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Sample records for disease-like pathological features

  1. Memantine Attenuates Alzheimer's Disease-Like Pathology and Cognitive Impairment.

    PubMed

    Wang, Xiaochuan; Blanchard, Julie; Grundke-Iqbal, Inge; Iqbal, Khalid

    2015-01-01

    Deficiency of protein phosphatase-2A is a key event in Alzheimer's disease. An endogenous inhibitor of protein phosphatase-2A, inhibitor-1, I1PP2A, which inhibits the phosphatase activity by interacting with its catalytic subunit protein phosphatase-2Ac, is known to be upregulated in Alzheimer's disease brain. In the present study, we overexpressed I1PP2A by intracerebroventricular injection with adeno-associated virus vector-1-I1PP2A in Wistar rats. The I1PP2A rats showed a decrease in brain protein phosphatase-2A activity, abnormal hyperphosphorylation of tau, neurodegeneration, an increase in the level of activated glycogen synthase kinase-3beta, enhanced expression of intraneuronal amyloid-beta and spatial reference memory deficit; littermates treated identically but with vector only, i.e., adeno-associated virus vector-1-enhanced GFP, served as a control. Treatment with memantine, a noncompetitive NMDA receptor antagonist which is an approved drug for treatment of Alzheimer's disease, rescued protein phosphatase-2A activity by decreasing its demethylation at Leu309 selectively and attenuated Alzheimer's disease-like pathology and cognitive impairment in adeno-associated virus vector-1-I1PP2A rats. These findings provide new clues into the possible mechanism of the beneficial therapeutic effect of memantine in Alzheimer's disease patients.

  2. Dyrk1 inhibition improves Alzheimer's disease-like pathology.

    PubMed

    Branca, Caterina; Shaw, Darren M; Belfiore, Ramona; Gokhale, Vijay; Shaw, Arthur Y; Foley, Christopher; Smith, Breland; Hulme, Christopher; Dunckley, Travis; Meechoovet, Bessie; Caccamo, Antonella; Oddo, Salvatore

    2017-10-01

    There is an urgent need for the development of new therapeutic strategies for Alzheimer's disease (AD). The dual-specificity tyrosine phosphorylation-regulated kinase-1A (Dyrk1a) is a protein kinase that phosphorylates the amyloid precursor protein (APP) and tau and thus represents a link between two key proteins involved in AD pathogenesis. Furthermore, Dyrk1a is upregulated in postmortem human brains, and high levels of Dyrk1a are associated with mental retardation. Here, we sought to determine the effects of Dyrk1 inhibition on AD-like pathology developed by 3xTg-AD mice, a widely used animal model of AD. We dosed 10-month-old 3xTg-AD and nontransgenic (NonTg) mice with a Dyrk1 inhibitor (Dyrk1-inh) or vehicle for eight weeks. During the last three weeks of treatment, we tested the mice in a battery of behavioral tests. The brains were then analyzed for the pathological markers of AD. We found that chronic Dyrk1 inhibition reversed cognitive deficits in 3xTg-AD mice. These effects were associated with a reduction in amyloid-β (Aβ) and tau pathology. Mechanistically, Dyrk1 inhibition reduced APP and insoluble tau phosphorylation. The reduction in APP phosphorylation increased its turnover and decreased Aβ levels. These results suggest that targeting Dyrk1 could represent a new viable therapeutic approach for AD. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  3. Beneficial effects of exercise in a transgenic mouse model of Alzheimer's disease-like Tau pathology.

    PubMed

    Belarbi, Karim; Burnouf, Sylvie; Fernandez-Gomez, Francisco-Jose; Laurent, Cyril; Lestavel, Sophie; Figeac, Martin; Sultan, Audrey; Troquier, Laetitia; Leboucher, Antoine; Caillierez, Raphaëlle; Grosjean, Marie-Eve; Demeyer, Dominique; Obriot, Hélène; Brion, Ingrid; Barbot, Bérangère; Galas, Marie-Christine; Staels, Bart; Humez, Sandrine; Sergeant, Nicolas; Schraen-Maschke, Susanna; Muhr-Tailleux, Anne; Hamdane, Malika; Buée, Luc; Blum, David

    2011-08-01

    Tau pathology is encountered in many neurodegenerative disorders known as tauopathies, including Alzheimer's disease. Physical activity is a lifestyle factor affecting processes crucial for memory and synaptic plasticity. Whether long-term voluntary exercise has an impact on Tau pathology and its pathophysiological consequences is currently unknown. To address this question, we investigated the effects of long-term voluntary exercise in the THY-Tau22 transgenic model of Alzheimer's disease-like Tau pathology, characterized by the progressive development of Tau pathology, cholinergic alterations and subsequent memory impairments. Three-month-old THY-Tau22 mice and wild-type littermates were assigned to standard housing or housing supplemented with a running wheel. After 9 months of exercise, mice were evaluated for memory performance and examined for hippocampal Tau pathology, cholinergic defects, inflammation and genes related to cholesterol metabolism. Exercise prevented memory alterations in THY-Tau22 mice. This was accompanied by a decrease in hippocampal Tau pathology and a prevention of the loss of expression of choline acetyltransferase within the medial septum. Whereas the expression of most cholesterol-related genes remained unchanged in the hippocampus of running THY-Tau22 mice, we observed a significant upregulation in mRNA levels of NPC1 and NPC2, genes involved in cholesterol trafficking from the lysosomes. Our data support the view that long-term voluntary physical exercise is an effective strategy capable of mitigating Tau pathology and its pathophysiological consequences.

  4. Memantine Attenuates Alzheimer’s Disease-Like Pathology and Cognitive Impairment

    PubMed Central

    Wang, Xiaochuan; Blanchard, Julie; Iqbal, Khalid

    2015-01-01

    Deficiency of protein phosphatase-2A is a key event in Alzheimer’s disease. An endogenous inhibitor of protein phosphatase-2A, inhibitor-1, I1PP2A, which inhibits the phosphatase activity by interacting with its catalytic subunit protein phosphatase-2Ac, is known to be upregulated in Alzheimer’s disease brain. In the present study, we overexpressed I1PP2A by intracerebroventricular injection with adeno-associated virus vector-1-I1PP2A in Wistar rats. The I1PP2A rats showed a decrease in brain protein phosphatase-2A activity, abnormal hyperphosphorylation of tau, neurodegeneration, an increase in the level of activated glycogen synthase kinase-3beta, enhanced expression of intraneuronal amyloid-beta and spatial reference memory deficit; littermates treated identically but with vector only, i.e., adeno-associated virus vector-1-enhanced GFP, served as a control. Treatment with memantine, a noncompetitive NMDA receptor antagonist which is an approved drug for treatment of Alzheimer’s disease, rescued protein phosphatase-2A activity by decreasing its demethylation at Leu309 selectively and attenuated Alzheimer’s disease-like pathology and cognitive impairment in adeno-associated virus vector-1-I1PP2A rats. These findings provide new clues into the possible mechanism of the beneficial therapeutic effect of memantine in Alzheimer’s disease patients. PMID:26697860

  5. Neutrophils promote Alzheimer's disease-like pathology and cognitive decline via LFA-1 integrin.

    PubMed

    Zenaro, Elena; Pietronigro, Enrica; Della Bianca, Vittorina; Piacentino, Gennj; Marongiu, Laura; Budui, Simona; Turano, Ermanna; Rossi, Barbara; Angiari, Stefano; Dusi, Silvia; Montresor, Alessio; Carlucci, Tommaso; Nanì, Sara; Tosadori, Gabriele; Calciano, Lucia; Catalucci, Daniele; Berton, Giorgio; Bonetti, Bruno; Constantin, Gabriela

    2015-08-01

    Inflammation is a pathological hallmark of Alzheimer's disease, and innate immune cells have been shown to contribute to disease pathogenesis. In two transgenic models of Alzheimer's disease (5xFAD and 3xTg-AD mice), neutrophils extravasated and were present in areas with amyloid-β (Aβ) deposits, where they released neutrophil extracellular traps (NETs) and IL-17. Aβ42 peptide triggered the LFA-1 integrin high-affinity state and rapid neutrophil adhesion to integrin ligands. In vivo, LFA-1 integrin controlled neutrophil extravasation into the CNS and intraparenchymal motility. In transgenic Alzheimer's disease models, neutrophil depletion or inhibition of neutrophil trafficking via LFA-1 blockade reduced Alzheimer's disease-like neuropathology and improved memory in mice already showing cognitive dysfunction. Temporary depletion of neutrophils for 1 month at early stages of disease led to sustained improvements in memory. Transgenic Alzheimer's disease model mice lacking LFA-1 were protected from cognitive decline and had reduced gliosis. In humans with Alzheimer's disease, neutrophils adhered to and spread inside brain venules and were present in the parenchyma, along with NETs. Our results demonstrate that neutrophils contribute to Alzheimer's disease pathogenesis and cognitive impairment and suggest that the inhibition of neutrophil trafficking may be beneficial in Alzheimer's disease.

  6. Familial Prion Disease with Alzheimer Disease-Like Tau Pathology and Clinical Phenotype

    PubMed Central

    Jayadev, Suman; Nochlin, David; Poorkaj, Parvoneh; Steinbart, Ellen J.; Mastrianni, James A.; Montine, Thomas J.; Ghetti, Bernardino; Schellenberg, Gerard D.; Bird, Thomas D.; Leverenz, James B.

    2011-01-01

    Objective To describe the Alzheimer disease (AD)-like clinical and pathological features, including marked neurofibrillary tangle (NFT) pathology, of a familial prion disease due to a rare nonsense mutation of the prion gene (PRNP). Methods Longitudinal clinical assessments were available for the proband and her mother. After death, both underwent neuropathological evaluation. PRNP was sequenced after failure to find immunopositive Aβ deposits in the proband and the documentation of prion protein (PrP) immunopositive pathology. Results The proband presented at age 42 years with a 3-year history of progressive short-term memory impairment and depression. Neuropsychological testing found impaired memory performance, with relatively preserved attention and construction. She was diagnosed with AD and died at age 47 years. Neuropathologic evaluation revealed extensive limbic and neocortical NFT formation and neuritic plaques consistent with a Braak stage of VI. The NFTs were immunopositive, with multiple tau antibodies, and electron microscopy revealed paired helical filaments. However, the neuritic plaques were immunonegative for Aβ, whereas immunostaining for PrP was positive. The mother of the proband had a similar presentation, including depression, and had been diagnosed clinically and pathologically as AD. Reevaluation of her brain tissue confirmed similar tau and PrP immunostaining findings. Genetic analysis revealed that both the proband and her mother had a rare PRNP mutation (Q160X) that resulted in the production of truncated PrP. Interpretation We suggest that PRNP mutations that result in a truncation of PrP lead to a prolonged clinical course consistent with a clinical diagnosis of AD and severe AD-like NFTs. PMID:21416485

  7. Beneficial effects of caffeine in a transgenic model of Alzheimer's disease-like tau pathology.

    PubMed

    Laurent, Cyril; Eddarkaoui, Sabiha; Derisbourg, Maxime; Leboucher, Antoine; Demeyer, Dominique; Carrier, Sébastien; Schneider, Marion; Hamdane, Malika; Müller, Christa E; Buée, Luc; Blum, David

    2014-09-01

    Tau pathology found in Alzheimer's disease (AD) is crucial in cognitive decline. Epidemiologic evidences support that habitual caffeine intake prevents memory decline during aging and reduces the risk to develop Alzheimer's disease. So far, experimental studies addressed the impact of caffeine in models mimicking the amyloid pathology of AD. However, in vivo effects of caffeine in a model of AD-like tauopathy remain unknown. Here, we evaluated effects of chronic caffeine intake (0.3 g/L through drinking water), given at an early pathologic stage, in the THY-Tau22 transgenic mouse model of progressive AD-like tau pathology. We found that chronic caffeine intake prevents from the development of spatial memory deficits in tau mice. Improved memory was associated with reduced hippocampal tau phosphorylation and proteolytic fragments. Moreover, caffeine treatment mitigated several proinflammatory and oxidative stress markers found upregulated in the hippocampus of THY-Tau22 animals. Together, our data support that moderate caffeine intake is beneficial in a model of AD-like tau pathology, paving the way for future clinical evaluation in AD patients.

  8. Alzheimer's disease-like pathology has transient effects on the brain and blood metabolome.

    PubMed

    Pan, Xiaobei; Nasaruddin, Muhammad Bin; Elliott, Christopher T; McGuinness, Bernadette; Passmore, Anthony P; Kehoe, Patrick G; Hölscher, Christian; McClean, Paula L; Graham, Stewart F; Green, Brian D

    2016-02-01

    The pathogenesis of Alzheimer's disease (AD) is complex involving multiple contributing factors. The extent to which AD pathology affects the metabolome is still not understood nor is it known how disturbances change as the disease progresses. For the first time, we have profiled longitudinally (6, 8, 10, 12, and 18 months) both the brain and plasma metabolome of APPswe/PS1deltaE9 double transgenic and wild-type mice. A total of 187 metabolites were quantified using a targeted metabolomic methodology. Multivariate statistical analysis produced models that distinguished APPswe/PS1deltaE9 from wild-type mice at 8, 10, and 12 months. Metabolic pathway analysis found perturbed polyamine metabolism in both brain and blood plasma. There were other disturbances in essential amino acids, branched-chain amino acids, and also in the neurotransmitter serotonin. Pronounced imbalances in phospholipid and acylcarnitine homeostasis were evident in 2 age groups. AD-like pathology, therefore, affects greatly on both the brain and blood metabolomes, although there appears to be a clear temporal sequence whereby changes to brain metabolites precede those in blood.

  9. Amyloid accumulation is a late event in sporadic Alzheimer's disease-like pathology in nontransgenic rats

    PubMed Central

    Stefanova, Natalia A.; Muraleva, Natalia A.; Korbolina, Elena E.; Kiseleva, Elena; Maksimova, Kseniya Yi.; Kolosova, Nataliya G.

    2015-01-01

    The amyloid cascade hypothesis posits that deposition of the amyloid β (Aβ) peptide in the brain is a key event in the initiation of Alzheimer's disease (AD). Nonetheless, it now seems increasingly unlikely that amyloid toxicity is the cause of sporadic AD, which leads to cognitive decline. Here, using accelerated-senescence nontransgenic OXYS rats, we confirmed that aggregation of Aβ is a later event in AD-like pathology. We showed that an age-dependent increase in the levels of Aβ1–42 and extracellular Aβ deposits in the brain of OXYS rats occur later than do synaptic losses, neuronal cell death, mitochondrial structural abnormalities, and hyperphosphorylation of the tau protein. We identified the variants of the genes that are strongly associated with the risk of either late-onset or early-onset AD, including App, Apoe4, Bace1, Psen1, Psen2, and Picalm. We found that in OXYS rats nonsynonymous SNPs were located only in the genes Casp3 and Sorl1. Thus, we present proof that OXYS rats may be a model of sporadic AD. It is possible that multiple age-associated pathological processes may precede the toxic amyloid accumulation, which in turn triggers the final stage of the sporadic form of AD and becomes a hallmark event of the disease. PMID:25595891

  10. Capsaicin ameliorates stress-induced Alzheimer's disease-like pathological and cognitive impairments in rats.

    PubMed

    Jiang, Xia; Jia, Lin-Wei; Li, Xiao-Hong; Cheng, Xiang-Shu; Xie, Jia-Zhao; Ma, Zhi-Wei; Xu, Wei-Jie; Liu, Yue; Yao, Yun; Du, Lai-Ling; Zhou, Xin-Wen

    2013-01-01

    Hyperphosphorylated tau aggregated into neurofibrillary tangles is a hallmark lesion of Alzheimer's disease (AD) and is linked to synaptic and cognitive impairments. In animal models, cold water stress (CWS) can cause cognitive disorder and tau hyperphosphorylation. Capsaicin (CAP), a specific TRPV1 agonist, is neuroprotective against stress-induced impairment, but the detailed mechanisms are still elusive. Here, we investigated whether CAP mitigates CWS-induced cognitive and AD-like pathological alterations in rats. The animals were administered CAP (10 mg/kg in 0.2 ml, 0.1% ethanol) or a control (0.2 ml normal saline, 0.1% ethanol) by intragastric infusion 1 h before CWS treatment. Our results showed that CAP significantly attenuated CWS-induced spatial memory impairment and suppression of PP-DG long-term potentiation; CAP abolished CWS-induced dendritic regression and enhanced several memory-associated proteins decreased by CWS, such as synapsin I and PSD93; CAP also prevented CWS-induced tau hyperphosphorylation by abolishing inhibition of protein phosphatase 2A. Taken together, this study demonstrated that activation of TRPV1 can mitigate CWS-induced AD-like neuropathological alterations and cognitive impairment and may be a promising target for therapeutic intervention in AD.

  11. An antioxidant specifically targeting mitochondria delays progression of Alzheimer's disease-like pathology

    PubMed Central

    Stefanova, Natalia A.; Muraleva, Natalia A.; Maksimova, Kseniya Yi.; Rudnitskaya, Ekaterina A.; Kiseleva, Elena; Telegina, Darya V.; Kolosova, Nataliya

    2016-01-01

    Mitochondrial aberrations are observed in human Alzheimer's disease (AD) and in medical conditions that increase the risk of this disorder, suggesting that mitochondrial dysfunction may contribute to pathophysiology of AD. Here, using OXYS rats that simulate key characteristics of sporadic AD, we set out to determine the role of mitochondria in the pathophysiology of this disorder. OXYS rats were treated with a mitochondria-targeted antioxidant SkQ1 from age 12 to 18 months, that is, during active progression of AD-like pathology in these animals. Dietary supplementation with SkQ1 caused this compound to accumulate in various brain regions, and it was localized mostly to neuronal mitochondria. Via improvement of structural and functional state of mitochondria, treatment with SkQ1 alleviated the structural neurodegenerative alterations, prevented the neuronal loss and synaptic damage, increased the levels of synaptic proteins, enhanced neurotrophic supply, and decreased amyloid-β1-42 protein levels and tau hyperphosphorylation in the hippocampus of OXYS rats, resulting in improvement of the learning ability and memory. Collectively, these data support that mitochondrial dysfunction may play a key role in the pathophysiology of AD and that therapies with target mitochondria are potent to normalize a wide range of cellular signaling processes and therefore slow the progression of AD. PMID:27750209

  12. Neural stem cell transplantation enhances mitochondrial biogenesis in a transgenic mouse model of Alzheimer's disease-like pathology.

    PubMed

    Zhang, Wei; Gu, Guo-Jun; Shen, Xing; Zhang, Qi; Wang, Gang-Min; Wang, Pei-Jun

    2015-03-01

    Mitochondrial dysfunction, especially a defect in mitochondrial biogenesis, is an early and prominent feature of Alzheimer's disease (AD). Previous studies demonstrated that the number of mitochondria is significantly reduced in susceptible hippocampal neurons from AD patients. Neural stem cell (NSC) transplantation in AD-like mice can compensate for the neuronal loss resulting from amyloid-beta protein deposition. The effects of NSC transplantation on mitochondrial biogenesis and cognitive function in AD-like mice, however, are poorly understood. In this study, we injected NSCs or vehicle into 12-month-old amyloid precursor protein (APP)/PS1 transgenic mice, a mouse model of AD-like pathology. The effects of NSC transplantation on cognitive function, the amount of mitochondrial DNA, the expression of mitochondrial biogenesis factors and mitochondria-related proteins, and mitochondrial morphology were investigated. Our results show that in NSC-injected APP/PS1 (Tg-NSC) mice, the cognitive function, number of mitochondria, and expression of mitochondria-related proteins, specifically the mitochondrial fission factors (dynamin-related protein 1 [Drp1] and fission 1 [Fis1]) and the mitochondrial fusion factor optic atrophy 1 (OPA1), were significantly increased compared with those in age-matched vehicle-injected APP/PS1 (Tg-Veh) mice, whereas the expression of mitochondrial fusion factors mitofusion 1 (Mfn1) and Mfn2 was significantly decreased. These data indicate that NSC transplantation may enhance mitochondria biogenesis and further rescue cognitive deficits in AD-like mice.

  13. Impact of Changes in Neurotrophic Supplementation on Development of Alzheimer's Disease-Like Pathology in Oxys Rats.

    PubMed

    Rudnitskaya, E A; Kolosova, N G; Stefanova, N A

    2017-03-01

    Alzheimer's disease (AD) is the most common type of age-related dementia. The development of neurodegeneration in AD is closely related to alterations in neurotrophic supplementation of the brain, which may be caused either by disorder of neurotrophin metabolism or by modification of its availability due to changes in the microenvironment of neurons. The underlying mechanisms are not fully understood. In this work, we used senescence-accelerated OXYS rats as a unique model of the sporadic form of AD to examine the relationship of development of AD signs and changes in neurotrophic supplementation of the cortex. Based on comparative analysis of the transcriptome of the frontal cerebral cortex of OXYS and Wistar (control) rats, genes of a neurotrophin signaling pathway with different mRNA levels in the period prior to the development of AD-like pathology in OXYS rats (20 days) and in the period of its active manifestation (5 months) and progression (18 months) were identified. The most significant changes in mRNA levels in the cortex of OXYS rats occurred in the period from 5 to 18 months of age. These genes were associated with neurogenesis, neuronal differentiation, synaptic plasticity, and immune response. The results were compared to changes in the levels of brain-derived neurotrophic factor (BDNF), its receptors TrkB and p75(NTR), as well as with patterns of their colocalization, which reveal the balance of proneurotrophins and mature neurotrophins and their receptors. We found that alterations in neurotrophic balance indicating increased apoptosis precede the development of AD-like pathology in OXYS rats. Manifestation of AD-like pathology occurs against a background of activation of compensatory and regenerative processes including increased neurotrophic supplementation. Active progression of AD-like pathology in OXYS rats is accompanied by the suppression of activity of the neurotrophin system. Thus, the results confirm the importance of the neurotrophin

  14. Caffeine protects against oxidative stress and Alzheimer's disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet.

    PubMed

    Prasanthi, Jaya R P; Dasari, Bhanu; Marwarha, Gurdeep; Larson, Tyler; Chen, Xuesong; Geiger, Jonathan D; Ghribi, Othman

    2010-10-15

    Cholesterol has been linked to the pathogenesis of sporadic Alzheimer's disease (AD) as a risk factor increasing beta-amyloid (Abeta) and oxidative stress levels. Caffeine has antioxidant properties and has been demonstrated to reduce Abeta levels in transgenic mouse models of familial AD. However, the effects of caffeine on cholesterol-induced sporadic AD pathology have not been determined. In this study, we determined the effects of caffeine on Abeta levels, tau phosphorylation, oxidative stress generation, and caffeine-target receptors in rabbits fed a 2% cholesterol-enriched diet, a model system for sporadic AD. Our results showed that the cholesterol-enriched diet increased levels of Abeta, tau phosphorylation, and oxidative stress measured as increased levels of reactive oxygen species and isoprostanes, glutathione depletion, and increased levels of endoplasmic reticulum stress marker proteins. Additionally, the cholesterol-enriched diet reduced the levels of adenosine A(1) receptors (A(1)R) but not ryanodine or adenosine A(2A) receptors. Caffeine, administered at 0.5 and 30mg/day in the drinking water, reduced the cholesterol-induced increase in Abeta, phosphorylated tau, and oxidative stress levels and reversed the cholesterol-induced decrease in A(1)R levels. Our results suggest that even very low doses of caffeine might protect against sporadic AD-like pathology. Copyright 2010 Elsevier Inc. All rights reserved.

  15. Hydrogen Sulfide Ameliorates Homocysteine-Induced Alzheimer's Disease-Like Pathology, Blood-Brain Barrier Disruption, and Synaptic Disorder.

    PubMed

    Kamat, Pradip K; Kyles, Philip; Kalani, Anuradha; Tyagi, Neetu

    2016-05-01

    Elevated plasma total homocysteine (Hcy) level is associated with an increased risk of Alzheimer's disease (AD). During transsulfuration pathways, Hcy is metabolized into hydrogen sulfide (H2S), which is a synaptic modulator, as well as a neuro-protective agent. However, the role of hydrogen sulfide, as well as N-methyl-D-aspartate receptor (NMDAR) activation, in hyperhomocysteinemia (HHcy) induced blood-brain barrier (BBB) disruption and synaptic dysfunction, leading to AD pathology is not clear. Therefore, we hypothesized that the inhibition of neuronal NMDA-R by H2S and MK801 mitigate the Hcy-induced BBB disruption and synapse dysfunction, in part by decreasing neuronal matrix degradation. Hcy intracerebral (IC) treatment significantly impaired cerebral blood flow (CBF), and cerebral circulation and memory function. Hcy treatment also decreases the expression of cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) in the brain along with increased expression of NMDA-R (NR1) and synaptosomal Ca(2+) indicating excitotoxicity. Additionally, we found that Hcy treatment increased protein and mRNA expression of intracellular adhesion molecule 1 (ICAM-1), matrix metalloproteinase (MMP)-2, and MMP-9 and also increased MMP-2 and MMP-9 activity in the brain. The increased expression of ICAM-1, glial fibrillary acidic protein (GFAP), and the decreased expression of vascular endothelial (VE)-cadherin and claudin-5 indicates BBB disruption and vascular inflammation. Moreover, we also found decreased expression of microtubule-associated protein 2 (MAP-2), postsynaptic density protein 95 (PSD-95), synapse-associated protein 97 (SAP-97), synaptosomal-associated protein 25 (SNAP-25), synaptophysin, and brain-derived neurotrophic factor (BDNF) showing synapse dysfunction in the hippocampus. Furthermore, NaHS and MK801 treatment ameliorates BBB disruption, CBF, and synapse functions in the mice brain. These results demonstrate a neuro-protective effect of H2S over Hcy

  16. Aspirin-triggered lipoxin A4 stimulates alternative activation of microglia and reduces Alzheimer disease-like pathology in mice.

    PubMed

    Medeiros, Rodrigo; Kitazawa, Masashi; Passos, Giselle F; Baglietto-Vargas, David; Cheng, David; Cribbs, David H; LaFerla, Frank M

    2013-05-01

    Microglia play an essential role in innate immunity, homeostasis, and neurotropic support in the central nervous system. In Alzheimer disease (AD), these cells may affect disease progression by modulating the buildup of β-amyloid (Aβ) or releasing proinflammatory cytokines and neurotoxic substances. Discovering agents capable of increasing Aβ uptake by phagocytic cells is of potential therapeutic interest for AD. Lipoxin A4 (LXA4) is an endogenous lipid mediator with potent anti-inflammatory properties directly involved in inflammatory resolution, an active process essential for appropriate host responses, tissue protection, and the return to homeostasis. Herein, we demonstrate that aspirin-triggered LXA4 (15 μg/kg) s.c., twice a day, reduced NF-κB activation and levels of proinflammatory cytokines and chemokines, as well as increased levels of anti-inflammatory IL-10 and transforming growth factor-β. Such changes in the cerebral milieu resulted in recruitment of microglia in an alternative phenotype, as characterized by the up-regulation of YM1 and arginase-1 and the down-regulation of inducible nitric oxide synthase expression. Microglia in an alternative phenotype-positive cells demonstrated improved phagocytic function, promoting clearance of Aβ deposits and ultimately leading to reduction in synaptotoxicity and improvement in cognition. Our data indicate that activating LXA4 signaling may represent a novel therapeutic approach for AD. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. Lupus mastitis - peculiar radiological and pathological features

    PubMed Central

    Wani, Abdul Majid; Hussain, Waleed Mohd; Fatani, Mohamed I; Shakour, Bothaina Abdul

    2009-01-01

    Lupus mastitis is a form of lupus profundus that is seen in patients with systemic lupus erythematosus. It usually presents as a swelling (or swellings) in the breasts, with or without pain. The condition is recurrent and progresses along with the underlying disease, with fat necrosis, calcification, fibrosis, scarring, and breast atrophy. Lupus mastitis is often confused with malignancy and lymphoma and, in our part of the world, with tuberculosis. Confusion is especially likely when it occurs in an unusual clinical setting. In this article, we present a case that presented with unique radiological, pathological, and clinical features. Awareness of the various manifestations of lupus mastitis is essential if unnecessary interventions such as biopsies and surgeries, and their consequences, are to be avoided. PMID:19881078

  18. Clinical and pathological features of pachyonychia congenita.

    PubMed

    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.

  19. Laparoscopic adrenalectomy: pathologic features determine outcome

    PubMed Central

    Poulin, Eric C.; Schlachta, Christopher M.; Burpee, Stephen E.; Pace, Kenneth T.; Mamazza, Joseph

    2003-01-01

    Introduction The differential outcomes of laparoscopic adrenalectomy are not well described. Therefore, we evaluated these outcomes in the 3 groups most often seen clinically: bilateral adrenalectomy for Cushing's disease (group 1), pheochromocytoma (group 2) and unilateral adrenalectomy for non-pheochromocytoma (group 3). Methods We reviewed a longitudinal database of 72 consecutive cases of laparoscopic adrenalectomy carried out between 1997 and 2001 at the Centre for Minimally Invasive Surgery, University of Toronto. Results Patients in group 1 tended to be older (median 49 yr) and heavier (median 87 kg). They had a longer operating time (median 255 min), more postoperative complications (15%) and a longer median postoperative stay (4 d). Patients in group 2 had intermediate outcomes: a median operating time of 198 minutes, complication rate of 8.3% and a median postoperative hospital stay of 3 days. However, they had more intraoperative blood loss (median 150 mL). Group 3 patients had the best outcomes with the shortest median operating time (125 min), least blood loss (median 50 mL), fewer complications (6%) and shortest hospital stay (median 2 d). Conclusions Although the outcomes of laparoscopic adrenalectomy are uniformly good, on the basis of the underlying pathologic characteristics, patients can be divided into groups that have different expected outcomes. Patients requiring a unilateral adrenalectomy except for pheochromocytoma have the best recorded outcomes. Surgeons transferring to laparoscopic adrenalectomy would benefit from selecting patients in this group during their learning curve. PMID:14577705

  20. Basal cell carcinoma: clinical and pathological features.

    PubMed

    Di Stefani, A; Chimenti, S

    2015-08-01

    Basal cell carcinoma (BCC) is a slow-growing, locally invasive malignant epidermal skin neoplasm that represents the most common malignancy in Caucasians. The clinical presentation of BCC can be extremely variable: nodular, ulcerative, superficial, morpheiform, pigmented, and fibroepithelioma of Pinkus are the main clinical variants described. Clinical factors influencing negatively prognosis of BCC are: anatomic location, recurrence and/or persistance at site after treatment, and tumor size. A precise correlations between clinical and histopathological variants is not always possible, especially in biopsy samples. From a histopathological point of view various subtypes has been described: nodular, superficial, infiltrating, morpheiform, micronodular, fibroepithelial BCC and basosquamous carcinoma. A classification system based by growth pattern allows the identification of high-risk subtypes with potential tumor recurrence and aggressive biologic behavior such as infiltrating, morpheiform, micronodular and basosquamous subtypes. Further histopathological aspects determining high risk clinical morbidity are the level of invasion, perineural and lymphovascular invasion, involved surgical margins. The awareness of these clinicopathological features is helpful to better select the appropriate treatment management.

  1. Which ante mortem clinical features predict progressive supranuclear palsy pathology?

    PubMed

    Respondek, Gesine; Kurz, Carolin; Arzberger, Thomas; Compta, Yaroslau; Englund, Elisabet; Ferguson, Leslie W; Gelpi, Ellen; Giese, Armin; Irwin, David J; Meissner, Wassilios G; Nilsson, Christer; Pantelyat, Alexander; Rajput, Alex; van Swieten, John C; Troakes, Claire; Josephs, Keith A; Lang, Anthony E; Mollenhauer, Brit; Müller, Ulrich; Whitwell, Jennifer L; Antonini, Angelo; Bhatia, Kailash P; Bordelon, Yvette; Corvol, Jean-Christophe; Colosimo, Carlo; Dodel, Richard; Grossman, Murray; Kassubek, Jan; Krismer, Florian; Levin, Johannes; Lorenzl, Stefan; Morris, Huw; Nestor, Peter; Oertel, Wolfgang H; Rabinovici, Gil D; Rowe, James B; van Eimeren, Thilo; Wenning, Gregor K; Boxer, Adam; Golbe, Lawrence I; Litvan, Irene; Stamelou, Maria; Höglinger, Günter U

    2017-07-01

    Progressive supranuclear palsy (PSP) is a neuropathologically defined disease presenting with a broad spectrum of clinical phenotypes. To identify clinical features and investigations that predict or exclude PSP pathology during life, aiming at an optimization of the clinical diagnostic criteria for PSP. We performed a systematic review of the literature published since 1996 to identify clinical features and investigations that may predict or exclude PSP pathology. We then extracted standardized data from clinical charts of patients with pathologically diagnosed PSP and relevant disease controls and calculated the sensitivity, specificity, and positive predictive value of key clinical features for PSP in this cohort. Of 4166 articles identified by the database inquiry, 269 met predefined standards. The literature review identified clinical features predictive of PSP, including features of the following 4 functional domains: ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction. No biomarker or genetic feature was found reliably validated to predict definite PSP. High-quality original natural history data were available from 206 patients with pathologically diagnosed PSP and from 231 pathologically diagnosed disease controls (54 corticobasal degeneration, 51 multiple system atrophy with predominant parkinsonism, 53 Parkinson's disease, 73 behavioral variant frontotemporal dementia). We identified clinical features that predicted PSP pathology, including phenotypes other than Richardson's syndrome, with varying sensitivity and specificity. Our results highlight the clinical variability of PSP and the high prevalence of phenotypes other than Richardson's syndrome. The features of variant phenotypes with high specificity and sensitivity should serve to optimize clinical diagnosis of PSP. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

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

    PubMed

    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.

  3. A case of pathological gambling--its features and mangement.

    PubMed

    Lim, K D

    2001-05-01

    Pathological gambling (PG) represents the end spectrum of gambling behaviours. It is characterised by constantly recurring gambling behaviour which is maladaptive. This case illustrates how an Asian woman pathological gambler progresses through the different stages of development of the gambling habit, and how a multi-modal treatment approach has helped her regain psychosocial function. In addition, the maintenance factors, typical and atypical associated features, and difficulties in the management of such a case are highlighted.

  4. High-fat, high-sugar, and high-cholesterol consumption does not impact tau pathogenesis in a mouse model of Alzheimer's disease-like tau pathology.

    PubMed

    Gratuze, Maud; Julien, Jacinthe; Morin, Françoise; Calon, Frédéric; Hébert, Sébastien S; Marette, André; Planel, Emmanuel

    2016-11-01

    Aggregates of hyperphosphorylated tau protein are a pathological hallmark of Alzheimer's disease (AD). The origin of AD is multifactorial, and many metabolic disorders originating from overconsumption of fat, cholesterol, and sugar are associated with higher risk of AD later in life. However, the effects of fat, cholesterol, and sugar overconsumption on tau pathology in AD remain controversial. Using the hTau mice, a model of AD-like tau pathology, we assessed the effects of high-fat, high-cholesterol, and/or high-sugar diets on tau pathogenesis. Surprisingly, we found no effects of these compounds, even combined, on tau phosphorylation, O-GlcNAcylation, splicing, cleavage, and aggregation, suggesting that their overconsumption does not seem to worsen tau pathology in these mice.

  5. Feature Importance in Nonlinear Embeddings (FINE): Applications in Digital Pathology.

    PubMed

    Ginsburg, Shoshana B; Lee, George; Ali, Sahirzeeshan; Madabhushi, Anant

    2016-01-01

    Quantitative histomorphometry (QH) refers to the process of computationally modeling disease appearance on digital pathology images by extracting hundreds of image features and using them to predict disease presence or outcome. Since constructing a robust and interpretable classifier is challenging in a high dimensional feature space, dimensionality reduction (DR) is often implemented prior to classifier construction. However, when DR is performed it can be challenging to quantify the contribution of each of the original features to the final classification result. We have previously presented a method for scoring features based on their importance for classification on an embedding derived via principal components analysis (PCA). However, nonlinear DR involves the eigen-decomposition of a kernel matrix rather than the data itself, compounding the issue of classifier interpretability. In this paper we present feature importance in nonlinear embeddings (FINE), an extension of our PCA-based feature scoring method to kernel PCA (KPCA), as well as several NLDR algorithms that can be cast as variants of KPCA. FINE is applied to four digital pathology datasets to identify key QH features for predicting the risk of breast and prostate cancer recurrence. Measures of nuclear and glandular architecture and clusteredness were found to play an important role in predicting the likelihood of recurrence of both breast and prostate cancers. Compared to the t-test, Fisher score, and Gini index, FINE was able to identify a stable set of features that provide good classification accuracy on four publicly available datasets from the NIPS 2003 Feature Selection Challenge.

  6. Differential effects of voluntary treadmill exercise and caloric restriction on tau pathogenesis in a mouse model of Alzheimer's disease-like tau pathology fed with Western diet.

    PubMed

    Gratuze, Maud; Julien, Jacinthe; Morin, Françoise; Marette, André; Planel, Emmanuel

    2017-10-03

    Tau is a microtubule-associated protein that becomes pathological when it undergoes hyperphosphorylation and aggregation as seen in Alzheimer's disease (AD). AD is mostly sporadic, with environmental, biological and/or genetic risks factors, interacting together to promote the disease. In the past decade, reports have suggested that obesity in midlife could be one of these risk factors. On the other hand, caloric restriction and physical exercise have been reported to reduce the incidence and outcome of obesity as well as AD. We evaluated the impact of voluntary physical exercise and caloric restriction on tau pathology during 2months in hTau mice under high caloric diet in order to evaluate if these strategies could prevent AD-like pathology in obese conditions. We found no effects of obesity induced by Western diet on both Tau phosphorylation and aggregation compared to controls. However, exercise reduced tau phosphorylation while caloric restriction exacerbated its aggregation in the brains of obese hTau mice. We then examined the mechanisms underlying changes in tau phosphorylation and aggregation by exploring major tau kinases and phosphatases and key proteins involved in autophagy. However, there were no significant effects of voluntary exercise and caloric restriction on these proteins in hTau mice that could explain our results. In this study, we report differential effects of voluntary treadmill exercise and caloric restriction on tau pathogenesis in our obese mice, namely beneficial effect of exercise on tau phosphorylation and deleterious effect of caloric restriction on tau aggregation. Our results suggest that lifestyle strategies used to reduce metabolic disorders and AD must be selected and studied carefully to avoid exacerbation of pathologies. Copyright © 2017. Published by Elsevier Inc.

  7. Chronic Sleep Deprivation Exacerbates Learning-Memory Disability and Alzheimer's Disease-Like Pathologies in AβPP(swe)/PS1(ΔE9) Mice.

    PubMed

    Qiu, Hongyan; Zhong, Rujia; Liu, Hui; Zhang, Feng; Li, Song; Le, Weidong

    2016-01-01

    Recently, there is an increasing concern over the association between sleep disorders and Alzheimer's disease (AD). Clinical observations have reported that chronic sleep deprivation (SD) may serve as a risk factor for AD. However, the pathological evidence for this assumption is still lacking. In the present study, we examined the potential impacts of chronic SD on learning-memory and AD-related pathologies in AβPP(swe)/PS1(ΔE9) transgenic (TG) mice and their wild-type (WT) littermates. Results indicated that mice (both TG and WT) exposed to 2-month SD showed an altered amyloid-β protein precursor processing, an elevated level of phosphorylated tau protein, and impaired cognitive performance as compared to non-sleep deprivation (NSD) controls. Moreover, the SD-treated TG mice exhibited more amyloid-β(1-42) production and developed more senile plaques in the cortex and hippocampus than NSD-treated TG mice. In addition, SD caused a striking neuronal mitochondrial damage, caspase cascade activation, and neuronal apoptosis in the hippocampus of both TG and WT mice. More importantly, all these behavioral, neuropathological, and biochemical changes induced by chronic SD were long lasting and were irreversible during a 3-month normal housing condition. Collectively, these results indicate that chronic SD impairs learning and memory, exacerbates AD pathologies, and aggravates the mitochondria-mediated neuronal apoptosis in a long-lasting manner. Our findings provide important experimental evidence to prove that chronic SD is a risk factor for AD.

  8. Alzheimer's disease-like pathology in senescence-accelerated OXYS rats can be partially retarded with mitochondria-targeted antioxidant SkQ1.

    PubMed

    Stefanova, Natalia A; Muraleva, Natalia A; Skulachev, Vladimir P; Kolosova, Nataliya G

    2014-01-01

    We previously showed that mitochondria-targeted antioxidant SkQ1 (plastoquinonyl-decyltriphenylphosphonium) at nanomolar concentrations is capable of preventing and slowing down some cerebral dysfunctions in accelerated-senescence OXYS rats. Here we demonstrate that OXYS rats develop behavior, learning, and memory deficits against a background of neurodegeneration signs detected by magnetic resonance tomography and amyloid-β (Aβ) pathology similar to those seen in Alzheimer's disease (AD). Long-term treatment with SkQ1 (250 nmol/kg body weight daily from the age of 1.5 to 23 months) reduced the age-related alterations in behavior and spatial memory deficit in Morris water maze in OXYS and Wistar rats. Furthermore, this is the first report that SkQ1 treatment slows down pathological accumulation of AβPP, Aβ, and hyperphosphorylation of tau-protein in OXYS rats, as well as age-dependent changes in healthy Wistar rats. Our results support the possibility of using the OXYS strain as a rat model of AD-like pathology. It seems probable that the mitochondria-targeted antioxidant SkQ1 can be a good prophylactic strategy to maintain brain health and to treat AD.

  9. Selecting Disorder-Specific Features for Speech Pathology Fingerprinting

    PubMed Central

    Berisha, Visar; Sandoval, Steven; Utianski, Rene; Liss, Julie; Spanias, Andreas

    2014-01-01

    The general aim of this work is to learn a unique statistical signature for the state of a particular speech pathology. We pose this as a speaker identification problem for dysarthric individuals. To that end, we propose a novel algorithm for feature selection that aims to minimize the effects of speaker-specific features (e.g., fundamental frequency) and maximize the effects of pathology-specific features (e.g., vocal tract distortions and speech rhythm). We derive a cost function for optimizing feature selection that simultaneously trades off between these two competing criteria. Furthermore, we develop an efficient algorithm that optimizes this cost function and test the algorithm on a set of 34 dysarthric and 13 healthy speakers. Results show that the proposed method yields a set of features related to the speech disorder and not an individual's speaking style. When compared to other feature-selection algorithms, the proposed approach results in an improvement in a disorder fingerprinting task by selecting features that are specific to the disorder. PMID:25005047

  10. Childhood chronic inflammatory demyelinating polyneuropathy with nonuniform pathologic features.

    PubMed

    Luan, Xinghua; Zheng, Riliang; Chen, Bin; Yuan, Yun

    2010-08-01

    Nonuniform pathologic changes in chronic inflammatory demyelinating polyneuropathy were previously reported only in adult humans. We analyzed the pathologic features of 12 children, aged 2-17 years, with chronic inflammatory demyelinating polyneuropathy. Six patients manifested a preceding illness. Five patients presented a chronic, monophasic course, and seven presented a relapsing-remitting course. Three patients exhibited multiple cranial-nerve involvement. Five of 12 (41.7%) patients presented nonuniform features. Two subtypes of nonuniform lesions were revealed. One exhibited varying myelinated fiber content between nerve fascicles, and one exhibited onion bulbs involving a variable number of fascicles. Macrophages were evident in 11 patients, and the number of CD3-positive T cells in the nonuniform group was greater compared with the uniform group (P = 0.045). Our results demonstrate that childhood chronic inflammatory demyelinating polyneuropathy exhibits pathologically nonuniform features, thus providing more evidence to assist in differential diagnoses of pediatric patients. However, clinical and electrophysiologic features, as well as responses to treatment, were similar in the nonuniform and uniform groups.

  11. Caffeine protects against oxidative stress and Alzheimer’s disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet

    PubMed Central

    Prasanthi, Jaya R.P.; Dasari, Bhanu; Marwarha, Gurdeep; Larson, Tyler; Chen, Xuesong; Geiger, Jonathan D.; Ghribi, Othman

    2010-01-01

    Cholesterol has been linked to the pathogenesis of sporadic Alzheimer’s disease (AD) as a risk factor increasing β-amyloid (Aβ) and oxidative stress levels. Caffeine has anti-oxidant properties and has been demonstrated to reduce Aβ levels in transgenic mouse models of familial AD. However, the effects of caffeine on cholesterol-induced sporadic AD pathology have not been determined. In the present study, we determined the effects of caffeine on Aβ levels, tau phosphorylation, oxidative stress generation, and caffeine-target receptors in rabbits fed a 2% cholesterol-enriched diet, a model system for sporadic AD. Our results showed that the cholesterol-enriched diet increased levels of Aβ, tau phosphorylation as well as oxidative stress measured as increased levels of reactive oxygen species, isoprostanes, glutathione depletion, and increased levels of endoplasmic reticulum (ER) stress marker proteins. Additionally, the cholesterol-enriched diet reduced levels of adenosine A1 (A1R) but not ryanodine (RyR) or adenosine A2A (A2AR) receptors. Caffeine, administered at 0.5 mg and 30 mg/day in the drinking water, reduced cholesterol-induced increase in Aβ, phosphorylated tau and oxidative stress levels, and reversed cholesterol-induced decrease in A1R levels. Our results suggest that even very low doses of caffeine might protect against sporadic AD-like pathology. PMID:20638472

  12. [Pathological features of hepatocellular carcinoma carrying hepatitis C virus antigen].

    PubMed

    Liu, B; Zhu, S; Zhang, X

    1997-10-01

    To analyze the pathological features of hepatocellular carcinomas (HCCs) carrying different hepatitis virus antigens histopathologically and systematically. PAP and ABC kits were used in the immunohistochemical study, and CAS-200 System was applied in the image cytometry. As compared with HCCs carrying HBV marker(s), the HCCs carrying HCV marker showed more cases of clear cell type (7/9 vs 4/33), better differentiation of cancers, less necrosis of hepatocytes, milder lymphocyte infiltration in the hepatic sinuses or periportal areas (P < 0.01), higher incidence of bile ductule damages, and bore a close relation to the formation of lymphoid follicle in the surrounding tissues (P < 0.05). These patients were elder, with lower grade of symptoms and better prognosis after operation. HCCs carrying only HCAg have different pathological features and clinical characteristics from which carrying HBV marker(s). The results of image cytometry are in accordance with the biological behaviour of HCC.

  13. Pancreatic neuroendocrine tumours: correlation between MSCT features and pathological classification.

    PubMed

    Luo, Yanji; Dong, Zhi; Chen, Jie; Chan, Tao; Lin, Yuan; Chen, Minhu; Li, Zi-Ping; Feng, Shi-Ting

    2014-11-01

    We aimed to evaluate the multi-slice computed tomography (MSCT) features of pancreatic neuroendocrine neoplasms (P-NENs) and analyse the correlation between the MSCT features and pathological classification of P-NENs. Forty-one patients, preoperatively investigated by MSCT and subsequently operated on with a histological diagnosis of P-NENs, were included. Various MSCT features of the primary tumour, lymph node, and distant metastasis were analysed. The relationship between MSCT features and pathologic classification of P-NENs was analysed with univariate and multivariate models. Contrast-enhanced images showed significant differences among the three grades of tumours in the absolute enhancement (P = 0.013) and relative enhancement (P = 0.025) at the arterial phase. Univariate analysis revealed statistically significant differences among the tumours of different grades (based on World Health Organization [WHO] 2010 classification) in tumour size (P = 0.001), tumour contour (P < 0.001), cystic necrosis (P = 0.001), tumour boundary (P = 0.003), dilatation of the main pancreatic duct (P = 0.001), peripancreatic tissue or vascular invasion (P < 0.001), lymphadenopathy (P = 0.011), and distant metastasis (P = 0.012). Multivariate analysis suggested that only peripancreatic tissue or vascular invasion (HR 3.934, 95 % CI, 0.426-7.442, P = 0.028) was significantly associated with WHO 2010 pathological classification. MSCT is helpful in evaluating the pathological classification of P-NENs. • P-NENs are potentially malignant, and classification of P-NENs carries important prognostic value. • MSCT plays an important role in the diagnosis and staging of P-NENs. • Correlations between classification of P-NENs and imaging findings have not been systematically evaluated. • MSCT could predict P-NENs classification and may be a useful prognostication tool.

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

    PubMed

    Tam, Allison; Barker, Jocelyn; Rubin, Daniel

    2016-01-01

    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. 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. 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. ICHE may be a useful preprocessing step a digital pathology image processing pipeline.

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

    SciTech Connect

    Tam, Allison; Barker, Jocelyn; Rubin, Daniel

    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.

  16. Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer's disease-like amyloid pathology.

    PubMed

    Ferretti, Maria Teresa; Allard, Simon; Partridge, Vanessa; Ducatenzeiler, Adriana; Cuello, A Claudio

    2012-04-02

    A growing body of evidence indicates that inflammation is one of the earliest neuropathological events in Alzheimer's disease. Accordingly, we have recently shown the occurrence of an early, pro-inflammatory reaction in the hippocampus of young, three-month-old transgenic McGill-Thy1-APP mice in the absence of amyloid plaques but associated with intracellular accumulation of amyloid beta petide oligomers. The role of such a pro-inflammatory process in the progression of the pathology remained to be elucidated. To clarify this we administered minocycline, a tetracyclic derivative with anti-inflammatory and neuroprotective properties, to young, pre-plaque McGill-Thy1-APP mice for one month. The treatment ended at the age of three months, when the mice were still devoid of plaques. Minocycline treatment corrected the up-regulation of inducible nitric oxide synthase and cyclooxygenase-2 observed in young transgenic placebo mice. Furthermore, the down-regulation of inflammatory markers correlated with a reduction in amyloid precursor protein levels and amyloid precursor protein-related products. Beta-site amyloid precursor protein cleaving enzyme 1 activity and levels were found to be up-regulated in transgenic placebo mice, while minocycline treatment restored these levels to normality. The anti-inflammatory and beta-secretase 1 effects could be partly explained by the inhibition of the nuclear factor kappa B pathway. Our study suggests that the pharmacological modulation of neuroinflammation might represent a promising approach for preventing or delaying the development of Alzheimer's disease neuropathology at its initial, pre-clinical stages. The results open new vistas to the interplay between inflammation and amyloid pathology.

  17. Peripherally administered sera antibodies recognizing amyloid-β oligomers mitigate Alzheimer's disease-like pathology and cognitive decline in aged 3× Tg-AD mice.

    PubMed

    Wang, Hai-Chao; Yu, Yun-Zhou; Liu, Si; Zhao, Meng; Xu, Qing

    2016-04-04

    Active and passive immunotherapy targeting amyloid-β (Aβ) may be the most promising strategy to prevent or treat Alzheimer's disease (AD). Previously, immunization with the recombinant 6Aβ15-T antigen generated robust anti-Aβ serum antibodies that strongly recognized Aβ42 oligomers in different mice, markedly reduced the amyloid burden, and improved behavioral performance of immunized older AD mice. Here, we further determined that these anti-6Aβ15-T serum antibodies from different strains of mice displayed anti-Aβ antibody responses against the same epitopes in the Aβ1-15 region. Peripheral administration of anti-6Aβ15-T serum antibodies was also effective to mitigate AD-like pathology and cognitive decline in aged 3× Tg-AD mice. Specifically, the levels of Aβ and tau in the brains of 3× Tg-AD mice were significantly reduced after passive immunotherapy, which seemed necessary or beneficial to ameliorate memory impairment. In addition, our results showed that this immunotherapy also prevented presynaptic dynamin 1 degradation, which might help to further protect synaptic functions and allow functional recovery of cognition. Moreover, immunization with 6Aβ15-T in rabbits induced a similar antibody response as that in mice, and the rabbit serum antibodies reacted strongly with Aβ42 oligomers and inhibited oligomer-mediated neurotoxicity. We concluded that passive immunization with Aβ42 oligomer conformation-sensitive anti-6Aβ15-T serum antibodies is effective in providing potentially therapeutic effects in aged 3× Tg-AD mice by reducing Aβ and tau.

  18. Cystinosis distal myopathy, novel clinical, pathological and genetic features.

    PubMed

    Cabrera-Serrano, Macarena; Junckerstorff, Reimar C; Alisheri, Ali; Pestronk, Alan; Laing, Nigel G; Weihl, Conrad C; Lamont, Phillipa J

    2017-09-01

    Nephropathic cystinosis is an autosomal recessive lysosomal disease in which cystine cannot exit the lysosome to complete its degradation in the cytoplasm, thus accumulating in tissues. Some patients develop a distal myopathy involving mainly hand muscles. Myopathology descriptions from only 5 patients are available in the literature. We present a comprehensive clinical, pathological and genetic description of 3 patients from 2 families with nephropathic cystinosis. Intrafamiliar variability was detected in one family in which one sibling developed a severe distal myopathy while the other sibling did not show any signs of skeletal muscle involvement. One of the patients was on treatment with Cysteamine for over 12 years but still developed the usual complications of nephropathic cystinosis in his twenties. Novel pathological findings consisting in sarcoplasmic deposits reactive for slow myosin were identified. Three previously known and one novel mutation are reported. Nephropathic cystinosis should be included in the differential diagnosis of distal myopathies in those with early renal failure. Novel clinical and pathological features are reported here contributing to the characterization of the muscle involvement in nephropathic cystinosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Cutaneous syncytial myoepithelioma:: Clinico-pathological features and differential diagnosis.

    PubMed

    Pizzi, Marco; Facchin, Federico; Kohlscheen, Eva; Sartore, Leonardo; Salmaso, Roberto; Bassetto, Franco

    2016-10-01

    Cutaneous syncytial myoepithelioma (CSM) is a very rare tumor belonging to the spectrum of skin myoepithelial lesions. CSM usually affects the upper extremities of young to middle aged patients and is characterized by peculiar morphological and immunohistochemical features. Unlike classic myoepithelioma, CSM is composed by a densely packed proliferation of spindled to histiocytoid cells, which are variably positive for EMA, S100, SMA, and frequently negative for cytokeratins and GFAP. The peculiar histopathology and the extreme rarity of such lesion (less than 40 cases reported in the literature) can make the diagnosis of CSM a true challenge. In the present case, we report the clinico-pathological features of a primary CSM occurring in a 38 year-old Caucasian man. The differential diagnoses of such lesion are also briefly discussed.

  20. Automated Intelligibility Assessment of Pathological Speech Using Phonological Features

    NASA Astrophysics Data System (ADS)

    Middag, Catherine; Martens, Jean-Pierre; Van Nuffelen, Gwen; De Bodt, Marc

    2009-12-01

    It is commonly acknowledged that word or phoneme intelligibility is an important criterion in the assessment of the communication efficiency of a pathological speaker. People have therefore put a lot of effort in the design of perceptual intelligibility rating tests. These tests usually have the drawback that they employ unnatural speech material (e.g., nonsense words) and that they cannot fully exclude errors due to listener bias. Therefore, there is a growing interest in the application of objective automatic speech recognition technology to automate the intelligibility assessment. Current research is headed towards the design of automated methods which can be shown to produce ratings that correspond well with those emerging from a well-designed and well-performed perceptual test. In this paper, a novel methodology that is built on previous work (Middag et al., 2008) is presented. It utilizes phonological features, automatic speech alignment based on acoustic models that were trained on normal speech, context-dependent speaker feature extraction, and intelligibility prediction based on a small model that can be trained on pathological speech samples. The experimental evaluation of the new system reveals that the root mean squared error of the discrepancies between perceived and computed intelligibilities can be as low as 8 on a scale of 0 to 100.

  1. Pathological features of colorectal carcinomas in MYH-associated polyposis

    PubMed Central

    O’Shea, A M; Cleary, S P; Croitoru, M A; Kim, H; Berk, T; Monga, N; Riddell, R H; Pollett, A; Gallinger, S

    2009-01-01

    Aims MYH is a DNA glycosylase in the base excision repair pathway. Germ-line biallelic mutations in the MYH gene are associated with the development of multiple colorectal adenomas and colorectal carcinoma (CRC). A slightly increased risk of CRC is suggested in monoallelic MYH mutation carriers. The aim was to characterize the histopathological features of carcinomas from biallelics and monoallelics. Methods and results Clinicopathological features of 57 colorectal carcinomas from 50 patients identified in familial CRC registries were recorded. These included 16 cancers from 14 MYH biallelics; 25 cancers from 22 MYH monoallelics; and 16 cancers from 14 controls. Carcinomas in biallelics demonstrated tubular, papillary or cribriform patterns as the predominant histological subtype, and main histological groups differed according to mutation status (P = 0.0053). All biallelic cancers were low grade, with high-grade tumours more common in monoallelics and controls (P = 0.002). Synchronous polyps were observed in 75% of biallelics, 33% of monoallelics and 43% of controls (P = 0.035). Serrated carcinoma was the predominant type in 12% (3/25) of the monoallelics but in none of the biallelics or controls. MYH immunohistochemistry failed to distinguish between groups. Conclusions Neither pathological features nor immunohistochemistry could predict the MYH mutation status of CRCs in this study. PMID:18564191

  2. Prevalence, clinical, endoscopic and pathological features of duodenitis in children

    PubMed Central

    Alper, Arik; Hardee, Steven; Rojas-velasquez, Danilo; Escalera, Sandra; Morotti, Raffaella A; Pashankar, Dinesh S.

    2015-01-01

    Objectives While gastritis and esophagitis are well studied in children, there is very limited literature on duodenitis in children. We aimed to assess the prevalence, etiology, clinical, endoscopic, and pathological features in a large cohort of unselected children with duodenitis. Methods We reviewed the pathology reports of all upper endoscopies performed at our institution over 5 years to identify children with duodenitis. Biopsy sections were reviewed to confirm the diagnosis of duodenitis. Demographic, clinical, endoscopic data and presence of associated gastritis and esophagitis were noted in all children with duodenitis. Etiology of duodenitis was correlated with the patient's clinical diagnosis. Results Out of 2772 children who had endoscopy, 352 had duodenitis with the prevalence rate of 12.7%. Gastritis was seen in 64% of children with duodenitis compared with 46% of children without duodenitis (P < 0.001). Common indications for endoscopy in children with duodenitis were abdominal pain, positive celiac serology and diarrhea. The most common etiology was celiac disease (32%), followed by Crohn's disease (13%), ulcerative colitis (3%), and Helicobacter pylori infection (6%). In 63% of cases, endoscopic appearance of duodenum was normal. Cryptitis, villous changes and cellular infiltration were noted on histology. Conclusions Prevalence of duodenitis is 12.7% in children undergoing endoscopy. Celiac disease and inflammatory bowel disease are common causes of duodenitis. Associated gastritis is common in children with duodenitis and correlation of endoscopic appearance with histology is poor. PMID:26252915

  3. Mercury-Induced Membranous Nephropathy: Clinical and Pathological Features

    PubMed Central

    Li, Shi-Jun; Zhang, Su-Hua; Chen, Hui-Ping; Zeng, Cai-Hong; Zheng, Chun-Xia; Li, Lei-Shi

    2010-01-01

    Background and objectives: Long-term contact with mercury may induce membranous nephropathy (MN); however, the clinical pathologic features and pathogenesis of mercury-induced MN have not been investigated. Design, setting, participants, & measurements: The present study retrospectively evaluated 11 cases of mercury-induced MN to analyze its causes and its clinical and pathologic features. Results: A total of 10 women and 1 man ages 15 to 45 years were enrolled in the present study. Mercury exposure was caused by mercury-containing pills (five patients), skin lightening cream (four patients), hair-dyeing agents (one patient), and mercury vapor (one patient). The duration of contact with mercury ranged from 2 to 60 months, and the urinary mercury concentrations were 1.5 to 50 times higher than reference values. All patients presented with proteinuria and normal renal function; three had nephrotic syndrome. Light microscopy revealed thickened glomerular basement membrane and mildly proliferative mesangial cells. Acute tubulointerstitial injury occurred in three patients. The immunofluorescence findings showed granular deposits of IgG and C3 along the glomerular capillary wall, mostly accompanied by deposits of C4 and C1q. IgG1 and IgG4 (predominantly IgG1) deposits were observed along the glomerular capillary loops. Nine patients reached complete remission in follow-up after withdrawal from mercury exposure. Conclusions: Deposits of IgG1 subclasses in renal tissues indicated that the pathogenesis of mercury-induced MN differs from that of idiopathic MN. It is important that clinicians are aware that mercury exposure should be considered a possible cause of membranous nephropathy. PMID:20089494

  4. [The clinical-radiologic-pathologic features of imported pulmonary histoplasmosis].

    PubMed

    Gong, Pihua; Cao, Zhaolong; Mu, Xinlin; Dong, Xiaosong; Wang, Keqiang; Feng, Rui'e; Sun, Kunkun; Wang, Hui; Gao, Zhancheng

    2015-01-01

    pulmonary nodules provide valuable diagnostic clues for imported histoplasmosis. Clinical features with pathologic findings and good response to antifungal therapy could make the diagnosis even without pathogen detection if other etiology is unlikely.

  5. Alzheimer's disease like pathology induced six weeks after aggregated amyloid-beta injection in rats: increased oxidative stress and impaired long-term memory with anxiety-like behavior.

    PubMed

    Sharma, Sheetal; Verma, Sonia; Kapoor, Monika; Saini, Avneet; Nehru, Bimla

    2016-09-01

    Amyloid-beta (Aβ) peptide deposition into insoluble plaques is a pathological hallmark of Alzheimer's disease (AD), but soluble oligomeric Aβ is considered to be more potent and has been hypothesized to directly impair learning and memory. Also, evidences from some clinical studies indicated that Aβ oligomer formation is the major cause for early AD onset. However, the biochemical mechanism involved in the oligomer-induced toxicity is not very well addressed. So, thise present study was undertaken to study the effects of single intracerebroventricular (icv) injection of protofibrillar Aβ 1-42 on the behavioral and biochemical profile in rats. Rats were divided into two groups (n = 8 per group): (1) sham control group and (2) Aβ 1-42 injected group. A single dose of protofibrillar Aβ 1-42 (5 ul) through icv injection was bilaterally administered into the dorsal hippocampus, while sham control animals were administered with 5 µl of vehicle. The results demonstrated that the protofibrillar Aβ significantly inhibited long-term memory retention and increased anxiety levels as shown by the behavioral studies. The amyloid deposits were present inside the brain even six weeks after injection as confirmed by thioflavin-T staining and the neurodegeneration induced by these deposits was confirmed by Nissl's staining in hippocampal and cortical regions. The amyloid aggregates induced reactive oxygen species (ROS) production, acetylcholinesterase activity, nitrite levels, lipid peroxidation, and inhibited antioxidant enzyme activity in hippocampus, cortex, and striatum regions of rat brain after six weeks. The present study indicated that protofibrillar Aβ 1-42 injection altered long term memory, induced anxiety-like behavior and also developed Alzheimer's disease like pathology in rats.

  6. Pediatric surface osteosarcoma: clinical, pathologic, and radiologic features.

    PubMed

    Kaste, Sue C; Fuller, Christine E; Saharia, Ashish; Neel, Michael D; Rao, Bhaskar N; Daw, Najat C

    2006-08-01

    Osteosarcoma (OS) arising from the surface of bone is far less common than its intramedullary counterpart. Although surface OSs share some radiographic and clinical features, they can be divided into three distinct histologic subtypes. We reviewed the clinical, radiographic, and pathologic features of 14 cases of pediatric surface OS treated at St. Jude Children's Research Hospital between 1970 and 2003. Seven patients had parosteal, five had periosteal, and two had high-grade surface OS. The median age at diagnosis was 16.2 years (range, 13.6-18.5 years). Nine patients were male; 11 were Caucasian. None had metastatic disease at diagnosis. Primary tumor sites included distal femur (n = 6), mid to proximal femur (n = 4), and mid to proximal tibia (n = 4). All 14 patients were treated with surgery, and 7 (1 with parosteal, 4 with periosteal, 2 with high-grade tumors) received chemotherapy. One patient experienced pulmonary metastasis of periosteal OS 16 months and 43 months after diagnosis; long-term disease-free survival followed resection of the metastatic tumors. Twelve patients remained alive and disease-free a median of 10 years (range, 1.5-25.4 years) after diagnosis. One patient died of high-grade surface OS 1.8 years after diagnosis, and one patient with periosteal OS died of gastric cancer 18.2 years after diagnosis of OS. The histologic grade predicts the clinical behavior of pediatric surface OS. Complete resection is the treatment of choice regardless of tumor subtype. Whereas chemotherapy is not indicated for parosteal OS, its role in periosteal OS remains controversial.

  7. Effect of metabolic syndrome on pathologic features of prostate cancer.

    PubMed

    Kheterpal, Emil; Sammon, Jesse D; Diaz, Mireya; Bhandari, Akshay; Trinh, Quoc-Dien; Pokala, Naveen; Sharma, Pranav; Menon, Mani; Agarwal, Piyush K

    2013-10-01

    The prevalence of metabolic syndrome has been increasing worldwide, however its association with prostate cancer (CaP) is unclear. We reviewed patients undergoing robot assisted radical prostatectomy (RARP) to evaluate if those with metabolic syndrome had more aggressive disease. A prospective database of patients undergoing RARP between January 2005 and December 2008 (n = 2756) was queried for components of metabolic syndrome (BMI ≥ 30 and ≥ 2 of the following: hypertension, diabetes or elevated blood glucose, and dyslipidemia; n = 357). Patients with no components of metabolic syndrome were used as controls (n = 694). Biopsy and final pathology were compared between the 2 groups using all controls, and using best-matched controls (n = 357) based on greedy matching by propensity score. Compared with unmatched controls, metabolic syndrome patients had higher pathology Gleason grade (≥ 7: 78% vs. 64%, P < 0.001) and higher pathologic stage (≥ T3 disease: 43% vs. 31%, P < 0.001). After controlling for confounders, those with metabolic syndrome when compared with best-matched controls had maintained the greater pathology Gleason grade (≥ 7: 78% vs. 64%, P < 0.001) and pathologic stage (≥ T3 disease: 43% vs. 32%, P < 0.001). They also had significantly greater pathologic upgrading of Gleason grade 6 adenocarcinoma found on biopsy compared with best-matched controls (63% vs. 45%, P < 0.001). On pathology, a 2-fold increase in Gleason 8 and greater was noted between patients with metabolic syndrome and best-matched controls (15% vs. 8%). After controlling for confounders, patients with metabolic syndrome were found to have higher Gleason grade and tumor stage on final pathology and were more likely to have upgrading. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Breast cancer in young women: Pathologic features and molecular phenotype.

    PubMed

    Sabiani, Laura; Houvenaeghel, Gilles; Heinemann, Mellie; Reyal, Fabien; Classe, Jean Marc; Cohen, Monique; Garbay, Jean Rémy; Giard, Sylvia; Charitansky, Hélène; Chopin, Nicolas; Rouzier, Roman; Daraï, Emile; Coutant, Charles; Azuar, Pierre; Gimbergues, Pierre; Villet, Richard; Tunon de Lara, Christine; Lambaudie, Eric

    2016-10-01

    Controversy exists about the prognosis of breast cancer in young women. Our objective was to describe clinicopathological and prognostic features to improve adjuvant treatment indications. We conducted a retrospective multi centre study including fifteen French hospitals. Disease-free survival's data, clinical and pathological criteria were collected. 5815 patients were included, 15.6% of them where between 35 and 40 years old and 8.7% below 35. In 94% of the cases, a palpable masse was found in patients ≤35 years old. Triple negative and HER2 tumors were predominantly found in patients ≤35 (22.2% and 22.1%, p < 0.01). A young age ≤40 years (p < 0.001; hazard ratio [HR]: 2.05; 95% confidence limit [CL]: 1.60-2.63) or ≤35 years (p < 0.001; [HR]: 3.86; 95% [CL]: 2.69-5.53) impacted on the indication of chemotherapy. Age ≤35 (p < 0.001; [HR]: 2.01; 95% [CL]: 1.36-2.95) was a significantly negative factor on disease-free survival. Chemotherapy (p < 0.006; [HR]: 0.6; 95% [CL]: 0.40-0.86) and positive hormone receptor status (p < 0.001; [HR]: 0.6; 95% [CL]: 0.54-0.79) appeared to be protector factors. Patients under 36, had a significantly higher rate of local recurrence and distant metastasis compared to patients >35-40 (21.5 vs. 15.4% and 21.8 vs. 12.6%, p < 0.01). Young women present a different distribution of molecular phenotypes with more luminal B and triple negative tumors with a higher grade and more lymph node involvement. A young age, must be taken as a pejorative prognostic factor and must play a part in indication of adjuvant therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Cellular focal segmental glomerulosclerosis: Clinical and pathologic features.

    PubMed

    Stokes, M B; Valeri, A M; Markowitz, G S; D'Agati, V D

    2006-11-01

    Five pathologic variants of idiopathic focal segmental glomerulosclerosis (FSGS) are recognized: collapsing (COLL), cellular (CELL), glomerular tip lesion (GTL), perihilar, and not otherwise specified (NOS). The prognostic significance of CELL FSGS has not been determined. We compared the presenting clinical and pathologic characteristics in 225 patients with CELL (N=22), COLL (N=56), GTL (N=60), and NOS (N=87) variants of idiopathic FSGS. CELL, COLL, and tip lesion all showed greater frequency and severity of nephrotic syndrome, and shorter time to biopsy compared to NOS. Predictors of end-stage renal disease (ESRD) for all FSGS patients included initial serum creatinine, % global sclerosis, % COLL lesions, chronic tubulo-interstitial injury score, and lack of remission response. COLL FSGS had the highest rate of renal insufficiency at presentation, most extensive glomerular involvement and chronic tubulo-interstitial disease, fewest remissions (13.2%), and highest rate of ESRD (65.3%). GTL patients were older and showed the highest remission rate (75.8%) and lowest rate of ESRD (5.7%). CELL variant showed intermediate rates of remission (44.5%) and ESRD (27.8%) compared to COLL and tip lesion. CELL variant may include cases of unsampled tip or COLL lesion, underscoring the importance of adequate sampling. Our data support the view that CELL and COLL FSGS are not equivalent and validates an approach to pathologic classification that distinguishes between COLL, CELL, and tip lesion variants of FSGS.

  10. Distinctive features in speech pathology: phonology or phonemics?

    PubMed

    Parker, F

    1976-02-01

    Distinctive feature is not a unique concept within linguistic theory. It has two distinct bases: phonemic theory and generative theory. Phonemic theory assumes a direct correspondence between distinctive features (the elements of phonemes) and the speech signal. Although this assumption can be shown to be incorrect, it seems to be the one most widely held in speech science. Generative theory, on the other hand, assumes no such direct relation and consequently can account for certain linguistic phenomena that phonemic theory cannot. This theory then seems to be preferable to phonemic theory for a featural analysis of misarticulation. However, there is a problem. Chomsky and Halle's system (generative theory) as it stands does not deal with the link between what it conceives to be the lowest level of linguistic structure (the phonetic matrix) and speech production. Therefore, Chomsky and Halle's distinctive features cannot be applied fruitfully to all instances of misarticulation. The discrepancy that exists between phonological structure and the speech signal must be accounted for in a theory of speech production. This can be accomplished by recognizing a production matrix below the phonetic matrix, where segments are described in terms of production features. The crucial point is that no one-to-one relationship necessarily exists between distinctive features and production features.

  11. A new feature constituting approach to detection of vocal fold pathology

    NASA Astrophysics Data System (ADS)

    Hariharan, M.; Polat, Kemal; Yaacob, Sazali

    2014-08-01

    In the last two decades, non-invasive methods through acoustic analysis of voice signal have been proved to be excellent and reliable tool to diagnose vocal fold pathologies. This paper proposes a new feature vector based on the wavelet packet transform and singular value decomposition for the detection of vocal fold pathology. k-means clustering based feature weighting is proposed to increase the distinguishing performance of the proposed features. In this work, two databases Massachusetts Eye and Ear Infirmary (MEEI) voice disorders database and MAPACI speech pathology database are used. Four different supervised classifiers such as k-nearest neighbour (k-NN), least-square support vector machine, probabilistic neural network and general regression neural network are employed for testing the proposed features. The experimental results uncover that the proposed features give very promising classification accuracy of 100% for both MEEI database and MAPACI speech pathology database.

  12. TDP-43 and pathological subtype of Alzheimer’s disease impact clinical features

    PubMed Central

    Josephs, Keith A.; Whitwell, Jennifer L.; Tosakulwong, Nirubol; Weigand, Stephen D.; Murray, Melissa E.; Serie, Amanda M.; Petrucelli, Leonard; Senjem, Matthew L.; Ivnik, Robert J.; Parisi, Joseph E.; Petersen, Ronald C.; Dickson, Dennis W.

    2015-01-01

    Objective To determine whether the frequency of TDP-43 deposition in Alzheimer’s disease (AD) differs across pathologically defined AD subtypes (Hippocampal sparing [HpSp]; Typical and Limbic), and to further examine the relationship between TDP-43, pathological subtype, and clinical features in AD. Methods We identified all cases with pathologically-confirmed AD (NIA-Reagan intermediate-high probability, Braak stage IV–VI) independent of cognitive status (n=188). Neurofibrillary tangle counts were performed using thioflavin-S microscopy in hippocampus and three neocortical regions, and all cases were subtyped: HpSp AD Pathology (n=19); Typical AD Pathology (n=136); Limbic AD Pathology (n=33). TDP-43 immunoreactivity was performed in multiple brain regions to assess for the presence of TDP-43 and TDP-43 stage. All cases were clinically sub-classified at presentation as Amnestic AD Dementia versus Atypical AD Dementia. Statistical analysis was performed using linear and penalized logistic regression to assess associations with pathological subtype, and the effects of TDP-43, accounting for possible interactions between pathological subtype and TDP-43. Results TDP-43 deposition was frequent in Typical (59%) and Limbic AD pathologies (67%), but not HpSp AD Pathology (21%) (p=0.003). The observed associations of TDP-43 with greater memory loss, naming and functional decline, and smaller hippocampal volumes, closest to death, did not differ across AD pathological subtype. Clinical presentation was associated with pathological subtype (p=0.01), but not TDP-43 (p=0.69). Interpretation Although the frequency of TDP-43 deposition in AD varies by pathological subtype, the observed effects of TDP-43 on clinical/MRI features are consistent across pathological subtypes. Clinical presentation in AD is driven by pathological subtype, not by TDP-43. PMID:26224156

  13. Clinical and pathological features of patients with nemaline myopathy.

    PubMed

    Yin, Xi; Pu, Chuan Qiang; Wang, Qian; Liu, Jie Xiao; Mao, Yan Ling

    2014-07-01

    Nemaline myopathy (NM) is a rare congenital myopathy of great heterogeneity, characterized by the presence of rods in the cytoplasm of muscle fibers. This study aimed to summarize and analyze retrospectively the clinicopathological features of 28 patients with NM. Among the 28 patients, 15 were classified as of the typical congenital type, manifested as lower- or four-limb weakness as the first symptom and slowly progressive course. Six patients were classified as of childhood onset type, with lower-limb weakness and progressive course. Seven patients were classified as of the adult onset type, with rapidly progressive course and obvious muscle atrophy. Patient's 1, 16 and 23 had rapid clinical progression. On follow up, the three patients showed respiratory failure. Limb weakness in all patients was proximal‑dominant. Hypotonia was observed in most patients. High arched feet were also observed as dysmorfic features. In all patients, the creatine kinase (CK) level was normal or mildly elevated, and electromyography revealed myogenic changes. Nemaline bodies were observed under a light microscope in more than half of the patients' muscle fibers, and especially in type I fibers. All patients showed fiber type I predominance and atrophy. Modified Gömöri trichrome staining showed characteristic purple‑colored rods. Muscle electron microscopy revealed the presence of high electron‑dense nemaline bodies around the nucleus, and of a disorganized myofibrillar apparatus, with broken myofilaments and irregular myofibrils and Z lines. The 28 patients with NM shared a number of clinical features, such as proximal limb weakness, reduced deep tendon reflex and dysmorfic features. Differences were also observed between the three types of patients, with regards to course progression, disease severity and respiratory failure. In conclusion, patients with NM showed great clinical heterogeneity. The diagnosis of NM was mainly based on the muscle biopsy.

  14. Leiomyoma of the foot: sonographic features with pathologic correlation.

    PubMed

    Stock, Harlan; Perino, Giorgio; Athanasian, Edward; Adler, Ronald

    2011-02-01

    Leiomyomas arising outside of the uterus and gastrointestinal tract are uncommon, though these benign soft tissue neoplasms have been reported in the lower extremity and foot. To our knowledge, the sonographic appearance of a lower extremity leiomyoma has not been described in the literature. This report involves a case of leiomyoma of the foot and its sonographic imaging features. MR correlative imaging and histopathology are also provided.

  15. Compulsive features in behavioural addictions: the case of pathological gambling.

    PubMed

    el-Guebaly, Nady; Mudry, Tanya; Zohar, Joseph; Tavares, Hermano; Potenza, Marc N

    2012-10-01

    To describe, in the context of DSM-V, how a focus on addiction and compulsion is emerging in the consideration of pathological gambling (PG). A systematic literature review of evidence for the proposed re-classification of PG as an addiction. Findings include: (i) phenomenological models of addiction highlighting a motivational shift from impulsivity to compulsivity associated with a protracted withdrawal syndrome and blurring of the ego-syntonic/ego-dystonic dichotomy; (ii) common neurotransmitter (dopamine, serotonin) contributions to PG and substance use disorders (SUDs); (iii) neuroimaging support for shared neurocircuitries between 'behavioural' and substance addictions and differences between obsessive-compulsive disorder (OCD), impulse control disorders (ICDs) and SUDs; (iv) genetic findings more closely related to endophenotypic constructs such as compulsivity and impulsivity than to psychiatric disorders; (v) psychological measures such as harm avoidance identifying a closer association between SUDs and PG than with OCD; (vi) community and pharmacotherapeutic trials data supporting a closer association between SUDs and PG than with OCD. Adapted behavioural therapies, such as exposure therapy, appear applicable to OCD, PG or SUDs, suggesting some commonalities across disorders. PG shares more similarities with SUDs than with OCD. Similar to the investigation of impulsivity, studies of compulsivity hold promising insights concerning the course, differential diagnosis and treatment of PG, SUDs, and OCD. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

  16. Compulsive features in behavioral addictions: the case of pathological gambling

    PubMed Central

    el-Guebaly, Nady; Mudry, Tanya; Zohar, Joseph; Tavares, Hermano; Potenza, Marc N.

