. A proportion of the patients (in the region of 10%) develop large cell NHL and a smaller number develop other types of Hodgkin's disease. This progression is not due to therapy since it most frequently occurs in untreated patients. Characteristic polylobated RS cell variants are seen in NLPHD. These differ from classic RS cells in that they have a B-cell phenotype, they do not show light chain restriction and, therefore, they do not appear to be a clonal proliferation. Although current dogma states that classic RS cells must be identified before a diagnosis of HD, including NLPHD, is made, it is the author's contention, supported by immunohistochemistry, that this type of RS cell does not occur in NLPHD. Polylobated RS cell variants in the appropriate cellular setting are, in themselves, diagnostic of NLPHD. They also serve to differentiate NLPHD from progressive transformation of germinal centres, an unusual proliferative expansion that may occur in association with HD but which, in itself, appears to be an entirely benign, reactive process. Diffuse lymphocyte/histiocyte predominant HD (DLPHD) differs from NLPHD in its diffuse growth pattern and the frequent presence of larger numbers of histiocytes. Polylobated RS cells are characteristic of both diseases. In some biopsies

  11. The "Shaken Baby" syndrome: pathology and mechanisms.

    Science.gov (United States)

    Squier, Waney

    2011-11-01

    The "Shaken Baby" syndrome (SBS) is the subject of intense controversy; the diagnosis has in the past depended on the triad of subdural haemorrhage (SDH), retinal haemorrhage and encephalopathy. While there is no doubt that infants do suffer abusive injury at the hands of their carers and that impact can cause catastrophic intracranial damage, research has repeatedly undermined the hypothesis that shaking per se can cause this triad. The term non-accidental head injury has therefore been widely adopted. This review will focus on the pathology and mechanisms of the three physiologically associated findings which constitute the "triad" and are seen in infants suffering from a wide range of non-traumatic as well as traumatic conditions. "Sub" dural bleeding in fact originates within the deep layers of the dura. The potential sources of SDH include: the bridging veins, small vessels within the dura itself, a granulating haemorrhagic membrane and ruptured intracranial aneurysm. Most neuropathologists do not routinely examine eyes, but the significance of this second arm of the triad in the diagnosis of Shaken Baby syndrome is such that it merits consideration in the context of this review. While retinal haemorrhage can be seen clinically, dural and subarachnoid optic nerve sheath haemorrhage is usually seen exclusively by the pathologist and only rarely described by the neuroradiologist. The term encephalopathy is used loosely in the context of SBS. It may encompass anything from vomiting, irritability, feeding difficulties or floppiness to seizures, apnoea and fulminant brain swelling. The spectrum of brain pathology associated with retinal and subdural bleeding from a variety of causes is described. The most important cerebral pathology is swelling and hypoxic-ischaemic injury. Mechanical shearing injury is rare and contusions, the hallmark of adult traumatic brain damage, are vanishingly rare in infants under 1 year of age. Clefts and haemorrhages in the immediate

  12. Perinatal pathology: the role of the clinical pathological dialogue in problem solving

    Directory of Open Access Journals (Sweden)

    Gavino Faa

    2014-06-01

    Full Text Available Pathologists and clinicians come together and exchange views, they instil in one another doubts, they break down barriers. Asphyxia, respiratory distress, sepsis, multi-organ failure (MOF, cerebral ischemia and neuroprotection, necrotizing enteritis, renal and biliary pathology (including congenital nephrotic syndrome, injury caused by drugs, cardiac decompensation, placental pathology, neonatal issues in mothers with tumor: these are the topics debated, in the true sense of the word, by perinatologists and pathologists. In some pathologies (e.g. MOF the pathophysiology is surprisingly the same in the neonate and the adult.  Different disciplines deal for example with immunohistochemistry and metabolomics with the processing of thousands of data in search of something that cannot be found with the classic criteria of anamnesis, objective examination, laboratory tests and imaging. Big data and information science promise to change the world. To come to grips with the extreme biological complexity of our organism and each of our organs, the completeness of enormous amounts of data is of extraordinary value if assessed holistically with the “omic” disciplines. Thus we have the possibility of understanding our extraordinary interindividual variability. The new technologies and their application do not diminish the role of physicians: on the contrary, they represent a formidable instrument for extending their diagnostic potential and make possible 5-P medicine: personalized, prospective, predictive, preventive, participatory.  Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014 · Cagliari (Italy · October 25th, 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyken

  13. Trace copper levels in the drinking water, but not zinc or aluminum influence CNS Alzheimer-like pathology.

    Science.gov (United States)

    Sparks, D L; Friedland, R; Petanceska, S; Schreurs, B G; Shi, J; Perry, G; Smith, M A; Sharma, A; Derosa, S; Ziolkowski, C; Stankovic, G

    2006-01-01

    Mounting evidence suggests copper may influence the progression of Alzheimer's disease by reducing clearance of the amyloid beta protein (Abeta) from the brain. Previous experiments show that addition of only 0.12 PPM copper (one-tenth the Environmental Protection Agency Human consumption limits) to distilled water was sufficient to precipitate the accumulation of Abeta in the brains of cholesterol-fed rabbits (1). Here we report that addition of copper to the drinking water of spontaneously hypercholesterolemic Watanabe rabbits, cholesterol-fed beagles and rabbits, PS1/APP transgenic mice produced significantly enhanced brain levels of Abeta. In contrast to the effects of copper, we found that aluminum- or zinc-ion-supplemented distilled water did not have a significant effect on brain Ab accumulation in cholesterol-fed rabbits. We also report that administration of distilled water produced a reduction in the expected accumulation of Ab in three separate animal models. Collectively, these data suggest that water quality may have a significant influence on disease progression and Ab neuropathology in AD.

  14. [Cardiology in the Morgagni's anatomo pathological work].

    Science.gov (United States)

    de Micheli, Alfredo; Iturralde, Pedro; Aranda Fraustro, Alberto

    2015-01-01

    In the XVIII century, under the influence of the "systematic spirit", characteristic of the Enlightenment age, pathological anatomy was systematized in the Morgagni's fundamental treatise De sedibus et causis morborum per anatomen indagatis, published as letters in 1761. Certain biographical data of the author are reported here as well as some his more important contributions to cardiology such as the Morgagni's, Adams', Stokes' syndrome. His points of view on sudden death and his observations on post-infarct myocardial rupture, are related also. In his global evaluation of these facts, the speculative approach always predominates. Indeed, in these anatomist's works, we find a good example of the application of epistemologic principles to the medical field.

  15. Multimodal diagnosis and visualisation of oncologic pathologies

    Energy Technology Data Exchange (ETDEWEB)

    Zakharov, V P; Bratchenko, I A; Myakinin, O O; Artemyev, D N; Kornilin, D V [S.P. Korolev Samara State Aerospace University, Samara (Russian Federation); Kozlov, S V; Moryatov, A A [Samara State Medical University, Samara (Russian Federation)

    2014-08-31

    The combined application of optical coherence tomography, Raman and autofluorescence spectroscopy of biotissues for the analysis of human malignant neoplasms is demonstrated. Rapid investigation of vast biotissue regions (at the scale of entire organs) is possible using the autofluorescence response. After selection of possible zones of pathologies one can visualise the neoplasm topology in the zone of interest with micron precision by using optical coherence tomography. In the case of suspecting the malignancy the analysis of the biotissue Raman spectrum is carried out that allows identification of the neoplasm type with the sensitivity and specificity ∼85%. An experimental scheme is proposed with the combined use of the abovementioned methods, which is a prototype of the medical system for complex analysis of neoplasms. (laser biophotonics)

  16. Pathological Plasticity in Fragile X Syndrome

    Directory of Open Access Journals (Sweden)

    Brandon S. Martin

    2012-01-01

    Full Text Available Deficits in neuronal plasticity are common hallmarks of many neurodevelopmental disorders. In the case of fragile-X syndrome (FXS, disruption in the function of a single gene, FMR1, results in a variety of neurological consequences directly related to problems with the development, maintenance, and capacity of plastic neuronal networks. In this paper, we discuss current research illustrating the mechanisms underlying plasticity deficits in FXS. These processes include synaptic, cell intrinsic, and homeostatic mechanisms both dependent on and independent of abnormal metabotropic glutamate receptor transmission. We place particular emphasis on how identified deficits may play a role in developmental critical periods to produce neuronal networks with permanently decreased capacity to dynamically respond to changes in activity central to learning, memory, and cognition in patients with FXS. Characterizing early developmental deficits in plasticity is fundamental to develop therapies that not only treat symptoms but also minimize the developmental pathology of the disease.

  17. Identification errors in pathology and laboratory medicine.

    Science.gov (United States)

    Valenstein, Paul N; Sirota, Ronald L

    2004-12-01

    Identification errors involve misidentification of a patient or a specimen. Either has the potential to cause patients harm. Identification errors can occur during any part of the test cycle; however, most occur in the preanalytic phase. Patient identification errors in transfusion medicine occur in 0.05% of specimens; for general laboratory specimens the rate is much higher, around 1%. Anatomic pathology, which involves multiple specimen transfers and hand-offs, may have the highest identification error rate. Certain unavoidable cognitive failures lead to identification errors. Technology, ranging from bar-coded specimen labels to radio frequency identification tags, can be incorporated into protective systems that have the potential to detect and correct human error and reduce the frequency with which patients and specimens are misidentified.

  18. Molecular Pathology of Human Prion Diseases

    Directory of Open Access Journals (Sweden)

    2009-03-01

    Full Text Available Prion diseases are fatal neurodegenerative conditions in humans and animals. In this review, we summarize the molecular background of phenotypic variability, relation of prion protein (PrP to other proteins associated with neurodegenerative diseases, and pathogenesis of neuronal vulnerability. PrP exists in different forms that may be present in both diseased and non-diseased brain, however, abundant disease-associated PrP together with tissue pathology characterizes prion diseases and associates with transmissibility. Prion diseases have different etiological background with distinct pathogenesis and phenotype. Mutations of the prion protein gene are associated with genetic forms. The codon 129 polymorphism in combination with the Western blot pattern of PrP after proteinase K digestion serves as a basis for molecular subtyping of sporadic Creutzfeldt-Jakob disease. Tissue damage may result from several parallel, interacting or subsequent pathways that involve cellular systems associated with synapses, protein processing, oxidative stress, autophagy, and apoptosis.