    2011-01-01

    Aims To describe, in the context of DSM-V, how a focus on addiction and compulsion is emerging in the consideration of pathological gambling (PG). Methods A systematic literature review of evidence for the proposed re-classification of PG as an addiction. Results Findings include: 1. Phenomenological models of addiction highlighting a motivational shift from impulsivity to compulsivity associated with a protracted withdrawal syndrome and blurring of the ego-syntonic/ego-dystonic dichotomy; 2. Common neurotransmitter (dopamine, serotonin) contributions to PG and substance use disorders (SUDs); 3. Neuroimaging support for shared neurocircuitries between “behavioral” and substance addictions and differences between obsessive-compulsive disorder (OCD), impulse control disorders (ICDs) and SUDs; 4. Genetic findings more closely related to endophenotypic constructs like compulsivity and impulsivity than to psychiatric disorders; 5. Psychological measures such as harm avoidance identifying a closer association between SUDs and PG than with OCD; 6. Community and pharmaco-therapeutic trials data supporting a closer association between SUDs and PG than with OCD. Adapted behavioral therapies, such as exposure therapy appear applicable to OCD, PG, or SUDs, suggesting some commonalities across disorders. Conclusions PG shares more similarities with SUDs than with OCD. Similar to the investigation of impulsivity, studies of compulsivity hold promising insights concerning the course, differential diagnosis and treatment of PG, SUDs, and OCD. PMID:21985690

  17. Clinical and pathological features of alcohol-related brain damage.

    PubMed

    Zahr, Natalie M; Kaufman, Kimberley L; Harper, Clive G

    2011-05-01

    One of the sequelae of chronic alcohol abuse is malnutrition. Importantly, a deficiency in thiamine (vitamin B(1)) can result in the acute, potentially reversible neurological disorder Wernicke encephalopathy (WE). When WE is recognized, thiamine treatment can elicit a rapid clinical recovery. If WE is left untreated, however, patients can develop Korsakoff syndrome (KS), a severe neurological disorder characterized by anterograde amnesia. Alcohol-related brain damage (ARBD) describes the effects of chronic alcohol consumption on human brain structure and function in the absence of more discrete and well-characterized neurological concomitants of alcoholism such as WE and KS. Through knowledge of both the well-described changes in brain structure and function that are evident in alcohol-related disorders such as WE and KS and the clinical outcomes associated with these changes, researchers have begun to gain a better understanding of ARBD. This Review examines ARBD from the perspective of WE and KS, exploring the clinical presentations, postmortem brain pathology, in vivo MRI findings and potential molecular mechanisms associated with these conditions. An awareness of the consequences of chronic alcohol consumption on human behavior and brain structure can enable clinicians to improve detection and treatment of ARBD.

  18. The neuromuscular features of acromegaly: a clinical and pathological study.

    PubMed Central

    Khaleeli, A A; Levy, R D; Edwards, R H; McPhail, G; Mills, K R; Round, J M; Betteridge, D J

    1984-01-01

    A study of the neuromuscular features of acromegaly was performed in six patients. Clinical assessment was supplemented by quadriceps force measurements, plasma creatine kinase (CK) activities, electromyography (EMG) and nerve conduction studies. Muscle mass was measured by urinary creatinine/height indices (CHI) and cross sectional area (CSA) of thighs and calves on computed tomography. Quadriceps force/unit cross sectional area was derived. Needle biopsies of vastus lateralis were studied by histochemical and ultrastructural methods. Mean fibre area (MFA) and fibre type proportions were measured. Most of the subjects studied had muscle pain and proximal muscle weakness confirmed by quadriceps force measurements. This occurred in the absence of muscle wasting, as shown by cross sectional area measurements and normal or raised creatinine/height indices. "Myopathic" features were demonstrated by needle biopsy in half the patients and occasionally by electromyography and raised plasma creatine kinase activity. Abnormalities on needle biopsy included variation in fibre size, type 2 fibre atrophy and large type 1 MFA relative to type 2 MFA. Electronmicroscopy showed the non-specific findings of increased glycogen accumulation, excess lipofuscin pigment and myofilament loss. Images PMID:6481369

  19. Pathological features of olfactory neuroblastoma in an axolotl (Ambystoma mexicanum).

    PubMed

    Shioda, Chieko; Uchida, Kazuyuki; Nakayama, Hiroyuki

    2011-08-01

    A one-year-old, female Mexican axolotl (Ambystoma mexicanum) had a rough-surfaced, polypoid, pink tumor mass of approximately 10 mm in diameter in the oral cavity. Histologically, the tumor extended from the ethmoturbinate region and into the oral cavity and had replaced some of the maxillary bone tissue. The tumor mass was composed of a lobular architecture of small round-shaped tumor cells with occasional Flexner-Wintersteiner-like rosette formation. There were no metastatic lesions in the other organs. Immunohistochemically, the tumor cells were partly positive for several neural markers (class III beta-tubulin, S-100 protein, and doublecortin) and intensely positive for an epithelial marker (cytokeratin AE1/AE3). These results suggest that the present tumor originated from neuroectodermal tissue. Considering the location and histological and immunohistochemical features of the tumor, a diagnosis of olfactory neuroblastoma was made.

  20. Tuberculosis of the genitourinary tract: imaging features with pathological correlation.

    PubMed

    Muttarak, M; ChiangMai, W N; Lojanapiwat, B

    2005-10-01

    The prevalence of pulmonary and extrapulmonary tuberculosis (TB) has been increasing over the past decade, due to the rising number of people with acquired immunodeficiency syndrome and the development of drug-resistant strains of Mycobacterium tuberculosis. The genitourinary tract is the most common site of extrapulmonary TB. Diagnosis is often difficult because TB has a variety of clinical and radiological findings. It can mimic numerous other disease entities. A high level of clinical suspicion and familiarity with various radiological manifestations of TB allow early diagnosis and timely initiation of proper management. This pictorial essay illustrates the spectrum of imaging features of TB affecting the kidney, ureter, bladder, and the female and male genital tracts.

  1. Acute Chorioamnionitis and Funisitis: Definition, Pathologic Features, and Clinical Significance

    PubMed Central

    Kim, Chong Jai; Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol; Yoon, Bo Hyun; Kim, Yeon Mee

    2015-01-01

    ; however, in fetuses, it is a risk factor for short- and long-term complications (i.e. neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, and cerebral palsy). This article reviews the definition, pathogenesis, grading and staging, and clinical significance of the most common lesions in placental pathology. Illustrations of the lesions and diagrams of the mechanisms of disease are provided. PMID:26428501

  2. Clinico-pathological feature of pilomyxoid astrocytomas: three case reports.

    PubMed

    Nagaishi, Masaya; Yokoo, Hideaki; Hirato, Junko; Yoshimoto, Yuhei; Nakazato, Yoichi

    2011-04-01

    Pilomyxoid astrocytoma (PMA) is a newly identified variant of pilocytic astrocytoma (PA). We report three cases of PMA with comparison to seven cases of PA in terms of their clinicopathological features. The three cases occurred at the ages of 2, 36 and 6 years, and their tumors were located in the left basal ganglia, the pineal gland, and the cerebellum, respectively. They were diagnosed PMA by surgical specimens that showed a characteristic monomorphous architecture with an angiocentric growth pattern and myxoid background. One patient developed localized relapse at 6 months after the surgery, but the other patients remained alive without tumor progression more than 5 years after treatment. In analysis of the immunohistochemical association in PMA and PA, no specific staining was found to be useful for differential diagnosis of PMA from PA. The expression of biomarkers including O-6-methylguanine-DNA methyltransferase, p53, MIB-1, and EGF receptor neither distinguished PMA from PA nor correlated with outcome. But almost all PMA and PA that demonstrated prominent positivity for nestin showed a high MIB-1 labelling index (LI), and four of these five patients suffered a relapse in the early phase. These results suggest that immunohistochemical expression of nestin and MIB-1 LI may correlate with the aggressiveness of the tumor in PA and PMA.

  3. Diagnostic Clinical, Electrodiagnostic and Muscle Pathology Features of Spinal and Bulbar Muscular Atrophy.

    PubMed

    Jokela, Manu E; Udd, Bjarne

    2016-03-01

    Kennedy's disease or spinal and bulbar muscular atrophy (SBMA) is a multi-system disorder affecting adult males, which is characterized by weakness of limbs and faciobulbar muscles primarily due to loss of lower motor neurons. Besides the obvious motor neuronopathy, additional findings in a substantial proportion of SBMA patients include sensory neuropathy and signs of androgen deficiency, such as poor sexual functioning and reduced fertility with gynaecomastia. The presence of elevated glucose, liver pathology or dyslipidaemia is less consistent features. We review the striking clinical, electrodiagnostic and muscle pathology features characteristic of Kennedy's disease, which has some peculiar and diagnostically useful features not observed in many other neuromuscular disorders.

  4. An improved retinal vessel segmentation method based on high level features for pathological images.

    PubMed

    Ganjee, Razieh; Azmi, Reza; Gholizadeh, Behrouz

    2014-09-01

    Most of the retinal blood vessel segmentation approaches use low level features, resulting in segmenting non-vessel structures together with vessel structures in pathological retinal images. In this paper, a new segmentation method based on high level features is proposed which can process the structure of vessel and non-vessel independently. In this method, segmentation is done in two steps. First, using low level features segmentation is accomplished. Second, using high level features, the non-vessel components are removed. For evaluation, STARE database is used which is publicly available in this field. The results show that the proposed method has 0.9536 accuracy and 0.0191 false positive average on all images of the database and 0.9542 accuracy and 0.0236 false positive average on pathological images. Therefore, the proposed approach shows acceptable accuracy on all images compared to other state of the art methods, and the least false positive average on pathological images.

  5. Intelligibility Evaluation of Pathological Speech through Multigranularity Feature Extraction and Optimization.

    PubMed

    Fang, Chunying; Li, Haifeng; Ma, Lin; Zhang, Mancai

    2017-01-01

    Pathological speech usually refers to speech distortion resulting from illness or other biological insults. The assessment of pathological speech plays an important role in assisting the experts, while automatic evaluation of speech intelligibility is difficult because it is usually nonstationary and mutational. In this paper, we carry out an independent innovation of feature extraction and reduction, and we describe a multigranularity combined feature scheme which is optimized by the hierarchical visual method. A novel method of generating feature set based on S-transform and chaotic analysis is proposed. There are BAFS (430, basic acoustics feature), local spectral characteristics MSCC (84, Mel S-transform cepstrum coefficients), and chaotic features (12). Finally, radar chart and F-score are proposed to optimize the features by the hierarchical visual fusion. The feature set could be optimized from 526 to 96 dimensions based on NKI-CCRT corpus and 104 dimensions based on SVD corpus. The experimental results denote that new features by support vector machine (SVM) have the best performance, with a recognition rate of 84.4% on NKI-CCRT corpus and 78.7% on SVD corpus. The proposed method is thus approved to be effective and reliable for pathological speech intelligibility evaluation.

  6. Intelligibility Evaluation of Pathological Speech through Multigranularity Feature Extraction and Optimization

    PubMed Central

    Ma, Lin; Zhang, Mancai

    2017-01-01

    Pathological speech usually refers to speech distortion resulting from illness or other biological insults. The assessment of pathological speech plays an important role in assisting the experts, while automatic evaluation of speech intelligibility is difficult because it is usually nonstationary and mutational. In this paper, we carry out an independent innovation of feature extraction and reduction, and we describe a multigranularity combined feature scheme which is optimized by the hierarchical visual method. A novel method of generating feature set based on S-transform and chaotic analysis is proposed. There are BAFS (430, basic acoustics feature), local spectral characteristics MSCC (84, Mel S-transform cepstrum coefficients), and chaotic features (12). Finally, radar chart and F-score are proposed to optimize the features by the hierarchical visual fusion. The feature set could be optimized from 526 to 96 dimensions based on NKI-CCRT corpus and 104 dimensions based on SVD corpus. The experimental results denote that new features by support vector machine (SVM) have the best performance, with a recognition rate of 84.4% on NKI-CCRT corpus and 78.7% on SVD corpus. The proposed method is thus approved to be effective and reliable for pathological speech intelligibility evaluation. PMID:28194222

  7. Feature analysis of pathological speech signals using local discriminant bases technique.

    PubMed

    Umapathy, K; Krishnan, S

    2005-07-01

    Speech is an integral part of the human communication system. Various pathological conditions affect the vocal functions, inducing speech disorders. Acoustic parameters of speech are commonly used for the assessment of speech disorders and for monitoring the progress of the patient over the course of therapy. In the last two decades, signal-processing techniques have been successfully applied in screening speech disorders. In the paper, a novel approach is proposed to classify pathological speech signals using a local discriminant bases (LDB) algorithm and wavelet packet decompositions. The focus of the paper was to demonstrate the significance of identifying the signal subspaces that contribute to the discriminatory characteristics of normal and pathological speech signals in a computationally efficient way. Features were extracted from target subspaces for classification, and time-frequency decomposition was used to eliminate the need for segmentation of the speech signals. The technique was tested with a database of 212 speech signals (51 normal and 161 pathological) using the Daubechies wavelet (db4). Classification accuracies up to 96% were achieved for a two-group classification as normal and pathological speech signals, and 74% was achieved for a four-group classification as male normal, female normal, male pathological and female pathological signals.

  8. Uncommon non-Hodgkin lymphomas of childhood: pathological diagnosis, clinical features and treatment approaches.

    PubMed

    Sandlund, John T; Perkins, Sherrie L

    2015-06-01

    We provide a review of the pathological and clinical features for uncommon B-cell and T-cell lymphomas of childhood with a specific focus on advances in treatment approaches and outcomes. There is clearly a need for prospective investigation of both the clinical and biological features of the uncommon non-Hodgkin lymphoma subtypes in childhood. These results should lead to more uniform and more effective treatment approaches.

  9. The I1307K APC polymorphism in Ashkenazi Jews with colorectal cancer: clinical and pathologic features.

    PubMed

    Locker, Gershon Y; Kaul, Karen; Weinberg, David S; Gatalica, Zoran; Gong, Gordon; Peterman, Amy; Lynch, Jane; Klatzco, Lucy; Olopade, Olufunmilayo I; Bomzer, Charles A; Newlin, Anna; Keenan, Eileen; Tajuddin, Mohammed; Knezetic, Joseph; Coronel, Stephanie; Lynch, Henry T

    2006-08-01

    Colorectal cancer is common in Ashkenazi Jews. The I1307K APC mutation occurs in 6-7% of Ashkenazi Jews and increases the risk of colorectal cancer. This study aimed to describe the clinical, pathologic and epidemiologic features of colorectal cancer in I1307K carriers to determine whether there were any features which might warrant individual screening for the mutation. In all, 215 Ashkenazi Jews with a personal history of colorectal cancer were enrolled. Clinical and family history, pathology reports, and slides were obtained and blood drawn for I1307K determination. The presence of the mutation was determined by PCR from white blood cell DNA. Colorectal cancer pathology slides were read in a blinded fashion. Of the 215 enrolled patients, 26 (12.1%) tested positive for I1307K. There was no difference in the pathologic features between colorectal cancers in Ashkenazi carriers compared to noncarriers. There was no difference in the age at diagnosis or history of second or other primaries. Carriers had an increased likelihood of having a first-degree relative with colorectal cancer (50%) compared to noncarriers (28%, P < 0.04). We could find no distinguishing feature other than family history that characterizes I1307K positive colorectal cancers. We could find no group of Ashkenazi Jews with colorectal cancer for whom screening for I1307K would be clinically useful.

  10. MRI Features of Mucinous Cancer of the Breast: Correlation With Pathologic Findings and Other Imaging Methods.

    PubMed

    Bitencourt, Almir G V; Graziano, Luciana; Osório, Cynthia A B T; Guatelli, Camila S; Souza, Juliana A; Mendonça, Maria Helena S; Marques, Elvira F

    2016-02-01

    Mucinous breast carcinoma is an uncommon histologic type of invasive breast carcinoma that can be differentiated in pure and mixed forms, which have different prognosis and treatment. MRI features of both types of mucinous breast carcinomas are discussed, illustrated, and compared with pathologic findings and with other imaging methods, including mammography, ultrasound, and PET/CT.

  11. Six additional systematic lateral cores enhance sextant biopsy prediction of pathological features at radical prostatectomy.

    PubMed

    Singh, Herb; Canto, Eduardo I; Shariat, Shahrokh F; Kadmon, Dov; Miles, Brian J; Wheeler, Thomas M; Slawin, Kevin M

    2004-01-01

    We evaluated the contribution of 6 additional systematically obtained, laterally directed biopsy cores to traditional sextant biopsy for the prediction of final pathological findings in the radical prostatectomy specimen. We studied 178 consecutive patients with no history of prostate biopsy in whom prostate cancer was diagnosed during an initial systematic 12 core biopsy and who subsequently underwent radical prostatectomy. Of the systematic 12 cores we compared the subset of the 6 traditional sextant cores (S6C), the set of 6 laterally directed cores (L6C) and the complete 12 core set, which included the 6 traditional sextant and the 6 laterally directed cores. Biopsy Gleason score, number of positive cores, total cancer length and percent of tumor in the biopsy sets were examined for their ability to predict extracapsular extension, total tumor volume and pathological Gleason score. On univariable analyses the biopsy parameters of the complete 12 core set correlated more strongly with extracapsular extension and total tumor volume than the biopsy parameters of S6C or L6C. On multivariable analyses S6C and L6C were independent predictors of pathological features at prostatectomy. The addition of 6 systematically obtained, laterally directed cores to traditional sextant biopsy improved the ability to predict pathological features at prostatectomy by a statistically and prognostically significant margin. Preoperative nomograms that use data from a full complement of 12 systematic cores, specifying sextant and laterally directed biopsy cores, should demonstrate improved performance in predicting prostatectomy pathology.

  12. [A comparative study of pathological voice based on traditional acoustic characteristics and nonlinear features].

    PubMed

    Gan, Deying; Hu, Weiping; Zhao, Bingxin

    2014-10-01

    By analyzing the mechanism of pronunciation, traditional acoustic parameters, including fundamental frequency, Mel frequency cepstral coefficients (MFCC), linear prediction cepstrum coefficient (LPCC), frequency perturbation, amplitude perturbation, and nonlinear characteristic parameters, including entropy (sample entropy, fuzzy entropy, multi-scale entropy), box-counting dimension, intercept and Hurst, are extracted as feature vectors for identification of pathological voice. Seventy-eight normal voice samples and 73 pathological voice samples for /a/, and 78 normal samples and 80 pathological samples for /i/ are recognized based on support vector machine (SVM). The results showed that compared with traditional acoustic parameters, nonlinear characteristic parameters could be well used to distinguish between healthy and pathological voices, and the recognition rates for /a/ were all higher than those for /i/ except for multi-scale entropy. That is why the /a/ sound data is used widely in related research at home and abroad for obtaining better identification of pathological voices. Adopting multi-scale entropy for /i/ could obtain higher recognition rate than /a/ between healthy and pathological samples, which may provide some useful inspiration for evaluating vocal compensatory function.

  13. Clinical and Pathologic Features of a Suspected Selenium Deficiency in Captive Plains Zebras.

    PubMed

    Chen, Feilan; Gao, Jie; Wu, Denghu; Xu, Lei; Han, Wenli; Zhang, Denghua; Bi, Xiaoyun; He, Mingzhong; Pan, Yongquan

    2017-03-01

    Previous studies have shown that selenium (Se) deficiency is associated with nutritional myopathy, known as white muscle disease (WMD), in horses. However, correlations between Se deficiency and clinical findings, such as hematologic biochemical values and pathological features, have not been evaluated in captive plains zebras. The purpose of the present study was to investigate the clinical and pathologic features that may be caused by a Se deficiency in the captive plains zebra. Clinical findings, feed analyses, hematologic biochemical analyses, response to treatment, and pathologic examination were assessed in six affected plains zebras. The dietary concentration of Se in feed was also tested. Sudden death occurred in two cases during the first day of the onset of symptoms. Two zebras died at 4 days and two zebras survived after treatment. The clinical signs in affected animals were characterized by general weakness, astasia, and abnormal postural positions. The Se concentration in hay from the breeding stable was low, based on the reference value. Glutathione peroxidase (GSH-Px) activity was lower compared with the equine reference value. Multiple areas of subcutaneous steatitis and pale skeletal muscle and myocardium were revealed at gross necropsy. Degeneration and necrosis of myocardial and skeletal muscles, as well as congestion of the liver, lung, and kidney were found via histopathological examination. No suspected bacterial infections were found. Feed analyses, response to treatment, serum GSH-Px activity, and pathological features suggest that Se deficiency may have caused the disease in the six affected captive plains zebra.

  14. MR imaging features and staging of neuroendocrine carcinomas of the uterine cervix with pathological correlations.

    PubMed

    Duan, Xiaohui; Ban, Xiaohua; Zhang, Xiang; Hu, Huijun; Li, Guozhao; Wang, Dongye; Wang, Charles Qian; Zhang, Fang; Shen, Jun

    2016-12-01

    To determine MR imaging features and staging accuracy of neuroendocrine carcinomas (NECs) of the uterine cervix with pathological correlations. Twenty-six patients with histologically proven NECs, 60 patients with squamous cell carcinomas (SCCs), and 30 patients with adenocarcinomas of the uterine cervix were included. The clinical data, pathological findings, and MRI findings were reviewed retrospectively. MRI features of cervical NECs, SCCs, and adenocarcinomas were compared, and MRI staging of cervical NECs was compared with the pathological staging. Cervical NECs showed a higher tendency toward a homogeneous signal intensity on T2-weighted imaging and a homogeneous enhancement pattern, as well as a lower ADC value of tumour and a higher incidence of lymphadenopathy, compared with SCCs and adenocarcinomas (P < 0.05). An ADC value cutoff of 0.90 × 10(-3) mm(2)/s was robust for differentiation between cervical NECs and other cervical cancers, with a sensitivity of 63.3 % and a specificity of 95 %. In 21 patients who underwent radical hysterectomy and lymphadenectomy, the overall accuracy of tumour staging by MR imaging was 85.7 % with reference to pathology staging. Homogeneous lesion texture and low ADC value are likely suggestive features of cervical NECs and MR imaging is reliable for the staging of cervical NECs. • Cervical NECs show a tendency of lesion homogeneity and lymphadenopathy • Low ADC values are found in cervical NECs • MRI is an accurate imaging modality for the cervical NEC staging.

  15. Computer aided quantification of pathological features for flexor tendon pulleys on microscopic images.

    PubMed

    Liu, Yung-Chun; Chen, Hsin-Chen; Shih, Hui-Hsuan; Yang, Tai-Hua; Yang, Hsiao-Bai; Yang, Dee-Shan; Su, Fong-Chin; Sun, Yung-Nien

    2013-01-01

    Quantifying the pathological features of flexor tendon pulleys is essential for grading the trigger finger since it provides clinicians with objective evidence derived from microscopic images. Although manual grading is time consuming and dependent on the observer experience, there is a lack of image processing methods for automatically extracting pulley pathological features. In this paper, we design and develop a color-based image segmentation system to extract the color and shape features from pulley microscopic images. Two parameters which are the size ratio of abnormal tissue regions and the number ratio of abnormal nuclei are estimated as the pathological progression indices. The automatic quantification results show clear discrimination among different levels of diseased pulley specimens which are prone to misjudgments for human visual inspection. The proposed system provides a reliable and automatic way to obtain pathological parameters instead of manual evaluation which is with intra- and interoperator variability. Experiments with 290 microscopic images from 29 pulley specimens show good correspondence with pathologist expectations. Hence, the proposed system has great potential for assisting clinical experts in routine histopathological examinations.

  16. Pulmonary ground-glass opacity: computed tomography features, histopathology and molecular pathology

    PubMed Central

    Gao, Jian-Wei; Rizzo, Stefania; Ma, Li-Hong; Qiu, Xiang-Yu; Warth, Arne; Seki, Nobuhiko; Hasegawa, Mizue; Zou, Jia-Wei; Li, Qian; Femia, Marco

    2017-01-01

    The incidence of pulmonary ground-glass opacity (GGO) lesions is increasing as a result of the widespread use of multislice spiral computed tomography (CT) and the low-dose CT screening for lung cancer detection. Besides benign lesions, GGOs can be a specific type of lung adenocarcinomas or their preinvasive lesions. Evaluation of pulmonary GGO and investigation of the correlation between CT imaging features and lung adenocarcinoma subtypes or driver genes can be helpful in confirming the diagnosis and in guiding the clinical management. Our review focuses on the pathologic characteristics of GGO detected at CT, involving histopathology and molecular pathology.

  17. Longitudinal Validation of General and Specific Structural Features of Personality Pathology

    PubMed Central

    Wright, Aidan G.C.; Hopwood, Christopher J.; Skodol, Andrew E.; Morey, Leslie C.

    2016-01-01

    Theorists have long argued that personality disorder (PD) is best understood in terms of general impairments shared across the disorders as well as more specific instantiations of pathology. A model based on this theoretical structure was proposed as part of the DSM-5 revision process. However, only recently has this structure been subjected to formal quantitative evaluation, with little in the way of validation efforts via external correlates or prospective longitudinal prediction. We used the Collaborative Longitudinal Study of Personality Disorders dataset to: (1) estimate structural models that parse general from specific variance in personality disorder features, (2) examine patterns of growth in general and specific features over the course of 10 years, and (3) establish concurrent and dynamic longitudinal associations in PD features and a host of external validators including basic personality traits and psychosocial functioning scales. We found that general PD exhibited much lower absolute stability and was most strongly related to broad markers of psychosocial functioning, concurrently and longitudinally, whereas specific features had much higher mean stability and exhibited more circumscribed associations with functioning. However, both general and specific factors showed recognizable associations with normative and pathological traits. These results can inform efforts to refine the conceptualization and diagnosis of personality pathology. PMID:27819472

  18. Glioma Grading Using Cell Nuclei Morphologic Features in Digital Pathology Images

    PubMed Central

    Reza, Syed M. S.; Iftekharuddin, Khan M.

    2016-01-01

    This work proposes a computationally efficient cell nuclei morphologic feature analysis technique to characterize the brain gliomas in tissue slide images. In this work, our contributions are two-fold: 1) obtain an optimized cell nuclei segmentation method based on the pros and cons of the existing techniques in literature, 2) extract representative features by k-mean clustering of nuclei morphologic features to include area, perimeter, eccentricity, and major axis length. This clustering based representative feature extraction avoids shortcomings of extensive tile [1] [2] and nuclear score [3] based methods for brain glioma grading in pathology images. Multilayer perceptron (MLP) is used to classify extracted features into two tumor types: glioblastoma multiforme (GBM) and low grade glioma (LGG). Quantitative scores such as precision, recall, and accuracy are obtained using 66 clinical patients’ images from The Cancer Genome Atlas (TCGA) [4] dataset. On an average ~94% accuracy from 10 fold cross-validation confirms the efficacy of the proposed method. PMID:27942094

  19. Glioma grading using cell nuclei morphologic features in digital pathology images

    NASA Astrophysics Data System (ADS)

    Reza, Syed M. S.; Iftekharuddin, Khan M.

    2016-03-01

    This work proposes a computationally efficient cell nuclei morphologic feature analysis technique to characterize the brain gliomas in tissue slide images. In this work, our contributions are two-fold: 1) obtain an optimized cell nuclei segmentation method based on the pros and cons of the existing techniques in literature, 2) extract representative features by k-mean clustering of nuclei morphologic features to include area, perimeter, eccentricity, and major axis length. This clustering based representative feature extraction avoids shortcomings of extensive tile [1] [2] and nuclear score [3] based methods for brain glioma grading in pathology images. Multilayer perceptron (MLP) is used to classify extracted features into two tumor types: glioblastoma multiforme (GBM) and low grade glioma (LGG). Quantitative scores such as precision, recall, and accuracy are obtained using 66 clinical patients' images from The Cancer Genome Atlas (TCGA) [4] dataset. On an average ~94% accuracy from 10 fold crossvalidation confirms the efficacy of the proposed method.

  20. Tissue classification of liver pathological tissue specimens image using spectral features

    NASA Astrophysics Data System (ADS)

    Hashimoto, Emi; Ishikawa, Masahiro; Shinoda, Kazuma; Hasegawa, Madoka; Komagata, Hideki; Kobayashi, Naoki; Mochidome, Naoki; Oda, Yoshinao; Iwamoto, Chika; Ohuchida, Kenoki; Hashizume, Makoto

    2017-03-01

    In digital pathology diagnosis, accurate recognition and quantification of the tissue structure is an important factor for computer-aided diagnosis. However, the classification accuracy of cytoplasm is low in Hematoxylin and eosin (HE) stained liver pathology specimens because the RGB color values of cytoplasm are almost similar to that of fibers. In this paper, we propose a new tissue classification method for HE stained liver pathology specimens by using hyperspectral image. At first we select valid spectra from the image to make a clear distinction between fibers and cytoplasm, and then classify five types of tissue based on the bag of features (BoF). The average classification accuracy for all tissues was improved by 11% in the case of using BoF of RGB and selected spectra bands in comparison with using only RGB. In particular, the improvement reached to 24% for fibers and 5% for cytoplasm.

  1. Detection of bacterial antigens and Alzheimer's disease-like pathology in the central nervous system of BALB/c mice following intranasal infection with a laboratory isolate of Chlamydia pneumoniae.

    PubMed

    Little, Christopher S; Joyce, Timothy A; Hammond, Christine J; Matta, Hazem; Cahn, David; Appelt, Denah M; Balin, Brian J

    2014-01-01

    Pathology consistent with that observed in Alzheimer's disease (AD) has previously been documented following intranasal infection of normal wild-type mice with Chlamydia pneumoniae (Cpn) isolated from an AD brain (96-41). In the current study, BALB/c mice were intranasally infected with a laboratory strain of Cpn, AR-39, and brain and olfactory bulbs were obtained at 1-4 months post-infection (pi). Immunohistochemistry for amyloid beta or Cpn antigens was performed on sections from brains of infected or mock-infected mice. Chlamydia-specific immunolabeling was identified in olfactory bulb tissues and in cerebrum of AR-39 infected mice. The Cpn specific labeling was most prominent at 1 month pi and the greatest burden of amyloid deposition was noted at 2 months pi, whereas both decreased at 3 and 4 months. Viable Cpn was recovered from olfactory bulbs of 3 of 3 experimentally infected mice at 1 and 3 months pi, and in 2 of 3 mice at 4 months pi. In contrast, in cortical tissues of infected mice at 1 and 4 months pi no viable organism was obtained. At 3 months pi, only 1 of 3 mice had a measurable burden of viable Cpn from the cortical tissues. Mock-infected mice (0 of 3) had no detectable Cpn in either olfactory bulbs or cortical tissues. These data indicate that the AR-39 isolate of Cpn establishes a limited infection predominantly in the olfactory bulbs of BALB/c mice. Although infection with the laboratory strain of Cpn promotes deposition of amyloid beta, this appears to resolve following reduction of the Cpn antigen burden over time. Our data suggest that infection with the AR-39 laboratory isolate of Cpn results in a different course of amyloid beta deposition and ultimate resolution than that observed following infection with the human AD-brain Cpn isolate, 96-41. These data further support that there may be differences, possibly in virulence factors, between Cpn isolates in the generation of sustainable AD pathology.

  2. Pathology

    SciTech Connect

    Rubin, E.; Farber, J.L. )

    1988-01-01

    This book contains 29 chapters. Some of the titles are: Genetic and Systemic Diseases; Cell Injury; Inflammation; The Gastrointestinal o Tract; The Pancreas; Environmental and Nutritional Pathology; Infectious and Parasitic Diseases; and Blood Vessels.

  3. A novel recombinant 6Aβ15-THc-C chimeric vaccine (rCV02) mitigates Alzheimer’s disease-like pathology, cognitive decline and synaptic loss in aged 3 × Tg-AD mice

    PubMed Central

    Yu, Yun-Zhou; Liu, Si; Wang, Hai-Chao; Shi, Dan-Yang; Xu, Qing; Zhou, Xiao-Wei; Sun, Zhi-Wei; Huang, Pei-Tang

    2016-01-01

    Alzheimer’s disease (AD) is a neurodegenerative disorder that impairs memory and cognition. Targeting amyloid-β (Aβ) may be currently the most promising immunotherapeutic strategy for AD. In this study, a recombinant chimeric 6Aβ15-THc-C immunogen was formulated with alum adjuvant as a novel Aβ B-cell epitope candidate vaccine (rCV02) for AD. We examined its efficacy in preventing the cognitive deficit and synaptic impairment in 3 × Tg-AD mice. Using a toxin-derived carrier protein, the rCV02 vaccine elicited robust Aβ-specific antibodies that markedly reduced AD-like pathology and improved behavioral performance in 3 × Tg-AD mice. Along with the behavioral improvement in aged 3 × Tg-AD mice, rCV02 significantly decreased calpain activation concurrent with reduced soluble Aβ or oligomeric forms of Aβ, probably by preventing dynamin 1 and PSD-95 degradation. Our data support the hypothesis that reducing Aβ levels in rCV02-immunized AD mice increases the levels of presynaptic dynamin 1 and postsynaptic PSD-95 allowing functional recovery of cognition. In conclusion, this novel and highly immunogenic rCV02 shows promise as a new candidate prophylactic vaccine for AD and may be useful for generating rapid and strong Aβ-specific antibodies in AD patients with pre-existing memory Th cells generated after immunization with conventional tetanus toxoid vaccine. PMID:27255752

  4. The impact of digital image processing artefacts mimicking pathological features associated with restorations.

    PubMed

    Brettle, D; Carmichael, F

    2011-08-26

    Image processing of digital X-ray images is known to have the potential to produce artefacts that may mimic pathology. A study was conducted at a UK dental radiology conference to demonstrate this effect in dentistry. Sixteen digital X-rays of single teeth containing restorations were randomly presented in both unprocessed and processed formats to an auditorium of 42 participants. Participants interactively scored each image on a scale from 1-5 where 1 was definitely no pathology and 5 was definitely pathology. The display conditions were confirmed for each participant using a validated threshold contrast test. The results show that 52% (81/157) of responses at level 1 for the unprocessed images changed to levels 4 or 5 after image processing. This study illustrates the potential for image processing artefacts to mimic pathology particularly at high contrast boundaries and introduces the risk of unnecessary interventions. In order to minimise this risk, it is recommended that for digital radiographs containing pathology relating to high contrast boundaries, non-related high contrast features such as unrelated restorations or tooth/bone margins are also considered to exclude the possibility of artefact. If there is doubt, reference should be made to the unprocessed data.

  5. Glycogen storage diseases: a brief review and update on clinical features, genetic abnormalities, pathologic features, and treatment.

    PubMed

    Hicks, John; Wartchow, Eric; Mierau, Gary

    2011-10-01

    Glycogen storage diseases (GSD) affect primarily the liver, skeletal muscle, heart, and sometimes the central nervous system and the kidneys. These unique diseases are quite varied in age of onset of symptoms, morbidity, and mortality. Glycogen storage diseases are classified according to their individual enzyme deficiency. Each of these enzymes regulates synthesis or degradation of glycogen. Interestingly, there is great phenotypic variation and variable clinical courses even when a specific enzyme is altered by mutation. Depending on the specific mutation in an enzyme, a GSD patient may have a favorable or unfavorable prognosis. With neonatal or infantile forms, some GSDs lead to death within the first year of life, whereas other glycogen storage diseases are relatively asymptomatic or may cause only exercise intolerance. The paper provides a brief review and update of glycogen storage diseases, with respect to clinical features, genetic abnormalities, pathologic features, and treatment.

  6. Preventing eating disorder pathology: common and unique features of successful eating disorders prevention programs.

    PubMed

    Ciao, Anna C; Loth, Katie; Neumark-Sztainer, Dianne

    2014-07-01

    Over the past two decades, the field of eating disorders has made remarkable strides in identifying, evaluating, and disseminating successful prevention programs. The current review identifies and discusses nine distinct eating disorders prevention programs that reduce existing eating disorder pathology or prevent the onset of future pathology. Each program was evaluated in one or more controlled trial with a follow-up period of at least six months. We review the evidence base for these nine successful programs and discuss their common and unique features. Based on authors' descriptions of their programs in published trials, we found that all programs were theory-driven, targeted one or more eating disorder risk factor (e.g., body dissatisfaction), were delivered across multiple group sessions, and included at least some interactive content. Most programs included content related to healthy eating/nutrition, media literacy/sociocultural pressures, and body acceptance/body satisfaction. Notably, there was wide variation in some participant features (e.g., participant age, sex, risk status) and intervention features (e.g., setting and format, length and dose, providers), suggesting that a variety of programs are beneficial in impacting eating disorder pathology. Implications and directions for future research are discussed, including an increased focus on universal and indicated prevention programs, expanding programs to a wider age range and a broader spectrum of weight-related problems, and rigorous evaluation of programs through efficacy, effectiveness, and implementation research.

  7. Preventing Eating Disorder Pathology: Common and Unique Features of Successful Eating Disorders Prevention Programs

    PubMed Central

    Ciao, Anna C.; Loth, Katie; Neumark-Sztainer, Dianne

    2014-01-01

    Over the past two decades, the field of eating disorders has made remarkable strides in identifying, evaluating, and disseminating successful prevention programs. The current review identifies and discusses nine distinct eating disorders prevention programs that reduce existing eating disorder pathology or prevent the onset of future pathology. Each program was evaluated in one or more controlled trial with a follow-up period of at least six months. We review the evidence base for these nine successful programs and discuss their common and unique features. Based on authors’ descriptions of their programs in published trials, we found that all programs were theory-driven, targeted one or more eating disorder risk factor (e.g., body dissatisfaction), were delivered across multiple group sessions, and included at least some interactive content. Most programs included content related to healthy eating/nutrition, media literacy/sociocultural pressures, and body acceptance/body satisfaction. Notably, there was wide variation in some participant features (e.g., participant age, sex, risk status) and intervention features (e.g., setting and format, length and dose, providers), suggesting that a variety of programs are beneficial in impacting eating disorder pathology. Implications and directions for future research are discussed, including an increased focus on universal and indicated prevention programs, expanding programs to a wider age range and a broader spectrum of weight-related problems, and rigorous evaluation of programs through efficacy, effectiveness, and implementation research. PMID:24821099

  8. Assessment of pathological prostate cancer characteristics in men with favorable biopsy features on predominantly sextant biopsy.

    PubMed

    Chun, Felix K-H; Suardi, Nazareno; Capitanio, Umberto; Jeldres, Claudio; Ahyai, Sascha; Graefen, Markus; Haese, Alexander; Steuber, Thomas; Erbersdobler, Andreas; Montorsi, Francesco; Huland, Hartwig; Karakiewicz, Pierre I

    2009-03-01

    The rate of insignificant prostate cancer (IPCa) is increasing. To examine three end points in patients with a single, positive core and no high-grade prostate cancer (PCa) at biopsy, namely (1) rate of clinical IPCa at radical prostatectomy (RP), defined as organ-confined PCa with a Gleason score of 6 or lower and tumor volume<0.5 cc; (2) rate of pathologically unfavorable PCa at RP (Gleason 7-10 or non-organ-confined disease); and (3) ability to predict either insignificant or unfavorable PCa at RP. Retrospective analysis of 209 men with one positive biopsy core showing Gleason 6 or lower. : Detailed clinical and RP data were used in multivariable logistic regression models. Their bias-corrected accuracy estimates were quantified using the area under the curve (AUC) method. At RP, IPCa was present in 28 patients (13.4%) and pathologically unfavorable PCa, defined as Gleason 7 or higher or non-organ-confined PCa, was reported in 70 (33.5%) of 209 men; when Gleason 8 or higher or non-organ-confined PCa was considered, the proportion fell to 11%. Our multivariable models predicting different categories of pathologically unfavorable PCa at RP had an accuracy rate between 56% and 68% for predicting IPCa at RP versus 65.1% to 66.1% and 61.7% for the IPCa nomograms of Kattan et al and Nakanishi et al, respectively. Our data are not applicable to screening because they originate from a referral population. Despite highly favorable biopsy features, between 11% and 33% of men had unfavorable PCa at RP and only a minority (13.4%) had pathologically confirmed IPCa. Neither clinically insignificant nor pathologically unfavorable features could be predicted with sufficient accuracy for clinical decision making.

  9. Imaging Characteristics of Pathologically Proven Thymic Hyperplasia: Identifying Features That Can Differentiate True From Lymphoid Hyperplasia

    PubMed Central

    Araki, Tetsuro; Sholl, Lynette M.; Gerbaudo, Victor H.; Hatabu, Hiroto; Nishino, Mizuki

    2014-01-01

    OBJECTIVE The purpose of this article is to investigate the imaging characteristics of pathologically proven thymic hyperplasia and to identify features that can differentiate true hyperplasia from lymphoid hyperplasia. MATERIALS AND METHODS Thirty-one patients (nine men and 22 women; age range, 20–68 years) with pathologically confirmed thymic hyperplasia (18 true and 13 lymphoid) who underwent preoperative CT (n = 27), PET/CT (n = 5), or MRI (n = 6) were studied. The length and thickness of each thymic lobe and the transverse and anterior-posterior diameters and attenuation of the thymus were measured on CT. Thymic morphologic features and heterogeneity on CT and chemical shift on MRI were evaluated. Maximum standardized uptake values were measured on PET. Imaging features between true and lymphoid hyperplasia were compared. RESULTS No significant differences were observed between true and lymphoid hyperplasia in terms of thymic length, thickness, diameters, morphologic features, and other qualitative features (p > 0.16). The length, thickness, and diameters of thymic hyperplasia were significantly larger than the mean values of normal glands in the corresponding age group (p < 0.001). CT attenuation of lymphoid hyperplasia was significantly higher than that of true hyperplasia among 15 patients with contrast-enhanced CT (median, 47.9 vs 31.4 HU; Wilcoxon p = 0.03). The receiver operating characteristic analysis yielded greater than 41.2 HU as the optimal threshold for differentiating lymphoid hyperplasia from true hyperplasia, with 83% sensitivity and 89% specificity. A decrease of signal intensity on opposed-phase images was present in all four cases with in- and opposed-phase imaging. The mean maximum standardized uptake value was 2.66. CONCLUSION CT attenuation of the thymus was significantly higher in lymphoid hyperplasia than in true hyperplasia, with an optimal threshold of greater than 41.2 HU in this cohort of patients with pathologically confirmed

  10. [Clinical, radiologic, pathological features and diagnosis of 14 cases with interstitial lung disease in children].

    PubMed

    2011-02-01

    The pediatric interstitial lung disease is a group of poorly understood disease entities. This study aimed to better understand the clinical features, radiological manifestations and pathological patterns of pediatric interstitial lung disease. Patients with diffuse lung disease seen in the year 2009 in 7 hospitals were studied by the Pediatric Interstitial Lung Disease Cooperative Group. Nineteen patients underwent lung biopsy, 11 cases were male, 8 were female and their age ranged from 1 year and 4 months to 13 years. Respiratory tract secretions were obtained for bacterial culture, respiratory virus antigen examination, mycoplasma antibody, EB virus, cytomegalovirus, and herpes simplex viruses antibody detection were performed. The CT or HRCT of the lung and blood-gas analysis and lung biopsy were performed for all the patients. One case underwent open lung biopsy, two cases received percutaneous biopsy, and other 16 cases were experienced video-assisted thoracoscopic biopsy. Five cases had been excluded, for one case had fungal infection, one had abnormal pneumoangiogram, one had sclerosing hemangioma, and two had no sufficient data. The remaining 14 cases were included into the analysis. All the 14 cases had cough, 12 of them also had tachypnoea, four cases had rales and five had clubbing. High resolution CT showed that 12 cases had ground-glass opacification, 1 had diffuse micronodular opacities, the pathological pattern of this case was pulmonary alveolar microlithiasis, and in the case of diffuse reticulonodular opacities and cysts, the pathology of the lung was NSIP. All the 14 cases had the proof of the diagnosis or the type of the pathology. Four cases were diagnosed by pathology of the lung, including 1 case of pulmonary alveolar microlithiasis, 2 cases of pulmonary alveolar proteinosis, 1 case of lipoid pneumonia. Clinical-radiologic-pathologic (C-R-P) diagnosis of the other 10 cases were as follows: 4 cases had secondary interstitial lung disease, one

  11. An autopsy study of combined pulmonary fibrosis and emphysema: correlations among clinical, radiological, and pathological features.

    PubMed

    Inomata, Minoru; Ikushima, Soichiro; Awano, Nobuyasu; Kondoh, Keisuke; Satake, Kohta; Masuo, Masahiro; Kusunoki, Yuji; Moriya, Atsuko; Kamiya, Hiroyuki; Ando, Tsunehiro; Yanagawa, Noriyo; Kumasaka, Toshio; Ogura, Takashi; Sakai, Fumikazu; Azuma, Arata; Gemma, Akihiko; Takemura, Tamiko

    2014-06-28

    Clinical evaluation to differentiate the characteristic features of pulmonary fibrosis and emphysema is often difficult in patients with combined pulmonary fibrosis and emphysema (CPFE), but diagnosis of pulmonary fibrosis is important for evaluating treatment options and the risk of acute exacerbation of interstitial pneumonia of such patients. As far as we know, it is the first report describing a correlation among clinical, radiological, and whole-lung pathological features in an autopsy cases of CPFE patients. Experts retrospectively reviewed the clinical charts and examined chest computed tomography (CT) images and pathological findings of an autopsy series of 22 CPFE patients, and compared these with findings from 8 idiopathic pulmonary fibrosis (IPF) patients and 17 emphysema-alone patients. All patients had a history of heavy smoking. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC%) was significantly lower in the emphysema-alone group than the CPFE and IPF-alone groups. The percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) was significantly lower in the CPFE group than the IPF- and emphysema-alone groups. Usual interstitial pneumonia (UIP) pattern was observed radiologically in 15 (68.2%) CPFE and 8 (100%) IPF-alone patients and was pathologically observed in all patients from both groups. Pathologically thick-cystic lesions involving one or more acini with dense wall fibrosis and occasional fibroblastic foci surrounded by honeycombing and normal alveoli were confirmed by post-mortem observation as thick-walled cystic lesions (TWCLs). Emphysematous destruction and enlargement of membranous and respiratory bronchioles with fibrosis were observed in the TWCLs. The cystic lesions were always larger than the cysts of honeycombing. The prevalence of both radiological and pathological TWCLs was 72.7% among CPFE patients, but no such lesions were observed in patients with IPF or emphysema alone (p=0.001). The extent of

  12. An autopsy study of combined pulmonary fibrosis and emphysema: correlations among clinical, radiological, and pathological features

    PubMed Central

    2014-01-01

    Background Clinical evaluation to differentiate the characteristic features of pulmonary fibrosis and emphysema is often difficult in patients with combined pulmonary fibrosis and emphysema (CPFE), but diagnosis of pulmonary fibrosis is important for evaluating treatment options and the risk of acute exacerbation of interstitial pneumonia of such patients. As far as we know, it is the first report describing a correlation among clinical, radiological, and whole-lung pathological features in an autopsy cases of CPFE patients. Methods Experts retrospectively reviewed the clinical charts and examined chest computed tomography (CT) images and pathological findings of an autopsy series of 22 CPFE patients, and compared these with findings from 8 idiopathic pulmonary fibrosis (IPF) patients and 17 emphysema-alone patients. Results All patients had a history of heavy smoking. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC%) was significantly lower in the emphysema-alone group than the CPFE and IPF-alone groups. The percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) was significantly lower in the CPFE group than the IPF- and emphysema-alone groups. Usual interstitial pneumonia (UIP) pattern was observed radiologically in 15 (68.2%) CPFE and 8 (100%) IPF-alone patients and was pathologically observed in all patients from both groups. Pathologically thick-cystic lesions involving one or more acini with dense wall fibrosis and occasional fibroblastic foci surrounded by honeycombing and normal alveoli were confirmed by post-mortem observation as thick-walled cystic lesions (TWCLs). Emphysematous destruction and enlargement of membranous and respiratory bronchioles with fibrosis were observed in the TWCLs. The cystic lesions were always larger than the cysts of honeycombing. The prevalence of both radiological and pathological TWCLs was 72.7% among CPFE patients, but no such lesions were observed in patients with IPF or emphysema

  13. A Joint Time-Frequency and Matrix Decomposition Feature Extraction Methodology for Pathological Voice Classification

    NASA Astrophysics Data System (ADS)

    Ghoraani, Behnaz; Krishnan, Sridhar

    2009-12-01

    The number of people affected by speech problems is increasing as the modern world places increasing demands on the human voice via mobile telephones, voice recognition software, and interpersonal verbal communications. In this paper, we propose a novel methodology for automatic pattern classification of pathological voices. The main contribution of this paper is extraction of meaningful and unique features using Adaptive time-frequency distribution (TFD) and nonnegative matrix factorization (NMF). We construct Adaptive TFD as an effective signal analysis domain to dynamically track the nonstationarity in the speech and utilize NMF as a matrix decomposition (MD) technique to quantify the constructed TFD. The proposed method extracts meaningful and unique features from the joint TFD of the speech, and automatically identifies and measures the abnormality of the signal. Depending on the abnormality measure of each signal, we classify the signal into normal or pathological. The proposed method is applied on the Massachusetts Eye and Ear Infirmary (MEEI) voice disorders database which consists of 161 pathological and 51 normal speakers, and an overall classification accuracy of 98.6% was achieved.

  14. A rare case of primary pulmonary artery myofibroblastic sarcoma--imaging and pathologic features.

    PubMed

    Jing, Ran; Tang, Hao; Shen, Kangjun; Luo, Junming; Zhou, Xinmin

    2014-02-01

    Primary myofibroblastic sarcomas of the pulmonary artery are very uncommon, but early detection is critical. Common clinical symptoms include shortness of breath, chest discomfort, and syncope. Patients diagnosed with a pulmonary tumor have a high risk of fatal pulmonary embolism. In this case study, we identified and diagnosed pulmonary artery myofibroblastic sarcoma in a young man by its imaging and pathologic characters. Surgery to excise the tumor was successfully performed and the operation was considered to have improved his prognosis. Postoperative examinations did not show any evidence of residual tumor, recurrence, or metastasis in the lungs or cardiac tissue. Based on the results of this case study, we concluded that the imaging and pathologic features of primary pulmonary artery myofibroblastic sarcoma can assist physicians in making a prompt diagnosis and an immediate surgical and treatment plan to greatly improve prognosis.

  15. CT Features and Pathological Correlation of Primitive Neuroectodermal Tumor of the Kidney.

    PubMed

    Dong, Junqiang; Xing, Jingjing; Limbu, Hangsha Hang; Yue, Songwei; Su, Lei; Zhang, Dandan; Gao, Jianbo

    2015-09-01

    The purpose of the study was to analyze the computed tomography (CT) findings of primitive neuroectodermal tumor (PNET) of the kidney and correlate them pathologically. Ten cases of pathologically confirmed renal PNET were collected and retrospectively reviewed. The CT features that were analyzed include tumor size, shape, margins, density, nature of enhancement, presence of thrombosis, and metastasis, etc. These parameters were correlated with pathological findings and combined with literature review. The median age of the patients was 30 years. CT images showed solitary, large, ill-defined, irregular, or lobulated heterogeneous mass. Invasive growth toward the renal cortex and pelvis with renal cortical interruptions were seen in eight cases with one case exhibiting invasion that extended beyond the renal capsule with soft tissue seen in the perirenal fat pace. The tumors were confined to the kidney contour with enlargement of kidney in six of the cases. Cystic changes with mural nodules were detected in three cases. Eight cases showed persistent moderate enhancement during the nephrographic phase. Irregular septum-like structures were seen in four cases. Thrombosis was detected in eight cases. Lymph node metastasis was detected in eight cases with bilateral lung metastasis in two and bone metastasis in one. Renal PNET is a rare highly aggressive disease affecting younger people. It should be considered as a strong differential when well confined, yet large tumors that cause enlargement of the kidney are seen and also when tumors expressing cystic changes along with mural nodules are seen. Although renal PNET has certain other characteristic CT features, pathological and immunohistochemistry report must also be sought for definitive diagnosis.

  16. PREDICTING FIFTEEN-YEAR CANCER-SPECIFIC MORTALITY BASED ON THE PATHOLOGICAL FEATURES OF PROSTATE CANCER

    PubMed Central

    Eggener, Scott E.; Scardino, Peter T.; Walsh, Patrick C.; Han, Misop; Partin, Alan W.; Trock, Bruce J.; Feng, Zhaoyong; Wood, David P.; Eastham, James A.; Yossepowitch, Ofer; Rabah, Danny M.; Kattan, Michael W.; Yu, Changhong; Klein, Eric A.; Stephenson, Andrew J.

    2014-01-01

    Purpose Long-term prostate cancer-specific mortality (PCSM) after radical prostatectomy is poorly defined in the era of widespread screening. An understanding of the treated natural history of screen-detected cancers and the pathological risk factors for PCSM are needed for treatment decision-making. Methods Using Fine and Gray competing risk regression analysis, the clinical and pathological data and follow-up information of 11,521 patients treated by radical prostatectomy at four academic centers from 1987 to 2005 were modeled to predict PCSM. The model was validated on 12,389 patients treated at a separate institution during the same period. Results The overall 15-year PCSM was 7%. Primary and secondary pathological Gleason grade 4–5 (P < 0.001 for both), seminal vesicle invasion (P < 0.001), and year of surgery (P = 0.002) were significant predictors of PCSM. A nomogram predicting 15-year PCSM based on standard pathological parameters was accurate and discriminating with an externally-validated concordance index of 0.92. Stratified by patient age, 15-year PCSM for Gleason score ≤ 6, 3+4, 4+3, and 8–10 ranged from 0.2–1.2%, 4.2–6.5%, 6.6–11%, and 26–37%, respectively. The 15-year PCSM risks ranged from 0.8–1.5%, 2.9–10%, 15–27%, and 22–30% for organ-confined cancer, extraprostatic extension, seminal vesicle invasion, and lymph node metastasis, respectively. Only 3 of 9557 patients with organ-confined, Gleason score ≤ 6 cancers have died from prostate cancer. Conclusions The presence of poorly differentiated cancer and seminal vesicle invasion are the prime determinants of PCSM after radical prostatectomy. The risk of PCSM can be predicted with unprecedented accuracy once the pathological features of prostate cancer are known. PMID:21239008

  17. Inflammation induced by infection potentiates tau pathological features in transgenic mice.

    PubMed

    Sy, Michael; Kitazawa, Masashi; Medeiros, Rodrigo; Whitman, Lucia; Cheng, David; Lane, Thomas E; Laferla, Frank M

    2011-06-01

    Comorbidities that promote the progression of Alzheimer's disease (AD) remain to be uncovered and evaluated in animal models. Because elderly individuals are vulnerable to viral and bacterial infections, these microbial agents may be considered important comorbidities that could potentiate an already existing and tenuous inflammatory condition in the brain, accelerating cognitive decline, particularly if the cellular and molecular mechanisms can be defined. Researchers have recently demonstrated that triggering inflammation in the brain exacerbates tau pathological characteristics in animal models. Herein, we explore whether inflammation induced via viral infection, compared with inflammation induced via bacterial lipopolysaccharide, modulates AD-like pathological features in the 3xTg-AD mouse model and provide evidence to support the hypothesis that infectious agents may act as a comorbidity for AD. Our study shows that infection-induced acute or chronic inflammation significantly exacerbates tau pathological characteristics, with chronic inflammation leading to impairments in spatial memory. Tau phosphorylation was increased via a glycogen synthase kinase-3β-dependent mechanism, and there was a prominent shift of tau from the detergent-soluble to the detergent-insoluble fraction. During chronic inflammation, we found that inhibiting glycogen synthase kinase-3β activity with lithium reduced tau phosphorylation and the accumulation of insoluble tau and reversed memory impairments. Taken together, infectious agents that trigger central nervous system inflammation may serve as a comorbidity for AD, leading to cognitive impairments by a mechanism that involves exacerbation of tau pathological characteristics. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  18. Distinguishing features of endometrial pathology after exposure to the progesterone receptor modulator mifepristone.

    PubMed

    Fiscella, Julietta; Bonfiglio, Thomas; Winters, Paul; Eisinger, Steven H; Fiscella, Kevin

    2011-07-01

    There is growing interest in the use of progesterone receptor modulators such as mifepristone for treatment of gynecologic and other conditions, but interest in progesterone receptor modulators is dampened by the effects of the agents on the endometrium. In this study, we examined the endometria of women exposed to mifepristone for treatment of leiomyomas in doses of 2.5 and 5 mg and compared them to unexposed endometria. We assessed the reliability of these features by comparing agreement in ratings between pathologists who were blinded to each other's readings. We assessed distinguishing features between exposed and unexposed groups by comparing frequency of features between groups. We found that key features could be reliably assessed by pathologists experienced in endometrial pathology. We observed several features (nonsynchronous endometrium, large fluid filled glands, and abnormal blood vessels) that distinguished endometrial samples that were and were not exposed to the drug. These findings suggest several features that can be tracked during studies involving mifepristone and, potentially, other progesterone receptor modulators.

  19. DISTINGUISHING FEATURES OF ENDOMETRIAL PATHOLOGY FOLLOWING EXPOSURE TO THE PROGESTERONE RECEPTOR MODULATOR MIFEPRISTONE

    PubMed Central

    Fiscella, Julietta; Bonfiglio, Thomas; Winters, Paul; Eisinger, Steven H; Fiscella, Kevin

    2011-01-01

    There is growing interest in use of progesterone receptor modulators (PRM) such as mifepristone for treatment of gynecological and other conditions, but interest in PRMs is dampened by effects of the agents on the endometrium. In this study, we examined the endometria of women exposed to mifepristone for treatment of leiomyomas in doses of 2.5 mg and 5 mg and compared them to unexposed endometria. We assessed the reliability of these features by comparing agreement in ratings between pathologists who were blinded to each other's readings. We assessed distinguishing features between exposed and unexposed groups by comparing frequency of features between groups. We found that key features could be reliably assessed by pathologists experienced in endometrial pathology. We observed several features (non synchronous endometrium, large fluid filled glands and abnormal blood vessels) that distinguished endometrial samples that were and were not exposed to the drug. These findings suggest several features that can be tracked during studies involving mifepristone and potentially other PRMs. PMID:21315422

  20. Unusual malignant tumors of the breast: MRI features and pathologic correlation.

    PubMed

    Linda, Anna; Zuiani, Chiara; Girometti, Rossano; Londero, Viviana; Machin, Piernicola; Brondani, Giovanni; Bazzocchi, Massimo

    2010-08-01

    Unusual malignant breast tumors are well-differentiated subtypes of invasive ductal carcinoma, including mucinous, tubular, medullary and papillary carcinomas, and account for about 10% of malignant breast tumors. They are increasingly being encountered during magnetic resonance imaging (MRI) examinations of the breast. Therefore, breast radiologists should be aware of their appearance on MRI. This review provides an overview of MRI characteristics of a range of unusual tumors (mucinous carcinoma, medullary carcinoma, tubular carcinoma, intraductal papillary carcinoma, intracystic papillary carcinoma and invasive papillary carcinoma), highlighting specific clues for diagnosis and correlating MRI and pathologic features. Many unusual breast tumors exhibit MRI features similar to those of benign or low suspicious lesions (oval shape, well-defined margins, high signal intensity on T2-weighted images, continuous increase kinetics, i.e. type I dynamic curve), leading to a possible misdiagnosis. Nevertheless, an understanding of pathologic features of these tumors, especially tissue content (mucinous, fibrous) and growth pattern, can help to define some specific clues for their diagnosis.

  1. [Clinical and pathological features of breast cancer in a population of Mexico].

    PubMed

    Maffuz-Aziz, Antonio; Labastida-Almendaro, Sonia; Espejo-Fonseca, Aura; Rodríguez-Cuevas, Sergio

    Breast cancer is the most common among women in our country, and its treatment is based on prognostic factors to categorize patients into different risk groups. In this study, the clinical and pathological features that play a role as a prognostic factor in a representative population with breast cancer in México are described. A descriptive analysis of the clinical and pathological features of women diagnosed with breast cancer, in a period from June 2005 to May 2014; registered in a database and calculated by simple frequencies. A total of 4,411 patients were included, the average age at diagnosis was 53 years, 19.7% were diagnosed by mammography screening program and 80.3% derived from any signs or symptoms. Regarding the stages at diagnosis, 6.8% were carcinoma in situ, 36% at early stages (I and IIA), 45% locally advanced (IIB to IIIC), 7.7% metastatic and 3.9% unclassifiable. A 79% were ductal histology, lobular 7.8% and the rest, other types. Of ductal carcinomas, 9.1% were grade I, 54.1% grade II, and 34.6% grade III. Regarding the biological subtypes, 65.7% were luminal, 10.9% luminal Her positive, 8.7% pure Her 2 positive and 14.6% triple negative. In the present study, we described the clinical and pathologic features of a group of Mexican women with breast cancer that might reflect a national landscape, and represent the prognostic factors to determine groups of risk and treatment decisions. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  2. Neoplastic diseases of the spermatic cord: an overview of pathological features, evaluation, and management.

    PubMed

    Dagur, Gautam; Gandhi, Jason; Kapadia, Kailash; Inam, Rafid; Smith, Noel L; Joshi, Gargi; Khan, Sardar Ali

    2017-02-01

    Extracellular tumors found with the spermatic cord, known as neoplasms, are usually identified to be benign. However, the accurate and timely diagnosis of spermatic cord masses is highly crucial, especially when most results are often overlooked or unclear. In this review, we discuss the anatomy and embryology of the spermatic cord. Upon rooting these fundamental concepts, we discuss an array of benign and malignant neoplastic tumors, including their origin, pathological features, clinical evaluation and management, as well as other case-specific characteristics of unique presentation. Many of these neoplasms are based on local neurological, vascular, muscular, bone, soft tissue, or lymphatic origin, while others have metastasized from particular areas of the body.

  3. Early Controversies over Athetosis: I. Clinical Features, Differentiation from other Movement Disorders, Associated Conditions, and Pathology

    PubMed Central

    Lanska, Douglas J.

    2013-01-01

    Background Since the description of athetosis in 1871 by American neurologist William Alexander Hammond (1828–1900) the disorder has been a source of controversy, as were many aspects of Hammond’s career. Methods Primary sources have been used to review controversies in the 50-year period since the initial description of athetosis, in particular those concerning clinical features, differentiation from other movement disorders, associated conditions, and pathology. Controversies concerning treatment will be addressed in a subsequent article. Results Hammond struggled to establish athetosis as a distinct clinical–pathological entity, and had successfully predicted the striatal pathology in his initial case (albeit somewhat serendipitously). Athetosis was, nevertheless, considered by many neurologists to be a form of post-hemiplegic chorea or part of a continuum between chorea and dystonia. European neurologists, and particularly the French, initially ignored or discounted the concept. Additional controversies arose over whether the movements persisted during sleep, whether athetosis was, or could be, associated with imbecility or insanity, and how it should be treated. Discussion Some controversies concerning athetosis served to identify areas where knowledge was insufficient to make accurate statements, despite prior self-assured or even dogmatic statements to the contrary. Other controversies illustrated established prejudices, even if these biases were often only apparent with the greater detachment of hindsight. PMID:23450262

  4. Pathologic stratification of operable lung adenocarcinoma using radiomics features extracted from dual energy CT images

    PubMed Central

    Lee, Ho Yun; Sohn, Insuk; Kim, Hye Seung; Son, Ji Ye; Kwon, O Jung; Choi, Joon Young; Lee, Kyung Soo; Shim, Young Mog

    2017-01-01

    Purpose To evaluate the usefulness of surrogate biomarkers as predictors of histopathologic tumor grade and aggressiveness using radiomics data from dual-energy computed tomography (DECT), with the ultimate goal of accomplishing stratification of early-stage lung adenocarcinoma for optimal treatment. Results Pathologic grade was divided into grades 1, 2, and 3. Multinomial logistic regression analysis revealed i-uniformity and 97.5th percentile CT attenuation value as independent significant factors to stratify grade 2 or 3 from grade 1. The AUC value calculated from leave-one-out cross-validation procedure for discriminating grades 1, 2, and 3 was 0.9307 (95% CI: 0.8514–1), 0.8610 (95% CI: 0.7547–0.9672), and 0.8394 (95% CI: 0.7045–0.9743), respectively. Materials and Methods A total of 80 patients with 91 clinically and radiologically suspected stage I or II lung adenocarcinoma were prospectively enrolled. All patients underwent DECT and F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, followed by surgery. Quantitative CT and PET imaging characteristics were evaluated using a radiomics approach. Significant features for a tumor aggressiveness prediction model were extracted and used to calculate diagnostic performance for predicting all pathologic grades. Conclusions Quantitative radiomics values from DECT imaging metrics can help predict pathologic aggressiveness of lung adenocarcinoma. PMID:27880938

  5. Image and pathological features of Ewing's sarcoma in the oral and maxillofacial region.

    PubMed

    Huang, Lingzhi; Chen, Xiaofang; Li, Lezhi

    2016-06-28

    To systematically evaluate the image and pathological features of Ewing's sarcoma (ES) in the oral and maxillofacial region.
 Eight patients with ES in the oral and maxillofacial region were enrolled for this study. The X-ray, computed tomography (CT), and magnetic resonance imaging (MRI) of ES and the pathological data were systematically evaluated.
 X-ray image showed a diffuse radiolucency with cystic component and ill-defined borders for bone lesion. CT showed that there was osteolytic mass with extensive bone destruction and soft tissue infiltration, but no periosteal reactions were observed. MRI demonstrated that ES showed an inhomogeneous structure and blurred borders with invasion to adjacent soft tissue for bone lesion. Similar manifestation also showed in MRI images for patients with soft tissues. Histologically, ES composed of small round cells, and expressed CD99, neuron specific enolase (NSE) and vimentin (Vim) in all patients. Desmin (Des), CD34, epithelial membrane antigen (EMA), chromogranin A (ChgA), etc, were negatively expressed in ES cells.
 X-ray, CT, and MRI are helpful to determine the property, extent and the relationship of ES with the surrounding tissues. Immunohistochemical stain of CD99, NSE, and Vim are helpful to confirm the pathological diagnosis of ES.

  6. Image mining for investigative pathology using optimized feature extraction and data fusion.

    PubMed

    Chen, Wenjin; Meer, Peter; Georgescu, Bogdan; He, Wei; Goodell, Lauri A; Foran, David J

    2005-07-01

    In many subspecialties of pathology, the intrinsic complexity of rendering accurate diagnostic decisions is compounded by a lack of definitive criteria for detecting and characterizing diseases and their corresponding histological features. In some cases, there exists a striking disparity between the diagnoses rendered by recognized authorities and those provided by non-experts. We previously reported the development of an Image Guided Decision Support (IGDS) system, which was shown to reliably discriminate among malignant lymphomas and leukemia that are sometimes confused with one another during routine microscopic evaluation. As an extension of those efforts, we report here a web-based intelligent archiving subsystem that can automatically detect, image, and index new cells into distributed ground-truth databases. Systematic experiments showed that through the use of robust texture descriptors and density estimation based fusion the reliability and performance of the governing classifications of the system were improved significantly while simultaneously reducing the dimensionality of the feature space.

  7. Acinar Cell Carcinoma of the Pancreas: Overview of Clinicopathologic Features and Insights into the Molecular Pathology.

    PubMed

    La Rosa, Stefano; Sessa, Fausto; Capella, Carlo

    2015-01-01

    Acinar cell carcinomas (ACCs) of the pancreas are rare pancreatic neoplasms accounting for about 1-2% of pancreatic tumors in adults and about 15% in pediatric subjects. They show different clinical symptoms at presentation, different morphological features, different outcomes, and different molecular alterations. This heterogeneous clinicopathological spectrum may give rise to difficulties in the clinical and pathological diagnosis with consequential therapeutic and prognostic implications. The molecular mechanisms involved in the onset and progression of ACCs are still not completely understood, although in recent years, several attempts have been made to clarify the molecular mechanisms involved in ACC biology. In this paper, we will review the main clinicopathological and molecular features of pancreatic ACCs of both adult and pediatric subjects to give the reader a comprehensive overview of this rare tumor type.

  8. Acinar Cell Carcinoma of the Pancreas: Overview of Clinicopathologic Features and Insights into the Molecular Pathology

    PubMed Central

    La Rosa, Stefano; Sessa, Fausto; Capella, Carlo

    2015-01-01

    Acinar cell carcinomas (ACCs) of the pancreas are rare pancreatic neoplasms accounting for about 1–2% of pancreatic tumors in adults and about 15% in pediatric subjects. They show different clinical symptoms at presentation, different morphological features, different outcomes, and different molecular alterations. This heterogeneous clinicopathological spectrum may give rise to difficulties in the clinical and pathological diagnosis with consequential therapeutic and prognostic implications. The molecular mechanisms involved in the onset and progression of ACCs are still not completely understood, although in recent years, several attempts have been made to clarify the molecular mechanisms involved in ACC biology. In this paper, we will review the main clinicopathological and molecular features of pancreatic ACCs of both adult and pediatric subjects to give the reader a comprehensive overview of this rare tumor type. PMID:26137463

  9. Hypertension is the primary component of metabolic syndrome associated with pathologic features of kidney cancer.

    PubMed

    Kocher, Neil J; Rjepaj, Chris; Robyak, Haley; Lehman, Erik; Raman, Jay D

    2017-01-01

    To determine whether individual and/or cumulative components of metabolic syndrome (obesity, hypertension, dyslipidemia, and hyperglycemia) are associated with pathologic features of kidney cancer. A review of our kidney tumor database identified 462 patients who underwent partial or radical nephrectomy for renal cell carcinoma. The NCEP ATP-III criteria were used to define metabolic syndrome (MetS). Linear fixed effects modeling and ordinal logistic regression examined the relationship between MetS (individual and cumulative components) and pathologic characteristics. Two hundred and seventy-eight men and 184 women with a median age of 58 years, BMI of 31 kg/m(2), tumor size of 3.7 cm, and nephrometry score of 6 were included. Ninety-seven (21 %) patients met NCEP ATP-III criteria for MetS. Hypertension was the only individual component of MetS associated with pathologic features of kidney cancer including increased tumor size [geometric mean ratio 1.17 (1.05-1.32), P = 0.03], higher tumor grade [OR 1.49 (1.03-2.17), P = 0.04], increasing nephrometry score [OR 1.77 (1.28-2.48), P = 0.001], and non-clear cell histology [OR 1.42 (1.01-2.02), P = 0.05]. Furthermore, combinations of MetS components were associated with increased tumor grade (P = 0.02), tumor stage (P = 0.02), nephrometry score (P ≤ 0.001), and non-clear cell histology (P = 0.02), only when hypertension was included. MetS is composed of four risk factors each implicated in carcinogenesis. We identified hypertension as the primary component associated with specific pathologic features of kidney cancer. Further studies are necessary to elucidate whether the effect of hypertension is a function of severity and/or chronicity.

  10. Clinical, Pathological, and Molecular Features of Lung Adenocarcinomas with AXL Expression

    PubMed Central

    Suda, Kenichi; Shimizu, Shigeki; Sakai, Kazuko; Mizuuchi, Hiroshi; Tomizawa, Kenji; Takemoto, Toshiki; Nishio, Kazuto; Mitsudomi, Tetsuya

    2016-01-01

    The receptor tyrosine kinase AXL is a member of the Tyro3-Axl-Mer receptor tyrosine kinase subfamily. AXL affects several cellular functions, including growth and migration. AXL aberration is reportedly a marker for poor prognosis and treatment resistance in various cancers. In this study, we analyzed clinical, pathological, and molecular features of AXL expression in lung adenocarcinomas (LADs). We examined 161 LAD specimens from patients who underwent pulmonary resections. When AXL protein expression was quantified (0, 1+, 2+, 3+) according to immunohistochemical staining intensity, results were 0: 35%; 1+: 20%; 2+: 37%; and 3+: 7% for the 161 samples. AXL expression status did not correlate with clinical features, including smoking status and pathological stage. However, patients whose specimens showed strong AXL expression (3+) had markedly poorer prognoses than other groups (P = 0.0033). Strong AXL expression was also significantly associated with downregulation of E-cadherin (P = 0.025) and CD44 (P = 0.0010). In addition, 9 of 12 specimens with strong AXL expression had driver gene mutations (6 with EGFR, 2 with KRAS, 1 with ALK). In conclusion, we found that strong AXL expression in surgically resected LADs was a predictor of poor prognosis. LADs with strong AXL expression were characterized by mesenchymal status, higher expression of stem-cell-like markers, and frequent driver gene mutations. PMID:27100677

  11. Clinical, Pathologic, and Genetic Features of Wilms Tumors With WTX Gene Mutation.

    PubMed

    Alexandrescu, Sanda; Akhavanfard, Sara; Harris, Marian H; Vargas, Sara O

    2017-01-01

    Clinical and pathologic features of patients with WTX-mutated Wilms tumor (WT) have not been studied in detail. We characterize the clinical and pathologic findings in WT with WTX abnormalities and provide comparison with WT without WTX mutation. Clinical, gross, and microscopic features in 35 patients with WT were examined. Karyotype was examined in a subset of cases. All cases had been previously analyzed for WTX, WT1, and CTNNB1 aberrations via array comparative genomic hybridization; OncoMap 4 high throughput genotyping was performed on 18 cases. Eleven tumors had WTX abnormality. No significant differences were identified between patients with mutated versus nonmutated WTX with respect to gender (45% versus 33% male), age (mean 3.9 versus 4.1 years), tumor size (mean 12.7 cm versus 12.8 cm), anaplasia (9% versus 12%), rhabdomyoblastic differentiation (18% versus 8%), cartilage differentiation (9% versus 4%), mucinous epithelial differentiation (9% versus 4%), nephrogenic rests (28% versus 21%), or relapse rate (11% versus 25%). Mutations in KRAS, MYC, and PIK3R1 were restricted to WTX-mutated WT, mutations in AKT, CKDN2A, EFGR, HRAS, MET, and RET were restricted to WT without WTX mutation, and mutations in BRAF, CTTNB1, NRAS, PDGFRA, and STK11 were seen in both groups. Our study revealed no clinical or pathologic distinctions between WT with and without WTX abnormality. This similarity lends support to the concept of a common tumorigenic pathway between WT with aberrant WTX and those without.

  12. MRL/MpJ mice show unique pathological features after experimental kidney injury.

    PubMed

    Shiozuru, Daichi; Ichii, Osamu; Kimura, Junpei; Nakamura, Teppei; Elewa, Yaser Hosny Ali; Otsuka-Kanazawa, Saori; Kon, Yasuhiro

    2016-02-01

    Clarification of the renal repair process is crucial for developing novel therapeutic strategies for kidney injury. MRL/MpJ mice have a unique repair process characterized by low scar formation. The pathological features of experimentally injured MRL/MpJ and C57BL/6 mouse kidneys were compared to examine the renal repair process. The dilation and atrophy of renal tubules were observed in folic acid (FA)-induced acute kidney injury (AKI) in both strains, and the histopathological injury scores and number of interleukin (IL)-1F6-positive damaged distal tubules and kidney injury molecule 1 (KIM-1)-positive damaged proximal tubules drastically increased 1 day after AKI induction. However, KIM-1-positive tubules and the elevation of serum renal function markers were significantly fewer and lower, respectively, in MRL/MpJ mice at days 2 and 7 after AKI. After traumatic kidney injury (TKI) via needle puncture, severe tubular necrotic lesions in the punctured area and fibrosis progressed in both strains. Indices for fibrosis such as aniline blue-positive area, number of alpha smooth muscle actin-positive myofibroblasts, and messenger RNA expression levels of Tgfb1 and Mmp2 indicated lower fibrotic activity in MRL/MpJ kidneys. Characteristically, only MRL/MpJ kidneys manifested remarkable calcification around the punctured area beginning 7 days after TKI. The pathological features of injured MRL/MpJ and C57BL/6 kidneys differed, especially those of kidneys with mild proximal tubular injuries after FA-induced AKI. Lower fibrotic activity and increased calcification after TKI were observed in MRL/MpJ kidneys. These findings clarified the unique pathological characteristics of MRL/MpJ mouse kidneys and contribute to understanding of the renal repair process after kidney injury.

  13. Pathologic features of breast cancer associated with complete response to neoadjuvant chemotherapy: importance of tumor necrosis.

    PubMed

    Pu, Robert T; Schott, Anne F; Sturtz, David E; Griffith, Kent A; Kleer, Celina G

    2005-03-01

    Breast cancer patients with a complete pathologic response after neoadjuvant chemotherapy have a better prognosis than incomplete responders. The predictive value of the histologic characteristics of the tumor prior to neoadjuvant treatment has not been well defined, and there are no guidelines for reporting tumor characteristics in the core biopsy report. Histologic and nuclear grades, presence of tumor necrosis and angiolymphatic invasion (ALI), and estrogen receptor (ER), progesterone receptor (PR), and HER-2/neu expression were assessed in core biopsies of 55 patients with invasive carcinomas. Patients were then uniformly treated with four cycles of doxorubicin/docetaxel followed by excisions and lymph node dissections. Complete pathologic response (pCR) was defined as having no invasive carcinoma at excision. Noncomplete pathologic response was defined as having invasive carcinoma at excision. Five of the 55 patients (9%) achieved pCR. Of the 5 complete responders, 4 (80%) had tumor necrosis in the core biopsy specimens, while only 8 of the 46 (17%) noncomplete responders (pNR) had this feature (P = 0.0086). Higher histologic and nuclear grades, ER, PR status, and HER-2/neu overexpression were not associated with pCR. The presence of ALI in the core biopsy, post-therapy excision, or both was associated with axillary lymph node metastases (P = 0.0062, P = 0.0249, and P = 0.0021, respectively). Although preliminary, our study suggests that the presence of tumor necrosis and ALI in the core biopsy may be important features to be included in the standard report.

  14. Clinical Features, Treatment, and Prognostic Factors of Chordoid Meningioma: Radiological and Pathological Features in 60 Cases of Chordoid Meningioma.

    PubMed

    Yang, Yang; Li, Da; Cao, Xiao-Yu; Hao, Shu-Yu; Wang, Liang; Wu, Zhen; Zhang, Jun-Ting

    2016-09-01

    As one subtype of meningiomas, chordoid meningiomas (CMs) are rarely described. In this study, the authors aimed to analyze the incidence, clinical features, treatment, and prognostic factors of CMs. Among 9873 cases of meningioma surgically treated between 2003 and 2013 at Beijing Tiantan Hospital, cases of CM were chosen for analysis and were reviewed retrospectively. To ascertain which factors were related with progression-free survival (PFS), statistical analysis was performed. Sixty cases of pathologically confirmed and surgically treated CMs were identified. They accounted for 0.61 % of the entire series of meningioma. Simpson Grade I, II, III, and IV resection was performed in 26, 19, 9, and 6 patients, respectively. Fifty-four patients were followed up for 25-141 months after operation. Of these patients, 19 received postoperative adjuvant radiotherapy. Seventeen patients experienced tumor progression, and median PFS was 54 months. The 3- and 5-year PFS rates were 89.7% and 57.1%, respectively. Two patients died of tumor recurrence and 1 died of unrelated reason. Univariate analysis demonstrated tumor shape and extent of resection were significantly associated with prognosis. Multivariate analysis revealed only extent of resection was an independent prognosis factor for PFS. CM is a rare subtype of World Health Organization grade II meningioma. It more frequently involved the adult patients and was without sex predilection. The confirmed diagnosis relied on pathological validation. Total resection whenever possible is recommended to prolong PFS of patients. The value of adjuvant radiotherapy for CM need to be further studied. Copyright © 2016. Published by Elsevier Inc.

  15. Clinical, pathologic, and molecular features of early-onset colorectal carcinoma.

    PubMed

    Yantiss, Rhonda K; Goodarzi, Mahmoud; Zhou, Xi K; Rennert, Hanna; Pirog, Edyta C; Banner, Barbara F; Chen, Yao-Tseng

    2009-04-01

    The incidence of colorectal carcinoma has increased among patients <40 years of age for unclear reasons. In this study, we describe the clinical, pathologic, and molecular features of colorectal carcinomas that developed in young patients. We compiled a study group of 24 patients <40 years of age with colorectal carcinoma, and 45 patients > or =40 years of age served as controls. Cases were evaluated for clinical risk factors of malignancy and pathologic features predictive of outcome. The tumors were immunohistochemically stained for O6-methylguanine methyltransferase, MLH-1, MSH-2, MSH-6, beta-catenin, chemokine (C-X-C motif) receptor 4, epidermal growth factor receptor, TP53, p16, survivin, and alpha-methylacyl-CoA racemase; assessed for microsatellite instability and mutations in beta-catenin, APC, EGFR, PIK3CA, KRAS, and BRAF; evaluated for micro-RNA expression (miR-21, miR-20a, miR-183, miR-192, miR-145, miR-106a, miR-181b, and miR-203); and examined for evidence of human papillomavirus infection. One study patient each had ulcerative colitis and hereditary nonpolyposis colorectal cancer. Ninety-two percent of tumors from young patients occurred in the distal colon (P=0.006), particularly the rectum (58%, P=0.02), and 75% were stage III or IV. Tumors from young patients showed more frequent lymphovascular (81%, P=0.03) and/or venous (48%, P=0.003) invasion, an infiltrative growth pattern (81%, P=0.03), and alpha-methylacyl-CoA racemase expression (83%, P=0.02) compared with controls. Carcinomas in this group showed significantly increased expression of miR-21, miR-20a, miR-145, miR-181b, and miR-203 (P< or =0.005 for all comparisons with controls). These results indicate that early-onset carcinomas commonly show pathologic features associated with aggressive behavior. Posttranslational regulation of mRNA and subsequent protein expression may be particularly important to the development of colorectal carcinomas in young patients.

  16. The Research of Feature Extraction Method of Liver Pathological Image Based on Multispatial Mapping and Statistical Properties

    PubMed Central

    Liu, Huiling; Xia, Bingbing; Yi, Dehui

    2016-01-01

    We propose a new feature extraction method of liver pathological image based on multispatial mapping and statistical properties. For liver pathological images of Hematein Eosin staining, the image of R and B channels can reflect the sensitivity of liver pathological images better, while the entropy space and Local Binary Pattern (LBP) space can reflect the texture features of the image better. To obtain the more comprehensive information, we map liver pathological images to the entropy space, LBP space, R space, and B space. The traditional Higher Order Local Autocorrelation Coefficients (HLAC) cannot reflect the overall information of the image, so we propose an average correction HLAC feature. We calculate the statistical properties and the average gray value of pathological images and then update the current pixel value as the absolute value of the difference between the current pixel gray value and the average gray value, which can be more sensitive to the gray value changes of pathological images. Lastly the HLAC template is used to calculate the features of the updated image. The experiment results show that the improved features of the multispatial mapping have the better classification performance for the liver cancer. PMID:27022407

  17. The Research of Feature Extraction Method of Liver Pathological Image Based on Multispatial Mapping and Statistical Properties.

    PubMed

    Liu, Huiling; Jiang, Huiyan; Xia, Bingbing; Yi, Dehui

    2016-01-01

    We propose a new feature extraction method of liver pathological image based on multispatial mapping and statistical properties. For liver pathological images of Hematein Eosin staining, the image of R and B channels can reflect the sensitivity of liver pathological images better, while the entropy space and Local Binary Pattern (LBP) space can reflect the texture features of the image better. To obtain the more comprehensive information, we map liver pathological images to the entropy space, LBP space, R space, and B space. The traditional Higher Order Local Autocorrelation Coefficients (HLAC) cannot reflect the overall information of the image, so we propose an average correction HLAC feature. We calculate the statistical properties and the average gray value of pathological images and then update the current pixel value as the absolute value of the difference between the current pixel gray value and the average gray value, which can be more sensitive to the gray value changes of pathological images. Lastly the HLAC template is used to calculate the features of the updated image. The experiment results show that the improved features of the multispatial mapping have the better classification performance for the liver cancer.

  18. Predicting non-small cell lung cancer prognosis by fully automated microscopic pathology image features

    PubMed Central

    Yu, Kun-Hsing; Zhang, Ce; Berry, Gerald J.; Altman, Russ B.; Ré, Christopher; Rubin, Daniel L.; Snyder, Michael

    2016-01-01

    Lung cancer is the most prevalent cancer worldwide, and histopathological assessment is indispensable for its diagnosis. However, human evaluation of pathology slides cannot accurately predict patients' prognoses. In this study, we obtain 2,186 haematoxylin and eosin stained histopathology whole-slide images of lung adenocarcinoma and squamous cell carcinoma patients from The Cancer Genome Atlas (TCGA), and 294 additional images from Stanford Tissue Microarray (TMA) Database. We extract 9,879 quantitative image features and use regularized machine-learning methods to select the top features and to distinguish shorter-term survivors from longer-term survivors with stage I adenocarcinoma (P<0.003) or squamous cell carcinoma (P=0.023) in the TCGA data set. We validate the survival prediction framework with the TMA cohort (P<0.036 for both tumour types). Our results suggest that automatically derived image features can predict the prognosis of lung cancer patients and thereby contribute to precision oncology. Our methods are extensible to histopathology images of other organs. PMID:27527408

  19. Pathological features and clinical outcomes of breast cancer according to levels of oestrogen receptor expression.

    PubMed

    Zhang, Zhang; Wang, Jianmin; Skinner, Kristin A; Shayne, Michelle; Hajdu, Steven I; Bu, Hong; Hicks, David G; Tang, Ping

    2014-10-01

    Historically, nuclear staining of ≥10% of invasive tumour cells has been used for oestrogen receptor (ER) positivity. In 2010, ASCO/CAP guidelines recommended the cut-off value be changed to nuclear staining of ≥1%. This study will analyse the relationships between levels of ER expression and clinicopathological features and clinical outcomes, with an emphasis on the ER 1-10% subgroup. We analysed clinicopathological features in five subgroups based on ER expression levels in 1700 consecutive invasive breast cancer patients diagnosed and treated at our institution between 2000 and 2011. Of the cases, 24% had ER expression <1%, 2% were ER 1-10%, 5% were 11-50%, 5% were 51-70% and 64% were 71-100%. We observed four subgroups of patient cohorts (ER <1%, 1-10%, 11-70% and 71-100%) that were unique in Nottingham grade, nuclear grade, progesterone receptor expression and disease-free survival. Of the 341 patients with follow-up data, we found no significant differences in pathological features between patients in the ER 11-50% and ER 51-70% subgroups. These data support the important role of ER in breast cancer, and the importance of accurate testing and quantitative reporting for ER. Tumours with ER 1-10% are not common, and further studies are needed to understand more clearly this subgroup of breast cancer. © 2014 John Wiley & Sons Ltd.

  20. Prevalence and Clinical, Endoscopic, and Pathological Features of Duodenitis in Children.

    PubMed

    Alper, Arik; Hardee, Steven; Rojas-Velasquez, Danilo; Escalera, Sandra; Morotti, Raffaella A; Pashankar, Dinesh S

    2016-02-01

    Although gastritis and esophagitis are well studied in children, there is very limited literature on duodenitis in children. We aimed to assess the prevalence, etiology, clinical, endoscopic, and pathological features in a large cohort of unselected children with duodenitis. We reviewed the pathology reports of all the upper endoscopies performed at our institution during 5 years to identify children with duodenitis. Biopsy sections were reviewed to confirm the diagnosis of duodenitis. Demographic, clinical, endoscopic data, and the presence of associated gastritis and esophagitis were noted in all of the children with duodenitis. The etiology of duodenitis was correlated with the patients' clinical diagnosis. Out of 2772 children who had endoscopy, 352 had duodenitis with the prevalence rate of 12.7%. Gastritis was seen in 64% of children with duodenitis compared with 46% of children without duodenitis (P < 0.001). Common indications for endoscopy in children with duodenitis were abdominal pain, positive celiac serology, and diarrhea. The most common etiology was celiac disease (32%), followed by Crohn disease (13%), ulcerative colitis (3%), and Helicobacter pylori infection (6%). In 63% of cases, the endoscopic appearance of duodenum was normal. Cryptitis, villous changes, and cellular infiltration were noted on histology. Prevalence of duodenitis is 12.7% in children undergoing endoscopy. Celiac disease and inflammatory bowel disease are common causes of duodenitis. Associated gastritis is common in children with duodenitis, and the correlation of endoscopic appearance with histology is poor.

  1. Chlamydia trachomatis pneumonitis in the C57BL/KsJ mouse: pathologic and immunologic features.

    PubMed

    Harrison, H R; Lee, S M; Lucas, D O

    1982-12-01

    Pneumonitis occurred in both normal and diabetic C57BL/KsJ mice, inoculated with a Chlamydia trachomatis strain isolated from a human infant . Animals were inoculated intranasally under light ether anesthesia. Control animals receiving carrier medium did not develop pulmonary disease. The pneumonitis was focal and involved interstitial and peribronchial structures. Pathological changes were most pronounced at 10 to 14 days after inoculation, but no animals died of their disease. The early cellular response was polymorphonuclear (4 to 6 days); this was followed by a predominantly mononuclear cell infiltrate. Immunopathological examination revealed immunoglobulin- and complement-bearing cells in a peribronchial distribution, corresponding to the mononuclear infiltrates seen by light microscopy. Infected animals seroconverted to C. trachomatis. Specific antichlamydial IgM antibody was detected at days 6 through 21 and higher titer IgG at days 10 through 28. Splenic lymphocyte stimulation responses to chlamydial antigen were observed at 10 and 21 days. C. trachomatis was cultured only from 6-day lung tissue. The histopathological and immunopathological features of the pneumonitis were similar in normal and diabetic mice. In addition, humoral and cellular immunoresponsiveness to chlamydial infection were not compromised in the diabetics. This animal model resembles human infant chlamydial pneumonitis in its pathological manifestations and may increase our understanding of the human disease.

  2. Segmental necrotising enterocolitis: pathological and clinical features of 22 cases in Bangladesh.

    PubMed Central

    Butler, T; Dahms, B; Lindpaintner, K; Islam, M; Azad, M A; Anton, P

    1987-01-01

    To describe the pathology and clinical features of segmental necrotising enterocolitis (SNE) in children and adults, 22 diarrhoeal patients (median age two years, range two months to 50 years) in Bangladesh with this lesion detected at autopsy were examined and compared with two groups of diarrhoeal control patients. Gross pathology consisted of purplish or black mucosal or transmural discoloration with erosions or ulcerations in segments of the jejunum or ileum of 18 cases and of the colon alone in four cases. Two patients had intestinal perforations. Microscopically all specimens showed coagulation necrosis or haemorrhagic necrosis indicative of mucosal ischaemia. In 20 cases there was submucosal oedema and nine showed pneumatosis of the bowel. From 11, one or more of the invasive diarrhoeal pathogens Shigella, Campylobacter and Entamoeba histolytica were detected. From the comparison with controls significant associations were found for a long duration of diarrhoea, blood and mucus in stool, abdominal distension or tenderness, shock not attributable to hypovolaemia, septicaemia, and low concentration of serum protein (p less than 0.05). These findings indicated that segmental necrotising enterocolitis develops sometimes as a fatal complication of prolonged diarrhoeal illnesses associated with shock and hypoproteinaemia and is caused by ischaemic injury to the intestinal mucosa. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:3428668

  3. Diprosopia/dicephalia in calves in northern Italy: clinical and aetio-pathological features.

    PubMed

    Biasibetti, E; D'Angelo, A; Bellino, C; Gay, L; Gianella, P; Capucchio, M T

    2011-12-01

    Cephalic parapagia, a rare congenital anomaly caused by the fusion of two monozygotic embryos, is characterized by a single body and a spectrum of duplication of craniofacial structures. The authors describe the clinical and pathological aspects of the parapagus conjoined twin defect in nine calves referred to the Department of Animal Pathology, Turin, between 1999 and 2009. The majority of the calves (eight cases) presented two snouts that shared three or four eyes (diprosopia); one calf presented two separate skulls fused at the foramen magnum (dicephalia). Bilateral inferior brachygnathia was observed in four calves. Post-mortem examination of the skull revealed complete brain duplication with fusion at the caudal portion of the brainstem in all calves. Histological features of the cerebral hemispheres and brainstem were normal; moderate disorganization of the cerebellar cortex was noted in two cases. Cardiac malformations were observed in three calves. No aetiologic cause was determined. This article underscores the importance of diprosopia in cattle species and suggests the need for more detailed investigations to better understand its pathogenesis.

  4. The York platelet syndrome: a fourth case with unusual pathologic features.

    PubMed

    White, James G; Pakzad, Kourosh; Meister, Lynn

    2013-01-01

    The present report describes a fourth patient with platelet pathological features identical to those found in the first three cases with the York platelet syndrome (YPS), as well as other findings that suggest he may be a variant. His platelets contain the same giant opaque and target organelles found earlier, as well as enlarged organelles with a gray appearing matrix. It is possible that the giant structures have the same source, but are at different stages of development. The fourth patient has platelet pathology suggestive of other thrombocyte disorders. He has many large platelets and normal sized thrombocytes nearly devoid of alpha granules. As a result, he was originally thought to have the gray platelet syndrome. He also has significant numbers of platelets attached to platelets and platelets in platelets as seen in patients with the X-linked GATA-1 mutation. Some of the fourth YPS patient's platelets contained massive alpha granules suggesting the possibility of the Paris Trousseau Jacobson Syndrome. Yet, none of these other platelet disorders had giant dense organelles like those found in YPS thrombocytes. As a result, it is reasonable to include this child with the other three, and diagnose him as a patient with the YPS.

  5. A Retrospective Study on Pathologic Features and Racial Disparities in Prostate Cancer

    PubMed Central

    Bigler, Steven A.; Pound, Charles R.; Zhou, Xinchun

    2011-01-01

    We reviewed more than 3,000 pathology reports on prostate cancer-related surgical specimens and analyzed racial disparities in histological and clinical features at the time of initial biopsy, diagnosis of prostate cancer, and prostatectomy, as well as in characteristics of tumor evolution between African American and Caucasian patients. As compared to Caucasians, African American patients had younger age, higher cancer detection rate, higher Gleason score of prostate cancer, and more bilateral involvement of the prostate. African Americans also had larger prostates, greater volume of tumor, and more positive margins. The diagnosis of HGPIN or ASAP in prostate biopsies and African American race conferred an increased risk of diagnosis of prostate cancer. The interval between prior noncancerous biopsy and the subsequent biopsy with diagnosis of prostate cancer was shorter in men with HGPIN, with ASAP, or of African American race. PMID:22135747

  6. Dysfunctional tubular endoplasmic reticulum constitutes a pathological feature of Alzheimer's disease.

    PubMed

    Sharoar, M G; Shi, Q; Ge, Y; He, W; Hu, X; Perry, G; Zhu, X; Yan, R

    2016-09-01

    Pathological features in Alzheimer's brains include mitochondrial dysfunction and dystrophic neurites (DNs) in areas surrounding amyloid plaques. Using a mouse model that overexpresses reticulon 3 (RTN3) and spontaneously develops age-dependent hippocampal DNs, here we report that DNs contain both RTN3 and REEPs, topologically similar proteins that can shape tubular endoplasmic reticulum (ER). Importantly, ultrastructural examinations of such DNs revealed gradual accumulation of tubular ER in axonal termini, and such abnormal tubular ER inclusion is found in areas surrounding amyloid plaques in biopsy samples from Alzheimer's disease (AD) brains. Functionally, abnormally clustered tubular ER induces enhanced mitochondrial fission in the early stages of DN formation and eventual mitochondrial degeneration at later stages. Furthermore, such DNs are abrogated when RTN3 is ablated in aging and AD mouse models. Hence, abnormally clustered tubular ER can be pathogenic in brain regions: disrupting mitochondrial integrity, inducing DNs formation and impairing cognitive function in AD and aging brains.

  7. Neoplastic diseases of the spermatic cord: an overview of pathological features, evaluation, and management

    PubMed Central

    Dagur, Gautam; Gandhi, Jason; Kapadia, Kailash; Inam, Rafid; Smith, Noel L.; Joshi, Gargi

    2017-01-01

    Extracellular tumors found with the spermatic cord, known as neoplasms, are usually identified to be benign. However, the accurate and timely diagnosis of spermatic cord masses is highly crucial, especially when most results are often overlooked or unclear. In this review, we discuss the anatomy and embryology of the spermatic cord. Upon rooting these fundamental concepts, we discuss an array of benign and malignant neoplastic tumors, including their origin, pathological features, clinical evaluation and management, as well as other case-specific characteristics of unique presentation. Many of these neoplasms are based on local neurological, vascular, muscular, bone, soft tissue, or lymphatic origin, while others have metastasized from particular areas of the body. PMID:28217455

  8. Estimation of T2* Relaxation Time of Breast Cancer: Correlation with Clinical, Imaging and Pathological Features

    PubMed Central

    Seo, Mirinae; Jahng, Geon-Ho; Sohn, Yu-Mee; Rhee, Sun Jung; Oh, Jang-Hoon; Won, Kyu-Yeoun

    2017-01-01

    Objective The purpose of this study was to estimate the T2* relaxation time in breast cancer, and to evaluate the association between the T2* value with clinical-imaging-pathological features of breast cancer. Materials and Methods Between January 2011 and July 2013, 107 consecutive women with 107 breast cancers underwent multi-echo T2*-weighted imaging on a 3T clinical magnetic resonance imaging system. The Student's t test and one-way analysis of variance were used to compare the T2* values of cancer for different groups, based on the clinical-imaging-pathological features. In addition, multiple linear regression analysis was performed to find independent predictive factors associated with the T2* values. Results Of the 107 breast cancers, 92 were invasive and 15 were ductal carcinoma in situ (DCIS). The mean T2* value of invasive cancers was significantly longer than that of DCIS (p = 0.029). Signal intensity on T2-weighted imaging (T2WI) and histologic grade of invasive breast cancers showed significant correlation with T2* relaxation time in univariate and multivariate analysis. Breast cancer groups with higher signal intensity on T2WI showed longer T2* relaxation time (p = 0.005). Cancer groups with higher histologic grade showed longer T2* relaxation time (p = 0.017). Conclusion The T2* value is significantly longer in invasive cancer than in DCIS. In invasive cancers, T2* relaxation time is significantly longer in higher histologic grades and high signal intensity on T2WI. Based on these preliminary data, quantitative T2* mapping has the potential to be useful in the characterization of breast cancer. PMID:28096732

  9. BRMS1 gene expression may be associated with clinico-pathological features of breast cancer.

    PubMed

    Lin, Li-Zhong; Cai, Miao-Guo; Dai, Yue-Chu; Zheng, Zhi-Bao; Jiang, Fang-Fang; Shi, Li-Li; Pan, Yin; Song, Han-Bing

    2017-08-31

    Our aim is to investigate whether or not the breast cancer metastasis suppressor 1 (BRMS1) gene expression is directly linked to clinico-pathological features of breast cancer. Following a stringent inclusion and exclusion criteria, case-control studies with associations between BRMS1 and breast cancer were selected from articles obtained by way of searches conducted through an electronic database. All statistical analyses were performed with Stata 12.0 (Stata Corp, College Station, TX, U.S.A.). Ultimately, 1,263 patients with breast cancer were found in a meta-analysis retrieved from a total that included 12 studies. Results of our meta-analysis suggested that BRMS1 protein in breast cancer tissues was significantly lower in comparison with normal breast tissues (odds ratio, OR = 0.08, 95% confidence interval (CI) = 0.04-0.15). The BRMS1 protein in metastatic breast cancer tissue was decreased than from that was found in non-metastatic breast cancer tissue (OR = 0.20, 95%CI = 0.13-0.29), and BRMS1 protein in tumor-node-metastasis (TNM) stages 1 and 2 was found to be higher than TNM stages 3 and 4 (OR = 4.62, 95%CI = 2.77-7.70). BRMS1 protein in all three major types of breast cancer was lower than that of control tissues respectively. We also found strong correlations between BRMS1 mRNA levels and TNM stage and tumor size. The results our meta-analysis showed that reduction in BRMS1 expression level was linked directly to clinico-pathological features of breast cancer significantly; therefore, suggesting the loss of expression or reduced levels of BRMS1 is potentially a strong indicator of the metastatic capacity of breast cancer with poor prognosis. © 2017 The Author(s).

  10. Estimation of T2* Relaxation Time of Breast Cancer: Correlation with Clinical, Imaging and Pathological Features.

    PubMed

    Seo, Mirinae; Ryu, Jung Kyu; Jahng, Geon-Ho; Sohn, Yu-Mee; Rhee, Sun Jung; Oh, Jang-Hoon; Won, Kyu-Yeoun

    2017-01-01

    The purpose of this study was to estimate the T2* relaxation time in breast cancer, and to evaluate the association between the T2* value with clinical-imaging-pathological features of breast cancer. Between January 2011 and July 2013, 107 consecutive women with 107 breast cancers underwent multi-echo T2*-weighted imaging on a 3T clinical magnetic resonance imaging system. The Student's t test and one-way analysis of variance were used to compare the T2* values of cancer for different groups, based on the clinical-imaging-pathological features. In addition, multiple linear regression analysis was performed to find independent predictive factors associated with the T2* values. Of the 107 breast cancers, 92 were invasive and 15 were ductal carcinoma in situ (DCIS). The mean T2* value of invasive cancers was significantly longer than that of DCIS (p = 0.029). Signal intensity on T2-weighted imaging (T2WI) and histologic grade of invasive breast cancers showed significant correlation with T2* relaxation time in univariate and multivariate analysis. Breast cancer groups with higher signal intensity on T2WI showed longer T2* relaxation time (p = 0.005). Cancer groups with higher histologic grade showed longer T2* relaxation time (p = 0.017). The T2* value is significantly longer in invasive cancer than in DCIS. In invasive cancers, T2* relaxation time is significantly longer in higher histologic grades and high signal intensity on T2WI. Based on these preliminary data, quantitative T2* mapping has the potential to be useful in the characterization of breast cancer.

  11. Correlation of computed tomography with pathological features in angiomatous nasal polyps.

    PubMed

    Dai, Li-Bo; Zhou, Shui-Hong; Ruan, Ling-Xiang; Zheng, Zhou-Jun

    2012-01-01

    Angiomatous nasal polyps (ANPs), also known as angiectatic polyps, have rarely been reported in the literature. ANPs are characterized by extensive vascular proliferation and ectasia. ANPs can grow rapidly and exhibit aggressive clinical behavior that could simulate malignancy preoperatively, and they are easily confused with other diseases. In the present study, we analyzed the correlation between the computed tomography (CT) findings of nasal angiomatous polyps and their pathological features. We evaluated CT findings and pathological features of 31 surgically proven ANPs. The study population included 16 males and 15 females aged between 27 and 81 years (mean age, 53.5 years). On CT, the masses were heterogeneous; they had a soft tissue density and filled the maxillary and/or nasal cavities. Calcifications were found in 2 of the 31 cases. The lesions showed a clear boundary (15/31). The low-density shading on CT was related to the inflammatory, necrotic, and cystic changes, and the high-density shading on CT was related to hemorrhagic areas of the mass. On contrast-enhanced CT, the center of the lesions was non-enhanced with peripheral intensification due to occlusion or compression of feeder vessels of the polyp center, and the inflammatory cells and neovascularization around the edge of the mass. The most common site of maxillary wall erosion was the medial wall (21/31), followed by the posterior lateral wall (3/31), upper wall (2/31), and septum (3/31). Of these, the nasal cavity and/or maxillary sinus were enlarged in 28 cases. These findings were associated with the chronic progress of nasal angiomatous changes. CT of ANPs may demonstrate benign bone changes associated with the lesions and may also reflect the fact that ANPs do not invade peripheral soft tissue. CT demonstrated these lesions consistently and provided information useful for surgical planning.

  12. Respiratory bronchiolitis-associated interstitial lung disease: radiologic features with clinical and pathologic correlation.

    PubMed

    Park, Jai Soung; Brown, Kevin K; Tuder, Rubin M; Hale, Valerie A E; King Jr, Talmadge E; Lynch, David A

    2002-01-01

    The purpose of this work was to describe the radiographic and CT findings in patients with respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) and to correlate them with clinical, physiologic, and pathologic features. RB-ILD was proved pathologically in all 21 patients. Sixteen (76%) patients were current smokers, and five (24%) patients were ex-smokers. The mean cigarette consumption was 38.7 pack-years. Chest radiographs and CT scans were semiquantitatively analyzed and correlated with clinical findings, physiologic measures, and a pathologic score of disease extent. The major radiographic findings were bronchial wall thickening in 16 patients (76%) and ground-glass opacity in 12 patients (57%). The predominant initial CT findings were central bronchial wall thickening (proximal to subsegmental bronchi) in 19 patients (90%), peripheral bronchial wall thickening (distal to subsegmental bronchi) in 18 patients (86%), centrilobular nodules in 15 patients (71%), and ground-glass opacity in 14 patients (67%), None of these CT findings had a significant zonal predominance. Other findings were upper lung predominant centrilobular emphysema (57%) and patchy areas of hypoattenuation (38%) with a lower lung predominance. Radiologic findings were similar in both current and ex-smokers. The amount of ground-glass opacity correlated inversely with arterial oxygen saturation ( r = -0.67, p = 0.04), and the areas of hypoattenuation correlated with alveolar-arterial oxygen gradient ( r = 0.56, p = 0.04). The extent of centrilobular nodules correlated with the extent of macrophages in respiratory bronchioles ( r = 0.53, p = 0.03) and with chronic inflammation of respiratory bronchioles ( r = 0.57, p = 0.02). The extent of ground-glass opacity correlated with the amount of macrophage accumulation in the alveoli and alveolar ducts ( r = 0.56, p < 0.01 and r = 0.54, p = 0.04, respectively). At follow-up CT after steroid treatment and smoking cessation, in nine

  13. The Hybrid Feature Selection Algorithm Based on Maximum Minimum Backward Selection Search Strategy for Liver Tissue Pathological Image Classification.

    PubMed

    Liu, Huiling; Jiang, Huiyan; Zheng, Ruiping

    2016-01-01

    We propose a novel feature selection algorithm for liver tissue pathological image classification. To improve the efficiency of feature selection, the same feature values of positive and negative samples are removed in rough selection. To obtain the optimal feature subset, a new heuristic search algorithm, which is called Maximum Minimum Backward Selection (MMBS), is proposed in precise selection. MMBS search strategy has the following advantages. (1) For the deficiency of Discernibility of Feature Subsets (DFS) evaluation criteria, which makes the class of small samples invalid for unbalanced samples, the Weighted Discernibility of Feature Subsets (WDFS) evaluation criteria are proposed as the evaluation strategy of MMBS, which is also available for unbalanced samples. (2) For the deficiency of Sequential Forward Selection (SFS) and Sequential Backward Selection (SBS), which can only add or only delete feature, MMBS decides whether to add the feature to feature subset according to WDFS criteria for each feature firstly; then it decides whether to remove the feature from feature subset according to SBS algorithm. In this way, the better feature subset can be obtained. The experiment results show that the proposed hybrid feature selection algorithm has good classification performance for liver tissue pathological image.

  14. The Hybrid Feature Selection Algorithm Based on Maximum Minimum Backward Selection Search Strategy for Liver Tissue Pathological Image Classification

    PubMed Central

    2016-01-01

    We propose a novel feature selection algorithm for liver tissue pathological image classification. To improve the efficiency of feature selection, the same feature values of positive and negative samples are removed in rough selection. To obtain the optimal feature subset, a new heuristic search algorithm, which is called Maximum Minimum Backward Selection (MMBS), is proposed in precise selection. MMBS search strategy has the following advantages. (1) For the deficiency of Discernibility of Feature Subsets (DFS) evaluation criteria, which makes the class of small samples invalid for unbalanced samples, the Weighted Discernibility of Feature Subsets (WDFS) evaluation criteria are proposed as the evaluation strategy of MMBS, which is also available for unbalanced samples. (2) For the deficiency of Sequential Forward Selection (SFS) and Sequential Backward Selection (SBS), which can only add or only delete feature, MMBS decides whether to add the feature to feature subset according to WDFS criteria for each feature firstly; then it decides whether to remove the feature from feature subset according to SBS algorithm. In this way, the better feature subset can be obtained. The experiment results show that the proposed hybrid feature selection algorithm has good classification performance for liver tissue pathological image. PMID:27563344

  15. Cognition, Language, and Clinical Pathological Features of Non-Alzheimer’s Dementias: An Overview

    PubMed Central

    Reilly, Jamie; Rodriguez, Amy; Lamy, Martine; Neils-Strunjas, Jean

    2010-01-01

    There are many distinct forms of dementia whose pharmacological and behavioral management differ. Differential diagnosis among the dementia variants currently relies upon a weighted combination of genetic and protein biomarkers, neuroanatomical integrity, and behavior. Diagnostic specificity is complicated by a high degree of overlap in the initial presenting symptoms across dementia subtypes. For this reason, reliable markers are of considerable diagnostic value. Communication disorders have proven to be among the strongest predictors for discriminating among dementia subtypes. As such, Speech-Language Pathologists may be poised to make an increasingly visible contribution to dementia diagnosis and its ongoing management. The value and durability of this potential contribution, however, demands an improved discipline-wide knowledge base about the unique features associated with different dementia variants. To this end we provide an overview of cognition, language, and clinical pathological features of four of the most common non-Alzheimer’s dementias: Frontotemporal Dementia, Vascular Dementia, Lewy Body Disease Dementia, and Parkinson’s Disease Dementia. PMID:20493496

  16. Comparison of clinical features in pathologically confirmed PSP and MSA patients followed at a tertiary center.

    PubMed

    Xie, Tao; Kang, Un J; Kuo, Sheng-Han; Poulopoulos, Markos; Greene, Paul; Fahn, Stanley

    2015-01-01

    The clinical diagnosis of progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) remains challenging due to heterogeneity of the diseases. Here we compared the clinical features of PSP and MSA to gain insight into their diagnosis and prognosis, particularly the prognostic value of down-gaze palsy latency in PSP progression. We reviewed clinical features of pathologically confirmed 10 PSP and 13 MSA patients, incidentally matched in age-at-onset, gender, and disease duration, followed at Columbia University Medical Center during 1994-2009. The final antemortem diagnosis was incorrect in 30% of PSP (all lacking down-gaze palsy) and 23% of MSA patients. Falls in the first year of the disease, pyramidal involvement and freezing of gait during the course were similar between PSP and MSA. Ataxia and apraxia were in 50% of the PSP patients. Parkinsonism responsive to levodopa treatment was in 30% of the PSP (all with resting tremor) and 50% of the MSA patients. Dysautonomia in MSA could occur as early as 3 years preceding the motor symptoms, with 46% within the first year of the motor onset, but 15% did not have dysautonomia in life. The latency of down-gaze palsy and urogenital dysfunction and MMSE scores at first visit in PSP, and the latency of falls and wheelchair confinement in MSA were all associated with the disease progression. We confirmed most of the previously published characterizations, and identified for the first time the prognostic value of down-gaze palsy latency in PSP progression.

  17. Pathological features of oxalate nephrosis in a population of koalas (Phascolarctos cinereus) in South Australia.

    PubMed

    Speight, K N; Boardman, W; Breed, W G; Taggart, D A; Woolford, L; Haynes, J I

    2013-03-01

    The wild and captive koala population of the Mt Lofty Ranges in South Australia has a high level of renal dysfunction in which crystals consistent with calcium oxalate have been observed in the kidneys. This study aimed to describe the pathological features of the renal disease in this population, confirm the composition of renal crystals as calcium oxalate, and determine whether any age or sex predispositions exist for this disease. A total of 51 koalas (28 wild rescues, 23 captive) were examined at necropsy, of which 28 (55%) were found to have gross and/or histological evidence of oxalate nephrosis. Histopathological features included intratubular and interstitial inflammation, tubule dilation, glomerular atrophy, tubule loss, and cortical fibrosis. Calcium oxalate crystals were demonstrated using a combination of polarization microscopy, alizarin red S staining, infrared spectroscopy, and energy-dispersive X-ray analysis with scanning electron microscopy. Uric acid and phosphate deposits were also shown to be present but were associated with minimal histopathological changes. No significant differences were found between the numbers of affected captive and wild rescued koalas; also, there were no sex or age predispositions identified, but it was found that oxalate nephrosis may affect koalas <2 years of age. The findings of this study suggest that oxalate nephrosis is a leading disease in this koala population. Possible causes of this disease are currently under investigation.

  18. Does the choice of display system influence perception and visibility of clinically relevant features in digital pathology images?

    NASA Astrophysics Data System (ADS)

    Kimpe, Tom; Rostang, Johan; Avanaki, Ali; Espig, Kathryn; Xthona, Albert; Cocuranu, Ioan; Parwani, Anil V.; Pantanowitz, Liron

    2014-03-01

    Digital pathology systems typically consist of a slide scanner, processing software, visualization software, and finally a workstation with display for visualization of the digital slide images. This paper studies whether digital pathology images can look different when presenting them on different display systems, and whether these visual differences can result in different perceived contrast of clinically relevant features. By analyzing a set of four digital pathology images of different subspecialties on three different display systems, it was concluded that pathology images look different when visualized on different display systems. The importance of these visual differences is elucidated when they are located in areas of the digital slide that contain clinically relevant features. Based on a calculation of dE2000 differences between background and clinically relevant features, it was clear that perceived contrast of clinically relevant features is influenced by the choice of display system. Furthermore, it seems that the specific calibration target chosen for the display system has an important effect on the perceived contrast of clinically relevant features. Preliminary results suggest that calibrating to DICOM GSDF calibration performed slightly worse than sRGB, while a new experimental calibration target CSDF performed better than both DICOM GSDF and sRGB. This result is promising as it suggests that further research work could lead to better definition of an optimized calibration target for digital pathology images resulting in a positive effect on clinical performance.

  19. The comparison of pathology in ferrets infected by H9N2 avian influenza viruses with different genomic features.

    PubMed

    Gao, Rongbao; Bai, Tian; Li, Xiaodan; Xiong, Ying; Huang, Yiwei; Pan, Ming; Zhang, Ye; Bo, Hong; Zou, Shumei; Shu, Yuelong

    2016-01-15

    H9N2 avian influenza virus circulates widely in poultry and has been responsible for sporadic human infections in several regions. Few studies have been conducted on the pathogenicity of H9N2 AIV isolates that have different genomic features. We compared the pathology induced by a novel reassortant H9N2 virus and two currently circulating H9N2 viruses that have different genomic features in ferrets. The results showed that the three viruses can induce infections with various amounts of viral shedding in ferrets. The novel H9N2 induced respiratory infection, but no pathological lesions were observed in lung tissues. The other two viruses induced mild to intermediate pathological lesions in lung tissues, although the clinical signs presented mildly in ferrets. The pathological lesions presented a diversity consistent with viral replication in ferrets.

  20. Correlation between three-dimensional ultrasound features and pathological prognostic factors in breast cancer.

    PubMed

    Jiang, Jun; Chen, Ya-qing; Xu, Yi-zhuan; Chen, Ming-li; Zhu, Yun-kai; Guan, Wen-bin; Wang, Xiao-jin

    2014-06-01

    To investigate the correlation of three-dimensional (3D) ultrasound features with prognostic factors in invasive ductal carcinoma. Surgical resection specimens of 85 invasive ductal carcinomas of 85 women who had undergone 3D ultrasound were included. Morphology features and vascularization perfusion on 3D ultrasound were evaluated. Pathologic prognostic factors, including tumour size, histological grade, lymph node status, oestrogen and progesterone receptor status (ER, PR), c-erbB-2 and p53 expression, and microvessel density (MVD) were determined. Correlations of 3D ultrasound features and prognostic factors were analysed. The retraction pattern in the coronal plane had a significant value as an independent predictor of a small tumour size (P = 0.014), a lower histological grade (P = 0.009) and positive ER or PR expression status (P = 0.001, 0.044). The retraction pattern with a hyperechoic ring only existed in low-grade and ER-positive tumours. The presence of the hyperechoic ring strengthened the ability of the retraction pattern to predict a good prognosis of breast cancer. The increased intra-tumour vascularization index (VI, the mean tumour vascularity) reflected a higher histological grade (P = 0.025) and had a positive correlation with MVD (r = 0.530, P = 0.001). The retraction pattern and histogram indices of VI provided by 3D ultrasound may be useful in predicting prognostic information about breast cancer. Three-dimensional ultrasound can potentially provide prognostic evaluation of breast cancer. The retraction pattern and hyperechoic ring in the coronal plane suggest good prognosis. The increased intra-tumour vascularization index reflects a higher histological grade. The intra-tumour vascularization index is positively correlated with microvessel density.

  1. Clinical and pathologic features of young endometrial cancer patients with loss of mismatch repair expression.

    PubMed

    Grzankowski, Kassondra S; Shimizu, David M; Kimata, Chieko; Black, Michael; Terada, Keith Y

    2012-09-01

    This study examines premenopausal and early menopause patients in a unique population with endometrial cancer and loss of mismatch repair (MMR) gene expression. The purpose is to compare clinical and pathologic differences in patients with loss of expression (LOE) to those with normal expression (NE). Endometrial cancer patients under age 60 in-between 1998 and 2008 were identified from a single tumor registry. Clinical and pathologic data were abstracted from records. Staining for expression of MSH6, MSH2, MLH1, and PMS2 were performed on archived tissue blocks. Statistical analysis was performed. 158 patients were analyzed; 58% Asian, 34% Pacific Islander, and 8% Caucasian. 31 demonstrated LOE of at least one MMR gene; 127 retained NE. 50% Caucasian, 21.9% Asian, and 12.5% Pacific Island populations had LOE of one or more MMR genes. LOE was found to have a higher incidence of Grade III (p=0.0013) and stage 3-4 tumors (p=0.0079), mean depth of myometrial invasion (p=0.0019), lymphovascular space invasion (p=0.0020), nodal metastases (p=0.0157), and a lower incidence of Grade I (p=0.0020) and stage 1A tumors (p=0.0085). LOE had a significantly lower mean BMI (p=0.0001). 35% of patients in the NE vs zero in the LOE group had a BMI greater than 40. Younger patients with LOE endometrial cancer appear to represent a clinically significant subgroup of patients without features characteristically found in classic type 1 endometrial cancer generally demonstrating lower BMI and tumors associated with poor prognostic characteristics. It is unclear if the distinctive ethnicity found in Hawaii has a significant impact on outcome. Further investigation is necessary to identify appropriate treatment strategies. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Clinical and pathological features of five-year survivors after pancreatectomy for pancreatic adenocarcinoma.

    PubMed

    Kimura, Kenjiro; Amano, Ryosuke; Nakata, Bunzo; Yamazoe, Sadaaki; Hirata, Keiichiro; Murata, Akihiro; Miura, Kotaro; Nishio, Kohei; Hirakawa, Toshiki; Ohira, Masaichi; Hirakawa, Kosei

    2014-11-27

    Clinical factors determining short-term survival after pancreatectomy have been well studied, but factors predicting long-term survival with curative resection are poorly understood in pancreatic carcinoma. Our objective was to identify clinical and pathological features of five-year disease-free survivors after surgical resection of pancreatic adenocarcinoma. The clinical and pathological data from 147 patients who underwent a potentially curative resection for pancreatic adenocarcinoma at our institution between 1988 and 2012 were retrospectively analyzed. Of 147 patients, 18 survived for more than five years after surgery without disease recurrence. A univariate analyses demonstrated that: two or fewer lymph node metastases (P=0.014), a preoperative serum carbohydrate antigen 19-9 (CA19-9) level of 40 U/mL or less (P=0.0018), an absence of intrapancreatic nerve invasion (P=0.028), and undergoing an R0 resection (P=0.011) were significantly associated with five-year survival. A logistic regression model identified the following independent cancer-related predictors of five-year survivors: having two or fewer lymph node metastases (odds ratio (OR): 6.02; 95% confidence interval (CI): 1.08 to 112.98; P=0.0385), a preoperative serum CA19-9 level of 40 U/mL or less (OR: 5.02; 95% CI: 1.68 to 16.48; P=0.0036), and undergoing an R0 resection (OR: 3.63; 95% CI: 1.12 to 14.28; P=0.0316). We conclude that number of lymph node metastases being two or less, a preoperative serum CA19-9 level of 40 U/mL or less, and undergoing an R0 resection may be independent predictive factors to identify actual five-year survivors after pancreatectomy for pancreatic adenocarcinoma.

  3. Large Cell Neuroendocrine Carcinoma of the Lung: Clinico-Pathologic Features, Treatment, and Outcomes.

    PubMed

    Naidoo, Jarushka; Santos-Zabala, Maria L; Iyriboz, Tunc; Woo, Kaitlin M; Sima, Camelia S; Fiore, John J; Kris, Mark G; Riely, Gregory J; Lito, Piro; Iqbal, Afsheen; Veach, Stephen; Smith-Marrone, Stephanie; Sarkaria, Inderpal S; Krug, Lee M; Rudin, Charles M; Travis, William D; Rekhtman, Natasha; Pietanza, Maria C

    2016-09-01

    Large cell neuroendocrine carcinoma (LCNEC) accounts for approximately 3% of lung cancers. Pathologic classification and optimal therapies are debated. We report the clinicopathologic features, treatment and survival of a series of patients with stage IV LCNEC. Cases of pathologically-confirmed stage IV LCNEC evaluated at Memorial Sloan Kettering Cancer Center from 2006 to 2013 were identified. We collected demographic, treatment, and survival data. Available radiology was evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. Forty-nine patients with stage IV LCNEC were identified. The median age was 64 years, 63% of patients were male, and 88% were smokers. Twenty-three patients (n = 23/49; 47%) had brain metastases, 17 at diagnosis and 6 during the disease course. Seventeen LCNEC patients (35%) had molecular testing, of which 24% had KRAS mutations (n = 4/17). Treatment data for first-line metastatic disease was available on 37 patients: 70% (n = 26) received platinum/etoposide and 30% (n = 11) received other regimens. RECIST was completed on 23 patients with available imaging; objective response rate was 37% (95% confidence interval, 16%-62%) with platinum/etoposide, while those treated with other first-line regimens did not achieve a response. Median overall survival was 10.2 months (95% confidence interval, 8.6-16.4 months) for the entire cohort. Patients with stage IV LCNEC have a high incidence of brain metastases. KRAS mutations are common. Patients with stage IV LCNEC do not respond as well to platinum/etoposide compared with historic data for extensive stage small-cell lung cancer; however, the prognosis is similar. Prospective studies are needed to define optimum therapy for stage IV LCNEC. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Evaluation of epidemiological, clinical, and pathological features of neuroaxonal dystrophy in Quarter Horses.

    PubMed

    Aleman, Monica; Finno, Carrie J; Higgins, Robert J; Puschner, Birgit; Gericota, Barbara; Gohil, Kishorchandra; LeCouteur, Richard A; Madigan, John E

    2011-09-15

    To describe epidemiological, clinical, and pathological features of neuroaxonal dystrophy in Quarter Horses (QHs) on a single farm. Prospective case series. Animals-148 horses. Neurologic, pathological, and toxicological evaluations were completed in selected neurologically affected horses over a 2-year period. Descriptive statistical analysis was performed. 87 QHs and 1 QH-crossbred horse were affected. Most (50/88 [56.8%]) affected horses were 1 to 2 years old (median age, 2 years [range, 2 months to 34 years]). Neurologic deficits included obtundation (53/88 [60%] horses), decreased to absent menace response (33/88 [37.5%]), proprioceptive positioning deficits, wide-based stance, ataxia, and dysmetria (88/88 [100%]). Most (78/88 [88.6%]) horses had mild ataxia, but some (10/88 [11.4%]) had moderate to severe ataxia. Low serum concentrations of vitamin E (≤ 2 mg/L) were detected in 3 index case horses and 16 of 17 randomly selected horses (13/14 affected and 3/3 unaffected) during study year 1. Dietary vitamin E supplementation did not improve neurologic deficits in affected horses; vitamin E administration in pregnant mares appeared to decrease but not prevent disease development among offspring born the following year. Lesions detected at necropsy included bilaterally symmetric neuroaxonal degeneration with axonal spheroids in the nucleus gracilis, nucleus cuneatus medialis, nucleus cuneatus lateralis, and nucleus thoracicus (5/5 horses). Neuroaxonal dystrophy should be considered in evaluation of young horses with ataxia and proprioceptive positioning deficits. Vitamin E deficiency may contribute to disease severity.

  5. Improved biochemical outcome with adjuvant radiotherapy after radical prostatectomy for prostate cancer with poor pathologic features

    SciTech Connect

    Vargas, Carlos; Kestin, Larry L. . E-mail: lkestin@beaumont.edu; Weed, Dan W.; Krauss, Daniel; Vicini, Frank A.; Martinez, Alvaro A.

    2005-03-01

    Purpose: The indications for adjuvant external beam radiotherapy (EBRT) after radical prostatectomy (RP) are poorly defined. We performed a retrospective comparison of our institution's experience treating prostate cancer with RP vs. RP followed by adjuvant EBRT. Methods and materials: Between 1987 and 1998, 617 patients with clinical Stage T1-T2N0M0 prostate cancer underwent RP. Patients who underwent preoperative androgen deprivation and those with positive lymph nodes were excluded. Of the 617 patients, 34 (5.5%) with an undetectable postoperative prostate-specific antigen (PSA) level underwent adjuvant prostatic fossa RT at a median of 0.25 year (range, 0.1-0.6) postoperatively because of poor pathologic features. The median total dose was 59.4 Gy (range, 50.4-66.6 Gy) in 1.8-2.0-Gy fractions. These 34 RP+RT patients were compared with the remaining 583 RP patients. Biochemical failure was defined as any postoperative PSA level {>=}0.1 ng/mL and any postoperative PSA level {>=}0.3 ng/mL (at least 30 days after surgery). Administration of androgen deprivation was also scored as biochemical failure when applying either definition. The median clinical follow-up was 8.2 years (range, 0.1-11.2 years) for RP and 8.4 years (range, 0.3-13.8 years) for RP+RT. Results: Radical prostatectomy + radiation therapy patients had a greater pathologic Gleason score (mean, 7.3 vs. 6.5; p < 0.01) and pathologic T stage (median, T3a vs. T2c; p < 0.01). Age (median, 65.7 years) and pretreatment PSA level (median, 7.9 ng/mL) were similar between the treatment groups. Extracapsular extension was present in 72% of RP+RT patients vs. 27% of RP patients (p < 0.01). The RP+RT patients were more likely to have seminal vesicle invasion (29% vs. 9%, p < 0.01) and positive margins (73% vs. 36%, p < 0.01). Despite these poor pathologic features, the 5-year biochemical control (BC) rate (PSA < 0.1 ng/mL) was 57% for RP+RT and 47% for RP (p = 0.28). For patients with extracapsular extension, the

  6. Vasculopathy-related clinical and pathological features are associated with severe juvenile dermatomyositis.

    PubMed

    Gitiaux, Cyril; De Antonio, Marie; Aouizerate, Jessie; Gherardi, Romain K; Guilbert, Thomas; Barnerias, Christine; Bodemer, Christine; Brochard-Payet, Karine; Quartier, Pierre; Musset, Lucile; Chazaud, Bénédicte; Desguerre, Isabelle; Bader-Meunier, Brigitte

    2016-03-01

    Outcome of JDM is highly heterogeneous. Our objective was to determine clinical and muscle biopsy features associated with poor outcome and response to treatment. Clinical data and muscle biopsy were obtained from a monocentric cohort of 29 patients. Clinical subgroups were defined by latent class model analysis of initial and follow-up parameters. Myopathological features were analysed using validated scores. Capillary loss was determined on reconstructions of transversal sections and assessed in the different age groups to take into account variations of muscle capillarization during post-natal development. Regression models were used to identify initial predictors of therapeutic response. Two distinct homogeneous subgroups of patients were identified according to clinical severity and pathological findings. The smallest group of patients (7/29) presented with severe JDM. Compared with the other group (22/29), patients had more severe muscle weakness at disease onset, low remission rate at 12 months, frequent subcutaneous limb oedema or gastrointestinal (GI) involvement and higher myopathological scores (capillary dropout, perifascicular necrosis/regeneration, fibres with internal myonuclei and fibrosis subscores). Relevance of capillary dropout to JDM severity was substantiated by age-based analysis, confirming its major role in JDM pathophysiology. Most of these manifestations could be related to vasculopathy (limb oedema, GI involvement, capillary dropout). Furthermore, Childhood Myositis Assessment Scale <34 with either GI involvement or muscle endomysial fibrosis at disease onset were the best predictors of poor response to treatment. Vasculopathy is prominent in severe JDM. Simple criteria can be used at initial evaluation to identify patients requiring a more intensive therapy. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Somatic molecular changes and histo-pathological features of colorectal cancer in Tunisia

    PubMed Central

    Aissi, Sana; Buisine, Marie Pierre; Zerimech, Farid; Kourda, Nadia; Moussa, Amel; Manai, Mohamed; Porchet, Nicole

    2013-01-01

    AIM: To determine correlations between family history, clinical features and mutational status of genes involved in the progression of colorectal cancer (CRC). METHODS: Histo-pathological features and molecular changes [KRAS, BRAF and CTNNB1 genes mutations, microsatellite instability (MSI) phenotype, expression of mismatch repair (MMR) and mucin (MUC) 5AC proteins, mutation and expression analysis of TP53, MLH1 promoter hypermethylation analysis] were examined in a series of 51 unselected Tunisian CRC patients, 10 of them had a proven or probable hereditary disease, on the track of new tumoral markers for CRC susceptibility in Tunisian patients. RESULTS: As expected, MSI and MMR expression loss were associated to the presence of familial CRC (75% vs 9%, P < 0.001). However, no significant associations have been detected between personal or familial cancer history and KRAS (codons 12 and 13) or TP53 (exons 4-9) alterations. A significant inverse relationship has been observed between the presence of MSI and TP53 accumulation (10.0% vs 48.8%, P = 0.0335) in CRC tumors, suggesting different molecular pathways to CRC that in turn may reflect different environmental exposures. Interestingly, MUC5AC expression was significantly associated to the presence of MSI (46.7% vs 8.3%, P = 0.0039), MMR expression loss (46.7% vs 8.3%, P = 0.0039) and the presence of familial CRC (63% vs 23%, P = 0.039). CONCLUSION: These findings suggest that MUC5AC expression analysis may be useful in the screening of Tunisian patients with high risk of CRC. PMID:23983431

  8. Identifying features of 'pathological demand avoidance' using the Diagnostic Interview for Social and Communication Disorders (DISCO).

    PubMed

    O'Nions, Elizabeth; Gould, Judith; Christie, Phil; Gillberg, Christopher; Viding, Essi; Happé, Francesca

    2016-04-01

    The term 'pathological demand avoidance' (PDA) was coined by Elizabeth Newson to describe children within the autism spectrum who exhibit obsessive resistance to everyday demands and requests (Newson et al., Arch Dis Child 88:595-600, 2003). Clinical accounts describe avoidance strategies including apparently strategic use of distraction or socially shocking behaviour, and obsessive need for control, reflected in domineering behaviour to peers and adults. Educational and management approaches effective for PDA reportedly differ from those for 'typical' autism spectrum disorders (ASD), and include novelty, humour and flexibility. Identification of PDA in individuals with ASD may have important implications for management (Eaton and Banting, J Learn Disabil Offending Behav 3:150-157, 2012). Despite increasing interest, no clinician-rated instrument for PDA has been developed. Here, items relevant to PDA were identified from the Diagnostic Interview for Social and Communication Disorder (DISCO) (Wing et al., J Child Psychol Psychiatry 43:307-325, 2002). The most PDA-specific subset of relevant DISCO items was selected, based on low endorsement in general across a sample of 153 individuals assessed for possible ASD using the DISCO. Having selected 11 DISCO PDA items for the measure, a subset of individuals with a high number of these features was identified (N = 27). Consistent with Newson's descriptions, this high scoring group was characterised by lack of co-operation, use of apparently manipulative behaviour, socially shocking behaviour, difficulties with other people, anxiety and sudden behavioural changes from loving to aggression. All but one case met criteria for an ASD. This study brings the field a step closer to a clinician-rated measure of PDA features and highlights the need for further elucidation of the PDA phenotype.

  9. The behavioural/dysexecutive variant of Alzheimer’s disease: clinical, neuroimaging and pathological features

    PubMed Central

    Pijnenburg, Yolande A. L.; Perry, David C.; Cohn-Sheehy, Brendan I.; Scheltens, Nienke M. E.; Vogel, Jacob W.; Kramer, Joel H.; van der Vlies, Annelies E.; Joie, Renaud La; Rosen, Howard J.; van der Flier, Wiesje M.; Grinberg, Lea T.; Rozemuller, Annemieke J.; Huang, Eric J.; van Berckel, Bart N. M.; Miller, Bruce L.; Barkhof, Frederik; Jagust, William J.; Scheltens, Philip; Seeley, William W.; Rabinovici, Gil D.

    2015-01-01

    A ‘frontal variant of Alzheimer’s disease’ has been described in patients with predominant behavioural or dysexecutive deficits caused by Alzheimer’s disease pathology. The description of this rare Alzheimer’s disease phenotype has been limited to case reports and small series, and many clinical, neuroimaging and neuropathological characteristics are not well understood. In this retrospective study, we included 55 patients with Alzheimer’s disease with a behavioural-predominant presentation (behavioural Alzheimer’s disease) and a neuropathological diagnosis of high-likelihood Alzheimer’s disease (n = 17) and/or biomarker evidence of Alzheimer’s disease pathology (n = 44). In addition, we included 29 patients with autopsy/biomarker-defined Alzheimer’s disease with a dysexecutive-predominant syndrome (dysexecutive Alzheimer’s disease). We performed structured chart reviews to ascertain clinical features. First symptoms were more often cognitive (behavioural Alzheimer’s disease: 53%; dysexecutive Alzheimer’s disease: 83%) than behavioural (behavioural Alzheimer’s disease: 25%; dysexecutive Alzheimer’s disease: 3%). Apathy was the most common behavioural feature, while hyperorality and perseverative/compulsive behaviours were less prevalent. Fifty-two per cent of patients with behavioural Alzheimer’s disease met diagnostic criteria for possible behavioural-variant frontotemporal dementia. Overlap between behavioural and dysexecutive Alzheimer’s disease was modest (9/75 patients). Sixty per cent of patients with behavioural Alzheimer’s disease and 40% of those with the dysexecutive syndrome carried at least one APOE ε4 allele. We also compared neuropsychological test performance and brain atrophy (applying voxel-based morphometry) with matched autopsy/biomarker-defined typical (amnestic-predominant) Alzheimer’s disease (typical Alzheimer’s disease, n = 58), autopsy-confirmed/Alzheimer’s disease biomarker-negative behavioural

  10. The behavioural/dysexecutive variant of Alzheimer's disease: clinical, neuroimaging and pathological features.

    PubMed

    Ossenkoppele, Rik; Pijnenburg, Yolande A L; Perry, David C; Cohn-Sheehy, Brendan I; Scheltens, Nienke M E; Vogel, Jacob W; Kramer, Joel H; van der Vlies, Annelies E; La Joie, Renaud; Rosen, Howard J; van der Flier, Wiesje M; Grinberg, Lea T; Rozemuller, Annemieke J; Huang, Eric J; van Berckel, Bart N M; Miller, Bruce L; Barkhof, Frederik; Jagust, William J; Scheltens, Philip; Seeley, William W; Rabinovici, Gil D

    2015-09-01

    A 'frontal variant of Alzheimer's disease' has been described in patients with predominant behavioural or dysexecutive deficits caused by Alzheimer's disease pathology. The description of this rare Alzheimer's disease phenotype has been limited to case reports and small series, and many clinical, neuroimaging and neuropathological characteristics are not well understood. In this retrospective study, we included 55 patients with Alzheimer's disease with a behavioural-predominant presentation (behavioural Alzheimer's disease) and a neuropathological diagnosis of high-likelihood Alzheimer's disease (n = 17) and/or biomarker evidence of Alzheimer's disease pathology (n = 44). In addition, we included 29 patients with autopsy/biomarker-defined Alzheimer's disease with a dysexecutive-predominant syndrome (dysexecutive Alzheimer's disease). We performed structured chart reviews to ascertain clinical features. First symptoms were more often cognitive (behavioural Alzheimer's disease: 53%; dysexecutive Alzheimer's disease: 83%) than behavioural (behavioural Alzheimer's disease: 25%; dysexecutive Alzheimer's disease: 3%). Apathy was the most common behavioural feature, while hyperorality and perseverative/compulsive behaviours were less prevalent. Fifty-two per cent of patients with behavioural Alzheimer's disease met diagnostic criteria for possible behavioural-variant frontotemporal dementia. Overlap between behavioural and dysexecutive Alzheimer's disease was modest (9/75 patients). Sixty per cent of patients with behavioural Alzheimer's disease and 40% of those with the dysexecutive syndrome carried at least one APOE ε4 allele. We also compared neuropsychological test performance and brain atrophy (applying voxel-based morphometry) with matched autopsy/biomarker-defined typical (amnestic-predominant) Alzheimer's disease (typical Alzheimer's disease, n = 58), autopsy-confirmed/Alzheimer's disease biomarker-negative behavioural variant frontotemporal dementia (n = 59

  11. Magnetic resonance imaging and incidental findings of lateral ankle pathologic features with asymptomatic ankles.

    PubMed

    Saxena, Amol; Luhadiya, Amit; Ewen, Brynn; Goumas, Chris

    2011-01-01

    We prospectively evaluated 102 magnetic resonance imaging (MRI) examinations in 100 patients with asymptomatic lateral ankles. The patients were undergoing MRI for other ankle pathologic features, including medial ankle, posterior ankle, soft tissue masses, or Achilles tendon pain. No patient had had a recent lateral ankle injury or any surgery. Whether the anterior talofibular ligament, calcaneofibular ligament, and peroneal tendons were intact, torn, or absent was recorded. The average patient age was 46.4 years. Of the 100 patients, 67 (66%) had no history of a lateral ankle sprain, and 35 (34%) had sustained 1 or more sprains in the remote past. Also, 72 had an intact anterior talofibular ligament (71%), 90 had an intact calcaneofibular ligament (89%), 67 had intact peroneus brevis tendons (66%), and 68 (67%) had intact peroneus longus tendons. One accessory peroneal tendon was noted. Approximately 30% of asymptomatic patients undergoing MRI had abnormal anterior talofibular ligaments and peronei. Because the published data show that functional rehabilitation is successful for 90% of symptomatic lateral ankle patients, caution is warranted if choosing surgical treatment on the basis of the MRI findings alone. Copyright © 2011 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  12. Cavernous Sinus: A Comprehensive Review of its Anatomy, Pathologic Conditions, and Imaging Features.

    PubMed

    Bakan, A A; Alkan, A; Kurtcan, S; Aralaşmak, A; Tokdemir, S; Mehdi, E; Özdemir, H

    2015-06-01

    The purpose of this article was to review the anatomy of the cavernous sinus (CS), illustrate numerous lesions that can affect the CS, and emphasize the imaging characteristics for each lesion to further refine the differential diagnoses. The CS, notwithstanding its small size, contains a complicated and crucial network that consists of the carotid artery, the venous plexus, and cranial nerves. The wide-ranging types of pathologies that can involve the CS can be roughly classified as tumoral, congenital, infectious/inflammatory/granulomatous, and vascular. Conditions that affect the CS usually lead to symptoms that are similar to each other; thus, for diagnosis, imaging procedures are required. Radiological evaluations are also required to detect pre- and postoperative CS invasion. Magnetic resonance imaging, which can be supplemented with thin-section contrast-enhanced sequences, is the preferred imaging technique for evaluating the CS. For correct diagnosis of CS lesions and accurate evaluations of CS invasions, it is essential to carefully analyze the anatomical structures within the CS and to acquire precise knowledge about the imaging features of CS lesions, which may frequently overlap.

  13. Small bowel adenocarcinoma in Crohn disease: CT-enterography features with pathological correlation.

    PubMed

    Soyer, Philippe; Hristova, Lora; Boudghène, Frank; Hoeffel, Christine; Dray, Xavier; Laurent, Valérie; Fishman, Elliot K; Boudiaf, Mourad

    2012-06-01

    The aim of this study was to analyze the clinical, pathological, and CT-enterography findings of small bowel adenocarcinomas in Crohn disease patients. Clinical, histopathological, and imaging findings were retrospectively evaluated in seven Crohn disease patients with small bowel adenocarcinoma. CT-enterography examinations were reviewed for morphologic features and location of tumor, presence of stratification, luminal stenosis, proximal dilatation, adjacent lymph nodes, and correlated with findings at histological examination. The tumor was located in the terminal (n = 6) or distal (n = 1) ileum. On CT-enterography, the tumor was visible in five patients, whereas two patients had no visible tumor. Four different patterns were individualized including small bowel mass (n = 2), long stenosis with heterogeneous submucosal layer (n = 2), short and severe stenosis with proximal small bowel dilatation (n = 2), and sacculated small bowel loop with irregular and asymmetric circumferential thickening (n = 1). Stratification, fat stranding, and comb sign were present in two, two, and one patients, respectively. Identification of a mass being clearly visible suggests strongly the presence of small bowel adenocarcinoma in Crohn disease patients but adenocarcinoma may be completely indistinguishable from benign fibrotic or acute inflammatory stricture. Knowledge of these findings is critical to help suggest the diagnosis of this rare but severe complication of Crohn disease.

  14. DNA methylation Profiles in Primary Cutaneous Melanomas are Associated with Clinically Significant Pathologic Features

    PubMed Central

    Thomas, Nancy E.; Slater, Nathaniel A.; Edmiston, Sharon N.; Zhou, Xin; Kuan, Pei-Fen; Groben, Pamela A.; Carson, Craig C.; Hao, Honglin; Parrish, Eloise; Moschos, Stergios J.; Berwick, Marianne; Ollila, David W.; Conway, Kathleen

    2014-01-01

    Summary DNA methylation studies have elucidated a methylation signature distinguishing primary melanomas from benign nevi and provided new insights about genes that may be important in melanoma development. However, it is unclear whether methylation differences among primary melanomas are related to tumor pathologic features with known clinical significance. We utilized the Illumina Golden Gate Cancer Panel array to investigate the methylation profiles of 47 primary cutaneous melanomas. Array-wide methylation patterns revealed a positive association of methylation with Breslow thickness and mutated BRAF, a negative association with mitotic rate, and a weak association with ulceration. Hierarchical clustering on CpG sites exhibiting the most variable methylation (n=235) divided the melanoma samples into three clusters, including a highly-methylated cluster that was positively associated with Breslow thickness and an intermediately-methylated cluster associated with Breslow thickness and mitotic rate. Our findings provide support for the existence of methylation-defined subsets in melanomas, with increased methylation associated with Breslow thickness. PMID:24986547

  15. C9orf72 BAC transgenic mice display typical pathologic features of ALS/FTD

    PubMed Central

    O'Rourke, Jacqueline G.; Bogdanik, Laurent; Muhammad, A.K.M.G.; Gendron, Tania F.; Kim, Kevin J.; Austin, Andrew; Cady, Janet; Liu, Elaine; Zarrow, Jonah; Grant, Sharday; Ho, Ritchie; Bell, Shaughn; Carmona, Sharon; Simpkinson, Megan; Lall, Deepti; Wu, Kathryn; Daughrity, Lillian; Dickson, Dennis W.; Harms, Matthew B.; Petrucelli, Leonard; Lee, Edward B.; Lutz, Cathleen M.; Baloh, Robert H.

    2015-01-01

    Summary Noncoding expansions of a hexanucleotide repeat (GGGGCC) in the C9orf72 gene are the most common cause of familial amyotrophic lateral sclerosis and frontotemporal dementia. Here we report transgenic mice carrying a bacterial artificial chromosome (BAC) containing the full human C9orf72 gene with either a normal allele (15 repeats) or disease-associated expansion (~100-1000 repeats; C9-BACexp). C9-BACexp mice displayed pathologic features seen in C9orf72 expansion patients, including widespread RNA foci and repeat associated non-ATG (RAN) translated dipeptides, which were suppressed by antisense oligonucleotides targeting human C9orf72. Nucleolin distribution was altered supporting that either C9orf72 transcripts or RAN dipeptides promote nucleolar dysfunction. Despite early and widespread production of RNA foci and RAN dipeptides in C9-BACexp mice, behavioral abnormalities and neurodegeneration were not observed even at advanced ages, supporting the hypothesis that RNA foci and RAN dipeptides occur presymptomatically, and are not sufficient to drive neurodegeneration in mice at levels seen in patients. PMID:26637796

  16. C9orf72 BAC Transgenic Mice Display Typical Pathologic Features of ALS/FTD.

    PubMed

    O'Rourke, Jacqueline G; Bogdanik, Laurent; Muhammad, A K M G; Gendron, Tania F; Kim, Kevin J; Austin, Andrew; Cady, Janet; Liu, Elaine Y; Zarrow, Jonah; Grant, Sharday; Ho, Ritchie; Bell, Shaughn; Carmona, Sharon; Simpkinson, Megan; Lall, Deepti; Wu, Kathryn; Daughrity, Lillian; Dickson, Dennis W; Harms, Matthew B; Petrucelli, Leonard; Lee, Edward B; Lutz, Cathleen M; Baloh, Robert H

    2015-12-02

    Noncoding expansions of a hexanucleotide repeat (GGGGCC) in the C9orf72 gene are the most common cause of familial amyotrophic lateral sclerosis and frontotemporal dementia. Here we report transgenic mice carrying a bacterial artificial chromosome (BAC) containing the full human C9orf72 gene with either a normal allele (15 repeats) or disease-associated expansion (∼100-1,000 repeats; C9-BACexp). C9-BACexp mice displayed pathologic features seen in C9orf72 expansion patients, including widespread RNA foci and repeat-associated non-ATG (RAN) translated dipeptides, which were suppressed by antisense oligonucleotides targeting human C9orf72. Nucleolin distribution was altered, supporting that either C9orf72 transcripts or RAN dipeptides promote nucleolar dysfunction. Despite early and widespread production of RNA foci and RAN dipeptides in C9-BACexp mice, behavioral abnormalities and neurodegeneration were not observed even at advanced ages, supporting the hypothesis that RNA foci and RAN dipeptides occur presymptomatically and are not sufficient to drive neurodegeneration in mice at levels seen in patients.

  17. Clinical and pathological features of hair coat abnormalities in curly coated retrievers from UK and Sweden.

    PubMed

    Bond, R; Varjonen, K; Hendricks, A; Chang, Y M; Brooks Brownlie, H

    2016-12-01

    To gain information on hair loss amongst curly coated retrievers by questionnaire and to define the clinical and pathological features of hair coat abnormalities in affected dogs in the United Kingdom and Sweden. Questionnaires were completed by members of the Curly Coated Retriever Clubs. Fourteen dogs (six in the United Kingdom, eight in Sweden) were clinically examined and skin/hair samples collected for microscopy and histopathology. Blood was collected for haematological, biochemical and endocrine assays. Of 90 dogs surveyed, 39 had current or previous episodes of symmetrical, non-pruritic alopecia and or frizzy coat changes, usually affecting caudal thighs, axillae, dorsum and neck before 18 months of age; 23 dogs had a waxing/waning course. Examined dogs generally matched the pattern described in questionnaires. Hair shaft anomalies comprised occasional distorted anagen bulbs (10 dogs) and transverse fractures (8 dogs). Vertical histopathological sections showed infundibular hyperkeratosis (28 of 30 sections) and low-grade pigment clumping (17 of 30). Subtle telogenisation of hair follicles was unequivocally confirmed by transverse histomorphometric analyses. The follicular dysplasia of curly coated retriever reported here is similar to that of Irish water spaniels and Chesapeake Bay retrievers but distinct from that of Portuguese water dogs. The genetic basis requires further assessment. © 2016 British Small Animal Veterinary Association.

  18. Clinical and pathological feature of bone marrow granulomas: A modern Australian series.

    PubMed

    Crispin, P; Holmes, A

    2017-10-06

    Marrow granulomas have been commonly associated with mycobacterial infections, prompting extensive investigations in some cases where they are found, but in the setting of changing infectious epidemiology, there is a lack of recent data to guide the search for probable causes. A retrospective case series examining the clinical and pathological findings in all cases where marrow granulomas were reported over a 10-year period at The Canberra Hospital, Australia. Of the 6062 marrow biopsies performed, 73 (1.2%) from 66 individuals had confirmed granulomas. Some patients had multiple potential causes found. B-cell non-Hodgkin Lymphoma, sarcoidosis and autoimmune disease were the most frequently observed causes. Infections were less common in this cohort than in the previous series, with no tuberculosis seen. The presence of granulomas in the marrow did not signify the presence of active malignancy in the marrow. There were no associations with any specific morphological characteristics of the granulomas and the presumed causes. Marrow granulomas are seen in a variety conditions. Neither their presence nor their morphological features are a guide to further investigations, which should be determined by the clinical presentation as appropriate. © 2017 John Wiley & Sons Ltd.

  19. Solid pseudopapillary neoplasm of the pancreas: CT imaging features and radiologic-pathologic correlation

    PubMed Central

    Anil, Gopinathan; Zhang, Junwei; Al-Hamar, Nawal Ebrahim; Nga, Min En

    2017-01-01

    PURPOSE We aimed to evaluate the imaging features of solid pseudopapillary neoplasm (SPN) of the pancreas with an emphasis on radiologic-pathologic correlation. METHODS Ten patients (all female; mean age, 32 years) with histologic or cytologic diagnosis of SPN encountered between January 2007 and December 2013 were included in this study. Preoperative computed tomography (CT) images were reviewed for location, attenuation, enhancement pattern, margin, shape, size, morphology, presence of capsule and calcification. CT appearances were correlated with histopathologic findings. RESULTS Tumors in the distal pancreatic body and tail had a tendency to be larger (mean size 12.6 cm vs. 4.0 cm). Six of the nine tumors that were resected had a fibrous pseudocapsule at histology, five of which could be identified on CT scan. Eight lesions had mixed hypoenhancing solid components and cystic areas corresponding to tumor necrosis and hemorrhage. The two smallest lesions were purely solid and nonencapsulated. Varied patterns of calcification were seen in four tumors. Three of the four pancreatic tail tumors invaded the spleen. At a median follow-up of 53 months, there was no evidence of recurrence in the nine patients who underwent surgical resection of the tumor. CONCLUSION A mixed solid and cystic pancreatic mass in a young woman is suggestive of SPN. However, smaller lesions may be completely solid. Splenic invasion can occur in pancreatic tail SPNs; however, in this series it did not adversely affect the long-term outcome. PMID:28089954

  20. Genetics Home Reference: Huntington disease-like syndrome

    MedlinePlus

    ... Twitter Home Health Conditions Huntington disease-like syndrome Huntington disease-like syndrome Printable PDF Open All Close ... collapse boxes. Description As its name suggests, a Huntington disease -like (HDL) syndrome is a condition that ...

  1. Comparative analysis of imaging and pathology features of mucinous carcinoma of the breast.

    PubMed

    Zhang, Ling; Jia, Ningyang; Han, Lujun; Yang, Lei; Xu, Weimin; Chen, Weiguo

    2015-04-01

    The purpose of the study was to explore the relationship between the mammographic features, MR features, and pathological manifestations of PMBCs and MMBCs. Twenty-seven cases of mucinous breast carcinoma confirmed in surgical biopsy, including 18 cases of PMBC and 9 cases of MMBC, were included (mean age, 51.2 and 53.3 years, respectively). All patients underwent preoperative mammography, and 13 of 27 patients underwent preoperative MR imaging (MRI), 4 of whom underwent diffusion-weighted imaging. All mammographic and MRI information, such as the size, shape, borders of the mass, and evidence of calcification were classified according to the American Collage of Radiology (ACR) Breast Imaging-Reporting And Data System (BI-RADS) mammography/MR lexicon. The signal intensity of the mass was visually classified as low, iso, high, strongly high, or mixed in accordance with surrounding mammary gland tissues. The pattern of internal enhancement of the mass included homogeneity, rim enhancement, central enhancement, dark internal septation, and enhancing internal septation. The kinetic curve pattern was categorized into 3 types: persistent, plateau, or washout. There was no significant difference PMBC and MMBC in the shape of tumor, calcifications, T2 signal intensity, internal mass enhancement, kinetic curve assessment, and positivity for estrogen receptor (ER), progesterone receptor (PR), and human epidermalgrowth factor receptor-2 (HER-2). The PMBC tumors were larger than MMBC tumors (P < .001), and MMBC tended to present as an ill-circumscribed mass (P = .043). The ADC values of the 5 lesions of 4 mucinous breast carcinoma (MBCs) ranged from 0.771 to 2.252 × 10(3) mm(2)/s, markedly greater than that of conventional infiltrating ductal carcinoma (IDC). The ADC values of MMBC were visibly less than those of PMBC for the former mixed with massive tumor cells of IDC. MBC commonly presented as masses with well circumscribed, round, or lobular shapes. The remaining cases

  2. An improved high order texture features extraction method with application to pathological diagnosis of colon lesions for CT colonography

    NASA Astrophysics Data System (ADS)

    Song, Bowen; Zhang, Guopeng; Lu, Hongbing; Wang, Huafeng; Han, Fangfang; Zhu, Wei; Liang, Zhengrong

    2014-03-01

    Differentiation of colon lesions according to underlying pathology, e.g., neoplastic and non-neoplastic, is of fundamental importance for patient management. Image intensity based textural features have been recognized as a useful biomarker for the differentiation task. In this paper, we introduce high order texture features, beyond the intensity, such as gradient and curvature, for that task. Based on the Haralick texture analysis method, we introduce a virtual pathological method to explore the utility of texture features from high order differentiations, i.e., gradient and curvature, of the image intensity distribution. The texture features were validated on database consisting of 148 colon lesions, of which 35 are non-neoplastic lesions, using the random forest classifier and the merit of area under the curve (AUC) of the receiver operating characteristics. The results show that after applying the high order features, the AUC was improved from 0.8069 to 0.8544 in differentiating non-neoplastic lesion from neoplastic ones, e.g., hyperplastic polyps from tubular adenomas, tubulovillous adenomas and adenocarcinomas. The experimental results demonstrated that texture features from the higher order images can significantly improve the classification accuracy in pathological differentiation of colorectal lesions. The gain in differentiation capability shall increase the potential of computed tomography (CT) colonography for colorectal cancer screening by not only detecting polyps but also classifying them from optimal polyp management for the best outcome in personalized medicine.

  3. A retrospective cohort study identifying the principal pathological features useful in the diagnosis of inclusion body myositis.

    PubMed

    Brady, Stefen; Squier, Waney; Sewry, Caroline; Hanna, Michael; Hilton-Jones, David; Holton, Janice L

    2014-04-28

    The current pathological diagnostic criteria for sporadic inclusion body myositis (IBM) lack sensitivity. Using immunohistochemical techniques abnormal protein aggregates have been identified in IBM, including some associated with neurodegenerative disorders. Our objective was to investigate the diagnostic utility of a number of markers of protein aggregates together with mitochondrial and inflammatory changes in IBM. Retrospective cohort study. The sensitivity of pathological features was evaluated in cases of Griggs definite IBM. The diagnostic potential of the most reliable features was then assessed in clinically typical IBM with rimmed vacuoles (n=15), clinically typical IBM without rimmed vacuoles (n=9) and IBM mimics-protein accumulation myopathies containing rimmed vacuoles (n=7) and steroid-responsive inflammatory myopathies (n=11). Specialist muscle services at the John Radcliffe Hospital, Oxford and the National Hospital for Neurology and Neurosurgery, London. Individual pathological features, in isolation, lacked sensitivity and specificity. However, the morphology and distribution of p62 aggregates in IBM were characteristic and in a myopathy with rimmed vacuoles, the combination of characteristic p62 aggregates and increased sarcolemmal and internal major histocompatibility complex class I expression or endomysial T cells were diagnostic for IBM with a sensitivity of 93% and specificity of 100%. In an inflammatory myopathy lacking rimmed vacuoles, the presence of mitochondrial changes was 100% sensitive and 73% specific for IBM; characteristic p62 aggregates were specific (91%), but lacked sensitivity (44%). We propose an easily applied diagnostic algorithm for the pathological diagnosis of IBM. Additionally our findings support the hypothesis that many of the pathological features considered typical of IBM develop later in the disease, explaining their poor sensitivity at disease presentation and emphasising the need for revised pathological criteria

  4. A retrospective cohort study identifying the principal pathological features useful in the diagnosis of inclusion body myositis

    PubMed Central

    Brady, Stefen; Squier, Waney; Sewry, Caroline; Hanna, Michael; Hilton-Jones, David; Holton, Janice L

    2014-01-01

    Objective The current pathological diagnostic criteria for sporadic inclusion body myositis (IBM) lack sensitivity. Using immunohistochemical techniques abnormal protein aggregates have been identified in IBM, including some associated with neurodegenerative disorders. Our objective was to investigate the diagnostic utility of a number of markers of protein aggregates together with mitochondrial and inflammatory changes in IBM. Design Retrospective cohort study. The sensitivity of pathological features was evaluated in cases of Griggs definite IBM. The diagnostic potential of the most reliable features was then assessed in clinically typical IBM with rimmed vacuoles (n=15), clinically typical IBM without rimmed vacuoles (n=9) and IBM mimics—protein accumulation myopathies containing rimmed vacuoles (n=7) and steroid-responsive inflammatory myopathies (n=11). Setting Specialist muscle services at the John Radcliffe Hospital, Oxford and the National Hospital for Neurology and Neurosurgery, London. Results Individual pathological features, in isolation, lacked sensitivity and specificity. However, the morphology and distribution of p62 aggregates in IBM were characteristic and in a myopathy with rimmed vacuoles, the combination of characteristic p62 aggregates and increased sarcolemmal and internal major histocompatibility complex class I expression or endomysial T cells were diagnostic for IBM with a sensitivity of 93% and specificity of 100%. In an inflammatory myopathy lacking rimmed vacuoles, the presence of mitochondrial changes was 100% sensitive and 73% specific for IBM; characteristic p62 aggregates were specific (91%), but lacked sensitivity (44%). Conclusions We propose an easily applied diagnostic algorithm for the pathological diagnosis of IBM. Additionally our findings support the hypothesis that many of the pathological features considered typical of IBM develop later in the disease, explaining their poor sensitivity at disease presentation and

  5. Association between pathology and texture features of multi parametric MRI of the prostate

    NASA Astrophysics Data System (ADS)

    Kuess, Peter; Andrzejewski, Piotr; Nilsson, David; Georg, Petra; Knoth, Johannes; Susani, Martin; Trygg, Johan; Helbich, Thomas H.; Polanec, Stephan H.; Georg, Dietmar; Nyholm, Tufve

    2017-10-01

    The role of multi-parametric (mp)MRI in the diagnosis and treatment of prostate cancer has increased considerably. An alternative to visual inspection of mpMRI is the evaluation using histogram-based (first order statistics) parameters and textural features (second order statistics). The aims of the present work were to investigate the relationship between benign and malignant sub-volumes of the prostate and textures obtained from mpMR images. The performance of tumor prediction was investigated based on the combination of histogram-based and textural parameters. Subsequently, the relative importance of mpMR images was assessed and the benefit of additional imaging analyzed. Finally, sub-structures based on the PI-RADS classification were investigated as potential regions to automatically detect maligned lesions. Twenty-five patients who received mpMRI prior to radical prostatectomy were included in the study. The imaging protocol included T2, DWI, and DCE. Delineation of tumor regions was performed based on pathological information. First and second order statistics were derived from each structure and for all image modalities. The resulting data were processed with multivariate analysis, using PCA (principal component analysis) and OPLS-DA (orthogonal partial least squares discriminant analysis) for separation of malignant and healthy tissue. PCA showed a clear difference between tumor and healthy regions in the peripheral zone for all investigated images. The predictive ability of the OPLS-DA models increased for all image modalities when first and second order statistics were combined. The predictive value reached a plateau after adding ADC and T2, and did not increase further with the addition of other image information. The present study indicates a distinct difference in the signatures between malign and benign prostate tissue. This is an absolute prerequisite for automatic tumor segmentation, but only the first step in that direction. For the specific

  6. Surgical treatment of microinvasive cervical cancer: analysis of pathologic features with implications on radicality.

    PubMed

    Yoneda, Juliana Yoko; Braganca, Joana Froes; Sarian, Luis Otavio; Borba, Patrícia Patury; Conceição, Jose Carlos J; Zeferino, Luiz Carlos

    2015-05-01

    To evaluate pathologic features with implications on surgical radicality in women treated with radical hysterectomy and pelvic lymphadenectomy for cervical cancer stage IA1 with lymph vascular space invasion (LVSI) and stage IA2 by correlating findings in conization and hysterectomy specimens. Women with cervical cancer stage IA1 with LVSI and stage IA2 diagnosed by loop electrosurgical excisional procedure or cold knife conization were treated with radical hysterectomy and pelvic lymphadenectomy from January 1999 to December 2011 in 2 institutions. Fifty patients were enrolled: 40 with stage IA2 and 10 with stage IA1 with LVSI. Median age was 43 (30-67) years. All patients underwent cervical conization for diagnosis (45 loop electrosurgical excisional procedure, 5 cold knife). Lymph vascular space invasion was detected in 15 patients (30%). Two patients had positive pelvic nodes. No parametrial involvement was detected in the entire cohort. Positive margins were present in 35 patients, and residual disease was detected in 22 patients (44%). Positive margins predicted residual disease at radical hysterectomy (P = 0.02). Medium follow-up time was 51 months. One patient developed a pelvic recurrence, and there were no disease-related deaths. Patients with positive margins in cone biopsy specimens have an increased risk of residual disease at radical hysterectomy and require careful evaluation before conservative surgery. Pelvic lymph node evaluation is essential because lymph node metastasis may occur even in early stages. The lack of parametrial invasion in this study reinforces the knowledge that the select group of patients with microinvasive cervical carcinoma stages IA1 LVSI and stage IA2 have a very low risk of parametrial infiltration. Less radical surgery can be carefully considered for these patients.