  19. A preliminary pathological study on human allotransplantation

    Institute of Scientific and Technical Information of China (English)

    WANG Hui-jun 王慧君; DING Yan-qing 丁彦青; PEI Guo-xian 裴国献; GU Li-qiang 顾立强; ZHU Li-jun 朱立军

    2003-01-01

    Objective: To observe the survival of hand allograft under the state of immunosuppression and the pathological changes of rejection in the recovery process.Methods: The biopsies of the skin, nerve, muscle, tendon and bone tissue of hand allografts during different stages from 1 day to 7 months after operation were observed using routine histological technique.Results: No significant changes due to rejection in skin, nerve, muscle and bone tissue were observed.But different degrees of weak rejective changes were found on the wall of blood vessels; in the muscle and nerve the reactions were markedly stronger than those found in skin tissues.Conclusions: The rejection in deep tissues should be monitored in controlling the rejection of hand allograft.

  20. Tomographic and pathological findings in pulmonary sarcoidosis

    Energy Technology Data Exchange (ETDEWEB)

    Melo, Alessandro Severo Alves de; Marchiori, Edson [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Dept. of Radiology; Capone, Domenico [Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ (Brazil). Dept. of Pneumology

    2011-07-15

    Objective: To analyze radiological findings observed at high-resolution computed tomography in patients with sarcoidosis, and establishing their correlation with pathological findings. Materials and Methods: High-resolution computed tomography findings in ten patients with sarcoidosis were reviewed and correlated with findings in specimens obtained by surgical biopsy or at necropsy of four of such patients. Results: The most frequently observed finding was presence of nodules with perilymphatic distribution, predominating along bronchovascular sheaths and pleural surface, with subpleural nodules and nodular scissurae. Other less frequent findings were ground-glass attenuation and interlobular septa thickening. Conclusion: In general, all the mentioned findings demonstrated anatomopathological correlation with development of granulomas in these regions. (author)

  1. [The rise and fall of pathology techniques].

    Science.gov (United States)

    van den Tweel, Jan G; van Diest, Paul J

    2011-01-01

    For the past 150 years the most constant factor in the pathologist's histopathological diagnostic work-up has been haematoxylin staining. This technique, in combination with later additional staining techniques, determined knowledge on a cellular level for a long time. The invention of the transmission electron microscope added an ultrastructural dimension, and for many decennia in the middle of the twentieth century this was an important diagnostic tool. Enzyme histochemistry and morphometry came next, but these techniques never really became important as they were largely overtaken by immunohistochemistry and molecular diagnostics. These, in their turn, will face competition from proteomics and other forms of genomics. It seems likely that the trusty light microscope will lose out to digital microscopy, which is developing rapidly and offers the possibility to make a diagnosis at a distance. Pathology will continue to be a specialty on the move.

  2. [Psychic experience of pathological machine gamblers].

    Science.gov (United States)

    Avtonomov, D A

    2011-01-01

    The author presents results of the psychopathological phenomena and subjective experience study of 38 patients with the verified diagnosis "Pathological addiction to gambling" (F63.0) without psychotic disorders. In 84,2% cases, the patients preferred slot machine gambling. The causes of such preferences were analyzed. The phenomenology of the psychic experience of the patients who are slot machine gamblers is presented. With the formation of the addiction, the gamblers began to think about slot machines as human beings (creatures), feel attachment to them, see the individuality in them, and experience slot machines as live and real partners in imaginative or even verbal dialogs. Two main "forms of contact" with slot machines were elicited and described: verbal and non-verbal. The gambler has been gradually depleted the image of himself and experiences the "loss of contact" with his own features, qualities, wishes, and intentions. The data obtained may be helpful in psychotherapeutic and rehabilitative work with such patients.

  3. Huntington's Disease: Calcium Dyshomeostasis and Pathology Models.

    Science.gov (United States)

    Kolobkova, Y A; Vigont, V A; Shalygin, A V; Kaznacheyeva, E V

    2017-01-01

    Huntington's disease (HD) is a severe inherited neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and mental impairment. At the molecular level, HD is caused by a mutation in the first exon of the gene encoding the huntingtin protein. The mutation results in an expanded polyglutamine tract at the N-terminus of the huntingtin protein, causing the neurodegenerative pathology. Calcium dyshomeostasis is believed to be one of the main causes of the disease, which underlies the great interest in the problem among experts in molecular physiology. Recent studies have focused on the development of animal and insect HD models, as well as patient-specific induced pluripotent stem cells (HD-iPSCs), to simulate the disease's progression. Despite a sesquicentennial history of HD studies, the issues of diagnosis and manifestation of the disease have remained topical. The present review addresses these issues.

  4. The silent organizational pathology of insidious intimidation.

    Science.gov (United States)

    Zimmerman, Theresa; Amori, Geri

    2011-01-01

    While organizations are valiantly striving to address acts of disruption among physicians and nurses, a silent and yet equally disruptive pathology is spreading through the veins of the organization. This behavior is found among all ranks and responsibilities, from the C-suite to the housekeeping staff. It occurs daily and is rarely reported. It continues because its nature is such that it is difficult to measure, the victims often feel helpless, and the perpetrators are often those in positions that are not normally perceived to be as essential to the flow of patient care. Nonetheless, this insidious intimidation chills communication, reduces morale, and ultimately harms patients. Organizations that desire a culture of safety and comfort must address this behavior through individual coaching, education of all staff, a willingness to tackle system frustrations that amplify and perpetuate the behavior, and establish processes for dealing fairly and firmly with the behavior.

  5. Calcaneal chondroblastoma with pathologic fracture and recurrence.

    Science.gov (United States)

    Dutt, Laksha; Schade, Valerie L; Manoso, Mark W

    2015-01-01

    Chondroblastomas account for 80% of cases. Local recurrence rates of ≤38% have been reported, most often because of inadequate resection, and have been associated with malignant conversion and metastasis. Adjuvant therapies can help minimize the incidence of local recurrence. Long-term follow-up examinations are recommended, given the protracted interval that can exist between recurrence and the potential for malignant conversion and metastasis. We present the case of a young, healthy, active male with a calcaneal chondroblastoma and associated pathologic fracture whose initial treatment consisted of curettage, hydrogen peroxide lavage, and allogeneic bone grafting. Recurrence developed at 15 months postoperatively and was treated with repeat curettage, high-speed burring, and reconstruction with steel Steinman pins and polymethylmethacrylate, resulting in no pain or recurrence at the 5-month follow-up point.

  6. [Forensic medicine and the overlap with pathology].

    Science.gov (United States)

    Riepert, T

    2010-07-01

    Forensic medicine incorporates research, teaching and professional service. In the routine practice this encompasses interdisciplinary cooperation with physicians, natural scientists and the legal profession. Lectures in forensic medicine include the correct performance of an external examination of corpses, which every physician must be capable of, just as medical questions and the evidential documentation of injuries. Clinical forensic medicine encompasses the examination and documentation of living victims of physical and/or sexual violence. For further training to become a specialist for forensic medicine it is mandatory to undertake a 6-month training period in pathology. Fatalities with an unclear or unnatural manner of death must be registered with the police. On suspicion of third party involvement the public prosecutor will request a legal autopsy, which is carried out and documented by two physicians in accordance with the penal code. Imaging procedures are standard for an autopsy. Extensive samples are taken for additional testing, such as toxicological and molecular biological investigations.

  7. Immunotherapy against amyloid pathology in Alzheimer's disease.

    Science.gov (United States)

    Galimberti, Daniela; Ghezzi, Laura; Scarpini, Elio

    2013-10-15

    The first drugs developed for Alzheimer's disease (AD), anticholinesterase inhibitors (AchEI), increase acetylcholine levels, previously demonstrated to be reduced in AD. To date, four AchEI are approved for the treatment of mild to moderate AD. A further therapeutic option available for moderate to severe AD is memantine. These treatments are symptomatic, whereas drugs under development are supposed to modify pathological steps leading to AD, thus acting on the evolution of the disease. For this reason they are currently termed "disease modifying" drugs. To block the progression of the disease, they have to interfere with pathogenic steps at the basis of clinical symptoms, including the deposition of extracellular amyloid beta (Aβ) plaques and of intracellular neurofibrillary tangles. The most innovative approach is represented by the vaccination and passive immunization against Aβ peptide. In this article, current knowledge about concluded and ongoing clinical trials with both vaccination with different antigens and passive immunization will be reviewed and discussed.

  8. Pathological changes waterproof membranes and their identification

    Directory of Open Access Journals (Sweden)

    Novotný Marek

    2017-01-01

    Full Text Available With the development of waterproofing systems based on synthetic membranes, especially mPVC, there is an increase in pathological changes of these membranes. Competing manufacturers and pressure on price of the final product have resulted in usage of unstable or low quality raw materials. After production, these materials keep their specific characteristics, however, their aging is accelerated, i.e. they lose their essential qualitative characteristics very quickly. Very important is the detection of these processes which is possible using chemical analysis (gas chromatography, IR analysis and others as well as using visual inspection of surface by microscope, including 3D modeling. Very important are weldability tests which identify glass transition temperature of the material. The results can then be used as a basis for correct identification of problems with weldability, nonweldability of synthetic membranes, respectively, as well as for identification of normal or abnormal aging of these materials.

  9. Orofacial granulomatosis: clinical signs of different pathologies.

    Science.gov (United States)

    Troiano, Giuseppe; Dioguardi, Mario; Giannatempo, Giovanni; Laino, Luigi; Testa, Nunzio Francesco; Cocchi, Roberto; De Lillo, Alfredo; Lo Muzio, Lorenzo

    2015-01-01

    Orofacial granulomatosis (OFG) is an uncommon disease characterized by persistent or recurrent soft tissue enlargement, oral ulceration and a variety of other orofacial features. It could be an oral manifestation of a systemic disease. For a correct differential diagnosis, local and systemic conditions characterized by granulomatous inflammation should be excluded using appropriate clinical and laboratory investigations. In fact, the diagnosis of OFG may be confirmed only by histopathological identification of noncaseating granulomas. The literature from 1943 to 2014 was reviewed with emphasis on the etiology of OFG and on clinical manifestations of systemic pathologies associated with OFG. The precise cause of OFG is still unknown, although several theories have been suggested, such as infection, hereditary factors and allergy. OFG is a disease that has a wide spectrum of presentation, which may include the oral manifestation of a systemic condition such as Crohn's disease, sarcoidosis, granulomatosis with polyangiitis and Melkersson-Rosenthal syndrome.