  7. [Clinico-pathological features of papillary thyroid cancer coexistent with Hashimoto's thyroiditis].

    PubMed

    Molnár, Sarolta; Győry, Ferenc; Nagy, Endre; Méhes, Gábor; Molnár, Csaba

    2017-02-01

    Former studies suggest the frequent coexistence of Hashimoto's thyreoditis with papillary thyroid cancer, frequently featured by multifocal carcinogenesis but lower clinical stages compared to thyroid cancers lacking thyroiditis. We examined the clinico-pathological correlations between Hashimoto's thyroditis and papillary thyroid cancer in our region in the North-Eastern part of Hungary. We included a total of 230 patients with papillary thyroid cancer who underwent thyroid surgery at the Surgical Department of the University of Debrecen. Patients' sex, age, multifocality of thyroid cancer and clinical stage were evaluated. Cases included 40 patients (17.4%) with (4 male, 36 female) and 190 (82.6%) patients without HT (44 male, 146 female). Hashimoto's thyroiditis related thyroid cancer was almost exclusively associated with the papillary histological type. Multifocality of papillary cancer was significantly more frequent with coexisting Hashimoto's thyroiditis (16/40; 40.0%) compared to cases uninvolved (45/190; 23.7%; p = 0.034). In contrast, lymph node metastasis was significantly less frequent among patients with Hashimoto's thyroiditis (4 pN1 [36.4%]; 7 pN0 [63.6%]) then without it (34 pN1 [82.9%]; 7 pN0 [17.1%]; p = 0.002). Higher frequency and multifocality of papillary thyroid cancer might be the consequence of preexisting Hashimoto's thyroiditis to be considered as a preneoplastic stimulus supporting carcinogenesis, though the exact pathomechanism of this correlation is not clear yet. Orv. Hetil., 2017, 158(5), 178-182.

  8. Specific features of cytological and colposcopical pattern in pregnant women with benign cervix uteri pathology in anamnesis.

    PubMed

    Bysaha, Nataliya Yu

    2016-01-01

    a tendency of increasing incidence of the cervix uteri precancer and cancer in women of reproductive age is noticed recently being related to the growth of number of the sexually-transmitted infections. The cervix uteri pathology incidence in women of fertile age is 20-25%. to study the specific features of the cytological and colposcopical pattern in pregnant patients with benign cervix uteri pathology in the anamnesis and the character of its change post partum. we have examined 195 women during their pregnancy and 3-5 months post partum. All pregnant women, alongside with generally accepted clinical and laboratory examinations, were subjected to the simple and extended colposcopy, cytology of the targeted smears and, according to indications, the histological studies of bioptate. according to the results of the colcoscopical studies and the signs of the cervix uteri pathology found, the patients were divided into several groups. A control group included 49 pregnant women. The clinical and instrumental examination of 146 women with cervix uteri pathology has been carried out both during pregnancy and post partum. the structure of the clinical forms of benign and premalignant changes in the cervix uteri epithelium in pregnant patients has been found. Specific features of the cytological and colposcopical pattern in pregnant patients with benign cervix uteri pathology in anamnesis have been studied. The relationship between the parity of pregnancy, delivery, route of delivery and regress of both benign and premalignant changes in the cervix uteri epithelium 3-5 months post partum has been determined.

  9. The Characteristics of Herpes Simplex Virus Type 1 Infection in Rhesus Macaques and the Associated Pathological Features

    PubMed Central

    Fan, Shengtao; Cai, Hongzhi; Xu, Xingli; Feng, Min; Wang, Lichun; Liao, Yun; Zhang, Ying; He, Zhanlong; Yang, Fengmei; Yu, Wenhai; Wang, Jingjing; Zhou, Jumin; Li, Qihan

    2017-01-01

    As one of the major pathogens for human herpetic diseases, herpes simplex virus type 1 (HSV1) causes herpes labialis, genital herpes and herpetic encephalitis. Our aim here was to investigate the infectious process of HSV1 in rhesus macaques and the pathological features induced during this infection. Clinical symptoms that manifested in the rhesus macaque during HSV1 infection included vesicular lesions and their pathological features. Viral distribution in the nervous tissues and associated pathologic changes indicated the typical systematic pathological processes associated with viral distribution of HSV1. Interestingly, vesicular lesions recurred in oral skin or in mucosa associated with virus shedding in macaques within four to five months post-infection, and viral latency-associated transcript (LAT) mRNA was found in the trigeminal ganglia (TG) on day 365 post-infection. Neutralization testing and enzyme-linked immunospot (ELISpot) detection of specific T cell responses confirmed the specific immunity induced by HSV1 infection. Thus, rhesus macaques could serve as an infectious model for HSV1 due to their typical clinical symptoms and the pathological recurrence associated with viral latency in nervous tissues. PMID:28146109

  10. A comparison of the clinico-pathological features with stool pathogens in patients hospitalised with the symptom of diarrhoea.

    PubMed

    Watson, B; Ellis, M; Mandal, B; Dunbar, E; Whale, K; Brennand, J

    1986-01-01

    The clinico-pathological features of 515 adult patients admitted to a major Regional Infectious Diseases Unit in United Kingdom with the symptom complex of diarrhoea were compared to the pathogens detected in their stool specimens. Routine clinical examination supported by basic pathological and laboratory investigations identified 138 (28%) in whom the cause of diarrhoea was extragastrointestinal or non-infectious gastrointestinal. Of the 351 patients (72%) with infectious gastroenteritis 72 (21%) had campylobacter, 59 (17%) had salmonella (22% bacteraemic) and 16 (5%) shigella. Clostridium difficile toxin accounted for a further 15 (4%)--antibiotics had been the antecedent cause in only one half of these. Routine microscopical examination of the faeces for red and white cells distinguished many with "culture positive" diarrhoea from those with "culture negative" infectious diarrhoea. Although there are no clinico-pathological features which are unique to a particular pathogen and unequivocally suggest a particular pathogen, certain features did tend to present more often in association with particular microorganisms, and this knowledge may suggest a bacterial diagnosis whilst awaiting the definitive results of stool microbiology. These features include prior antimicrobial therapy with positive sigmoidoscopical/histological features: Cl. difficile; protracted diarrhoea in elderly severely dehydrated patients: salmonellosis; foreign travel in males with bloody diarrhoea: shigellosis; abdominal pain in younger patients with a small degree of vomiting: campylobacteriosis. Early diagnosis may then prove useful in rationalizing initial therapy, particularly the appropriate use of antimicrobials.

  11. Immunohistochemical angiogenic biomarkers in hepatocellular carcinoma and cirrhosis: correlation with pathological features

    PubMed Central

    Ribeiro, Osmar Damasceno; Canedo, Nathalie Henriques Silva; Pannain, Vera Lucia

    2016-01-01

    OBJECTIVE: To investigate immunohistochemical markers of angiogenesis and their association with pathological prognostic features in hepatocellular carcinoma and cirrhotic liver. METHODS: Vascular endothelial growth factor, CD105, and cyclooxygenase-2 were immunohistochemically detected in 52 hepatocellular carcinoma tissue samples and 48 cirrhotic liver tissue samples. Semiquantitative measurements of vascular endothelial growth factor and cyclooxygenase-2 were evaluated considering the degree and intensity of immunostaining based on a 7-point final scoring scale. CD105 microvascular density (MVD-CD105) was measured using automated analysis. Morphological aspects evaluated in the hepatocellular carcinoma samples included size (≤2 and >2 cm), differentiation grade, and microvascular invasion. RESULTS: The mean vascular endothelial growth factor immunoreactivity score was slightly higher in the hepatocellular carcinoma samples (4.83±1.35) than the cirrhotic liver (4.38±1.28) samples. There was a significant and direct correlation between these mean scores (rs=0.645, p=0.0001). Cyclooxygenase-2 was expressed in all the cirrhotic liver samples but was only found in 78% of the hepatocellular carcinoma samples. The mean cyclooxygenase-2 score was higher in the cirrhotic liver samples (4.85±1.38) than the hepatocellular carcinoma samples (2.58±1.68), but there was no correlation between the scores (rs=0.177, p=0.23). The mean CD105 percentage in the hepatocellular carcinoma samples (11.2%) was lower than that in the cirrhotic samples (16.9%). There was an inverse relationship in MVD-CD105 expression between the hepatocellular carcinoma and cirrhotic samples (rs=-0.78, p=0.67). There were no significant associations between vascular endothelial growth factor expression and morphological characteristics. Cyclooxygenase-2 and CD105 were associated with hepatocellular carcinoma differentiation grade (p=0.003 and p=0.05, respectively). CONCLUSION: Vascular endothelial

  12. A case of aggressive solid pseudopapillary neoplasm: Comparison of clinical and pathologic features with non-aggressive cases.

    PubMed

    Watanabe, Yukihiro; Okamoto, Kojun; Okada, Katsuya; Aikawa, Masayasu; Koyama, Isamu; Yamaguchi, Hiroshi

    2017-04-01

    Solid pseudopapillary neoplasms (SPNs) may have an aggressive clinical course, but clinical predictors of this condition have not been thoroughly evaluated. We performed a retrospective study of 11 cases of SPN managed in our hospital between January 2007 and April 2015. Of these 11 cases, we encountered a single case with an aggressive clinical course. Histological, immunohistochemical, and clinical features were compared to identify predictors of poor prognosis. The 11 patients comprised four women and seven men with a median age of 41 years (range, 26-58 years). Clinical symptoms were nonspecific and the median tumor size was 4.6 cm (range, 1.4-18 cm). The patient with an aggressive clinical course developed multiple liver metastases within three months and died seven months after surgery. Pathological features of the tumor in this case included lymph node metastases, a diffuse growth pattern, extensive tumor necrosis, high mitotic rate, and immunohistochemistry. These features were not observed in patients who survived without recurrence at a median follow-up of 25 months (range, 6-82 months). Characteristic pathological features and a high proliferative index, as assessed by Ki-67 staining, may predict poor outcome in cases of SPN. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  13. Pathological Features in the LmnaDhe/+ Mutant Mouse Provide a Novel Model of Human Otitis Media and Laminopathies

    PubMed Central

    Zhang, Yan; Yu, Heping; Xu, Min; Han, Fengchan; Tian, Cong; Kim, Suejin; Fredman, Elisha; Zhang, Jin; Benedict-Alderfer, Cindy; Zheng, Qing Yin

    2013-01-01

    Genetic predisposition is recognized as an important pathogenetic factor in otitis media (OM) and associated diseases. Mutant Lmna mice heterozygous for the disheveled hair and ears allele (LmnaDhe/+) exhibit early-onset, profound hearing deficits and other pathological features mimicking human laminopathy associated with the LMNA mutation. We assessed the effects of the LmnaDhe/+ mutation on development of OM and pathological abnormalities characteristic of laminopathy. Malformation and abnormal positioning of the eustachian tube, accompanied by OM, were observed in all of the LmnaDhe/+ mice (100% penetrance) as early as postnatal day P12. Scanning electronic microscopy revealed ultrastructural damage to the cilia in middle ears that exhibited OM. Hearing assessment revealed significant hearing loss, paralleling that in human OM. Expression of NF-κB, TNF-α, and TGF-β, which correlated with inflammation and/or bony development, was up-regulated in the ears or in the peritoneal macrophages of LmnaDhe/+ mice. Rugous, disintegrative, and enlarged nuclear morphology of peritoneal macrophages and hyperphosphatemia were found in LmnaDhe/+ mutant mice. Taken together, these features resemble the pathology of human laminopathies, possibly revealing some profound pathology, beyond OM, associated with the mutation. The LmnaDhe/+ mutant mouse provides a novel model of human OM and laminopathy. PMID:22819531

  14. Soft-Tissue Sarcomas of the Abdomen and Pelvis: Radiologic-Pathologic Features, Part 1-Common Sarcomas: From the Radiologic Pathology Archives.

    PubMed

    Levy, Angela D; Manning, Maria A; Al-Refaie, Waddah B; Miettinen, Markku M

    2017-01-01

    Soft-tissue sarcomas are a diverse group of rare mesenchymal malignancies that can arise at any location in the body and affect all age groups. These sarcomas are most common in the extremities, trunk wall, retroperitoneum, and head and neck. In the adult population, soft-tissue sarcomas arising in the abdomen and pelvis are often large masses at the time of diagnosis because they are usually clinically silent or cause vague or mild symptoms until they invade or compress vital organs. In contrast, soft-tissue sarcomas arising from the abdominal wall come to clinical attention earlier in the course of disease because they cause a palpable mass, abdominal wall deformity, or pain that is more clinically apparent. The imaging features of abdominal and pelvic sarcomas and abdominal wall sarcomas can be nonspecific and overlap with more common pathologic conditions, making diagnosis difficult or, in some cases, delaying diagnosis. Liposarcoma (well-differentiated and dedifferentiated liposarcomas), leiomyosarcoma, and gastrointestinal stromal tumor (GIST) are the most common intra-abdominal primary sarcomas. Any soft-tissue sarcoma can arise in the abdominal wall. Knowledge of the classification and pathologic features of soft-tissue sarcomas, the anatomic locations where they occur, and their cross-sectional imaging features helps the radiologist establish the diagnosis or differential diagnosis so that patients with soft-tissue sarcomas can receive optimal treatment and management. In part 1 of this article, the most common soft-tissue sarcomas (liposarcoma, leiomyosarcoma, and GIST) are reviewed, with a discussion on anatomic locations, classification, clinical considerations, and differential diagnosis. Part 2 will focus on the remainder of the soft-tissue sarcomas occurring in the abdomen and pelvis.

  15. [MDCT features and anatomic-pathological basis of the diseases in central thoracic-abdominal junctional region].

    PubMed

    Ye, Yilan; Yang, Zhigang; Li, Hua; Deng, Wen; Li, Yuan; Guo, Yingkun

    2012-02-01

    This paper is to determine relationship between MDCT features and anatomic-pathology of the diseases in central thoracic-abdominal junctional region. 3 cadavers were cut transversely and another 3 vertically to observe the anatomy of thoracic-abdominal junctional zone. 93 patients with diseases in central thoracic-abdominal junctional zone were scanned with MDCT. The correlation between MDCT features of the diseases in central thoracic-abdominal junctional region and the anatomic-pathology of the diseases in this region was evaluated. On cadaver sections, central thoracic-abdominal junctional region was an area between anterior chest wall and dorsal spine in vertical direction. The region was separated into upper and lower sections by diaphragm. The upper section mainly contains heart and pericardium, while the lower contains broad ligament and left lobe of liver. The hiatus of diaphragm are vena caval foramen, esophageal foramen and aortic foramen in anterior-posterior turn. In the present study, 23 patients had portal hypertension, 18 had dissection of aorta, 8 got diseases in inferior vena cava, 9 had lymphoma, 12 got diseases in multiple vertebrae, 7 had lower thoracic esophageal carcinoma accompanied with metastasis in upper abdominal lymph nodes, 9 had carcinoma of abdominal esophagus and/or gastric cardia, 4 had esophageal hiatal hernia and 3 patients had neurogenic tumor in posterior mediastinum and/or superior spatium retroperitoneale. The MDCT features and distribution of the diseases in central thoracic-abdominal junctional region influence the anatomic-pathology characteristics in this region.

  16. Prediction of pathologic femoral fractures in patients with lung cancer using machine learning algorithms: Comparison of computed tomography-based radiological features with clinical features versus without clinical features.

    PubMed

    Oh, Eunsun; Seo, Sung Wook; Yoon, Young Cheol; Kim, Dong Wook; Kwon, Sunyoung; Yoon, Sungroh

    2017-01-01

    The purpose of this article is to compare the predictive power of two models trained with computed tomography (CT)-based radiological features and both CT-based radiological and clinical features for pathologic femoral fractures in patients with lung cancer using machine learning algorithms. Between January 2010 and December 2014, 315 lung cancer patients with metastasis to the femur were included. Among them, 84 patients who underwent CT scan and were followed up for more than 3 months were enrolled. We examined clinical and radiological risk factors affecting pathologic fracture through logistic regression. Predictive analysis was performed using five different supervised learning algorithms. The power of predictive model trained with CT-based radiological features was compared to those trained with both CT-based radiological and clinical features. In multivariate logistic regression, female sex (odds ratio = 0.25, p = 0.0126), osteolysis (odds ratio = 7.62, p = 0.0239), and absence of radiation therapy (odds ratio = 10.25, p = 0.0258) significantly increased the risk of pathologic fracture in proximal femur. The predictive model trained with both CT-based radiological and clinical features showed the highest area under the receiver operating characteristic curve (0.80 ± 0.14, p < 0.0001) through gradient boosting algorithm. We believe that machine learning algorithms may be useful in the prediction of pathologic femoral fracture, which are multifactorial problem.

  17. Asbestosis and other pulmonary fibrosis in asbestos-exposed workers: high-resolution CT features with pathological correlations.

    PubMed

    Arakawa, Hiroaki; Kishimoto, Takumi; Ashizawa, Kazuto; Kato, Katsuya; Okamoto, Kenzo; Honma, Koichi; Hayashi, Seiji; Akira, Masanori

    2016-05-01

    The purpose was to identify distinguishing CT features of pathologically diagnosed asbestosis, and correlate diagnostic confidence with asbestos body burden. Thirty-three workers (mean age at CT: 73 years) with clinical diagnoses of asbestosis, who were autopsied (n = 30) or underwent lobectomy (n = 3), were collected. Two radiologists independently scored high-resolution CT images for various CT findings and the likelihood of asbestosis was scored. Two pathologists reviewed the pathology specimens and scored the confidence of their diagnoses. Asbestos body count was correlated with CT and pathology scores. Pathologically, 15 cases were diagnosed as asbestosis and 18 cases with various lung fibroses other than asbestosis. On CT, only the score of the subpleural curvilinear lines was significantly higher in asbestosis (p = 0.03). Accuracy of CT diagnosis of asbestosis with a high confidence ranged from 0.73 to 0.79. Asbestos body count positively correlated with CT likelihood of asbestosis (r = 0.503, p = 0.003), and with the confidence level of pathological diagnosis (r = 0.637, p < 0.001). Subpleural curvilinear lines were the only clue for the diagnosis of asbestosis. However, this was complicated by other lung fibrosis, especially at low asbestos body burden. • Various patterns of pulmonary fibrosis occurred in asbestos-exposed workers. • The fibre burden in lungs paralleled confident CT diagnosis of asbestosis. • The fibre burden in lungs paralleled confident pathological diagnosis of asbestosis. • Subpleural curvilinear lines were an important CT finding favouring asbestosis.

  18. Computerized Macular Pathology Diagnosis in Spectral Domain Optical Coherence Tomography Scans Based on Multiscale Texture and Shape Features

    PubMed Central

    Liu, Yu-Ying; Chen, Mei; Wollstein, Gadi; Duker, Jay S.; Fujimoto, James G.; Schuman, Joel S.; Rehg, James M.

    2011-01-01

    Purpose. To develop an automated method to identify the normal macula and three macular pathologies (macular hole [MH], macular edema [ME], and age-related macular degeneration [AMD]) from the fovea-centered cross sections in three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) images. Methods. A sample of SD-OCT macular scans (macular cube 200 × 200 or 512 × 128 scan protocol; Cirrus HD-OCT; Carl Zeiss Meditec, Inc., Dublin, CA) was obtained from healthy subjects and subjects with MH, ME, and/or AMD (dataset for development: 326 scans from 136 subjects [193 eyes], and dataset for testing: 131 scans from 37 subjects [58 eyes]). A fovea-centered cross-sectional slice for each of the SD-OCT images was encoded using spatially distributed multiscale texture and shape features. Three ophthalmologists labeled each fovea-centered slice independently, and the majority opinion for each pathology was used as the ground truth. Machine learning algorithms were used to identify the discriminative features automatically. Two-class support vector machine classifiers were trained to identify the presence of normal macula and each of the three pathologies separately. The area under the receiver operating characteristic curve (AUC) was calculated to assess the performance. Results. The cross-validation AUC result on the development dataset was 0.976, 0.931, 0939, and 0.938, and the AUC result on the holdout testing set was 0.978, 0.969, 0.941, and 0.975, for identifying normal macula, MH, ME, and AMD, respectively. Conclusions. The proposed automated data-driven method successfully identified various macular pathologies (all AUC > 0.94). This method may effectively identify the discriminative features without relying on a potentially error-prone segmentation module. PMID:21911579

  19. Characterization of the Pathological and Biochemical Markers that Correlate to the Clinical Features of Autism

    DTIC Science & Technology

    2009-10-01

    mental retardation, seizures, cerebral palsy , and neuropsychiatric disor- ders (Barkovich et al., 2005; Guerrini and Marini, 2006; Sarnat and Flores...Dissociations of cerebral cortex, subcortical and cerebral white matter volumes in autistic boys. Brain 126:1182-1192. Hollander, E., E. Anagnostou, W...indicate that epilepsy-associated pathology includes patchy or laminar neuronal loss and gliosis in the cerebral cortex in one or both hemispheres

  20. Characterization of the Pathological and Biochemical Markers that Correlate to the Clinical Features of Autism

    DTIC Science & Technology

    2012-08-01

    and cerebellum (Wegiel et al 2012). Pathological effects of N-terminally truncated Aβ are not known but contribution of oxidative stress to Aβ...autism and autism associated with idic15. Aβ accumulation in neurons initiates oxidative stress resulting in lipids peroxidation. Accumulation of Aβ...and timetable. Material : We examined 72 subjects including: 32 brains of autistic people, 12 brains of individuals with autism associated with

  1. Predicting and replacing the pathological Gleason grade with automated gland ring morphometric features from immunofluorescent prostate cancer images.

    PubMed

    Khan, Faisal M; Scott, Richard; Donovan, Michael; Fernandez, Gerardo

    2017-04-01

    The Gleason grade is the most common architectural and morphological assessment of prostate cancer severity and prognosis. There have been numerous algorithms developed to approximate and duplicate the Gleason scoring system, mostly developed in standard H&E brightfield microscopy. Immunofluorescence (IF) image analysis of tissue pathology has recently been proven to be robust in developing prognostic assessments of disease, particularly in prostate cancer. We leverage a method of segmenting gland rings in IF images for predicting the pathological Gleason, both the clinical and the image specific grades, which may not necessarily be the same. We combine these measures with nuclear specific characteristics. In 324 images from 324 patients, our individual features correlate well univariately with the Gleason grades and in a multivariate setting have an accuracy of 85% in predicting the Gleason grade. Additionally, these features correlate strongly with clinical progression outcomes [concordance index (CI) of 0.89], significantly outperforming the clinical Gleason grades (CI of 0.78). Finally, in multivariate models for multiple prostate cancer progression endpoints, replacing the Gleason with these features results in equivalent or improved performances. This work presents the first assessment of morphological gland unit features from IF images for predicting the Gleason grade, and even replacing it in prostate cancer prognostics.

  2. Pathological and immunological features of canine necrotising meningoencephalitis and granulomatous meningoencephalitis.

    PubMed

    Uchida, Kazuyuki; Park, Eunsil; Tsuboi, Masaya; Chambers, James K; Nakayama, Hiroyuki

    2016-07-01

    Necrotising meningoencephalitis (NME) and granulomatous meningoencephalitis (GME) are idiopathic inflammatory diseases of the canine central nervous system (CNS). Typical NME occurs predominantly in small breeds of dogs, such as Pug, Maltese and Yorkshire terriers. Although there is no specific breed predisposition to GME, toy and terrier breeds appear to be overrepresented. Recent molecular investigations have identified genetic risk factors for NME in Pug, Maltese and other toy breed dogs; however, details of the pathogenesis of this disease remain to be clarified. NME is characterised pathologically by necrotic lesions with mononuclear cell infiltration in the meninges and perivascular spaces. On the basis of the distribution pattern of major necrotic foci, NME can be divided into cortex dominant and white matter dominant types; the latter is designated necrotising leucoencephalitis (NLE). Lesions in GME are characterised by the accumulation of lymphocytes and macrophages with epithelioid morphology, forming granulomas around blood vessels. Some common genetic factors and/or some additional triggers, such as infection or vaccination, may play a role in the pathogenesis of NME, NLE and GME; however, the host immune responses may define the pathological phenotypes. Different cytokine and chemokine responses are seen in NME, NLE and GME, whilst autoantibodies against astrocytes are detected predominantly in NME. This review focuses on the pathological and immunological characteristics of these canine idiopathic inflammatory CNS disorders. Copyright © 2016. Published by Elsevier Ltd.

  3. Motor neurons derived from ALS-related mouse iPS cells recapitulate pathological features of ALS.

    PubMed

    Park, Ju-Hwang; Park, Hang-Soo; Hong, Sunghoi; Kang, Seongman

    2016-12-09

    Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disease characterized by the loss of motor neurons in the spinal cord and brain. Mutations in Cu/Zn superoxide dismutase 1 (SOD1) are known to induce ALS. Although many research models have been developed, the exact pathological mechanism of ALS remains unknown. The recently developed induced pluripotent stem (iPS) cell technology is expected to illuminate the pathological mechanisms and new means of treatment for neurodegenerative diseases. To determine the pathological mechanism of ALS, we generated mouse iPS (miPS) cells from experimental ALS transgenic mice and control mice and characterized the cells using molecular biological methods. The generated miPS cells expressed many pluripotent genes and differentiated into three germ layers in vitro and in vivo. Motor neurons derived from ALS-related miPS cells recapitulated the pathological features of ALS. The ALS-model motor neurons showed SOD1 aggregates, as well as decreased cell survival rate and neurite length compared with wild-type motor neurons. Our study will be helpful in revealing the mechanism of motor neuronal cell death in ALS.

  4. Motor neurons derived from ALS-related mouse iPS cells recapitulate pathological features of ALS

    PubMed Central

    Park, Ju-Hwang; Park, Hang-Soo; Hong, Sunghoi; Kang, Seongman

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disease characterized by the loss of motor neurons in the spinal cord and brain. Mutations in Cu/Zn superoxide dismutase 1 (SOD1) are known to induce ALS. Although many research models have been developed, the exact pathological mechanism of ALS remains unknown. The recently developed induced pluripotent stem (iPS) cell technology is expected to illuminate the pathological mechanisms and new means of treatment for neurodegenerative diseases. To determine the pathological mechanism of ALS, we generated mouse iPS (miPS) cells from experimental ALS transgenic mice and control mice and characterized the cells using molecular biological methods. The generated miPS cells expressed many pluripotent genes and differentiated into three germ layers in vitro and in vivo. Motor neurons derived from ALS-related miPS cells recapitulated the pathological features of ALS. The ALS-model motor neurons showed SOD1 aggregates, as well as decreased cell survival rate and neurite length compared with wild-type motor neurons. Our study will be helpful in revealing the mechanism of motor neuronal cell death in ALS. PMID:27932790

  5. Mitosis detection in breast cancer pathology images by combining handcrafted and convolutional neural network features.

    PubMed

    Wang, Haibo; Cruz-Roa, Angel; Basavanhally, Ajay; Gilmore, Hannah; Shih, Natalie; Feldman, Mike; Tomaszewski, John; Gonzalez, Fabio; Madabhushi, Anant

    2014-10-01

    Breast cancer (BCa) grading plays an important role in predicting disease aggressiveness and patient outcome. A key component of BCa grade is the mitotic count, which involves quantifying the number of cells in the process of dividing (i.e., undergoing mitosis) at a specific point in time. Currently, mitosis counting is done manually by a pathologist looking at multiple high power fields (HPFs) on a glass slide under a microscope, an extremely laborious and time consuming process. The development of computerized systems for automated detection of mitotic nuclei, while highly desirable, is confounded by the highly variable shape and appearance of mitoses. Existing methods use either handcrafted features that capture certain morphological, statistical, or textural attributes of mitoses or features learned with convolutional neural networks (CNN). Although handcrafted features are inspired by the domain and the particular application, the data-driven CNN models tend to be domain agnostic and attempt to learn additional feature bases that cannot be represented through any of the handcrafted features. On the other hand, CNN is computationally more complex and needs a large number of labeled training instances. Since handcrafted features attempt to model domain pertinent attributes and CNN approaches are largely supervised feature generation methods, there is an appeal in attempting to combine these two distinct classes of feature generation strategies to create an integrated set of attributes that can potentially outperform either class of feature extraction strategies individually. We present a cascaded approach for mitosis detection that intelligently combines a CNN model and handcrafted features (morphology, color, and texture features). By employing a light CNN model, the proposed approach is far less demanding computationally, and the cascaded strategy of combining handcrafted features and CNN-derived features enables the possibility of maximizing the performance

  6. Mitosis detection in breast cancer pathology images by combining handcrafted and convolutional neural network features

    PubMed Central

    Wang, Haibo; Cruz-Roa, Angel; Basavanhally, Ajay; Gilmore, Hannah; Shih, Natalie; Feldman, Mike; Tomaszewski, John; Gonzalez, Fabio; Madabhushi, Anant

    2014-01-01

    Abstract. Breast cancer (BCa) grading plays an important role in predicting disease aggressiveness and patient outcome. A key component of BCa grade is the mitotic count, which involves quantifying the number of cells in the process of dividing (i.e., undergoing mitosis) at a specific point in time. Currently, mitosis counting is done manually by a pathologist looking at multiple high power fields (HPFs) on a glass slide under a microscope, an extremely laborious and time consuming process. The development of computerized systems for automated detection of mitotic nuclei, while highly desirable, is confounded by the highly variable shape and appearance of mitoses. Existing methods use either handcrafted features that capture certain morphological, statistical, or textural attributes of mitoses or features learned with convolutional neural networks (CNN). Although handcrafted features are inspired by the domain and the particular application, the data-driven CNN models tend to be domain agnostic and attempt to learn additional feature bases that cannot be represented through any of the handcrafted features. On the other hand, CNN is computationally more complex and needs a large number of labeled training instances. Since handcrafted features attempt to model domain pertinent attributes and CNN approaches are largely supervised feature generation methods, there is an appeal in attempting to combine these two distinct classes of feature generation strategies to create an integrated set of attributes that can potentially outperform either class of feature extraction strategies individually. We present a cascaded approach for mitosis detection that intelligently combines a CNN model and handcrafted features (morphology, color, and texture features). By employing a light CNN model, the proposed approach is far less demanding computationally, and the cascaded strategy of combining handcrafted features and CNN-derived features enables the possibility of maximizing the

  7. [Relationship between pathological features and 64-MSCT findings of pulmonary nodules in patients with coal workers' pneumoconiosis].

    PubMed

    Wang, Xu; Li, Baoping; Zeng, Qingyu; Zhou, Yunzhi; Yin, Xiaoming; Deng, Maosong; Chen, Budong; Zhang, Yansong; Li, Yi; Chang, Xin; Liu, Jianxin

    2014-09-01

    To analyze the relationship between the pathological features and 64-multislice spiral computed tomography (64-MSCT) findings of pulmonary nodules in autopsies from patients with coal workers' pneumoconiosis (CWP), to investigate the optimal imaging method for the distribution of pulmonary nodules, and to provide data for the establishment of CT diagnostic criteria for CWP. Cadaveric lung specimens were collected from 7 CWP patients. All of them were men, aged 42∼77 years (mean, 60.00±13.00 years), and their dust exposure time was 5∼30 years (mean, 15.4±8.01 years). The cadaveric lung specimens were treated by aeration, sectioning, and immobilization and were then examined by coronary 64-MSCT. The primitive images were reconstructed into the maximumintensity projection (MIP) images (slice thickness: 3 mm, 5 mm, and 8 mm). The sensitivities of imaging methods with different slice thickness were evaluated based on the pathology and anatomy of local pulmonary nodules, and the correlation between pathological results and radiological findings was analyzed. There were significant differences between the stages determined by pathological examination and high-kV chest radiography (before death) (χ(2) = 4.667, P < 0.05; kappa value = 0.167, P < 0.05). A total of 271 nodules were found in all pathological sections, including peribronchovascular nodules (27, 9.9%), centrilobular nodules (67, 24.6%), interlobular nodules (65, 24.3%), nodules within 5 mm from the pleura (45, 16.5%), pleural plaque-like nodules on the lateral chest wall (45, 16.5%), and nodules on the interlobar pleura (22, 8.1%). The likelihood ratio was the highest (0.981) between 5-mm MIP images and pathological results according to the chi-square test. The stage of pulmonary nodules determined by pathological examination is significantly different from that determined by high-kV chest radiography. The 5-mm MIP images of 64-MSCT provide a good reflection of the local pathology and anatomy of pulmonary

  8. CT features and pathologic characteristics of IgG4-related systemic disease of submandibular gland.

    PubMed

    Wang, Zhiwei; Feng, Ruie; Chen, Yu; Duan, Miao; Wang, Man; Jin, Zhengyu; Rumboldt, Zoran; Zhang, Zhuhua

    2015-01-01

    The submandibular gland is one of the most frequently affected salivary gland in IgG4-related systemic disease, usually demonstrate homogeneous attenuation on CT imaging as reported, but without much pathological comparison of many cases. This article is to investigate and analyze the typical CT findings and pathologic characteristics of IgG4-related systemic disease (IgG4-RSD) of submandibular gland. A retrospective analysis of the preoperative CT findings in patients with IgG4-RSD of submandibular glands who underwent surgical resection between January 2010 and February 2014 was performed. Twenty patients (16 women) were identified, with a mean age of 58.1±10.2 years. All patients presented with painless submandibular gland swelling. Diffuse gland enlargement, with clear margins and homogeneous density, was found on non-enhanced CT scans in all cases. There were no calcifications or stones within the involved glands. Based on contrast-enhanced CT appearance the patients could be divided into two groups: 11 cases showed homogeneous gland enhancement; and multiple hyperenhancing foci, with a crazy-paving pattern, were detected in 9 cases, which were in consistent with the pathologic findings. The maximum submandibular gland diameter on transverse images was significantly larger (P=0.008) in patients with crazy-paving appearance (32±4 mm) compared to patients with homogeneous enhancement (28±3 mm). It is concluded that the submandibular glands with IgG4-RSD can be characterized by either homogenous appearance or crazy-paving pattern on contrast-enhanced CT imaging.

  9. Clinical and Pathological Features of Childhood-Onset Nemaline Myopathy: A Report of Four Cases

    PubMed Central

    Jiang, Chao; Wang, Jianping; Lu, Haidong

    2012-01-01

    We examined whether immunological abnormalities can be found in the specimens of four childhood-onset nemaline myopathy (NM) patients without autoimmune diseases. Pathological examination revealed that nemaline rods were found in all specimens. The immunohistochemical results showed that CD4 positive cells and some other cells were gathered among the necrotic muscle fibers. We conclude that immunological abnormalities are present in the specimens of certain childhood-onset NM patients without autoimmune diseases. Further evaluation of the immunological changes is warranted in childhood-onset NM patients. PMID:22899938

  10. Length-adaptive graph search for automatic segmentation of pathological features in optical coherence tomography images

    NASA Astrophysics Data System (ADS)

    Keller, Brenton; Cunefare, David; Grewal, Dilraj S.; Mahmoud, Tamer H.; Izatt, Joseph A.; Farsiu, Sina

    2016-07-01

    We introduce a metric in graph search and demonstrate its application for segmenting retinal optical coherence tomography (OCT) images of macular pathology. Our proposed "adjusted mean arc length" (AMAL) metric is an adaptation of the lowest mean arc length search technique for automated OCT segmentation. We compare this method to Dijkstra's shortest path algorithm, which we utilized previously in our popular graph theory and dynamic programming segmentation technique. As an illustrative example, we show that AMAL-based length-adaptive segmentation outperforms the shortest path in delineating the retina/vitreous boundary of patients with full-thickness macular holes when compared with expert manual grading.

  11. Intra- and Inter-database Study for Arabic, English, and German Databases: Do Conventional Speech Features Detect Voice Pathology?

    PubMed

    Ali, Zulfiqar; Alsulaiman, Mansour; Muhammad, Ghulam; Elamvazuthi, Irraivan; Al-Nasheri, Ahmed; Mesallam, Tamer A; Farahat, Mohamed; Malki, Khalid H

    2016-10-10

    A large population around the world has voice complications. Various approaches for subjective and objective evaluations have been suggested in the literature. The subjective approach strongly depends on the experience and area of expertise of a clinician, and human error cannot be neglected. On the other hand, the objective or automatic approach is noninvasive. Automatic developed systems can provide complementary information that may be helpful for a clinician in the early screening of a voice disorder. At the same time, automatic systems can be deployed in remote areas where a general practitioner can use them and may refer the patient to a specialist to avoid complications that may be life threatening. Many automatic systems for disorder detection have been developed by applying different types of conventional speech features such as the linear prediction coefficients, linear prediction cepstral coefficients, and Mel-frequency cepstral coefficients (MFCCs). This study aims to ascertain whether conventional speech features detect voice pathology reliably, and whether they can be correlated with voice quality. To investigate this, an automatic detection system based on MFCC was developed, and three different voice disorder databases were used in this study. The experimental results suggest that the accuracy of the MFCC-based system varies from database to database. The detection rate for the intra-database ranges from 72% to 95%, and that for the inter-database is from 47% to 82%. The results conclude that conventional speech features are not correlated with voice, and hence are not reliable in pathology detection.

  12. [Pathological features and origin of primary pineal mixed germ cell tumors].

    PubMed

    XIAO, Gang; FANG, Lu-xiong; QIU, Bing-hui; QI, Song-tao

    2011-03-01

    To investigate the origin of mixed germ cell tumors in the pineal region based on the image data, surgical findings and pathological examination of the tumor. The preoperative CT and magnetic resonance imaging (MRI) findings and tumor specimens were retrospectively analyzed in 15 cases of pineal mixed germ cell tumors confirmed by postoperative histological examination between January 2000 and September 2010. Radiographic examination of the tumor revealed calcification in 12 cases, cystic changes in 10 cases, and the presence of lipid in 5 cases. On the anteroposterior images, the tumors appeared round or elliptic with smooth edge in 6 cases, and showed irregular shape with multiple processes on the edge in 9 cases. Surgical exploration found all the tumors located in the the suprapineal recess enclosed by the arachnoidal envelope of the Galen vein. Pathologically, 13 specimens contained germinoma component, 9 contained teratoma component, 4 had embryonic carcinoma component, 3 had choriocarcinoma component, 7 showed yolk sac tumor component, and 3 showed rhabdomyoma component. Germinoma components were found on the tumor margin in 7 specimens, and intermingled germinoma and other components were found in 10 specimens. Pineal mixed germ cell tumor originates from the residue germ cells around the pineal gland, and most likely evolves from single primordial germ cells.

  13. Pathological features in marine birds affected by the prestige's oil spill in the north of Spain.

    PubMed

    Balseiro, A; Espí, A; Márquez, I; Pérez, V; Ferreras, M C; Marín, J F García; Prieto, J M

    2005-04-01

    A total of 2,465 seabirds, mainly common murres (Uria aalge), razorbills (Alca torda), and puffins (Fratercula arctica) that beached in the northwestern part of Spain after the "Prestige" oil spill on 19 November 2002 were examined by pathological methods. Birds were divided into three groups: dead birds with the body covered (group 1) or uncovered (group 2) by oil and birds recovered alive but which died after being treated at a rescue center (group 3). The main gross lesions were severe dehydration and emaciation. Microscopically, hemosiderin deposits, related to cachexia and/or hemolytic anemia, were observed in those birds harboring oil in the intestine. Severe aspergillosis and ulcers in the ventriculus were found only in group 3 birds, probably because of stress associated with attempted rehabilitation at the rescue center. The mild character of the pathological changes suggests that petroleum oil toxicosis causes multiple sublethal changes that have an effect on the ability of the birds to survive at sea, especially weak and young, inexperienced animals. Dehydration and exhaustion seem to be the most likely cause of death.

  14. [Relationship between vasculogenic mimicry and clinic pathological features in laryngeal carcinoma].

    PubMed

    Feng, Yan; Wang, Binquan; Liang, Gang; Wen, Shuxin; Sun, Ruifang

    2015-12-01

    To investigate the presence of vasculogenic mimicry in laryngeal squamous cell carcino- ma and explore its clinical significance. The presence of vasculogenic mimicry and expression of endotheli- um-dependent vessel in 138 laryngeal squamous cell carcinomas cases were detected by the immunohistochemistry and tissue microarray. Metlab software was used to evaluate the relationship among vasculogenic mimicry, mi- crovessel density and clinic pathological parameters in laryngeal carcinoma. We found vasculogenic mimicry in 32 (26.23%) of 122 laryngeal carcinoma samples. The mean of microvessel density is 12.61 per high-power field. The vasculogenic mimicry and expression of endothelium-dependent vessel were not significantly related to patient age or gender, tumor location, pathology grade, T stage or N stage (P > 0.05). However, the vasculo- genic mimicry and the mean of microvessel density were a little higher in patients older than 60, with poorly differ- entiated and patients with N₁₋₃ stage. Vasculogenic mimicry was positively correlatedwith microvessel density (r = 0.1927, P < 0.05). Vasculogenic mimicry can occur in laryngeal carcinoma. Moreover, vasculogenic mimicry may be associated with recurrence and metastasis in laryngeal carcinoma.

  15. Clinical and pathologic features of West Nile virus infection in native North American owls (Family strigidae).

    PubMed

    Fitzgerald, S D; Patterson, J S; Kiupel, M; Simmons, H A; Grimes, S D; Sarver, C F; Fulton, R M; Steficek, B A; Cooley, T M; Massey, J P; Sikarskie, J G

    2003-01-01

    Since the initial report of West Nile virus in the northeastern United States in 1999, the virus has spread rapidly westward and southward across the country. In the summer of 2002, several midwestern states reported increased cases of neurologic disease and mortality associated with West Nile virus infection in various native North American owl species. This report summarizes the clinical and pathologic findings for 13 captive and free-ranging owls. Affected species were all in the family Strigidae and included seven snowy owls (Nyctea scandiaca), four great-horned owls (Bubo virginianus), a barred owl (Strix varia), and a short-eared owl (Asio flammeus). Neurologic signs identified included head tilt, uncoordinated flight, paralysis, tremors, and seizures. Owls that died were screened for flaviviral proteins by immunohistochemical staining of formalin-fixed tissues, followed by specific polymerase chain reaction assay to confirm West Nile virus with fresh tissues when available. Microscopic lesions were widespread, involving brain, heart, liver, kidney, and spleen, and were typically nonsuppurative with infiltration by predominantly lymphocytes and plasma cells. Lesions in owls were much more severe than those previously reported in corvids such as crows, which are considered highly susceptible to infection and are routinely used as sentinel species for monitoring for the presence and spread of West Nile virus. This report is the first detailed description of the pathology of West Nile virus infection in Strigiformes and indicates that this bird family is susceptible to natural infection with West Nile virus.

  16. Comparative pathologic features and development of Sphaeridiotrema globulus (Trematoda) infections in the mute swan and domestic chicken and chicken chorioallantois.

    PubMed

    Huffman, J E; Fried, B; Roscoe, D E; Cali, A

    1984-02-01

    The natural infection of Sphaeridiotrema globulus in the mute swan and the experimental infection in the chicken resulted in an ulcerative hemorrhagic enteritis. Swans and chickens died from the resultant blood loss. Culturing of the parasite on the chorioallantoic membrane of the chicken egg resulted in hemorrhage and a cellular response of the chorioallantois to the trematode. Experimental infections in the domestic chicken and chicken embryo can be of use for the study of ulcerative hemorrhagic enteritis produced by the trematode, pathologic features, identification of the metacercaria to the adult, and developmental aspects of the parasite.

  17. Graph theory for feature extraction and classification: a migraine pathology case study.

    PubMed

    Jorge-Hernandez, Fernando; Garcia Chimeno, Yolanda; Garcia-Zapirain, Begonya; Cabrera Zubizarreta, Alberto; Gomez Beldarrain, Maria Angeles; Fernandez-Ruanova, Begonya

    2014-01-01

    Graph theory is also widely used as a representational form and characterization of brain connectivity network, as is machine learning for classifying groups depending on the features extracted from images. Many of these studies use different techniques, such as preprocessing, correlations, features or algorithms. This paper proposes an automatic tool to perform a standard process using images of the Magnetic Resonance Imaging (MRI) machine. The process includes pre-processing, building the graph per subject with different correlations, atlas, relevant feature extraction according to the literature, and finally providing a set of machine learning algorithms which can produce analyzable results for physicians or specialists. In order to verify the process, a set of images from prescription drug abusers and patients with migraine have been used. In this way, the proper functioning of the tool has been proved, providing results of 87% and 92% of success depending on the classifier used.

  18. Hematological and pathological features of massive hepatic necrosis in two radiated tortoises (Astrochelys radiata)

    PubMed Central

    KIDO, Nobuhide; ITAGAKI, Iori; KIRYU, Daisuke; OMIYA, Tomoko; ONO, Kaori

    2016-01-01

    Two radiated tortoises (Astrochelys radiata) exhibited anorexia and hypokinesia. In both cases, hematological and serum biochemical examinations revealed high alkaline phosphatase levels, moderately high aspartate aminotransferase levels and white blood cell counts approximately within the normal range. Despite being treated, the tortoises died 9 and 43 days after the first clinical examination. Gross pathological examinations revealed that the livers of both animals were extremely swollen and contained pale yellow necrotic tissue. Histopathological assessment revealed that the livers contained a massive area of hepatic necrosis surrounded by migration of macrophages and multinucleated giant cells. In one of the cases, severe fibrosis was observed. The present study provides reference information for similar cases in the future. PMID:27746414

  19. The Imaging and Pathological Features of Metastatic Leiomyosarcoma in the Gallbladder

    PubMed Central

    Guo, Yi; Chen, Eleanor; Davidson, Darin J.; Pillarisetty, Venu G.; Jones, Robin L.

    2016-01-01

    Uterine leiomyosarcoma is a rare and aggressive malignancy with poor overall prognosis. There have been few reports of metastatic leiomyosarcoma in the gallbladder. We report a case of a 41-year-old female who underwent total abdominal hysterectomy due to presumed uterine fibroids. The postoperative pathology revealed high-grade pleomorphic leiomyosarcoma, with involvement of the uterine serosal surface. She subsequently underwent exploratory laparotomy, followed by pelvic radiation and chemotherapy. Since initial management she has developed metastatic disease and has been under treatment and surveillance for 11 years. She has undergone multiple surgical procedures and numerous lines of systemic therapy for metastatic leiomyosarcoma, including cholecystectomy for a metastatic lesion in the gallbladder. There have been no previous reports of metastatic leiomyosarcoma in the gallbladder. Despite extensive metastatic disease this patient has had prolonged survival with multi-modality management. PMID:28191293

  20. Evaluation of the Relationships Between Computed Tomography Features, Pathological Findings, and Prognostic Risk Assessment in Gastrointestinal Stromal Tumors.

    PubMed

    Iannicelli, Elsa; Carbonetti, Francesco; Federici, Giulia Francesca; Martini, Isabella; Caterino, Salvatore; Pilozzi, Emanuela; Panzuto, Francesco; Briani, Chiara; David, Vincenzo

    The aim of this study was to correlate computed tomography (CT) findings with pathology in gastrointestinal stromal tumors (GISTs). A retrospective evaluation of CT images of 44 patients with GISTs was performed. Computed tomography findings analyzed were location, size, margins, degree and pattern of contrast enhancement, angiogenesis, necrosis, signs of invasion, peritoneal effusion, peritoneal implants, surface ulceration, and calcifications.Associations between CT features and mitotic rate, Miettinen classes of risk, lesions size, and among CT features were investigated. χ Test and Fisher test were performed. Mitotic rate was associated with margins (P = 0.016) and with adjacent organ invasion (P = 0.043). Pattern of contrast enhancement (P = 0.002), angiogenesis (P = 0.006), necrosis (P = 0.006), invasion of adjacent organs (P = 0.011), and margins (P = 0.006) were associated with classes of risk. Several associations (P < 0.05) between lesion size and CT features and among all the investigated CT features were found. Computed tomography features could reflect GIST biology being associated with the mitotic rate and with classes of risk.

  1. Clinical and Anatomical Features as well as Pathological Conditions of Surgically Treated Adult Patients with Occipitalization of the Atlas

    PubMed Central

    Shimizu, Takachika; Fueki, Keisuke; Ino, Masatake; Toda, Naofumi; Tanouchi, Tetsu; Manabe, Nodoka

    2016-01-01

    Background This paper intends to clarify clinical and anatomical features as well as pathological conditions of surgically treated adult patients with occipitalization of the atlas. Methods The authors reviewed 12 consecutive adult patients with occipitalization of the atlas who underwent surgery for myleopathy in our hospital. Mainly using preoperative computed tomography and three-dimensional computed tomography angiography, we investigated their anomalies of the osseous structures and vertebral artery at the cervical spine including the craniovertebral junction (CVJ). We also developed a new classification system for occipitalization of the atlas. Results Atlantoaxial subluxation (AAS) was detected in 9 patients (75%). The condition of AAS was irreducible in 7 patients. Among these 7 patients, deformity at the lateral atlantoaxial joints was detected in 2 patients. C2-3 fusion was detected in 6 patients (67%) among 9 patients with AAS. Anomalies of the VA were detected in 11 patients (92%). Occipitalization of the atlas was classified into three types according to their pathological conditions. In type 1 (2 patients) the medial atlantoaxial joint is semi-dislocated and the lateral atlantoaxial joints are severely deformed. Type 2 (7 patients) exhibits AAS but the lateral atlantoaxial joints are not deformed. Type 3 (3 patients) is not associated with AAS and therefore does not exhibit osseous stenosis at the CVJ. In type 3 the myelopathy was caused by another coexisting condition. Conclusions Occipitalization of the atlas is classified into three types. The main pathological condition in both types 1 and 2 is AAS. Reduction of AAS is essential in both; however, reduction of AAS in type 1 is more technically demanding than in type 2. The pathological conditions of type 3 are completely different from those of the others, so an accurate diagnosis must be made. The new classification system is a useful guide for surgeons when planning surgical strategies. PMID

  2. Congenital hereditary corneal oedema of Maumenee: its clinical features, management, and pathology.

    PubMed Central

    Kirkness, C M; McCartney, A; Rice, N S; Garner, A; Steele, A D

    1987-01-01

    The clinical and histological features of congenital hereditary corneal oedema in 23 patients are presented. The series includes cases of both recessive and dominant inheritance. Although the condition is present at birth or in early childhood, visual development appears to be little impaired, if at all. Penetrating keratoplasty carries a relatively good surgical prognosis and can produce a substantial visual gain even when carried out late in life. Images PMID:3548808

  3. Autoscope: automated otoscopy image analysis to diagnose ear pathology and use of clinically motivated eardrum features

    NASA Astrophysics Data System (ADS)

    Senaras, Caglar; Moberly, Aaron C.; Teknos, Theodoros; Essig, Garth; Elmaraghy, Charles; Taj-Schaal, Nazhat; Yu, Lianbo; Gurcan, Metin

    2017-03-01

    In this study, we propose an automated otoscopy image analysis system called Autoscope. To the best of our knowledge, Autoscope is the first system designed to detect a wide range of eardrum abnormalities by using high-resolution otoscope images and report the condition of the eardrum as "normal" or "abnormal." In order to achieve this goal, first, we developed a preprocessing step to reduce camera-specific problems, detect the region of interest in the image, and prepare the image for further analysis. Subsequently, we designed a new set of clinically motivated eardrum features (CMEF). Furthermore, we evaluated the potential of the visual MPEG-7 descriptors for the task of tympanic membrane image classification. Then, we fused the information extracted from the CMEF and state-of-the-art computer vision features (CVF), which included MPEG-7 descriptors and two additional features together, using a state of the art classifier. In our experiments, 247 tympanic membrane images with 14 different types of abnormality were used, and Autoscope was able to classify the given tympanic membrane images as normal or abnormal with 84.6% accuracy.

  4. Pathologic features of metastatic lymph nodes identified from prophylactic central neck dissection in patients with papillary thyroid carcinoma.

    PubMed

    Lee, Hyoung Shin; Park, Chanwoo; Kim, Sung Won; Noh, Woong Jae; Lim, Soo Jin; Chun, Bong Kwon; Kim, Beom Su; Hong, Jong Chul; Lee, Kang Dae

    2016-10-01

    The importance of pathologic features of metastatic lymph nodes (LNs), such as size, number, and extranodal extension, has been recently emphasized in patients with papillary thyroid carcinoma (PTC). We evaluated the characteristics of metastatic LNs identified after prophylactic central neck dissection (CND) in patients with PTC. We performed a retrospective review of 1,046 patients who underwent unilateral or bilateral thyroidectomy with ipsilateral prophylactic CND. We reviewed the characteristics of the metastatic LNs and analyzed their correlation to the clinicopathologic characteristics of the primary tumor. Cervical LN metastasis after prophylactic CND was identified in 280 out of 1046 patients (26.8 %). The size of metastatic foci (≥2 mm) was independently correlated with primary tumor size (≥1 cm) (p = 0.016, OR = 1.88). Primary tumor size (≥1 cm) was also correlated to the number of metastatic LNs (≥5) (p = 0.004, OR = 3.14) and extranodal extension (p = 0.021, OR = 2.41) in univariate analysis. The size of the primary tumor affects pathologic features of subclinical LN metastasis in patients with PTC. Patients with primary tumors ≥1 cm have an increased risk of larger LN metastases (≥2 mm), an increased number of LN metastases (≥5), and a higher incidence of ENE, which should be considered in decision for prophylactic CND.

  5. Verrucous lesions of the oral cavity treated with surgery: Analysis of clinico-pathologic features and outcome

    PubMed Central

    Sadasivan, Anjana; Thankappan, Krishnakumar; Rajapurkar, Mayuri; Shetty, Sharankumar; Sreehari, Sreekala; Iyer, Subramania

    2012-01-01

    Objective: Verrucous lesions of the oral cavity can be of varied histopathology. The present study evaluates the clinico-pathological features of verrucous lesions of the oral cavity and analyzes the treatment outcomes. Materials and Methods: This is a retrospective study of 15 consecutive patients who presented with verrucous lesions of the oral cavity, during the 5-year period from January 2006 to December 2010. Demographic, clinico-pathological features, treatment details, and outcomes were analyzed. Results: Fifteen patients with verrucous lesions of the oral cavity were treated with surgery as the primary modality. The mean age was 62.8 years (range 35–85 years). Wide excision of the primary lesion with adequate mucosal and soft-tissue margins was carried out. Free-flap reconstruction was done in eight patients. All patients remain loco-regionally controlled with good functional speech and swallowing outcome. Conclusions: Verrucous lesions of the oral cavity are a distinct clinical entity with varied histopathology. A surgical excision with wide margins and appropriate reconstruction is necessary to optimize the disease and functional outcome. PMID:22557899

  6. Verrucous lesions of the oral cavity treated with surgery: Analysis of clinico-pathologic features and outcome.

    PubMed

    Sadasivan, Anjana; Thankappan, Krishnakumar; Rajapurkar, Mayuri; Shetty, Sharankumar; Sreehari, Sreekala; Iyer, Subramania

    2012-01-01

    Verrucous lesions of the oral cavity can be of varied histopathology. The present study evaluates the clinico-pathological features of verrucous lesions of the oral cavity and analyzes the treatment outcomes. This is a retrospective study of 15 consecutive patients who presented with verrucous lesions of the oral cavity, during the 5-year period from January 2006 to December 2010. Demographic, clinico-pathological features, treatment details, and outcomes were analyzed. Fifteen patients with verrucous lesions of the oral cavity were treated with surgery as the primary modality. The mean age was 62.8 years (range 35-85 years). Wide excision of the primary lesion with adequate mucosal and soft-tissue margins was carried out. Free-flap reconstruction was done in eight patients. All patients remain loco-regionally controlled with good functional speech and swallowing outcome. Verrucous lesions of the oral cavity are a distinct clinical entity with varied histopathology. A surgical excision with wide margins and appropriate reconstruction is necessary to optimize the disease and functional outcome.

  7. Long-term pathological and immunohistochemical features in the liver after intraoperative whole-liver irradiation in rats.

    PubMed

    Imaeda, Masumi; Ishikawa, Hitoshi; Yoshida, Yukari; Takahashi, Takeo; Ohkubo, Yu; Musha, Atsushi; Komachi, Mayumi; Nakazato, Yoichi; Nakano, Takashi

    2014-07-01

    Radiation therapy (RT) has become particularly important recently for treatment of liver tumors, but there are few experimental investigations pertaining to radiation-induced liver injuries over long-term follow-up periods. Thus, the present study examined pathological liver features over a 10-month period using an intraoperative whole-liver irradiation model. Liver function tests were performed in blood samples, whereas cell death, cell proliferation, and fibrotic changes were evaluated pathologically in liver tissues, which were collected from irradiated rats 24 h, 1, 2, 4 and 40 weeks following administration of single irradiation doses of 0 (control), 15 or 30 Gy. The impaired liver function, increased hepatocyte number, and decreased apoptotic cell proportion observed in the 15 Gy group, but not the 30 Gy group, returned to control group levels after 40 weeks; however, the Ki-67 indexes in the 15 Gy group were still higher than those in the control group after 40 weeks. Azan staining showed a fibrotic pattern in the irradiated liver in the 30 Gy group only, but the expression levels of alpha smooth muscle actin (α-SMA) and transforming growth factor-beta 1 (TGF-β1) in both the 15 and 30 Gy groups were significantly higher than those in the control group (P < 0.05). There were differences in the pathological features of the irradiated livers between the 15 Gy and 30 Gy groups, but TGF-β1 and α-SMA expression patterns supported the gradual progression of radiation-induced liver fibrosis in both groups. These findings will be useful in the future development of protective drugs for radiation-induced liver injury.

  8. Leukoencephalopathy with cerebral calcifications and cysts: clinical and pathological features in two adults.

    PubMed

    Liu, Xuejun; Zheng, Xueping; Sui, Qinglan; Xu, Wenjian; Zee, Chi-Shing

    2016-03-01

    Two adult patients diagnosed with Leukoencephalopathy with cerebral calcifications and cysts (LCC) were presented. Both patients had a long-term (8-10 years) following-up. Radiological findings of both patients revealed the characteristic signs of LCC: cerebral white matter abnormalities, calcifications, and cysts. In case 1, the initial CT scan showed a low-density area in the right frontal lobe and it had developed into a large cystic lesion after 8 years. Histopathological determination revealed that the cyst wall was associated with hemorrhage, angiomatous formation, and some Rosenthal fibers. In case 2, a major cystic lesion was located at the left parietal lobe which was resected and an old hematoma was found inside the cyst. Nine years later, the follow-up neuroimaging of case 2 showed a remarkable improvement of white matter abnormalities and cystic lesions. Hemorrhagic fluid was observed inside the cysts. Additionally, follow-up CT and MR scans showed a rapid enlargement of cystic lesions accompanied with hemorrhagic fluid levels after a year. Then, a major cyst was surgically removed to relieve pressure symptoms. Pathology of the resected cyst exhibited an organized hemorrhage inside the cyst and a large amount of hemosiderin surrounding the cyst wall. In conclusion, our two cases demonstrated that angiomatous changes subsequent with hemorrhage may be the major mechanism of cyst formation and development.

  9. Cigarette smoking and drinking water source: correlation with clinical features and pathology of superficial bladder carcinoma.

    PubMed

    Serretta, Vincenzo; Altieri, Vincenzo; Morgia, Giuseppe; Allegro, Rosalinda; Ruggirello, Antonina; Di Lallo, Alessandra; Carrieri, Giuseppe; Melloni, Darvinio

    2009-01-01

    Water source and cigarette smoking are related to clinical characteristics and pathology of superficial transitional cell carcinoma of the bladder. Tumor number, dimension, G-grade, T-stage, recurrences, cigarette smoking and water supply were recorded in patients harboring Ta-T1 G1-3 transitional cell carcinoma of the bladder. Of 577 patients, 61% had multiple and 36% recurrent tumors. Two hundred and forty-one patients (42%) were current smokers and 188 (33%) were former smokers. Bottled water was the only drinkable source for 249 (45%) patients, municipal water supply for 177 (32%), artesian wells for 38 (7%), spring water for 7 (1%) and mixed source for 89 (16%). By adopting a cut-off of 30 years of smoking, patients affected by recurrent tumors varied from 22 to 43% (p = 0.0001). T1 tumors were more frequent in patients drinking nonbottled water (p = 0.03). Nonbottled supply was more frequent in never smokers (p = 0.015) and could represent a weak risk factor not detectable in smokers. Cigarette smoking correlates with the number of recurrences. T1 tumors were statistically more frequent in patients taking nonbottled drinking water. Chlorinated water supply was more frequent among patients who did not present cigarette smoking as a risk factor. Copyright 2009 S. Karger AG, Basel.

  10. Polyp detection rate and pathological features in patients undergoing a comprehensive colonoscopy screening

    PubMed Central

    Asadzadeh Aghdaei, Hamid; Nazemalhosseini Mojarad, Ehsan; Ashtari, Sara; Pourhoseingholi, Mohmad Amin; Chaleshi, Vahid; Anaraki, Fakhrosadat; Haghazali, Mehrdad; Zali, Mohammad Reza

    2017-01-01

    AIM To identify the prevalence, and clinical and pathologic characteristic of colonic polyps among Iranian patients undergoing a comprehensive colonoscopy, and determine the polyp detection rate (PDR) and adenoma detection rate (ADR). METHODS In this cross-sectional study, demographics and epidemiologic characteristics of 531 persons who underwent colonoscopies between 2014 and 2015 at Mehrad gastrointestinal clinic were determined. Demographics, indication for colonoscopy, colonoscopy findings, number of polyps, and histopathological characteristics of the polyps were examined for each person. RESULTS Our sample included 295 (55.6%) women and 236 (44.4%) men, with a mean age of 50.25 ± 14.89 years. Overall PDR was 23.5% (125/531). ADR and colorectal cancer detection rate in this study were 12.8% and 1.5%, respectively. Polyps were detected more significantly frequently in men than in women (52.8% vs 47.2%, P < 0.05). Polyps can be seen in most patients after the age of 50. The average age of patients with cancer was significantly higher than that of patients with polyps (61.3 years vs 56.4 years, P < 0.05). The majority of the polyps were adenomatous. More than 50% of the polyps were found in the rectosigmoid part of the colon. CONCLUSION The prevalence of polyps and adenomas in this study is less than that reported in the Western populations. In our patients, distal colon is more susceptible to developing polyps and cancer than proximal colon. PMID:28251034

  11. [Obstructive uropathy secondary to vesico-ureteral endometriosis: clinical, radiologic and pathologic features].

    PubMed

    Calvo Pulido, J; Márquez Moreno, A J; Julve Villalta, E; Antuña Calle, F M; Ortega Jiménez, M V; Sánchez Carrillo, J J; Amores Ramírez, F; Martín Palanca, A

    2009-10-01

    To report the case of a 37 year-old woman suffering from endometriosis of the urinary tract, that presented with lumbar and pelvic pain associated to cyclic recurrent haematuria. Following history, physical examination, abdomino-pelvic ultrasound (USS), CT scan and cystoscopy with biopsies, surgical treatment was indicated Imaging (USS-CT ) revealed a protrusion of the left bladder hemi-trigone with a nodular, irregular thickening and ipsilateral grade II-III/IV uretero-hydronefrosis. Cistoscopy confirmed a swollen and oedematous lesion in left hemi-trigone that seemed extrinsic in origin. With the clinical diagnosis of a possible neoplasia of gynaecological origin, the patient underwent surgical treatment consisting in radical hysterectomy with bilateral oophorectomy, partial cystectomy and left ureteroneocystostomy. The frequency of endometriosis in the urinary tract is relatively low and therefore, endometriosis presenting with ureteral obstruction (uretero-hydronephrosis) has been rarely reported in the literature and should be part of the differential diagnosis in young women, especially if symptoms are cyclic. The treatment is surgery and the final diagnosis by pathology report.

  12. Ultrastructural pathological features of unilateral renal artery stenosis in the rats

    PubMed Central

    Liu, Xin; Mao, Yonghui; He, Xuemei; Wang, Mei; Gan, Liangying

    2015-01-01

    Renal artery stenosis (RAS) is one of the main reasons of renovascular hypertension and its pathogenesis remains unclear. In this study, we aimed to investigate histopathological characteristics in a rat model of RAS. Sprague-Dawley (SD) male rats were randomly divided into unilateral RAS group (Model group, n = 30) and Sham group (n = 30). The left renal artery was clamped with miniature silver clip for the rats in RAS group, while it was exposed but not clamped for the rats in Sham group. After the surgery, the rats were randomly divided into ten subgroups based on the time after surgery (n = 3). Blood pressure, urinary albumin/creatinine ratio, and serum albumin and creatinine levels were measured. The kidneys were dissected for histological and electron microscopy analysis. The results showed that systolic blood pressure was significantly higher since 4 weeks after surgery compared to before surgery. There were no significant differences in urinary albumin/creatinine ratio as well as serum albumin and creatinine levels in Model and Sham groups. During the early acute renal ischemia the stenotic kidney exhibited acute tubular injury, podocyte injury and some crescent formation, and the main components of crescent are podocytes. Although renal tubules and vascular lesions gradually recover and crescent disappears, segmental lesions of podocyte appear in the late stage of RAS. These data reveal ultrastructural pathological changes during RAS, and suggest the role of podocyte lesions in chronic renal ischemia. PMID:26191171

  13. Clinical and pathological features of hereditary mixed polyposis syndrome: report on a South African family.

    PubMed

    Ibirogba, S B; Algar, U; Goldberg, P A; Duffield, M; Vorster, A; Ramesar, R

    2008-08-01

    Hereditary mixed polyposis syndrome is characterised by multiple large-bowel polyps of differing histological types including a mixture of atypical juvenile polyps, hyperplastic polyps and adenomas. Affected individuals are thought to have an increased risk of malignancy, possibly via the juvenile polyposis pathway. A 51-year-old woman (with a history of a colectomy for polyps during childhood) presented with rectal bleeding. Endoscopy demonstrated small rectal polyps which were hyperplastic on histology. A family tree was drawn up and the three children of the proband underwent flexible sigmoidoscopy. Endoscopic surveillance of the three children revealed one who had a similar phenotype to the mother. This child underwent colectomy and ileorectal anastomosis. The pathological specimen revealed more than 70 polyps, with a combination of juvenile retention, hyperplastic, adenomatous and inflammatory polyps. A second child had multiple small hyperplastic polyps, and the third had a normal colon. Although the gene locus for the disorder has been mapped, neither the gene nor the disease-causing mutation has been defined. A rare inherited polyposis syndrome has been identified in a South African family. Where clinical suspicion of a possible inherited condition exists, investigating at-risk first-degree relatives confirms the inherited nature of the disease. It is possible to use genetic haplotyping (i.e. with a range of markers in the area of the gene) to provide statistical risk to immediate relatives and therefore those at highest risk.

  14. Clinico-pathological features of breast myxoma: report of a case with histogenetic considerations.

    PubMed

    Magro, Gaetano; Cavanaugh, Barbara; Palazzo, Juan

    2010-05-01

    We herein report the clinical, radiological, and pathological findings of a rare case of myxoma occurring in the breast parenchyma of a 75-year-old female. The tumor was incidentally detected at a mammographic screening and, ultrasonographically, presented as an ovoid mass. Histologically, an encapsulated hypocellular, myxoid tumor with low vascularization was evident. Neoplastic cells were round- to spindle/stellate-shaped and stained with vimentin and focally with calponin. We emphasize that morphology remains preeminent in the diagnosis of a breast myxoma, while immunohistochemistry may assist in ruling out other tumor entities. Differential diagnosis with all benign and malignant myxoid lesions, primarily occurring in the breast, is provided. The histogenesis of breast myxoma is unknown. The lack of expression of desmin, alpha-smooth muscle actin, CD34, CD99, CD10, bcl-2 protein, and estrogen/progesterone/androgen receptors, all markers characteristically expressed by "the benign spindle cell tumors of the mammary stroma," would suggest that breast myxoma does not fall into this tumor category and that its putative precursor mesenchymal cell resides in the interlobular stroma.

  15. Pathological features in dead on arrival broilers with special reference to heart disorders.

    PubMed

    Nijdam, E; Zailan, A R M; van Eck, J H H; Decuypere, E; Stegeman, J A

    2006-07-01

    A gross postmortem investigation was done on 302 broilers that died between catching and slaughter to establish predisposing factors for dying in this period. Special attention was paid to heart disorders, which were established by determining the ratio of the right ventricle mass to the total ventricle mass (RV:TV) and to postmortem changes in hearts and lungs of broilers that were dead on arrival (DOA). Macroscopic pathologic lesions were found in 89.4% of DOA broilers. Signs of infectious diseases appeared to be most frequent (64.9%), followed by heart and circulation disorders (42.4%), and trauma (29.5%). The RV:TV was significantly higher for DOA broilers in comparison with slaughtered broilers. The prevalence of hearts with an abnormal RV:TV in DOA broilers was 34.4 vs. 4.1% in slaughtered broilers. The DOA broilers with an abnormal heart ratio more frequently showed ascites and hydropericardium. Postmortem changes in lungs depend on the position of the carcass the first several hours after death. Broilers, which remain in dorsal recumbency for several hours after death, develop engorged lungs. A good health status as well as more attention for the catching and crating process is crucial in decreasing the percentage of DOA broilers. Prevention of an increased heart ratio and of ascites will improve the livability in the broiler house and also decrease the DOA rate enormously.

  16. Pathologic features and clinical outcome of central neurocytoma: analysis of 15 cases.

    PubMed

    Li, Yu; Ye, Xiu-Feng; Qian, Guo; Yin, Yu; Pan, Qian-Guan

    2012-12-01

    To get better recognition of central neurocytoma and diminish misdiagnosis. A retrospective review identified 15 cases of central neurocytoma. All cases of central neurocytoma were analyzed for their clinical symptoms, pathologic changes, immunohistochemical staining, prognosis and differential diagnosis. Clinical follow up was performed. There were 8 males and 7 females aged 10-64 years (median 32.93 years). The most common presenting symptoms were those related to increased intracranial pressure (ICP), including headache (100%), papilledema (93%) and vomiting (80%). All tumors were located in the ventricular system. The tumors were composed of uniform cells with round nuclei and a fine chromatin pattern, and in some areas, small cells with perinuclear halo could be seen. In particular, the anuclear areas may have a fine fibrillary matrix (neuropil). Nuclear atypia and vascular proliferation appeared in two cases, respectively. Focal necrosis could be seen in one case. Immunohistochemical findings included expression of synaptophysin (15/15), neuron specific enolase (12/15) and glial fibrillary acidic protein (GFAP) (3/15). MIB-1 proliferation index ranged from 0.8-12.5%, and was more than 2% in 3 of 15 cases assessed. Follow-up information of 11 patients was available. Central neurocytoma has a favorable prognosis in general, but in some cases, the clinical course could be aggressive. Increase of GFAP positivity, proliferation index and vascular proliferation might suggest a more malignant process.

  17. Relationship among clinical, pathological and bio-molecular features in low-grade epilepsy-associated neuroepithelial tumors.

    PubMed

    Vornetti, Gianfranco; Marucci, Gianluca; Zenesini, Corrado; de Biase, Dario; Michelucci, Roberto; Tinuper, Paolo; Tallini, Giovanni; Giulioni, Marco

    2017-10-01

    The aim of this study was to evaluate the relationship between molecular markers and clinicopathological features in patients operated on for low-grade epilepsy-associated neuroepithelial tumors. Molecular-genetic signatures are becoming increasingly important in characterizing these lesions, which represent the second most common cause of focal epilepsy in patients undergoing epilepsy surgery. Data from 22 patients operated on for histopathologically confirmed low-grade epilepsy-associated neuroepithelial tumors were retrospectively collected. All specimens were examined for BRAF and IDH mutational status, 1p/19q codeletion and CD34 expression. The relationship between bio-molecular markers and several demographic, clinical and pathological features were analyzed. BRAF mutation was found in 11 (50.0%) patients and CD34 expression in 13 (59.1%). No patients presented IDH mutation or 1p/19q codeletion. Multiple seizure types were present in 5 (45.5%) patients with BRAF mutation and in none of those with BRAF wild type (p=0.035). Moreover, BRAF mutation was predominant in right-sided lesions (p=0.004) and CD34 expression was significantly associated with a longer duration of epilepsy (p=0.027). Several other clinicopathological features, such as association with focal cortical dysplasia and postoperative seizure outcome, showed no significant correlation with molecular markers. Further studies are necessary both to confirm these data in larger cohort of patients and to investigate possible relationships between molecular markers and other clinicopathological features. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Core Biopsy of Vascular Neoplasms of the Breast: Pathologic Features, Imaging, and Clinical Findings.

    PubMed

    Mantilla, Jose G; Koenigsberg, Tova; Reig, Beatriu; Shapiro, Nella; Villanueva-Siles, Esperanza; Fineberg, Susan

    2016-10-01

    Vascular lesions (VLs) of the breast present a diagnostic challenge on breast core biopsy (BCBx). We report on 27 VLs presenting on BCBx. The mean patient age was 60 years, and mean size was 7.5 mm (range, 1.6 to 16 mm). Presentation included palpable mass in 6 (22%), incidental in 6 (22%), and an imaging abnormality in 15 (56%) cases. Imaging impression included hematoma (24%), lymph node (10%), fat necrosis (10%), tortuous vessel (5%), and not provided in 52%. The lesions were classified on the basis of BCBx or BCBx and excision (available in 16 pts) as follows: 1 low-grade angiosarcoma, 8 angiolipomas, 6 capillary hemangiomas, 4 cavernous hemangiomas, 2 hemangiomas (not otherwise specified), 1 papillary endothelial hyperplasia, and 5 perilobular hemangiomas. The angiosarcoma was 9 mm, detected incidentally by magnetic resonance imaging, and showed dissection of stromal collagen, infiltration of glands, high cellularity, moderate cytologic atypia, scant mitotic activity, and Ki-67 reactivity of 10%. Among the 26 benign VLs, worrisome histologic features were noted in 14 on BCBx, including anastomosing vascular channels in 9, moderate cytologic atypia in 4, high cellularity in 2, Ki-67>10% in 2, mitotic activity in 1, and infiltration of glands in 1. Of the 12 VLs without worrisome features, the lesion extended to edge of core in 8, precluding complete evaluation. BCBx of VLs presents diagnostic challenges due to overlapping clinicopathologic and radiologic features with low-grade angiosarcoma. If completeness of removal is documented on BCBx, and cytoarchitectural changes are not worrisome, follow-up could be considered rather than excision. However, only 4 of these cases fulfilled those criteria.

  19. Columnar cell lesions of the canine mammary gland: pathological features and immunophenotypic analysis.

    PubMed

    Ferreira, Enio; Gobbi, Helenice; Saraiva, Bruna S; Cassali, Geovanni D

    2010-02-23

    It has been suggested that columnar cell lesions indicate an alteration of the human mammary gland involved in the development of breast cancer. They have not previously been described in canine mammary gland. The aim of this paper is describe the morphologic spectrum of columnar cell lesions in canine mammary gland specimens and their association with other breast lesions. A total of 126 lesions were subjected to a comprehensive morphological review based upon the human breast classification system for columnar cell lesions. The presence of preinvasive (epithelial hyperplasia and in situ carcinoma) and invasive lesions was determined and immunophenotypic analysis (estrogen receptor (ER), progesterone receptor (PgR), high molecular weight cytokeratin (34betaE-12), E-cadherin, Ki-67, HER-2 and P53) was perfomed. Columnar cell lesions were identified in 67 (53.1%) of the 126 canine mammary glands with intraepithelial alterations. They were observed in the terminal duct lobular units and characterized at dilated acini may be lined by several layers of columnar epithelial cells with elongated nuclei. Of the columnar cell lesions identified, 41 (61.2%) were without and 26 (38.8%) with atypia. Association with ductal hyperplasia was observed in 45/67 (67.1%). Sixty (89.5%) of the columnar cell lesions coexisted with neoplastic lesions (20 in situ carcinomas, 19 invasive carcinomas and 21 benign tumors). The columnar cells were ER, PgR and E-cadherin positive but negative for cytokeratin 34betaE-12, HER-2 and P53. The proliferation rate as measured by Ki-67 appeared higher in the lesions analyzed than in normal TDLUs. Columnar cell lesions in canine mammary gland are pathologically and immunophenotypically similar to those in human breast. This may suggest that dogs are a suitable model for the comparative study of noninvasive breast lesions.

  20. Management of germ cell tumors with somatic type malignancy: pathological features, prognostic factors and survival outcomes.

    PubMed

    Rice, Kevin R; Magers, Martin J; Beck, Stephen D W; Cary, K Clint; Einhorn, Lawrence H; Ulbright, Thomas M; Foster, Richard S

    2014-11-01

    Germ cell tumors with somatic type malignancy are rare, occurring in approximately 2.7% to 8.6% of germ cell tumor cases. Prognostic factors and optimal management remain poorly defined. The Indiana University testis cancer database was queried from 1979 to 2011 for patients demonstrating germ cell tumor with somatic type malignancy at orchiectomy or subsequent resection. Patients with transformation to primitive neuroectodermal tumor only were excluded from study due to distinct management. Chart review, pathological review and survival analysis were performed. A total of 121 patients met the study inclusion criteria. The most common somatic type malignancy histologies were sarcoma (59), carcinoma (31) and sarcomatoid yolk sac tumor (17). Of these patients 32 demonstrated somatic type malignancy at germ cell tumor diagnosis. For those with delayed identification, median time from germ cell tumor to somatic type malignancy diagnosis was 33 months. This interval was longest for carcinomas (108 months). At a median followup of 71 months, 5-year cancer specific survival was 64%. Predictors of poorer cancer specific survival included somatic type malignancy diagnosed at late relapse (p = 0.017), referral to Indiana University for reoperative retroperitoneal lymph node dissection (p = 0.026) and grade (p = 0.026). None of these factors maintained prognostic significance on multivariate analysis. Somatic type malignancy histology subtype, stage, risk category and number of resections were not predictive of cancer specific survival. Germ cell tumor with somatic type malignancy is associated with poorer cancer specific survival than traditional germ cell tumor. Established prognostic factors for germ cell tumor lose predictive value in the setting of somatic type malignancy. Aggressive and serial resections are often necessary to optimize cancer specific survival. Tumor grade is an important prognostic factor in sarcomas and sarcomatoid yolk sac tumors. Copyright

  1. Symptomatic white matter changes in mild traumatic brain injury resemble pathologic features of early Alzheimer dementia.

    PubMed

    Fakhran, Saeed; Yaeger, Karl; Alhilali, Lea

    2013-10-01

    To evaluate white matter integrity in patients with mild traumatic brain injury (TBI) who did not have morphologic abnormalities at conventional magnetic resonance (MR) imaging with diffusion-tensor imaging to determine any relationship between patterns of white matter injury and severity of postconcussion symptoms. The institutional review board approved this study, with waiver of informed consent. Diffusion-tensor images from 64 consecutive patients with mild TBI obtained with conventional MR imaging were evaluated retrospectively. Fractional anisotropy (FA) maps were generated as a measure of white matter integrity. All patients underwent a neurocognitive evaluation. Correlations between skeletonized FA values in white matter, total concussion symptom score, and findings of sleep and wake disturbances were analyzed with regression analysis that used tract-based spatial statistics. Total concussion symptom scores varied from 2 to 97 (mean ± standard deviation, 32.7 ± 24.4), with 34 patients demonstrating sleep and wake disturbances. Tract-based spatial statistics showed a significant correlation between high total concussion symptom score and reduced FA at the gray matter-white matter junction (P < .05), most prominently in the auditory cortex (P < .05). FA in the parahippocampal gyri was significantly decreased in patients with sleep and wake disturbances relative to patients without such disturbances (0.26 and 0.37, respectively; P < .05). The distribution of white matter abnormalities in patients with symptomatic mild TBI is strikingly similar to the distribution of pathologic abnormalities in patients with early Alzheimer dementia, a finding that may help direct research strategies. © RSNA, 2013.

  2. Clinical and pathological features of fat embolism with acute respiratory distress syndrome.

    PubMed

    Kao, Shang Jyh; Yeh, Diana Yu-Wung; Chen, Hsing I

    2007-09-01

    FES (fat embolism syndrome) is a clinical problem, and, although ARDS (acute respiratory distress syndrome) has been considered as a serious complication of FES, the pathogenesis of ARDS associated with FES remains unclear. In the present study, we investigated the clinical manifestations, and biochemical and pathophysiological changes, in subjects associated with FES and ARDS, to elucidate the possible mechanisms involved in this disorder. A total of eight patients with FES were studied, and arterial blood pH, PaO(2) (arterial partial pressure of O(2)), PaCO(2) (arterial partial pressure of CO(2)), biochemical and pathophysiological data were obtained. These subjects suffered from crash injuries and developed FES associated with ARDS, and each died within 2 h after admission. In the subjects, chest radiography revealed that the lungs were clear on admission, and pulmonary infiltration was observed within 2 h of admission. Arterial blood pH and PaO(2) declined, whereas PaCO(2) increased. Plasma PLA(2) (phospholipase A(2)), nitrate/nitrite, methylguanidine, TNF-alpha (tumour necrosis factor-alpha), IL-1beta (interleukin-1beta) and IL-10 (interleukin-10) were significantly elevated. Pathological examinations revealed alveolar oedema and haemorrhage with multiple fat droplet depositions and fibrin thrombi. Fat droplets were also found in the arterioles and/or capillaries in the lung, kidney and brain. Immunohistochemical staining identified iNOS (inducible nitric oxide synthase) in alveolar macrophages. In conclusion, our clinical analysis suggests that PLA(2), NO, free radicals and pro-inflammatory cytokines are involved in the pathogenesis of ARDS associated with FES. The major source of NO is the alveolar macrophages.

  3. A note on the stability and discriminability of graph-based features for classification problems in digital pathology

    NASA Astrophysics Data System (ADS)

    Cruz-Roa, Angel; Xu, Jun; Madabhushi, Anant

    2015-01-01

    Nuclear architecture or the spatial arrangement of individual cancer nuclei on histopathology images has been shown to be associated with different grades and differential risk for a number of solid tumors such as breast, prostate, and oropharyngeal. Graph-based representations of individual nuclei (nuclei representing the graph nodes) allows for mining of quantitative metrics to describe tumor morphology. These graph features can be broadly categorized into global and local depending on the type of graph construction method. While a number of local graph (e.g. Cell Cluster Graphs) and global graph (e.g. Voronoi, Delaunay Triangulation, Minimum Spanning Tree) features have been shown to associated with cancer grade, risk, and outcome for different cancer types, the sensitivity of the preceding segmentation algorithms in identifying individual nuclei can have a significant bearing on the discriminability of the resultant features. This therefore begs the question as to which features while being discriminative of cancer grade and aggressiveness are also the most resilient to the segmentation errors. These properties are particularly desirable in the context of digital pathology images, where the method of slide preparation, staining, and type of nuclear segmentation algorithm employed can all dramatically affect the quality of the nuclear graphs and corresponding features. In this paper we evaluated the trade off between discriminability and stability of both global and local graph-based features in conjunction with a few different segmentation algorithms and in the context of two different histopathology image datasets of breast cancer from whole-slide images (WSI) and tissue microarrays (TMA). Specifically in this paper we investigate a few different performance measures including stability, discriminability and stability vs discriminability trade off, all of which are based on p-values from the Kruskal-Wallis one-way analysis of variance for local and global

  4. Perturbations of the endocannabinoid system in mantle cell lymphoma: correlations to clinical and pathological features

    PubMed Central

    Wasik, Agata M.; Nygren, Lina; Almestrand, Stefan; Zong, Fang; Flygare, Jenny; Wennerholm, Stefanie Baumgartner; Saft, Leonie; Andersson, Patrik; Kimby, Eva; Wahlin, Björn E.; Christensson, Birger; Sander, Birgitta

    2014-01-01

    The cannabinoid receptors are upregulated in many types of cancers, including mantle cell lymphoma (MCL) and have been suggested to constitute novel therapeutic targets. The expression pattern of the key members of the endocannabinoid system was analyzed in a well-characterized MCL patient cohort and correlated to biological features. 107 tumor tissues were analyzed for the mRNA levels of cannabinoid receptors 1 and 2 (CNR1 and CNR2) and the two main enzymes regulating the endocannabinoid anandamide levels in tissue: NAPEPLD and FAAH (participating in synthesis and degradation, respectively). NAPEPLD, CNR1 and CNR2 were overexpressed while FAAH expression was reduced in MCL compared to non-malignant B-cells. Both low CNR1 and high FAAH levels correlated with lymphocytosis (p=0.016 and p=0.022, respectively) and with leukocytosis (p=0.0018 and p=0.047). Weak to moderate CNR1 levels were a feature of SOX11 negative MCL (p=0.006). Both high CNR2 and high FAAH levels correlated to anemia (p=0.0006 and p=0.038, respectively). In conclusion, the relative expression of the anandamide synthesizing and metabolizing enzymes in MCL is heavily perturbed. This finding, together with high expression of cannabinoid receptors, could favor enhanced anandamide signaling and suggest that targeting the endocannabinoid system might be considered as part of lymphoma therapy. PMID:25594062

  5. Correlating DWI MRI with pathological and other features of Jakob-Creutzfeldt disease

    PubMed Central

    Geschwind, Michael D.; Potter, Christopher A.; Sattavat, Mamta; Garcia, Paul A.; Rosen, Howard J.; Miller, Bruce L.; DeArmond, Stephen J.

    2009-01-01

    Diffusion-weighted (DWI) MRI is a highly sensitive and specific test for diagnosis of sporadic Jakob-Creutzfeldt disease (sCJD); however, the neuropathological origin of DWI signal abnormalities including other clinical features have not been well-defined. We describe a case of sCJD with brain MRI taken 15 days prior to death, which provided an opportunity to correlate clinical, EEG, MRI and neuropathological findings in order to better understand which sCJD-specific neuropathological changes underlie the DWI abnormalities. Clinical findings correlated well with both EEG and MRI changes. Neuropathological analysis showed that hyperintensities on DWI MRI correlated best with the vacuolation score (r=0.78, p=0.0005) and PrPSc load (r=0.77; p=0.0006), followed by reactive astrocytic gliosis (r=0.63, p=0.008). This case provides further evidence that DWI abnormalities correlate well with the clinical features and with PrPSc accumulation and vacuolation. PMID:19266702

  6. Correlating DWI MRI with pathologic and other features of Jakob-Creutzfeldt disease.

    PubMed

    Geschwind, Michael D; Potter, Christopher A; Sattavat, Mamta; Garcia, Paul A; Rosen, Howard J; Miller, Bruce L; DeArmond, Stephen J

    2009-01-01

    Diffusion-weighted (DWI) magnetic resonance imaging (MRI) is a highly sensitive and specific test for diagnosis of sporadic Jakob-Creutzfeldt disease (sCJD); however, the neuropathologic origin of DWI signal abnormalities including other clinical features has not been well defined. We describe a case of sCJD with brain MRI taken 15 days before death, which provided an opportunity to correlate clinical, electroencephalogram, MRI, and neuropathologic findings to better understand which sCJD-specific neuropathologic changes underlie the DWI abnormalities. Clinical findings correlated well with both electroencephalogram and MRI changes. Neuropathologic analysis showed that hyperintensities on DWI MRI correlated best with the vacuolation score (r=0.78, P=0.0005) and PrP(Sc) load (r=0.77; P=0.0006), followed by reactive astrocytic gliosis (r=0.63, P=0.008). This case provides further evidence that DWI abnormalities correlate well with the clinical features and with PrP(Sc) accumulation and vacuolation.

  7. Optimization of a 3D Dynamic Culturing System for In Vitro Modeling of Frontotemporal Neurodegeneration-Relevant Pathologic Features.

    PubMed

    Tunesi, Marta; Fusco, Federica; Fiordaliso, Fabio; Corbelli, Alessandro; Biella, Gloria; Raimondi, Manuela T

    2016-01-01

    Frontotemporal lobar degeneration (FTLD) is a severe neurodegenerative disorder that is diagnosed with increasing frequency in clinical setting. Currently, no therapy is available and in addition the molecular basis of the disease are far from being elucidated. Consequently, it is of pivotal importance to develop reliable and cost-effective in vitro models for basic research purposes and drug screening. To this respect, recent results in the field of Alzheimer's disease have suggested that a tridimensional (3D) environment is an added value to better model key pathologic features of the disease. Here, we have tried to add complexity to the 3D cell culturing concept by using a microfluidic bioreactor, where cells are cultured under a continuous flow of medium, thus mimicking the interstitial fluid movement that actually perfuses the body tissues, including the brain. We have implemented this model using a neuronal-like cell line (SH-SY5Y), a widely exploited cell model for neurodegenerative disorders that shows some basic features relevant for FTLD modeling, such as the release of the FTLD-related protein progranulin (PRGN) in specific vesicles (exosomes). We have efficiently seeded the cells on 3D scaffolds, optimized a disease-relevant oxidative stress experiment (by targeting mitochondrial function that is one of the possible FTLD-involved pathological mechanisms) and evaluated cell metabolic activity in dynamic culture in comparison to static conditions, finding that SH-SY5Y cells cultured in 3D scaffold are susceptible to the oxidative damage triggered by a mitochondrial-targeting toxin (6-OHDA) and that the same cells cultured in dynamic conditions kept their basic capacity to secrete PRGN in exosomes once recovered from the bioreactor and plated in standard 2D conditions. We think that a further improvement of our microfluidic system may help in providing a full device where assessing basic FTLD-related features (including PRGN dynamic secretion) that may be

  8. Pathological features of Cryptosporidium andersoni-induced lesions in SCID mice.

    PubMed

    Masuno, Koichi; Yanai, Tokuma; Sakai, Hiroki; Satoh, Masaaki; Kai, Chieko; Nakai, Yutaka

    2013-07-01

    To assess the infectivity and the istopathological features of Cryptosporidium andersoni (C. andersoni) in laboratory animals, SCID mice were orally inoculated with oocysts of C. andersoni. Starting one week after inoculation, the SCID mice began shedding oocysts, and this continued for ten weeks. Histopathologically, myriads of C. andersoni were observed on the apical surface of the epithelium in the gastric pit of the glandular stomach. There were few lesions in the gastric epithelium except C. andersoni adhesion. In the lamina propria of the affected mucosa, minimum infiltration of inflammatory cells was observed. Immunohistochemically, C. andersoni demonstrated a positive reaction to a number of primary antibodies of Cryptosporidium parvum. In the experiment described here, few increases were seen in apoptotic epithelial cells in the affected mucosas of the SCID mice, and the nuclear augmentation was not enhanced. It was hypothesized that the absence of apoptosis and cell division were due to a lack of inflammatory cell reaction in the lamina propria.

  9. Parkinson disease: insights in clinical, genetic and pathological features of monogenic disease subtypes.

    PubMed

    Crosiers, David; Theuns, Jessie; Cras, Patrick; Van Broeckhoven, Christine

    2011-10-01

    In the past 15 years, insights in clinical and genetic characteristics of Parkinson disease (PD) have increased substantially. Sequence or copy number variants in at least six genes (SNCA, LRRK2, PARK2, PINK1, DJ-1 and ATP13A2) have been identified to cause monogenic forms of PD. Routine clinical testing for mutations in these genes is feasible and available, but overlapping phenotypes in monogenic and sporadic PD complicate straightforward diagnostic screening. Primarily, a positive familial history and an early onset age should prompt clinicians to consider genetic testing. Based on a literature review on clinical and neuropathological features of PD patients carrying a pathogenic mutation we propose guidelines for genetic diagnostic testing in clinical practice. However, the absence of disease-modifying therapies and the variable penetrance of most known mutations currently limit the usefulness of genetic diagnostic testing for PD in clinical practice.

  10. Examining the relation of osteochondral lesions of the talus to ligamentous and lateral ankle tendinous pathologic features: a comprehensive MRI review in an asymptomatic lateral ankle population.

    PubMed

    Galli, Melissa M; Protzman, Nicole M; Mandelker, Eiran M; Malhotra, Amit D; Schwartz, Edward; Brigido, Stephen A

    2014-01-01

    Given the frequency and burden of ankle sprains, the pathologic features identified on magnetic resonance imaging (MRI) scans are widely known in the symptomatic population. Ankle MRI pathologic features in the asymptomatic population, however, are poorly understood. Such examinations are rarely undertaken unless an ankle has been injured or is painful. We report the systematic MRI findings from the reports of 108 consecutive asymptomatic lateral ankles (104 patients). Our purpose was to (1) report the prevalence of osteochondral lesions of the talus (OLTs) and pathologic features of the medial and lateral ligaments, peroneal tendons, and superior peroneal retinaculum (SPR); (2) correlate the presence of OLTs with the pathologic features of the medial and lateral ligaments, peroneal tendons, and SPR; and (3) correlate ligamentous discontinuity with the peroneal pathologic features, OLTs, and SPR pathologic features. A total of 16 OLTs (14.81%) were present (13 medial and 3 lateral). Of the 16 patients with OLTs, 8 (50.00%) had concomitant peroneal pathologic findings. Healthy medial and lateral ligaments were noted in 41 patients (37.96%), and ligamentous discontinuity was grade I in 25 (23.15%), II in 32 (29.63%), III in 5 (4.63%), and grade IV in 5 patients (4.63%). A weak positive correlation was found between attenuation or tears of the superficial deltoid and medial OLTs (phi coefficient = 0.23, p = .0191) and a moderate positive correlation between tears of the posterior talofibular ligament and lateral OLTs (phi coefficient = 0.30, p = .0017). Additionally, a moderate positive correlation between ligamentous discontinuity and tendinopathy of the peroneus brevis was noted [Spearman's coefficient(106) = 0.29, p = .0024]. These findings add to the evidence of concomitant pathologic features in the asymptomatic population. To definitively assess causation and evaluate the clinical evolution of radiologic findings, future, prospective, longitudinal

  11. RET/PTC Translocations and Clinico-Pathological Features in Human Papillary Thyroid Carcinoma

    PubMed Central

    Romei, Cristina; Elisei, Rossella

    2012-01-01

    Thyroid carcinoma is the most frequent endocrine cancer accounting for 5–10% of thyroid nodules. Papillary histotype (PTC) is the most prevalent form accounting for 80% of all thyroid carcinoma. Although much is known about its epidemiology, pathogenesis, clinical, and biological behavior, the only documented risk factor for PTC is the ionizing radiation exposure. Rearrangements of the Rearranged during Transfection (RET) proto-oncogene are found in PTC and have been shown to play a pathogenic role. The first RET rearrangement, named RET/PTC, was discovered in 1987. This rearrangement constitutively activates the transcription of the RET tyrosine-kinase domain in follicular cell, thus triggering the signaling along the MAPK pathway and an uncontrolled proliferation. Up to now, 13 different types of RET/PTC rearrangements have been reported but the two most common are RET/PTC1 and RET/PTC3. Ionizing radiations are responsible for the generation of RET/PTC rearrangements, as supported by in vitro studies and by the evidence that RET/PTC, and particularly RET/PTC3, are highly prevalent in radiation induced PTC. However, many thyroid tumors without any history of radiation exposure harbor similar RET rearrangements. The overall prevalence of RET/PTC rearrangements varies from 20 to 70% of PTCs and they are more frequent in childhood than in adulthood thyroid cancer. Controversial data have been reported on the relationship between RET/PTC rearrangements and the PTC prognosis. RET/PTC3 is usually associated with a more aggressive phenotype and in particular with a greater tumor size, the solid variant, and a more advanced stage at diagnosis which are all poor prognostic factors. In contrast, RET/PTC1 rearrangement does not correlate with any clinical–pathological characteristics of PTC. Moreover, the RET protein and mRNA expression level did not show any correlation with the outcome of patients with PTC and no correlation between RET/PTC rearrangements and the

  12. S-phase fractions of colorectal carcinomas related to pathologic and clinical features

    SciTech Connect

    Meyer, J.S.; Prioleau, P.G.

    1981-09-01

    The S-phase fractions (SPFs) of epithelial cells in 100 resected colorectal carcinomas were measured by in vitro exposure to tritiated thymidine and autoradiography. The frequency distribution of SPFs was gaussian with a median of 17.8 per hundred in 90 unirradiated carcinomas, whereas in ten carcinomas given radiation therapy preoperatively, it was positively skewed with a median of 6.9. Analysis of the unirradiated carcinomas showed no relationship between SPF and various clinical and morphologic features that included age, race, sex, site, size, Dukes' stage, histologic grade of the tumor, number of metastasis-bearing regional lymph nodes, presence of adenomas of the large bowel, survival or relapse-free survival of the patient, or SPF or adjacent normal colorectal crypts. The results show no evidence that colorectal carcinomas can be divided into kinetic subsets. The spatial orientation of labeled cells in autoradiographs indicated presence of a nonproliferative fraction of cells in many tumors that may modulate response to radiation therapy and chemotherapy.

  13. Predicting the pathological features of the mesorectum before the laparoscopic approach to rectal cancer.

    PubMed

    Fernández Ananín, Sonia; Targarona, Eduardo M; Martinez, Carmen; Pernas, Juan Carlos; Hernández, Diana; Gich, Ignasi; Sancho, Francesc J; Trias, Manuel

    2014-12-01

    Pelvic anatomy and tumour features play a role in the difficulty of the laparoscopic approach to total mesorectal excision in rectal cancer. The aim of the study was to analyse whether these characteristics also influence the quality of the surgical specimen. We performed a prospective study in consecutive patients with rectal cancer located less than 12 cm from the anal verge who underwent laparoscopic surgery between January 2010 and July 2013. Exclusion criteria were T1 and T4 tumours, abdominoperineal resections, obstructive and perforated tumours, or any major contraindication for laparoscopic surgery. Dependent variables were the circumferential resection margin (CMR) and the quality of the mesorectum. Sixty-four patients underwent laparoscopic sphincter-preserving total mesorectal excision. Resection was complete in 79.1% of specimens and CMR was positive in 9.7%. Univariate analysis showed tumour depth (T status) (P = 0.04) and promontorium-subsacrum angle (P = 0.02) independently predicted CRM (circumferential resection margin) positivity. Tumour depth (P < 0.05) and promontorium-subsacrum axis (P < 0.05) independently predicted mesorectum quality. Multivariate analysis identified the promontorium-subsacrum angle (P = 0.012) as the only independent predictor of CRM. Bony pelvis dimensions influenced the quality of the specimen obtained by laparoscopy. These measurements may be useful to predict which patients will benefit most from laparoscopic surgery and also to select patients in accordance with the learning curve of trainee surgeons.

  14. Adaptive multiple feature method (AMFM) for early detecton of parenchymal pathology in a smoking population

    NASA Astrophysics Data System (ADS)

    Uppaluri, Renuka; McLennan, Geoffrey; Enright, Paul; Standen, James; Boyer-Pfersdorf, Pamela; Hoffman, Eric A.

    1998-07-01

    Application of the Adaptive Multiple Feature Method (AMFM) to identify early changes in a smoking population is discussed. This method was specifically applied to determine if differences in CT images of smokers (with normal lung function) and non-smokers (with normal lung function) could be found through computerized texture analysis. Results demonstrated that these groups could be differentiated with over 80.0% accuracy. Further, differences on CT images between normal appearing lung from non-smokers (with normal lung function) and normal appearing lung from smokers (with abnormal lung function) were also investigated. These groups were differentiated with over 89.5% accuracy. In analyzing the whole lung region by region, the AMFM characterized 38.6% of a smoker lung (with normal lung function) as mild emphysema. We can conclude that the AMFM detects parenchymal patterns in the lungs of smokers which are different from normal patterns occurring in healthy non-smokers. These patterns could perhaps indicate early smoking-related changes.

  15. Herpes Simplex Virus Type 1 infection: overview on relevant clinico-pathological features.

    PubMed

    Arduino, Paolo G; Porter, Stephen R

    2008-02-01

    Herpes Simplex Virus Type 1 (HSV-1) is a nuclear replicating enveloped virus, usually acquired through direct contact with infected lesions or body fluids (typically saliva). The prevalence of HSV-1 infection increases progressively from childhood, the seroprevalence being inversely related to socioeconomic background. Primary HSV-1 infections in children are either asymptomatic or following an incubation period of about 1 week gives rise to mucocutaneous vesicular eruptions. Herpetic gingivostomatitis typically affects the tongue, lips, gingival, buccal mucosa and the hard and soft palate. Most primary oro-facial HSV infection is caused by HSV-1, infection by HSV-2 is increasingly common. Recurrent infections, which occur at variable intervals, typically give rise to vesiculo-ulcerative lesions at mucocutaneous junctions particularly the lips (herpes labialis). Recurrent HSV-1 infection within the mouth is uncommon in otherwise healthy patients, although in immunocompromised patients, recurrent infection can be more extensive and/or aggressive. The diagnosis of common herpetic infection can usually be based upon the clinical history and presenting features. Confirmatory laboratory diagnosis is, however, required when patients are, or may be, immunocompromised.

  16. Extramedullary plasmacytoma-like posttransplantation lymphoproliferative disorders: clinical and pathologic features.

    PubMed

    Richendollar, Bill G; Hsi, Eric D; Cook, James R

    2009-10-01

    Most monomorphic posttransplantation lymphoproliferative disorders (PTLDs) resemble diffuse large B-cell lymphoma or Burkitt lymphoma. Rare cases of PTLD resembling extramedullary plasmacytomas have also been described. This report describes the clinical, histologic, phenotypic, and genotypic findings in 4 cases of plasmacytoma-like PTLD (2 nodal, 1 adenoidal, and 1 cutaneous) and compares the findings with extramedullary involvement by plasma cell neoplasms arising in immunocompetent patients. Plasmacytoma-like PTLDs characteristically arise late after transplantation (mean, 7.0 years), show a variable association with Epstein-Barr virus (2/4 cases positive), and demonstrate histologic and phenotypic findings that overlap with immunocompetent extramedullary plasma cell neoplasms. None of the patients with plasmacytoma-like PTLD developed lytic bone lesions, and 3 of 4 patients had complete responses (>2 years) to reduction of immunosuppression, confirming the role of immunosuppression in the pathogenesis of these lesions. This report, which represents the first case series of plasmacytoma-like PTLD, clarifies the features of this rare subtype of PTLD.

  17. A solitary uterine relapse in T-cell Acute Lymphoblastic Leukaemia: CT features and pathologic correlation.

    PubMed

    Mazzei, M A; Bettini, G; Pozzessere, C; Guerrini, S; Defina, M; Ambrosio, M R; Aprile, L; Bocchia, M; Volterrani, L

    2016-01-01

    T-cell Acute Lymphoblastic Leukemia (T-cell ALL) is a rare haematological neoplasia, that affects children and less commonly adults. Female genital tract and particularly uterus involvement in acute ALL is rare. This report presents the CT features of a 64-year-old woman with uterine relapse of T-cell ALL, occurring 11 months after the diagnosis, as a second, unique relapse of disease. The patient was asymptomatic when a CT examination showed a homogenous thickness of the uterine wall in comparison with the previous CT examination. Histology from biopsy specimens, obtained through hysteroscopy, confirmed T-cell ALL localisation (TdT+, CD10+, CD3c+ and CD2+). The uterus could be a site of relapse in patients suffering from ALL. Even though an MRI examination could better demonstrate the disease in cases of suspected female genital tract involvement by ALL, the comparison of differences between a present and a previous CT examination is sufficient to suspect the diagnosis.

  18. Ameloblastomas: Clinicopathological features from 70 cases diagnosed in a single Oral Pathology service in an 8-year period

    PubMed Central

    Filizzola, Andressa-Incerte; Bartholomeu-dos-Santos, Teresa-Cristina-Ribeiro

    2014-01-01

    Ameloblastomas are odontogenic tumors that can present some distinct clinicopathological profiles when comparing different populations and studies. Objectives: The aim of the present study was to analyze the clinicopathological features from a series of ameloblastomas diagnosed in a single Oral Pathology service in Brazil in an 8-year period. Study Design: The files were revised and all cases diagnosed as ameloblastomas in the period were retrieved. All hematoxylin and eosin stained histological slides were reviewed and all clinical and radiological information were obtained through a review of the laboratory forms. Data were descriptively analyzed and a comparison was performed with the different ameloblastomas subtypes. Results: Seventy ameloblastomas composed the final sample, including 57 (81%) solid/multicystic, 9 (13%) unicystic, 2 (3%) desmoplastic and 2 (3%) peripheral ameloblastomas. Mean age of the affected patients was in the forth decade of life and there was a slight male predominance. Most tumors presented as multilocular radiolucencies, were located in the posterior mandible and showed the follicular and plexiform histological patterns. There was no difference on the mean age of the patients affected by solid and unicystic ameloblastomas. Conclusions: The present results showed that the clinicopathological features of the ameloblastomas included in this Brazilian sample were similar to the features described in most other worldwide populations. Key words:Ameloblastoma, solid, unicystic, review, epidemiology, histology. PMID:25129244

  19. MUC1 Expression by Immunohistochemistry Is Associated with Adverse Pathologic Features in Prostate Cancer: A Multi-Institutional Study

    PubMed Central

    Eminaga, Okyaz; Wei, Wei; Hawley, Sarah J.; Auman, Heidi; Newcomb, Lisa F.; Simko, Jeff; Hurtado-Coll, Antonio; Troyer, Dean A.; Carroll, Peter R.; Gleave, Martin E.; Lin, Daniel W.; Nelson, Peter S.; Thompson, Ian M.; True, Lawrence D.; McKenney, Jesse K.; Feng, Ziding; Fazli, Ladan; Brooks, James D.

    2016-01-01

    Background The uncertainties inherent in clinical measures of prostate cancer (CaP) aggressiveness endorse the investigation of clinically validated tissue biomarkers. MUC1 expression has been previously reported to independently predict aggressive localized prostate cancer. We used a large cohort to validate whether MUC1 protein levels measured by immunohistochemistry (IHC) predict aggressive cancer, recurrence and survival outcomes after radical prostatectomy independent of clinical and pathological parameters. Material and Methods MUC1 IHC was performed on a multi-institutional tissue microarray (TMA) resource including 1,326 men with a median follow-up of 5 years. Associations with clinical and pathological parameters were tested by the Chi-square test and the Wilcoxon rank sum test. Relationships with outcome were assessed with univariable and multivariable Cox proportional hazard models and the Log-rank test. Results The presence of MUC1 expression was significantly associated with extracapsular extension and higher Gleason score, but not with seminal vesicle invasion, age, positive surgical margins or pre-operative serum PSA levels. In univariable analyses, positive MUC1 staining was significantly associated with a worse recurrence free survival (RFS) (HR: 1.24, CI 1.03–1.49, P = 0.02), although not with disease specific survival (DSS, P>0.5). On multivariable analyses, the presence of positive surgical margins, extracapsular extension, seminal vesicle invasion, as well as higher pre-operative PSA and increasing Gleason score were independently associated with RFS, while MUC1 expression was not. Positive MUC1 expression was not independently associated with disease specific survival (DSS), but was weakly associated with overall survival (OS). Conclusion In our large, rigorously designed validation cohort, MUC1 protein expression was associated with adverse pathological features, although it was not an independent predictor of outcome after radical

  20. MUC1 Expression by Immunohistochemistry Is Associated with Adverse Pathologic Features in Prostate Cancer: A Multi-Institutional Study.

    PubMed

    Eminaga, Okyaz; Wei, Wei; Hawley, Sarah J; Auman, Heidi; Newcomb, Lisa F; Simko, Jeff; Hurtado-Coll, Antonio; Troyer, Dean A; Carroll, Peter R; Gleave, Martin E; Lin, Daniel W; Nelson, Peter S; Thompson, Ian M; True, Lawrence D; McKenney, Jesse K; Feng, Ziding; Fazli, Ladan; Brooks, James D

    2016-01-01

    The uncertainties inherent in clinical measures of prostate cancer (CaP) aggressiveness endorse the investigation of clinically validated tissue biomarkers. MUC1 expression has been previously reported to independently predict aggressive localized prostate cancer. We used a large cohort to validate whether MUC1 protein levels measured by immunohistochemistry (IHC) predict aggressive cancer, recurrence and survival outcomes after radical prostatectomy independent of clinical and pathological parameters. MUC1 IHC was performed on a multi-institutional tissue microarray (TMA) resource including 1,326 men with a median follow-up of 5 years. Associations with clinical and pathological parameters were tested by the Chi-square test and the Wilcoxon rank sum test. Relationships with outcome were assessed with univariable and multivariable Cox proportional hazard models and the Log-rank test. The presence of MUC1 expression was significantly associated with extracapsular extension and higher Gleason score, but not with seminal vesicle invasion, age, positive surgical margins or pre-operative serum PSA levels. In univariable analyses, positive MUC1 staining was significantly associated with a worse recurrence free survival (RFS) (HR: 1.24, CI 1.03-1.49, P = 0.02), although not with disease specific survival (DSS, P>0.5). On multivariable analyses, the presence of positive surgical margins, extracapsular extension, seminal vesicle invasion, as well as higher pre-operative PSA and increasing Gleason score were independently associated with RFS, while MUC1 expression was not. Positive MUC1 expression was not independently associated with disease specific survival (DSS), but was weakly associated with overall survival (OS). In our large, rigorously designed validation cohort, MUC1 protein expression was associated with adverse pathological features, although it was not an independent predictor of outcome after radical prostatectomy.

  1. A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis.

    PubMed

    Barr, Andrew J; Campbell, T Mark; Hopkinson, Devan; Kingsbury, Sarah R; Bowes, Mike A; Conaghan, Philip G

    2015-08-25

    Bone is an integral part of the osteoarthritis (OA) process. We conducted a systematic literature review in order to understand the relationship between non-conventional radiographic imaging of subchondral bone, pain, structural pathology and joint replacement in peripheral joint OA. A search of the Medline, EMBASE and Cochrane library databases was performed for original articles reporting association between non-conventional radiographic imaging-assessed subchondral bone pathologies and joint replacement, pain or structural progression in knee, hip, hand, ankle and foot OA. Each association was qualitatively characterised by a synthesis of the data from each analysis based upon study design, adequacy of covariate adjustment and quality scoring. In total 2456 abstracts were screened and 139 papers were included (70 cross-sectional, 71 longitudinal analyses; 116 knee, 15 hip, six hand, two ankle and involved 113 MRI, eight DXA, four CT, eight scintigraphic and eight 2D shape analyses). BMLs, osteophytes and bone shape were independently associated with structural progression or joint replacement. BMLs and bone shape were independently associated with longitudinal change in pain and incident frequent knee pain respectively. Subchondral bone features have independent associations with structural progression, pain and joint replacement in peripheral OA in the hip and hand but especially in the knee. For peripheral OA sites other than the knee, there are fewer associations and independent associations of bone pathologies with these important OA outcomes which may reflect fewer studies; for example the foot and ankle were poorly studied. Subchondral OA bone appears to be a relevant therapeutic target. PROSPERO registration number: CRD 42013005009.

  2. Mixed acinar-endocrine carcinoma of the pancreas: new clinical and pathological features in a contemporary series.

    PubMed

    Yu, Run; Jih, Lily; Zhai, Jing; Nissen, Nicholas N; Colquhoun, Steven; Wolin, Edward; Dhall, Deepti

    2013-04-01

    The objective of this study was to characterize the novel clinical and pathological features of mixed acinar-endocrine carcinoma of the pancreas. This was a retrospective review of medical records and surgical pathology specimens of patients with a diagnosis of mixed acinar-endocrine carcinoma of the pancreas at Cedars-Sinai Medical Center between 2005 and 2011. Additional immunohistochemistry was performed on the specimens of some patients. Five patients were identified. The median age at presentation was 74 years (range, 59-89 years), and all patients were male. The presenting symptoms were all related to tumor mass effects. The median size of the tumor was 10 cm (range, 3.9-16 cm). Preoperative clinical diagnosis aided by fine-needle aspiration biopsy was incorrect in all 5 cases. Most tumors (3/5) exhibited predominantly endocrine differentiation without hormonal production. Only 10% to 30% of cells were truly amphicrine, whereas most were differentiated into either endocrine or acinar phenotype. The clinical behavior ranged from moderate to aggressive with postoperative survival from 2.5 months to more than 3 years. Four patients received neoadjuvant or adjuvant chemotherapy with variable responses. Mixed acinar-endocrine carcinoma of the pancreas appears to be not uncommon in men, may harbor predominantly endocrine component, is often misdiagnosed by cytology, and exhibits variable clinical behavior. Mixed acinar-endocrine carcinoma of the pancreas should be considered in older patients with sizable pancreatic mass and may warrant aggressive surgical resection and chemotherapy.

  3. Effects of clinical, laboratuary and pathological features on successful sperm retrieval in non-obstructive azoospermia

    PubMed Central

    Güneri, Çağrı; Alkibay, Turgut; Tunç, Lütfi

    2016-01-01

    Objective The study aims to evaluate the correlation of testicular sperm extraction (TESE) and histopathology with various features of non-obstructive azoospermia (NOA) cases who consulted to our university-based infertility clinic, and the probability of prompting couples about TESE success and to investigate the cost reduction chance through cost-beneficial aspects. Material and methods One hundred and twenty-five patients were enrolled in this study. Age, unprotected intercourse period, age of puberty, and concomittant diseases were noted. Testicular volumes were measured. The correlations between genetic test results and serum levels of Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), free testosterone, prolactine were investigated. Results The incidence of NOA among infertile men was found to be 15.1%. Median age of the cases was 33.1 years. Decrease in TESE success rate was seen in the group aged >30, and those who practiced unprotected intercourse for more than 10 years. TESE success rate was 40 percent. The required negative correlation between FSH levels, and testicular volume was not observed when the patient had additional diseases and/or genitourinary surgery. FSH and LH levels were significantly different between TESE- positive and negative groups (p=0.006, and p=0.001 respectively). Success rate in bilateral TESE group was 14.2%, and 96% of TESE- negative patients had bilateral TESE. Fifteen of 118 patients had Y chromosome microdeletions. These results were similar in both TESE- positive and negative group. Conclusion None of the parameters investigated herein predicted succesful TESE outcomes. However, in cases with increased FSH and AZFa/AZFb deletion before application of bilateral TESE, in cases of increased FSH and AZFa/AZFb deletion, detailed information should be given to these patients about low success rates and risk of disease inheritance which may reduce procedural costs. Knowing groups with poor prognosis, may help

  4. Clinicopathologic features of myositis patients with CD8-MHC-1 complex pathology.

    PubMed

    Ikenaga, Chiseko; Kubota, Akatsuki; Kadoya, Masato; Taira, Kenichiro; Uchio, Naohiro; Hida, Ayumi; Maeda, Meiko Hashimoto; Nagashima, Yu; Ishiura, Hiroyuki; Kaida, Kenichi; Goto, Jun; Tsuji, Shoji; Shimizu, Jun

    2017-09-05

    To determine the clinical features of myositis patients with the histopathologic finding of CD8-positive T cells invading non-necrotic muscle fibers expressing major histocompatibility complex class 1 (CD8-MHC-1 complex), which is shared by polymyositis (PM) and inclusion body myositis (IBM), in relation to the p62 immunostaining pattern of muscle fibers. All 93 myositis patients with CD8-MHC-1 complex who were referred to our hospital from 1993 to 2015 were classified on the basis of the European Neuromuscular Center (ENMC) diagnostic criteria for IBM (Rose, 2013) or PM (Hoogendijk, 2004) and analyzed. The 93 patients included were 17 patients with PM, 70 patients with IBM, and 6 patients who neither met the criteria for PM nor IBM in terms of muscle weakness distribution (unclassifiable group). For these PM, IBM, and unclassifiable patients, their mean ages at diagnosis were 63, 70, and 64 years; autoimmune disease was present in 7 (41%), 13 (19%), and 4 (67%); hepatitis C virus infection was detected in 0%, 13 (20%), and 2 (33%); and p62 was immunopositive in 0%, 66 (94%), and 2 (33%), respectively. Of the treated patients, 11 of 16 PM patients and 4 of 6 p62-immunonegative patients in the unclassifiable group showed responses to immunotherapy, whereas all 44 patients with IBM and 2 p62-immunopositive patients in the unclassifiable group were unresponsive to immunotherapy. CD8-MHC-1 complex is present in patients with PM, IBM, or unclassifiable group. The data may serve as an argument for a trial of immunosuppressive treatment in p62-immunonegative patients with unclassifiable myositis. © 2017 American Academy of Neurology.

  5. Programmed death ligand 1 expression in hepatocellular carcinoma: Relationship With clinical and pathological features.

    PubMed

    Calderaro, Julien; Rousseau, Benoît; Amaddeo, Giuliana; Mercey, Marion; Charpy, Cécile; Costentin, Charlotte; Luciani, Alain; Zafrani, Elie-Serge; Laurent, Alexis; Azoulay, Daniel; Lafdil, Fouad; Pawlotsky, Jean-Michel

    2016-12-01

    The prognosis of hepatocellular carcinoma (HCC) remains poor, with only one third of patients eligible for curative treatments and very limited survival benefits with the use of sorafenib, the current standard of care for advanced disease. Recently, agents targeting the programmed death ligand 1 (PD-L1)/programmed death receptor 1 (PD-1) immune checkpoint were shown to display impressive antitumor activity in various solid or hematological malignancies, including HCC. PD-L1 immunohistochemical expression is thought to represent a biomarker predictive of drug sensitivity. Here, we investigated PD-L1 expression in a series of 217 HCCs and correlated our results with clinical and histological features and immunohistochemical markers (PD-1, cytokeratin 19, glutamine synthetase, and β-catenin expression). PD-L1 expression by neoplastic cells was significantly associated with common markers of tumor aggressiveness (high serum alpha-fetoprotein levels, P = 0.038; satellite nodules, P < 0.001; macrovascular invasion, P < 0.001; microvascular invasion, P < 0.001; poor differentiation, P < 0.001) and with the progenitor subtype of HCC (cytokeratin 19 expression, P = 0.031). High PD-L1 expression by inflammatory cells from the tumor microenvironment also correlated with high serum alpha-fetoprotein levels (P < 0.001), macrovascular invasion (P = 0.001), poor differentiation (P = 0.001), high PD-1 expression (P < 0.001), and the so-called lymphoepithelioma-like histological subtype of HCC (P = 0.003).

  6. Nanotheranostics of Circulating Tumor Cells, Infections and Other Pathological Features In Vivo

    PubMed Central

    Kim, Jin-Woo; Galanzha, Ekaterina I.; Zaharoff, David A.; Griffin, Robert J.; Zharov, Vladimir P.

    2013-01-01

    Many life-threatening diseases are disseminated through biological fluids, such as blood, lymph and cerebrospinal fluid. The migration of tumor cells through the vascular circulation is a mandatory step in metastasis, which is responsible for ∼90% of cancer-associated mortality. Circulating pathogenic bacteria, viruses, or blood clots lead to other serious conditions including bacteremia, sepsis, viremia and infarction. Therefore, technologies capable of detecting circulating tumor cells (CTCs), circulating bacterial cells (CBCs), circulating endothelial cells (CECs), cancer biomarkers such as microparticles and exosomes, which contain important microRNA signatures, and other abnormal features in biological fluids may facilitate early diagnosis and treatment of metastatic cancers, infections and adverse cardiovascular events. Unfortunately, even in a disease setting, circulating abnormal cells are rare events that are easily obscured by the overwhelming background material in whole blood. Existing detection methods mostly rely on ex vivo analyses of limited volumes (a few mL) of whole blood. These small volumes limit the probability of detecting CTCs, CECs, CBCs and other rare phenomena. In vivo detection platforms capable of continuously monitoring the entire circulation may substantially increase the probability of detecting circulating abnormal cells and, in particular, increase the opportunity to identify exceedingly rare and potentially dangerous subsets of these cells, such as circulating cancer stem cells (CCSCs). In addition, in vivo detection technologies capable of destroying and/or capturing circulating abnormal cells may inhibit disease progression. This article reviews novel therapeutic and diagnostic (theranostic) platforms integrating in vivo realtime early diagnosis of CTCs, CECs, CBCs and other abnormal objects in circulation. This critical review particularly focuses on nanotechnology-based theranostic (nanotheranostic) approaches, especially in

  7. Usual interstitial pneumonia end-stage features from explants with radiologic and pathological correlations.

    PubMed

    Rabeyrin, Maud; Thivolet, Françoise; Ferretti, Gilbert R; Chalabreysse, Lara; Jankowski, Adrien; Cottin, Vincent; Pison, Christophe; Cordier, Jean-François; Lantuejoul, Sylvie

    2015-08-01

    Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe idiopathic interstitial pneumonia, with typical high-resolution computed tomography (HRCT) features and histologic pattern of usual interstitial pneumonia (UIP); its main differential diagnosis is fibrotic nonspecific interstitial pneumonia (F-NSIP). Usual interstitial pneumonia was mainly described from lung biopsies, and little is known on explants. Twenty-two UIP/IPF explants were analyzed histologically and compared with previous open lung biopsies (OLBs; n = 11) and HRCT (n = 19), when available. Temporospatial heterogeneity and subpleural and paraseptal fibrosis were similarly found in UIP/IPF explants and OLB (91%-95%). Fibroblastic foci were found in 82% of OLBs and 100% of explants, with a higher mean score in explants (P = .023). Honeycombing was present in 64% of OLBs and 95% of explants, with a higher mean score in explants (P = .005). Almost 60% of UIP/IPF explants showed NSIP areas and 41% peribronchiolar fibrosis; inflammation, bronchiolar metaplasia, and vascular changes were more frequent in UIP/IPF explants; and Desquamative Interstitial Pneumonia (DIP)-like areas were not common (18%-27%). Numerous large airspace enlargements with fibrosis were frequent in UIP/IPF explants (59%). On HRCT, honeycombing was observed in 95% of the cases and ground-glass opacities in 53%, correlating with NSIP areas or acute exacerbation at histology. Six patients had combined IPF and emphysema. Lesions were more severe in UIP/IPF explants, reflecting the worsening of the disease. Usual interstitial pneumonia/IPF explants more frequently presented with confounding lesions such as NSIP areas, peribronchiolar fibrosis, and airspace enlargements with fibrosis sometimes associated with emphysema.

  8. Pathological features and diagnosis of intraductal papillary mucinous neoplasm of the pancreas.

    PubMed

    Castellano-Megías, Víctor M; Andrés, Carolina Ibarrola-de; López-Alonso, Guadalupe; Colina-Ruizdelgado, Francisco

    2014-09-15

    Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a noninvasive epithelial neoplasm of mucin-producing cells arising in the main duct (MD) and/or branch ducts (BD) of the pancreas. Involved ducts are dilated and filled with neoplastic papillae and mucus in variable intensity. IPMN lacks ovarian-type stroma, unlike mucinous cystic neoplasm, and is defined as a grossly visible entity (≥ 5 mm), unlike pancreatic intraepithelial neoplasm. With the use of high-resolution imaging techniques, very small IPMNs are increasingly being identified. Most IPMNs are solitary and located in the pancreatic head, although 20%-40% are multifocal. Macroscopic classification in MD type, BD type and mixed or combined type reflects biological differences with important prognostic and preoperative clinical management implications. Based on cytoarchitectural atypia, IPMN is classified into low-grade, intermediate-grade and high-grade dysplasia. Based on histological features and mucin (MUC) immunophenotype, IPMNs are classified into gastric, intestinal, pancreatobiliary and oncocytic types. These different phenotypes can be observed together, with the IPMN classified according to the predominant type. Two pathways have been suggested: gastric phenotype corresponds to less aggressive uncommitted cells (MUC1 -, MUC2 -, MUC5AC +, MUC6 +) with the capacity to evolve to intestinal phenotype (intestinal pathway) (MUC1 -, MUC2 +, MUC5AC +, MUC6 - or weak +) or pancreatobiliary /oncocytic phenotypes (pyloropancreatic pathway) (MUC1 +, MUC 2-, MUC5AC +, MUC 6 +) becoming more aggressive. Prognosis of IPMN is excellent but critically worsens when invasive carcinoma arises (about 40% of IPMNs), except in some cases of minimal invasion. The clinical challenge is to establish which IPMNs should be removed because of their higher risk of developing invasive cancer. Once resected, they must be extensively sampled or, much better, submitted in its entirety for microscopic study to

  9. Clinical, pathological and biological features associated with BRAF mutations in non-small cell lung cancer

    PubMed Central

    Cardarella, Stephanie; Ogino, Atsuko; Nishino, Mizuki; Butaney, Mohit; Shen, Jeanne; Lydon, Christine; Yeap, Beow Y.; Sholl, Lynette M.; Johnson, Bruce E.; Jänne, Pasi A.

    2013-01-01

    Purpose BRAF mutations are found in a subset of non-small cell lung cancers (NSCLCs). We examined the clinical characteristics and treatment outcomes of patients with NSCLC harboring BRAF mutations. Experimental Design Using DNA sequencing, we successfully screened 883 NSCLC patients for BRAF mutations between 7/1/09 and 7/16/12. Baseline characteristics and treatment outcomes were compared between patients with and without BRAF mutations. Wild type controls consisted of NSCLC patients without a somatic alteration in BRAF, KRAS, EGFR, and ALK. In vitro studies assessed the biological properties of selected non-V600E BRAF mutations identified from NSCLC patients. Results Of 883 tumors screened, 36 (4%) harbored BRAF mutations (V600E: 18; non-V600E: 18) and 257 were wild type for BRAF, EGFR, KRAS, and ALK negative. Twenty-nine of the 36 BRAF mutant patients were smokers. There were no distinguishing clinical features between BRAF mutant and wild type patients. Advanced NSCLC patients with BRAF mutations and wild type tumors showed similar response rates and progression-free survival (PFS) to platinum-based combination chemotherapy and no difference in overall survival. Within the BRAF cohort, patients with V600E mutated tumors had a shorter PFS to platinum-based chemotherapy compared to those with non-V600E mutations, although this did not reach statistical significance (4.1 versus 8.9 months; P=0.297). We identified five BRAF mutations not previously reported in NSCLC; two of the five were associated with increased BRAF kinase activity. Conclusions BRAF mutations occur in 4% of NSCLCs and half are non-V600E. Prospective trials are ongoing to validate BRAF as a therapeutic target in NSCLC. PMID:23833300

  10. Pathological features and diagnosis of intraductal papillary mucinous neoplasm of the pancreas

    PubMed Central

    Castellano-Megías, Víctor M; Andrés, Carolina Ibarrola-de; López-Alonso, Guadalupe; Colina-Ruizdelgado, Francisco

    2014-01-01

    Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a noninvasive epithelial neoplasm of mucin-producing cells arising in the main duct (MD) and/or branch ducts (BD) of the pancreas. Involved ducts are dilated and filled with neoplastic papillae and mucus in variable intensity. IPMN lacks ovarian-type stroma, unlike mucinous cystic neoplasm, and is defined as a grossly visible entity (≥ 5 mm), unlike pancreatic intraepithelial neoplasm. With the use of high-resolution imaging techniques, very small IPMNs are increasingly being identified. Most IPMNs are solitary and located in the pancreatic head, although 20%-40% are multifocal. Macroscopic classification in MD type, BD type and mixed or combined type reflects biological differences with important prognostic and preoperative clinical management implications. Based on cytoarchitectural atypia, IPMN is classified into low-grade, intermediate-grade and high-grade dysplasia. Based on histological features and mucin (MUC) immunophenotype, IPMNs are classified into gastric, intestinal, pancreatobiliary and oncocytic types. These different phenotypes can be observed together, with the IPMN classified according to the predominant type. Two pathways have been suggested: gastric phenotype corresponds to less aggressive uncommitted cells (MUC1 -, MUC2 -, MUC5AC +, MUC6 +) with the capacity to evolve to intestinal phenotype (intestinal pathway) (MUC1 -, MUC2 +, MUC5AC +, MUC6 - or weak +) or pancreatobiliary /oncocytic phenotypes (pyloropancreatic pathway) (MUC1 +, MUC 2-, MUC5AC +, MUC 6 +) becoming more aggressive. Prognosis of IPMN is excellent but critically worsens when invasive carcinoma arises (about 40% of IPMNs), except in some cases of minimal invasion. The clinical challenge is to establish which IPMNs should be removed because of their higher risk of developing invasive cancer. Once resected, they must be extensively sampled or, much better, submitted in its entirety for microscopic study to

  11. Long Noncoding RNA H19 in Digestive System Cancers: A Meta-Analysis of Its Association with Pathological Features.

    PubMed

    Lin, Yang; Xu, Lijian; Wei, Wei; Zhang, Xiaohui; Ying, Rongchao

    2016-01-01

    Long noncoding RNA (lncRNA) H19 has been reported to be upregulated in malignant digestive tumors, but its clinical relevance is not yet established. The meta-analysis was to investigate the association between H19 expression and pathological features of digestive system cancers. The databases of PubMed, EMBase, Web of Science, CNKI, and WanFang were searched for the related studies. A total of 478 patients from 6 studies were finally included. The meta-analysis showed that the patient group of high H19 expression had a higher risk of poorly differentiated grade, deep tumor invasion (T2 stage or more), lymph node metastasis, and advanced TNM stage than the group of low H19 expression, although there was no difference between them in terms of distant metastasis. Therefore, the high expression of lncRNA H19 might predict poor oncological outcomes of patients with digestive system cancers.

  12. Oral squamous cell carcinoma: clinicopathological features from 346 cases from a single Oral Pathology service during an 8-year period

    PubMed Central

    PIRES, Fábio Ramôa; RAMOS, Amanda Barreto; de OLIVEIRA, Jade Bittencourt Coutinho; TAVARES, Amanda Serra; da LUZ, Priscilla Silva Ribeiro; dos SANTOS, Teresa Cristina Ribeiro Bartholomeu

    2013-01-01

    Epidemiological data from oral squamous cell carcinoma (OSCC) is mostly derived from North American, European and East Asian populations. Objective The aim of this study was to report the demographic and clinicopathological features from OSCC diagnosed in an Oral Pathology service in southeastern Brazil in an 8-year period. Material and Methods All OSCC diagnosed from 2005 to 2012 were reviewed, including histological analysis of all hematoxylin and eosin stained slides and review of all demographic and clinical information from the laboratory records. Results A total of 346 OSCC was retrieved and males represented 67% of the sample. Mean age of the patients was 62.3 years-old and females were affected a decade older than males (p<0.001). Mean time of complaint with the tumors was 10 months and site distribution showed that the border of the tongue (37%), alveolar mucosa/gingiva (20%) and floor of mouth/ventral tongue (19%) were the most common affected sites. Mean size of the tumors was 3.4 cm, with no differences for males and females (p=0.091) and males reported both tobacco and alcohol consumption more frequently than females. Histological grade of the tumors revealed that 27%, 40% and 21% of the tumors were, respectively, classified as well-, moderately- and poorly-differentiated OSCC, 26 cases (7.5%) were microinvasive OSCC and 17 cases were OSCC variants. OSCC in males mostly affected the border of tongue, floor of mouth/ventral tongue and alveolar mucosa/gingival, while they were more frequent on the border of tongue, alveolar mucosa/gingival and buccal mucosa/buccal sulcus in females (p=0.004). Conclusions The present data reflect the epidemiological characteristics of OSCC diagnosed in a public Oral Pathology laboratory in southeastern Brazil and have highlighted several differences in clinicopathological features when comparing male and female OSCC-affected patients. PMID:24212993

  13. Triggers, risk factors and clinico-pathological features of urticaria in dogs - a prospective observational study of 24 cases.

    PubMed

    Rostaher, Ana; Hofer-Inteeworn, Natalie; Kümmerle-Fraune, Claudia; Fischer, Nina Maria; Favrot, Claude

    2017-02-01

    Urticaria and anaphylaxis are frequently encountered in veterinary practice, but little is known about the causes and relative frequencies of these reactions. This study was designed to improve current knowledge on the triggers, risk factors and clinico-pathological features of urticaria. Twenty four dogs with signs of urticaria with or without anaphylaxis. The study included dogs with cutaneous immediate-type hypersensitivity reactions. The cases were grouped by clinical severity into either an urticaria or an anaphylaxis group. All treatments and diagnostic tests (haematology, biochemical profile, allergy investigation) were recorded. A causality algorithm for urticaria and anaphylaxis (ALUA) was designed to determine the probability of the identified triggers and cofactors. Disease incidence, breed, age and gender predispositions were evaluated statistically. Sixteen of 24 urticaria cases were associated with anaphylaxis whilst 8 of 24 were confined to the skin. The annual hospital incidence was 0.12%. Females seemed to be over-represented (2.4:1) and most of the dog breeds were pure breed (22 of 24), with Rhodesian ridgeback, boxer, beagle, Jack Russell terrier, French bulldog and Vizslas over-represented. In addition to skin lesions, the most frequently and severely affected organ systems were the gastrointestinal and cardiovascular systems. The predominant blood abnormalities were elevated lipase and alanine aminotransferase values. Insects, food and drugs were the most commonly identified triggers. To the best of our knowledge, this is the first study describing the trigger factors and clinico-pathological features of dogs with urticaria in veterinary medicine. Insects, food and drugs were the most frequently detected triggers. © 2016 ESVD and ACVD.

  14. RUNX1 mutations in acute myeloid leukemia are associated with distinct clinico-pathologic and genetic features.

    PubMed

    Gaidzik, V I; Teleanu, V; Papaemmanuil, E; Weber, D; Paschka, P; Hahn, J; Wallrabenstein, T; Kolbinger, B; Köhne, C H; Horst, H A; Brossart, P; Held, G; Kündgen, A; Ringhoffer, M; Götze, K; Rummel, M; Gerstung, M; Campbell, P; Kraus, J M; Kestler, H A; Thol, F; Heuser, M; Schlegelberger, B; Ganser, A; Bullinger, L; Schlenk, R F; Döhner, K; Döhner, H

    2016-11-01

    We evaluated the frequency, genetic architecture, clinico-pathologic features and prognostic impact of RUNX1 mutations in 2439 adult patients with newly-diagnosed acute myeloid leukemia (AML). RUNX1 mutations were found in 245 of 2439 (10%) patients; were almost mutually exclusive of AML with recurrent genetic abnormalities; and they co-occurred with a complex pattern of gene mutations, frequently involving mutations in epigenetic modifiers (ASXL1, IDH2, KMT2A, EZH2), components of the spliceosome complex (SRSF2, SF3B1) and STAG2, PHF6, BCOR. RUNX1 mutations were associated with older age (16-59 years: 8.5%; ⩾60 years: 15.1%), male gender, more immature morphology and secondary AML evolving from myelodysplastic syndrome. In univariable analyses, RUNX1 mutations were associated with inferior event-free (EFS, P<0.0001), relapse-free (RFS, P=0.0007) and overall survival (OS, P<0.0001) in all patients, remaining significant when age was considered. In multivariable analysis, RUNX1 mutations predicted for inferior EFS (P=0.01). The effect of co-mutation varied by partner gene, where patients with the secondary genotypes RUNX1(mut)/ASXL1(mut) (OS, P=0.004), RUNX1(mut)/SRSF2(mut) (OS, P=0.007) and RUNX1(mut)/PHF6(mut) (OS, P=0.03) did significantly worse, whereas patients with the genotype RUNX1(mut)/IDH2(mut) (OS, P=0.04) had a better outcome. In conclusion, RUNX1-mutated AML is associated with a complex mutation cluster and is correlated with distinct clinico-pathologic features and inferior prognosis.

  15. Experimentally induced orchitis associated with Arcanobacterium pyogenes: clinical, ultrasonographic, seminological and pathological features.

    PubMed

    Gouletsou, P G; Fthenakis, G C; Cripps, P J; Papaioannou, N; Lainas, T; Psalla, D; Amiridis, G S

    2004-10-01

    The objectives of this study were to describe the features of experimentally induced orchitis associated with Arcanobacterium pyogenes and confirm the pathogenicity of the organism for the ovine testicle. One testicle of each of nine rams was inoculated with 1.3 +/- 10(4) colony-forming-units of an A. pyogenes isolate and regular clinical, ultrasonographic, bacteriological and seminological examinations were carried out up to 204 days after challenge. The rams were sequentially euthanatized 3, 6, 9, 18, 30, 50, 71, 113 and 204 days after challenge and a gross- and histopathological examination of their testicles was performed. All rams developed clinical orchitis and general signs. The initial ultrasonographic findings were changes of size and echogenicity of the genitalia, whilst in the long-standing phase they were wider appearance of the mediastinum testis, presence of hyperechogenic foci, changes of echogenicity of the genitalia and increased echogenicity of the scrotum and tunics. The following changes in semen evaluation parametres were recorded: the pH, the percentage of dead sperms, the percentage of abnormal sperms and the number of nonsperm round cells increased, whilst the mass motility, the individual motility and the sperm concentration decreased; the following sperm defects were observed: misshapen or piriform heads, sperms with coiled tails, sperms without tail and sperms with proximal cytoplasmic droplet; at the early stages neutrophils were the prevailing nonsperm round cell type, later the proportion of immature germ cells increased and in the long-standing phase there were enlogated spermatids and leucocytes; it is noteworthy that semen evaluation parametres were restored to normal at the late stages of the disease. A. pyogenes was consistently isolated from the semen samples after challenge, as well as from the dissected genitalia. The salient post-mortem findings were: initially, subcutaneous oedema, fluid into the vaginal cavity, congested and

  16. Features of Patients With Nonfluent/Agrammatic Primary Progressive Aphasia With Underlying Progressive Supranuclear Palsy Pathology or Corticobasal Degeneration.

    PubMed

    Santos-Santos, Miguel A; Mandelli, Maria Luisa; Binney, Richard J; Ogar, Jennifer; Wilson, Stephen M; Henry, Maya L; Hubbard, H Isabel; Meese, Minerva; Attygalle, Suneth; Rosenberg, Lynne; Pakvasa, Mikhail; Trojanowski, John Q; Grinberg, Lea T; Rosen, Howie; Boxer, Adam L; Miller, Bruce L; Seeley, William W; Gorno-Tempini, Maria Luisa

    2016-06-01

    We provide novel evidence of specific clinical and neuroimaging features that may help for the in vivo prediction of underlying pathology in patients with nonfluent/agrammatic primary progressive aphasia (nfvPPA) and progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD) proved by autopsy. To characterize the neurological, cognitive, and neuroimaging features of patients with nfvPPA-in whom either PSP or CBD was eventually confirmed at autopsy-at initial presentation and at 1-year follow-up. A prospective longitudinal clinical-pathological study was conducted in a tertiary research clinic that specialized in cognitive disorders. Fourteen patients were evaluated between January 2002 and December 2014. Inclusion criteria for the study were a clinical diagnosis of nfvPPA; the availability of speech, language, and cognitive testing for at least 1 evaluation; magnetic resonance imaging within 6 months of initial evaluation; and a postmortem pathological diagnosis of PSP or CBD. Ten matched healthy control participants were also included. Clinical, cognitive, and neuroimaging longitudinal data were analyzed to characterize the whole nfvPPA-4-repeat-tau group and identify differences between nfvPPA-PSP and nfvPPA-CBD both at presentation and longitudinally. Patient groups did not differ significantly in age, sex, or handedness (nfvPPA-PSP group: median [interquartile range (IQR)] age, 74 [67-76] years; 1 of 5 male [20%]; 1 of 5 left-handed [20%]; and nfvPPA-CBD group: mean [IQR] age, 65 [54-81] years; 3 of 9 male [33%]; 0 left-handed). Motor speech impairment and left frontal white matter atrophy were the most prominent common features. At presentation, dysarthria (Motor Speech Examination median [IQR] score: nfvPPA-PSP, 4 [2-7]; nfvPPA-CBD, 0 [0-4]; P = .02), depression (Geriatric Depression Scale median [IQR] score: nfvPPA-PSP, 19 [3-28]; nfvPPA-CBD, 4 [0-16]; P = .04), and relatively selective white matter atrophy were typical of the nfv

  17. Differences in Clinical and Pathological Features of Renal Cell Carcinoma Between Japanese Patients After Kidney Transplantation and Those on Hemodialysis.

    PubMed

    Takagi, Toshio; Kondo, Tsunenori; Okumi, Masayoshi; Ishida, Hideki; Tanabe, Kazunari

    2017-04-01

    We compared the clinical features, pathological features, and prognoses of patients with renal cell carcinoma (RCC) arising in the native kidney after kidney transplantation (RCC-transplant) or on hemodialysis (RCC-HD), and analyzed predictive factors for survival at a Japanese single institution. This cohort included 42 patients in the RCC-transplant group and 467 patients in the RCC-HD group. RCC-transplant patients were younger (53 years vs. 56 years, P = 0.0358) and had less frequent symptoms (12% vs. 27%, P = 0.0344) than RCC-HD patients. Although tumor size, tumor stage, and histological subtype were not significantly different, the RCC-transplant group had less frequent multifocal occurrences and ACDK. Overall 5-year survival (RCC-transplant, 80%; RCC-hemodialysis, 76%; P = 0.3217) and 5-year cancer-specific survival (CSS; RCC-transplant, 84%; RCC-hemodialysis, 89%; P = 0.8916) were not significantly different between the two groups. Tumor stage and grade were significant predictors for CSS. Although kidney transplantation and hemodialysis were not associated with CSS, tumor stage was an independent predictor of CSS.

  18. Paget disease of the vulva: a histologic study of 56 cases correlating pathologic features and disease course.

    PubMed

    Shaco-Levy, Ruthy; Bean, Sarah M; Vollmer, Robin T; Papalas, John A; Bentley, Rex C; Selim, Maria Angelica; Robboy, Stanley J

    2010-01-01

    The Duke experience with 56 vulvar Paget disease patients was analyzed emphasizing pathologic features and controversial issues. Nearly all patients were Caucasian, and their mean age was 69 years. The average length of follow-up was 5.6 years. For each case, the following histologic features were evaluated and their association with disease course was examined: pseudo-invasion, adnexal involvement, signet-ring cells, cytologic atypia, glands formation, epidermal acantholysis, parakeratosis, hyperkeratosis, and chronic inflammation. The recurrence rate after surgical management was 32%, with epidermal acantholysis being the only statistically significant risk factor. Stromal invasion occurred in 10 patients (18%), and was not a statistically significant adverse prognostic indicator, although the single patient who died of the disease had the deepest stromal invasion. Recurrence was more common after resections with positive surgical margins, but this correlation was not statistically significant. Intraoperative frozen section analysis of the margins did not reduce recurrence rate, nor was it useful in attaining permanent free margins. The Paget cells were consistently reactive with cytokeratin-7 and carcinoembryonic antigen and unreactive with S-100 protein, HMB-45, and Mart-1. In addition, the tumor cells were usually positive for mucin stains. This profile helps distinguish vulvar Paget disease from its mimics, Pagetoid squamous cell carcinoma and malignant melanoma.

  19. Combining radiomic features with a miRNA classifier may improve prediction of malignant pathology for pancreatic intraductal papillary mucinous neoplasms.

    PubMed

    Permuth, Jennifer B; Choi, Jung; Balarunathan, Yoganand; Kim, Jongphil; Chen, Dung-Tsa; Chen, Lu; Orcutt, Sonia; Doepker, Matthew P; Gage, Kenneth; Zhang, Geoffrey; Latifi, Kujtim; Hoffe, Sarah; Jiang, Kun; Coppola, Domenico; Centeno, Barbara A; Magliocco, Anthony; Li, Qian; Trevino, Jose; Merchant, Nipun; Gillies, Robert; Malafa, Mokenge

    2016-12-27

    Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic cancer precursors incidentally discovered by cross-sectional imaging. Consensus guidelines for IPMN management rely on standard radiologic features to predict pathology, but they lack accuracy. Using a retrospective cohort of 38 surgically-resected, pathologically-confirmed IPMNs (20 benign; 18 malignant) with preoperative computed tomography (CT) images and matched plasma-based 'miRNA genomic classifier (MGC)' data, we determined whether quantitative 'radiomic' CT features (+/- the MGC) can more accurately predict IPMN pathology than standard radiologic features 'high-risk' or 'worrisome' for malignancy. Logistic regression, principal component analyses, and cross-validation were used to examine associations. Sensitivity, specificity, positive and negative predictive value (PPV, NPV) were estimated. The MGC, 'high-risk,' and 'worrisome' radiologic features had area under the receiver operating characteristic curve (AUC) values of 0.83, 0.84, and 0.54, respectively. Fourteen radiomic features differentiated malignant from benign IPMNs (p<0.05) and collectively had an AUC=0.77. Combining radiomic features with the MGC revealed an AUC=0.92 and superior sensitivity (83%), specificity (89%), PPV (88%), and NPV (85%) than other models. Evaluation of uncertainty by 10-fold cross-validation retained an AUC>0.80 (0.87 (95% CI:0.84-0.89)). This proof-of-concept study suggests a noninvasive radiogenomic approach may more accurately predict IPMN pathology than 'worrisome' radiologic features considered in consensus guidelines.

  20. Optimization of a 3D Dynamic Culturing System for In Vitro Modeling of Frontotemporal Neurodegeneration-Relevant Pathologic Features

    PubMed Central

    Tunesi, Marta; Fusco, Federica; Fiordaliso, Fabio; Corbelli, Alessandro; Biella, Gloria; Raimondi, Manuela T.

    2016-01-01

    Frontotemporal lobar degeneration (FTLD) is a severe neurodegenerative disorder that is diagnosed with increasing frequency in clinical setting. Currently, no therapy is available and in addition the molecular basis of the disease are far from being elucidated. Consequently, it is of pivotal importance to develop reliable and cost-effective in vitro models for basic research purposes and drug screening. To this respect, recent results in the field of Alzheimer’s disease have suggested that a tridimensional (3D) environment is an added value to better model key pathologic features of the disease. Here, we have tried to add complexity to the 3D cell culturing concept by using a microfluidic bioreactor, where cells are cultured under a continuous flow of medium, thus mimicking the interstitial fluid movement that actually perfuses the body tissues, including the brain. We have implemented this model using a neuronal-like cell line (SH-SY5Y), a widely exploited cell model for neurodegenerative disorders that shows some basic features relevant for FTLD modeling, such as the release of the FTLD-related protein progranulin (PRGN) in specific vesicles (exosomes). We have efficiently seeded the cells on 3D scaffolds, optimized a disease-relevant oxidative stress experiment (by targeting mitochondrial function that is one of the possible FTLD-involved pathological mechanisms) and evaluated cell metabolic activity in dynamic culture in comparison to static conditions, finding that SH-SY5Y cells cultured in 3D scaffold are susceptible to the oxidative damage triggered by a mitochondrial-targeting toxin (6-OHDA) and that the same cells cultured in dynamic conditions kept their basic capacity to secrete PRGN in exosomes once recovered from the bioreactor and plated in standard 2D conditions. We think that a further improvement of our microfluidic system may help in providing a full device where assessing basic FTLD-related features (including PRGN dynamic secretion) that may

  1. Determination of esophageal eosinophil counts and other histologic features of eosinophilic esophagitis by pathology trainees is highly accurate.

    PubMed

    Rusin, Spencer; Covey, Shannon; Perjar, Irina; Hollyfield, Johnny; Speck, Olga; Woodward, Kimberly; Woosley, John T; Dellon, Evan S

    2017-04-01

    Many studies of eosinophilic esophagitis (EoE) use expert pathology review, but it is unknown whether less experienced pathologists can reliably assess EoE histology. We aimed to determine whether trainee pathologists can accurately quantify esophageal eosinophil counts and identify associated histologic features of EoE, as compared with expert pathologists. We used a set of 40 digitized slides from patients with varying degrees of esophageal eosinophilia. Each of 6 trainee pathologists underwent a teaching session and used our validated protocol to determine eosinophil counts and associated EoE findings. The same slides had previously been evaluated by expert pathologists, and these results comprised the criterion standard. Eosinophil counts were correlated, and agreement was calculated for the diagnostic threshold of 15 eosinophils per high-power field as well as for associated EoE findings. Peak eosinophil counts were highly correlated between the trainees and the criterion standard (ρ ranged from 0.87 to 0.92; P<.001 for all). Peak counts were also highly correlated between trainees (0.75-0.91; P<.001), and results were similar for mean counts. Agreement was excellent for determining if a count exceeded the diagnostic threshold (κ ranged from 0.83 to 0.89; P<.001). Agreement was very good for eosinophil degranulation (κ = 0.54-0.83; P<.01) and spongiosis (κ = 0.44-0.87; P<.01) but was lower for eosinophil microabscesses (κ = 0.37-0.64; P<.01). In conclusion, using a teaching session, digitized slide set, and validated protocol, the agreement between pathology trainees and expert pathologists for determining eosinophil counts was excellent. Agreement was very good for eosinophil degranulation and spongiosis but less so for microabscesses. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. BRAF V600E mutation in metastatic colorectal cancer: Methods of detection and correlation with clinical and pathologic features.

    PubMed

    Roma, Cristin; Rachiglio, Anna Maria; Pasquale, Raffaella; Fenizia, Francesca; Iannaccone, Alessia; Tatangelo, Fabiana; Antinolfi, Giuseppe; Parrella, Paola; Graziano, Paolo; Sabatino, Lina; Colantuoni, Vittorio; Botti, Gerardo; Maiello, Evaristo; Normanno, Nicola

    2016-08-02

    The screening for BRAF V600E mutation is employed in clinical practice for its prognostic and potentially predictive role in patients with metastatic colorectal carcinoma (mCRC). Little information is available on the sensitivity and specificity of the testing methods to detect this mutation in CRC. By using serial dilution of BRAF mutant DNA with wild type DNA, we found that the sensitivity of allelic discrimination-Real Time PCR was higher than PCR-Sequencing (10% vs 20%). In agreement, the Real Time PCR assay displayed increased analytical sensitivity in detecting the BRAF V600E mutation as compared with PCR-Sequencing in a cohort of 510 consecutive CRCs (21 vs 16 cases). Targeted resequencing demonstrated that all cases negative by PCR-Sequencing had an allelic frequency of the BRAF mutation <20%, thus suggesting tumor heterogeneity. The association of BRAF mutations with clinical and pathological features was assessed next in a cohort of 840 KRAS exon 2 wild type CRC patients screened with the Real Time PCR assay. The BRAF V600E mutation frequency in this cohort was 7.8% that increased to 33.4% in females over 70 y of age with right-sided tumor location. BRAF mutations were also detected in 4.4% of male patients with left-sided tumors and aged <70 y. Fourteen of 61 (22.9%) BRAF V600E mutation bearing patients exhibited microsatellite instability (MSI) as assessed by T17 mononucleotide sequence within intron 8 of HSP110. Our study indicates that Real Time PCR-based assays are more sensitive than PCR-Sequencing to detect the BRAF V600E mutation in CRC and that BRAF mutations screening should not be restricted to selected patients on the basis of the clinical-pathological characteristics.

  3. Expression profile of SIX family members correlates with clinic-pathological features and prognosis of breast cancer

    PubMed Central

    Xu, Han-Xiao; Wu, Kong-Ju; Tian, Yi-Jun; Liu, Qian; Han, Na; He, Xue-Lian; Yuan, Xun; Wu, Gen Sheng; Wu, Kong-Ming

    2016-01-01

    Abstract Sineoculis homeobox homolog (SIX) family proteins, including SIX1, SIX2, SIX3, SIX4, SIX5, and SIX6, have been implicated in the initiation and progression of breast cancer, but the role of each member in breast tumor is not fully understood. We conducted a systematic review and meta-analysis to evaluate the association between the mRNA levels of all 6 members and clinic-pathological characteristics and clinical outcome of breast cancer patients based on the PRISMA statement criteria. ArrayExpress and Oncomine were searched for eligible databases published up to December 10, 2015. The association between the mRNA expression of SIX family members and clinic-pathological features and prognosis was measured by the odds ratio (OR), hazard ratio (HR), and the corresponding 95% confidence interval (CI), respectively. All statistical analyses were performed using STATA software. In total, 20 published Gene Expression Omnibus (GEO) databases with 3555 patients were analyzed. Our analysis revealed that patients with SIX1 overexpression had worse overall survival (OS) (HR: 1.28, 95% CI: 1.03–1.58) and shorter relapse-free survival (RFS) (HR: 1.28, 95% CI: 1.05–1.56), and much worse prognosis for luminal breast cancer patients with SIX1 overexpression (OS: HR: 1.64, 95% CI: 1.13–2.39; RFS: HR: 1.43, 95% CI: 1.06–1.93). We found that patients with higher SIX2 level had shorter time to both relapse and metastasis. However, high SIX3 mRNA level was a protective factor for OS and RFS of basal-like breast cancer patients. Our study suggested that members of SIX family played distinct roles in breast cancer. Detailed analysis of the expression of the SIX family members might provide useful information to predict breast cancer progression and prognosis. PMID:27399099

  4. Clinical and pathological features of familial frontotemporal dementia caused by C9ORF72 mutation on chromosome 9p.

    PubMed

    Hsiung, Ging-Yuek R; DeJesus-Hernandez, Mariely; Feldman, Howard H; Sengdy, Pheth; Bouchard-Kerr, Phoenix; Dwosh, Emily; Butler, Rachel; Leung, Bonnie; Fok, Alice; Rutherford, Nicola J; Baker, Matt; Rademakers, Rosa; Mackenzie, Ian R A

    2012-03-01

    Frontotemporal dementia and amyotrophic lateral sclerosis are closely related clinical syndromes with overlapping molecular pathogenesis. Several families have been reported with members affected by frontotemporal dementia, amyotrophic lateral sclerosis or both, which show genetic linkage to a region on chromosome 9p21. Recently, two studies identified the FTD/ALS gene defect on chromosome 9p as an expanded GGGGCC hexanucleotide repeat in a non-coding region of the chromosome 9 open reading frame 72 gene (C9ORF72). In the present study, we provide detailed analysis of the clinical features and neuropathology for 16 unrelated families with frontotemporal dementia caused by the C9ORF72 mutation. All had an autosomal dominant pattern of inheritance. Eight families had a combination of frontotemporal dementia and amyotrophic lateral sclerosis while the other eight had a pure frontotemporal dementia phenotype. Clinical information was available for 30 affected members of the 16 families. There was wide variation in age of onset (mean = 54.3, range = 34-74 years) and disease duration (mean = 5.3, range = 1-16 years). Early diagnoses included behavioural variant frontotemporal dementia (n = 15), progressive non-fluent aphasia (n = 5), amyotrophic lateral sclerosis (n = 9) and progressive non-fluent aphasia-amyotrophic lateral sclerosis (n = 1). Heterogeneity in clinical presentation was also common within families. However, there was a tendency for the phenotypes to converge with disease progression; seven subjects had final clinical diagnoses of both frontotemporal dementia and amyotrophic lateral sclerosis and all of those with an initial progressive non-fluent aphasia diagnosis subsequently developed significant behavioural abnormalities. Twenty-one affected family members came to autopsy and all were found to have transactive response DNA binding protein with M(r) 43 kD (TDP-43) pathology in a wide neuroanatomical distribution. All had involvement of the extramotor

  5. Huntington's disease and Huntington's disease-like syndromes: an overview.

    PubMed

    Gövert, Felix; Schneider, Susanne A

    2013-08-01

    The differential diagnosis of chorea syndromes may be complex and includes various genetic disorders such as Huntington's disease and mimicking disorders called Huntington's disease-like (HDL) phenotypes. To familiarize clinicians with these (in some cases very rare) conditions we will summarize the main characteristics. HDL disorders are rare and account for about 1% of cases presenting with a Huntington's disease phenotype. They share overlapping clinical features, so making the diagnosis purely on clinical grounds may be challenging, however presence of certain characteristics may be a clue (e.g. prominent orofacial involvement in neuroferritinopathy etc.), Information of ethnic descent will also guide genetic work-up [HDL2 in Black Africans; dentatorubral-pallidoluysian atrophy (DRPLA) in Japanese etc.], Huntington's disease, the classical HDL disorders (except HDL3) and DRPLA are repeat disorders with anticipation effect and age-dependent phenotype in some, but genetic underpinnings may be more complicated in the other chorea syndromes. With advances in genetics more and more rare diseases are disentangled, allowing molecular diagnoses in a growing number of choreic patients. Hopefully, with better understanding of their pathophysiology we are moving towards mechanistic therapies.

  6. Optimal selection of wavelet-packet-based features using genetic algorithm in pathological assessment of patients' speech signal with unilateral vocal fold paralysis.

    PubMed

    Behroozmand, Roozbeh; Almasganj, Farshad

    2007-04-01

    Unilateral vocal fold paralysis (UVFP) is one of the most severe types of neurogenic laryngeal disorder in which the patients, due to their vocal cords malfunction, are confronted by some serious problems. As the effect of such pathologies would be significantly evident in the reduced quality and feature variation of dysphonic voices, this study is designed to scrutinize the piecewise variation of some specific types of these features, known as energy and entropy, all over the frequency range of pathological speech signals. In order to do so, the wavelet-packet coefficients, in five consecutive levels of decomposition, are used to extract the energy and entropy measures at different spectral sub-bands. As the decomposition procedure leads to a set of high-dimensional feature vectors, genetic algorithm is invoked to search for a group of optimal sub-band indexes for which the extracted features result in the highest recognition rate for pathological and normal subjects' classification. The results of our simulations, using support vector machine classifier, show that the highest recognition rate, for both optimized energy and entropy measures, is achieved at the fifth level of wavelet-packet decomposition. It is also found that entropy feature, with the highest recognition rate of 100% vs. 93.62% for energy, is more prominent in discriminating patients with UVFP from normal subjects. Therefore, entropy feature, in comparison with energy, demonstrates a more efficient description of such pathological voices and provides us a valuable tool for clinical diagnosis of unilateral laryngeal paralysis.

  7. Concordance of Pathologic Features Between Metastatic Sites and the Primary Tumor in Surgically Resected Metastatic Renal Cell Carcinoma.