  10. Clinical Pathological Analysis of Synovial Sarcoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    OBJECTIVE To investigate the clinical diagnosis and differential diagnosis of synovial sarcoma (SS).METHODS A total of 41 paraffin-embedded synovial sarcoma samples were examined by H&E staining, immunohistochemistry staining and the reverse transcriptase polymerase chain reaction (RT-PCR), in order to provide a scientific bases for diagnosis and differential diagnosis.RESULTS Twelve cases were a biphasic type, 22 cases were a monophasic fibrous type, and 7 cases were a poorly differentiated type. Thirty-six cases were both CK (and/or EMA) and Vim positive. Five cases were only Vim positive. A SYT-SSX fusion gene was detected in 18 cases by RT-PCR.CONCLUSION By observation of the histomorphology, immunohistochemistry markers and detection of a SYT-SSX fusion gene, we can make a clinical pathological diagnosis of synovial sarcoma.

  11. Chondroblastoma patella presenting as a pathological fracture

    Directory of Open Access Journals (Sweden)

    Gudi Narayan

    2008-01-01

    Full Text Available A 24-year-old male presented with an inability to walk after a trivial fall. He had pain and mild swelling anterior to the right knee for the past one year. X-ray showed a transverse fracture of patella with a lytic lesion occupying most of the two halves of the patella. Fine needle aspiration cytology (FNAC of the lytic lesion revealed a few osteoclastic giant cells and occasional osteoblasts against a hemorrhagic background. Patellectomy was performed. Histology revealed trabecular bone admixed with proliferating chondroid tissue at places admixed with myxoid and fibrous tissue with focal areas of calcification suggestive of chondroblastoma. Focal areas showed osteoclastic giant cells with areas of hemorrhage. The purpose is to present a rare tumor occurring at an unusual site which presented as pathological fracture.

  12. Pathological love: impulsivity, personality, and romantic relationship.

    Science.gov (United States)

    Sophia, Eglacy C; Tavares, Hermano; Berti, Marina P; Pereira, Ana P; Lorena, Andrea; Mello, Cidália; Gorenstein, Clarice; Zilberman, Monica L

    2009-05-01

    Pathological love (PL)--behavior characterized by providing repetitive and uncontrolled care and attention to the partner in a romantic relationship--is a rarely studied condition, despite not being rare and causing suffering. This study aims at investigating impulsivity, personality, and characteristics related to the romantic relationship in this population. Eighty-nine individuals (50 with PL; 39 individuals with no psychiatric disorder) were compared regarding impulsivity, personality, type of attachment, satisfaction with romantic relationship, and love style. Individuals with PL have higher levels of impulsivity (Promantic relationships (PRelationship Assessment Scale). Individuals with PL present personality traits and relationship aspects that must be taken into account in devising assessment and therapeutic strategies for this population.

  13. Epicardial Fat: Physiological, Pathological, and Therapeutic Implications

    Science.gov (United States)

    Salazar, Juan; Luzardo, Eliana; Mejías, José Carlos; Ferreira, Antonio; Rivas-Ríos, José Ramón; Bermúdez, Valmore

    2016-01-01

    Epicardial fat is closely related to blood supply vessels, both anatomically and functionally, which is why any change in this adipose tissue's behavior is considered a potential risk factor for cardiovascular disease development. When proinflammatory adipokines are released from the epicardial fat, this can lead to a decrease in insulin sensitivity, low adiponectin production, and an increased proliferation of vascular smooth muscle cells. These adipokines move from one compartment to another by either transcellular passing or diffusion, thus having the ability to regulate cardiac muscle activity, a phenomenon called vasocrine regulation. The participation of these adipokines generates a state of persistent vasoconstriction, increased stiffness, and weakening of the coronary wall, consequently contributing to the formation of atherosclerotic plaques. Therefore, epicardial adipose tissue thickening should be considered a risk factor in the development of cardiovascular disease, a potential therapeutic target for cardiovascular pathology and a molecular point of contact for “endocrine-cardiology.” PMID:27213076

  14. The use of digital images in pathology.

    Science.gov (United States)

    Furness, P N

    1997-11-01

    Digital images are routinely used by the publishing industry, but most diagnostic pathologists are unfamiliar with the technology and its possibilities. This review aims to explain the basic principles of digital image acquisition, storage, manipulation and use, and the possibilities provided not only in research, but also in teaching and in routine diagnostic pathology. Images of natural objects are usually expressed digitally as 'bitmaps'--rectilinear arrays of small dots. The size of each dot can vary, but so can its information content in terms, for example, of colour, greyscale or opacity. Various file formats and compression algorithms are available. Video cameras connected to microscopes are familiar to most pathologists; video images can be converted directly to a digital form by a suitably equipped computer. Digital cameras and scanners are alternative acquisition tools of relevance to pathologists. Once acquired, a digital image can easily be subjected to the digital equivalent of any conventional darkroom manipulation and modern software allows much more flexibility, to such an extent that a new tool for scientific fraud has been created. For research, image enhancement and analysis is an increasingly powerful and affordable tool. Morphometric measurements are, after many predictions, at last beginning to be part of the toolkit of the diagnostic pathologist. In teaching, the potential to create dramatic yet informative presentations is demonstrated daily by the publishing industry; such methods are readily applicable to the classroom. The combination of digital images and the Internet raises many possibilities; for example, instead of seeking one expert diagnostic opinion, one could simultaneously seek the opinion of many, all around the globe. It is inevitable that in the coming years the use of digital images will spread from the laboratory to the medical curriculum and to the whole of diagnostic pathology.

  15. Punch Biopsy Results of Nasopharynx Pathologies

    Directory of Open Access Journals (Sweden)

    İsa Özbay

    2016-03-01

    Full Text Available Objective: Although nasopharynx (NF has an anatomi­cally distant sites to view, biopsy can be taken easily from NF by the help of an endoscope in order to reach a defini­tive diagnosis. In this study, NF pathology results in the patient group were analyzed retrospectively. Methods: NF biopsy results of 80 patients who were ad­mitted to Ear, Nose and Throat (ENT clinic of Dumlupınar University Evliya Celebi Education and Research Hospital between September 2012-February 2016 were included in the study, retrospectively. NF has been viewed to rule out NF cancer under general or local anesthesia by rigid or flexible endoscopes and punch biopsies were taken. Results: NF patients who underwent biopsy were com­posed of 25 (31.2% females and 55 (68.8% males and the average age was 35.33. Histopathological results in 3 patients (3.7% were malignant. The pathology (96.3% were identified as chronic lymphoid hyperplasia and lym­phoid processes in the remaining 77 patients. 4 patients underwent repeat biopsy follow-on clinical suspicion of malignancy, but ultimately malignancy was not observed. Conclusion: NF biopsy is a method which is easily ap­plied in the examination of the cancer and other masses of NF. In this study, age, sex, clinical and histopathologic analysis of the patients who underwent NF biopsies were discussed in the light of the literature. J Clin Exp Invest 2016; 7 (1: 83-86

  16. Hippocrates' humoral pathology in nowaday's reflections.

    Science.gov (United States)

    Bujalkova, M; Straka, S; Jureckova, A

    2001-01-01

    Ancient medicine integrated three components: experience (empirical observation), religion/magic and speculations of natural philosophers. The Greek medicine out-achieved medicine of other ancient nations in starting to investigate the true causes of health and diseases and thus laying foundations for the diagnosis, prognosis and treatment. Hippocrates, the most famous physician of the ancient times, made a synthesis of existing philosophical opinions from the point of view of a physician. His 58 writings were preserved in the collection "Corpus Hippocraticum". The most relevant writing in it--"Peri fyseos anthropu" (On the nature of man)--is ascribed to Hippocrates' son-in-law Polybos to whom we are grateful for the ancient humoral-pathological theory. In explaining human organism and its processes the author integrated ancient teachings on 4 basic humors (humoral theory), elements and qualities with observations of manifestations of health and disease. Normal condition (health) was defined as balance between the body fluids (eukrasia) and external environment. If this balance is disturbed, the result is dyskrasia, i.e. disease studied by pathology. According to Hippocrates disease causes can be understood only through empirical study. A man has a power to overcome disease, but to achieve it the right diet is necessary to keep harmony in body fluids of an organism. The role of a physician was just to support the nature. "Prognosis", another writing included in "Corpus Hippocraticum", reflects Hippocrates' understanding of prognosis as a necessary development of diagnosis based on past knowledge (anamnesis) and present observation. Ideas of Hippocrates and his medical school are still valuable and inspiring especially for today's very sophisticated medicine--concept of fighting diseases by natural means: maintaining healthy lifestyle and harmony within the organism, or an effort for perfect understanding of human creature and for humanization of medicine. (Fig. 3

  17. Advances in the pathology of penile carcinomas.

    Science.gov (United States)

    Chaux, Alcides; Cubilla, Antonio L

    2012-06-01

    The incidence of penile cancer varies from country to country, with the highest figures reported for countries in Africa, South America, and Asia and lowest in the United States and Europe. Causes of this variation are not clear, but they are thought to be related to human papillomavirus infection, smoking, lack of circumcision, chronic inflammation, and poor genital hygiene. Most penile tumors are squamous cell carcinomas, and a variegated spectrum of distinct morphologies is currently recognized. Each one of these subtypes has distinctive pathologic and clinical features. About half of penile carcinomas are usual squamous cell carcinomas, and the rest corresponds to verrucous, warty, basaloid, warty-basaloid, papillary, pseudohyperplastic, pseudoglandular, adenosquamous, sarcomatoid, and cuniculatum carcinomas. Previous studies have found a consistent association of tumor cell morphology and human papillomavirus presence in penile carcinomas. Those tumors composed of small- to intermediate-sized, basaloid ("blue") cells are often human papillomavirus positive, whereas human papillomavirus prevalence is lower in tumors showing large, keratinizing, maturing eosinophilic ("pink") cells. Human papillomavirus-related tumors affect younger patients, whereas human papillomavirus-unrelated tumors are seen in older patients with phimosis, lichen sclerosus, or squamous hyperplasia. This morphologic distinctiveness is also observed in penile intraepithelial neoplasia. The specific aim of this review is to provide a detailed discussion on the macroscopic and microscopic features of all major subtypes of penile cancer. We also discuss the role of pathologic features in the prognosis of penile cancer, the characteristics of penile precursor lesions, and the use of immunohistochemistry for the diagnosis of invasive and precursor lesions.