    PubMed

    Psutka, Sarah P; Cheville, John C; Costello, Brian A; Stewart-Merrill, Suzanne B; Lohse, Christine M; Leibovich, Bradley C; Boorjian, Stephen A; Thompson, R Houston

    2016-10-01

    To evaluate the concordance of pathologic features in metastatic renal cell carcinoma (RCC) between the primary nephrectomy and metastasectomy specimens. Primary nephrectomy (n = 454) and matched metastasectomy specimens (n = 680) from patients treated between 1970 and 2009 for RCC were re-reviewed by 1 urologic pathologist in a blinded fashion. RCC histologic subtype, grade, coagulative necrosis, and the presence of sarcomatoid differentiation were compared between the primary and the metastatic tumor with kappa statistics. Concordance with the primary tumor was observed for subtype in 647 (95%, kappa = 0.71) of the metastases, for grade in 411 (60%, kappa = 0.35), necrosis in 460 (68%, kappa = 0.32), and sarcomatoid differentiation in 643 (95%, kappa = 0.60). Upgrading was observed in 100%, 63%, and 13% of patients with grades 1, 2, and 3 primary tumors, respectively (no patient had a grade 1 metastatic lesion). Metastatic tumors treated with metastasectomy within 30 days of nephrectomy (n = 145) had similar rates of concordant subtype, necrosis, and sarcomatoid differentiation to those undergoing metastasectomy beyond 30 days from nephrectomy (P >.05 for all), but had higher rates of concordant grade (71% vs 58%, P = .003). Pre-metastasectomy exposure to systemic targeted or immunotherapy was not associated with a change in concordance of histopathologic features. Among 454 surgically managed metastatic RCC patients, we observed a high degree of concordance for histologic subtype and sarcomatoid differentiation, and varying degrees of discordance for grade and coagulative tumor necrosis, between primary and metastatic tumors. Further investigation is warranted to understand the biologic and therapeutic implications of these observations. Published by Elsevier Inc.

  8. Correlation of pathologic features with CpG island methylator phenotype (CIMP) by quantitative DNA methylation analysis in colorectal carcinoma.

    PubMed

    Ogino, Shuji; Odze, Robert D; Kawasaki, Takako; Brahmandam, Mohan; Kirkner, Gregory J; Laird, Peter W; Loda, Massimo; Fuchs, Charles S

    2006-09-01

    Extensive gene promoter methylation in colorectal carcinoma has been termed the CpG island methylator phenotype (CIMP). Previous studies on CIMP used primarily methylation-specific polymerase chain reaction (PCR), which, unfortunately, may detect low levels of methylation that has little or no biological significance. Utilizing quantitative real-time PCR (MethyLight), we measured DNA methylation in a panel of 5 CIMP-specific gene promoters (CACNA1G, CDKN2A (p16), CRABP1, MLH1, and NEUROG1) in 459 colorectal carcinomas obtained from 2 large prospective cohort studies. CIMP was defined as tumors that showed methylation in >or=4/5 promoters. CIMP was significantly associated with the presence of mucinous or signet ring cell morphology, marked Crohn's-like lymphoid reaction, tumor infiltrating lymphocytes, marked peritumoral lymphocytic reaction, tumor necrosis, tumor cell sheeting, and poor differentiation. All these features have previously been associated with microsatellite instability (MSI). Therefore, we divided the 459 colorectal carcinomas into 6 subtypes, namely, MSI-high (MSI-H)/CIMP, MSI-H/non-CIMP, MSI-low (MSI-L)/CIMP, MSI-L/non-CIMP, microsatellite stable/CIMP, and micro satellite sstable/non-CIMP. Compared with MSI-H/non-CIMP, MSI-H/CIMP was associated with marked tumor infiltrating lymphocytes, tumor necrosis, sheeting, and poor differentiation (all Ppathologic features that have previously been shown to be associated with MSI are also significantly associated with CIMP. Both MSI and CIMP appear to play a role in the pathogenesis of specific morphologic patterns of colorectal carcinoma.

  9. Targeted disruption of the Hexa gene results in mice with biochemical and pathologic features of Tay-Sachs disease

    SciTech Connect

    Proia, R.L.; Yamanaka, S.; Johnson, M.D.

    1994-09-01

    Tay-Sachs disease, the prototype of the G{sub M2} gangliosidoses, is a catastrophic neurodegenerative disorder of infancy. The disease is caused by mutations in the HEXA gene resulting in an absence of the lysosomal enzyme, {beta}-hexosaminidase A. As consequence of the enzyme deficiency, G{sub M2} ganglioside accumulates progressively, beginning early in fetal life, to excessive amounts in the central nervous system (CNS). Rapid mental and motor deterioration starting in the first year of life leads to death by 2 to 4 years of age. Through the targeted disruption of the Hexa gene in embryonic stem cells, we have produced mice with biochemical and neuropathologic features of Tay-Sachs disease. The mutant mice exhibited less than 1% of normal {beta}-hexosaminidase A activity and accumulated G{sub M2} ganglioside in their CNS in an age-dependent manner. The accumulated ganglioside was stored in neurons as membranous cytoplasmic bodies characteristically found in the neurons of Tay-Sachs disease patients. At three to five months of age the mutant mice showed no apparent defects in motor or memory function. These {beta}-hexosaminidase A deficient mice should be useful for devising strategies to introduce functional enzymes and genes into the CNS. This model may also be valuable for studying the biochemical and pathologic changes occurring during the course of the disease.

  10. Molecular profiles of BRCA1-mutated and matched sporadic breast tumours: relation with clinico-pathological features

    PubMed Central

    Berns, E M J J; Staveren, I L van; Verhoog, L; Ouweland, A M W van de; Gelder, M Meijer-van; Meijers-Heijboer, H; Portengen, H; Foekens, J A; Dorssers, L C J; Klijn, J G M

    2001-01-01

    About 5–10% of breast cancers are hereditary; a genetically and clinically heterogeneous disease in which several susceptibility genes, including BRCA1, have been identified. While distinct tumour features can be used to estimate the likelihood that a breast tumour is caused by a BRCA1 germline mutation it is not yet possible to categorize a BRCA1 mutated tumour. The aim of the present study is to molecularly classify BRCA1 mutated breast cancers by resolving gene expression patterns of BRCA1 and matched sporadic surgical breast tumour specimens. The expression profiles of 6 frozen breast tumour tissues with a proven BRCA1 gene mutation were weighed against those from 12 patients without a known family history but who had similar clinico-pathological characteristics. In addition two fibroblast cultures, the breast cancer cell-line HCC1937 and its corresponding B-lymphoblastoid cell line (heterozygous for mutation BRCA1 5382insC) and an epithelial ovarian cancer cell line (A2780) were studied. Using a high density membrane based array for screening of RNA isolated from these samples and standard algorithms and software, we were able to distinguish subgroups of sporadic cases and a group consisting mainly of BRCA1-mutated breast tumours. Furthermore this pilot analysis revealed a gene cluster that differentially expressed genes related to cell substrate formation, adhesion, migration and cell organization in BRCA1-mutated tumours compared to sporadic breast tumours. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11506493

  11. Pathological and Clinical Features and Management of Central Nervous System Hemangioblastomas in von Hippel-Lindau Disease

    PubMed Central

    Kobayashi, Natsuki; Nakanowatari, Satoshi

    2014-01-01

    Central nervous system (CNS) hemangioblastoma is the most common manifestation of von Hippel-Lindau (VHL) disease. It is found in 70–80% of VHL patients. Hemangioblastoma is a rare form of benign vascular tumor of the CNS, accounting for 2.0% of CNS tumors. It can occur sporadically or as a familial syndrome. CNS hemangioblastomas are typically located in the posterior fossa and the spinal cord. VHL patients usually develop a CNS hemangioblastoma at an early age. Therefore, they require a special routine for diagnosis, treatment and follow-up. The surgical management of symptomatic tumors depend on many factors such as symptom, location, multiplicity, and progression of the tumor. The management of asymptomatic tumors in VHL patients are controversial since CNS hemangioblastomas grow with intermittent quiescent and rapid-growth phases. Preoperative embolization of large solid hemangioblastomas prevents perioperative hemorrhage but is not necessary in every case. Radiotherapy should be reserved for inoperable tumors. Because of complexities of VHL, a better understanding of the pathological and clinical features of hemangioblastoma in VHL is essential for its proper management. PMID:28326249

  12. Comparisons of complete RNA-2 sequences, pathological and serological features among three Japanese isolates of Arabis mosaic virus.

    PubMed

    Imura, Yoshiyuki; Oka, Hiroko; Kimata, Kosuke; Nasu, Morimasa; Nakahama, Katsuhiko; Maeda, Takanori

    2008-12-01

    Arabis mosaic virus lily and narcissus isolates (ArMV-Li and ArMV-Na) induced severe necrotic spots on Chenopodium quinoa, whereas ArMV butterbur isolate (ArMV-Bu) caused symptomless infection in the plant. The accumulation level of ArMV-Bu in upper non-inoculated leaves of C. quinoa was comparable to that of ArMV-Li or -Na. The agar gel double-diffusion test using an antiserum against ArMV-Li showed ArMV-Li was closely related to ArMV-Na, but not to ArMV-Bu. The RNAs-2 of ArMV-Li, -Na, and -Bu consist of 3707, 3709, and 3789 nucleotides, and they contain one open reading frame encoding a putative polyprotein of 1083, 1084, and 1122 amino acids, respectively. The overall identity of RNA-2 of ArMV-Li displayed more than 90% with ArMV-Na, but less than 70% with ArMV-Bu. A phylogenetic analysis of 2A sequences from ArMV isolates revealed ArMV-Bu was not categorized in any cluster. ArMV-Bu is a unique isolate from the point of view of pathological and serological features, and nucleotide sequence.

  13. Targeted disruption of the Hexa gene results in mice with biochemical and pathologic features of Tay-Sachs disease.

    PubMed Central

    Yamanaka, S; Johnson, M D; Grinberg, A; Westphal, H; Crawley, J N; Taniike, M; Suzuki, K; Proia, R L

    1994-01-01

    Tay-Sachs disease, the prototype of the GM2 gangliosidoses, is a catastrophic neurodegenerative disorder of infancy. The disease is caused by mutations in the HEXA gene resulting in an absence of the lysosomal enzyme, beta-hexosaminidase A. As a consequence of the enzyme deficiency, GM2 ganglioside accumulates progressively, beginning early in fetal life, to excessive amounts in the central nervous system. Rapid mental and motor deterioration starting in the first year of life leads to death by 2-4 years of age. Through the targeted disruption of the mouse Hexa gene in embryonic stem cells, we have produced mice with biochemical and neuropathologic features of Tay-Sachs disease. The mutant mice displayed < 1% of normal beta-hexosaminidase A activity and accumulated GM2 ganglioside in their central nervous system in an age-dependent manner. The accumulated ganglioside was stored in neurons as membranous cytoplasmic bodies characteristically found in the neurons of Tay-Sachs disease patients. At 3-5 months of age, the mutant mice showed no apparent defects in motor or memory function. These beta-hexosaminidase A-deficient mice should be useful for devising strategies to introduce functional enzyme and genes into the central nervous system. This model may also be valuable for studying the biochemical and pathologic changes occurring during the course of the disease. Images PMID:7937929

  14. Spatial-Temporal [{sup 18}F]FDG-PET Features for Predicting Pathologic Response of Esophageal Cancer to Neoadjuvant Chemoradiation Therapy

    SciTech Connect

    Tan, Shan; Kligerman, Seth; Chen, Wengen; Lu, Minh; Kim, Grace; Feigenberg, Steven; D'Souza, Warren D.; Suntharalingam, Mohan; Lu, Wei

    2013-04-01

    Purpose: To extract and study comprehensive spatial-temporal {sup 18}F-labeled fluorodeoxyglucose ([{sup 18}F]FDG) positron emission tomography (PET) features for the prediction of pathologic tumor response to neoadjuvant chemoradiation therapy (CRT) in esophageal cancer. Methods and Materials: Twenty patients with esophageal cancer were treated with trimodal therapy (CRT plus surgery) and underwent [{sup 18}F]FDG-PET/CT scans both before (pre-CRT) and after (post-CRT) CRT. The 2 scans were rigidly registered. A tumor volume was semiautomatically delineated using a threshold standardized uptake value (SUV) of ≥2.5, followed by manual editing. Comprehensive features were extracted to characterize SUV intensity distribution, spatial patterns (texture), tumor geometry, and associated changes resulting from CRT. The usefulness of each feature in predicting pathologic tumor response to CRT was evaluated using the area under the receiver operating characteristic curve (AUC) value. Results: The best traditional response measure was decline in maximum SUV (SUV{sub max}; AUC, 0.76). Two new intensity features, decline in mean SUV (SUV{sub mean}) and skewness, and 3 texture features (inertia, correlation, and cluster prominence) were found to be significant predictors with AUC values ≥0.76. According to these features, a tumor was more likely to be a responder when the SUV{sub mean} decline was larger, when there were relatively fewer voxels with higher SUV values pre-CRT, or when [{sup 18}F]FDG uptake post-CRT was relatively homogeneous. All of the most accurate predictive features were extracted from the entire tumor rather than from the most active part of the tumor. For SUV intensity features and tumor size features, changes were more predictive than pre- or post-CRT assessment alone. Conclusion: Spatial-temporal [{sup 18}F]FDG-PET features were found to be useful predictors of pathologic tumor response to neoadjuvant CRT in esophageal cancer.

  15. Pathologic features of dilated cardiomyopathy with localized noncompaction in a child with deletion 1p36 syndrome.

    PubMed

    Pearce, F Bennett; Litovsky, Silvio H; Dabal, Robert J; Robin, Nathaniel; Dure, Leon J; George, James F; Kirklin, James K

    2012-01-01

    Dilated cardiomyopathy and ventricular noncompaction have been reported in association with deletion 1p36 syndrome. Previous descriptions include echocardiographic and/or gross pathologic descriptions. There are no previous reports of microscopic findings. We report a case with descriptions of echocardiographic, gross pathologic, and microscopic findings.

  16. Clinical features and pathological joint changes in dogs with erosive immune-mediated polyarthritis: 13 cases (2004–2012)

    PubMed Central

    Shaughnessy, Magen L.; Sample, Susannah J.; Abicht, Carter; Heaton, Caitlin; Muir, Peter

    2017-01-01

    OBJECTIVE To evaluate the clinical features and pathological joint changes in dogs with erosive immune-mediated polyarthritis (IMPA). DESIGN Retrospective case series. ANIMALS 13 dogs with erosive IMPA and 66 dogs with nonerosive IMPA. PROCEDURES The medical record database of a veterinary teaching hospital was reviewed to identify dogs with IMPA that were examined between October 2004 and December 2012. For each IMPA-affected dog, information extracted from the medical record included signalment, diagnostic test results, radiographic findings, and treatments administered. Dogs were classified as having erosive IMPA if review of radiographs revealed the presence of bone lysis in multiple joints, and descriptive data were generated for those dogs. All available direct smears of synovial fluid samples underwent cytologic evaluation. The synovial fluid total nucleated cell count and WBC differential were estimated and compared between dogs with erosive IMPA and dogs with nonerosive IMPA. RESULTS 13 of 79 (16%) dogs had erosive IMPA. Dogs with erosive IMPA had a mean ± SD age of 7.1 ± 2.4 years and bodyweight of 8.3 ± 3.4 kg (18.3 ± 7.5 lb). All 13 dogs had erosive lesions in their carpal joints. The estimated median synovial fluid lymphocyte count for dogs with erosive IMPA was significantly greater than that for dogs with nonerosive IMPA. All dogs received immunosuppressive therapy with leflunomide (n = 9), prednisone (3), or prednisone-azathioprine (1). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated erosive IMPA most commonly affected the carpal joints of middle-aged small-breed dogs. Further genetic analyses and analysis of lymphocyte-subsets is warranted for dogs with erosive IMPA. Word count = 256 PMID:27823373

  17. Chromosome region maintenance 1 expression and its association with clinical pathological features in primary carcinoma of the liver

    PubMed Central

    XIE, QIAO-LING; LIU, YUE; ZHU, YING

    2016-01-01

    Liver cancer is the third leading cause of cancer-associated mortality worldwide. Recurrence and metastasis are the major factors affecting the prognosis; thus, investigation of the underlying molecular mechanisms of invasion and metastasis, and detection of novel drug target may improve the mortality rate of liver cancer patients. Chromosome region maintenance 1 (CRM1) recognizes specific leucine-rich nuclear export signal sequences, and its overexpression is associated with tumor-suppressor gene inactivation, proliferation, invasion and resistance to chemotherapy. The aim of the present study was to examine the association of CRM1 expression with the clinical and pathological features of primary liver cancer. In total, 152 cases diagnosed with liver cancer were included. CRM1 expression was detected in cancer tissues and adjacent normal tissues by immunohistochemical assay. No statistically significant difference was found between the CRM1 expression levels in tumor and adjacent normal tissues (P=0.106). However, CRM1 expression in adjacent normal tissues was higher compared with that in tumor tissues in the negative hepatitis B envelope antigen (HBeAg; P=0.029) and low differentiation (P=0.004) groups. In tumor tissues, CRM1 expression was significantly correlated with differentiation (P=0.045), whereas in adjacent normal tissues, CRM1 expression was significantly correlated with the tumor diameter (P=0.004). Therefore, it can be concluded that CRM1 is highly expressed in both tumor and adjacent normal tissues. Furthermore, CRM1 expression is associated with the tumor differentiation degree and diameter. Lower differentiation and larger tumor diameter resulted in higher CRM1 expression in adjacent normal tissues, and higher tendency for invasion and metastasis. In addition, the risk of invasion and metastasis remains in chronic hepatitis B patients with negative HBeAg. PMID:27347018

  18. Chromosome region maintenance 1 expression and its association with clinical pathological features in primary carcinoma of the liver.

    PubMed

    Xie, Qiao-Ling; Liu, Yue; Zhu, Ying

    2016-07-01

    Liver cancer is the third leading cause of cancer-associated mortality worldwide. Recurrence and metastasis are the major factors affecting the prognosis; thus, investigation of the underlying molecular mechanisms of invasion and metastasis, and detection of novel drug target may improve the mortality rate of liver cancer patients. Chromosome region maintenance 1 (CRM1) recognizes specific leucine-rich nuclear export signal sequences, and its overexpression is associated with tumor-suppressor gene inactivation, proliferation, invasion and resistance to chemotherapy. The aim of the present study was to examine the association of CRM1 expression with the clinical and pathological features of primary liver cancer. In total, 152 cases diagnosed with liver cancer were included. CRM1 expression was detected in cancer tissues and adjacent normal tissues by immunohistochemical assay. No statistically significant difference was found between the CRM1 expression levels in tumor and adjacent normal tissues (P=0.106). However, CRM1 expression in adjacent normal tissues was higher compared with that in tumor tissues in the negative hepatitis B envelope antigen (HBeAg; P=0.029) and low differentiation (P=0.004) groups. In tumor tissues, CRM1 expression was significantly correlated with differentiation (P=0.045), whereas in adjacent normal tissues, CRM1 expression was significantly correlated with the tumor diameter (P=0.004). Therefore, it can be concluded that CRM1 is highly expressed in both tumor and adjacent normal tissues. Furthermore, CRM1 expression is associated with the tumor differentiation degree and diameter. Lower differentiation and larger tumor diameter resulted in higher CRM1 expression in adjacent normal tissues, and higher tendency for invasion and metastasis. In addition, the risk of invasion and metastasis remains in chronic hepatitis B patients with negative HBeAg.

  19. CD44v6 expression in inflammatory bowel disease is associated with activity detected by endoscopy and pathological features.

    PubMed

    Camacho, F I; Muñoz, C; Sánchez-Verde, L; Sáez, A I; Alcántara, M; Rodríguez, R

    1999-08-01

    Overexpression of CD44v6 in colon crypt epithelial cells has been suggested to have diagnostic potential in differentiating ulcerative colitis from other forms of colon inflammation, including Crohn's disease. Our aim was to determine the value of CD44v6 expression in inflammatory bowel disease (IBD) and to look for possible associations between CD44v6 expression and activity of this disease. CD44v6 expression was studied using immunohistochemical techniques in 100 surgical and endoscopic colon samples of ulcerative colitis (n = 71) and Crohn's disease (n = 29), and in every case disease activity was studied by endoscopy and microscopic examination. Fifty-five of 71 (77.5%) samples of ulcerative colitis showed monoclonal antibody 2F10 stained colon epithelium, as did 16 of 29 (55.2%) samples of Crohn's disease. CD44v6 was detected in 88.2% (15 of 17) of cases of IBD with severe disease activity and in 100% of eight cases of severe ulcerative colitis. Our study showed a strong association between CD44v6 expression and the activity of IBD (P = 0.007). CD44v6 expression in IBD is significantly associated with activity detected by means of endoscopy and pathological features. Our data suggest that CD44v6 expression may have some usefulness in conjunction with other factors as a means of evaluating the disease activity. Moreover, CD44v6 expression was higher in ulcerative colitis than Crohn's disease (P = 0.02), although this does not confirm the utility of monoclonal antibody 2F10 in differential diagnosis between ulcerative colitis and Crohn's disease, as there was a notable percentage of positive samples of Crohn's disease.

  20. Combining radiomic features with a miRNA classifier may improve prediction of malignant pathology for pancreatic intraductal papillary mucinous neoplasms

    PubMed Central

    Permuth, Jennifer B.; Choi, Jung; Balarunathan, Yoganand; Kim, Jongphil; Chen, Dung-Tsa; Chen, Lu; Orcutt, Sonia; Doepker, Matthew P.; Gage, Kenneth; Zhang, Geoffrey; Latifi, Kujtim; Hoffe, Sarah; Jiang, Kun; Coppola, Domenico; Centeno, Barbara A.; Magliocco, Anthony; Li, Qian; Trevino, Jose; Merchant, Nipun; Gillies, Robert; Malafa, Mokenge

    2016-01-01

    Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic cancer precursors incidentally discovered by cross-sectional imaging. Consensus guidelines for IPMN management rely on standard radiologic features to predict pathology, but they lack accuracy. Using a retrospective cohort of 38 surgically-resected, pathologically-confirmed IPMNs (20 benign; 18 malignant) with preoperative computed tomography (CT) images and matched plasma-based ‘miRNA genomic classifier (MGC)’ data, we determined whether quantitative ‘radiomic’ CT features (+/- the MGC) can more accurately predict IPMN pathology than standard radiologic features ‘high-risk’ or ‘worrisome’ for malignancy. Logistic regression, principal component analyses, and cross-validation were used to examine associations. Sensitivity, specificity, positive and negative predictive value (PPV, NPV) were estimated. The MGC, ‘high-risk,’ and ‘worrisome’ radiologic features had area under the receiver operating characteristic curve (AUC) values of 0.83, 0.84, and 0.54, respectively. Fourteen radiomic features differentiated malignant from benign IPMNs (p<0.05) and collectively had an AUC=0.77. Combining radiomic features with the MGC revealed an AUC=0.92 and superior sensitivity (83%), specificity (89%), PPV (88%), and NPV (85%) than other models. Evaluation of uncertainty by 10-fold cross-validation retained an AUC>0.80 (0.87 (95% CI:0.84-0.89)). This proof-of-concept study suggests a noninvasive radiogenomic approach may more accurately predict IPMN pathology than ‘worrisome’ radiologic features considered in consensus guidelines. PMID:27589689

  1. Clinical, diagnostic and pathologic features of presumptive cases of Chlamydia pecorum-associated arthritis in Australian sheep flocks.

    PubMed

    Walker, Evelyn; Moore, Cecily; Shearer, Patrick; Jelocnik, Martina; Bommana, Sankhya; Timms, Peter; Polkinghorne, Adam

    2016-09-08

    Arthritis is an economically significant disease in lambs and is usually the result of a bacterial infection. One of the known agents of this disease is Chlamydia pecorum, a globally recognised livestock pathogen associated with several diseases in sheep, cattle and other hosts. Relatively little published information is available on the clinical, diagnostic and pathologic features of C. pecorum arthritis in sheep, hindering efforts to enhance our understanding of this economically significant disease. In this case series, a combination of standard diagnostic testing used routinely by veterinarians, such as the Chlamydia complement fixation text (CFT), veterinary clinical examinations, and additional screening via C. pecorum specific qPCR was used to describe putative chlamydial infections in five sheep flocks with suspected ovine arthritis. Five separate cases involving multiple lambs (aged six to ten months) of different breeds with suspected C. pecorum arthritis are presented. In two of the five cases, arthritic lambs exhibited marked depression and lethargy. Arthritis with concurrent conjunctivitis was present in four out of five lamb flocks examined. Chlamydia CFT demonstrated medium to high positive antibody titres in all flocks examined. C. pecorum shedding was evident at multiple sites including the conjunctiva, rectum and vagina, as determined via qPCR. Two of the five flocks received antimicrobials and all flocks recovered uneventfully regardless of treatment. This case series highlights the features a field veterinarian may encounter in cases of suspected ovine chlamydial arthritis. Our analysis suggests a presumptive diagnosis of chlamydial arthritis in lambs can be made when there is evidence of joint stiffness with or without synovial effusion and elevated chlamydia antibody titres. C. pecorum-specific qPCR was found to be a useful ancillary diagnostic tool, detecting Chlamydia positivity in low or negative CFT titre animals. Variables such as symptom

  2. Features and machine learning classification of connected speech samples from patients with autopsy proven Alzheimer's disease with and without additional vascular pathology.

    PubMed

    Rentoumi, Vassiliki; Raoufian, Ladan; Ahmed, Samrah; de Jager, Celeste A; Garrard, Peter

    2014-01-01

    Mixed vascular and Alzheimer-type dementia and pure Alzheimer's disease are both associated with changes in spoken language. These changes have, however, seldom been subjected to systematic comparison. In the present study, we analyzed language samples obtained during the course of a longitudinal clinical study from patients in whom one or other pathology was verified at post mortem. The aims of the study were twofold: first, to confirm the presence of differences in language produced by members of the two groups using quantitative methods of evaluation; and secondly to ascertain the most informative sources of variation between the groups. We adopted a computational approach to evaluate digitized transcripts of connected speech along a range of language-related dimensions. We then used machine learning text classification to assign the samples to one of the two pathological groups on the basis of these features. The classifiers' accuracies were tested using simple lexical features, syntactic features, and more complex statistical and information theory characteristics. Maximum accuracy was achieved when word occurrences and frequencies alone were used. Features based on syntactic and lexical complexity yielded lower discrimination scores, but all combinations of features showed significantly better performance than a baseline condition in which every transcript was assigned randomly to one of the two classes. The classification results illustrate the word content specific differences in the spoken language of the two groups. In addition, those with mixed pathology were found to exhibit a marked reduction in lexical variation and complexity compared to their pure AD counterparts.

  3. Evaluation of wavelet spectral features in pathological detection and discrimination of yellow rust and powdery mildew in winter wheat with hyperspectral reflectance data

    NASA Astrophysics Data System (ADS)

    Shi, Yue; Huang, Wenjiang; Zhou, Xianfeng

    2017-04-01

    Hyperspectral absorption features are important indicators of characterizing plant biophysical variables for the automatic diagnosis of crop diseases. Continuous wavelet analysis has proven to be an advanced hyperspectral analysis technique for extracting absorption features; however, specific wavelet features (WFs) and their relationship with pathological characteristics induced by different infestations have rarely been summarized. The aim of this research is to determine the most sensitive WFs for identifying specific pathological lesions from yellow rust and powdery mildew in winter wheat, based on 314 hyperspectral samples measured in field experiments in China in 2002, 2003, 2005, and 2012. The resultant WFs could be used as proxies to capture the major spectral absorption features caused by infestation of yellow rust or powdery mildew. Multivariate regression analysis based on these WFs outperformed conventional spectral features in disease detection; meanwhile, a Fisher discrimination model exhibited considerable potential for generating separable clusters for each infestation. Optimal classification returned an overall accuracy of 91.9% with a Kappa of 0.89. This paper also emphasizes the WFs and their relationship with pathological characteristics in order to provide a foundation for the further application of this approach in monitoring winter wheat diseases at the regional scale.

  4. Isolation Housing Exacerbates Alzheimer's Disease-Like Pathophysiology in Aged APP/PS1 Mice.

    PubMed

    Huang, Huang; Wang, Linmei; Cao, Min; Marshall, Charles; Gao, Junying; Xiao, Na; Hu, Gang; Xiao, Ming

    2015-01-07

    Alzheimer's disease is a neurodegenerative disease characterized by gradual declines in social, cognitive, and emotional functions, leading to a loss of expected social behavior. Social isolation has been shown to have adverse effects on individual development and growth as well as health and aging. Previous experiments have shown that social isolation causes an early onset of Alzheimer's disease-like phenotypes in young APP695/PS1-dE9 transgenic mice. However, the interactions between social isolation and Alzheimer's disease still remain unknown. Seventeen-month-old male APP695/PS1-dE9 transgenic mice were either singly housed or continued group housing for 3 months. Then, Alzheimer's disease-like pathophysiological changes were evaluated by using behavioral, biochemical, and pathological analyses. Isolation housing further promoted cognitive dysfunction and Aβ plaque accumulation in the hippocampus of aged APP695/PS1-dE9 transgenic mice, associated with increased γ-secretase and decreased neprilysin expression. Furthermore, exacerbated hippocampal atrophy, synapse and myelin associated protein loss, and glial neuroinflammatory reactions were observed in the hippocampus of isolated aged APP695/PS1-dE9 transgenic mice. The results demonstrate that social isolation exacerbates Alzheimer's disease-like pathophysiology in aged APP695/PS1-dE9 transgenic mice, highlighting the potential role of group life for delaying or counteracting the Alzheimer's disease process. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  5. Ethanol extract of the tuber of Alisma orientale reduces the pathologic features in a chronic obstructive pulmonary disease mouse model.

    PubMed

    Kim, Kyun Ha; Song, Hyuk-Hwan; Ahn, Kyung-Seop; Oh, Sei-Ryang; Sadikot, Ruxana T; Joo, Myungsoo

    2016-07-21

    The tuber of Alismataceae Alisma orientale Juzepzuk has been prescribed as a remedy for treating the diseases associated with body fluid dysfunction such as edema and inflammatory lung diseases. Chronic obstructive pulmonary disease (COPD) is a debilitating, inflammatory lung disease without effective treatment. Along with persistent inflammation, autophagy has been recently reported to contribute to COPD. Here, by employing a murine model, we examined whether the tuber of the plant is effective against COPD MATERIALS AND METHODS: The ethanol extract of the tuber of A. orientale Juzepzuk (EEAO) was fingerprinted by HPLC. For the establishment of COPD lung, mice received single intratracheal (i.t.) spraying of elastase and LPS per week for 2 weeks. After approximated to the dose prescribed typically to patients, EEAO was administered to the lung 2h after each LPS treatment. Morphometric analyses, semi-quantitative RT-PCR, and western blot were performed to evaluate the effects of EEAO on emphysema, inflammation, and autophagy in mouse lungs. The effect of EEAO on autophagy was also assessed by western blot at the cellular level with murine macrophages and human lung epithelial cells. When receiving i.t. elastase and LPS for 2 weeks, mice developed emphysema and inflammation in the lung. EEAO treatment, however, significantly reduced emphysema and inflammatory cell infiltration to the lung with concomitant decrease of the production of pro-inflammatory cytokines including TNF-α, IL-6, and TGF-β, signature cytokines of COPD. Unlike control mice, the lungs of the COPD mice expressed LC3-II, a biomarker for autophagy formation, which was decreased by EEAO treatment. EEAO also lowered the expression of LC3-II in murine macrophage, RAW 264.7, and human lung epithelial cell, BEAS-2B, which was associated with EEAO activating mTOR. EEAO relieved COPD pathologic features in a mouse model, which was associated with suppression of lung inflammation, emphysema, and autophagy

  6. Can Early Rehabilitation Prevent Posttraumatic Osteoarthritis in the Patellofemoral Joint after Anterior Cruciate Ligament Rupture? Understanding the Pathological Features.

    PubMed

    Chang, Nai-Jen; Shie, Ming-You; Lee, Kuan-Wei; Chou, Pei-Hsi; Lin, Chih-Chan; Chu, Chih-Jou

    2017-04-14

    Knee instability resulting from anterior cruciate ligament (ACL) rupture is a high-risk factor for posttraumatic osteoarthritis (PTOA) in the patellofemoral joint (PFJ). However, whether non-weight-bearing and weight-bearing treatments have chondroprotective effects remains unclear. Twenty-four adult New Zealand White male rabbits were employed in this study. All animals received ACL transection in the right knee and sham surgery in the left knee. The rabbits were randomly assigned to the following groups: (I) In the sedentary (SED) group, the rabbits (n = 6) were simply kept in their cage; (II) In the continuous passive motion (CPM) group, the rabbits (n = 6) performed CPM exercise for 7 days, starting from the first postoperative day; (III) In the active treadmill exercise (TRE) group, the rabbits (n = 6) performed TRE for 2 weeks; (IV) In the CPM + TRE group, the rabbits (n = 6) executed CPM exercise, followed by TRE. Two joint surfaces (the retropatella and femoral trochlear groove) were assessed at 4 weeks after operation. Although the gross appearance in each group was comparable, histological examination revealed significant differences in the articular cartilage status. The CPM group exhibited a greater thickness of articular cartilage, maintenance of tidemark continuity, abundant glycosaminoglycan (GAG), and significantly lower inflammatory cytokine 9, e.g., tumor necrosis factor-alpha (TNF-α) 0 levels, with modest cell apoptosis (i.e., caspase-3). By contrast, the TRE group displayed the worst pathological features: an irregular cartilage surface and chondrocyte disorganization, reduced cartilage thickness, breakdown of the tidemark, depletion of collagen fibers, loss of GAG, and the highest levels of TNF-α and caspase-3 expression. Furthermore, the CPM + TRE group had more favorable outcomes than the SED group, indicating that suitable exercise is needed. The sham treatment displayed no variance in the changes in the two joint surfaces among groups

  7. Association between BRCA Mutation Status, Pathological Findings, and Magnetic Resonance Imaging Features in Patients with Breast Cancer at Risk for the Mutation.

    PubMed

    Noh, Jae Myoung; Han, Boo-Kyung; Choi, Doo Ho; Rhee, Sun Jung; Cho, Eun Yoon; Huh, Seung Jae; Park, Won; Park, Hyojung; Nam, Seok Jin; Lee, Jeong Eon; Kil, Won-Ho

    2013-09-01

    We investigated the relationship between BRCA mutations, pathological findings, and magnetic resonance imaging (MRI) features in patients with breast cancer at risk for the mutation. Genetic testing for BRCA mutations was performed in 275 breast cancer patients with at least one risk factor for the mutation. Using the breast imaging reporting and data system MR lexicon, morphological and kinetic features were reviewed on MRI scans of 230 tumors in 209 patients. The relationship between BRCA mutations, pathologic findings, and MRI data was examined, and disease recurrence was estimated. BRCA mutations were detected in 48 patients (23.0%), of which 21 (10.0%) were in BRCA1, and 25 (12.0%) in BRCA2. Additionally, two patients (1.0%) had mutations in both genes. Cancers in patients with BRCA1 mutations more frequently showed a higher nuclear grade (p=0.0041), and triple-negative (TN) phenotype (p<0.0001). On MRI scans, the cancers were seen as mass-type in 182 out of 230 lesions (79.1%), and nonmass type in 48 cases (20.9%). Among the features indentified by MRI, rim enhancement was significantly associated with molecular subtypes based on immunohistochemistry (p<0.0001), and nuclear grade (p=0.0387) in multiple logistic regression analysis. Rim enhancement on MRI, along with advanced pathologic N stage, was associated with increased disease recurrence (p=0.0023) based on multivariate analysis. However, the proportion of mass and nonmass tumors, and the distribution of morphological shape, margin, internal enhancement, and kinetic features assessed by MRI were not different according to BRCA mutation status. BRCA1 mutations were associated with aggressive pathological characteristics, and the TN phenotype. Rim enhancement was frequently seen on MRI scans of high-grade cancers and in the TN phenotype. And it was a significant predictor of disease recurrence. However, a direct association with BRCA mutations was not observed.

  8. In phyllodes tumour of the breast expression of c-kit but not of ALDH1A1 is associated with adverse clinico-pathological features.

    PubMed

    Chougule, Abhijit; Bal, Amanjit; Das, Ashim; Kohli, Pavneet Singh; Singh, Gurpreet

    2016-12-01

    Attempts at identification of an ideal prognostic/predictive biomarker in phyllodes tumour (PT) have not been fruitful so far. Studies evaluating c-kit expression in PT have shown contradictory results. Recently aldehyde dehydrogenase 1A1 (ALDH1A1) was proposed as a stem cell marker for malignant PT but its expression has not been studied in benign and borderline tumours. We aimed to evaluate expression and prognostic significance of c-kit and ALDH1A1 in different grades of PT. Epithelial and stromal c-kit and ALDH1A1 expression were studied in 104 PT cases (86 primary and 18 recurrent tumours) and compared with different clinico-pathological features and recurrence rates. Stromal c-kit expression at 1 % cutoff correlated with increasing tumour grade, larger tumour size, hypercellularity, nuclear atypia, stromal overgrowth, infiltrative margins and mitotic count. These associations, however, were lost with higher (5 or 10 %) cutoffs. Conversely, decreased c-kit expression in the epithelial component correlated with increasing tumour grade, regardless of the cutoffs used. Stromal ALDH1A1 expression did not have significant associations with tumour grade or other adverse clinico-pathological features, regardless of different cutoffs. None of the cases showed significant epithelial ALDH1A1 expression. Expression of c-kit was associated with poorer overall survival (p = 0.011), while ALDH1A1 expression was associated with shorter recurrence-free survival (p = 0.036). In conclusion, c-kit expression was associated with higher tumour grade and adverse clinico-pathological features. However, these associations are cutoff dependent, partly explaining the variability in previously reported studies. ALDH1A1 expression did not have significant correlations with tumour grade and adverse clinico-pathological variables.

  9. Predictive value of 18F-FDG PET and CT morphologic features for recurrence in pathological stage IA non-small cell lung cancer.

    PubMed

    Ko, Kai-Hsiung; Hsu, Hsian-He; Huang, Tsai-Wang; Gao, Hong-Wei; Cheng, Cheng-Yi; Hsu, Yi-Chih; Chang, Wei-Chou; Chu, Chi-Ming; Chen, Jia-Hong; Lee, Shih-Chun

    2015-01-01

    Patients with pathological stage IA non-small cell lung cancer (NSCLC) may relapse despite complete surgical resection without lymphovascular invasion. A method of selecting a high-risk group for adjuvant therapy is necessary. The aim of this study was to assess the predictive value of F-fluorodeoxyglucose (FDG) uptake and the morphologic features of computed tomography (CT) for recurrence in pathological stage IA NSCLC.One hundred forty-five patients with pathological stage IA NSCLC who underwent pretreatment with FDG positron emission tomography and CT evaluations were retrospectively enrolled. The associations among tumor recurrence and patient characteristics, maximal standard uptake value (SUVmax) of primary tumors, and CT imaging features were investigated using univariate and multivariate analyses. A receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of these factors.Tumor recurrence developed in 21 (14.5%) of the 145 patients, and the 5-year recurrence-free survival rate was 77%. The univariate analysis demonstrated that SUVmax, the grade of histological differentiation, tumor size, and the presence of bronchovascular bundle thickening were significant predictive factors (P < 0.05). A higher SUVmax (≥2.5) (P = 0.021), a lower ground-glass opacity ratio (≤17%) (P = 0.014), and the presence of bronchovascular bundle thickening (P = 0.003) were independent predictive factors of tumor recurrence in the multivariate analysis. The use of this predictive model yielded a greater area under the ROC curve (0.877), which suggests good discrimination.The combined evaluation of FDG uptake and CT morphologic features may be helpful in the prediction of recurrence in patients with pathological stage IA NSCLC and in the stratification of a high-risk group for postoperative adjuvant therapy or prospective clinical trials.

  10. Clinical-Pathologic Features and Long-Term Outcomes of Tubular Carcinoma of the Breast Compared With Invasive Ductal Carcinoma Treated With Breast Conservation Therapy

    SciTech Connect

    Liu, Gene-Fu F.; Yang Qifeng; Haffty, Bruce G.; Moran, Meena S.

    2009-12-01

    Purpose: To evaluate our institutional experience of treating tubular carcinoma of the breast (TC) and invasive ductal carcinoma (IDC) with conservative surgery and radiation therapy, to compare clinical-pathologic features and long-term outcomes. Methods and Materials: A review of our institution's tumor registry from 1975 to 2007, followed by a central pathology review of available slides, yielded 71 cases of Stage I/II TC and 2,238 cases of Stage I/II IDC treated with breast conservation therapy. Clinical-pathologic features and outcomes were analyzed by subtype to detect significant differences. Results: The median follow-up was 7 years. The TC cohort presented more frequently with pT1 disease (97% vs. 80%, p = 0.0007), pN0 disease (95% vs. 74%, p = 0.0004), hormone-receptor positivity (ER+, 89% vs. 62%, p = 0.0001; PR+, 81% vs. 52%, p = 0.0001), and HER-2 negativity (89% vs. 71%, p = 0.04). Clinical outcomes also favored the TC cohort, with lower rates of breast cancer-related death (1% vs. 10%; p = 0.0109) and distant metastasis (1% vs. 13%; p = 0.0028) and higher rates of 10-year overall (90% vs. 80%; p = 0.033), cause-specific (99% vs. 86%; p = 0.011), and disease-free (99% vs. 82%; p = 0.003) survival. There was a nonsignificant trend toward improved breast cancer relapse-free survival for the TC cohort (95% vs. 87%; p = 0.062) but no difference in nodal relapse-free survival or contralateral breast cancer relapse-free survival (all p values >0.05) between the cohorts. Conclusion: Our institutional experience suggests that TC, when compared with IDC, is associated with more favorable clinical-pathologic features and comparable, if not superior, outcomes after breast conservation therapy, suggesting the appropriateness of a conservative approach to this rare subtype.

  11. [Formation and structural features of morbidity in miners with professional pathology of the peripheral nervous system and the musculoskeletal system].

    PubMed

    Shpagina, L N

    2014-01-01

    There were studied polypathy rates, their relationship with the professional pathology in Kuzbass miners. There was performed the analysis of an array of more than 2000 patients with occupational pathology and also 1800 records from for the coal miners hospitals for patients with no signs of occupational diseases. The rise in morbidity rate of polypathies was turned out to be associated with a very low proportion (less than 20%) of patients' preventive visits. It is advisable to introduce the financial incentives for doctors share for the rise of the number of healthy individuals in the enterprise, for detection rate of chronic general and occupational diseases at the early stages of the disease and for reducing of incidence of polypathies.

  12. [Clinical and pathological features in IgA nephropathy with IgG deposition in the glomerular mesangial area].

    PubMed

    Xu, Xiao-Meng; Zhu, Shuang-Shuang; Wang, Xiao-Hong; Shao, Xiao-Fei; Li, Bin; Zhang, Ying; Liu, Qin; Li, Jia-Min; Wang, Hong-Lei; Li, Yong-Qiang; Zou, He-Qun

    2017-03-20

    To investigate the relationship between the clinical and pathological findings in IgA nephropathy with or without IgG deposition in the glomerular mesangial area. The data were collected from 122 patients with a diagnosis of IgA nephropathy by renal biopsy in the Third Affiliated Hospital of Southern Medical University between November, 2009 and February, 2016. All the samples were examined by light microscopy, immunofluorescence and electron microscopy. According to the results of immunofluorescence assay, the patients were divided into IgA group (n=63) and IgA-IgG group (n=59). The pathological classification of IgA nephropathy was analyzed according to Oxford classification and Lee's classification. The clinical and pathological findings were compared between the two groups. Compared with the patients with IgA nephropathy but without IgG deposition, patients with IgA nephropathy with IgG deposition had higher serum creatinine, higher 24-h urine protein, higher blood uric acid, higher triglyceride levels (P<0.05) and lower eGFR (P<0.05); more of these patients were in Lee's grade IV-V, had renal tubular atrophy and/or interstitial fibrosis, and had MEST scores more than 3 (P<0.05). Patients with IgA nephropathy with IgG deposition in the glomerular mesangial have severer clinical symptoms and more serious pathological changes. Measures should be taken to control IgG deposition in patients with IgA nephropathy to delay the progress of the disease.

  13. IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline

    PubMed Central

    Fu, Amy K. Y.; Hung, Kwok-Wang; Yuen, Michael Y. F.; Zhou, Xiaopu; Mak, Deejay S. Y.; Chan, Ivy C. W.; Cheung, Tom H.; Zhang, Baorong; Fu, Wing-Yu; Liew, Foo Y.; Ip, Nancy Y.

    2016-01-01

    Alzheimer’s disease (AD) is a devastating condition with no known effective treatment. AD is characterized by memory loss as well as impaired locomotor ability, reasoning, and judgment. Emerging evidence suggests that the innate immune response plays a major role in the pathogenesis of AD. In AD, the accumulation of β-amyloid (Aβ) in the brain perturbs physiological functions of the brain, including synaptic and neuronal dysfunction, microglial activation, and neuronal loss. Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD. Therefore, we investigated the potential therapeutic role of IL-33 in AD, using transgenic mouse models. Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice. IL-33 administration reduces soluble Aβ levels and amyloid plaque deposition by promoting the recruitment and Aβ phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation. Furthermore, IL-33 injection modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1β, IL-6, and NLRP3, in the cortices of APP/PS1 mice. Collectively, our results demonstrate a potential therapeutic role for IL-33 in AD. PMID:27091974

  14. TU-C-12A-09: Modeling Pathologic Response of Locally Advanced Esophageal Cancer to Chemo-Radiotherapy Using Quantitative PET/CT Features, Clinical Parameters and Demographics

    SciTech Connect

    Zhang, H; Chen, W; Kligerman, S; D’Souza, W; Suntharalingam, M; Lu, W; Tan, S; Kim, G

    2014-06-15

    Purpose: To develop predictive models using quantitative PET/CT features for the evaluation of tumor response to neoadjuvant chemo-radiotherapy (CRT) in patients with locally advanced esophageal cancer. Methods: This study included 20 patients who underwent tri-modality therapy (CRT + surgery) and had {sup 18}F-FDG PET/CT scans before initiation of CRT and 4-6 weeks after completion of CRT but prior to surgery. Four groups of tumor features were examined: (1) conventional PET/CT response measures (SUVmax, tumor diameter, etc.); (2) clinical parameters (TNM stage, histology, etc.) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, using cross-validations to avoid model over-fitting. Prediction accuracy was assessed via area under the receiver operating characteristic curve (AUC), and precision was evaluated via confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). Using spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications), significantly better than using conventional PET/CT measures or clinical parameters and demographics alone. For groups with a large number of tumor features (groups 3 and 4), the SVM model achieved significantly higher accuracy than the LR model. Conclusion: The SVM model using all features

  15. Modeling Pathologic Response of Esophageal Cancer to Chemoradiation Therapy Using Spatial-Temporal {sup 18}F-FDG PET Features, Clinical Parameters, and Demographics

    SciTech Connect

    Zhang, Hao; Tan, Shan; Chen, Wengen; Kligerman, Seth; Kim, Grace; D'Souza, Warren D.; Suntharalingam, Mohan; Lu, Wei

    2014-01-01

    Purpose: To construct predictive models using comprehensive tumor features for the evaluation of tumor response to neoadjuvant chemoradiation therapy (CRT) in patients with esophageal cancer. Methods and Materials: This study included 20 patients who underwent trimodality therapy (CRT + surgery) and underwent {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) both before and after CRT. Four groups of tumor features were examined: (1) conventional PET/CT response measures (eg, standardized uptake value [SUV]{sub max}, tumor diameter); (2) clinical parameters (eg, TNM stage, histology) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, cross-validations being used to avoid model overfitting. Prediction accuracy was assessed by area under the receiver operating characteristic curve (AUC), and precision was evaluated by confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). With the use of spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications)—results that were significantly better than when conventional PET/CT measures or clinical parameters and demographics alone were used. For groups with many tumor features (groups 3 and 4), the SVM model achieved significantly higher

  16. Clinical, pathological, and genetic features of limb-girdle muscular dystrophy type 2A with new calpain 3 gene mutations in seven patients from three Japanese families.

    PubMed

    Kawai, H; Akaike, M; Kunishige, M; Inui, T; Adachi, K; Kimura, C; Kawajiri, M; Nishida, Y; Endo, I; Kashiwagi, S; Nishino, H; Fujiwara, T; Okuno, S; Roudaut, C; Richard, I; Beckmann, J S; Miyoshi, K; Matsumoto, T

    1998-11-01

    We report on the clinical, pathological, and genetic features of 7 patients with limb-girdle muscular dystrophy type 2A (LGMD2A) from three Japanese families. The mean age of onset was 9.7+/-3.1 years (mean+/-SD), and loss of ambulance occurred at 38.5+/-2.1 years. Muscle atrophy was predominant in the pelvic and shoulder girdles, and proximal limb muscles. Muscle pathology revealed dystrophic changes. In two families, an identical G to C mutation at position 1080 the in calpain 3 gene was identified, and a frameshift mutation (1796insA) was found in the third family. The former mutation results in a W360R substitution in the proteolytic site of calpain 3, and the latter in a deletion of the Ca2+-binding domain.

  17. Endorectal T2-weighted MRI does not differentiate between favorable and adverse pathologic features in men with prostate cancer who would qualify for active surveillance.

    PubMed

    Guzzo, Thomas J; Resnick, Matthew J; Canter, Daniel J; Bivalacqua, Trinity J; Rosen, Mark A; Bergey, Meredith R; Magerfleisch, Laurie; Tomazewski, John E; Wein, Alan J; Malkowicz, S Bruce

    2012-01-01

    With the increased diagnosis of low grade, low volume, potentially non-lethal disease, active surveillance (AS) has become an increasingly popular alternative for select men with low-risk prostate cancer. The absence of precise clinical staging modalities currently makes it difficult to predict which patients are most appropriate for AS. The goal of our study was to evaluate the ability of endorectal MRI (eMRI) to predict adverse pathologic features in patients who would otherwise qualify for an AS program. We retrospectively reviewed our institution's radical prostatectomy (RP) database from 1991 to 2007 and identified 172 patients who would have qualified for AS and underwent preoperative staging eMRI with T2-weighted (T2W) sequences. MRI findings were correlated to final pathology in order to assess the ability of staging eMRI to predict adverse pathologic features in patients suitable for AS. The mean age of our cohort was 59.8 ± 6.2 years. The mean PSA at the time of diagnosis was 5.2 ± 2.2 ng/ml. In 51% of patients, no discrete tumor was visualized on eMRI and in 49% of patients a discrete tumor was detected. At the time of RP, Gleason score upgrading, extracapsular extension, and a positive surgical margin occurred in 17%, 6%, and 5% of cases, respectively. Patients with documented tumor on eMRI did not have an increased incidence of adverse pathologic findings with regard to tumor volume (P = 0.31), extra-capsular extension (P = 0.82), Gleason upgrading (P = 0.92), seminal vesicle invasion (P = 0.97), or positive surgical margin rate (P = 0.95) compared with those in whom no tumor was seen. Discrete tumor identification on eMRI is not predictive of adverse pathologic features in patients who would otherwise qualify for AS. eMRI likely does not provide additional information when prospectively evaluating patients for AS protocols. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Clinical and pathological features of amyotrophic lateral sclerosis caused by mutation in the C9ORF72 gene on chromosome 9p

    PubMed Central

    Stewart, Heather; Rutherford, Nicola J.; Briemberg, Hannah; Krieger, Charles; Cashman, Neil; Fabros, Marife; Baker, Matt; Fok, Alice; DeJesus-Hernandez, Mariely; Eisen, Andrew; Rademakers, Rosa; Mackenzie, Ian R. A.

    2012-01-01

    Two studies recently identified a GGGGCC hexanucleotide repeat expansion in a non-coding region of the chromosome 9 open reading frame 72 gene (C9ORF72) as the cause of chromosome 9p-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In a cohort of 231 probands with ALS, we identified the C9ORF72 mutation in 17 familial (27.4 %) and six sporadic (3.6%) cases. Patients with the mutation presented with typical motor features of ALS, although subjects with the C9ORF72 mutation had more frequent bulbar onset, compared to those without this mutation. Dementia was significantly more common in ALS patients and families with the C9ORF72 mutation and was usually early-onset FTD. There was striking clinical heterogeneity among the members of individual families with the mutation. The associated neuropathology was a combination of ALS with TDP-ir inclusions and FTLD-TDP. In addition to TDP-43-immunoreactive pathology, a consistent and specific feature of cases with the C9ORF72 mutation was the presence of ubiquitin-positive, TDP-43-negative inclusions in a variety of neuroanatomical regions, such as the cerebellar cortex. These findings support the C9ORF72 mutation as an important newly-recognized cause of ALS, provide a more detailed characterization of the associated clinical and pathological features and further demonstrate the clinical and molecular overlap between ALS and FTD. PMID:22228244

  19. Is active surveillance a safe alternative in the management of localized prostate cancer? Pathological features of radical prostatectomy specimens in potential candidates for active surveillance.

    PubMed

    Norman, Z; Militza, P; Andres, F; Daniela, F; Alejandro, M; Catherine, S; Juan, F

    2014-01-01

    Active surveillance (AS) has become an accepted alternative for patients with low risk prostate cancer. The purpose of AS is to defer definitive therapy in these patients to avoid treatment-related complications. Our aim was to determine the pathological features of the surgical specimen from potential AS candidates that underwent radical prostatectomy (RP). We retrospectively reviewed a group of patients submitted to RP who met criteria for AS: Gleason score (GS) ≤ 3+3 = 6, PSA ≤ 10ng/mL, T1c - T2a,< 1/3 of positive cores, < 50% of involvement in any core and PSA density < 0.15. We determined the concordance between GS in biopsy and RP specimen (RPS). Other pathological features of the RPS were also analyzed, including surgical margins, extracapsular extension, seminal vesicles and lymph node involvement. We identified 167 patients subjected to RP that met the criteria for AS. Fifty two patients (31.1%) had a GS > 6 in the RPS (GS 7 n = 49; GS 8 n = 3). Extracapsular extension, seminal vesicle and lymph node involvement was found in 6.1%, 3.1% and 1.2% of the specimens, respectively. In this study a significant proportion of potential candidates for AS showed features of aggressive and/or high-risk tumors in the RPS. Therefore, before considering a patient for an AS protocol, a proper and strict selection must be performed, and informed consent is crucial for these patients.

  20. Clinical and pathological features of amyotrophic lateral sclerosis caused by mutation in the C9ORF72 gene on chromosome 9p.

    PubMed

    Stewart, Heather; Rutherford, Nicola J; Briemberg, Hannah; Krieger, Charles; Cashman, Neil; Fabros, Marife; Baker, Matt; Fok, Alice; DeJesus-Hernandez, Mariely; Eisen, Andrew; Rademakers, Rosa; Mackenzie, Ian R A

    2012-03-01

    Two studies recently identified a GGGGCC hexanucleotide repeat expansion in a non-coding region of the chromosome 9 open-reading frame 72 gene (C9ORF72) as the cause of chromosome 9p-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In a cohort of 231 probands with ALS, we identified the C9ORF72 mutation in 17 familial (27.4%) and six sporadic (3.6%) cases. Patients with the mutation presented with typical motor features of ALS, although subjects with the C9ORF72 mutation had more frequent bulbar onset, compared to those without this mutation. Dementia was significantly more common in ALS patients and families with the C9ORF72 mutation and was usually early-onset FTD. There was striking clinical heterogeneity among the members of individual families with the mutation. The associated neuropathology was a combination of ALS with TDP-ir inclusions and FTLD-TDP. In addition to TDP-43-immunoreactive pathology, a consistent and specific feature of cases with the C9ORF72 mutation was the presence of ubiquitin-positive, TDP-43-negative inclusions in a variety of neuroanatomical regions, such as the cerebellar cortex. These findings support the C9ORF72 mutation as an important newly recognized cause of ALS, provide a more detailed characterization of the associated clinical and pathological features and further demonstrate the clinical and molecular overlap between ALS and FTD.

  1. A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease

    PubMed Central

    Wolf, Heike; Stroobants, Stijn; D'Hooge, Rudi; Hermans-Borgmeyer, Irm; Lüllmann-Rauch, Renate; Dierks, Thomas; Lübke, Torben

    2016-01-01

    ABSTRACT Fucosidosis is a rare lysosomal storage disorder caused by the inherited deficiency of the lysosomal hydrolase α-L-fucosidase, which leads to an impaired degradation of fucosylated glycoconjugates. Here, we report the generation of a fucosidosis mouse model, in which the gene for lysosomal α-L-fucosidase (Fuca1) was disrupted by gene targeting. Homozygous knockout mice completely lack α-L-fucosidase activity in all tested organs leading to highly elevated amounts of the core-fucosylated glycoasparagine Fuc(α1,6)-GlcNAc(β1-N)-Asn and, to a lesser extent, other fucosylated glycoasparagines, which all were also partially excreted in urine. Lysosomal storage pathology was observed in many visceral organs, such as in the liver, kidney, spleen and bladder, as well as in the central nervous system (CNS). On the cellular level, storage was characterized by membrane-limited cytoplasmic vacuoles primarily containing water-soluble storage material. In the CNS, cellular alterations included enlargement of the lysosomal compartment in various cell types, accumulation of secondary storage material and neuroinflammation, as well as a progressive loss of Purkinje cells combined with astrogliosis leading to psychomotor and memory deficits. Our results demonstrate that this new fucosidosis mouse model resembles the human disease and thus will help to unravel underlying pathological processes. Moreover, this model could be utilized to establish diagnostic and therapeutic strategies for fucosidosis. PMID:27491075

  2. Seven-Year Course of Borderline Personality Disorder Features: Borderline Pathology Is as Unstable as Depression during Adolescence.

    PubMed

    Conway, Christopher C; Hipwell, Alison E; Stepp, Stephanie D

    2017-07-01

    Borderline personality disorder (PD) historically is construed as an unremitting condition with poor prognosis. The present study takes a new approach to examining stability and change in borderline PD by explaining symptom expression in terms of an unchanging foundation-termed borderline proneness-on one hand, and transitory influences on the other. We monitored borderline PD symptoms annually in a large sample of high-risk adolescent girls (N = 2,450) from ages 14 to 20. Trait-state-occasion modeling revealed that just over half (52-57%) of borderline PD symptom variation was attributable to fixed borderline proneness, whereas the remainder was subject to change across yearly measurement occasions. This degree of stability was no larger than the corresponding estimate for depression, a condition known for its variable course. Our results indicate that, contrary to its reputation, borderline pathology is not set in stone, and it fluctuates in response to situational influences.

  3. Differences in pathological and clinical features of breast cancer in Arab as compared to Jewish women in Northern Israel.

    PubMed

    Zidan, Jamal; Sikorsky, Natalya; Basher, Walid; Sharabi, Adi; Friedman, Eitan; Steiner, Mariana

    2012-08-15

    Breast cancer (BC) does not affect ethnic groups equally. BC mortality is higher in Israeli Palestinian Arab women than among Israeli Jewish women. This study aims to compare clinical, biological and pathological characteristics of breast cancer in the two populations. Records of 1,140 women with BC treated at Northern Israel between 2002 and 2007 were reviewed: 872 Jews and 268 Arabs. Age at diagnosis, tumor stage, pathological differentiation, estrogen receptor (ER) and HER-2 expression were evaluated. The main age at diagnosis was 49.9 years for Arabs and 59.4 years for Jews (p < 0.0001). Mean tumor size was < 2 cm in 25% of Arabs and 53% of Jews (p < 0.0001). Lymph node metastases presented in 64.6% of Arabs and 37.2% of Jews (p < 0.0001). Stage I disease was 19% in Arab and 49.2% in Jewish women while Stages III and IV disease was 42% and 11.3% respectively (p < 0.001). ER was positive in 69% of Arabs and in 78.5% of Jews (p < 0.001). Poorly differentiated tumors were found in 28.8% of Arabs vs. 12.8% in Jews (p < 0.0001). Overexpression of HER-2 was present in 35.4% of Arab and 22% of Jewish women (p < 0.001). We found that race is an important predictive factor for breast cancer. Arab women are diagnosed at younger age, with more advanced stage and biologically more aggressive disease than in Jewish women. Socioeconomic factors alone are not sufficient to explain significant effects of race on tumor characteristics. Findings suggest a different genetic susceptibility in the two populations which needs further research. Copyright © 2011 UICC.

  4. Assessment of the degree of asymmetry of pathological features in neurodegenerative diseases. What is the significance for brain banks?

    PubMed

    King, Andrew; Bodi, Istvan; Nolan, Matthew; Troakes, Claire; Al-Sarraj, Safa

    2015-10-01

    Brain banks allow researchers access to tissue from well-characterised neurodegenerative disease cases. Fixed tissue employed for diagnosis is often not appropriate for research and frozen tissue is therefore made available. Many brain banks use a protocol where half the brain is fixed and half frozen. Recently a study has shown that there can be asymmetry in protein deposition between the hemispheres especially with tau and TDP-43. We aimed to test this hypothesis by prospectively taking bilateral cortical blocks from 30 brains on arrival, and immunostaining to assess the degree of asymmetry. In 6 out 14 cases of AD (Alzheimer's Disease) (Modified Braak Stage V-VI), there was some asymmetrical staining for tau. In 2 cases, there was moderate discrepancy for tau staining between left and right calcarine cortices. However, careful analysis in both these cases revealed discrepancies in tau staining in adjacent regions even on the same side. The α-synuclein staining showed asymmetry in one case only, the Aβ showed only mild asymmetry in 3 cases of AD. The TDP-43 pathology appeared symmetrical in the 2 cases of frontotemporal lobar degeneration with motor neurone disease, but there was asymmetry noted when seen in conjunction with AD. In conclusion, there is the potential for asymmetrical pathology in neurodegenerative diseases and caution should be maintained when freezing half and fixing half of the brain in neurodegenerative diseases. Nevertheless, marked variability in staining can also be identified in adjacent cortical areas so there is no guarantee that an alternative strategy would be superior.

  5. Atypical MRI features in soft-tissue arteriovenous malformation: a novel imaging appearance with radiologic-pathologic correlation.

    PubMed

    Patel, Anand S; Schulman, Joshua M; Ruben, Beth S; Hoffman, William Y; Dowd, Christopher F; Frieden, Ilona J; Hess, Christopher P

    2015-09-01

    The absence of a discrete mass, surrounding signal abnormality and solid enhancement are imaging features that have traditionally been used to differentiate soft-tissue arteriovenous malformations from vascular tumors on MRI. We have observed that these findings are not uncommon in arteriovenous malformations, which may lead to misdiagnosis or inappropriate treatment. To estimate the frequency of atypical MRI features in soft-tissue arteriovenous malformations and assess their relationship to lesion size, location, tissue type involved and vascular architecture. Medical records, MRI and histopathology were reviewed in consecutive patients with soft-tissue arteriovenous malformations in a multidisciplinary vascular anomalies clinic. Arteriovenous malformations were divided into those with and without atypical MRI findings (perilesional T2 signal abnormality, enhancement and/or a soft-tissue mass). Lesion location, size, tissue involved and vascular architecture were also compared between groups. Tissue stains were reviewed in available biopsy or resection specimens to assess relationships between MRI findings and histopathology. Thirty patients with treatment-naïve arteriovenous malformations were included. Fifteen lesions demonstrated atypical MRI. There was no difference in age, gender, lesion size or involved body part between the groups. However, more than half of the atypical lesions demonstrated multicompartmental involvement, and tiny intralesional flow voids were more common in atypical arteriovenous malformations. Histopathology also differed in atypical cases, showing densely packed endothelial cells with connective tissue architectural distortion and edema. Arteriovenous malformations may exhibit features of a vascular tumor on MRI, particularly when multicompartmental and/or containing tiny internal vessels. These features are important to consider in suspected fast-flow vascular malformations and may have implications with respect to their treatment.

  6. Telangiectasis in CREST syndrome and systemic sclerosis: correlation of clinical and pathological features with response to pulsed dye laser treatment.

    PubMed

    Halachmi, Shlomit; Gabari, Osama; Cohen, Sarit; Koren, Romelia; Amitai, Dan Ben; Lapidoth, Moshe

    2014-01-01

    Telangiectasia are cardinal features of systemic sclerosis (SS) and calcinosis, Raynaud's syndrome, esophageal motility, sclerodactyly, telangiectasias (CREST) syndrome. The etiology of telangiectasia in these syndromes is unknown, but vascular dysfunction has been proposed. However, the telangiectasia of CREST have anecdotally been considered relatively resistant to pulse dye laser (PDL), the treatment of choice for classic telangiectasia. The study was designed to test whether SS/CREST telangiectasia require more treatments than sporadic telangiectasia and to identify clinical and histological features that could explain such an effect. Nineteen skin biopsies from patients with SS or CREST and 10 control biopsies were examined and compared for features that may predict a differential response to PDL. Sixteen cases of SS or CREST treated with PDL between 1997 and 2007 were evaluated and response to treatment was compared with 20 patients with sporadic telangiectasis. Relative to normal skin, CREST/scleroderma telangiectasia exhibited thickened vessels in 17 out of 19 sections and thickened collagen fibers in the reticular or deep dermis in all sections. The number of treatments required to clear SS/CREST telangiectasia was approximately twofold higher. SS/CREST telangiectasia are more resistant to PDL but can be effectively cleared with more treatments.

  7. Pathological features and survival outcomes of very young patients with early breast cancer: how much is "very young"?

    PubMed

    Cancello, Giuseppe; Maisonneuve, Patrick; Mazza, Manuelita; Montagna, Emilia; Rotmensz, Nicole; Viale, Giuseppe; Pruneri, Giancarlo; Veronesi, Paolo; Luini, Alberto; Gentilini, Oreste; Goldhirsch, Aron; Colleoni, Marco

    2013-12-01

    We collected information on 497 consecutive breast cancer patients aged less than 35 years operated at the European Institute of Oncology. The main aim of the study is to compare biological and clinical features dividing the population by age: <25 years, 25-29 and 30-34 years old. Pattern of recurrence and survival were also analyzed. Patients aged <25 years had 81.8% poorly differentiated tumors compared with 66.7% and 56.5% in the 25-29 and 30-34 groups, respectively; no other significant difference were found in the distribution of clinical and immunohistochemical features The distribution of Luminal A and B, Triple Negative and HER2 subtypes (immunohistochemically defined) was not statistically different among the three age groups. No difference was found in the incidence of loco-regional relapses, distant metastases, disease-free survival (p = 0.79) and overall survival (p = 0.99) between the three age groups. This latter findings was confirmed using age as a continuous variable assuming a linear association between age and the outcomes considered, too. In conclusion, our data indicate that the group of patients with breast cancer below 35 years is essentially a homogenous group when classical clinical and immunohistochemical features were considered. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Significant differences in demographic, clinical, and pathological features in relation to smoking and alcohol consumption among 1,633 head and neck cancer patients

    PubMed Central

    Moyses, Raquel Ajub; López, Rossana Verónica Mendoza; Cury, Patrícia Maluf; Siqueira, Sheila Aparecida Coelho; Curioni, Otávio Alberto; de Gois Filho, José Francisco; Figueiredo, David Livingstone Alves; Head; GENCAPO, Neck Genome Project; Tajara, Eloiza Helena; Michaluart, Pedro

    2013-01-01

    OBJECTIVE: As a lifestyle-related disease, social and cultural disparities may influence the features of squamous cell carcinoma of the head and neck in different geographic regions. We describe demographic, clinical, and pathological aspects of squamous cell carcinoma of the head and neck according to the smoking and alcohol consumption habits of patients in a Brazilian cohort. METHODS: We prospectively analyzed the smoking and alcohol consumption habits of 1,633 patients enrolled in five São Paulo hospitals that participated in the Brazilian Head and Neck Genome Project – Gencapo. RESULTS: The patients who smoked and drank were younger, and those who smoked were leaner than the other patients, regardless of alcohol consumption. The non-smokers/non-drinkers were typically elderly white females who had more differentiated oral cavity cancers and fewer first-degree relatives who smoked. The patients who drank presented significantly more frequent nodal metastasis, and those who smoked presented less-differentiated tumors. CONCLUSIONS: The patients with squamous cell carcinoma of the head and neck demonstrated demographic, clinical, and pathological features that were markedly different according to their smoking and drinking habits. A subset of elderly females who had oral cavity cancer and had never smoked or consumed alcohol was notable. Alcohol consumption seemed to be related to nodal metastasis, whereas smoking correlated with the degree of differentiation. PMID:23778492

  9. Expression of Estrogen Receptor Beta Predicts Oncologic Outcome of pT3 Upper Urinary Tract Urothelial Carcinoma Better Than Aggressive Pathological Features

    PubMed Central

    Luo, Hao Lun; Sung, Ming Tse; Tsai, Eing Mei; Lin, Chang Shen; Lee, Nai Lun; Chung, Yueh-Hua; Chiang, Po Hui

    2016-01-01

    Upper urinary tract urothelial carcinoma (UT-UC) is rare and treatment options or prognostic markers are limited. There is increasing evidence indicating that urothelial carcinoma may be an endocrine-related cancer. The aim of this study was to analyze the prognostic effect of estrogen receptor beta (ERβ) on the outcome of UT-UC. From 2005 to 2012, this study included 105 patients with pT3 UT-UC. Perioperative factors, pathological features, and ERβ immunostaining were reviewed and prognostic effects were examined by multivariate analysis. This study divided patients into either the ERβ-high (n = 52) or ERβ-low (n = 53) group and analyzed their oncologic outcomes. All pathological features except infiltrating tumor architecture (significantly higher incidence in ERβ-low group, p = 0.004) are symmetric in both groups. Low ERβ expression was significantly correlated with local recurrence and distant metastasis in univariate analysis (p = 0.035 and 0.004, respectively) and multivariate analysis (p = 0.05 and 0.008, respectively). Cell line study also proved that knock down of ERβ cause less UTUC proliferation and migration. In addition, ERβ agonist also enhanced the cytotoxic and migration inhibition effect of cisplatin and ERβ antagonist cause the UTUC cell more resistant to cisplatin. This result may help identify patients in need of adjuvant therapy or develop potential targeted therapy. PMID:27052470

  10. Presenting features and short-term outcome according to pathologic variant in childhood primary focal segmental glomerulosclerosis.

    PubMed

    Silverstein, Douglas M; Craver, Randall

    2007-07-01

    This was a retrospective analysis of children in one center who had primary (idiopathic) FSGS. There were 41 patients: 34.1% female, 65.9% male, 80.5% black, and 19.5% white. At presentation, the mean age was 10.9 +/- 0.9 yr. The mean time of follow-up was 3.9 +/- 0.5 yr. During the observation period, the systolic BP (SBP) and diastolic BP (DBP) remained stable, serum albumin rose slightly, and the GFR was stable. Among those who received corticosteroids at presentation, 21.2% were steroid sensitive. At last follow-up among all patients, 71% were in remission, 78% had stage 1 or 2 chronic kidney disease, and 4.9% had reached ESRD. At last follow-up, the GFR was significantly higher (P = 0.01) in patients who were initially steroid sensitive. Ethnicity had no effect on clinical data or response to therapy. The pathologic variants were as follows: Cellular, 32%; collapsing, 24%; and not otherwise specified (NOS), 44%. The chronicity scores were as follows: Cellular, 4.3; collapsing 6.4; and NOS, 4.0 (significantly higher, P = 0.02, in collapsing versus NOS). At presentation, SBP (P = 0.03) and DBP (P = 0.03) were significantly higher and GFR was lower (P = 0.03) in patients with the collapsing compared with NOS variant. Remission after the initial course of corticosteroids was less common with the collapsing variant. At last follow-up, SBP (P = 0.02) and DBP (P = 0.04) were significantly higher in patients with the collapsing versus NOS variant. The short-term outcome in pediatric primary FSGS is generally favorable, but a more guarded prognosis exists for patients with collapsing FSGS.

  11. A Model Based on Pathologic Features of Superficial Esophageal Adenocarcinoma Complements Clinical Node Staging in Determining Risk of Metastasis to Lymph Nodes

    PubMed Central

    Davison, Jon M.; Landau, Michael S.; Luketich, James D.; McGrath, Kevin M.; Foxwell, Tyler J.; Landsittel, Douglas P.; Gibson, Michael K.; Nason, Katie S.

    2016-01-01

    Background & Aims It is important to identify superficial (T1) gastroesophageal adenocarcinomas (EAC) that are most or least likely to metastasize to lymph nodes, to select appropriate therapy. We aimed to develop a risk stratification model for metastasis of superficial EAC to lymph nodes using pathologic features of the primary tumor. Methods We collected pathology data from 210 patients with T1 EAC who underwent esophagectomy from1996 through 2012 on factors associated with metastatsis to lymph nodes (tumor size, grade, angio-lymphatic invasion, and submucosal invasion). Using these variables, we developed a multivariable logistic model to generate 4 categories for estimated risk of metastasis (<5% risk, 5%–10% risk, 15%–20% risk, or >20% risk). The model was validated in a separate cohort of 39 patients who underwent endoscopic resection of superficial EAC and subsequent esophagectomy, with node stage analysis. Results We developed a model based on 4 pathologic factors that determined risk of metastasis to range from 2.9% to 60% for patients in the first cohort. In the endoscopic resection validation cohort, higher risk scores were associated with increased detection of lymph node metastases at esophagectomy (P=.025). Among patients in the first cohort who did not have lymph node metastases detected before surgery (cN0), those with high risk scores (>20% risk) had 11-fold greater odds for having lymph node metastases at esophagectomy compared to patients with low risk scores (95% confidence interval, 2.3–52 fold). Increasing risk scores were associated with reduced patient survival time (P<.001) and shorter time to tumor recurrence (P<.001). Patients without lymph node metastases (pT1N0) but high risk scores had reduced times of survival (P<.001) and time to tumor recurrence (P=.001) after esophagectomy than patients with pT1N0 tumors and lower risk scores. Conclusions Pathologic features of primary superficial EACs can be used, along with the

  12. Clinical and pathological features of kidney transplant patients with concurrent polyomavirus nephropathy and rejection-associated endarteritis.

    PubMed

    McGregor, Stephanie M; Chon, W James; Kim, Lisa; Chang, Anthony; Meehan, Shane M

    2015-12-24

    To describe the clinicopathologic features of concurrent polyomavirus nephropathy (PVN) and endarteritis due to rejection in renal allografts. We searched our electronic records database for cases with transplant kidney biopsies demonstrating features of both PVN and acute rejection (AR). PVN was defined by the presence of typical viral cytopathic effect on routine sections and positive polyomavirus SV40 large-T antigen immunohistochemistry. AR was identified by endarteritis (v1 by Banff criteria). All cases were subjected to chart review in order to determine clinical presentation, treatment course and outcomes. Outcomes were recorded with a length of follow-up of at least one year or time to nephrectomy. Of 94 renal allograft recipients who developed PVN over an 11-year period at our institution, we identified 7 (7.4%) with viral cytopathic changes, SV40 large T antigen staining, and endarteritis in the same biopsy specimen, indicative of concurrent PVN and AR. Four arose after reduction of immunosuppression (IS) (for treatment of PVN in 3 and tuberculosis in 1), and 3 patients had no decrease of IS before developing simultaneous concurrent disease. Treatment consisted of reduced oral IS and leflunomide for PVN, and anti-rejection therapy. Three of 4 patients who developed endarteritis in the setting of reduced IS lost their grafts to rejection. All 3 patients with simultaneous PVN and endarteritis cleared viremia and were stable at 1 year of follow up. Patients with endarteritis and PVN arising in a background of reduced IS had more severe rejection and poorer outcome. Concurrent PVN and endarteritis may be more frequent than is currently appreciated and may occur with or without prior reduction of IS.

  13. Clinical and pathological features of kidney transplant patients with concurrent polyomavirus nephropathy and rejection-associated endarteritis

    PubMed Central

    McGregor, Stephanie M; Chon, W James; Kim, Lisa; Chang, Anthony; Meehan, Shane M

    2015-01-01

    AIM: To describe the clinicopathologic features of concurrent polyomavirus nephropathy (PVN) and endarteritis due to rejection in renal allografts. METHODS: We searched our electronic records database for cases with transplant kidney biopsies demonstrating features of both PVN and acute rejection (AR). PVN was defined by the presence of typical viral cytopathic effect on routine sections and positive polyomavirus SV40 large-T antigen immunohistochemistry. AR was identified by endarteritis (v1 by Banff criteria). All cases were subjected to chart review in order to determine clinical presentation, treatment course and outcomes. Outcomes were recorded with a length of follow-up of at least one year or time to nephrectomy. RESULTS: Of 94 renal allograft recipients who developed PVN over an 11-year period at our institution, we identified 7 (7.4%) with viral cytopathic changes, SV40 large T antigen staining, and endarteritis in the same biopsy specimen, indicative of concurrent PVN and AR. Four arose after reduction of immunosuppression (IS) (for treatment of PVN in 3 and tuberculosis in 1), and 3 patients had no decrease of IS before developing simultaneous concurrent disease. Treatment consisted of reduced oral IS and leflunomide for PVN, and anti-rejection therapy. Three of 4 patients who developed endarteritis in the setting of reduced IS lost their grafts to rejection. All 3 patients with simultaneous PVN and endarteritis cleared viremia and were stable at 1 year of follow up. Patients with endarteritis and PVN arising in a background of reduced IS had more severe rejection and poorer outcome. CONCLUSION: Concurrent PVN and endarteritis may be more frequent than is currently appreciated and may occur with or without prior reduction of IS. PMID:26722657

  14. Isolated IgG4-related interstitial lung disease: unusual histological and radiological features of a pathologically proven case.

    PubMed

    Wibmer, Thomas; Kropf-Sanchen, Cornelia; Rüdiger, Stefan; Blanta, Ioanna; Stoiber, Kathrin M; Rottbauer, Wolfgang; Schumann, Christian

    2013-03-19

    IgG4-related lung disease is commonly associated with autoimmune pancreatitis. Recently, isolated IgG4-related interstitial lung disease (ILD) without other organ involvement has newly been reported in two cases with clinical features of nonspecific interstitial pneumonitis (NSIP).We report the first case of an isolated IgG4-related ILD in a 78-year-old man with dry cough and dyspnea, whose clinical findings proved to be different from NSIP. Serum IgG4 levels were increased. Chest CT scan revealed bilateral consolidations especially in the lower lobes, enlarged mediastinal and hilar lymph nodes and pleural effusions. Video-assisted thoracoscopic (VATS) lung biopsy revealed a pattern similar to usual interstitial pneumonia (UIP) and an abundant IgG4-positive plasma cell infiltration. He was effectively treated by steroid therapy.Increasing recognition of IgG4 related diseases has led to a growing number of new entities. The novel concept of isolated IgG4-related ILD as a pulmonary manifestation of a systemic IgG4-related disorder should be taken into account as a possible differential diagnosis of ILD and mass-forming lesions, even when no other organ manifestation is clinically apparent at the time of diagnosis. Lung specific diagnostic criteria and algorithms are required to enhance diagnostic accuracy in cases of possible IgG4-related ILD.

  15. Isolated IgG4-related interstitial lung disease: unusual histological and radiological features of a pathologically proven case

    PubMed Central

    2013-01-01

    IgG4-related lung disease is commonly associated with autoimmune pancreatitis. Recently, isolated IgG4-related interstitial lung disease (ILD) without other organ involvement has newly been reported in two cases with clinical features of nonspecific interstitial pneumonitis (NSIP). We report the first case of an isolated IgG4-related ILD in a 78-year-old man with dry cough and dyspnea, whose clinical findings proved to be different from NSIP. Serum IgG4 levels were increased. Chest CT scan revealed bilateral consolidations especially in the lower lobes, enlarged mediastinal and hilar lymph nodes and pleural effusions. Video-assisted thoracoscopic (VATS) lung biopsy revealed a pattern similar to usual interstitial pneumonia (UIP) and an abundant IgG4-positive plasma cell infiltration. He was effectively treated by steroid therapy. Increasing recognition of IgG4 related diseases has led to a growing number of new entities. The novel concept of isolated IgG4-related ILD as a pulmonary manifestation of a systemic IgG4-related disorder should be taken into account as a possible differential diagnosis of ILD and mass-forming lesions, even when no other organ manifestation is clinically apparent at the time of diagnosis. Lung specific diagnostic criteria and algorithms are required to enhance diagnostic accuracy in cases of possible IgG4-related ILD. PMID:23509921

  16. Primary and Secondary T-cell Lymphomas of the Breast: Clinico-pathologic Features of 11 Cases

    PubMed Central

    Gualco, Gabriela; Chioato, Lucimara; Harrington, William J.; Weiss, Lawrence M.; Bacchi, Carlos E.

    2009-01-01

    Breast involvement by non-Hodgkin lymphomas is rare, and exceptional for T-cell lymphomas; we studied the morphologic, immunophenotypic, and clinical features of 11 patients with T-cell non-Hodgkin lymphomas involving the breast. Four cases fulfilled the definition criteria for primary breast lymphomas, 3 females and 1 male, with a median age of 51 years. One primary breast lymphomas was T-cell lymphoma unspecified, other was subcutaneous panniculitis-like T-cell lymphoma, and 2 cases were anaplastic large cell lymphomas. One of the anaplastic large cell lymphoma cases was found surrounding a silicone breast implant and presented as clinically as mastitis; whereas the other case occurred in a man. T-cell lymphoma secondarily involved the breast in 7 patients, all women and 1 bilateral, with a median age of 29 years. These secondary breast lymphomas occurred as part of widespread nodal or leukemic disease. Three patients had adult T-cell leukemia/lymphoma, including the patient with bilateral lesions, 3 others had precursor T-lymphoblastic lymphoma/leukemia, and the other presented with a peripheral-T-cell lymphoma nonotherwise specified type. Breast T-cell lymphomas are very infrequent and are morphologically and clinically heterogeneous. PMID:19318917

  17. Clinico-Pathologic Features of Fatal Disease Attributed to New Variants of Endotheliotropic Herpesviruses in Two Asian Elephants (Elephas maximus)

    PubMed Central

    Garner, M. M.; Helmick, K.; Ochsenreiter, J.; Richman, L. K.; Latimer, E.; Wise, A. G.; Maes, R. K.; Kiupel, M.; Nordhausen, R. W.; Zong, J. C.; Hayward, G. S.

    2013-01-01

    The first herpesviruses described in association with serious elephant disease were referred to as endotheliotropic herpesviruses (EEHV) because of their ability to infect capillary endothelial cells and cause potentially fatal disease. Two related viruses, EEHV1 and EEHV2, have been described based on genetic composition. This report describes the similarities and differences in clinicopathologic features of 2 cases of fatal endotheliotropic herpesvirus infections in Asian elephants caused by a previously unrecognized virus within the betaherpesvirus subfamily that is markedly divergent from the 2 previously studied fatal probosciviruses, based on polymerase chain reaction sequence analysis of 2 segments of the viral genome. In addition to ascites, widespread visceral edema, petechiae, and capillary damage previously reported, important additional findings with EEHV3 infection were the presence of grossly visible renal medullary hemorrhage, a tropism for larger veins and arteries in various tissues, relatively high density of renal herpetic inclusions, and involvement of the retinal vessels. These findings indicate a less selective organ tropism, and this may confer a higher degree of virulence for EEHV3. PMID:19112123

  18. [Amyloid beta-related angiitis: brain lesions showing leptomeningeal gadolinium enhancement on MRI and characteristic surgical pathologic features].

    PubMed

    Koike, Yuka; Ouchi, Haruka; Sato, Tomoe; Shimbo, Junsuke; Sato, Aki; Sasaki, Osamu; Shibuya, Hiroyuki; Okamoto, Kouichirou; Kakita, Akiyoshi; Igarashi, Shuichi

    2013-06-01

    Amyloid-β-related angiitis (ABRA) of the CNS occurs in association with vasculitis of small-and medium-sized leptomeningeal arteries. Here, we describe the clinicopathological features of a 76-year-old man with ABRA. The patient suffered progressive truncal oscillation, aphasia, and recent memory disturbance with a subacute disease onset. His cerebrospinal fluid showed a mild increase in protein levels (101 mg/dL) and pleocytosis (8/mm(3)). High-intensity brain lesion were detected on T(2)-weighted and FLAIR MRI scans, and prominent spread of gadolinium enhancement spreading was observed through the sulci of the left occipital and temporal lobes and left cerebellar hemisphere. A biopsy of the left temporal lesion showed a granulomatous and angiodestructive inflammation with infiltration of many CD4(+) T-lymphocytes and multinucleated giant cells and with fibrinoid necrosis of the arterial walls in the subarachnoid space. Immunolabeling for Aβ(1-40) revealed the abundant deposition of this protein in the affected arteries. On the basic of the diagnosis of ABRA, immunosuppressive therapy was conducted, and it ameliorated the clinical course.

  19. Correlation of minimal extrathyroidal extension with pathologic features of lymph node metastasis in patients with papillary thyroid carcinoma.

    PubMed

    Lee, Hyoung Shin; Park, Chanwoo; Kim, Sung Won; Park, Taejung; Chun, Bong Kwon; Hong, Jong Chul; Lee, Kang Dae

    2015-11-01

    The impact of minimal extrathyroidal extension (mETE) to the prognosis of patients with papillary thyroid carcinoma (PTC) is controversial. In this study, we investigated whether mETE is related to the aggressive biology of metastatic lymph node (LN) in patients with PTC. A retrospective review of 369 patients who had biopsy-confirmed cervical LN metastasis after initial surgery for PTC was conducted. The correlations of mETE with the specific features of metastatic LNs such as the LN size, number, LN ratio, and presence of extranodal extension (ENE) were statistically analyzed. Size of the primary tumor (≥1 cm) had independent correlations to mETE (HR = 5.750). While mETE was related to number of metastatic LNs (≥5), LN ratio (≥0.31) and ENE in univariate analysis, only ENE (HR = 2.322) was independently correlated to mETE in our series. Along with mETE, size of primary tumor (≥1 cm) had significant impact on ENE (HR = 2.107). Minimal ETE particularly those with larger primary tumor (≥1 cm) may be still considered as a significant factor regarding the management of cervical LNs in patients with PTC. © 2015 Wiley Periodicals, Inc.

  20. A comparison of the pathological, clinical and radiographical, features of cryptogenic organising pneumonia, acute fibrinous and organising pneumonia and granulomatous organising pneumonia.

    PubMed

    Feinstein, Marc B; DeSouza, Shilpa A; Moreira, Andre L; Stover, Diane E; Heelan, Robert T; Iyriboz, Tunç A; Taur, Ying; Travis, William D

    2015-06-01

    Cryptogenic organising pneumonia (COP) and acute fibrinous and organising pneumonia (AFOP) are recognised patterns of organising pneumonia (OP), a condition that resembles pneumonia but is not caused by infection. We have recognised granulomatous organising pneumonia (GOP) to be a similar histopathological entity where non-necrotising granulomata are intimately associated with the organising connective tissue. To what degree COP, AFOP and GOP represent distinct clinical and pathological disorders is unknown. This cross-sectional study sought to compare the pathological, clinical, and radiographical features of these OP patterns. Surgical lung biopsy specimens were reviewed for consecutive patients referred with OP to a metropolitan cancer centre. Clinical information and CT images were acquired from the hospital electronic medical record to determine the clinical and CT characteristics of each OP pattern. Sixty-one patients (35 men, 26 women), mean age 61.5 years (range 8-85 years), were available for analysis. Of these, 43 patients (70%) had at least one prior cancer; 27 (44%) had received chemotherapy and 18 (30%) had received radiation. Approximately, half (32 patients) had respiratory symptoms, most commonly cough, dyspnoea and/or wheezing. While symptoms and mortality rates were not different among OP groups, AFOP patients more commonly had fever (p=0.04). GOP patients less commonly had received chemotherapy (p=0.03) and were more likely to present as masses/nodules (p=0.04). AFOP and GOP, a newly described OP form, possess clinical and pathological findings that set it apart from a COP, suggesting an emerging spectrum of OP. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. Structural and Mechanistic Insights into Development of Chemical Tools to Control Individual and Inter-Related Pathological Features in Alzheimer's Disease.

    PubMed

    Lee, Hyuck Jin; Korshavn, Kyle J; Nam, Younwoo; Kang, Juhye; Paul, Thomas J; Kerr, Richard A; Youn, Il Seung; Ozbil, Mehmet; Kim, Kwang S; Ruotolo, Brandon T; Prabhakar, Rajeev; Ramamoorthy, Ayyalusamy; Lim, Mi Hee

    2017-02-21

    To elucidate the involvement of individual and inter-related pathological factors [i.e., amyloid-β (Aβ), metals, and oxidative stress] in the pathogenesis of Alzheimer's disease (AD), chemical tools have been developed. Characteristics required for such tool construction, however, have not been clearly identified; thus, the optimization of available tools or new design has been limited. Here, key structural properties and mechanisms that can determine tools' regulatory reactivities with multiple pathogenic features found in AD are reported. A series of small molecules was built up through rational structural selection and variations onto the framework of a tool useful for in vitro and in vivo metal-Aβ investigation. Variations include: (i) location and number of an Aβ interacting moiety; (ii) metal binding site; and (iii) denticity and structural flexibility. Detailed biochemical, biophysical, and computational studies were able to provide a foundation of how to originate molecular formulas to devise chemical tools capable of controlling the reactivities of various pathological components through distinct mechanisms. Overall, this multidisciplinary investigation illustrates a structure-mechanism-based strategy of tool invention for such a complicated brain disease.

  2. Squamous Cell Carcinoma: Clinical and Pathological Features and Associated Risk Factors in an Observational Study of 118 Patients.

    PubMed

    Díaz-Corpas, T; Morales-Suárez-Varela, M; Rausell Fontestad, N; Fuertes Prósper, A; Marquina-Vila, A; Jordá-Cuevas, E

    2015-12-01

    In the latest edition of its cancer staging manual, the American Joint Committee on Cancer (AJCC) revised the criteria for staging squamous cell carcinoma (SCC) by introducing high-risk tumor features to define tumor stage (T) and help to identify tumors with a higher risk of metastasis. The aim of this study was to investigate the characteristics associated with SCC meeting the high-risk criteria defined by the AJCC for T2 lesions. We performed a case-case observational study in which patients with SCC were included over a period of 18 months. We collected clinical, anthropometric, and tumor data, and analyzed these using PASW Statistics (SPSS) version 18. One-hundred eighteen patients, the majority of whom were men, were included. Mean age was 77 years. Over 70% of the tumors were located in the head region and a majority of tumors measured 2 cm or less. The prevalence of SCC T2 was 61.9%. The risk factors significantly associated with SCC T2 were an age of over 85 years (odds ratio [OR], 4.48), location in the head and neck region (OR, 3.38), presence of solar elastosis in the peritumoral tissue (OR, 2.08), a higher tumor growth rate (>1.5 mm·wk(-1); OR, 5.73), and higher cumulative exposure to smoking (>20 pack-years, OR, 3.63). Advanced age, location in the head and neck region, presence of solar elastosis, high tumor growth rate, and high cumulative smoking exposure were all significantly associated with the presence of SCC T2. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

  3. Clinical and Pathologic Features of H-Type Bovine Spongiform Encephalopathy Associated with E211K Prion Protein Polymorphism

    PubMed Central

    Greenlee, Justin J.; Smith, Jodi D.; West Greenlee, M. Heather; Nicholson, Eric M.

    2012-01-01

    The majority of bovine spongiform encephalopathy (BSE) cases have been ascribed to the classical form of the disease. H-type and L-type BSE cases have atypical molecular profiles compared to classical BSE and are thought to arise spontaneously. However, one case of H-type BSE was associated with a heritable E211K mutation in the prion protein gene. The purpose of this study was to describe transmission of this unique isolate of H-type BSE when inoculated into a calf of the same genotype by the intracranial route. Electroretinograms were used to demonstrate preclinical deficits in retinal function, and optical coherence tomography was used to demonstrate an antemortem decrease in retinal thickness. The calf rapidly progressed to clinical disease (9.4 months) and was necropsied. Widespread distribution of abnormal prion protein was demonstrated within neural tissues by western blot and immunohistochemistry. While this isolate is categorized as BSE-H due to a higher molecular mass of the unglycosylated PrPSc isoform, a strong labeling of all 3 PrPSc bands with monoclonal antibodies 6H4 and P4, and a second unglycosylated band at approximately 14 kDa when developed with antibodies that bind in the C-terminal region, it is unique from other described cases of BSE-H because of an additional band 23 kDa demonstrated on western blots of the cerebellum. This work demonstrates that this isolate is transmissible, has a BSE-H phenotype when transmitted to cattle with the K211 polymorphism, and has molecular features that distinguish it from other cases of BSE-H described in the literature. PMID:22715405

  4. Clinical and pathologic features of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism.

    PubMed

    Greenlee, Justin J; Smith, Jodi D; West Greenlee, M Heather; Nicholson, Eric M

    2012-01-01

    The majority of bovine spongiform encephalopathy (BSE) cases have been ascribed to the classical form of the disease. H-type and L-type BSE cases have atypical molecular profiles compared to classical BSE and are thought to arise spontaneously. However, one case of H-type BSE was associated with a heritable E211K mutation in the prion protein gene. The purpose of this study was to describe transmission of this unique isolate of H-type BSE when inoculated into a calf of the same genotype by the intracranial route. Electroretinograms were used to demonstrate preclinical deficits in retinal function, and optical coherence tomography was used to demonstrate an antemortem decrease in retinal thickness. The calf rapidly progressed to clinical disease (9.4 months) and was necropsied. Widespread distribution of abnormal prion protein was demonstrated within neural tissues by western blot and immunohistochemistry. While this isolate is categorized as BSE-H due to a higher molecular mass of the unglycosylated PrP(Sc) isoform, a strong labeling of all 3 PrP(Sc) bands with monoclonal antibodies 6H4 and P4, and a second unglycosylated band at approximately 14 kDa when developed with antibodies that bind in the C-terminal region, it is unique from other described cases of BSE-H because of an additional band 23 kDa demonstrated on western blots of the cerebellum. This work demonstrates that this isolate is transmissible, has a BSE-H phenotype when transmitted to cattle with the K211 polymorphism, and has molecular features that distinguish it from other cases of BSE-H described in the literature.

  5. Adenyl cyclase activator forskolin protects against Huntington's disease-like neurodegenerative disorders

    PubMed Central

    Mehan, Sidharth; Parveen, Shaba; Kalra, Sanjeev

    2017-01-01

    Long term suppression of succinate dehydrogenase by selective inhibitor 3-nitropropionic acid has been used in rodents to model Huntington's disease where mitochondrial dysfunction and oxidative damages are primary pathological hallmarks for neuronal damage. Improvements in learning and memory abilities, recovery of energy levels, and reduction of excitotoxicity damage can be achieved through activation of Adenyl cyclase enzyme by a specific phytochemical forskolin. In this study, intraperitoneal administration of 10 mg/kg 3-nitropropionic acid for 15 days in rats notably reduced body weight, worsened motor cocordination (grip strength, beam crossing task, locomotor activity), resulted in learning and memory deficits, greatly increased acetylcholinesterase, lactate dehydrogenase, nitrite, and malondialdehyde levels, obviously decreased adenosine triphosphate, succinate dehydrogenase, superoxide dismutase, catalase, and reduced glutathione levels in the striatum, cortex and hippocampus. Intragastric administration of forskolin at 10, 20, 30 mg/kg dose-dependently reversed these behavioral, biochemical and pathological changes caused by 3-nitropropionic acid. These results suggest that forskolin exhibits neuroprotective effects on 3-nitropropionic acid-induced Huntington's disease-like neurodegeneration. PMID:28400813

  6. Cross-sectional and longitudinal features of non-fluent/agrammatic primary progressive aphasia with underlying corticobasal degeneration or progressive supranuclear palsy pathology

    PubMed Central

    Santos-Santos, Miguel A.; Mandelli, Maria Luisa; Binney, Richard J.; Ogar, Jennifer; Wilson, Stephen M.; Henry, Maya L.; Hubbard, H. Isabel; Meese, Minerva; Attygalle, Suneth; Rosenberg, Lynne; Pakvasa, Mikhail; Trojanowski, John Q.; Grinberg, Lea T.; Rosen, Howie; Boxer, Adam L.; Miller, Bruce L.; Seeley, William W; Gorno-Tempini, Maria Luisa

    2016-01-01

    Importance We provide novel evidence of specific clinical and neuroimaging features that may help for the in vivo prediction of underlying pathology in non-fluent/agrammatic primary progressive aphasia (nfvPPA) patients with progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD) proved by autopsy. Objective To characterize the neurological, cognitive and neuroimaging features of patients with nvfPPA- in whom either PSP or CBD was eventually confirmed at autopsy- at initial presentation and at 1-year follow-up. Design, Setting, and Participants Prospective longitudinal clinical-pathological study was conducted in a tertiary research clinic that specialized in cognitive disorders. Patients (n=14) were evaluated between January 2002 and December 2014. Inclusion criteria were: a clinical diagnosis of nfvPPA; the availability of speech, language, and cognitive testing for at least one evaluation; magnetic resonance imaging within 6 months of initial evaluation, and a postmortem pathological diagnosis of PSP or CBD. Main Outcomes and Measures Clinical, cognitive, and neuroimaging longitudinal data were analyzed to characterize the whole nfvPPA-4R tau group and identify differences between nfvPPA-PSP and nfvPPA-CBD at presentation and longitudinally. Results Patient groups did not differ significantly in age, gender or handedness (nfvPPA-PSP: median [interquartile range] age 74 [67–76] years, 1/5 male: 1/4 left-handed; nfvPPA-CBD 65 [54–81] years, 3/9 male, 0/9 left-handed). Motor speech impairment and left frontal white matter atrophy were the most prominent common features. At presentation, dysarthria (Motor Speech Examination score median [interquartile range] nfvPPA-PSP: 4 [2–7], nfvPPA-CBD 0 [0–4]; p=0.02), depression (Geriatric Depression Scale score median [interquartile range] nfvPPA-PSP 19 [3–28], nfvPPA-CBD 4 [0–16]; p=0.04) and relatively selective white matter atrophy were typical of nfvPPA-PSP, while greater grey matter atrophy

  7. A TNFRSF14-FcɛRI-mast cell pathway contributes to development of multiple features of asthma pathology in mice

    PubMed Central

    Sibilano, Riccardo; Gaudenzio, Nicolas; DeGorter, Marianne K.; Reber, Laurent L.; Hernandez, Joseph D.; Starkl, Philipp M.; Zurek, Oliwia W.; Tsai, Mindy; Zahner, Sonja; Montgomery, Stephen B.; Roers, Axel; Kronenberg, Mitchell; Yu, Mang; Galli, Stephen J.

    2016-01-01

    Asthma has multiple features, including airway hyperreactivity, inflammation and remodelling. The TNF superfamily member TNFSF14 (LIGHT), via interactions with the receptor TNFRSF14 (HVEM), can support TH2 cell generation and longevity and promote airway remodelling in mouse models of asthma, but the mechanisms by which TNFSF14 functions in this setting are incompletely understood. Here we find that mouse and human mast cells (MCs) express TNFRSF14 and that TNFSF14:TNFRSF14 interactions can enhance IgE-mediated MC signalling and mediator production. In mouse models of asthma, TNFRSF14 blockade with a neutralizing antibody administered after antigen sensitization, or genetic deletion of Tnfrsf14, diminishes plasma levels of antigen-specific IgG1 and IgE antibodies, airway hyperreactivity, airway inflammation and airway remodelling. Finally, by analysing two types of genetically MC-deficient mice after engrafting MCs that either do or do not express TNFRSF14, we show that TNFRSF14 expression on MCs significantly contributes to the development of multiple features of asthma pathology. PMID:27982078

  8. "High-grade" central acellular carcinoma and matrix-producing carcinoma of the breast: correlation between ultrasonographic findings and pathological features.

    PubMed

    Yamaguchi, Rin; Tanaka, Maki; Mizushima, Yasuko; Hirai, Yoshitake; Yamaguchi, Miki; Terasaki, Hiroshi; Yokoyama, Toshiro; Tsuchiya, Shin-ichi; Nakashima, Osamu; Yano, Hirohisa

    2011-09-01

    High-grade carcinoma with a large central acellular zone (central acellular carcinoma, CAC) and matrixproducing carcinoma (MPC) are aggressive tumors that both have a central myxomatous acellular zone. Their characteristic morphology may be useful in diagnostic imaging. Ultrasonographic findings based on the Breast Imaging Recording and Data System (BI-RADS) and detailed histological features were evaluated in 11 cases of CAC and 2 cases of MPC to characterize their features. Safranin-O staining was undertaken for the evaluation of central acellular zones in these tumors. Overall, ultrasonography demonstrated heterogeneous hyperechoic lesions in the center of the hypoechoic mass. Posterior echo enhancement was observed in all but 1 case. One case was classified as malignant and the others as "borderline." Histologically, cancer tissue was located in the periphery of the tumor with a ring-like structure and fewer cellular central areas comprising hyaline cartilage myxoid material such as those stained by safranin-O. The present study showed that the pathological findings of CACs and MPCs accurately reflect the ultrasonographic findings. Tumors that showed hyperechoic areas in the center of the hypoechoic mass, with posterior echo enhancement indicating acellular zones composed by myxochondroid material, and that were also relatively round on ultrasonography may be benign, but evaluation is required to exclude CAC and MPC.

  9. Increase in primary surgical treatment of T1 and T2 oropharyngeal squamous cell carcinoma and rates of adverse pathologic features: National Cancer Data Base.

    PubMed

    Cracchiolo, Jennifer R; Baxi, Shrujal S; Morris, Luc G; Ganly, Ian; Patel, Snehal G; Cohen, Marc A; Roman, Benjamin R

    2016-05-15

    There has been increasing interest in the primary surgical treatment of patients with early T classification (T1-T2) oropharyngeal squamous cell carcinoma (OPSCC), with the stated goal of de-escalating or avoiding adjuvant treatment. Herein, the authors sought to determine the degree to which this interest has translated into changes in practice patterns, and the rates of adverse postoperative pathologic features. Patients with T1 to T2 OPSCC in the National Cancer Data Base who were treated from 2004 through 2013 were categorized as receiving primary surgical or primary radiation-based treatment. Trends in treatment selection and factors related to the selection of primary surgery were examined. The rates of adverse pathologic features including positive surgical margins, extracapsular spread (ECS), and advanced T and N classifications after surgery were analyzed. Of 8768 patients with T1 to T2 OPSCC, 68% underwent primary surgical treatment, increasing from 56% in 2004 to 82% in 2013 (P<.0001). The highest versus lowest volume hospitals treated 78% versus 59% of patients with primary surgery (odds ratio, 2.23; 95% confidence interval, 1.55-3.22 [P<.0001]). Higher lymph node classification was found to be predictive of lower rates of primary surgery, but the majority of patients with clinical N2/N3 disease underwent primary surgery. Among patients treated with surgery, positive surgical margins were present in 24% and ECS in 25% of patients. The rate of positive surgical margins decreased over time (P<.0001) and was observed less often at high-volume centers (P<.0001). Among candidates for single-modality therapy (those with clinical T1-T2/N0-N1 disease), 33% had positive surgical margins and/or ECS and 47% had at least 1 adverse feature (T3-T4 disease, N2-N3 disease, positive surgical margins, and/or ECS). Primary surgical treatment among patients with early T classification OPSCC has become more widespread. Cancer 2016;122:1523-32. © 2016 American Cancer

  10. Clinical-pathological features and treatment modalities associated with recurrence in DCIS and micro-invasive carcinoma: Who to treat more and who to treat less.

    PubMed

    Toss, Angela; Palazzo, Juan; Berger, Adam; Guiles, Frances; Sendecki, Jocelyn Andrel; Simone, Nicole; Anne, Rani; Avery, Tiffany; Jaslow, Rebecca; Lazar, Melissa; Tsangaris, Theodore; Cristofanilli, Massimo

    2016-10-01

    The primary aim in the management of DCIS is the prevention of recurrence and contralateral tumor. Risk factors for DCIS recurrence and appropriate treatments are still widely debated. Adjuvant therapies after surgical resection reduce recurrences and contralateral disease, but these treatments have significant financial costs, side effects and there is a group of low-risk patients who would not gain additional benefit. The aim of our analysis was to identify clinical-pathological features and treatment modalities associated with recurrence in DCIS and microinvasive carcinoma. In the Thomas Jefferson University Cancer Registry of Philadelphia, we identified 865 patients with DCIS or micro-invasive carcinoma treated between 2003 and 2013. Associations between recurrence and demographic factors (age at diagnosis, ethnicity), biological features (ER, PR and HER2) and treatment modalities (surgery, radiotherapy and endocrine treatment) were assessed. Our single institution register-based study showed that distribution of age at diagnosis and biological features did not significantly differ among ethnic groups. Younger women and micro-invasive carcinoma patients were more likely to undergo mastectomy, while African Americans were more likely to take endocrine therapy and undergo radiotherapy. In our sample only ER/PR negative DCIS were associated with significantly higher recurrence rate. Moreover, we reported a high rate of HER2 positive recurrences, suggesting that expression of this oncogene may represent a potential biomarker for DCIS at high risk of recurrence. To better define the molecular profile of the subgroup at worse prognosis might help to identify biomarkers predictive of recurrence or second tumors, identifying patients candidates for more appropriate treatments.

  11. Consideration of the Pathological Features of Pediatric Congenital Heart Diseases Which Are Ideally Suitable for Diagnosing With Multidetector-row CT

    PubMed Central

    Hayabuchi, Yasunobu; Inoue, Miki; Watanabe, Noriko; Sakata, Miho; Ohnishi, Tatsuya; Kagami, Shoji

    2011-01-01

    Background A lots of articles published regarding the usefulness of multidetector-row computed tomography (MDCT) in children with congenital heart disease (CHD) mostly describe that it can be an alternative to the invasive catheterization and angiography. The unique diagnostic features of this imaging modality have been largely ignored or disregarded. We described the pathological conditions that cannot be diagnosed by conventional angiography with cardiac catheterization but can be accurately diagnosed by MDCT. Methods We retrospectively reviewed non-ECG-gated MDCT images acquired from 452 children and young adults with CHD between 2005 and 2010 in our institute. In this article, we focused on the diagnostic advantages of MDCT, and indicated five pathological conditions. (1) When Blalock-Taussig shunt total occlusion prevents catheter insertion into the artificial vessel and angiography is ruled out, the peripheral pulmonary artery during the peripheral pulmonary artery can be imaged and diagnosed using MDCT based on blood flow supplied from many small collateral vessels originating from the aorta. (2) The location and protrusion of the device in the vessel after coil embolization to treat patent ductus arteriosus can be accurately visualized by virtual endoscopy using MDCT. (3) Calcification of patches, synthetic blood vessels, and other prostheses that is indistinct on conventional angiograms is clear on MDCT. (4) Simultaneous MDCT observations of the anatomical relationships between arterial and venous systems on the same image can clarify the detail diagnosis for surgical treatment. (5) Compression of the airways by the great vessels and pulmonary segmental emphysematous change can be diagnosed by MDCT. Results and Conclusions Among patients with CHD, MDCT is useful not only as a non-invasive alternative to conventional angiography, but also as a tool for specific morphological diagnoses. In the future, it will be necessary to accumulate experience in the

  12. Degree of hydronephrosis predicts adverse pathological features and worse oncologic outcomes in patients with high-grade urothelial carcinoma of the upper urinary tract.

    PubMed

    Chung, Paul H; Krabbe, Laura-Maria; Darwish, Oussama M; Westerman, Mary E; Bagrodia, Aditya; Gayed, Bishoy A; Haddad, Ahmed Q; Kapur, Payal; Sagalowsky, Arthur I; Lotan, Yair; Margulis, Vitaly

    2014-10-01

    To evaluate degree of hydronephrosis (HN) as a surrogate for adverse pathological features and oncologic outcomes in patients with high-grade (HG) and low-grade (LG) upper tract urothelial carcinomas (UTUCs). We retrospectively reviewed 141 patients with localized UTUCs that underwent extirpative surgery at a tertiary referral center. Preoperative imaging was used to evaluate presence and degree of ipsilateral HN. We evaluated degree of HN (none/mild vs. moderate/severe), pathological findings, and oncologic outcomes. HG UTUC was present in 113 (80%) patients, muscle-invasive disease (≥pT2) in 49 (35%), and non-organ-confined disease (≥pT3) in 41 (29%). At a median follow-up of 34 months, 49 (35%) patients experienced intravesical recurrence, 28 (20%) developed local/systemic recurrence, and 24 (17%) died of UTUC. HN was graded as none/mild in 77 (55%) patients and moderate/severe in 64 (45%). In patients with HG UTUC, but not LG, degree of HN was associated with advanced pathological stage (P<0.001), positive lymph nodes (P = 0.01), local/systemic recurrence-free survival (hazard ratio [HR] = 5.5, P = 0.02), and cancer-specific survival (HR = 5.2, P = 0.02). On multivariable analysis of preoperative factors, degree of HN in patients with HG UTUC was associated with muscle invasion (HR = 9.3; 95% CI: 3.08-28.32; P<0.001), non-organ-confined disease (HR = 4.5; 95% CI: 1.66-12.06; P = 0.003), local/systemic recurrence-free survival (HR = 2.5; 95% CI: 1.07-5.64; P = 0.04), and cancer-specific survival (HR = 2.6; 95% CI: 1.05-6.22; P = 0.04). Degree of HN can serve as a surrogate for advanced disease and predict worse oncologic outcomes in HG UTUC. Degree of HN was not predictive of intravesical or local/systemic recurrence in LG UTUC. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Ultrasound assessment of synovial pathologic features in rheumatoid arthritis using comprehensive multiplane images of the second metacarpophalangeal joint: identification of the components that are reliable and influential on the global assessment of the whole joint.

    PubMed

    Ikeda, Kei; Seto, Yohei; Narita, Akihiro; Kawakami, Atsushi; Kawahito, Yutaka; Ito, Hiromu; Matsushita, Isao; Ohno, Shigeru; Nishida, Keiichiro; Suzuki, Takeshi; Kaneko, Atsushi; Ogasawara, Michihiro; Fukae, Jun; Henmi, Mihoko; Sumida, Takayuki; Kamishima, Tamotsu; Koike, Takao

    2014-03-01

    The aim of this pilot study was to provide groundwork that could be utilized to optimize the global ultrasound (US) assessment of the whole joint for synovial pathologic features in patients with rheumatoid arthritis (RA). US images of the second metacarpophalangeal joint in 8 predefined imaging planes, comprising regions that comprehensively capture the synovial pathologic features of the whole joint, were obtained from 30 patients with RA. Twelve experienced sonographers evaluated these images at the level of both the individual image and the whole joint, using a visual analog scale (VAS) to assess pathologic severity. Interrater reproducibility of the VAS scores was evaluated with intraclass correlation coefficients (ICCs), and factors that independently influenced the global assessment of the whole joint were identified using multiple linear regression analysis. A total of 14,276 VAS scores were analyzed. Interrater reproducibility of any eligible VAS assessment of synovial pathologic features was good (ICC 0.65). US assessment of synovial pathologic features in joints with mild inflammation was less reproducible than that in joints with severe inflammation. Although the most severely affected region in a joint did not always represent the average pathologic severity among the 8 regions, global assessment of the whole joint strongly correlated with assessment of the most severely affected region (P < 0.001). Importantly, the standard, midline imaging plane was not the most influential plane on the global assessment of the whole joint. Assessment of synovial fluid accumulation was not reproducible (ICCs 0.20-0.42) and did not substantially influence the global assessment of synovial inflammation (β = 0.06). The results of this study provide a unique data set that could be utilized to optimize the global US assessment of synovial pathologic features of the whole joint in patients with RA. Copyright © 2014 by the American College of Rheumatology.

  14. [Comparative study of clinical and pathological features of breast cancer in women with 40 years old and younger vs 70 years old and older].

    PubMed

    Cuan Martínez, Juan Ramón; Mainero Ratchelous, Fernando Enrique; Aguilar Gallegos, Israel Uriban; Bernechea Miranda, Abel; Buenrostro Pineda, Marco Antonio; Burgos Portillo, Iván; Cortés Herrera, Ana Edelmira Angeles; Burguete Vera, José Juan

    2008-06-01

    Invasive breast cancer is the most common neoplasia in women attended at IMSS health system since 2004. To compare clinical and radiological characteristics on initial appraisal, as well as surgical treatment, pathological features and adjuvant treatment in women with primary breast cancer of 40 years old and younger vs 70 years old and older. Clinical, radiological and pathological data of 150 patients with breast cancer treated at Hospital de ginecoobstetricia Luis Castelazo Ayala, from January 2003 to June 2006 were collected, and after divided in two groups: 1) patients with 40 years old and younger (n = 50), and 2) patients with 70 years old and older (n = 100). Tumoral size and radiological characteristics were similar in both groups. Group 1 and group 2 had 22 and 13%, respectively, of family history of breast cancer. Fine needle biopsy has positive predictive value of 50% for group 1, and 36% for group 2. Conservative surgery was less common at group 2. Most frequent histological type in both groups was infiltrating ductal carcinoma, followed by infiltrating lobular carcinoma, most common in older women (19 vs 12%), and we found more well differentiated ductal carcinomas in the group of 70 years old and older (12 vs 4%). Seventy-six percent of group 1 and 75% of group 2 were classified as early stage breast cancer (stages I and II). Cytotoxic therapy was offered mostly to group 1, 92 vs 35%. Radiotherapy (80 vs 59%), and hormonal therapy was given only to 56% of group 1 vs 80% of group 2. Clinical and staging features were similar in both groups. Family history was more influential to group 1. Fine needle biopsy has a low positive predictive value for diagnostic. Well-differentiated carcinomas were higher in patients of group 2, and group 1 had more high-grade carcinomas. There was a trend to perform more conservative surgery at group 1, as well as they underwent more adjuvant chemotherapy and radiotherapy. Use of hormonal therapy was more common at group 2.

  15. Renal cell carcinoma co-existent with other renal disease: clinico-pathological features in pre-dialysis patients and those receiving dialysis or renal transplantation.

    PubMed

    Peces, Ramón; Martínez-Ara, Jorge; Miguel, José Luis; Arrieta, Javier; Costero, Olga; Górriz, José Luis; Picazo, Mari-Luz; Fresno, Manuel

    2004-11-01

    Patients on chronic dialysis are prone to developing acquired cystic kidney disease (ACKD), which may lead to the development of renal cell carcinoma (RCC). The risk factors for the development of RCC so far have not been determined in pre-dialysis patients with co-existent renal disease. The aim of this study was to evaluate the clinico-pathological features of RCC in pre-dialysis patients with associated renal diseases or in those undergoing chronic dialysis and renal transplantation. We studied 32 kidneys from 31 patients with RCC and associated renal diseases. Of those, 18 kidneys were from 17 patients not on renal replacement therapy (RRT) when diagnosed with RCC; 14 patients received dialysis or dialysis followed by renal transplantation. Several clinico-pathological features were analysed and compared between the two groups. Overall, there was a preponderance of males (75%); nephrosclerosis was the predominant co-existent disease (31%). The median intervals from renal disease to RCC in the dialysis and transplanted groups were significantly longer than in the pre-dialysis group (15.8+/-1.1 vs 2.4+/-0.7 years, P<0.0001). In contrast to pre-dialysis RCC, the dialysis and transplant RCC groups had greater frequency of ACKD (100 vs 28%, P<0.0001), papillary type RCC (43 vs 11%, P<0.05) and multifocal tumours (43 vs 5%, P<0.05). At the end of the study, 71% of dialysis and transplanted patients and 72% of pre-dialysis patients were alive. ACKD develops in dialysis patients, as it does in those with renal disease prior to RRT. The duration of renal disease, rather than the dialysis procedure itself, appears to be the main determinant of ACKD and RCC. The RCC occurring in patients with ACKD and prolonged RRT is more frequently of the papillary type and multifocal than the RCC occurring in patients with no or few acquired cysts and a short history of renal disease. Long-term outcomes did not differ between the two groups.

  16. Small Bowel Carcinomas in Coeliac or Crohn's Disease: Clinico-pathological, Molecular, and Prognostic Features. A Study From the Small Bowel Cancer Italian Consortium.

    PubMed

    Vanoli, Alessandro; Di Sabatino, Antonio; Furlan, Daniela; Klersy, Catherine; Grillo, Federica; Fiocca, Roberto; Mescoli, Claudia; Rugge, Massimo; Nesi, Gabriella; Fociani, Paolo; Sampietro, Gianluca; Ardizzone, Sandro; Luinetti, Ombretta; Calabrò, Antonio; Tonelli, Francesco; Volta, Umberto; Santini, Donatella; Caio, Giacomo; Giuffrida, Paolo; Elli, Luca; Ferrero, Stefano; Latella, Giovanni; Ciardi, Antonio; Caronna, Roberto; Solina, Gaspare; Rizzo, Aroldo; Ciacci, Carolina; D'Armiento, Francesco P; Salemme, Marianna; Villanacci, Vincenzo; Cannizzaro, Renato; Canzonieri, Vincenzo; Reggiani Bonetti, Luca; Biancone, Livia; Monteleone, Giovanni; Orlandi, Augusto; Santeusanio, Giuseppe; Macciomei, Maria C; D'Incà, Renata; Perfetti, Vittorio; Sandri, Giancarlo; Silano, Marco; Florena, Ada M; Giannone, Antonino G; Papi, Claudio; Coppola, Luigi; Usai, Paolo; Maccioni, Antonio; Astegiano, Marco; Migliora, Paola; Manca, Rachele; Martino, Michele; Trapani, Davide; Cerutti, Roberta; Alberizzi, Paola; Riboni, Roberta; Sessa, Fausto; Paulli, Marco; Solcia, Enrico; Corazza, Gino R

    2017-08-01

    An increased risk of small bowel carcinoma [SBC] has been reported in coeliac disease [CD] and Crohn's disease [CrD]. We explored clinico-pathological, molecular, and prognostic features of CD-associated SBC [CD-SBC] and CrD-associated SBC [CrD-SBC] in comparison with sporadic SBC [spo-SBC]. A total of 76 patients undergoing surgical resection for non-familial SBC [26 CD-SBC, 25 CrD-SBC, 25 spo-SBC] were retrospectively enrolled to investigate patients' survival and histological and molecular features including microsatellite instability [MSI] and KRAS/NRAS, BRAF, PIK3CA, TP53, HER2 gene alterations. CD-SBC showed a significantly better sex-, age-, and stage-adjusted overall and cancer-specific survival than CrD-SBC, whereas no significant difference was found between spo-SBC and either CD-SBC or CrD-SBC. CD-SBC exhibited a significantly higher rate of MSI and median tumour-infiltrating lymphocytes [TIL] than CrD-SBC and spo-SBC. Among the whole SBC series, both MSI─which was the result of MLH1 promoter methylation in all but one cases─and high TIL density were associated with improved survival at univariable and stage-inclusive multivariable analysis. However, only TILs retained prognostic power when clinical subgroups were added to the multivariable model. KRAS mutation and HER2 amplification were detected in 30% and 7% of cases, respectively, without prognostic implications. In comparison with CrD-SBC, CD-SBC patients harbour MSI and high TILs more frequently and show better outcome. This seems mainly due to their higher TIL density, which at multivariable analysis showed an independent prognostic value. MSI/TIL status, KRAS mutations and HER2 amplification might help in stratifying patients for targeted anti-cancer therapy.

  17. Syndromic versus non-syndromic sporadic gastrin-producing neuroendocrine tumors of the duodenum: comparison of pathological features and biological behavior.

    PubMed

    Rosentraeger, M Johannes; Garbrecht, Nele; Anlauf, Martin; Raffel, Andreas; Knoefel, Wolfram T; Wiedenmann, Bertram; Klöppel, Günter

    2016-03-01

    Sporadic gastrin-producing neuroendocrine tumors of the duodenum present either with the Zollinger-Ellison syndrome (ZES) or with unspecific symptoms. While syndromic gastrin-producing neuroendocrine tumors often show metastases at the time of diagnosis, those without a syndrome do not. The aim of the study was to search for clinicopathological features that may distinguish the two categories of gastrin-producing duodenal tumors. In a retrospective study, we analyzed the clinical and pathological data in a series of 41 patients with syndromic (i.e., gastrinomas) or non-syndromic duodenal gastrin-producing neuroendocrine tumors (ns-gas-NETs). Twenty-four (59 %) of the 41 patients had tumors that were associated with a ZES and were classified as gastrinomas. These tumors showed a higher Ki-67 index than that of the ns-gas-NETs (1.74 vs. 0.85 %, p = 0.012). In addition, they had more lymph node metastases (75 vs. 6 %, p < 0.001) and showed liver metastases and thus presented much more frequently in TNM stage ≥III (75 vs. 6 %; p < 0.001) than their non-syndromic counterparts. Gastrinomas were removed surgically, ns-gas-NETs endoscopically. We did not observe any significant differences in overall survival or recurrence of disease. Duodenal gastrinomas show no clear morphological features that distinguish them from their non-syndromic counterparts. However, the patients with gastrinomas present in a more advanced stage of disease and need surgical treatment, while non-syndromic gastrin-producing duodenal NETs may be cured by complete endoscopical removal.

  18. Eco-epidemiological and pathological features of wildlife mortality events related to cyanobacterial bio-intoxication in the Kruger National Park, South Africa.

    PubMed

    Bengis, Roy; Govender, Danny; Lane, Emily; Myburgh, Jan; Oberholster, Paul; Buss, Peter; Prozesky, Leon; Keet, Dewald

    2016-10-31

    Over the past decade, several clustered, multispecies, wildlife mortality events occurred in the vicinity of two man-made earthen dams in the southern and south central regions of the Kruger National Park, South Africa. On field investigation, heavy cyanobacterial blooms were visible in these impoundments and analysis of water samples showed the dominance of Microcystis spp. (probably Microcystis aeruginosa). Macroscopic lesions seen at necropsy and histopathological lesions were compatible with a diagnosis of cyanobacterial intoxication. Laboratory toxicity tests and assays also confirmed the presence of significant levels of microcystins in water from the two dams. These outbreaks occurred during the dry autumn and early winter seasons when water levels in these dams were dropping, and a common feature was that all the affected dams were supporting a large number of hippopotamuses (Hippopotamus amphibius). It is hypothesised that hippopotamus' urine and faeces, together with agitation of the sediments, significantly contributed to internal loading of phosphates and nitrogen - leading to eutrophication of the water in these impoundments and subsequent cyanobacterial blooms. A major cause for concern was that a number of white rhinoceros (Ceratotherium simum) were amongst the victims of these bio-intoxication events. This publication discusses the eco-epidemiology and pathology of these clustered mortalities, as well as the management options considered and eventually used to address the problem.

  19. Pathogenic insights from Huntington's disease-like 2 and other Huntington's disease genocopies.

    PubMed

    Margolis, Russell L; Rudnicki, Dobrila D

    2016-12-01

    Huntington's disease-like 2 (HDL2) is a rare, progressive, autosomal dominant neurodegenerative disorder that genetically, clinically, and pathologically closely resembles Huntington's disease. We review HDL2 pathogenic mechanisms and examine the implications of these mechanisms for Huntington's disease and related diseases. HDL2 is caused by a CTG/CAG repeat expansion in junctophilin-3. Available data from cell and animal models and human brain suggest that HDL2 is a complex disease in which transcripts and proteins expressed bidirectionally from the junctophilin-3 locus contribute to pathogenesis through both gain-and loss-of-function mechanisms. Recent advances indicate that the pathogenesis of Huntington's disease is equally complex, despite the emphasis on toxic gain-of-function properties of the mutant huntingtin protein. Studies examining in parallel the genetic, clinical, neuropathological, and mechanistic similarities between Huntington's disease and HDL2 have begun to identify points of convergence between the pathogenic pathways of the two diseases. Comparisons to other diseases that are phenotypically or genetically related to Huntington's disease and HDL2 will likely reveal additional common pathways. The ultimate goal is to identify shared therapeutic targets and eventually develop therapies that may, at least in part, be effective across multiple similar rare diseases, an essential approach given the scarcity of resources for basic and translational research.

  20. [Specific features of the development of pathology of the upper respiratory tracts in the workers employed in the ore mining industry in the subarctic regions].

    PubMed

    Fedina, I N; Sineva, E L

    2009-01-01

    Criteria for the risk of development of occupational pathology of the upper respiratory tracts in the workers employed in the ore mining industry have been proposed based on the results of evaluation of the occurrence of pathological changes, morpho-functional characteristics of upper respiratory tract mucosa, and immunological properties. These criteria provide a basis for the development of differential approach to the choice of priority hygienic and medical preventive measures designed to a lower the risk of respiratory organ pathology.

  1. Clinical and pathological features of toxoplasmosis in free-ranging common wombats (Vombatus ursinus) with multilocus genotyping of Toxoplasma gondii type II-like strains.

    PubMed

    Donahoe, Shannon L; Šlapeta, Jan; Knowles, Graeme; Obendorf, David; Peck, Sarah; Phalen, David N

    2015-04-01

    Toxoplasma gondii is a cosmopolitan zoonotic protozoan parasite with the capacity to infect virtually any warm blooded vertebrate species. Australian native marsupials are thought to be highly susceptible to toxoplasmosis; however, most reports are in captive animals and little is known about T. gondii associated disease in free-ranging marsupials, including wombats (Vombatus ursinus). This study describes the clinical and pathological features of eight cases of toxoplasmosis in free-ranging common wombats in Tasmania and New South Wales (NSW) from 1992 to 2013, including a morbidity and mortality event investigated in the Southern Highlands NSW in the autumn of 2010. The diagnosis of T. gondii infection was confirmed using either immunohistochemistry, molecular diagnostics or both. Utilizing the combination of direct DNA sequencing of B1, SAG1, 5'- and 3'-SAG2, alt.SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico DNA markers and virtual RFLP to genetically characterize two of the T. gondii strains, we found a nonarchetypal type II-like strain (ToxoDB PCR-RFLP genotype #1) and an atypical type II-like strain (ToxoDB PCR-RFLP genotype #3) to be the causal agents of toxoplasmosis in wombats from the 2010 morbidity and mortality event. This study suggests that T. gondii may act as a significant disease threat to free-ranging common wombats. Our findings indicate neurologic signs are a very common clinical presentation in common wombats with toxoplasmosis and T. gondii infection should be considered as a likely differential diagnosis for any common wombat exhibiting signs of blindness, head tilt, circling and changes in mentation.

  2. A novel NREM and REM parasomnia with sleep breathing disorder associated with antibodies against IgLON5: a case series, pathological features, and characterization of the antigen

    PubMed Central

    Sabater, Lidia; Gaig, Carles; Gelpi, Ellen; Bataller, Luis; Lewerenz, Jan; Torres-Vega, Estefanía; Contreras, Angeles; Giometto, Bruno; Compta, Yaroslau; Embid, Cristina; Vilaseca, Isabel; Iranzo, Alex; Santamaría, Joan; Dalmau, Josep; Graus, Francesc

    2014-01-01

    ) against IgLON5, member of a family of neuronal cell adhesion molecules. Only 1/285 controls (with progressive supranuclear palsy) had IgLON5 antibodies. Neuropathology showed neuronal loss and extensive deposits of hyperphosphorylated tau mainly involving the tegmentum of the brainstem and hypothalamus. Interpretation IgLON5-antibodies identify a unique NREM and REM parasomnia with sleep breathing dysfunction and pathological features suggesting a tauopathy. Funding Fondo de Investigaciones Sanitarias. Centros de Investigación Biomédica en Red de enfermedades neurodegenerativas (CIBERNED) and Respiratorias (CIBERES), Ministerio de Economía y Competitividad, Fundació la Marató TV3 and the National Institutes of Health. PMID:24703753

  3. The Characteristics of Herpes Simplex Virus Type 1 Infection in Rhesus Macaques and the Associated Pathological Features.

    PubMed

    Fan, Shengtao; Cai, Hongzhi; Xu, Xingli; Feng, Min; Wang, Lichun; Liao, Yun; Zhang, Ying; He, Zhanlong; Yang, Fengmei; Yu, Wenhai; Wang, Jingjing; Zhou, Jumin; Li, Qihan

    2017-01-30

    As one of the major pathogens for human herpetic diseases, herpes simplex virus type 1 (HSV1) causes herpes labialis, genital herpes and herpetic encephalitis. Our aim here was to investigate the infectious process of HSV1 in rhesus macaques and the pathological features induced during this infection. Clinical symptoms that manifested in the rhesus macaque during HSV1 infection included vesicular lesions and their pathological features. Viral distribution in the nervous tissues and associated pathologic changes indicated the typical systematic pathological processes associated with viral distribution of HSV1.Interestingly, vesicular lesions recurred in oral skin or in mucosa associated with virus shedding in macaques within four to five months post-infection,and viral latency-associated transcript (LAT) mRNA was found in the trigeminal ganglia (TG)on day 365 post-infection. Neutralization testing and enzyme-linked immunospot (ELISpot) detection of specific T cell responses confirmed the specific immunity induced by HSV1 infection. Thus, rhesus macaques could serve as an infectious model for HSV1 due to their typical clinical symptoms and the pathological recurrence associated with viral latency in nervous tissues.

  4. A Systematic Review of the Huntington Disease-Like 2 Phenotype.

    PubMed

    Anderson, David G; Walker, Ruth H; Connor, Myles; Carr, Jonathan; Margolis, Russell L; Krause, Amanda

    2017-01-01

    Huntington Disease-like 2 (HDL2) is a neurodegenerative disorder similar to Huntington Disease (HD) in its clinical phenotype, genetic characteristics, neuropathology and longitudinal progression. Proposed specific differences include an exclusive African ancestry, lack of eye movement abnormalities, increased Parkinsonism, and acanthocytes in HDL2. The objective was to determine the similarities and differences between HD and HDL2 by establishing the clinical phenotype of HDL2 with the published cases. A literature review of all clinically described cases of HDL2 until the end of 2016 was performed and a descriptive analysis was carried out. Sixty-nine new cases were described between 2001 and 2016. All cases had likely African ancestry, and most were found in South Africa and the USA. Many features were found to be similar to HD, including a strong negative correlation between repeat length and age of onset. Chorea was noted in 48/57 cases (84%). Dementia was reported in 74% patients, and Parkinsonism in 37%. Psychiatric features were reported in 44 out of 47 cases. Patients with chorea had lower expanded repeat lengths compared to patients without chorea. Eye movements were described in 19 cases, 8 were abnormal. Acanthocytes were detected in 4 of the 13 patients tested. Nineteen out of 20 MRIs were reported as abnormal with findings similar to HD. This review clarifies some aspects of the HDL2 phenotype and highlights others which require further investigation. Features that are unique to HDL2 have been documented in a minority of subjects and require prospective validation.

  5. Early-stage atherosclerosis in poloxamer 407-induced hyperlipidemic mice: pathological features and changes in the lipid composition of serum lipoprotein fractions and subfractions.

    PubMed

    Korolenko, Tatyana A; Johnston, Thomas P; Tuzikov, Fedor V; Tuzikova, Natalia A; Pupyshev, Alexandr B; Spiridonov, Victor K; Goncharova, Natalya V; Maiborodin, Igor V; Zhukova, Natalia A

    2016-01-22

    , biochemical and physiological changes documented in the present study using poloxamer 407-treated mice are related to the symptoms of early atherosclerosis in humans, it is suggested that the poloxamer 407-induced mouse model of hyperlipidemia and atherosclerosis might prove beneficial as an experimental animal model with which to evaluate the pathological features observed in early-stage atherosclerosis.

  6. Computational Pathology

    PubMed Central

    Louis, David N.; Feldman, Michael; Carter, Alexis B.; Dighe, Anand S.; Pfeifer, John D.; Bry, Lynn; Almeida, Jonas S.; Saltz, Joel; Braun, Jonathan; Tomaszewski, John E.; Gilbertson, John R.; Sinard, John H.; Gerber, Georg K.; Galli, Stephen J.; Golden, Jeffrey A.; Becich, Michael J.

    2016-01-01

    Context We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general. Objective To define the scope and needs of computational pathology. Data Sources A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments. Conclusions The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and non-pathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology. PMID:26098131

  7. Pathological gambling.

    PubMed

    Hollander, E; Buchalter, A J; DeCaria, C M

    2000-09-01

    With increasing access to gambling facilities through casinos, the Internet, and other venues, PG is a rapidly emerging mental health concern. This impulse-control disorder tends to be comorbid with a wide range of other disorders and is reportedly associated with a high rate of suicide. For most gamblers, gambling is a form of entertainment, but for many individuals, the activity leads to far-reaching disruption of family and work. The personal and societal financial ramifications are severe, and many individuals with PG end up in the criminal justice system. An understanding of the neurobiology of PG is beginning to surface. 5-HT is linked to behavioral initiation and disinhibition, which are important in the onset of the gambling cycle and the difficulty in ceasing the behavior. Norepinephrine is associated with the arousal and risk taking in patients with PG. Dopamine is linked to positive and negative reward, the addictive component of this disorder. Effective treatment strategies for pathological gamblers are emerging. Potentially useful pharmacologic agents include SRIs (clomipramine and fluvoxamine), mood stabilizers for pathological gamblers with comorbid bipolar disorders (lithium), and naltrexone. Cognitive-behavioral psychotherapies offer promising results in the treatment of patients with this disorder. To devise prevention and early-intervention programs, research is needed to identify specific features of the individuals at risk for gambling problems. Education targeting vulnerable youth that show early signs of gambling behavior may be worthwhile and should be investigated further. Funding is necessary to support these endeavors, so perhaps a portion of tax revenues generated from the gambling industry should go toward specialized treatment facilities, educational efforts, and research into the neurobiology and treatment of PG.

  8. Intranasal BMP9 Ameliorates Alzheimer Disease-Like Pathology and Cognitive Deficits in APP/PS1 Transgenic Mice

    PubMed Central

    Wang, Zigao; Xiong, Lu; Wan, Wenbin; Duan, Lijie; Bai, Xiaojing; Zu, Hengbing

    2017-01-01

    Alzheimer’s disease (AD) is the most common type of dementia and has no effective therapies. Previous studies showed that bone morphogenetic protein 9 (BMP9), an important factor in the differentiation and phenotype maintenance of cholinergic neurons, ameliorated the cholinergic defects resulting from amyloid deposition. These findings suggest that BMP9 has potential as a therapeutic agent for AD. However, the effects of BMP9 on cognitive function in AD and its underlying mechanisms remain elusive. In the present study, BMP9 was delivered intranasally to 7-month-old APP/PS1 mice for 4 weeks. Our data showed that intranasal BMP9 administration significantly improved the spatial and associative learning and memory of APP/PS1 mice. We also found that intranasal BMP9 administration significantly reduced the amyloid β (Aβ) plaques overall, inhibited tau hyperphosphorylation, and suppressed neuroinflammation in the transgenic mouse brain. Furthermore, intranasal BMP9 administration significantly promoted the expression of low-density lipoprotein receptor-related protein 1 (LRP1), an important membrane receptor involved in the clearance of amyloid β via the blood-brain barrier (BBB), and elevated the phosphorylation levels of glycogen synthase kinase-3β (Ser9), which is considered the main kinase involved in tau hyperphosphorylation. Our results suggest that BMP9 may be a promising candidate for treating AD by targeting multiple key pathways in the disease pathogenesis. PMID:28228716

  9. Musculoskeletal Pathology.

    PubMed

    Peat, Frances J; Kawcak, Christopher E

    2015-08-01

    The current understanding of pathology as it relates to common diseases of the equine musculoskeletal system is reviewed. Conditions are organized under the fundamental categories of developmental, exercise-induced, infectious, and miscellaneous pathology. The overview of developmental pathology incorporates the new classification system of juvenile osteochondral conditions. Discussion of exercise-induced pathology emphasizes increased understanding of the contribution of cumulative microdamage caused by repetitive cyclic loading. Miscellaneous musculoskeletal pathology focuses on laminitis, which current knowledge indicates should be regarded as a clinical syndrome with a variety of possible distinct mechanisms of structural failure that are outlined in this overview. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. The pathology of sarcoidosis.

    PubMed

    Gal, Anthony A; Koss, Michael N

    2002-09-01

    Sarcoidosis is a multisystemic disease characterized by a nonnecrotizing granulomatous inflammatory process that can progress through various stages of activity. The distinctive histology of sarcoidosis is often associated with various morphologic findings in the lung and other organs. The rare variants, necrotizing sarcoidal granulomas and nodular sarcoidosis, share some of the histologic features of typical sarcoidosis, but may have different clinical and pathologic manifestations. The clinician and pathologist should be aware of the diverse pathologic appearances of sarcoidosis.

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

    PubMed

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Therapeutic Approach of a High Functioning Individual With Traumatic Brain Injury and Subsequent Emotional Volatility With Features of Pathological Laughter and Crying With Dextromethorphan/Quinidine

    PubMed Central

    Garcia-Baran, Dynela; Johnson, Thomas M.; Wagner, Joyce; Shen, Joann; Geers, Michelle

    2016-01-01

    Abstract Pathological laughing and crying, or pseudobulbar affect (PBA), has been described in patients with neurological disorders such as multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, stroke, and traumatic brain injury (TBI) since the 19th century (Schiffer 2005). The syndrome is characterized by inappropriate episodes of laughing or crying after minor stimuli. It was first coined a disinhibition of cortical control by Kinnier Wilson in 1924. It was observed in brain disease and seen with mild TBI. It can impair social and occupational function and is largely underrecognized in clinical settings. PBA is usually treated with antidepressants and dopaminergic agents. In this case we treated a military recruit with TBI with Nuedexta—a dextromethorphan/Quinidine derivative with a subsequent decrease in his episodes. PMID:27015166

  13. Therapeutic Approach of a High Functioning Individual With Traumatic Brain Injury and Subsequent Emotional Volatility With Features of Pathological Laughter and Crying With Dextromethorphan/Quinidine.

    PubMed

    Garcia-Baran, Dynela; Johnson, Thomas M; Wagner, Joyce; Shen, Joann; Geers, Michelle

    2016-03-01

    Pathological laughing and crying, or pseudobulbar affect (PBA), has been described in patients with neurological disorders such as multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, stroke, and traumatic brain injury (TBI) since the 19th century (Schiffer 2005). The syndrome is characterized by inappropriate episodes of laughing or crying after minor stimuli. It was first coined a disinhibition of cortical control by Kinnier Wilson in 1924. It was observed in brain disease and seen with mild TBI. It can impair social and occupational function and is largely underrecognized in clinical settings. PBA is usually treated with antidepressants and dopaminergic agents. In this case we treated a military recruit with TBI with Nuedexta-a dextromethorphan/Quinidine derivative with a subsequent decrease in his episodes.

  14. Profiles of extracellular miRNA in cerebrospinal fluid and serum from patients with Alzheimer's and Parkinson's diseases correlate with disease status and features of pathology.

    PubMed

    Burgos, Kasandra; Malenica, Ivana; Metpally, Raghu; Courtright, Amanda; Rakela, Benjamin; Beach, Thomas; Shill, Holly; Adler, Charles; Sabbagh, Marwan; Villa, Stephen; Tembe, Waibhav; Craig, David; Van Keuren-Jensen, Kendall

    2014-01-01

    The discovery and reliable detection of markers for neurodegenerative diseases have been complicated by the inaccessibility of the diseased tissue--such as the inability to biopsy or test tissue from the central nervous system directly. RNAs originating from hard to access tissues, such as neurons within the brain and spinal cord, have the potential to get to the periphery where they can be detected non-invasively. The formation and extracellular release of microvesicles and RNA binding proteins have been found to carry RNA from cells of the central nervous system to the periphery and protect the RNA from degradation. Extracellular miRNAs detectable in peripheral circulation can provide information about cellular changes associated with human health and disease. In order to associate miRNA signals present in cell-free peripheral biofluids with neurodegenerative disease status of patients with Alzheimer's and Parkinson's diseases, we assessed the miRNA content in cerebrospinal fluid and serum from postmortem subjects with full neuropathology evaluations. We profiled the miRNA content from 69 patients with Alzheimer's disease, 67 with Parkinson's disease and 78 neurologically normal controls using next generation small RNA sequencing (NGS). We report the average abundance of each detected miRNA in cerebrospinal fluid and in serum and describe 13 novel miRNAs that were identified. We correlated changes in miRNA expression with aspects of disease severity such as Braak stage, dementia status, plaque and tangle densities, and the presence and severity of Lewy body pathology. Many of the differentially expressed miRNAs detected in peripheral cell-free cerebrospinal fluid and serum were previously reported in the literature to be deregulated in brain tissue from patients with neurodegenerative disease. These data indicate that extracellular miRNAs detectable in the cerebrospinal fluid and serum are reflective of cell-based changes in pathology and can be used to assess

  15. Pathology of hereditary nephritis

    PubMed Central

    Joshi, V. V.

    1968-01-01

    This report describes the renal pathology in three siblings with hereditary nephritis. All three cases showed combined features of chronic glomerulonephritis, pyelonephritis, and interstitial nephritis. Foam cells were seen in only one case. These findings support the contention of Krickstein, Gloor, and Balogh (1966) that the renal changes in hereditary nephritis are those of a mixed nephritis. Images PMID:5717545

  16. Oral pathology.

    PubMed

    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.

  17. [Clinical and pathological features of gastrointestinal stromal tumors (GIST) in a single institution: A descriptive study and review of the literature].

    PubMed

    Flores-Funes, Diego; Lirón-Ruiz, Ramón José; Pérez-Guarinos, Carmen Victoria; Martín-Lorenzo, Juan Gervasio; Torralba-Martínez, José Antonio; Giménez-Bascuñana, Alberto; Chaves-Benito, María Asunción; Aguayo-Albasini, José Luis

    This study was aimed to assess the main clinical, pathological and therapeutic characteristics of a cohort of gastrointestinal stromal tumors (GIST). Observational study including 66 patients diagnosed with GIST admitted to our hospital between 2002 and 2015. Parameters related to medical history, clinical manifestations, medical and surgical treatment, histopathology, and morbi-mortality were studied. A review of the literature was included to correlate with the results. The most frequent location of GIST in our patients was the stomach (65.2%), in which the gastric fondo was the predominant region. The most common clinical manifestation was gastrointestinal hemorrhage (45.5%), followed by incidental finding after imaging or invasive procedures (33.3%). 58 patients underwent surgery (90.6%), 15.5% were urgent. A total of 69% of the GISTs had a size between 2 and 10cm. The one-year mortality was 7.9%, all cases related to local or remote extension, or surgical complications. There is a large clinical variability among GIST cases. The first choice of treatment is surgery, which is feasible in most cases and should be as conservative as possible. The prognosis varies depending on the size and proliferation index, thus close follow-up should be performed. No tumor marker is clearly associated with a poor prognosis. New molecular biology studies are needed in order to find therapeutic targets. Copyright © 2017 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Clinical and Pathological Features of Pheochromocytoma in the Horse: A Multi-Center Retrospective Study of 37 Cases (2007-2014).

    PubMed

    Luethy, D; Habecker, P; Murphy, B; Nolen-Walston, R

    2016-01-01

    Pheochromocytoma is the most common adrenal medullary neoplasm of domestic animals, but it is rare in horses. Antemortem diagnosis in horses is difficult, with clinical signs often being vague or non-specific. The objective of this study was to describe the clinical, laboratory, and pathologic findings of pheochromocytoma in horses. Thirty-seven horses diagnosed with pheochromocytoma based on postmortem examination from 2007 to 2014. Retrospective case series. Pheochromocytoma was identified in 37/4094 horses during postmortem examination. Clinical signs consistent with pheochromocytoma had been observed antemortem in only 7 cases, with the remainder being incidental findings. Colic was the most common presenting complaint (13 of 37 cases) and tachycardia was noted in 95% of cases (median heart rate of 86 bpm in clinical cases). Hyperlactatemia (median, 4.9 mmol/L) and hyperglycemia (median, 184 mg/dL) were the most common clinicopathologic abnormalities. Hemoperitoneum caused by rupture of pheochromocytoma was noted in 4/7 clinical cases. Concurrent endocrine abnormalities (eg, thyroid adenoma, adrenal hyperplasia, pituitary pars intermedia hyperplasia or adenoma, parathyroid C-cell carcinoma) were found in 27/37 horses, with 8/37 horses having lesions consistent with multiple endocrine neoplasia syndrome as described in humans. Pheochromocytoma was diagnosed in 0.95% of horses presented for necropsy. The majority of these were incidental findings, but pheochromocytoma was thought to contribute to clinical findings in 19% of cases, and multiple endocrine neoplasms were commonly seen. Usually an incidental finding at necropsy, pheochromocytoma may cause acute death from intraperitoneal exsanguination and should be considered in horses presenting with colic, tachycardia, and hemoperitoneum. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  19. Assessment of Molecular, Antigenic, and Pathological Features of Canine Influenza A(H3N2) Viruses That Emerged in the United States.

    PubMed

    Pulit-Penaloza, Joanna A; Simpson, Natosha; Yang, Hua; Creager, Hannah M; Jones, Joyce; Carney, Paul; Belser, Jessica A; Yang, Genyan; Chang, Jessie; Zeng, Hui; Thor, Sharmi; Jang, Yunho; Killian, Mary Lea; Jenkins-Moore, Melinda; Janas-Martindale, Alicia; Dubovi, Edward; Wentworth, David E; Stevens, James; Tumpey, Terrence M; Davis, C Todd; Maines, Taronna R

    2017-09-15

    A single subtype of canine influenza virus (CIV), A(H3N8), was circulating in the United States until a new subtype, A(H3N2), was detected in Illinois in spring 2015. Since then, this CIV has caused thousands of infections in dogs in multiple states. In this study, genetic and antigenic properties of the new CIV were evaluated. In addition, structural and glycan array binding features of the recombinant hemagglutinin were determined. Replication kinetics in human airway cells and pathogenesis and transmissibility in animal models were also assessed. A(H3N2) CIVs maintained molecular and antigenic features related to low pathogenicity avian influenza A(H3N2) viruses and were distinct from A(H3N8) CIVs. The structural and glycan array binding profile confirmed these findings and revealed avian-like receptor-binding specificity. While replication kinetics in human airway epithelial cells was on par with that of seasonal influenza viruses, mild-to-moderate disease was observed in infected mice and ferrets, and the virus was inefficiently transmitted among cohoused ferrets. Further adaptation is needed for A(H3N2) CIVs to present a likely threat to humans. However, the potential for coinfection of dogs and possible reassortment of human and other animal influenza A viruses presents an ongoing risk to public health.

  20. Radiologic-pathologic correlation of musculoskeletal lesions

    SciTech Connect

    Hudson, T.M.

    1987-01-01

    This atlas correlates the pathologic and radiologic features of a wide variety of lesions of the bone and soft tissue. Multiple imaging techniques are illustrated with an emphasis on plain radiographs. The author stresses the interpretation of radiographic images in terms of underlying pathology rather than as isolated images. Illustrations of plain radiographs and other radiographic imaging techniques are correlated with numerous micro- and macroscopic pathologic illustrations showing typical histologic and gross pathologic features.

  1. B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements are aggressive neoplasms with clinical and pathologic features distinct from Burkitt lymphoma and diffuse large B-cell lymphoma.

    PubMed

    Snuderl, Matija; Kolman, Olga K; Chen, Yi-Bin; Hsu, Jessie J; Ackerman, Adam M; Dal Cin, Paola; Ferry, Judith A; Harris, Nancy Lee; Hasserjian, Robert P; Zukerberg, Lawrence R; Abramson, Jeremy S; Hochberg, Ephraim P; Lee, Hang; Lee, Alfred I; Toomey, Christiana E; Sohani, Aliyah R

    2010-03-01

    B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements, also known as "double-hit" lymphomas (DHL), are rare neoplasms characterized by highly aggressive clinical behavior, complex karyotypes, and a spectrum of pathologic features overlapping with Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and B-lymphoblastic lymphoma/leukemia (B-LBL). The clinical and pathologic spectrum of this rare entity, including comparison to other high-grade B-cell neoplasms, has not been well defined. We conducted a retrospective analysis of clinical and pathologic features of 20 cases of DHL seen at our institution during a 5-year period. In addition, we carried out case-control comparisons of DHL with BL and International Prognostic Index (IPI)-matched DLBCL. The 11 men and 9 women had a median age of 63.5 years (range 32 to 91). Six patients had a history of grade 1 to 2 follicular lymphoma; review of the prior biopsy specimens in 2 of 5 cases revealed blastoid morphology. Eighteen patients had Ann Arbor stage 3 or 4 disease and all had elevated serum lactate dehydrogenase (LDH) levels at presentation. Extranodal disease was present in 17/20 (85%), bone marrow involvement in 10/17 (59%) and central nervous system (CNS) disease in 5/11 (45%). Nineteen patients were treated with combination chemotherapy, of whom 18 received rituximab and 14 received CNS-directed therapy. Fourteen patients (70%) died within 8 months of diagnosis. Median overall survival in the DHL group (4.5 mo) was inferior to both BL (P=0.002) and IPI-matched DLBCL (P=0.04) control patients. Twelve DHL cases (60%) were classified as B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL, 7 cases (35%) as DLBCL, not otherwise specified, and 1 case as B-LBL. Distinguishing features from BL included expression of Bcl2 (P<0.0001), Mum1/IRF4 (P=0.006), Ki-67 <95% (P<0.0001), and absence of EBV-EBER (P=0.006). DHL commonly contained the t(8;22) rather than the t(8;14) seen

  2. B-cell Lymphomas with Concurrent IGH-BCL2 and MYC Rearrangements Are Aggressive Neoplasms with Clinical and Pathologic Features Distinct from Burkitt Lymphoma and Diffuse Large B-cell Lymphoma

    PubMed Central

    Snuderl, Matija; Kolman, Olga K.; Chen, Yi-Bin; Hsu, Jessie J.; Ackerman, Adam M.; Dal Cin, Paola; Ferry, Judith A.; Lee Harris, Nancy; Hasserjian, Robert P.; Zukerberg, Lawrence R.; Abramson, Jeremy S.; Hochberg, Ephraim P.; Lee, Hang; Lee, Alfred I.; Toomey, Christiana E.; Sohani, Aliyah R.

    2011-01-01

    B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements, also known as “double-hit” lymphomas (DHL), are rare neoplasms characterized by highly aggressive clinical behavior, complex karyotypes, and a spectrum of pathological features overlapping with Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and B-lymphoblastic lymphoma/leukemia (B-LBL). The clinical and pathological spectrum of this rare entity, including comparison to other high-grade B-cell neoplasms, has not been well defined. We conducted a retrospective analysis of clinical and pathologic features of 20 cases of DHL seen at our institution during a 5-year period. In addition, we performed case-control comparisons of DHL with BL and International Prognostic Index (IPI)-matched DLBCL. The 11 men and 9 women had a median age of 63.5 years (range 32-91). Six patients had a history of grade 1-2 follicular lymphoma (FL); review of the prior biopsy specimens in 2 of 5 cases revealed blastoid morphology. Eighteen patients had Ann Arbor stage 3 or 4 disease and all had elevated serum lactate dehydrogenase (LDH) levels at presentation. Extranodal disease was present in 17/20 (85%), bone marrow involvement in 10/17 (59%) and central nervous system (CNS) disease in 5/11 (45%). Nineteen patients were treated with combination chemotherapy, of whom 18 received rituximab and 14 received CNS-directed therapy. Fourteen patients (70%) died within 8 months of diagnosis. Median overall survival in the DHL group (4.5 months) was inferior to both BL (p=0.002) and IPI-matched DLBCL (p=0.04) control patients. Twelve DHL cases (60%) were classified as B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL, 7 cases (35%) as DLBCL, not otherwise specified, and 1 case as B-LBL. Distinguishing features from BL included expression of Bcl2 (p<0.0001), Mum1/IRF4 (p=0.006), Ki-67 <95% (p<0.0001), and absence of EBV-EBER (p=0.006). DHL commonly contained the t(8;22) rather than the t(8

  3. A Murine Niemann-Pick C1 I1061T Knock-In Model Recapitulates the Pathological Features of the Most Prevalent Human Disease Allele

    PubMed Central

    Praggastis, Maria; Tortelli, Brett; Zhang, Jessie; Fujiwara, Hideji; Sidhu, Rohini; Chacko, Anita; Chen, Zhouji; Chung, Chan; Lieberman, Andrew P.; Sikora, Jakub; Davidson, Cristin; Walkley, Steven U.; Pipalia, Nina H.; Maxfield, Frederick R.; Schaffer, Jean E.

    2015-01-01

    Niemann-Pick Type C1 (NPC1) disease is a rare neurovisceral, cholesterol–sphingolipid lysosomal storage disorder characterized by ataxia, motor impairment, progressive intellectual decline, and dementia. The most prevalent mutation, NPC1I1061T, encodes a misfolded protein with a reduced half-life caused by ER-associated degradation. Therapies directed at stabilization of the mutant NPC1 protein reduce cholesterol storage in fibroblasts but have not been tested in vivo because of lack of a suitable animal model. Whereas the prominent features of human NPC1 disease are replicated in the null Npc1−/− mouse, this model is not amenable to examining proteostatic therapies. The objective of the present study was to develop an NPC1 I1061T knock-in mouse in which to test proteostatic therapies. Compared with the Npc1−/− mouse, this Npc1tm(I1061T)Dso model displays a less severe, delayed form of NPC1 disease with respect to weight loss, decreased motor coordination, Purkinje cell death, lipid storage, and premature death. The murine NPC1I1061T protein has a reduced half-life in vivo, consistent with protein misfolding and rapid ER-associated degradation, and can be stabilized by histone deacetylase inhibition. This novel mouse model faithfully recapitulates human NPC1 disease and provides a powerful tool for preclinical evaluation of therapies targeting NPC1 protein variants with compromised stability. PMID:26019327

  4. Loss of presenilin function causes Alzheimer's disease-like neurodegeneration in the mouse.

    PubMed

    Chen, Qian; Nakajima, Akira; Choi, Se Hoon; Xiong, Xiaoli; Tang, Ya-Ping

    2008-05-15

    Accumulating evidence has indicated that gain-of-function in beta-amyloid production may be not the necessary mechanism for mutant presenilin-1 (PS1) or PS2 to cause familial Alzheimer's disease (AD). In the present article, we show that conditional knockout of PS1 from the adult stage in the forebrain of mice with the PS2 null mutation triggers robust AD-like neurodegeneration including brain shrinkage, cortical and hippocampal atrophy,ventricular enlargement, severe neuronal loss, gliosis, tau hyperphosphorylation, neurofillament tangle-like structures, and intracellular filaments. Learning and memory functions in these mice are almost completely lost. Notably, there is no beta-amyloid deposition, indicating that presenilin dysfunction can directly cause neurodegeneration without the involvement of beta-amyloid. Furthermore, neurodegeneration occurs in a progressive manner following aging, suggesting that an accumulating effect of presenilin dysfunction over time might be a pathogenic mechanism for the involvement of mutant PS1/PS2 in causing AD. These results validate a mouse model characterized by the presence of many features of AD pathology. Furthermore, the demonstration of AD-like neurodegeneration in the absence of beta-amyloid deposition challenges the long-standing beta-amyloid cascade hypothesis and encourages an open debate on the role of beta-amyloid in causing AD. Most important, our results strongly suggest that to develop gamma-secretase inhibitors for the pharmacological treatment of AD may be not a reasonable strategy because antagonism of presenilin function may worsen neurodegeneration.

  5. Inguinoscrotal pathology

    PubMed Central

    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

  6. Clinico-pathological features and somatic gene alterations in refractory ceramic fibre-induced murine mesothelioma reveal mineral fibre-induced mesothelioma identities

    PubMed Central

    Andujar, Pascal; Lecomte, Céline; Renier, Annie; Fleury-Feith, Jocelyne; Kheuang, Laurence; Daubriac, Julien; Janin, Anne; Jaurand, Marie-Claude

    2007-01-01

    Although human malignant mesothelioma (HMM) is mainly caused by asbestos exposure, refractory ceramic fibres (RCFs) have been classified as possibly carcinogenic to humans on the basis of their biological effects in rodents’ lung and pleura and in cultured cells. Hence, further investigations are needed to clarify the mechanism of fibre-induced carcinogenicity and to prevent use of harmful particles. In a previous study, mesotheliomas were found in hemizygous Nf2 (Nf2+/−) mice exposed to asbestos fibres, and showed similar alterations in genes at the Ink4 locus and in Trp53 as described in HMM. Here we found that Nf2+/− mice developed mesotheliomas after intra-peritoneal inoculation of a RCF sample (RCF1). Clinical features in exposed mice were similar to those observed in HMM, showing association between ascite and mesothelioma. Early passages of 12 mesothelioma cell cultures from ascites developed in RCF1-exposed Nf2+/− mice demonstrated frequent inactivation by deletion of genes at the Ink4 locus, and low rate of Trp53 point and insertion mutations. Nf2 gene was inactivated in all cultures. In most cases, co-inactivation of genes at the Ink4 locus and Nf2 was found and, at a lower rate, of Trp53 and Nf2. These results are the first to identify mutations in RCF-induced mesothelioma. They suggest that nf2 mutation is complementary of p15Ink4b, p16Ink4a and p19Arf or p53 mutations and show similar profile of gene alterations resulting from exposure to ceramic or asbestos fibres in Nf2+/− mice, also consistent with the one found in HMM. These somatic genetic changes define different pathways of mesothelial cell transformation. PMID:17272307

  7. Clinico-pathological features and somatic gene alterations in refractory ceramic fibre-induced murine mesothelioma reveal mineral fibre-induced mesothelioma identities.

    PubMed

    Andujar, Pascal; Lecomte, Céline; Renier, Annie; Fleury-Feith, Jocelyne; Kheuang, Laurence; Daubriac, Julien; Janin, Anne; Jaurand, Marie-Claude

    2007-07-01

    Although human malignant mesothelioma (HMM) is mainly caused by asbestos exposure, refractory ceramic fibres (RCFs) have been classified as possibly carcinogenic to humans on the basis of their biological effects in rodents' lung and pleura and in cultured cells. Hence, further investigations are needed to clarify the mechanism of fibre-induced carcinogenicity and to prevent use of harmful particles. In a previous study, mesotheliomas were found in hemizygous Nf2 (Nf2(+/-)) mice exposed to asbestos fibres, and showed similar alterations in genes at the Ink4 locus and in Trp53 as described in HMM. Here we found that Nf2(+/-) mice developed mesotheliomas after intra-peritoneal inoculation of a RCF sample (RCF1). Clinical features in exposed mice were similar to those observed in HMM, showing association between ascite and mesothelioma. Early passages of 12 mesothelioma cell cultures from ascites developed in RCF1-exposed Nf2(+/-) mice demonstrated frequent inactivation by deletion of genes at the Ink4 locus, and low rate of Trp53 point and insertion mutations. Nf2 gene was inactivated in all cultures. In most cases, co-inactivation of genes at the Ink4 locus and Nf2 was found and, at a lower rate, of Trp53 and Nf2. These results are the first to identify mutations in RCF-induced mesothelioma. They suggest that nf2 mutation is complementary of p15(Ink4b), p16(Ink4a) and p19(Arf) or p53 mutations and show similar profile of gene alterations resulting from exposure to ceramic or asbestos fibres in Nf2(+/-) mice, also consistent with the one found in HMM. These somatic genetic changes define different pathways of mesothelial cell transformation.