  18. Clinical pathology of primary bile reflux gastritis

    Directory of Open Access Journals (Sweden)

    Ping YAO

    2011-05-01

    Full Text Available Objective To analyze the clinical and pathological features of primary bile reflux gastritis(BRG.Methods Endoscopy,Helicobacter pylori(H.pylori detection,and histopathologic examination were performed in 218 patients with primary BRG(observed group and 236 patients with simple chronic gastritis(SCG,control group as identified by gastroscope in order to analyze the endoscopic abnormalities,the frequency of H.pylori infection,pathological features and scores of inflammation.Results The frequency of H.pylori infection was 39.0%(85/218 in the observed group,which was significantly lower than that in the control group [52.1%(123/236].The topographic abnormalities of the antral mucosa as detected by gastroscopy,i.e.,congestion,hemorrhagic spots,erosion were not significantly different between BRG and SCG patients(P > 0.05.The scores of chronic and active inflammation were higher in patients when H.pylori infection was present than in patients without H.pylori infection in both groups(P < 0.05.The scores of inflammation,the detection rates of the antral intestinal metaplasia,antral atrophy and atypical hyperplasia were all higher in observed group than in control group(P < 0.05.The incidence of lengthening of gastric pits,telangiectasis or interstitial edema in BRG patients was also significantly higher than those in SCG patients(P < 0.05.Conclusions Primary BRG shows features of chemical gastritis with a higher tendency toward mucosal atrophy,intestinal metaplasia and atypical hyperplasia.Gastropic examination and biopsy should be emphasized.

  19. Spontaneous reproductive pathology in female guinea pigs.

    Science.gov (United States)

    Veiga-Parga, Tamara; La Perle, Krista M D; Newman, Shelley J

    2016-11-01

    Reproductive pathology of domestic guinea pigs is underreported to date. To provide a comprehensive review of uterine disease in guinea pigs, we performed a retrospective study of the pathology archives of the University of Tennessee, College of Veterinary Medicine. By histology, 13 of 37 uterine lesions in 23 animals were neoplastic; the other 24 nonneoplastic lesions included cystic endometrial hyperplasia (16 of 24), endometrial hemorrhage (3 of 24), pyometra (2 of 24), polyp (2 of 24), and mucometra (1 of 24). The most common guinea pig uterine neoplasms were uterine leiomyomas (6 of 13), followed by adenomas (3 of 13) and leiomyosarcomas (1 of 13). Other neoplasms included anaplastic tumors of unknown origin (2 of 13) and choriocarcinoma (1 of 13). Both anaplastic tumors and the choriocarcinoma were positive for vimentin. The choriocarcinoma was positive for HSD83B1, indicating a trophoblastic origin and its final diagnosis. All were negative for cytokeratin and smooth muscle. In multiple animals, more than 1 tumor or lesion was reported. Estrogen receptor and progesterone receptor expression was nearly 100% in uterine neoplasms. Nearly all animals for which data were available had cystic rete ovarii (18 of 19); the animal with no cystic rete ovarii had paraovarian cysts. In our study, female pet guinea pigs had a tendency to develop cystic endometrial hyperplasia and uterine neoplasia. Factors for the development of these lesions could be cystic rete ovarii, hormone dysregulation, and/or age. Other factors could contribute to the development of uterine lesions. As in other species, early ovariohysterectomy could decrease the prevalence of uterine lesions.

  20. Corneal stromal dystrophies: a clinical pathologic study

    Directory of Open Access Journals (Sweden)

    Elvira Barbosa Abreu

    2012-12-01

    Full Text Available INTRODUCTION: Corneal dystrophy is defined as bilateral and symmetric primary corneal disease, without previous associated ocular inflammation. Corneal dystrophies are classified according to the involved corneal layer in superficial, stromal, and posterior dystrophy. Incidence of each dystrophy varies according to the geographic region studied. PURPOSE: To evaluate the prevalence of stromal corneal dystrophies among corneal buttons specimens obtained by penetrating keratoplasty (PK in an ocular pathology laboratory and to correlate the diagnosis with patient age and gender. METHODS: Corneal button cases of penetrating keratoplasty from January-1996 to May-2009 were retrieved from the archives of The Henry C. Witelson Ophthalmic Pathology Laboratory and Registry, Montreal, Canada. The cases with histopathological diagnosis of stromal corneal dystrophies were stained with special stains (Peroxid acid Schiff, Masson trichrome, Congo red analyzed under polarized light, and alcian blue for classification and correlated with epidemiological information (age at time of PK and gender from patients' file. RESULTS: 1,300 corneal buttons cases with clinical diagnose of corneal dystrophy were retrieved. Stromal corneal dystrophy was found in 40 (3.1% cases. Lattice corneal dystrophy was the most prevalent with 26 cases (65%. Nineteen were female (73.07% and the PK was performed at average age of 59.3 years old. Combined corneal dystrophy was found in 8 (20% cases, 5 (62.5% of them were female and the average age of the penetrating keratoplasty was 54.8 years old. Granular corneal dystrophy was represented by 5 (12.5% cases, and 2 (40% of them were female. Penetrating keratoplasty was performed at average age of 39.5 years old in granular corneal dystrophy cases. Macular corneal dystrophy was present in only 1 (2.5% case, in a 36 years old female. CONCLUSION: Systematic histopathological approach and evaluation, including special stains in all stromal

  1. The Role of Metacognition in Pathological Gambling: A Mediation Model.

    Science.gov (United States)

    Mansueto, Giovanni; Pennelli, Michele; De Palo, Valeria; Monacis, Lucia; Sinatra, Maria; De Caro, Maria Fara

    2016-03-01

    Pathological gambling involves multitudinous costs related to financial, legal, and public health care aspects, as well as to specific psychological disorders. Despite the overall evidence suggesting that comorbid disorders represent a risk factor for pathological gambling, there is scant evidence on the appropriate treatments for gamblers with such disorders. In this context, metacognitive therapy is an interesting approach because it considers psychological disorders as a result of the activation of perseverative cognitive processes and attentional strategies in response to inner events. Several studies report that metacognition is associated with different psychological problems. This study investigated the relationship among comorbid disorders, metacognition, and pathological gambling. 69 pathological gamblers at the first hospital admission and 58 controls drawn from general population (matched for age, gender, education) completed a battery of self report instruments: Symptom Checklist-90-R, Metacognition Questionnaire 30, South Oaks Gambling Scale. Compared to controls, pathological gamblers showed higher level of comorbid symptomatology and metacognition. Correlation analyses showed that: comorbid symptomatology and metacognition were positively and significantly correlated with pathological gambling; metacognition was positively and significantly associated with comorbid symptomatology. Mediation analysis indicated that dysfunctional metacognitive strategies could have an indirect effect on pathological gambling mediated by concurrent psychological disorders. These findings provide some implications for gambling treatment programs: pathological gamblers should be screened for psychiatric disorders, and metacognitive therapy could be considered a correct treatment of pathological gamblers. Metacognitive therapy might lead to the reduction of the pathological gambling by the diminishing of the concurrent psychological disorders.

  2. Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation

    Directory of Open Access Journals (Sweden)

    Sara Calafate

    2015-05-01

    Full Text Available Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer’s disease (AD. Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close distance between the cells, enhance the propagation of Tau pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in an artificial neuronal network using microfluidic devices, synapses and synaptic activity are promoting neuronal Tau pathology propagation in parallel to the non-synaptic mechanisms. Our work indicates that the physical presence of synaptic contacts between neurons facilitate Tau pathology propagation. These findings can have implications for synaptic repair therapies, which may turn out to have adverse effects by promoting propagation of Tau pathology.

  3. Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation.

    Science.gov (United States)

    Calafate, Sara; Buist, Arjan; Miskiewicz, Katarzyna; Vijayan, Vinoy; Daneels, Guy; de Strooper, Bart; de Wit, Joris; Verstreken, Patrik; Moechars, Diederik

    2015-05-26

    Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer's disease (AD). Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close distance between the cells, enhance the propagation of Tau pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in an artificial neuronal network using microfluidic devices, synapses and synaptic activity are promoting neuronal Tau pathology propagation in parallel to the non-synaptic mechanisms. Our work indicates that the physical presence of synaptic contacts between neurons facilitate Tau pathology propagation. These findings can have implications for synaptic repair therapies, which may turn out to have adverse effects by promoting propagation of Tau pathology.

  4. Analysis of mouse model pathology: a primer for studying the anatomic pathology of genetically engineered mice.

    Science.gov (United States)

    Cardiff, Robert D; Miller, Claramae H; Munn, Robert J

    2014-06-02

    This primer of pathology is intended to introduce investigators to the structure (morphology) of cancer with an emphasis on genetically engineered mouse (GEM) models (GEMMs). We emphasize the necessity of using the entire biological context for the interpretation of anatomic pathology. Because the primary investigator is responsible for almost all of the information and procedures leading up to microscopic examination, they should also be responsible for documentation of experiments so that the microscopic interpretation can be rendered in context of the biology. The steps involved in this process are outlined, discussed, and illustrated. Because GEMMs are unique experimental subjects, some of the more common pitfalls are discussed. Many of these errors can be avoided with attention to detail and continuous quality assurance.

  5. The effects of pathological gaming on aggressive behavior

    OpenAIRE

    Lemmens, J.S.; Valkenburg, P.M.; Peter, J.

    2011-01-01

    Studies have shown that pathological involvement with computer or video games is related to excessive gaming binges and aggressive behavior. Our aims for this study were to longitudinally examine if pathological gaming leads to increasingly excessive gaming habits, and how pathological gaming may cause an increase in physical aggression. For this purpose, we conducted a two-wave panel study among 851 Dutch adolescents (49% female) of which 540 played games (30% female). Our analyses indicated...

  6. Summary of the 4th nordic symposium on digital pathology

    Directory of Open Access Journals (Sweden)

    Claes Lundström

    2017-01-01

    Full Text Available The Nordic symposium on digital pathology (NDP was created to promote knowledge exchange across stakeholders in health care, industry, and academia. In 2016, the 4th NDP installment took place in Linköping, Sweden, promoting development and collaboration in digital pathology for the benefit of routine care advances. This article summarizes the symposium, gathering 170 attendees from 13 countries. This summary also contains results from a survey on integrated diagnostics aspects, in particular radiology-pathology collaboration.

  7. [Contact thermography in breast pathology. A critical review].

    Science.gov (United States)

    Sforza, M; Ballerini, A; Russo, R; Carzaniga, P L; Vertemati, G

    1991-04-30

    The paper reports the Authors' experience in over 12,000 patients affected by manifest or presumed breast pathologies examined using contact thermography and assess the number of correct responses. This technique proved reliable in patients aged under 30 with benign pathologies or palpable nodules. On the other hand, it was not reliable in the case of pathologies with negative objectivity, and therefore in the context of screening programmes for the early diagnosis of tumours.