  8. Management of prostate cancer patients with locally adverse pathologic features after radical prostatectomy: feasibility of active surveillance for cases with Gleason grade 3 + 4 = 7.

    PubMed

    Shangguan, Xun; Dong, Baijun; Wang, Yanqing; Xu, Fan; Shao, Xiaoguang; Sha, Jianjun; Zhu, Yinjie; Pan, Jiahua; Xue, Wei

    2017-01-01

    To evaluate the ability of the new Gleason grade groups (GGGs) to stratify risk in prostate cancer patients with locally adverse pathologic features after radical prostatectomy (RP) thereby allowing more accurate assessment for planning eventual adjuvant therapy. Data on 172 patients with locally adverse pathologic features (including seminal vesicle invasion, extracapsular extension, or positive surgical margins) who had been treated with wait and see policy after RP were retrospectively analyzed for biochemical recurrence (BCR)-free survival. Kaplan-Meier survival analysis and Cox proportional hazard regression models were used to test the association between the GGGs and BCR. Finally, concordance indices of different grading classifications were calculated to evaluate the predictive accuracy for biochemical failure after RP. The five-year BCR-free survival rates were 71.2, 66.9, 25.7, 17.4, and 8.3 % for GGG 1-5 assessed on surgical specimens (p < 0.001, log-rank test). In the two-way log-rank test, men with prostatectomy GGG 2 had a lower progression risk relative to GGG 3 (p = 0.001), though similar risk as GGG 1 (p = 0.105). In multivariate Cox regression analysis, specimen GGG ≥3 and early postoperative PSA ≥0.1 ng/ml were independent risk factors for biochemical failure (p < 0.001). In addition, GGGs had higher predictive accuracy compared with the alternate classification system (improvement in concordance index by 0.036-0.141). For the appropriate patient, depending on age, physical condition, early postoperative PSA, patient desire, etc., could be a candidate for wait and see policy with specimen GGG 2 disease, so to distinguish this from GGG 3 may facilitate discussions at the point of treatment decision making.

  9. Pathology of radiation myelopathy

    PubMed Central

    Burns, R. J.; Jones, A. N.; Robertson, J. S.

    1972-01-01

    After nothing the rarity of papers describing the pathology of delayed radiation necrosis of the spinal cord, the clinical and pathological findings from four cases are presented. The main pathological features are asymmetric demyelination of the lateral columns and to a lesser degree the posterior and anterior columns of white matter, with coagulative necrosis at the level of irradiation which affected the grey matter to a lesser degree. There is ascending and descending secondary tract degeneration, and poor glial response in the lesions themselves. Vascular changes, mainly hyalilne thickening of arteriolar walls, are present, but not in degree sufficient to explain the primary lesion. The discussion of the pathogenesis of the myelopathy weighs the merits of a primary vascular lesion against those of a primary effect of the radiation on neural tissue. The latter is favoured. Images PMID:4647860

  10. Prediction of Low versus High Recurrence Scores in Estrogen Receptor-Positive, Lymph Node-Negative Invasive Breast Cancer on the Basis of Radiologic-Pathologic Features: Comparison with Oncotype DX Test Recurrence Scores.

    PubMed

    Dialani, Vandana; Gaur, Shantanu; Mehta, Tejas S; Venkataraman, Shambhavi; Fein-Zachary, Valerie; Phillips, Jordana; Brook, Alexander; Slanetz, Priscilla J

    2016-08-01

    Purpose To review mammographic, ultrasonographic (US), and magnetic resonance (MR) imaging features and pathologic characteristics of estrogen receptor (ER)-positive, lymph node-negative invasive breast cancer and to determine the relationship of these characteristics to Oncotype DX (Genomic Health, Redwood City, Calif) test recurrence scores (ODRS) for breast cancer recurrence. Materials and Methods This institutional review board-approved retrospective study was performed in a single large academic medical center. The study population included patients with ER-positive, lymph node-negative invasive breast cancer who underwent genomic testing from January 1, 2009, to December 31, 2013. Imaging features of the tumor were classified according to the Breast Imaging Reporting and Data System lexicon by breast imagers who were blinded to the ODRS. Mammography was performed in 86% of patients, US was performed in 84%, and MR imaging was performed in 33%, including morphologic and kinetic evaluation. Images from each imaging modality were evaluated. Each imaging finding, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status, and tumor grade were then individually correlated with ODRS. Analysis of variance was used to determine differences for each imaging feature. Regression analysis was used to calculate prediction of recurrence on the basis of imaging features combined with histopathologic features. Results The 319 patients had a mean age ± standard deviation of 55 years ± 8.7 (range, 31-82 years). Imaging features with a positive correlation with ODRS included a well-circumscribed oval mass (P = .024) at mammography, vascularity (P = .047) and posterior enhancement (P = .004) at US, and lobulated mass (P = .002) at MR imaging. Recurrence scores were predicted by using these features in combination with PR and HER2 status and tumor grade by using the threshold of more than 30 as a high recurrence score. With a regression tree, there

  11. Genomic Classifier Augments the Role of Pathological Features in Identifying Optimal Candidates for Adjuvant Radiation Therapy in Patients With Prostate Cancer: Development and Internal Validation of a Multivariable Prognostic Model.

    PubMed

    Dalela, Deepansh; Santiago-Jiménez, María; Yousefi, Kasra; Karnes, R Jeffrey; Ross, Ashley E; Den, Robert B; Freedland, Stephen J; Schaeffer, Edward M; Dicker, Adam P; Menon, Mani; Briganti, Alberto; Davicioni, Elai; Abdollah, Firas

    2017-06-20

    Purpose Despite documented oncologic benefit, use of postoperative adjuvant radiotherapy (aRT) in patients with prostate cancer is still limited in the United States. We aimed to develop and internally validate a risk-stratification tool incorporating the Decipher score, along with routinely available clinicopathologic features, to identify patients who would benefit the most from aRT. Patient and Methods Our cohort included 512 patients with prostate cancer treated with radical prostatectomy at one of four US academic centers between 1990 and 2010. All patients had ≥ pT3a disease, positive surgical margins, and/or pathologic lymph node invasion. Multivariable Cox regression analysis tested the relationship between available predictors (including Decipher score) and clinical recurrence (CR), which were then used to develop a novel risk-stratification tool. Our study adhered to the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for development of prognostic models. Results Overall, 21.9% of patients received aRT. Median follow-up in censored patients was 8.3 years. The 10-year CR rate was 4.9% vs. 17.4% in patients treated with aRT versus initial observation ( P < .001). Pathologic T3b/T4 stage, Gleason score 8-10, lymph node invasion, and Decipher score > 0.6 were independent predictors of CR (all P < .01). The cumulative number of risk factors was 0, 1, 2, and 3 to 4 in 46.5%, 28.9%, 17.2%, and 7.4% of patients, respectively. aRT was associated with decreased CR rate in patients with two or more risk factors (10-year CR rate 10.1% in aRT v 42.1% in initial observation; P = .012), but not in those with fewer than two risk factors ( P = .18). Conclusion Using the new model to indicate aRT might reduce overtreatment, decrease unnecessary adverse effects, and reduce risk of CR in the subset of patients (approximately 25% of all patients with aggressive pathologic disease in our cohort) who benefit from this

  12. Punctate follicular porokeratosis: clinical and pathologic features.

    PubMed

    Trikha, Ritika; Wile, Anna; King, Joy; Ward, Kimberley H M; Brodell, Robert T

    2015-11-01

    Porokeratosis is a disorder of keratinization characterized by an abnormal cornoid lamella surrounding an annular, scaly plaque with an atrophic center. A histologic variant of this condition has been proposed, termed follicular porokeratosis, in cases where follicular involvement was contiguous with an annular cornoid lamella. There has been only 1 report of punctate follicular porokeratosis, in which cornoid lamellae originated exclusively from hair follicles with no associated annular plaque. The authors present the second case of punctate follicular porokeratosis, further supporting the contention that this entity is a unique form of porokeratosis rather than a histologic variant. A 56-year-old African American female presented to the dermatology clinic with a 3-month history of keratotic lesions localized on the right posterior shoulder. Examination revealed an area of perifollicular keratotic papules, each surrounded by an erythematous rim. Histopathology revealed a cornoid lamella originating within a hair follicle, with the parakeratotic column protruding through the follicular orifice. The static nature of the condition along with exclusive involvement of hair follicles supports the notion of punctate follicular porokeratosis as a distinct clinical entity. The diagnosis of this condition relies heavily on proper histopathologic sampling revealing punctate follicular cornoid lamellae.

  13. Clinical, biologic, and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials.

    PubMed

    Mourad, Nathalie; Mounier, Nicolas; Brière, Josette; Raffoux, Emmanuel; Delmer, Alain; Feller, Alfred; Meijer, Chris J L M; Emile, Jean-François; Bouabdallah, Réda; Bosly, André; Diebold, Jacques; Haioun, Corinne; Coiffier, Bertrand; Gisselbrecht, Christian; Gaulard, Philippe

    2008-05-01

    To evaluate the prognostic significance of clinicobiologic and pathological features in angioimmunoblastic T-cell lymphoma (AITL), 157 AITL patients were retrieved from the GELA LNH87-LNH93 randomized clinical trials. One hundred forty-seven patients received a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like regimen with intensified courses in half of them. Histologically, 41 cases were classified as "rich in large cells" and 116 as "classic" (including 19 rich in epithelioid cells, 14 rich in clear cells, and 4 with hyperplastic germinal centers). Sixty-two cases were scored for CD10 and CXCL13 expression according to the abundance of positive lymphoid cells. Median age was 62 years, with 81% advanced stage, 72% B symptoms, 65% anemia, 50% hypergammaglobulinemia, and 66% elevated LDH. Overall 7-year survival was 30%. In multivariate analysis, only male sex (P = .004), mediastinal lymphadenopathy (P = .041), and anemia (P = .042) adversely affected overall survival. Increase in large cells and high level of CD10 and CXCL13 did not affect survival. Intensive regimen did not improve survival. In conclusion, AITL is a morphologically heterogeneous T-cell lymphoma commonly expressing CXCL13 and CD10 and carrying few prognostic factors. It portends a poor prognosis even when treated intensively. However, AITL is not always lethal with 30% of patients alive at 7 years.

  14. Microscopic Disease Extension in Three Dimensions for Non-Small-Cell Lung Cancer: Development of a Prediction Model Using Pathology-Validated Positron Emission Tomography and Computed Tomography Features

    SciTech Connect

    Loon, Judith van; Siedschlag, Christian; Stroom, Joep; Blauwgeers, Hans; Suylen, Robert-Jan van; Knegjens, Joost; Rossi, Maddalena; Baardwijk, Angela van; Boersma, Liesbeth; Klomp, Houke; Vogel, Wouter; Burgers, Sjaak; Gilhuijs, Kenneth

    2012-01-01

    Purpose: One major uncertainty in radiotherapy planning of non-small-cell lung cancer concerns the definition of the clinical target volume (CTV), meant to cover potential microscopic disease extension (MDE) around the macroscopically visible tumor. The primary aim of this study was to establish pretreatment risk factors for the presence of MDE. The secondary aim was to establish the impact of these factors on the accuracy of positron emission tomography (PET) and computed tomography (CT) to assess the total tumor-bearing region at pathologic examination (CTV{sub path}). Methods and Materials: 34 patients with non-small-cell lung cancer who underwent CT and PET before lobectomy were included. Specimens were examined microscopically for MDE. The gross tumor volume (GTV) on CT and PET (GTV{sub CT} and GTV{sub PET}, respectively) was compared with the GTV and the CTV at pathologic examination, tissue deformations being taken into account. Using multivariate logistic regression, image-based risk factors for the presence of MDE were identified, and a prediction model was developed based on these factors. Results: MDE was found in 17 of 34 patients (50%). The MDE did not exceed 26 mm in 90% of patients. In multivariate analysis, two parameters (mean CT tumor density and GTV{sub CT}) were significantly associated with MDE. The area under the curve of the two-parameter prediction model was 0.86. Thirteen tumors (38%, 95% CI: 24-55%) were identified as low risk for MDE, being potential candidates for reduced-intensity therapy around the GTV. In the low-risk group, the effective diameter of the GTV{sub CT/PET} accurately represented the CTV{sub path}. In the high-risk group, GTV{sub CT/PET} underestimated the CTV{sub path} with, on average, 19.2 and 26.7 mm, respectively. Conclusions: CT features have potential to predict the presence of MDE. Tumors identified as low risk of MDE show lower rates of disease around the GTV than do high-risk tumors. Both CT and PET accurately

  15. Chronic exposure to low benzo[a]pyrene level causes neurodegenerative disease-like syndromes in zebrafish (Danio rerio).

    PubMed

    Gao, Dongxu; Wu, Meifang; Wang, Chonggang; Wang, Yuanchuan; Zuo, Zhenghong

    2015-10-01

    Previous epidemiological and animal studies report that exposure to environmental pollutant exposure links to neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Benzo[a]pyrene (BaP), a neurotoxic polycyclic aromatic hydrocarbon, has been increasingly released into the environment during recent decades. So far, the role of BaP on the development of neurodegenerative diseases remaind unclear. This study aimed to determine whether chronic exposure to low dose BaP would cause neurodegenerative disease-like syndromes in zebrafish (Danio rerio). We exposed zebrafish, from early embryogenesis to adults, to environmentally relevant concentrations of BaP for 230 days. Our results indicated that BaP decreased the brain weight to body weight ratio, locomotor activity and cognitive ability; induced the loss of dopaminergic neurons; and resulted in neurodegeneration. In addition, obvious cell apoptosis in the brain was found. Furthermore, the neurotransmitter levels of dopamine and 3,4-dihydroxyphenylacetic acid, the mRNA levels of the genes encoding dopamine transporter, Parkinson protein 7, phosphatase and tensin-induced putative kinase 1, ubiquitin carboxy-terminal hydrolase L1, leucine-rich repeat serine/threonine kinase 2, amyloid precursor protein b, presenilin 1 and presenilin 2 were significantly down-regulated by BaP exposure. These findings suggest that chronic exposure to low dose BaP could cause the behavioral, neuropathological, neurochemical, and genetic features of neurodegenerative diseases. This study provides clues that BaP may constitute an important environmental risk factor for neurodegenerative diseases in humans. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Pathological impact of SMN2 mis-splicing in adult SMA mice.

    PubMed

    Sahashi, Kentaro; Ling, Karen K Y; Hua, Yimin; Wilkinson, John Erby; Nomakuchi, Tomoki; Rigo, Frank; Hung, Gene; Xu, David; Jiang, Ya-Ping; Lin, Richard Z; Ko, Chien-Ping; Bennett, C Frank; Krainer, Adrian R

    2013-10-01

    Loss-of-function mutations in SMN1 cause spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. The related SMN2 gene expresses suboptimal levels of functional SMN protein, due to a splicing defect. Many SMA patients reach adulthood, and there is also adult-onset (type IV) SMA. There is currently no animal model for adult-onset SMA, and the tissue-specific pathogenesis of post-developmental SMN deficiency remains elusive. Here, we use an antisense oligonucleotide (ASO) to exacerbate SMN2 mis-splicing. Intracerebroventricular ASO injection in adult SMN2-transgenic mice phenocopies key aspects of adult-onset SMA, including delayed-onset motor dysfunction and relevant histopathological features. SMN2 mis-splicing increases during late-stage disease, likely accelerating disease progression. Systemic ASO injection in adult mice causes peripheral SMN2 mis-splicing and affects prognosis, eliciting marked liver and heart pathologies, with decreased IGF1 levels. ASO dose-response and time-course studies suggest that only moderate SMN levels are required in the adult central nervous system, and treatment with a splicing-correcting ASO shows a broad therapeutic time window. We describe distinctive pathological features of adult-onset and early-onset SMA. © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

  17. Pathological impact of SMN2 mis-splicing in adult SMA mice

    PubMed Central

    Sahashi, Kentaro; Ling, Karen K Y; Hua, Yimin; Wilkinson, John Erby; Nomakuchi, Tomoki; Rigo, Frank; Hung, Gene; Xu, David; Jiang, Ya-Ping; Lin, Richard Z; Ko, Chien-Ping; Bennett, C Frank; Krainer, Adrian R

    2013-01-01

    Loss-of-function mutations in SMN1 cause spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. The related SMN2 gene expresses suboptimal levels of functional SMN protein, due to a splicing defect. Many SMA patients reach adulthood, and there is also adult-onset (type IV) SMA. There is currently no animal model for adult-onset SMA, and the tissue-specific pathogenesis of post-developmental SMN deficiency remains elusive. Here, we use an antisense oligonucleotide (ASO) to exacerbate SMN2 mis-splicing. Intracerebroventricular ASO injection in adult SMN2-transgenic mice phenocopies key aspects of adult-onset SMA, including delayed-onset motor dysfunction and relevant histopathological features. SMN2 mis-splicing increases during late-stage disease, likely accelerating disease progression. Systemic ASO injection in adult mice causes peripheral SMN2 mis-splicing and affects prognosis, eliciting marked liver and heart pathologies, with decreased IGF1 levels. ASO dose–response and time-course studies suggest that only moderate SMN levels are required in the adult central nervous system, and treatment with a splicing-correcting ASO shows a broad therapeutic time window. We describe distinctive pathological features of adult-onset and early-onset SMA. PMID:24014320

  18. Exploring the role of microorganisms in the disease-like syndrome affecting the sponge Ianthella basta.

    PubMed

    Luter, Heidi M; Whalan, Steve; Webster, Nicole S

    2010-09-01

    A disease-like syndrome is currently affecting a large percentage of the Ianthella basta populations from the Great Barrier Reef and central Torres Strait. Symptoms of the syndrome include discolored, necrotic spots leading to tissue degradation, exposure of the skeletal fibers, and disruption of the choanocyte chambers. To ascertain the role of microbes in the disease process, a comprehensive comparison of bacteria, viruses, fungi, and other eukaryotes was performed in healthy and diseased sponges using multiple techniques. A low diversity of microbes was observed in both healthy and diseased sponge communities, with all sponges dominated by an Alphaproteobacteria, a Gammaproteobacteria, and a group I crenarchaeota. Bacterial cultivation, community analysis by denaturing gradient gel electrophoresis (Bacteria and Eukarya), sequencing of 16S rRNA clone libraries (Bacteria and Archaea), and direct visual assessment by electron microscopy failed to reveal any putative pathogens. In addition, infection assays could not establish the syndrome in healthy sponges even after direct physical contact with affected tissue. These results suggest that microbes are not responsible for the formation of brown spot lesions and necrosis in I. basta.

  19. Graft-versus-host disease-like erythroderma: a manifestation of thymoma-associated multiorgan autoimmunity

    PubMed Central

    Warren, Shay; Nehal, Kishwer; Querfeld, Christiane; Wong, Richard; Huang, James; Pulitzer, Melissa

    2016-01-01

    Thymoma associated multiorgan autoimmunity is a rare paraneoplastic disorder, clinicopathologically similar to graft versus host disease, which is thought to be mediated by dysfunctional negative thymocyte selection and abnormally low levels of Tregs. We report a 50 year old Chinese women with a history of malignant thymoma and myasthenia gravis who developed graft versus host disease- like erythroderma after instituting chemotherapy and undergoing myasthenia crisis. Clinically her rash presented as erythematous scaly papules, which evolved to psoriasiform patches and plaques with foci of vitiligo. Histopathologically the biopsy showed a predominantly interface dermatitis with necrotic keratinocytes extending to the upper levels of the epidermis, and florid basket weave orthokeratosis. Clinical and laboratory work-up ruled out common inflammatory or infectious causes, eventually favoring the diagnosis of TAMA with GVHD-like erythroderma. Unfortunately, the patient underwent multi-organ compromise and death due to respiratory failure from myasthenia crisis. Patients with TAMA have a poor clinical outlook; rare successful treatments include high dose oral steroids and additional modalities including bone marrow transplant and chemotherapeutic or biologic agents. As the predominant findings are in the skin, dermatologists and dermatopathologists are in a unique position to enable the early diagnosis and treatment of this unusual disease. PMID:26509934

  20. Nanotechnology: Toxicologic Pathology

    PubMed Central

    Hubbs, Ann F.; Sargent, Linda M.; Porter, Dale W.; Sager, Tina M.; Chen, Bean T.; Frazer, David G.; Castranova, Vincent; Sriram, Krishnan; Nurkiewicz, Timothy R.; Reynolds, Steven H.; Battelli, Lori A.; Schwegler-Berry, Diane; McKinney, Walter; Fluharty, Kara L.; Mercer, Robert R.

    2015-01-01

    Nanotechnology involves technology, science, and engineering in dimensions less than 100 nm. A virtually infinite number of potential nanoscale products can be produced from many different molecules and their combinations. The exponentially increasing number of nanoscale products will solve critical needs in engineering, science, and medicine. However, the virtually infinite number of potential nanotechnology products is a challenge for toxicologic pathologists. Because of their size, nanoparticulates can have therapeutic and toxic effects distinct from micron-sized particulates of the same composition. In the nanoscale, distinct intercellular and intracellular translocation pathways may provide a different distribution than that obtained by micron-sized particulates. Nanoparticulates interact with subcellular structures including microtubules, actin filaments, centrosomes, and chromatin; interactions that may be facilitated in the nanoscale. Features that distinguish nanoparticulates from fine particulates include increased surface area per unit mass and quantum effects. In addition, some nanotechnology products, including the fullerenes, have a novel and reactive surface. Augmented microscopic procedures including enhanced dark-field imaging, immunofluorescence, field-emission scanning electron microscopy, transmission electron microscopy, and confocal microscopy are useful when evaluating nanoparticulate toxicologic pathology. Thus, the pathology assessment is facilitated by understanding the unique features at the nanoscale and the tools that can assist in evaluating nanotoxicology studies. PMID:23389777

  1. The neurobiology of pathological gambling.

    PubMed

    Potenza, M N

    2001-07-01

    Despite relatively high prevalence rates and significant morbidity and mortality associated with pathological gambling (PG), our understanding of the neurobiological basis of PG lags in comparison to that for other psychiatric illnesses of comparable magnitude. An improved understanding of the neurobiology of PG would facilitate targeted investigations into more effective treatments. Emerging data suggest shared neurobiological features determine in part pathological gambling and substance use disorders. These findings both challenge current conceptualizations of addictions and provide a substantial basis of knowledge on which to design investigations into the understanding and treatment of pathological gambling. The findings that substance use disorders and the behavioral "addiction" of PG share common causative features raise the question as to what extent other compulsive disorders (eg, compulsive shopping, compulsive sexual behaviors, compulsive computer use) might be biologically related.

  2. Mass-forming primary angiitis of central nervous system with Rosai-Dorfmann disease-like massive histiocytosis with emperipolesis.

    PubMed

    Kim, Seong-Ik; Kim, Soo Hee; Cho, Hwa Jin; Kim, Hannah; Chung, Chun-Kee; Choi, Seung Hong; Park, Sung-Hye

    2015-08-01

    Primary angiitis of the central nervous system (PACNS) is a vasculitis restricted to the CNS without systemic involvement. We report a case of PACNS that was radiologically tumor-mimicking, and pathologically similar to the Rosai-Dorfmann disease. A 20-year-old woman presented with a focal facial motor seizure. Magnetic resonance image revealed heterogeneously enhanced well-demarcated solitary cerebral mass in the posterior frontal lobe. Histopathologically, the lesion showed lymphoplasmacytic vasculitis with massive parenchymal infiltration of large histiocytes with emperipolesis. Diffuse ischemic change, necrosis, hemorrhage of the brain parenchyma with neuronophagia, and extensive reactive gliosis by gemistocytic astrocytes were accompanying microscopic features. The patient was doing well for 3 years after complete resection of the lesion, except for occasional occurrence of alcohol- or sleep deprivation-associated seizure. We describe this unique case to provide evidence that mass formation can be developed in PACNS by accompanying parenchymal lymphohistiocytic infiltration, necrosis, and marked reactive gliosis. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

  3. Acute Monocytic Leukemia Masquerading Behçet's Disease-Like Illness at Onset in an Elderly Female

    PubMed Central

    Koba, Shigeru; Sekioka, Toshio; Takeda, Sorou; Miyagawa-Hayashino, Aya; Nishimura, Keisuke

    2016-01-01

    A previously healthy 74-year-old Japanese female was hospitalized with fever and high C-reactive protein. She developed palatal herpangina-like aphthous ulcers, localized intestinal wall thickening, terminal ileum ulcers, and an erythematous acneiform rash; thus Behçet's disease-like illness was suspected. Significant peripheral blood acute monocytosis developed during her hospitalization and acute monocytic leukemia (FAB M5b) with normal karyotype was diagnosed. By immunostaining, the infiltrating cells in the skin and the terminal ileum were identified as monocytic leukemic cells. This case exhibited a unique initial presentation of Behçet's disease-like illness associated with acute monocytic leukemia. PMID:27610252

  4. Curriculum Guidelines for Pathology and Oral Pathology.

    ERIC Educational Resources Information Center

    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)

  5. Junctophilin 3 (JPH3) expansion mutations causing Huntington disease like 2 (HDL2) are common in South African patients with African ancestry and a Huntington disease phenotype.

    PubMed

    Krause, Amanda; Mitchell, Claire; Essop, Fahmida; Tager, Susan; Temlett, James; Stevanin, Giovanni; Ross, Christopher; Rudnicki, Dobrila; Margolis, Russell

    2015-10-01

    Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline, and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p. A CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on chromosome 16q24.2 causes a Huntington disease-like phenotype (HDL2). All patients to date with HDL2 have some African ancestry. The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the JPH3 mutation. In a sample of unrelated South African individuals referred for diagnostic HD testing, 62% (106/171) of white patients compared to only 36% (47/130) of black patients had an expansion in HTT. However, 15% (20/130) of black South African patients and no white patients (0/171) had an expansion in JPH3, confirming the diagnosis of Huntington disease like 2 (HDL2). Individuals with HDL2 share many clinical features with individuals with HD and are clinically indistinguishable in many cases, although the average age of onset and diagnosis in HDL2 is 5 years later than HD and individual clinical features may be more prominent. HDL2 mutations contribute significantly to the HD phenotype in South Africans with African ancestry. JPH3 haplotype studies in 31 families, mainly from South Africa and North America, provide evidence for a founder mutation and support a common African origin for all HDL2 patients. Molecular testing in individuals with an HD phenotype and African ancestry should include testing routinely for JPH3 mutations.

  6. JUNCTOPHILIN 3 (JPH3) EXPANSION MUTATIONS CAUSING HUNTINGTON DISEASE LIKE 2 (HDL2) ARE COMMON IN SOUTH AFRICAN PATIENTS WITH AFRICAN ANCESTRY AND A HUNTINGTON DISEASE PHENOTYPE

    PubMed Central

    Krause, A; Mitchell, CL; Essop, F; Tager, S; Temlett, J; Stevanin, G; Ross, CA; Rudnicki, DD; Margolis, RL

    2015-01-01

    Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p. A CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on chromosome 16q24.2 causes a Huntington disease-like phenotype (HDL2). All patients to date with HDL2 have some African ancestry. The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the JPH3 mutation. In a sample of unrelated South African individuals referred for diagnostic HD testing, 62% (106/171) of white patients compared to only 36% (47/130) of black patients had an expansion in HTT. However, 15% (20/130) of black South African patients and no white patients (0/171) had an expansion in JPH3, confirming the diagnosis of Huntington disease like 2 (HDL2). Individuals with HDL2 share many clinical features with individuals with HD and are clinically indistinguishable in many cases, although the average age of onset and diagnosis in HDL2 is 5 years later than HD and individual clinical features may be more prominent. HDL2 mutations contribute significantly to the HD phenotype in South Africans with African ancestry. JPH3 haplotype studies in 31 families, mainly from South Africa and North America, provide evidence for a founder mutation and support a common African origin for all HDL2 patients. Molecular testing in individuals with an HD phenotype and African ancestry should include testing routinely for JPH3 mutations. PMID:26079385

  7. Relationships between the Circadian System and Alzheimer's Disease-Like Symptoms in Drosophila

    PubMed Central

    Dutta, Sudeshna; Holbrook, Scott D.; Kotwica-Rolinska, Joanna; Kretzschmar, Doris; Giebultowicz, Jadwiga M.

    2014-01-01

    Circadian clocks coordinate physiological, neurological, and behavioral functions into circa 24 hour rhythms, and the molecular mechanisms underlying circadian clock oscillations are conserved from Drosophila to humans. Clock oscillations and clock-controlled rhythms are known to dampen during aging; additionally, genetic or environmental clock disruption leads to accelerated aging and increased susceptibility to age-related pathologies. Neurodegenerative diseases, such as Alzheimer's disease (AD), are associated with a decay of circadian rhythms, but it is not clear whether circadian disruption accelerates neuronal and motor decline associated with these diseases. To address this question, we utilized transgenic Drosophila expressing various Amyloid-β (Aβ) peptides, which are prone to form aggregates characteristic of AD pathology in humans. We compared development of AD-like symptoms in adult flies expressing Aβ peptides in the wild type background and in flies with clocks disrupted via a null mutation in the clock gene period (per01). No significant differences were observed in longevity, climbing ability and brain neurodegeneration levels between control and clock-deficient flies, suggesting that loss of clock function does not exacerbate pathogenicity caused by human-derived Aβ peptides in flies. However, AD-like pathologies affected the circadian system in aging flies. We report that rest/activity rhythms were impaired in an age-dependent manner. Flies expressing the highly pathogenic arctic Aβ peptide showed a dramatic degradation of these rhythms in tune with their reduced longevity and impaired climbing ability. At the same time, the central pacemaker remained intact in these flies providing evidence that expression of Aβ peptides causes rhythm degradation downstream from the central clock mechanism. PMID:25171136

  8. Myelin-associated glycoprotein gene mutation causes Pelizaeus-Merzbacher disease-like disorder

    PubMed Central

    Elazar, Nimrod; Lerer, Israela; Schueler-Furman, Ora; Fellig, Yakov; Glick, Benjamin; Zimmerman, Bat-El; Azulay, Haim; Dotan, Shlomo; Goldberg, Sharon; Gomori, John M.; Ponger, Penina; Newman, J. P.; Marreed, Hodaifah; Steck, Andreas J.; Schaeren-Wiemers, Nicole; Mor, Nofar; Harel, Michal; Geiger, Tamar; Eshed-Eisenbach, Yael; Peles, Elior

    2015-01-01

    Pelizaeus-Merzbacher disease is an X-linked hypomyelinating leukodystrophy caused by mutations or rearrangements in PLP1. It presents in infancy with nystagmus, jerky head movements, hypotonia and developmental delay evolving into spastic tetraplegia with optic atrophy and variable movement disorders. A clinically similar phenotype caused by recessive mutations in GJC2 is known as Pelizaeus-Merzbacher-like disease. Both genes encode proteins associated with myelin. We describe three siblings of a consanguineous family manifesting the typical infantile-onset Pelizaeus-Merzbacher disease-like phenotype slowly evolving into a form of complicated hereditary spastic paraplegia with mental retardation, dysarthria, optic atrophy and peripheral neuropathy in adulthood. Magnetic resonance imaging and spectroscopy were consistent with a demyelinating leukodystrophy. Using genetic linkage and exome sequencing, we identified a homozygous missense c.399C>G; p.S133R mutation in MAG. This gene, previously associated with hereditary spastic paraplegia, encodes myelin-associated glycoprotein, which is involved in myelin maintenance and glia-axon interaction. This mutation is predicted to destabilize the protein and affect its tertiary structure. Examination of the sural nerve biopsy sample obtained in childhood in the oldest sibling revealed complete absence of myelin-associated glycoprotein accompanied by ill-formed onion-bulb structures and a relatively thin myelin sheath of the affected axons. Immunofluorescence, cell surface labelling, biochemical analysis and mass spectrometry-based proteomics studies in a variety of cell types demonstrated a devastating effect of the mutation on post-translational processing, steady state expression and subcellular localization of myelin-associated glycoprotein. In contrast to the wild-type protein, the p.S133R mutant was retained in the endoplasmic reticulum and was subjected to endoplasmic reticulum-associated protein degradation by the

  9. Prevalence of Peyronie's Disease-Like Symptoms in Men Presenting With Dupuytren Contractures.

    PubMed

    Shindel, Alan W; Sweet, Genevieve; Thieu, William; Durbin-Johnson, Blythe; Rothschild, Jennifer; Szabo, Robert

    2017-09-01

    Peyronie's disease (PD) and Dupuytren contractures (DC) are often comorbid and are believed to have a similar underlying pathophysiologic mechanism. To investigate the prevalence of PD-like symptoms (PDLS) in men with DC. From October 2013 to December 2016, men who were seen and evaluated for DC were offered the opportunity to participate in an anonymous survey. The survey assessed several basic demographic and sexual health factors and included items from the International Index of Erectile Function and the Erection Hardness Scale. Men who reported PDLS were asked a series of questions derived from the Peyronie's Disease Questionnaire and for their opinions on theoretical treatment modalities for sexual problems and penile deformity. Prevalence of PDLS in men with DC. One hundred forty men with DC were invited to participate; 85 surveys were returned (response rate = 61%). Twenty-two respondents (26%, 95% confidence interval = 17-35) reported PDLS. Approximately one fourth of all respondents had an Erection Hardness Scale score lower than 3. The most common specific PDLS concerns were penile curvature (91%), length loss (55%), narrowing (36%), and hinging (32%). In men with PDLS, 73% felt at least a little bothered by the symptoms when attempting sexual activity and 40% reported having sex less frequently because of the symptoms. Just 27% of men with PDLS had ever used a treatment for a sexual concern. In terms of treatments for penile deformities, 64% of men with PDLS expressed an interest in treatment administered in the form of an in-office procedure; 41% were potentially amenable to a surgical procedure. The prevalence of PDLS in men with DC is similar to the prevalence of DC in men diagnosed with PD. A substantial number of these men have distress and would consider standard-of-care treatments for PD. Shindel AW, Sweet G, Thieu W, et al. Prevalence of Peyronie's Disease-Like Symptoms in Men Presenting With Dupuytren Contractures. Sex Med 2017;5:e135-e141

  10. Indexing and filing of pathological illustrations.

    PubMed Central

    Brown, R A; Fawkes, R S; Beck, J S

    1975-01-01

    An inexpensive feature card retrieval system has been combined with the Systematised Nomenclature of Pathology (SNOP) to provide simple but efficient means of indexing and filing 2 in. x 2 in. transparencies within a department of pathology. Using this system 2400 transparencies and the associated index cards can be conveniently stored in one drawer of a standard filing cabinet. Images PMID:1123438

  11. Pathology of the parathyroid glands in hyperparathyroidism.

    PubMed

    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.

  12. [Nitric oxide in dengue pathology].

    PubMed

    Rodriguez-Ortega, M

    1998-01-01

    Nitric oxide (NO) is a multifunctional molecule that is involved in citotoxic as well as citoprotective processes, it's synthesis is highly regulated by the cell because an alteration in NO production is associated with a variety of pathologies, such as Septic, Anaphylactic and Hemorrhagic Shock. The clinical feature of dengue virus infection has a spectrum that goes from mild, dengue fever, to a severe disease, dengue hemorrhagic fever/dengue shock. Here, some evidences are discussed that links NO with the pathology of the severe disease cause by dengue virus.

  13. Pathology of intrahepatic cholangiocarcinoma

    PubMed Central

    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

  14. Tau pathology in aged cynomolgus monkeys is progressive supranuclear palsy/corticobasal degeneration- but not Alzheimer disease-like -Ultrastructural mapping of tau by EDX.

    PubMed

    Uchihara, Toshiki; Endo, Kentaro; Kondo, Hiromi; Okabayashi, Sachi; Shimozawa, Nobuhiro; Yasutomi, Yasuhiro; Adachi, Eijiro; Kimura, Nobuyuki

    2016-11-14

    Concomitant deposition of amyloid -beta protein (Aβ) and neuronal tau as neurofibrillary tangles in the human brain is a hallmark of Alzheimer disease (AD). Because these deposits increase during normal aging, it has been proposed that aging brains may also undergo AD-like changes. To investigate the neuropathological changes that occur in the aging primate brain, we examined 21 brains of cynomolgus monkeys (7-36 years old) for Aβ- and tau-positive lesions. We found, 1) extensive deposition of Aβ in brains of cynomolgus monkeys over 25 years of age, 2) selective deposition of 4-repeat tau as pretangles in neurons, and as coiled body-like structures in oligodendroglia-like cells and astrocytes, 3) preferential distribution of tau in the basal ganglia and neocortex rather than the hippocampus, and 4) age-associated increases in 30-34 kDa AT8- and RD4-positive tau fragments in sarkosyl-insoluble fractions. We further labeled tau-positive structures using diaminobezidine enhanced with nickel, and visualized nickel-labeled structures by energy-dispersive X-ray (EDX) analysis of ultrathin sections. This allowed us to distinguish between nickel-labeled tau and background electron-dense structures, and we found that tau localized to 20-25 nm straight filaments in oligodendroglia-like cells and neurons. Our results indicate that the cytopathology and distribution of tau deposits in aged cynomolgus brains resemble those of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) rather than AD. Thus, even in the presence of Aβ, age-associated deposition of tau in non-human primates likely does not occur through AD-associated mechanisms.

  15. Pathological findings in homocystinuria

    PubMed Central

    Gibson, J. B.; Carson, Nina A. J.; Neill, D. W.

    1964-01-01

    Pathological findings are described in four cases of a new aminoaciduria in which homocystine is excreted in the urine. All the patients were mentally retarded children. Three of them presented diagnostic features of Marfan's syndrome. Necropsy on one case and biopsy findings in the others are described. Fatty change occurs in the liver. The most striking lesions are vascular. Metachromatic medial degeneration of the aorta and of the elastic arteries in the necropsied case are considered in relation to Marfan's syndrome. Other changes, particularly thrombosis which is prevalent in homocystinuria, suggest the possibility of a platelet defect. The findings are discussed in respect of an upset in the metabolism of sulphur-containing amino-acids and with particular reference to Marfan's syndrome. Images PMID:14195630

  16. Pathology of oesophagitis.

    PubMed

    Maguire, Aoife; Sheahan, Kieran

    2012-05-01

    Endoscopic oesophageal biopsies are common in daily pathology practice. Inflammation and damage of the oesophageal mucosa is known as oesophagitis and is common worldwide. A variety of physical, chemical and infectious agents cause oesophagitis. The oesophagus has a limited range of responses to a wide variety of injuries, and so histopathological features of different diseases often overlap. The pathologist is reliant on the endoscopist for the 'macroscopic description' of the oesophagus. Access to the endoscopic images enhances the pathologist's overall interpretation of the case. Correlating clinical, endoscopic and microscopic findings may be crucial in arriving at the correct diagnosis. In this review, we present clinicopathological descriptions of the major types of oesophagitis. © 2011 Blackwell Publishing Limited.

  17. A Novel Antisense CAG Repeat Transcript at JPH3 Locus Mediating Expanded Polyglutamine Protein Toxicity in Huntington’s Disease-Like 2 (HDL2) Mice

    PubMed Central

    Wilburn, Brian; Rudnicki, Dobrila D.; Zhao, Jing; Weitz, Tara Murphy; Cheng, Yin; Gu, Xiaofeng; Greiner, Erin; Park, Chang Sin; Wang, Nan; Sopher, Bryce L.; La Spada, Albert R.; Osmand, Alex; Margolis, Russell L.; Sun, Yi E.; Yang, X. William

    2011-01-01

    SUMMARY Huntington’s disease like-2 (HDL2) is a phenocopy of Huntington’s disease caused by CTG/CAG repeat expansion at the Junctophilin-3 (JPH3) locus. The mechanisms underlying HDL2 pathogenesis remain unclear. Here we developed a BAC transgenic mouse model of HDL2 (BAC-HDL2) that exhibits progressive motor deficits, selective neurodegenerative pathology and ubiquitin-positive nuclear inclusions (NIs). Molecular analyses reveal a novel promoter at the transgene locus driving the expression of a CAG repeat transcript (HDL2-CAG) from the strand antisense to JPH3, which encodes an expanded polyglutamine (polyQ) protein. Importantly, BAC-HDL2 but not control BAC mice accumulate polyQ-containing NIs in a pattern strikingly similar to those in the patients. Furthermore, BAC mice with genetic silencing of the expanded CUG transcript still express HDL2-CAG transcript and manifest polyQ pathogenesis. Finally, studies of HDL2 mice and patients revealed CBP sequestration into NIs and evidence for interference of CBP-mediated transcriptional activation. These results suggest overlapping polyQ-mediated pathogenic mechanisms in HD and HDL2 PMID:21555070

  18. Shame regulation in personality pathology.

    PubMed

    Schoenleber, Michelle; Berenbaum, Howard

    2012-05-01

    Drawing on extant work on shame and emotion regulation, this article proposes that three broad forms of maladaptive shame regulation strategies are fundamental in much of personality pathology: Prevention (e.g., dependence, fantasy), used preemptively, lessens potential for shame; Escape (e.g., social withdrawal, misdirection) reduces current or imminent shame; Aggression, used after shame begins, refocuses shame into anger directed at the self (e.g., physical self-harm) or others (e.g., verbal aggression). This article focuses on the contributions of shame regulation to the development and maintenance of personality pathology, highlighting how various maladaptive shame regulation strategies may lead to personality pathology symptoms, associated features, and dimensions. Consideration is also given to the possible shame-related constructs necessitating emotion regulation (e.g., shame aversion and proneness) and the points in the emotion process when regulation can occur.

  19. Forensic Pathology Education in Pathology Residency

    PubMed Central

    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

  20. The differential diagnosis of Huntington's disease-like syndromes: 'red flags' for the clinician.

    PubMed

    Martino, Davide; Stamelou, Maria; Bhatia, Kailash P

    2013-06-01

    A growing number of progressive heredodegenerative conditions mimic the presentation of Huntington's disease (HD). Differentiating among these HD-like syndromes is necessary when a patient with a combination of movement disorders, cognitive decline, behavioural abnormalities and progressive disease course proves negative to the genetic testing for HD causative mutations, that is, IT15 gene trinucleotide-repeat expansion. The differential diagnosis of HD-like syndromes is complex and may lead to unnecessary and costly investigations. We propose here a guide to this differential diagnosis focusing on a limited number of clinical features ('red flags') that can be identified through accurate clinical examination, collection of historical data and a few routine ancillary investigations. These features include the ethnic background of the patient, the involvement of the facio-bucco-lingual and cervical district by the movement disorder, the co-occurrence of cerebellar features and seizures, the presence of peculiar gait patterns and eye movement abnormalities, and an atypical progression of illness. Additional help may derive from the cognitive-behavioural presentation of the patient, as well as by a restricted number of ancillary investigations, mainly MRI and routine blood tests. These red flags should be constantly updated as the phenotypic characterisation and identification of more reliable diagnostic markers for HD-like syndromes progress over the following years.

  1. The differential diagnosis of Huntington's disease-like syndromes: ‘red flags’ for the clinician

    PubMed Central

    Stamelou, Maria; Bhatia, Kailash P

    2013-01-01

    A growing number of progressive heredodegenerative conditions mimic the presentation of Huntington's disease (HD). Differentiating among these HD-like syndromes is necessary when a patient with a combination of movement disorders, cognitive decline, behavioural abnormalities and progressive disease course proves negative to the genetic testing for HD causative mutations, that is, IT15 gene trinucleotide-repeat expansion. The differential diagnosis of HD-like syndromes is complex and may lead to unnecessary and costly investigations. We propose here a guide to this differential diagnosis focusing on a limited number of clinical features (‘red flags’) that can be identified through accurate clinical examination, collection of historical data and a few routine ancillary investigations. These features include the ethnic background of the patient, the involvement of the facio-bucco-lingual and cervical district by the movement disorder, the co-occurrence of cerebellar features and seizures, the presence of peculiar gait patterns and eye movement abnormalities, and an atypical progression of illness. Additional help may derive from the cognitive–behavioural presentation of the patient, as well as by a restricted number of ancillary investigations, mainly MRI and routine blood tests. These red flags should be constantly updated as the phenotypic characterisation and identification of more reliable diagnostic markers for HD-like syndromes progress over the following years. PMID:22993450

  2. Loss of Polo ameliorates APP-induced Alzheimer's disease-like symptoms in Drosophila.

    PubMed

    Peng, Fei; Zhao, Yu; Huang, Xirui; Chen, Changyan; Sun, Lili; Zhuang, Luming; Xue, Lei

    2015-11-24

    The amyloid precursor protein (APP) has been implicated in the pathogenesis of Alzheimer's disease (AD). Despite extensive studies, little is known about the regulation of APP's functions in vivo. Here we report that expression of human APP in Drosophila, in the same temporal-spatial pattern as its homolog APPL, induced morphological defects in wings and larval NMJ, larva and adult locomotion dysfunctions, male choice disorder and lifespan shortening. To identify additional genes that modulate APP functions, we performed a genetic screen and found that loss of Polo, a key regulator of cell cycle, partially suppressed APP-induced morphological and behavioral defects in larval and adult stages. Finally, we showed that eye-specific expression of APP induced retina degeneration and cell cycle re-entry, both phenotypes were mildly ameliorated by loss of Polo. These results suggest Polo is an important in vivo regulator of the pathological functions of APP, and provide insight into the role of cell cycle re-entry in AD pathogenesis.

  3. Loss of Polo ameliorates APP-induced Alzheimer’s disease-like symptoms in Drosophila

    PubMed Central

    Peng, Fei; Zhao, Yu; Huang, Xirui; Chen, Changyan; Sun, Lili; Zhuang, Luming; Xue, Lei

    2015-01-01

    The amyloid precursor protein (APP) has been implicated in the pathogenesis of Alzheimer’s disease (AD). Despite extensive studies, little is known about the regulation of APP’s functions in vivo. Here we report that expression of human APP in Drosophila, in the same temporal-spatial pattern as its homolog APPL, induced morphological defects in wings and larval NMJ, larva and adult locomotion dysfunctions, male choice disorder and lifespan shortening. To identify additional genes that modulate APP functions, we performed a genetic screen and found that loss of Polo, a key regulator of cell cycle, partially suppressed APP-induced morphological and behavioral defects in larval and adult stages. Finally, we showed that eye-specific expression of APP induced retina degeneration and cell cycle re-entry, both phenotypes were mildly ameliorated by loss of Polo. These results suggest Polo is an important in vivo regulator of the pathological functions of APP, and provide insight into the role of cell cycle re-entry in AD pathogenesis. PMID:26597721

  4. Hairy cell leukemia: diagnostic pathology.

    PubMed

    Sharpe, Robert W; Bethel, Kelly J

    2006-10-01

    The pathology of HCL has been reviewed with a focus on the diagnostic hematopathology of this rare, but fascinating, disease. The discrimination of HCL from other B-cell lymphoproliferations, particularly HCL-V and SMZL, has been emphasized. The unique responsiveness of HCL to 2-CdA and other chemotherapeutic agents makes this distinction critical. Fortunately, HCL has consistent cytologic, histologic, cytochemical, and immunologic features that make classification reliable and reproducible. Less straightforward is the differential diagnosis of SMZL and HCL-V, problematic because of the rarity of both disorders, lack of discriminating evidence-based criteria, and perhaps a biologic kinship between these two disorders that share many clinical and pathologic features. Fortunately, this is not a clinically critical distinction.

  5. Ammonium chloride and tunicamycin are novel toxins for dopaminergic neurons and induce Parkinson's disease-like phenotypes in medaka fish.

    PubMed

    Matsui, Hideaki; Ito, Hidefumi; Taniguchi, Yoshihito; Takeda, Shunichi; Takahashi, Ryosuke

    2010-12-01

    Perturbations in protein folding and degradation are key pathological mechanisms in neurodegenerative diseases, including Parkinson's disease (PD). Recent evidence suggests that mishandling of proteins may play an important role in the pathogenesis of PD. We have utilized medaka fish to monitor the effects of injecting neurotoxins into the CSF space. In this study, ammonium chloride, tunicamycin, and lactacystin were tested for their ability to disturb lysosomal proteolysis, N-glycosylation in the endoplasmic reticulum, and proteasomal degradation, respectively. All of the substances tested induced selective loss of dopaminergic neurons, movement disorders and inclusion bodies. Among them, the features of the inclusion bodies that developed after ammonium chloride injection mimicked those of PD: co-localization of ubiquitin and phosphorylated α-synuclein, as well as the presence of LC3 protein in the inclusion bodies. Our study demonstrated that medaka fish are useful for examining the effects of environmental toxins and lysosome inhibition, and lysosome inhibitors may be factors in the development of PD.

  6. Dysbiotic gut microbiota causes transmissible Crohn's disease-like ileitis independent of failure in antimicrobial defence

    PubMed Central

    Clavel, Thomas; Calasan, Jelena; Lagkouvardos, Ilias; Haange, Sven Bastiaan; Jehmlich, Nico; Basic, Marijana; Dupont, Aline; Hornef, Mathias; von Bergen, Martin; Bleich, André; Haller, Dirk

    2016-01-01

    Objectives Dysbiosis of the intestinal microbiota is associated with Crohn's disease (CD). Functional evidence for a causal role of bacteria in the development of chronic small intestinal inflammation is lacking. Similar to human pathology, TNFdeltaARE mice develop a tumour necrosis factor (TNF)-driven CD-like transmural inflammation with predominant ileal involvement. Design Heterozygous TNFdeltaARE mice and wildtype (WT) littermates were housed under conventional (CONV), specific pathogen-free (SPF) and germ-free (GF) conditions. Microbial communities were analysed by high-throughput 16S ribosomal RNA gene sequencing. Metaproteomes were measured using LC-MS. Temporal and spatial resolution of disease development was followed after antibiotic treatment and transfer of microbial communities into GF mice. Granulocyte infiltration and Paneth cell function was assessed by immunofluorescence and gene expression analysis. Results GF-TNFdeltaARE mice were free of inflammation in the gut and antibiotic treatment of CONV-TNFdeltaARE mice attenuated ileitis but not colitis, demonstrating that disease severity and location are microbiota-dependent. SPF-TNFdeltaARE mice developed distinct ileitis-phenotypes associated with gradual loss of antimicrobial defence. 16S analysis and metaproteomics revealed specific compositional and functional alterations of bacterial communities in inflamed mice. Transplantation of disease-associated but not healthy microbiota transmitted CD-like ileitis to GF-TNFdeltaARE recipients and triggered loss of lysozyme and cryptdin-2 expression. Monoassociation of GF-TNFdeltaARE mice with the human CD-related Escherichia coli LF82 did not induce ileitis. Conclusions We provide clear experimental evidence for the causal role of gut bacterial dysbiosis in the development of chronic ileal inflammation with subsequent failure of Paneth cell function. PMID:25887379

  7. Characterization of the Pathological and Biochemical Markers that Correlate to the Clinical Features of Autism. Subproject 2: Contribution of Significant Delay of Neuronal Development and Metabolic Shift of Neurons to Clinical Phenotype of Autism

    DTIC Science & Technology

    2010-10-21

    of mental retardation, seizures, cerebral palsy , and neuropsychiatric disor- ders (Barkovich et al., 2005; Guerrini and Marini, 2006; Sarnat and Flores...ventral and dorsal tiers, and the lateral part. Neurons from both the ventral and dorsal tiers project to the striatum and cerebral cortex. The...subjects indicate that epilepsy-associated pathology includes patchy or laminar neuronal loss and gliosis in the cerebral cortex in one or both

  8. Structures of three polycystic kidney disease-like domains from Clostridium histolyticum collagenases ColG and ColH

    DOE PAGES

    Bauer, Ryan; Janowska, Katarzyna; Taylor, Kelly; ...

    2015-03-01

    Clostridium histolyticumcollagenases ColG and ColH are segmental enzymes that are thought to be activated by Ca2+-triggered domain reorientation to cause extensive tissue destruction. The collagenases consist of a collagenase module (s1), a variable number of polycystic kidney disease-like (PKD-like) domains (s2a and s2b in ColH and s2 in ColG) and a variable number of collagen-binding domains (s3 in ColH and s3a and s3b in ColG). The X-ray crystal structures of Ca2+-bound holo s2b (1.4 Å resolution,R= 15.0%,Rfree= 19.1%) and holo s2a (1.9 Å resolution,R= 16.3%,Rfree= 20.7%), as well as of Ca2+-free apo s2a (1.8 Å resolution,R= 20.7%,Rfree= 27.2%) and twomore » new forms of N-terminally truncated apo s2 (1.4 Å resolution,R= 16.9%,Rfree= 21.2%; 1.6 Å resolution,R= 16.2%,Rfree= 19.2%), are reported. The structurally similar PKD-like domains resemble the V-set Ig fold. In addition to a conserved β-bulge, the PKD-like domains feature a second bulge that also changes the allegiance of the subsequent β-strand. This β-bulge and the genesis of a Ca2+pocket in the archaeal PKD-like domain suggest a close kinship between bacterial and archaeal PKD-like domains. Different surface properties and indications of different dynamics suggest unique roles for the PKD-like domains in ColG and in ColH. Surface aromatic residues found on ColH s2a-s2b, but not on ColG s2, may provide the weak interaction in the biphasic collagen-binding mode previously found in s2b-s3.B-factor analyses suggest that in the presence of Ca2+the midsection of s2 becomes more flexible but the midsections of s2a and s2b stay rigid. The different surface properties and dynamics of the domains suggest that the PKD-like domains of M9B bacterial collagenase can be grouped into either a ColG subset or a ColH subset. The conserved properties of PKD-like domains in ColG and in ColH include Ca2+binding. Conserved residues not only interact with Ca2+, but also position the Ca2+-interacting water molecule. Ca

  9. Structures of three polycystic kidney disease-like domains from Clostridium histolyticum collagenases ColG and ColH

    PubMed Central

    Bauer, Ryan; Janowska, Katarzyna; Taylor, Kelly; Jordan, Brad; Gann, Steve; Janowski, Tomasz; Latimer, Ethan C.; Matsushita, Osamu; Sakon, Joshua

    2015-01-01

    Clostridium histolyticum collagenases ColG and ColH are segmental enzymes that are thought to be activated by Ca2+-triggered domain reorientation to cause extensive tissue destruction. The collagenases consist of a collagenase module (s1), a variable number of polycystic kidney disease-like (PKD-like) domains (s2a and s2b in ColH and s2 in ColG) and a variable number of collagen-binding domains (s3 in ColH and s3a and s3b in ColG). The X-ray crystal structures of Ca2+-bound holo s2b (1.4 Å resolution, R = 15.0%, R free = 19.1%) and holo s2a (1.9 Å resolution, R = 16.3%, R free = 20.7%), as well as of Ca2+-free apo s2a (1.8 Å resolution, R = 20.7%, R free = 27.2%) and two new forms of N-terminally truncated apo s2 (1.4 Å resolution, R = 16.9%, R free = 21.2%; 1.6 Å resolution, R = 16.2%, R free = 19.2%), are reported. The structurally similar PKD-like domains resemble the V-set Ig fold. In addition to a conserved β-bulge, the PKD-like domains feature a second bulge that also changes the allegiance of the subsequent β-strand. This β-bulge and the genesis of a Ca2+ pocket in the archaeal PKD-like domain suggest a close kinship between bacterial and archaeal PKD-like domains. Different surface properties and indications of different dynamics suggest unique roles for the PKD-like domains in ColG and in ColH. Surface aromatic residues found on ColH s2a-s2b, but not on ColG s2, may provide the weak interaction in the biphasic collagen-binding mode previously found in s2b-s3. B-factor analyses suggest that in the presence of Ca2+ the midsection of s2 becomes more flexible but the midsections of s2a and s2b stay rigid. The different surface properties and dynamics of the domains suggest that the PKD-like domains of M9B bacterial collagenase can be grouped into either a ColG subset or a ColH subset. The conserved properties of PKD-like domains in ColG and in ColH include Ca2+ binding. Conserved residues not only interact with Ca2+, but also position the Ca2

  10. Structures of three polycystic kidney disease-like domains from Clostridium histolyticum collagenases ColG and ColH.

    PubMed

    Bauer, Ryan; Janowska, Katarzyna; Taylor, Kelly; Jordan, Brad; Gann, Steve; Janowski, Tomasz; Latimer, Ethan C; Matsushita, Osamu; Sakon, Joshua

    2015-03-01

    Clostridium histolyticum collagenases ColG and ColH are segmental enzymes that are thought to be activated by Ca(2+)-triggered domain reorientation to cause extensive tissue destruction. The collagenases consist of a collagenase module (s1), a variable number of polycystic kidney disease-like (PKD-like) domains (s2a and s2b in ColH and s2 in ColG) and a variable number of collagen-binding domains (s3 in ColH and s3a and s3b in ColG). The X-ray crystal structures of Ca(2+)-bound holo s2b (1.4 Å resolution, R = 15.0%, Rfree = 19.1%) and holo s2a (1.9 Å resolution, R = 16.3%, Rfree = 20.7%), as well as of Ca(2+)-free apo s2a (1.8 Å resolution, R = 20.7%, Rfree = 27.2%) and two new forms of N-terminally truncated apo s2 (1.4 Å resolution, R = 16.9%, Rfree = 21.2%; 1.6 Å resolution, R = 16.2%, Rfree = 19.2%), are reported. The structurally similar PKD-like domains resemble the V-set Ig fold. In addition to a conserved β-bulge, the PKD-like domains feature a second bulge that also changes the allegiance of the subsequent β-strand. This β-bulge and the genesis of a Ca(2+) pocket in the archaeal PKD-like domain suggest a close kinship between bacterial and archaeal PKD-like domains. Different surface properties and indications of different dynamics suggest unique roles for the PKD-like domains in ColG and in ColH. Surface aromatic residues found on ColH s2a-s2b, but not on ColG s2, may provide the weak interaction in the biphasic collagen-binding mode previously found in s2b-s3. B-factor analyses suggest that in the presence of Ca(2+) the midsection of s2 becomes more flexible but the midsections of s2a and s2b stay rigid. The different surface properties and dynamics of the domains suggest that the PKD-like domains of M9B bacterial collagenase can be grouped into either a ColG subset or a ColH subset. The conserved properties of PKD-like domains in ColG and in ColH include Ca(2+) binding. Conserved residues not only interact with Ca(2+), but also

  11. Updates of pathologic myopia.

    PubMed

    Ohno-Matsui, Kyoko; Lai, Timothy Y Y; Lai, Chi-Chun; Cheung, Chiu Ming Gemmy

    2016-05-01

    Complications from pathologic myopia are a major cause of visual impairment and blindness, especially in east Asia. The eyes with pathologic myopia may develop loss of the best-corrected vision due to various pathologies in the macula, peripheral retina and the optic nerve. Despite its importance, the definition of pathologic myopia has been inconsistent. The refractive error or axial length alone often does not adequately reflect the 'pathologic myopia'. Posterior staphyloma, which is a hallmark lesion of pathologic myopia, can occur also in non-highly myopic eyes. Recently a revised classification system for myopic maculopathy has been proposed to standardize the definition among epidemiological studies. In this META-PM (meta analyses of pathologic myopia) study classification, pathologic myopia was defined as the eyes having chorioretinal atrophy equal to or more severe than diffuse atrophy. In addition, the advent of new imaging technologies such as optical coherence tomography (OCT) and three dimensional magnetic resonance imaging (3D MRI) has enabled the detailed observation of various pathologies specific to pathologic myopia. New therapeutic approaches including intravitreal injections of anti-vascular endothelial growth factor agents and the advance of vitreoretinal surgeries have greatly improved the prognosis of patients with pathologic myopia. The purpose of this review article is to provide an update on topics related to the field of pathologic myopia, and to outline the remaining issues which need to be solved in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Explaining pathological changes in axonal excitability through dynamical analysis of conductance-based models

    NASA Astrophysics Data System (ADS)

    Coggan, Jay S.; Ocker, Gabriel K.; Sejnowski, Terrence J.; Prescott, Steven A.

    2011-10-01

    Neurons rely on action potentials, or spikes, to relay information. Pathological changes in spike generation likely contribute to certain enigmatic features of neurological disease, like paroxysmal attacks of pain and muscle spasm. Paroxysmal symptoms are characterized by abrupt onset and short duration, and are associated with abnormal spiking although the exact pathophysiology remains unclear. To help decipher the biophysical basis for 'paroxysmal' spiking, we replicated afterdischarge (i.e. continued spiking after a brief stimulus) in a minimal conductance-based axon model. We then applied nonlinear dynamical analysis to explain the dynamical basis for initiation and termination of afterdischarge. A perturbation could abruptly switch the system between two (quasi-)stable attractor states: rest and repetitive spiking. This bistability was a consequence of slow positive feedback mediated by persistent inward current. Initiation of afterdischarge was explained by activation of the persistent inward current forcing the system to cross a saddle point that separates the basins of attraction associated with each attractor. Termination of afterdischarge was explained by the attractor associated with repetitive spiking being destroyed. This occurred when ultra-slow negative feedback, such as intracellular sodium accumulation, caused the saddle point and stable limit cycle to collide; in that regard, the active attractor is not truly stable when the slowest dynamics are taken into account. The model also explains other features of paroxysmal symptoms, including temporal summation and refractoriness.

  13. Explaining pathological changes in axonal excitability through dynamical analysis of conductance-based models

    PubMed Central

    Coggan, Jay S; Ocker, Gabriel K; Sejnowski, Terrence J; Prescott, Steven A

    2011-01-01

    Neurons rely on action potentials, or spikes, to relay information. Pathological changes in spike generation likely contribute to certain enigmatic features of neurological disease, like paroxysmal attacks of pain and muscle spasm. Paroxysmal symptoms are characterized by abrupt onset and short duration, and are associated with abnormal spiking although the exact pathophysiology remains unclear. To help decipher the biophysical basis for ‘paroxysmal’ spiking, we replicated afterdischarge (i.e. continued spiking after a brief stimulus) in a minimal conductance-based axon model. We then applied nonlinear dynamical analysis to explain the dynamical basis for initiation and termination of afterdischarge. A perturbation could abruptly switch the system between two (quasi-)stable attractor states: rest and repetitive spiking. This bistability was a consequence of slow positive feedback mediated by persistent inward current. Initiation of afterdischarge was explained by activation of the persistent inward current forcing the system to cross a saddle point that separates the basins of attraction associated with each attractor. Termination of afterdischarge was explained by the attractor associated with repetitive spiking being destroyed. This occurred when ultra-slow negative feedback, such as intracellular sodium accumulation, caused the saddle point and stable limit cycle to collide; in that regard, the active attractor is not truly stable when the slowest dynamics are taken into account. The model also explains other features of paroxysmal symptoms, including temporal summation and refractoriness. PMID:22058273

  14. The Frequency of Huntington Disease and Huntington Disease-Like 2 in the South African Population.

    PubMed

    Baine, Fiona K; Krause, Amanda; Greenberg, L Jacquie

    2016-01-01

    Huntington disease (HD) has most recently been estimated to affect between 10.6 and 13.7 per 100,000 individuals in European populations. However, prevalence is known to differ geographically. In South Africa, the only published estimates are from a survey performed in the 1970s, an era when the disease was believed to be rare or absent in black individuals and molecular confirmation was absent. The disease phenotype in South Africa is currently attributable to mutations in both the huntington and junctophilin-3 genes, which underlie the well-known HD and the rarer HD-like 2 (HDL2) respectively. This study aimed at providing improved minimum estimates of disease frequency in South Africa, based on molecular genetic testing data. A review of all testing records for HD and HDL2 over a 20-year period was undertaken. HDL2 is virtually indistinguishable on clinical features, thus necessitating its inclusion. Based on molecular diagnostic records, minimum estimates of disease frequency are: 5.1, 2.1 and 0.25 (per 100,000 individuals) for the white, mixed ancestry and black population groups respectively. Although ascertainment remains incomplete, these minimum estimates suggest that disease frequencies are significantly higher than those previously reported in South Africa. © 2016 S. Karger AG, Basel.

  15. The etiology of Ebola virus disease-like illnesses in Ebola virusnegative patients from Sierra Leone

    PubMed Central

    Li, Lei; Ji, Dong; Ji, Ying-Jie; Li, Chen; Gao, Xu-Dong; Wang, Li-Fu; Zhao, Min; Duan, Xue-Zhang; Duan, Hui-Juan

    2016-01-01

    During the 2014 Ebola virus disease (EVD) outbreak, less than half of EVD-suspected cases were laboratory tested as Ebola virus (EBOV)-negative, but disease identity remained unknown. In this study we investigated the etiology of EVD-like illnesses in EBOV-negative cases. From November 13, 2014 to March 16, 2015, EVD-suspected patients were admitted to Jui Government Hospital and assessed for EBOV infection by real-time PCR. Of 278 EBOV negative patients, 223 (80.21%), 142 (51.08%), 123 (44.24%), 114 (41.01%), 59 (21.22%), 35 (12.59%), and 12 (4.32%) reported fever, headache, joint pain, fatigue, nausea/vomiting, diarrhea, hemorrhage, respectively. Furthermore, 121 (43.52%), 44 (15.83%), 36 (12.95%), 33 (11.87%), 23 (8.27%), 10 (3.60%) patients were diagnosed as infection with malaria, HIV, Lassa fever, tuberculosis, yellow fever, and pneumonia, respectively. No significant differences in clinical features and symptoms were found between non-EVD and EVD patients. To the best of our knowledge, the present study is the first to explore the etiology of EVD-like illnesses in uninfected patients in Sierra Leone, highlighting the importance of accurate diagnosis to EVD confirmation. PMID:27058894

  16. The etiology of Ebola virus disease-like illnesses in Ebola virusnegative patients from Sierra Leone.

    PubMed

    Li, Wen-Gang; Chen, Wei-Wei; Li, Lei; Ji, Dong; Ji, Ying-Jie; Li, Chen; Gao, Xu-Dong; Wang, Li-Fu; Zhao, Min; Duan, Xue-Zhang; Duan, Hui-Juan

    2016-05-10

    During the 2014 Ebola virus disease (EVD) outbreak, less than half of EVD-suspected cases were laboratory tested as Ebola virus (EBOV)-negative, but disease identity remained unknown. In this study we investigated the etiology of EVD-like illnesses in EBOV-negative cases. From November 13, 2014 to March 16, 2015, EVD-suspected patients were admitted to Jui Government Hospital and assessed for EBOV infection by real-time PCR. Of 278 EBOV negative patients, 223 (80.21%), 142 (51.08%), 123 (44.24%), 114 (41.01%), 59 (21.22%), 35 (12.59%), and 12 (4.32%) reported fever, headache, joint pain, fatigue, nausea/vomiting, diarrhea, hemorrhage, respectively. Furthermore, 121 (43.52%), 44 (15.83%), 36 (12.95%), 33 (11.87%), 23 (8.27%), 10 (3.60%) patients were diagnosed as infection with malaria, HIV, Lassa fever, tuberculosis, yellow fever, and pneumonia, respectively. No significant differences in clinical features and symptoms were found between non-EVD and EVD patients. To the best of our knowledge, the present study is the first to explore the etiology of EVD-like illnesses in uninfected patients in Sierra Leone, highlighting the importance of accurate diagnosis to EVD confirmation.

  17. [Once again: theoretical pathology].

    PubMed

    Bleyl, U

    2010-07-01

    Theoretical pathology refers to the attempt to reintroduce methodical approaches from the humanities, philosophical logic and "gestalt philosophy" into medical research and pathology. Diseases, in particular disease entities and more complex polypathogenetic mechanisms of disease, have a "gestalt quality" due to the significance of their pathophysiologic coherence: they have a "gestalt". The Research group Theoretical Pathology at the Academy of Science in Heidelberg are credited with having revitalized the philosophical notion of "gestalt" for morphological and pathological diagnostics. Gestalt means interrelated schemes of pathophysiological significance in the mind of the diagnostician. In pathology, additive and associative diagnostic are simply not possible without considering the notion of synthetic entities in Kant's logic.

  18. periostin Null Mice Exhibit Dwarfism, Incisor Enamel Defects, and an Early-Onset Periodontal Disease-Like Phenotype

    PubMed Central

    Rios, Hector; Koushik, Shrinagesh V.; Wang, Haiyan; Wang, Jian; Zhou, Hong-Ming; Lindsley, Andrew; Rogers, Rhonda; Chen, Zhi; Maeda, Manabu; Kruzynska-Frejtag, Agnieszka; Feng, Jian Q.; Conway, Simon J.

    2005-01-01

    Periostin was originally identified as an osteoblast-specific factor and is highly expressed in the embryonic periosteum, cardiac valves, placenta, and periodontal ligament as well as in many adult cancerous tissues. To investigate its role during development, we generated mice that lack the periostin gene and replaced the translation start site and first exon with a lacZ reporter gene. Surprisingly, although periostin is widely expressed in many developing organs, periostin-deficient (perilacZ) embryos are grossly normal. Postnatally, however, ∼14% of the nulls die before weaning and all of the remaining perilacZ nulls are severely growth retarded. Skeletal analysis revealed that trabecular bone in adult homozygous skeletons was sparse, but overall bone growth was unaffected. Furthermore, by 3 months, the nulls develop an early-onset periodontal disease-like phenotype. Unexpectedly, these mice also show a severe incisor enamel defect, although there is no apparent change in ameloblast differentiation. Significantly, placing the perilacZ nulls on a soft diet that alleviated mechanical strain on the periodontal ligament resulted in a partial rescue of both the enamel and periodontal disease-like phenotypes. Combined, these data suggest that a healthy periodontal ligament is required for normal amelogenesis and that periostin is critically required for maintenance of the integrity of the periodontal ligament in response to mechanical stresses. PMID:16314533

  19. Pathological fear of cot death.

    PubMed

    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.

  20. Handheld computing in pathology

    PubMed Central

    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. Digital imaging in pathology.

    PubMed

    Park, Seung; Pantanowitz, Liron; Parwani, Anil Vasdev

    2012-12-01

    Advances in computing speed and power have made a pure digital work flow for pathology. New technologies such as whole slide imaging (WSI), multispectral image analysis, and algorithmic image searching seem poised to fundamentally change the way in which pathology is practiced. This article provides the practicing pathologist with a primer on digital imaging. Building on this primer, the current state of the art concerning digital imaging in pathology is described. Emphasis is placed on WSI and its ramifications, showing how it is useful in both anatomic (histology, cytopathology) and clinical (hematopathology) pathology. Future trends are also extrapolated.

  2. Pathology in Greece.

    PubMed

    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.

  3. Opportunities in Speech Pathology.

    ERIC Educational Resources Information Center

    Newman, Parley W.

    The importance of speech is discussed and speech pathology is described. Types of communication disorders considered are articulation disorders, aphasia, facial deformity, hearing loss, stuttering, delayed speech, voice disorders, and cerebral palsy; examples of five disorders are given. Speech pathology is investigated from these aspects: the…

  4. Radiographic pathology for technologists

    SciTech Connect

    Mace, J.D.; Kowalczyk, N.

    1988-01-01

    This book explains the fundamentals of disease mechanisms and relates this to the practice of radiologic science. Each chapter begins with a discussion of normal anatomy and physiology, then covers pathology and demonstrates how the pathology appears on film. Imaging modalities such as computed tomography, MRI, and ultrasound are also discussed. Clinical case studies are included.

  5. Pathology annual. Part 2

    SciTech Connect

    Fechner, R.E.; Rosen, P.P.

    1987-01-01

    This book contains 11 selections. Some of the titles are: Applications of in situ DNA hybridization technology to diagnostic surgical pathology; Neoplasms associated with immune deficiencies; Chronic gastritis: The pathologists's role; Necrosis in lymph nodes; Pathologic changes of osteochondrodysplasia in infancy: A review; and Immunoglobulin light chain nephropathies.

  6. Maternal Genetic Mutations as Gestational and Early Life Influences in Producing Psychiatric Disease-Like Phenotypes in Mice

    PubMed Central

    Gleason, Georgia; Zupan, Bojana; Toth, Miklos

    2011-01-01

    Risk factors for psychiatric disorders have traditionally been classified as genetic or environmental. Risk (candidate) genes, although typically possessing small effects, represent a clear starting point to elucidate downstream cellular/molecular pathways of disease. Environmental effects, especially during development, can also lead to altered behavior and increased risk for disease. An important environmental factor is the mother, demonstrated by the negative effects elicited by maternal gestational stress and altered maternal care. These maternal effects can also have a genetic basis (e.g., maternal genetic variability and mutations). The focus of this review is “maternal genotype effects” that influence the emotional development of the offspring resulting in life-long psychiatric disease-like phenotypes. We have recently found that genetic inactivation of the serotonin 1A receptor (5-HT1AR) and the fmr1 gene (encoding the fragile X mental retardation protein) in mouse dams results in psychiatric disease-like phenotypes in their genetically unaffected offspring. 5-HT1AR deficiency in dams results in anxiety and increased stress responsiveness in their offspring. Offspring of 5-HT1AR deficient dams display altered development of the hippocampus, which could be linked to their anxiety-like phenotype. Maternal inactivation of fmr1, like its inactivation in the offspring, results in a hyperactivity-like condition and is associated with receptor alterations in the striatum. These data indicate a high sensitivity of the offspring to maternal mutations and suggest that maternal genotype effects can increase the impact of genetic risk factors in a population by increasing the risk of the genetically normal offspring as well as by enhancing the effects of offspring mutations. PMID:21629836

  7. Voice data mining for laryngeal pathology assessment.

    PubMed

    Hemmerling, Daria; Skalski, Andrzej; Gajda, Janusz

    2016-02-01

    The aim of this study was to evaluate the usefulness of different methods of speech signal analysis in the detection of voice pathologies. Firstly, an initial vector was created consisting of 28 parameters extracted from time, frequency and cepstral domain describing the human voice signal based on the analysis of sustained vowels /a/, /i/ and /u/ all at high, low and normal pitch. Afterwards we used a linear feature extraction technique (principal component analysis), which enabled a reduction in the number of parameters and choose the most effective acoustic features describing the speech signal. We have also performed non-linear data transformation which was calculated using kernel principal components. The results of the presented methods for normal and pathological cases will be revealed and discussed in this paper. The initial and extracted feature vectors were classified using the k-means clustering and the random forest classifier. We found that reasonably good classification accuracies could be achieved by selecting appropriate features. We obtained accuracies of up to 100% for classification of healthy versus pathology voice using random forest classification for female and male recordings. These results may assist in the feature development of automated detection systems for diagnosis of patients with symptoms of pathological voice.

  8. Updates in ophthalmic pathology.

    PubMed

    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.

  9. Beyond acute appendicitis: imaging and pathologic spectrum of appendiceal pathology.

    PubMed

    Gaetke-Udager, Kara; Maturen, Katherine E; Hammer, Suntrea G

    2014-10-01

    While acute appendicitis is a common and important clinical problem, a variety of other disease processes can affect the appendix. Simple and perforated appendicitis, tip appendicitis, and stump appendicitis share a common clinical presentation including anorexia, right lower quadrant pain, and fever. By imaging, most cases of acute appendicitis exhibit luminal dilation, wall thickening, and periappendiceal inflammatory stranding. In tip appendicitis, these changes are isolated to the distal appendix, often with an obstructing appendicolith. Perforated appendicitis can exhibit mural discontinuity, periappendiceal abscess, and/or extraluminal appendicoliths. After appendectomy, the appendiceal remnant or "stump" can become inflamed, often necessitating repeat surgery. Inflammatory bowel disease can involve the terminal ileum, secondarily involving the appendix, or may primarily involve the appendix. Patient symptoms can be chronic in such cases, and mucosal hyperenhancement is a pronounced imaging feature. In asymptomatic patients without appendiceal inflammation, the appendix can be dilated by intraluminal material such as inspissated succus in cystic fibrosis or mucus from benign appendiceal mucocele. Finally, neoplasms such as typical appendiceal carcinoid tumor and mucinous adenocarcinoma can involve the appendix. Carcinoids are often small and incidentally discovered at pathologic examination, while malignant mucinous adenocarcinoma tends to present with advanced disease including pseudomyxoma peritonei. Cecal cancers can also obstruct the appendiceal lumen and cause acute appendicitis; an astute radiologist can recognize this prospectively and facilitate definitive resection (right hemicolectomy) at the time of surgery. Attention to mural features, cecal configuration, and periappendiceal inflammation is essential to the correct prospective diagnosis of complicated appendicitis and less common appendiceal pathologies.

  10. [Pathology- a new revival].

    PubMed

    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.

  11. [Pathological gambling: literature revue].

    PubMed

    Filteau, M J; Baruch, P; Vincent, P

    1992-03-01

    This paper summarizes the current literature on pathological gambling. Interest in gambling has been present in every society but treated as an object of sociopolitical or literary interest. It is only from the beginning of this century that psychiatry began to look at pathological gambling, first with Freud and his writing on Dostoïevsky then with other theories like the learning theory, studies on substance dependence, the links with affective syndromes and the psychobiological studies. These studies are presented and discussed. Finally, the authors offer some guidelines for an approach to a pathological gambler.

  12. Meeting report: Urinary Pathology; sixth Research Triangle Park Rodent Pathology Course.

    PubMed

    Boyle, M C; Boyle, M H

    2013-05-01

    Urinary system toxicity is a significant concern to pathologists in the hazard identification, drug and chemical safety evaluation, and diagnostic service industries worldwide. There are myriad known human and animal urinary system toxicants, and investigatory renal toxicology and pathology is continually evolving. The system-specific Research Triangle Park (RTP) Rodent Pathology Course biennially serves to update scientists on the latest research, laboratory techniques, and debates. The Sixth RTP Rodent Pathology Course, Urinary Pathology, featured experts from the government, pharmaceutical, academic, and diagnostic arenas sharing the state of the science in urinary pathology. Speakers presented on a wide range of topics including background lesions, treatment-related non-neoplastic and neoplastic lesions, transgenic rodent models of human disease, diagnostic imaging, biomarkers, and molecular analyses. These seminars were accompanied by case presentation sessions focused on usual and unusual lesions, grading schemes, and tumors.

  13. Pathological Gambling and Substance Use Disorders

    PubMed Central

    Wareham, Justin D.; Potenza, Marc N.

    2013-01-01

    Pathological gambling (PG) has been considered as a behavioral addiction having similarities with substance use disorders (SUDs). Shared features exist in diagnostic, clinical, physiological, and behavioral domains. Current conceptualizations of addiction, as well as experimental studies of PG and SUDs, are reviewed in order to provide a perspective on the areas of convergence between addictive behaviors in PG and SUDs. PMID:20575651

  14. Retroviruses and human pathology

    SciTech Connect

    Gallo, R.C.; Stehelin, D.; Varnier, O.E.

    1985-01-01

    This book contains four sections, each consisting of several papers. The section headings are: Retroviruses and the Murine Model System;Retroviruses and the Vertebrate Model System;Retroviruses and Human Pathology;and Retroviruses and Oncogenes.

  15. A program of training in chemical pathology for residents in pathology.

    PubMed

    Wong, E T; Umehara, M K; Sterling, R E

    1982-02-01

    We have developed a new program of instruction in chemical pathology for residents in pathology. The major features that differentiate this program from its predecessor are: first, an emphasis on principles rather than technical details of biochemical analysis; second, didactic instruction and practical experience in laboratory management and administration; and, third, instruction in interpretation and selection of laboratory tests. The organization, content, instructional approaches and learning objectives are described.

  16. Renal pathology in reptiles.

    PubMed

    Zwart, Peernel

    2006-01-01

    The class of Reptilia varies widely. Both the gross morphology and microscopic anatomy of the kidneys are specific for each species. In each species of reptile, the physiology of the renal system has adapted to the specific conditions of life, including, among other factors, the type of food, environmental temperature, and the availability of water. The pathology of the kidneys in reptiles has been poorly studied, but in recent years a number of investigators have specifically studied reptilian renal pathology.