  8. Expectations and essentials for the community practice of pathology

    OpenAIRE

    Horowitz, Richard E. MD

    2006-01-01

    In 3 surveys during the past 10 years, community hospital pathologists were asked what they want, need, or look for when employing a pathologist and, more specifically, what skills and knowledge a newly minted pathologist should have to be successful in the community practice of pathology. The most recent survey, done in spring of 2005, cited surgical pathology diagnosis, frozen section diagnosis, dissection, and fine-needle aspiration as essentials in anatomic pathology. For clinical gross, ...

  9. Clinical and Pathological Observation on Infectious Serositis of Duck

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    According to clinical and pathological observation in infectious serositis of duck, the main signs of this disease were diarrhoea, breathing with difficulty, head tremble and movement beyond coordination. The pathological changes that had been found in 30 experimental ducks were fibrous pericarditis, hepatitis, and encephalitis. The fibrous serositis, liver fatty degeneration or focus necrosis, nonsuppurative encephalitis and serous-fibrous pneumonia were typical pathological changes of histology.

  10. [Concept of occupational pathology service development in Kazakhstan].

    Science.gov (United States)

    Amanbekova, A U; Sakiev, K Z; Dzhakupbekova, G M; Ibrayeva, L K

    2015-01-01

    Improvement of occupational medical care management is aimed to preserve workers' health through better prevention, early diagnosis and rehabilitation of occupational diseases. Strategic directions of occupational pathology service development are improvement of legislation base on occupational diseases, modernization of occupational pathology service, development of personnel resources system, advancement of research activity in medical ecology, industrial hygiene and occupational pathology and increased efficiency of intra-sectoral and inter-agency interactions about workers' health preservation.

  11. Copper enhances amyloid-beta peptide neurotoxicity and non beta-aggregation: a series of experiments conducted upon copper-bound and copper-free amyloid-beta peptide.

    Science.gov (United States)

    Dai, Xueling; Sun, Yaxuan; Gao, Zhaolan; Jiang, Zhaofeng

    2010-05-01

    Alzheimer's disease is characterized by the abnormal aggregation of amyloid-beta peptide (Abeta) in extracellular deposits known as senile plaques. However, the nature of the toxic Abeta species and its precise mechanism of action remain unclear. Previous reports suggest that the histidine residues are involved in copper-Abeta interaction, by which resulting in the neurotoxicity of Abeta and free radical damage. Here, we employed a mutant Abeta (Abeta H13R) in which a histidine residue was replaced by arginine. Copper facilitated the precipitation of both wild-type and mutant Abeta in the spectrophotometric absorbance assay but suppressed beta-structure aggregates according to Thioflavine-T assay. Wild-type Abeta alone is more cytotoxic but produced less amount of H(2)O(2) than AbetaH13R-copper complexes, suggesting that Abeta-membrane interaction may also implicated in the pathologic progress. Abeta toxicity is in positive correlation to its competence to aggregate despite the aggregation is mainly composed of non-beta fibril substances. In short, these findings may provide further evidence on the role of copper in the pathogenesis of Alzheimer's disease.

  12. Characteristics, circumstances and pathology of sudden or unnatural deaths of cases with evidence of pathological hoarding.

    Science.gov (United States)

    Darke, Shane; Duflou, Johan

    2017-01-01

    The study aimed to determine the characteristics and circumstances of cases sudden or unnatural death (n = 61) with evidence of pathological hoarding, their major organ pathology and toxicology. The mean age was 65·8 yrs (a mean of 16.1 years of potential life lost), 62·3% were male, and 28·2% were obese. 95·1% lived alone, and 96·7% died in their residence, with no medical intervention. In all cases severe squalor and extensive hoarding were noted. The direct cause of death was attributed to disease in 75·4%, heart disease being a significant factor in 52·5%. Accidents causing death directly related to hoarding occurred in two cases. Autopsy revealed extensive pathology: severe coronary artery narrowing (42·4%), myocardial replacement fibrosis (44·1%), emphysema (39·0%), nephrosclerosis (46·6%). Signs of hypothermia were present in 14·8%, and diabetes was diagnosed in 21·3%. The most commonly detected substance was alcohol (32·1%). Medications for heart disease (5·4%) or diabetes (7·1%) were rare. The overall clinical picture was of an isolated group, with a heavy burden of physical disease and, in all probability, a high level of psychiatric disorders, who died alone in their homes.

  13. Error-free pathology: applying lean production methods to anatomic pathology.

    Science.gov (United States)

    Condel, Jennifer L; Sharbaugh, David T; Raab, Stephen S

    2004-12-01

    The current state of our health care system calls for dramatic changes. In their pathology department, the authors believe these changes may be accomplished by accepting the long-term commitment of applying a lean production system. The ideal state of zero pathology errors is one that should be pursued by consistently asking, "Why can't we?" The philosophy of lean production systems began in the manufacturing industry: "All we are doing is looking at the time from the moment the customer gives us an order to the point when we collect the cash. And we are reducing that time line by removing non-value added wastes". The ultimate goals in pathology and overall health care are not so different. The authors' intention is to provide the patient (customer) with the most accurate diagnostic information in a timely and efficient manner. Their lead histotechnologist recently summarized this philosophy: she indicated that she felt she could sleep better at night knowing she truly did the best job she could. Her chances of making an error (in cutting or labeling) were dramatically decreased in the one-by-one continuous flow work process compared with previous practices. By designing a system that enables employees to be successful in meeting customer demand, and by empowering the frontline staff in the development and problem solving processes, one can meet the challenges of eliminating waste and build an improved, efficient system.

  14. Web-based pathology practice examination usage

    Directory of Open Access Journals (Sweden)

    Edward C Klatt

    2014-01-01

    Full Text Available Context: General and subject specific practice examinations for students in health sciences studying pathology were placed onto a free public internet web site entitled web path and were accessed four clicks from the home web site menu. Subjects and Methods: Multiple choice questions were coded into. html files with JavaScript functions for web browser viewing in a timed format. A Perl programming language script with common gateway interface for web page forms scored examinations and placed results into a log file on an internet computer server. The four general review examinations of 30 questions each could be completed in up to 30 min. The 17 subject specific examinations of 10 questions each with accompanying images could be completed in up to 15 min each. The results of scores and user educational field of study from log files were compiled from June 2006 to January 2014. Results: The four general review examinations had 31,639 accesses with completion of all questions, for a completion rate of 54% and average score of 75%. A score of 100% was achieved by 7% of users, ≥90% by 21%, and ≥50% score by 95% of users. In top to bottom web page menu order, review examination usage was 44%, 24%, 17%, and 15% of all accessions. The 17 subject specific examinations had 103,028 completions, with completion rate 73% and average score 74%. Scoring at 100% was 20% overall, ≥90% by 37%, and ≥50% score by 90% of users. The first three menu items on the web page accounted for 12.6%, 10.0%, and 8.2% of all completions, and the bottom three accounted for no more than 2.2% each. Conclusions: Completion rates were higher for shorter 10 questions subject examinations. Users identifying themselves as MD/DO scored higher than other users, averaging 75%. Usage was higher for examinations at the top of the web page menu. Scores achieved suggest that a cohort of serious users fully completing the examinations had sufficient preparation to use them to support

  15. Oxidative stress in patients with endodontic pathologies

    Directory of Open Access Journals (Sweden)

    Vengerfeldt V

    2017-08-01

    Full Text Available Veiko Vengerfeldt,1 Reet Mändar,2,3 Mare Saag,1 Anneli Piir,2 Tiiu Kullisaar2 1Institute of Dental Sciences, Faculty of Medicine, University of Tartu, 2Institute of Biomedicine and Translational Medicine, Faculty of Medicine, University of Tartu, 3Competence Centre on Health Technologies, Tartu, Estonia Background: Apical periodontitis (AP is an inflammatory disease affecting periradicular tissues. It is a widespread condition but its etiopathogenetic mechanisms have not been completely elucidated and the current treatment options are not always successful.Purpose: To compare oxidative stress (OxS levels in the saliva and the endodontium (root canal [RC] contents in patients with different endodontic pathologies and in endodontically healthy subjects.Patients and methods: The study group of this comparison study included 22 subjects with primary chronic apical periodontitis (pCAP, 26 with posttreatment or secondary chronic apical periodontitis (sCAP, eight with acute periapical abscess, 13 with irreversible pulpitis, and 17 healthy controls. Resting saliva samples were collected before clinical treatment. Pulp samples (remnants of the pulp, tooth tissue, and/or previous root filling material were collected under strict aseptic conditions using the Hedström file. The samples were frozen to −80°C until analysis. OxS markers (myeloperoxidase [MPO], oxidative stress index [OSI], 8-isoprostanes [8-EPI] were detected in the saliva and the endodontium. Results: The highest MPO and 8-EPI levels were seen in pCAP and pulpitis, while the highest levels of OSI were seen in pCAP and abscess patients, as well as the saliva of sCAP patients. Controls showed the lowest OxS levels in both RC contents and saliva. Significant positive correlations between OxS markers, periapical index, and pain were revealed. Patients with pain had significantly higher OxS levels in both the endodontium (MPO median 27.9 vs 72.6 ng/mg protein, p=0.004; OSI 6.0 vs 10.4, p<0

  16. Ancestry and pathology in King Tutankhamun's family.

    Science.gov (United States)

    Hawass, Zahi; Gad, Yehia Z; Ismail, Somaia; Khairat, Rabab; Fathalla, Dina; Hasan, Naglaa; Ahmed, Amal; Elleithy, Hisham; Ball, Markus; Gaballah, Fawzi; Wasef, Sally; Fateen, Mohamed; Amer, Hany; Gostner, Paul; Selim, Ashraf; Zink, Albert; Pusch, Carsten M

    2010-02-17

    The New Kingdom in ancient Egypt, comprising the 18th, 19th, and 20th dynasties, spanned the mid-16th to the early 11th centuries bc. The late 18th dynasty, which included the reigns of pharaohs Akhenaten and Tutankhamun, was an extraordinary time. The identification of a number of royal mummies from this era, the exact relationships between some members of the royal family, and possible illnesses and causes of death have been matters of debate. To introduce a new approach to molecular and medical Egyptology, to determine familial relationships among 11 royal mummies of the New Kingdom, and to search for pathological features attributable to possible murder, consanguinity, inherited disorders, and infectious diseases. From September 2007 to October 2009, royal mummies underwent detailed anthropological, radiological, and genetic studies as part of the King Tutankhamun Family Project. Mummies distinct from Tutankhamun's immediate lineage served as the genetic and morphological reference. To authenticate DNA results, analytical steps were repeated and independently replicated in a second ancient DNA laboratory staffed by a separate group of personnel. Eleven royal mummies dating from circa 1410-1324 bc and suspected of being kindred of Tutankhamun and 5 royal mummies dating to an earlier period, circa 1550-1479 bc, were examined. Microsatellite-based haplotypes in the mummies, generational segregation of alleles within possible pedigree variants, and correlation of identified diseases with individual age, archeological evidence, and the written historical record. Genetic fingerprinting allowed the construction of a 5-generation pedigree of Tutankhamun's immediate lineage. The KV55 mummy and KV35YL were identified as the parents of Tutankhamun. No signs of gynecomastia and craniosynostoses (eg, Antley-Bixler syndrome) or Marfan syndrome were found, but an accumulation of malformations in Tutankhamun's family was evident. Several pathologies including Köhler disease

  17. Curbing activation: proprotein convertases in homeostasis and pathology

    National Research Council Canada - National Science Library

    Taylor, Neil A; Van De Ven, Wim J M; Creemers, John W M

    2003-01-01

    ... and is involved in the pathology of diseases such as cancer, viral infection, and Alzheimer's disease. Recent studies using PC inhibitors have demonstrated their potential as therapeutic targets...

  18. Pathologists overseas: coordinating volunteer pathology services for 19 years.

    Science.gov (United States)

    Hoenecke, Heinz; Lee, Victor; Roy, Indrojit

    2011-02-01

    Pathologists Overseas is a nonprofit organization that has been coordinating the efforts of volunteer pathologists and technologists for 19 years to improve and provide affordable pathology services to underserved patients worldwide. This is accomplished by aiding and establishing pathology laboratories, providing diagnostic pathology services, and training local physicians as pathologists. Projects have been completed or are currently active in Kenya, Eritrea, Madagascar, Ghana, Nepal, Bhutan, Peru, El Salvador, and St Lucia. The main challenge is finding enough volunteers to provide uninterrupted service to maintain a project. Our goal is to build on these experiences and continue to both support existing and establish more pathology laboratories worldwide.

  19. Role of mitochondria in parvovirus pathology.

    Directory of Open Access Journals (Sweden)

    Jonna Nykky

    Full Text Available Proper functioning of the mitochondria is crucial for the survival of the cell. Viruses are able to interfere with mitochondrial functions as they infect the host cell. Parvoviruses are known to induce apoptosis in infected cells, but the role of the mitochondria in parvovirus induced cytopathy is only partially known. Here we demonstrate with confocal and electron microscopy that canine parvovirus (CPV associated with the mitochondrial outer membrane from the onset of infection. During viral entry a transient depolarization of the mitochondrial transmembrane potential and increase in ROS level was detected. Subsequently, mitochondrial homeostasis was normalized shortly, as detected by repolarization of the mitochondrial membrane and decrease of ROS. Indeed, activation of cell survival signalling through ERK1/2 cascade was observed early in CPV infected cells. At 12 hours post infection, concurrent with the expression of viral non-structural protein 1, damage to the mitochondrial structure and depolarization of its membrane were apparent. Results of this study provide additional insight of parvovirus pathology and also more general information of virus-mitochondria association.

  20. [The molecular pathology of classical Hodgkin lymphoma].

    Science.gov (United States)

    Asano, Naoko

    2015-10-01

    In 1832, Dr. Thomas Hodgkin reported the first cases with this malignancy, which came to be named Hodgkin's disease. The cells that are a hallmark of this disease, Hodgkin and Reed-Sternberg (HRS) cells, account for only 1% of those in tumor tissues, with the majority of cells in Hodgkin lymphoma being of various inflammatory types. Advances in molecular techniques have contributed to molecular biological analysis of HRS cells. Intriguingly, HRS cells are derived from germinal center B-cells, but have lost their B-cell gene-expression and co-express non-B-cell genes. Multiple signaling pathways, including the NFκB and JAK/STAT pathways, show deregulated activity in HRS cells, suggesting an important role for these pathways in the pathogenesis of Hodgkin lymphoma. This article describes the molecular pathological characteristics of HRS cells: 1) the cellular origin of HRS cells, 2) deregulated gene expression in HRS cells, 3) genetic alterations and 4) epigenetic alterations in HRS cells, 5) the lost B-cell phenotype of HRS cells, 6) the role of EBV in Hodgkin lymphoma pathogenesis, and 7) micro-environmental interactions between HRS and reactive cells.

  1. Ocular pathology in congenital heart disease.

    Science.gov (United States)

    Mansour, A M; Bitar, F F; Traboulsi, E I; Kassak, K M; Obeid, M Y; Megarbane, A; Salti, H I

    2005-01-01

    To describe the ocular findings in subjects with congenital heart disease (CHD). In a prospective study, the same observer examined 240 consecutive patients with CHD admitted to the medical centre. Two independent geneticists performed identification of syndromes. The commonest anatomic cardiac anomalies were ventricular or atrial septal defects (62), tetralogy of Fallot (39), pulmonary stenosis (25), and transposition of the great arteries (24). The heart lesions were divided physiologically into volume overload (90), cyanotic (87), and obstructive (63). In all, 105 syndromic subjects included the velocardiofacial syndrome (18), Down's syndrome (17), CHARGE association (6), DiGeorge syndrome (5), Williams syndrome (3), Edwards syndrome (3), Noonan syndrome (3), VACTERL association (2), and Patau syndrome (trisomy 13) (2). The paediatric team recognized 51 patients as syndromic. Two independent geneticists recognized additional 54 patients as syndromic. Positive eye findings were present in 55% (132) and included retinal vascular tortuosity (46), optic disc hypoplasia (30), trichomegaly (15), congenital ptosis (12), strabismus (11), retinal haemorrhages (8), prominent eyes (7), and congenital cataract (6). There was a strong correlation between the retinal vascular tortuosity and both a low haematocrit (P=0.000) and a low arterial oxygen saturation (P=0.002). Patients with CHD are at a high risk for ocular pathology and need screening for various ocular abnormalities.

  2. Pathologic Collision of Inverted Papilloma with Esthesioneuroblastoma

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    Sana D Karam

    2014-03-01

    Full Text Available Background: Inverted papilloma (IP of the nasal cavity is a benign tumor that 0.5-4% of all nasal tumors and have been known to rarely undergo malignant transformation to squamous carcinoma an even more rarely adenocarcinoma. Synchronous association with low grade esthesioneuroblastoma (ENB has been reported in only one case report where a small sized lesion was treated with surgery alone. Here we report the first case of invasion of IP by high grade ENB with nodal metastasis that was treated with combined modality therapy.Case Presentation: A case of a 64 year-old African American gentleman presented to the otolaryngology with a three-month history of recurrent epistaxis. Imaging revealed a large right nasal cavity mass extending into the right sphenoid sinus but without intracranial extension. Surgical pathology revealed high grade ENB invading IP. An orbitofrontal craniotomy approach was used to achieve complete resection of the mass but with positive margins. Postoperative PET/CT showed nodal metastasis. The patient was then treated with adjuvant chemoradiation and remains without evidence of disease at 42 months post-treatment. We discuss the disease presentation, histopathologic features, and disease management with literature support.Conclusion: In this very rare disease presentation where two extremely rare malignancies collide, we show that aggressive management with trimodality therapy of surgery, adjuvant radiation with stereotactic radiosurgical boost, and adjuvant chemotherapy gives excellent results. Given the natural history of the disease, however, long follow up is needed to declare complete freedom from the disease.

  3. Sonography of pathological changes in the hand.

    Science.gov (United States)

    Dębek, Anna; Czyrny, Zbigniew; Nowicki, Paweł

    2014-03-01

    Everyday medical practice shows that most common problems within the hand result from overload, injuries and degeneration. Dorsal side pathologies such as de Quervain's and Wartenberg's disease, intersection syndrome or degenerative lesions of carpometa-carpal joint of the thumb discussed in the paper can be accurately diagnosed and differentiated by means of ultrasound examination. Ultrasound is similarly powerful in detection and grading of traumatic lesions involving extensor tendons and their sagittal bands or the flexor tendons and their pulleys. In the case of carpal tunnel syndrome one can not only visualize the median nerve but also other structures of the tunnel that may cause compression. Similarly ulnar nerve compression within the Guyon's canal can be well evaluated. In cases of nerve trauma one can precisely define the level, and in cases of nerve discontinuity, the distance between stumps can be measured which is important in surgery planning. Often nerve trauma is a sequelae of tendon reconstruction. In such cases scars and nerve entrapment can be depicted. Tumors within a hand are usually benign, of which the most common are ganglia. On ultrasound examination a connection between a ganglion and its source (usually a joint or sheath) can frequently be defined. The relationship of tumors to nerves, tendon sheaths or vessels may suggest their nature. Ultrasound with dynamic tissue assessment is a very valuable adjunct to clinical examination.

  4. Impulsive Behaviors in Patients With Pathological Buying.

    Science.gov (United States)

    Zander, Heike; Claes, Laurence; Voth, Eva M; de Zwaan, Martina; Müller, Astrid

    2016-09-01

    Aim To investigate impulsive behaviors in pathological buying (PB). Methods The study included three groups matched for age and gender: treatment seeking outpatients with PB (PB+), treatment seeking psychiatric inpatients without PB (PB-), and a healthy control group (HC). PB was assessed by means of the Compulsive Buying Scale and by the impulse control disorder (ICD) module of the research version of the Structured Clinical Interview for DSM-IV (SCID-ICD). All participants answered questionnaires concerning symptoms of borderline personality disorder, self-harming behaviors, binge eating and symptoms of attention deficit and hyperactivity disorder (ADHD). In addition, comorbid ICDs were assessed using the SCID-ICD. Results The PB+ and PB- groups did not differ with regard to borderline personality disorder or ADHD symptoms, but both groups reported significantly more symptoms than the HC group. Frequencies of self-harming behaviors did not differ between the three groups. Patients with PB were more often diagnosed with any current ICD (excluding PB) compared to those without PB and the HC group (38.7% vs. 12.9% vs. 12.9%, respectively, p=.017). Discussion Our findings confirm prior research suggesting more impulsive behaviors in patients with and without PB compared to healthy controls. The results of the questionnaire-based assessment indicate that outpatients with PB perceive themselves equally impulsive and self-harm as frequently as inpatients without PB; but they seem to suffer more often from an ICD as assessed by means of an interview.

  5. New insights in prolactin: pathological implications.

    Science.gov (United States)

    Bernard, Valérie; Young, Jacques; Chanson, Philippe; Binart, Nadine

    2015-05-01

    Prolactin is a hormone that is mainly secreted by lactotroph cells of the anterior pituitary gland, and is involved in many biological processes including lactation and reproduction. Animal models have provided insights into the biology of prolactin proteins and offer compelling evidence that the different prolactin isoforms each have independent biological functions. The major isoform, 23 kDa prolactin, acts via its membrane receptor, the prolactin receptor (PRL-R), which is a member of the haematopoietic cytokine superfamily and for which the mechanism of activation has been deciphered. The 16 kDa prolactin isoform is a cleavage product derived from native prolactin, which has received particular attention as a result of its newly described inhibitory effects on angiogenesis and tumorigenesis. The discovery of multiple extrapituitary sites of prolactin secretion also increases the range of known functions of this hormone. This Review summarizes current knowledge of the biology of prolactin and its receptor, as well as its physiological and pathological roles. We focus on the role of prolactin in human pathophysiology, particularly the discovery of the mechanism underlying infertility associated with hyperprolactinaemia and the identification of the first mutation in human PRLR.

  6. Role of mitochondria in parvovirus pathology.

    Science.gov (United States)

    Nykky, Jonna; Vuento, Matti; Gilbert, Leona

    2014-01-01

    Proper functioning of the mitochondria is crucial for the survival of the cell. Viruses are able to interfere with mitochondrial functions as they infect the host cell. Parvoviruses are known to induce apoptosis in infected cells, but the role of the mitochondria in parvovirus induced cytopathy is only partially known. Here we demonstrate with confocal and electron microscopy that canine parvovirus (CPV) associated with the mitochondrial outer membrane from the onset of infection. During viral entry a transient depolarization of the mitochondrial transmembrane potential and increase in ROS level was detected. Subsequently, mitochondrial homeostasis was normalized shortly, as detected by repolarization of the mitochondrial membrane and decrease of ROS. Indeed, activation of cell survival signalling through ERK1/2 cascade was observed early in CPV infected cells. At 12 hours post infection, concurrent with the expression of viral non-structural protein 1, damage to the mitochondrial structure and depolarization of its membrane were apparent. Results of this study provide additional insight of parvovirus pathology and also more general information of virus-mitochondria association.

  7. Clinical and pathological features of pachyonychia congenita.

    Science.gov (United States)

    Leachman, Sancy A; Kaspar, Roger L; Fleckman, Philip; Florell, Scott R; Smith, Frances J D; McLean, W H Irwin; Lunny, Declan P; Milstone, Leonard M; van Steensel, Maurice A M; Munro, Colin S; O'Toole, Edel A; Celebi, Julide T; Kansky, Aleksej; Lane, E Birgitte

    2005-10-01

    Pachyonychia congenita (PC) is a rare genodermatosis affecting the nails, skin, oral mucosae, larynx, hair, and teeth. Pathogenic mutations in keratins K6a or K16 are associated with the PC-1 phenotype whereas K6b and K17 mutations are associated with the PC-2 phenotype. Analysis of clinical, pathological, and genetic data from the literature and two research registries reveal that >97% of PC cases exhibit fingernail and toenail thickening, and painful plantar keratoderma. Prospective evaluation of 57 PC patients from 41 families revealed variable clinical findings: hyperhidrosis (79%), oral leukokeratosis (75%), follicular keratosis (65%), palmar keratoderma (60%), cutaneous cysts (35%), hoarseness or laryngeal involvement (16%), coarse or twisted hair (26%), early primary tooth loss (14%), and presence of natal or prenatal teeth (2%). Stratification of these data by keratin mutation confirmed the increased incidence of cyst formation and natal teeth among PC-2 patients, although cysts were more commonly seen in PC-1 than previously reported (25%-33%). Previously unreported clinical features of PC include development of painful oral and nipple lesions during breastfeeding, copious production of waxy material in ears, and inability to walk without an ambulatory aid (50%). Possible pathogenic mechanisms are discussed with respect to the clinicopathologic and genetic correlations observed.

  8. Minimally invasive surgery for Achilles tendon pathologies

    Directory of Open Access Journals (Sweden)

    Nicola Maffulli

    2010-07-01

    Full Text Available Nicola Maffulli1, Umile Giuseppe Longo2, Filippo Spiezia2, Vincenzo Denaro21Centre for Sports and Exercise Medicine, Barts and The London School of Medicine and Dentistry, London, England; 2Department of Orthopedic and Trauma Surgery, Campus Bio-Medico University, Rome, ItalyAbstract: Minimally invasive trauma and orthopedic surgery is increasingly common, though technically demanding. Its use for pathologies of the Achilles tendon (AT hold the promise to allow faster recovery times, shorter hospital stays, and improved functional outcomes when compared to traditional open procedures, which can lead to difficulty with wound healing because of the tenuous blood supply and increased chance of wound breakdown and infection. We present the recent advances in the field of minimally invasive AT surgery for tendinopathy, acute ruptures, chronic tears, and chronic avulsions of the AT. In our hands, minimally invasive surgery has provided similar results to those obtained with open surgery, with decreased perioperative morbidity, decreased duration of hospital stay, and reduced costs. So far, the studies on minimally invasive orthopedic techniques are of moderate scientific quality with short follow-up periods. Multicenter studies with longer follow-up are needed to justify the long-term advantages of these techniques over traditional ones.Keywords: tendinopathy, rupture, percutanous repair, less invasive

  9. Varieties of Pathological Self-Mutilation

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    Armando R. Favazza

    1990-01-01

    Full Text Available Pathological self-mutilation appears as a non-specific symptom as well as a specific syndrome. Since psychotic persons may commit horrifying acts, such as enucleation of an eye or amputation of a body part, identification of high risk patients is crucial. Stereotypical self-mutilation, such as head banging and biting off of fingertips, is associated with mental retardation and with the syndromes of Lesch-Nyhan, deLange, and Tourette. This type of self-mutilation is the focus of biological research or endorphins and on dopamine receptors. Skin cutting and burning, the most common type of self-mutilation, is often associated with personality disorders, post-traumatic stress disorder, and multiple personality disorder. When cutting and burning become established as responses to disturbing psychological symptoms on environmental events, a specific Axis I impulse disorder known as Repetitive Self Mutilation may be diagnosed. Patients with this newly identified syndrome may alternate their direct acts of self-mutilation with eating disorders and episodic alcoholism.

  10. Sonography of pathological changes in the hand

    Directory of Open Access Journals (Sweden)

    Anna Dębek

    2014-03-01

    Full Text Available Everyday medical practice shows that most common problems within the hand result from overload, injuries and degeneration. Dorsal side pathologies such as de Quervain’s and Wartenberg’s disease, intersection syndrome or degenerative lesions of carpometacarpal joint of the thumb discussed in the paper can be accurately diagnosed and differentiated by means of ultrasound examination. Ultrasound is similarly powerful in detection and grading of traumatic lesions involving extensor tendons and their sagittal bands or the flexor tendons and their pulleys. In the case of carpal tunnel syndrome one can not only visualize the median nerve but also other structures of the tunnel that may cause compression. Similarly ulnar nerve compression within the Guyon’s canal can be well evaluated. In cases of nerve trauma one can precisely define the level, and in cases of nerve discontinuity, the distance between stumps can be measured which is important in surgery planning. Often nerve trauma is a sequelae of tendon reconstruction. In such cases scars and nerve entrapment can be depicted. Tumors within a hand are usually benign, of which the most common are ganglia. On ultrasound examination a connection between a ganglion and its source (usually a joint or sheath can frequently be defined. The relationship of tumors to nerves, tendon sheaths or vessels may suggest their nature. Ultrasound with dynamic tissue assessment is a very valuable adjunct to clinical examination.

  11. Pathology of thyroid in acquired immunodeficiency syndrome

    Directory of Open Access Journals (Sweden)

    Dhaneshwar Namdeorao Lanjewar

    2016-01-01

    Full Text Available Background: The course of human immunodeficiency virus infection and the acquired immunodeficiency syndrome can be complicated by a variety of endocrine abnormalities, including abnormalities of thyroid gland. Materials and Methods: This study was designed to understand the spectrum of pathology of thyroid in Indian patients with AIDS. The present study describes the findings of retrospective autopsy findings of 158 patients with AIDS which revealed infectious diseases from a time period before the use of highly active antiretroviral regimen. Results: A wide range of bacterial, fungal, and viral infections were observed. Tuberculosis was recorded in 14 (09% patients, Cryptococcus neoformans in 11 (7% patients and cytomegalovirus in 3 (2% patients. Hashimoto's thyroiditis and lymphocytic thyroiditis were seen in 02 (01% patients each. One patient had dual infection comprising of tuberculosis and cytomegalovirus infection. The other microscopic findings observed were goiter (2 patients, interstitial fibrosis in thyroid (7 patients, and calcification in thyroid (8 patients. Conclusions: Abnormalities of thyroid are uncommon findings in patients with HIV infection however several case reports of thyroid involvement by infectious agents and neoplasm are described in these patients; hence patients with HIV infection should be closely followed up for development of goiter or abnormalities of thyroid functions.

  12. [Folic acid in physiology and pathology].

    Science.gov (United States)

    Czeczot, Hanna

    2008-08-13

    This paper presents current knowledge of the biological functions of folic acid, the effects of its deficiency in the organism, as well as the possibilities of its therapeutic use. Folic acid (folate, B9) is a vitamin of special importance in normal cellular functions. Tetrahydrofolate (TH4-folate) is the biologically active form of folic acid. The main role of folic acid in biochemistry is the single-carbon transfer reaction (e.g. transfer of a methyl, methylene, or formyl group). Folic acid is involved in the transformation of certain amino acids as well as in the synthesis of purines and dTMP (2'-deoxythymidine-5'-phosphate) needed for the synthesis of nucleic acid (DNA), required by all rapidly growing cells. In humans, folate deficiency results in serious pathologies, the most important of which are neural tube defects, megablastic anemia, acceleration of the arteriosclerotic process, changes in the central nervous system, and the development of certain types of cancer. To increase the intake of folic acid, preventive actions include dietary education, the main objectives of which are to increase the intake of natural folate in the daily diet, add folic acid to selected dietary products (e.g. fl our, pasta, rice), and encourage supplementation with folic acid-containing pharmaceuticals.

  13. AID Biology: A pathological and clinical perspective.

    Science.gov (United States)

    Choudhary, Meenal; Tamrakar, Anubhav; Singh, Amit Kumar; Jain, Monika; Jaiswal, Ankit; Kodgire, Prashant

    2017-09-21

    Activation-induced cytidine deaminase (AID), primarily expressed in activated mature B lymphocytes in germinal centers, is the key factor in adaptive immune response against foreign antigens. AID is responsible for producing high-affinity and high-specificity antibodies against an infectious agent, through the physiological DNA alteration processes of antibody genes by somatic hypermutation (SHM) and class-switch recombination (CSR) and functions by deaminating deoxycytidines (dC) to deoxyuridines (dU), thereby introducing point mutations and double-stranded chromosomal breaks (DSBs). The beneficial physiological role of AID in antibody diversification is outweighed by its detrimental role in the genesis of several chronic immune diseases, under non-physiological conditions. This review offers a comprehensive and better understanding of AID biology and its pathological aspects, as well as addresses the challenges involved in AID-related cancer therapeutics, based on various recent advances and evidence available in the literature till date. In this article, we discuss ways through which our interpretation of AID biology may reflect upon novel clinical insights, which could be successfully translated into designing clinical trials and improving patient prognosis and disease management.

  14. Arthroscopy of the knee without pathological findings.

    Science.gov (United States)

    Schlepckow, P; Weber, M; Hempel, K

    1994-01-01

    From 1983 to 1990, 82 knee arthroscopies (8.2%) carried out in our patients found nothing pathological. Sixty-four percent of these patients were active in sports, but trauma was noted in 32% of the cases only. Football and other ball games, skiing, and track and field athletics were the main causes. Twenty-six percent of the patients had undergone previous surgery in the affected knee. At a mean of 4.6 years postoperatively, clinical and radiological re-assessment was conducted so as to compare our pre- and intraoperative findings with the further course of events. We found that 48.2% of the patients were symptom-free after the diagnostic arthroscopy, 37.5% had persistent discomfort and 14.3% had a recurrence of discomfort after 6 months to 2 years. The objective measurement score (Zarins Rowe score), at 47.5 out of 50 points, was better than the subjective score, at 40 out of 50 points. Our diagnoses had to be changed retrospectively: meniscal lesions were diagnosed too frequently, while chondropathia patellae and instability were often missed. Additionally, complaints could be related to abnormal axis, limited range of motion of the hip or knee, leg length inequality and hypermobility. Being unable to verify a presumed intra-articular lesion arthroscopically is frustrating for both doctor and patient. Our data suggest that meniscal signs should be looked at more critically and emphasise the need for a complete evaluation of the whole locomotor system.

  15. Lung vasculitis and alveolar hemorrhage: pathology.

    Science.gov (United States)

    Fishbein, Gregory A; Fishbein, Michael C

    2011-06-01

    Pulmonary vasculitides are a diverse group of limited and systemic disorders associated with inflammation of pulmonary vessels and parenchyma. These diseases often have distinctive clinical, serological, and histopathological features-extrapulmonary sites of involvement, circulating autoantibodies, predispositions for small or large vessels, and others. Some have characteristic inflammatory lesions; others are characterized by the absence of such lesions. Frequently pathological findings overlap, rendering classification, and diagnosis a challenge. The anti-neutrophil cytoplasmic antibody (ANCA)-associated small-vessel diseases constitute the major pulmonary vasculitides. These include Wegener granulomatosis (WG), Churg Strauss syndrome (CSS), and microscopic polyangiitis (MPA). Less frequently, diseases such as polyarteritis nodosa, Takayasu arteritis, Behçet syndrome, and connective tissue diseases may involve pulmonary vessels, but these entities are better associated with extrapulmonary disease. Diffuse alveolar hemorrhage (DAH) is a severe manifestation of pulmonary vasculitis. DAH is most commonly seen in small-vessel vasculitides, specifically MPA and WG. Other syndromes associated with DAH include Goodpasture syndrome, Henoch-Schönlein purpura, and systemic lupus erythematosus. Less commonly, DAH may be secondary to infection or drugs/toxins. Furthermore, in the absence of discernable systemic disease, DAH may be idiopathic-referred to as isolated pulmonary capillaritis (IPC) or idiopathic pulmonary hemosiderosis (IPH), depending on the presence of capillaritis.

  16. [Dreams in normal and pathological aging].

    Science.gov (United States)

    Guénolé, Fabian; Marcaggi, Geoffrey; Baleyte, Jean-Marc; Garma, Lucile

    2010-06-01

    Although most of scientific knowledge in dream research is based on young adult studies, this article provides a review of the effects of normal and pathological aging on dream psychology. It starts with preliminary comments about epistemological and methodological principles of dream research, its singularities in aged persons, and the modifications of sleep physiology with age. The whole literature agrees that dream recall progressively decreases from the beginning of adulthood - not in old age - and that dream reports become less intense, perceptually and emotionally. This evolution occurs faster in men than women, with gender differences in the content of dreams. The chronological modifications could be explained partly by changes in lifestyle and attitude towards dreams in early adulthood, but mainly by modifications of sleep physiology, particularly the decrease and qualitative changes of rapid eye movement (REM) sleep. Dreams have usually little subjective importance in the mental life of aged persons. However, working with dreams can be a valuable tool for psychotherapy in the aged. According to the few existing data, patients suffering degenerative dementia dream much less than healthy aged persons. In Alzheimer's disease, this could be linked to the decrease of REM sleep, and atrophy of associative sensory areas of the cerebral cortex. Most studied aspects of dreaming in degenerative cognitive disorders are REM sleep behavior disorders, and nightmares induced by cholinesterase inhibitors. More studies are needed to better characterize the evolution of dreams with age, particularly studies performed in sleep laboratory.

  17. Mammary Fibromatosis: Sonographic Features and Pathologic Correlations

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    Jung, Hae Kyoung; Ko, Kyung Hee; Rho, Ji Young; Kang, Hye Yoon [Cha University College of Medicine, Pocheon (Korea, Republic of); Kim, Eun Kyung [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2010-09-15

    The purpose of this study was to determine if the sonographic features of mammary fibromatosis had correlation with the pathologic findings. We identified four cases of fibromatosis of the breast at our institution over a 10-year period. The patients were all women, and they ranged from 25 to 48 years of age (mean, 34.3 years). All four patients complained of palpable breast masses and were subsequently diagnosed with mammary fibromatosis. We retrospectively reviewed their imaging findings. Mammography obtained in one patient revealed architectural distortion. On sonography, all four cases showed spiculated, irregular, hypoechoic masses that could not be differentiated from malignant lesions. After surgical excision and vacuum assisted biopsy of the masses in four patients, there was no recurrence on clinical or sonographic follow-up over a 13-36 month period. Although mammary fibromatosis is a very rare condition, it should be included in the differential diagnosis when an un-calcified, spiculated, irregular and hypoechoic masses are encountered on breast sonography

  18. From pathological to professional: gambling stories

    Directory of Open Access Journals (Sweden)

    Andrada-Mihaela Istrate

    2011-11-01

    Full Text Available Theories on gambling are as disparate as they are diverse. While on the one hand gambling is condemned as being pathological, a curable addiction, on the other it is regarded as merely leisure. While playing on the exterior features of gambling, these two perspectives narrow the vistas of gambling research. I contribute to the debate by treating gambling (poker playing in particular through the meaning conveyed by players upon it, discussing games and play as part and parcel of everyday experience. My research is centered on how poker players make professional claims and the way they justify poker playing as a profession. By discussing games as world building practices (Schutz, 1945; Huizinga, 1950; Goffman, 1961 I deemphasize the deviant character gambling actuates and advert on its informative potential on emergent societal and cultural transformations. Making a living out of poker, making sense of the game, at the same time, as a lens that organizes their way of going through the world, players connect the reality of the world of daily life to the reality of the game. I argue that the horizons of this finite province of meaning (Schutz, 1945 are not confined to the world of poker, but communicate extensively with the wider reality through its characteristics, from its unique time structure and the pervasive identities created in the game, to the money players circulate.

  19. Pathology of Commentary in Persian Literary Texts

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    احمد رضی

    2011-10-01

    Full Text Available Today commentary work has a significant role and place among the readers of Persian literary texts and those interested in them. The growing importance of commentary works in helping the readers understand and popularity of commentary works, notably in recent decades, has caused different commentators with different knowledge level and abilities to write comments and foster this disorganized market. This study intends to investigate the published commentary works in the past decades, analyze their week points. To do so, over 250 works, which have been written and published between 1300 AP (circa 1921 AD and 1387 AP (circa2008 AD and an attempt has been made to classify, describe, and analyze their most important problems and week points, and at the end, the most important items of best commentary and best commentators have been explained. This article intends to analyz the most important problems and week points of commentary works, which can be summarized in seven broad categories: 1 content shortcomings; 2 inappropriate approach; 3 incongruence between the structure of commentary work and type of the work and the commentator's objective; 4 lack of attention towards the readership; 5 carelessness and incompetency of the commentator; 6 complex statement and insensible language; 7 inaudibility of introductions. Key words: research methodology, commentary works, pathology, literary works

  20. THE STUDY ON AUTOIMMUNE PATHOLOGY IN OSTEOARTHRITIS

    Institute of Scientific and Technical Information of China (English)

    翁习生; 李秉璐; 任玉珠; 邱贵兴

    1998-01-01

    Sixteen gatients with osteoarthritis (13 knees and 3 hips), 3 patients with rheurmatoid arthritis (RA) and 4 cadaver were studied for evidence of immune complex in the destroyed articular cartilaga tissues.Frozen sections of the articular cartilaga from artheoplasty were stained with fluoresceinated antthodies to human immunoglobulins IgG, IgA, IgM and complement C3. The results showed: 1. There were immune eomplexes linear deported in the surface of the irregular articular cartilage tissues and on some chondrocytea remained in most patients with osteoarthritis (14/16), The patterns of immune complexes are IgA,complement C3, lgG and IgM, their percentage is 81.25%, 75%, 75% and 50% respectively. 2. In a11 of 3 patients with RA, the surfaces of articular tissues were seen with patchy diffusely positive areas for IgA, IgG, IgM (excepting negative in 1 case) and complement C3. 3. There were no immune complexes deposited in the strfaces of 4 cases of normal articular tissues. The presence of immune complexes in the cartilages suggested that an autoimmune reaction participated in the pathological process of osteoarthritis and that the autoimmunity may be responsible for the continuous degeneration of the osteoarthritis.